CONGENITAL ANOMALIES IN CANADA 2013 A PERINATAL HEALTH SURVEILLANCE REPORT

CONGENITAL ANOMALIES IN CANADA 2013 A PERINATAL HEALTH SURVEILLANCE REPORT
P U B L I C H E A LT H A G E N C Y O F C A N A D A
CONGENITAL
ANOMALIES
IN CANADA 2013
A PERINATAL HEALTH SURVEILLANCE REPORT
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TO PROMOTE AND PROTECT THE HEALTH OF CANADIANS THROUGH LEADERSHIP, PARTNERSHIP, INNOVATION AND ACTION IN PUBLIC HEALTH.
— Public Health Agency of Canada
Également disponible en français sous le titre :
Les anomalies congénitales au Canada, 2013 : Rapport de surveillance sur la santé périnatale
Copies of this report are available from:
Maternal and Infant Health Section
Health Surveillance and Epidemiology Division
Centre for Chronic Disease Prevention
Health Promotion and Chronic Disease Prevention Branch
785 Carling Avenue
Ottawa, Ontario
K1A 0K9
Email: [email protected]
This publication can be made available in alternative formats upon request.
Suggested citation:
Public Health Agency of Canada. Congenital Anomalies in Canada 2013 : A Perinatal Health Surveillance Report. Ottawa, 2013.
© Her Majesty the Queen in Right of Canada, 2013
Publication date: September 2013
Cat.: HP35-40/2013E-PDF
ISBN: 978-1-100-22259-2
Pub.: 130043
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TABLE OF CONTENTS
CONTRIBUTORS AND ACKNOWLEDGEMENTS................................................................................................. 1
LIST OF FIGURES.................................................................................................................................................. 2
LIST OF TABLES.................................................................................................................................................... 3
FOREWORD.......................................................................................................................................................... 4
INTRODUCTION................................................................................................................................................... 5
CHAPTER 1. Overall Prevalence and Key Demographic Factors........................................................................ 10
CHAPTER 2. Down Syndrome............................................................................................................................. 18
CHAPTER 3. Neural Tube Defects....................................................................................................................... 25
CHAPTER 4. Congenital Heart Defects............................................................................................................... 33
CHAPTER 5. Orofacial Clefts............................................................................................................................... 42
CHAPTER 6. Limb Deficiency Defects................................................................................................................. 50
CHAPTER 7. Gastroschisis................................................................................................................................... 57
CHAPTER 8. Primary Prevention: Modifiable Risk Factors.................................................................................. 65
CHAPTER 9. Secondary Prevention: Prenatal Screening and Diagnosis............................................................. 73
CHAPTER 10. Management and Outcomes in Orofacial Clefts, Down Syndrome and Spina Bifida.................. 82
CONCLUSION..................................................................................................................................................... 91
APPENDIX A. How Data for the Canadian Congenital Anomalies Surveillance System (CCASS) are Derived... 94
APPENDIX B. Data Tables................................................................................................................................... 99
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CONTRIBUTORS
Albert E. Chudley, University of Manitoba
Philippe De Wals, Laval University
Alison M. Elliott, University of Manitoba
Jane A. Evans, University of Manitoba
K.S. Joseph, University of British Columbia
Ruth Kohut, Alberta Children’s Hospital,
Alberta Health Services
Julian Little, University of Ottawa
R. Brian Lowry, Alberta Children’s Hospital
Amanda MacFarlane, Health Canada
Aideen Moore, The Hospital for Sick Children
Erik Skarsgard, University of British Columbia
Michiel Van den Hof, Dalhousie University
R. Douglas Wilson, University of Calgary
Public Health Agency of Canada
Paromita Deb-Rinker, Nicolas L. Gilbert, Juan
Andrés León, Shiliang Liu, Wei Luo, Rachel
McMillan, Chantal Nelson, Neel Rancourt,
Jocelyn Rouleau
EDITORIAL BOARD MEMBERS
Lead Editor
R. Brian Lowry, Alberta Children’s Hospital
Jane A. Evans, University of Manitoba
Ruth Kohut, Alberta Children’s Hospital,
Alberta Health Services
Public Health Agency of Canada
Juan Andrés León, Wei Luo, Rachel McMillan,
Neel Rancourt, Jocelyn Rouleau
ACKNOWLEDGEMENTS
For scientific review of the report:
Laura Arbour, University of British Columbia
Susie Dzakpasu, Public Health Agency of Canada
Julian Little, University of Ottawa
Amanda MacFarlane, Health Canada
Phil Murphy, Newfoundland and
Labrador Provincial Perinatal Program
Reg Sauve, University of Calgary
Michiel Van den Hof, Dalhousie University
For production and additional editorial support
by Public Health Agency of Canada:
Sharon Bartholomew, Nicolas L. Gilbert,
Chantal Nelson, Victoria Otterman
For contributions to chapters containing
ACASS data:
Barbara Sibbald, Alberta Children’s Hospial
For external data used in this report:
Canadian Institute for Health Information (CIHI)
Alberta Congenital Anomalies Surveillance
System (ACASS)
Système de maintenance et d’exploitation des
données pour l’étude de la clientèle hospitalière
(MED-ÉCHO)
International Clearinghouse for Birth Defects
Surveillance and Research (ICBDSR)
European Surveillance of Congenital Anomalies
(EUROCAT)
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LIST OF FIGURES
Figure 1.1: Total congenital anomaly (CA) rate, Canada (excluding Québec), 1998–2009............................. 11
Figure 1.2: Total congenital anomaly (CA) rate in live births, Canada (excluding Québec), 1998–2009......... 11
Figure 1.3: Total congenital anomaly (CA) rate in stillbirths, Canada (excluding Québec), 1998–2009.......... 12
Figure 1.4: Percentage of stillborn congenital anomaly (CA) cases <750 g,
Canada (excluding Québec), 1998–2009...................................................................................... 12
Figure 1.5A: Total congenital anomaly (CA) rate, by province/territory,
Canada (excluding Québec), 2000–2009 combined..................................................................... 13
Figure 1.5B: Ratio of provincial/territorial congenital anomaly rate to national rate, Canada
(excluding Québec), 2000–2009 combined.................................................................................. 14
Figure 1.6: Total congenital anomaly (CA) rate, by gender, Canada (excluding Québec), 1998–2009........... 15
Figure 1.7: Ratio of total male to total female congenital anomaly cases,
Canada (excluding Québec), 1998–2009...................................................................................... 15
Figure 2.1: Down syndrome (DS) rate, Canada, 1998–2007............................................................................ 19
Figure 2.2A:Down syndrome (DS) rate, by province/territory, Canada, 1998–2007 combined ....................... 19
Figure 2.2B: Ratio of provincial/territorial Down syndrome rate to national rate,
Canada, 1998–2007 combined..................................................................................................... 20
Figure 3.1: Neural tube defect (NTD) rate, Canada, 1996–2007..................................................................... 26
Figure 3.2: Neural tube defect (NTD) rate, by province/territory and time period,
Canada, 1991–2007 combined..................................................................................................... 28
Figure 4.1: Congenital heart defect (CHD) rate, Canada (excluding Québec), 1998–2009............................ 34
Figure 4.2: Rate of selected congenital heart defects (CHD), Canada (excluding Québec), 1998–2009........ 34
Figure 4.3A:Congenital heart defect (CHD) rate, by province/territory,
Canada, 2000–2009 (Quèbec 1998–2007) combined................................................................... 37
Figure 4.3B: Ratio of provincial/territorial congenital heart defect rate to national rate,
Canada, 2000–2009, (Québec 1998–2007) combined.................................................................. 38
Figure 5.1: Total orofacial cleft (OFC) rate, Canada, 1998–2007..................................................................... 43
Figure 5.2A:Orofacial cleft (OFC) rate, by province/territory, Canada, 1998–2007.......................................... 43
Figure 5.2B: Ratio of provincial/territorial orofacial cleft rate to national rate,
Canada, 1998–2007 combined..................................................................................................... 44
Figure 6.1: Limb deficiency defect (LDD) rate, Canada, 1998–2007............................................................... 52
Figure 6.2A:Limb deficiency defect (LDD) rate, by province/territory, Canada, 1998–2007 combined........... 52
Figure 6.2B: Ratio of provincial/territorial limb deficiency defect rate to national rate,
Canada, 1998–2007 combined..................................................................................................... 53
Figure 7.1: Gastroschisis rate, Canada, 2002–2009......................................................................................... 59
Figure 7.2A:Gastroschisis rate, by province/territory, Canada, 2002–2009 combined..................................... 60
Figure 7.2B: Ratio of provincial/territorial gastroschisis rate to national rate,
Canada, 2000–2009 combined..................................................................................................... 61
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LIST OF TABLES
Table 2.1: Down syndrome (DS) rate in live births, Ontario and Québec, Canada, 1998–2007......................21
Table 2.2:
Down syndrome (DS) rate, by maternal age, Alberta,
Canada, 2000-2004, 2005-2009 and 2000–2009............................................................................22
Table 2.3:
Down syndrome international rates, by region/country, 1998–2007...............................................22
Table 2.4:
Percentage of mothers >35 years and Down syndrome terminations;
Down syndrome rate in live births, stillbirths and terminations, by region/country, 2007...............23
Table 3.1:
Prevalence of neural tube defects and relative risks compared to 1996, Canada, 1996–2007.......27
Table 3.2:
Birth prevalence of neural tube defects (NTDs) in USA and Europe...............................................29
Table 4.1:
Rates of specific congenital heart defects,
Alberta and Canada (excluding Québec), 2000–2009 and 1998–2009 ..........................................35
Table 4.2:
Congenital heart defect (CHD) international rates, by region/country, 2000-2005 combined .......36
Table 4.3:
Prevalence of specific subtypes of non-chromosomal congenital heart defects,
EUROCAT Registry, 2000–2005 ......................................................................................................36
Table 5.1:
Cleft lip with or without cleft palate international rate, by region/country, 2007............................45
Table 5.2:
Additional risk factors for orofacial clefts (OFC)..............................................................................46
Table 6.1:
Limb deficiency defect (LDD) international rate, by region/country, 2007......................................54
Table 7.1:
Gastroschisis international rate, by region/country, 2007................................................................62
Table 8.1:
Low nutrient intake/status as potential risk factors for congenital anomalies..................................67
Table 9.1:
Summary of screening and diagnostic factors used in prenatal testing, by trimester.....................74
Table 9.2:
Summary of ultrasound-guided diagnostic procedures, associated risks and accuracy..................75
Table 9.3:
Summary of prenatal screening options..........................................................................................76
Table 10.1: Common health concerns in children with Down syndrome ..........................................................84
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FOREWORD
MESSAGE FROM THE DEPUTY CHIEF PUBLIC HEALTH OFFICER
I am pleased to present
Congenital Anomalies in
Canada 2013: A Perinatal
Health Surveillance Report.
This surveillance report
provides comprehensive
national data and information
to improve our understanding
of congenital anomalies
in Canada.
Approximately 1 in 25 infants is diagnosed yearly
with one or more congenital anomalies. For families,
a congenital anomaly diagnosis can involve
profound psychological, emotional and financial
burdens. For those in public health, congenital
anomalies are an important perinatal health issue
due to the health resources they require for
management and treatment and because of their
ongoing impact on the health and well-being of
Canadian infants, children and their families. On the
bright side, public health strategies, such as folic
acid food fortification and supplementation to
prevent neural tube defects, have proven successful
in Canada.
The Public Health Agency of Canada conducts
national surveillance for congenital anomalies and
other key indicators of maternal, fetal and infant
health through the Canadian Perinatal Surveillance
System. Maintaining quality health surveillance is a
core role of the Agency and a crucial component in
preventing and controlling congenital anomalies
and other adverse perinatal outcomes. It serves to
provide timely identification and communication of
epidemiological trends, estimate the burden of
congenital anomalies, shed light on potential
teratogenic exposures and controllable risk factors,
and guide research. It can also be used to inform
reproductive and maternal and child health
programs, services and policies so that they better
meet the needs of Canadians who rely on them. To
this end, the Agency continues to work in
collaboration with the provinces and territories to
improve congenital anomalies surveillance at all
levels of public health.
It is my hope that this report will be a valuable
resource for healthcare providers, government
organizations and researchers to inform public
health programs and support evidence-based
decision making both in Canada and abroad. Our
ultimate goal is to contribute to reducing the
burden of congenital anomalies in Canada.
I would like to take this opportunity to thank the
many volunteer experts who have dedicated much
time and effort to the realization of this publication.
The Public Health Agency of Canada is pleased to
work with these individuals in our shared
commitment to improving the health of Canadians.
Dr. Gregory Taylor
Deputy Chief Public Health Officer
Public Health Agency of Canada
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INTRODUCTION
CONGENITAL ANOMALIES SURVEILLANCE IN CANADA, 2013
R. Brian Lowry
Juan Andrés León
This is the second national congenital anomalies
surveillance report from the Public Health Agency of
Canada’s Canadian Perinatal Surveillance System
(CPSS). The mission of the CPSS is to contribute to
improved health for pregnant women, mothers and
infants in Canada. Using data from 1998 to 2009,
the report serves to support this mission and
contribute to the Agency’s important function to
provide surveillance information.
The first report1 followed an inaugural scientific
meeting in Aylmer, Québec in 2000 to look at ways
of improving Congenital Anomalies (CAs)
Surveillance in Canada. Following that meeting, the
Canadian Congenital Anomalies Surveillance
Network (CCASN-hereafter referred to as the
Network), was created in 2002 as part of the CPSS.
The goals of the Network have been elaborated
elsewhere.2
Congenital Anomalies in Canada, 2013 provides a
concise overview of six important categories of CAs
in Canada, including Down syndrome, neural tube
defects, congenital heart defects, orofacial clefts,
limb deficiency defects and gastroschisis. It presents
national-level birth prevalence data and temporal
trends; provincial and territorial estimates (including
maps); and international comparisons.
Congenital anomalies, a term used synonymously
with birth defects, are abnormalities that are present
at birth, even if not diagnosed until months or years
later. They are usually structural in nature and can
be present from the time of conception (e.g., Down
syndrome), but largely occur in the embryonic
period (up to the end of the seventh week of
gestation e.g., spina bifida), or in the early fetal
period (eighth to sixteenth week). Occasionally
they are the result of later events such as
environmental insults in later gestation or
exacerbation of pre-existing conditions after
delivery (e.g., some forms of renal cysts).
In Canada, major CAs occur in approximately 3–5%
of newborn infants and in 8% to 10% of stillbirths.
They accounted for 23.2% of infant deaths from
2003–2007, including 23.3% of neonatal deaths,
(i.e., deaths 0–27 days after birth).3 CAs are
second only to immaturity as a leading cause
of infant deaths (1.1 and 1.5 per 1,000 live
births, respectively) and contributed to an
overall infant mortality rate of 5.0 per 1,000 live
births for 2006–2007.3
The World Health Assembly at their 2010 meeting
made a number of statements including the fact
that they were “deeply concerned that Birth Defects
are still not recognized as priorities in public health”
and passed a resolution urging member states to:
“raise awareness among all relevant
stakeholders, including government officials,
health professionals, civil society and the public
about the importance of birth defects as the
cause of child morbidity and mortality”.4
The Second International Conference on Birth
Defects and Disabilities in the Developing World in
September 2005 resulted in the Beijing Manifesto,
which called upon government leaders, health care
providers and Non-Governmental Organizations in
the developing world to take action, stating that:
“until governments focus on preventing birth
defects, infant mortality rates will continue
to be unacceptably high and any decrease
in childhood mortality will be hindered. We
must continue to collaborate to establish
and maintain birth defects surveillance and
monitoring systems, foster research on the
causes and prevention of birth defects and
genetic diseases and establish sustainable
technologically appropriate interventions for
the prevention and care of these conditions
including the provision of genetic services”.5
6 | CONGENITAL ANOMALIES IN CANADA 2013
Although significant steps have been made in
Canada towards better national data, there is still
much to be done. Correa and Kirby6 have discussed
areas of public health where CA surveillance data
plays an important contributing role such as
identifying health disparities and populations at risk,
trend analysis, outcome evaluation, and including
research and prevention. They also suggest that an
increased focus on issues including environmental
risk factors, classification of multiple and isolated
CAs and enabling data linkages would further
strengthen their application and utility.
In 2008 the Government of Canada announced
the Action Plan to Protect Human Health from
Environmental Contaminants which included a
component to enhance CA surveillance nationally.
The Action Plan made resources available to
Canadian jurisdictions to either develop new
surveillance systems or augment existing systems.
Prior to this time only two of ten Provinces and none
of the three Territories had surveillance systems
dedicated to congenital anomalies. It is planned
that national surveillance, which is currently
conducted through the Agency’s Canadian
Congenital Anomalies Surveillance System (CCASS),
will be enhanced as provincial and territorial systems
become established or strengthened. The quality of
data in regional, or provincial systems tends to be
better than in national systems.7,8
This work, linking the Agency with Provinces and
Territories, will maximize comparability across
jurisdictions by promoting the use of common
procedures for surveillance such as consistent data
variables, definitions and collection methods. In
other words, the proposed future model for CA
surveillance in Canada is expected to function
similar to that of the International Clearinghouse for
Birth Defects Surveillance and Research,9
EUROCAT10 and the U.S. National Birth Defects
Prevention Network (NBDPN)11 and will result in an
improved Canadian CA surveillance system.
WHAT CAN WE DO ABOUT
PRIMARY PREVENTION?
Aside from single gene and chromosomally caused
birth defects, the remaining CAs are largely
multifactorial, i.e., caused by the interaction of
genetic and environmental risk factors. Primary
prevention strategies were given a huge boost by
the success of folic acid supplementation, and more
particularly, food fortification in the reduction of
neural tube defects (NTDs) in Canada,12 the United
States13 and Chile.14 It takes a long time for a
scientific discovery to become part of medical
practice which, in the case of folic acid, took about
30 years and has been summarized by Rasmussen et
al.15 They also point out that the success of rubella
vaccination in helping to eliminate Congenital
Rubella Syndrome was due to public health
surveillance and evaluation. In contrast, it is much
harder to change human behaviour. This is
exemplified by the association between alcohol use
and Fetal Alcohol Spectrum Disorder, which is
entirely preventable.
Quality information on risk factors is essential for
developing strategies for primary prevention. Good
data are also emerging with respect to
socioeconomic status, maternal obesity, control of
diabetes, smoking, and the potential benefits of
multivitamin and folic acid usage. Although there is
an increasing body of literature on the effects of
environmental factors such as land waste sites, air
quality, pesticides, electromagnetic fields, as well as
occupational exposures, the evidence is conflicting
and hence does not allow primary prevention
strategies. Therefore, research that overcomes the
limitations of the evidence on these environmental
factors and occupational exposures needs to be
undertaken. Public health initiatives to reduce or
prevent exposures to well known risk factors such as
alcohol use, lack of rubella and varicella
immunization, as well as known teratogenic drugs
such as anti-epileptics (e.g., Valproic Acid,
Carbamazepine), Thalidomide, Isotretinoin, and
ACE Inhibitors should be strengthened.
Pharmacogenetic research may, in the future, aid in
the identification of women at higher risk for drug
induced birth defects.
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Obesity is becoming an increasing problem in
Canada, the United States and indeed in the
developing world. While pre-pregnancy obesity
(body mass index (BMI) ≥ 30 kg/m2) has been
suspected as a risk factor for many years, only in the
past decade has the evidence become more
compelling16-19 especially for NTDs17 and for
selected forms of congenital heart disease.19 Other
CA categories that have been observed to be
associated with maternal obesity are cleft palate,
cleft lip with or without cleft palate, anorectal
atresia, hydrocephalus and limb deficiencies.18
There is an inverse relationship between obesity
and gastroschisis as the latter outcome is more
often related to low prepregnancy BMI in addition
to young maternal age.
Carmichael et al. discussed the underlying
mechanisms that may be responsible for the
increased CA risk for obese and even overweight
women (BMI 25–29.9 kg/m2). 20 They include
nutrition and glycemic control related mechanisms.
Maternal obesity also increases the risk for perinatal
and postnatal problems. Weight reduction prior to
pregnancy thus can be a primary preventive
method. It is an accepted fact that the increased risk
of CAs in poorly controlled diabetic mothers can be
reduced to that of the general population risk with
good glycemic control.
Differences in the occurrence of disease and other
health outcomes by socioeconomic status (SES) are
indicators of disparities in health. SES is usually
estimated by parental income, education,
occupation or area of residence. Ethnicity is also an
influential factor but cannot easily be obtained from
Canadian databases as this information is lacking on
most birth registrations and similar documents.
Infant mortality and morbidity are higher in those
whose parents have lower incomes, even in
countries such as Canada and the United
Kingdom where there is universal healthcare,
indicating the importance of a broad range of
determinants of health.21
Individuals within families of lower SES index often
have other risk factors such as cigarette smoking,
alcohol drinking, poor nutrition, obesity and lack of
multivitamin supplements. Carmichael et al.22
adjusted their results for most of these factors and
still found an association between low SES and
increased risk of D-transposition of the great arteries
(dTGA), as well as a decreased risk of tetralogy of
Fallot (TOF). There was no association with risk of
orofacial clefts. No other types of anomalies were
studied. Yang et al.,23 using data from an NBDPN
study, found low maternal education was associated
with elevated risk for anencephaly and dTGA, while
low paternal education increased anencephaly, cleft
palate, TOF, and dTGA risks.
It seems all too evident that reduction of
socioeconomic inequalities will contribute to reduce
the birth prevalence of some CAs, but this will
require broadly based societal changes such as
providing opportunities and access to full
employment, assisted housing and more education.
This is a national public health challenge requiring
collaboration across many sectors and ongoing
public health surveillance and evaluation.
SUMMARY
The new thrust in reducing the burden of CAs is
primary prevention, but first we must have good
quality surveillance data to provide reliable
provincial, territorial and national prevalence rates.
Prevalence rates and primary prevention are the
subjects of several chapters in this report.
Secondary prevention and management of
selected congenital anomalies are dealt with in
separate chapters.
Folic acid has proven its effectiveness for prevention
of NTDs and when combined with multivitamins,
may reduce the risk for certain other congenital
anomalies. Behavioural changes in the population
will be required as part of the preventive efforts to
reduce or even eliminate the health consequences
associated with smoking, alcohol intake, overweight
and obesity. These will be much harder to achieve
and require effective interventions in the
preconception period. The initiative to enhance CA
surveillance nationally, developed by the Agency in
collaboration with volunteer experts from the
Network, is a significant step forward in the
prevention of CAs in Canada.
8 | CONGENITAL ANOMALIES IN CANADA 2013
REFERENCES
1. Health Canada. Congenital Anomalies in
Canada — A Perinatal Health Report, 2002.
Ottawa: Minister of Public Works and
Government Services Canada, 2002.
2. Public Health Agency of Canada. What is
CCASN? [Internet]. 2006 [cited 2011 Nov].
Available from: http://www.phac-aspc.gc.ca/
ccasn-rcsac/index-eng.php.
3. Public Health Agency of Canada. Perinatal
Health Indicators for Canada, 2011. Ottawa:
Public Health Agency of Canada, 2012.
4. World Health Organization. Birth Defects.
Sixty-Third World Health Assembly. Agenda
item 11.7. [Internet]. 2012 [cited 2012 Feb].
Available from: http://apps.who.int/gb/ebwha/
pdf_files/WHA63/A63_R17-en.pdf.
5. International Birth Defects Information Systems.
Beijing Manifesto: 2nd International Conference
on Birth Defects & Disabilities in the
Developing World, September 2005, Beijing,
China [Internet]. 2010 [cited 2012 Feb 13].
Available from: http://www.ibis-birthdefects.
org/start/icbd_manifesto.htm.
6. Correa A, Kirby RS. An expanded public health
role for birth defects surveillance. Birth Defects
Res A Clin Mol Teratol. 2010;88(12):1004-7.
7. Rouleau J, Arbuckle TE, Johnson KC, et al.
Description and limitations of the Canadian
Congenital Anomalies Surveillance System
(CCASS). Chronic Dis Can. 1995;16(1):37-42.
8. Lowry RB. Congenital anomalies surveillance in
Canada. Can J Public Health. 2008;99(6):483-5.
9. International Clearinghouse for Birth Defects.
Welcome to the ICBDSR [Internet]. 2011 [cited
2011 Nov]. Available from:
http://www.icbdsr.org.
10. Dolk H. EUROCAT: 25 Years of European
surveillance of congenital anomalies. Arch Dis
Child Fetal Neonatal Ed. 2005;90(5):F:355-8.
11. National Birth Defects Prevention Network.
Welcome [Internet]. 2011 [cited 2011 Nov].
Available from: www.nbdpn.org.
12. De Wals P, Tairou F, Val Allen MI, et al.
Reduction in neural-tube defects after folic acid
fortification in Canada. N Engl J Med. 2007;357
(2):135-42.
13. Honcin MA, Paulozzi LJ, Mathews TJ, et al.
Impact of folic acid fortification of the US food
supply on the occurrence of neural tube
defects. JAMA. 2001;285(23):2981-6.
14. Lopez-Camelo JS, Orioli IM, da Graca Dutra M,
et al. Reduction of birth prevalence rates of
neural tube defects after folic acid fortification in
Chile. Am J Med Genet A. 2005;135(2):120-5.
15. Rasmussen SA, Erickson JD, Reef SE, et al.
Teratology: from science to birth defects
prevention. Birth Defects Res A Clin Mol
Teratol. 2009;85(1):82-92.
16. Waller DK, Shaw GM, Rasmussen SA, et al.
Prepregnancy obesity as a risk factor for
structural birth defects. Arch Pediatr Adolesc
Med. 2007;161(8):745-50.
17. Rasmussen SA, Chu SY, Kim SY, et al. Maternal
obesity and risk of neural tube defects: a
Metaanalysis. Am J Obstet Gynecol.
2008;198(6):611-9.
18. Stothard KJ, Tennant PW, Bell R, et al. Maternal
overweight and obesity and the risk of
congenital anomalies: a systematic review and
meta-analysis. JAMA. 2009;301(6):636-50.
19. Gilboa SM, Correa A, Botto LD, et al.
Association between prepregnancy body mass
index and congenital heart defects. Am J
Obstet Gynecol. 2010;202(1):51.e1-10.
20. Carmichael SL, Rasmussen SA, Shaw GM.
Prepregnancy obesity: a complex risk factor for
selected birth defects. Birth Defects Res A Clin
Mol Teratol. 2010;88(10):804-10.
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21. Commission on Social Determinants of Health.
Closing the gap in a generation: health equity
through action on the social determinants of
health. Final Report of the Commission on
Social Determinants of Health. Geneva: World
Health Organization; 2008
22. Carmichael SL, Nelson V, Shaw GM, et al.
Socio-economic status and risk of conotruncal
heart defects and orofacial clefts. Paediatr
Perinat Epidemiol. 2003;17(3):264-71.
23. Yang J, Carmichael SL, Canfield M, et al.
Socioeconomic status in relation to selected
birth defects in a large multicentered US
case-control study. Am J Epidemiol.
2008;167(2):145-54.
10 | CONGENITAL ANOMALIES IN CANADA 2013
CHAPTER 1
OVERALL PREVALENCE AND KEY DEMOGRAPHIC FACTORS
Jane A. Evans
Chantal Nelson
In order to evaluate the impact of congenital
anomalies on individuals, families and the public
health system, it is important to have reliable
estimates of the number of affected births. This is
not straightforward as factors such as sources for
case ascertainment, criteria for inclusion and
exclusion and length of time of follow-up will all
impact on the overall birth prevalence. Currently,
the Public Health Agency of Canada’s Canadian
Congenital Anomalies Surveillance System (CCASS)
uses discharge abstract data (DAD) on newborns,
collected from provincial and territorial hospitals via
the Canadian Institute for Health Information (CIHI)
and the Québec Système de maintenance et
d’exploitation des données pour l’étude de la
clientèle hospitalière (MED-ÉCHO). More detailed
provincial data are also submitted to CCASS by the
Alberta Congenital Anomalies Surveillance System
(ACASS). The CCASS data from CIHI are limited for
surveillance purposes in several ways: they rely on
invalidated International Classification of Diseases
(ICD) codes; the anomalies are only ascertained in
infants less than 30 days of age because of
administrative reasons (Appendix A); they do not
contain easily available information on gestational
age; and they are restricted to live births and
stillbirths, thus not allowing capture of terminations
of pregnancy for congenital anomalies before 20
weeks of gestation.1 Using MED-ÉCHO data is also
problematic as there are differences in the coding of
anomalies in stillbirths and in inclusion and exclusion
criteria, especially with respect to less well defined
and/or minor defects.
In this report, most data on the six types of
anomalies selected for review are largely based on
CCASS data for all provinces and territories from
1998–2007. This section on overall prevalence rates
and key demographic factors is based on a slightly
different data set in order to be both more current
and more consistent. It includes cases from 1998–
2009 but relies only on CIHI data, thus Québec
cases are excluded.
The total frequency of major congenital anomalies
in live births and stillbirths is often estimated to be
3–5%, though few surveillance systems report an
overall figure because of considerable variation in
ascertainment, definitions and inclusion/exclusion
criteria. CCASS data for seven provinces—British
Columbia, Alberta, Saskatchewan, Manitoba,
Ontario, Prince Edward Island and Newfoundland
and Labrador (approximately 70% of births)—
indicated a rate of 420.1 per 10,000 total births (live
births and stillbirths) in 1984–1986 and a similar rate
of 423.1 per 10,000 in 1991–1993.2 Figure 1.1
shows the prevalence trend in total births from 1998
to 2009 and indicates that rates have declining over
this time period. The higher rates during 1998 to
2001 compared to those noted after 2001 may be
due to better ascertainment. Part of the decline
subsequent to 2001 can be attributed to a shorter
ascertainment period from one year to 30 days.
Other factors may include increasing use of prenatal
diagnosis and screening and a reduction in certain
malformations, especially neural tube defects, since
the mandatory fortification of certain grain products
with folic acid in 1998.
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FIGURE 1.1
Total congenital anomaly (CA) rate, Canada (excluding Québec),* 1998–2009
CA per 10.000 total births**
500
460.5
450
451.2
448.1
441.8
431.9
414.9
400
406.7
402.1
383.1
350
1998
1999
2000
2001
2002
2003
2004
2005
2006
377.5
2007
385.3
385.2
2008
2009
Source: Public Health Agency of Canada. Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
**Total births include live births and stillbirths.
FIGURE 1.2
Total congenital anomaly (CA) rate in live births, Canada (excluding Québec),* 1998–2009
CA per 10,000 live births
500
448.7
450
441.5
435.1
419.3
430.2
400
401.8
395.2
389.7
369.6
350
300
1998
1999
2000
2001
2002
2003
2004
2005
2006
362.2
2007
370.6
371.1
2008
2009
Source: Public Health Agency of Canada. Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
Figure 1.2 indicates that the decrease in rates
among live births has been notable, leading to a
birth prevalence below 400 per 10,000 in 2009.
However, as can be seen from Figure 1.3, the rates
in stillbirths seem to have increased slightly. This is
largely due to an increase in congenital anomalies in
stillbirths of low birth weight, such that over threequarters of the congenital anomalies in stillbirths are
seen in fetuses less than 750 g (Figure 1.4). There
has also been a significant increase in the
proportion of malformed stillbirths for which no
birth weight is available. These factors suggest that
most of the increase of congenital anomalies in
stillbirths (and the concomitant decrease in live
births), is due to a higher frequency of terminations
of pregnancy for fetal malformation at 21–24 weeks
continuing a trend that has been previously
documented.3 The true impact of prenatal diagnosis
and pregnancy terminations on stillbirths is,
however, difficult to assess as the coding of the
cause of a stillbirth as due to congenital
malformation or termination of pregnancy can
be somewhat arbitrary and is not consistent
across jurisdictions.
12 | CONGENITAL ANOMALIES IN CANADA 2013
FIGURE 1.3
Total congenital anomaly (CA) rate in stillbirths, Canada (excluding Québec),* 1998–2009
2,500
CA per 10,000 stillbirths
2,317.0
2,300
2,100
1,900
2,202.1
2,146.8
2,144.4
2,258.5
2,187.7
2,159.3
2,134.6
1,984.6
2,213.8
2,009.7
1,947.3
1,700
1,500
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Source: Public Health Agency of Canada. Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
FIGURE 1.4
Percentage of stillborn congenital anomaly (CA) cases <750 g, Canada (excluding Québec),* 1998–2009
90
80.9%
Percentage of total
stillborn cases with CA
80
73.2%
70
60
75.8%
73.6%
68.5%
66.3%
71.0%
69.8%
66.1%
63.1%
75.4%
71.4%
62.4%
65.6%
67.2%
73.9%
77.3%
68.9%
72.8%
74.4%
Of stillborn cases with
known birthweight
64.0%
Of all stillborn cases
55.4%
54.3%
2007
2008
50
57.3%
40
30
1998
1999
2000
2001
2002
2003
2004
2005
2006
Source: Public Health Agency of Canada. Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
2009
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From Figure 1.5A, it can be seen that there are
variations in rates between provinces and territories
ranging from a low of 347.8 (95% CI: 338.2–357.6)
per 10,000 total births in Manitoba to a high of
622.1(95% CI: 599.6–645.3) per 10,000 total births
in Newfoundland and Labrador. Confidence
intervals are wide in those areas where the numbers
of cases are small (fewer than 40 per year in each of
the Territories). Thus rates from such jurisdictions
should be interpreted with caution. In addition,
many factors will influence regional variation,
including methods of case ascertainment and
coding, the availability of prenatal diagnosis and
screening services and their utilization, as well as
the likelihood of pregnancy termination of
prenatally diagnosed cases.
FIGURE 1.5A
Total congenital anomaly (CA) rate, by province/territory, Canada (excluding Québec),* 2000–2009 combined
CANADA
Newfoundland and Labrador
Prince Edward Island
Nova Scotia
New Brunswick
Ontario
Manitoba
Saskatchewan
Alberta
British Columbia
Yukon
Northwest Territories
Nunavut
0
100
200
300
400
500
600
700
800
CA (95% CI) per 10,000 total births**
Source: Public Health Agency of Canada. Congenital Anomalies Surveillance System, 2000–2009.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths. CI—Confidence Interval
14 | CONGENITAL ANOMALIES IN CANADA 2013
FIGURE 1.5B
Ratio of provincial/territorial congenital anomaly rate to national rate,** Canada, (excluding Québec) 2000–2009 combined
Birth Prevalance Ratios
> 1.50
1.26 - 1.50
1.01 - 1.25
0.76 - 1.00
<0.76
No Cases or Suppressed
*
Statistical Significance
YT
NT
BC
AB*
NU*
NL*
SK*
MB*
ON*
QC
NL*
PE
NB*
NS*
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2000–2009.
**This ratio calculates the birth prevalence rate per 10,000 total births of each individual province/territory to the birth prevalence rate for Canada
during the specified time period. The birth prevalence for Canada includes cases for which province/territory is unknown.
***Québec was excluded because data were not available for all years.
It has long been recognized that overall congenital
anomaly rates, and those for the majority of
individual defects, are higher in males.4 From Figure
1.6, it can be seen that the birth prevalence has
fallen for both sexes. However, the ratio of male to
female cases has increased slightly with time (Figure
1.7). This could be due to a variety of factors
including higher rates of specific anomalies that are
restricted to males (hypospadias), or are more
common in males, such as Down syndrome and
renal agenesis. It could also be due to sex
differences in rates of survival, early termination for
fetal anomaly or the differing impact of preventive
strategies such as folic acid fortification on male and
female fetuses. Another factor could be a relative
increase in multiple congenital anomalies, which are
more common in males.
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FIGURE 1.6
Total congenital anomaly (CA) rate, by gender, Canada (excluding Québec),* 1998–2009
300
CA per 10,000 total births**
256.8
250
255.7
249.4
200
193.6
196.7
251.0
242.3
233.5
231.9
227.0
1998
1999
221.7
223.5
162.0
160.0
2008
2009
204.4
190.3
189.1
180.9
174.2
174.1
2004
2005
150
100
212.2
218.5
2000
2001
2002
2003
163.7
163.7
2006
2007
Male
Female
Source: Public Health Agency of Canada. Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths.
FIGURE 1.7
Ratio of total male to total female congenital anomaly cases, Canada (excluding Québec),* 1998–2009
1.45
Male cases/female cases
1.40
1.35
1.30
1.33
1.40
1.33
1.27
1.25
1.37
1.34
1.32
1.28
1.29
2002
2003
1.30
1.30
1.25
1.20
1.15
1.10
1.05
1.00
1998
1999
2000
2001
2004
2005
2006
2007
2008
2009
Source: Public Health Agency of Canada. Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
The inability to easily differentiate isolated birth
defects from various patterns of multiple congenital
anomalies (syndromes, sequences, associations,
etc.) in the CCASS data is another drawback of the
current system. An exploratory analysis of orofacial
clefts (OFCs) divided cases into those with a single
code for a CA and those with codes in addition to
the one for the OFC. While it has not yet been
possible to validate whether this adequately
distinguishes isolated cases from those with other
anomalies, the data do indicate that the decline in
cleft lip with or without cleft palate (CL ± CP)
observed over time (see Chapter 5), appears to be
more pronounced for “isolated” cases than for
more complex ones. In addition, the ratio of
“isolated” to complex ones appears to differ
between provinces.
16 | CONGENITAL ANOMALIES IN CANADA 2013
Further use of Canadian surveillance data to
evaluate trends in multiple anomalies, as has been
explored by others,5,6 would clearly be worthwhile.
Many risk factors, including environmental
teratogens, can cause multiple CAs (e.g., limb
deficiencies, heart defects and intestinal atresias
with thalidomide, central nervous system defects
and OFCs with maternal hyperthermia) or
combinations of major and minor defects (e.g., in
Fetal Alcohol Syndrome). Thus more detailed
analysis of anomaly codes would add considerably
to the value of surveillance data for monitoring the
impact of environmental risk factors. For example, a
case definition including codes for ear defects,
certain central nervous system defects and selected
heart malformations was used by the Atlanta Birth
Defects Surveillance System to identify cases of
isotretinoin embryopathy with a sensitivity of 45.5%
and a specificity of 99.9%. The positive predictive
value of the combination was 85%.6
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REFERENCES
1. Lowry RB. Congenital anomalies surveillance in
Canada. Can J Public Health. 2008;99(6):483-5.
2. Johnson KC, Rouleau J. Temporal trends in
Canadian birth defects birth prevalences,
1979-1993. Can J Public Health. 1997;88(3):
169-76.
3. Liu S, Joseph KS, Wen SW. Trends in fetal and
infant deaths caused by congenital anomalies.
Semin Perinatol. 2002;26(4):268-76.
4. Lisi A, Botto LD, Rittler M, et al. Sex and
congenital malformations: an international
perspective. Am J Med Genet A.
2005;134A(1):49-57.
5. Puho EH, Czeizel AE, Acs N, et al. Birth
outcomes of cases with unclassified multiple
congenital abnormalities and pregnancy
complications in their mothers depending on
the number of component defects. Populationbased case-control study. Congenit Anom
(Kyoto). 2008;48(3):126-36.
6. Lynberg MC, Khoury MJ, Lammer EJ, et al.
Sensitivity, specificity, and positive predictive
value of multiple malformations in isotretinoin
embryopathy surveillance. Teratology.
1990;42(5):513-9.
18 | CONGENITAL ANOMALIES IN CANADA 2013
CHAPTER 2
DOWN SYNDROME
Ruth Kohut
Jocelyn Rouleau
INTRODUCTION
RISK FACTORS
Down syndrome (DS) is one of the most common
congenital anomalies worldwide, occurring in
approximately 1 in 800 births.1,2 This chromosomal
disorder, associated with the presence of extra
chromosome 21 material, is characterized by a welldefined phenotype, intellectual delay, and a number
of major and minor congenital anomalies; most
commonly, congenital heart and gastrointestinal
defects.1,2
Advanced maternal age is the most significant
established risk factor for DS. Prenatal screening has
advanced in both accuracy and early detection such
that it has had a significant impact on the DS live
birth prevalence across all maternal ages,
worldwide. This will be further discussed in
Chapter 9.
Babies with chromosomal disorders, including DS,
tend to be small in size and have low birth weight.
Very low birth weight (401 to 1500 g) has been
reported to be twice as prevalent among infants
with DS as among total births.3 Excluding
complications of low birth weight, the overall oneyear survival of DS infants with and without
congenital heart defects has been reported
between 78–90% and 93–97% respectively.4
Congenital heart defects and respiratory infections
are the most frequently reported causes of deaths in
children and young adults with DS.4 Childhood
leukemia is commonly associated with DS, whereas
other malignancies are less frequent than expected.5
Awareness and monitoring of potential medical
health risks and early intervention greatly decrease
morbidity and improve the quality of life among
individuals with DS.6
In addition to advanced maternal age, having a
previously affected child or other family history of
DS are additional risk factors that warrant referral for
genetic counselling. The recurrence risk for fetal
trisomy after having had one affected child is
roughly 1%. A family history of DS and/or recurrent
miscarriages may suggest that a chromosome
translocation involving chromosome 21 is
segregating within the family, which can be
confirmed or ruled out by parental karyotyping.
PREVALENCE RATE OF DOWN SYNDROME
IN CANADA
As depicted in Figure 2.1, the birth prevalence of
Down syndrome in Canada for 1998–2007 was
relatively constant, averaging 14.1 per 10,000 total
births. This rate was similar to previously reported
rates for 1989–1997.7 Both the live birth and
stillbirth DS rates have also remained relatively
stable at 12.4 and 1.7 per 10,000 total births,
respectively. Congenital heart defects were reported
in 40.9% of DS cases, of which 98% were reported
as live births.
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FIGURE 2.1
Down syndrome (DS) rate, Canada, 1998–2007
18
DS per 10.000 total births*
17
16
15.1
15
14.2
14
15.0
14.9
14.1
14.5
13.3
13
13.8
13.4
13.0
12
11
10
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths.
FIGURE 2.2A
Down syndrome (DS) rate, by province/territory, Canada, 1998–2007 combined
CANADA
Newfoundland and Labrador
Prince Edward Island
Nova Scotia
New Brunswick
Quebec
Ontario
Manitoba
Saskatchewan
Alberta
British Columbia
Yukon §
Northwest Territories
Nunavut
0
10
20
30
40
DS (95% CI) per 10,000 total births*
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths.
§Rate suppressed due to small cell counts (<5). CI—Confidence Interval
50
20 | CONGENITAL ANOMALIES IN CANADA 2013
PROVINCIAL AND TERRITORIAL
PREVALENCE RATES
Québec to 21.5 (95% CI: 9.8–40.8) and 24.2 (95%
CI: 14.3–38.3) in Nunavut and Northwest Territories
respectively. Given the low number of cases and
total births (see Table B2.2 in Appendix), the high
rates in the less populated northern territories may
be due, in part, to chance and should therefore be
interpreted with caution.
Variation exists in the provincial and territorial DS
birth prevalence rates (live births and stillbirths) for
the ten years combined (Figure 2.2A and 2.2B). The
DS rate ranged from 11.2 (95% CI: 10.5–12.0) in
FIGURE 2.2B
Ratio of provincial/territorial Down syndrome rate to national rate,** Canada, 1998–2007 combined
Birth Prevalance Ratios
> 1.50
1.26 - 1.50
1.01 - 1.25
0.76 - 1.00
<0.76
No Cases or Suppressed
*
Statistical Significance
YT
NT*
BC*
AB
NU
NL
SK
MB
ON
NL
QC*
PE
NB
NS*
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
**This ratio calculates the birth prevalence rate per 10,000 total births of each individual province/territory to the birth prevalence rate for Canada
during the specified time period. The birth prevalence for Canada includes cases for which province/territories is unknown.
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Advanced maternal age, as well as access to, and
utilization of prenatal diagnosis and selective
termination of affected pregnancies influence the
birth prevalence of DS. Eighteen percent of total
births in Canada were to mothers 35 years of age or
older in 2007.8 Although the reported DS birth
prevalence rate in Nunavut was high, the proportion
of births to women over 35 years of age in this
territory was the lowest in Canada (8%) in 2007.
A similar observation was noted in the
Northwest Territories.
Roughly 60% of all births occur in the provinces of
Québec (21.7%) and Ontario (39.4%). A comparison
of DS live birth rates from 1998 to 2007 for these
two provinces is presented in Table 2.1. The DS live
birth rate in Québec was significantly lower than in
Ontario for the combined years (10.8 versus 12.5,
respectively). Further, 15.4% of live born deliveries
were to women of over 35 years in Québec
compared with 21.2% in Ontario in 2007 (rates
similar for 2003 to 2006).8 There was a significant
difference in live birth rates of DS between the two
provinces in 2006 and 2007. A downward trend is
noted in Québec that is not seen in Ontario. As the
data sources for live birth in these two provinces are
very comparable, this suggests that access to
prenatal diagnosis and resulting termination of
DS pregnancies may be higher in Québec
compared to Ontario.
TABLE 2.1
Down syndrome (DS) rate in live births, Ontario and Québec, Canada, 1998–2007
Ontario DS rates
per 10,000 live births (95% CI)
Year
Québec DS rates
per 10,000 live births (95% CI)
1998
10.6 (8.9–12.4)
13.4 (10.9–16.3)
1999
13.3(11.4–15.4)
12.3(9.9–15.2)
2000
13.0(11.1–15.1)
11.9(9.5–14.7)
2001
12.9(11.0–14.9)
9.4(7.3–12.0)
2002
12.8(11.0–14.9)
10.2(8.0–12.8)
2003
13.6(11.7–15.8)
10.5(8.3–13.2)
2004
11.9(10.1–13.8)
11.5(9.1–14.2)
2005
10.9 (9.3–12.8)
12.1(9.8–14.9)
2006
14.0(12.1–16.1)
9.1(7.2–11.4)
2007
12.1(10.3–14.0)
7.9 (6.1–10.0)
1998–2007
12.5(11.9–13.1)
10.8(10.1–11.6)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
CI—Confidence Interval
22 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE 2.2
Down syndrome (DS) rate, by maternal age, Alberta, Canada, 2000–2004, 2005–2009 and 2000–2009
DS rate by maternal age (95% CI)*
Year
<20
20–24
25–29
30–34
35–39
>40
Total
2000–2004
8.0
(3.7–15.1)
6.4
(4.2–9.5)
10.7
(8.2–13.7)
16.6
(13.4–20.4)
52.4
(43.7–62.4)
143.1
(110.3–182.8)
19.6
(17.7–21.7)
2005–2009
7.6
(3.5–14.4)
7.3
(5.0–10.3)
10.7
(8.5–13.3)
16.8
(13.9–20.1)
53.8
(45.9–62.6)
189.3
(156.1–227.8)
21.8
(19.9–23.7)
2000–2009
7.8
(4.6–12.3)
6.9
(5.2–8.9)
10.7
(9.0–12.6)
16.7
(14.5–19.1)
53.2
(47.3–59.7)
169.5
(145.5–196.5)
20.8
(19.5–22.2)
Source: Alberta Congenital Anomalies Surveillance System, 2011.
*Per 10,000 total births. Total births include live births, stillbirths and terminations of pregnancy.
CI—Confidence Interval
TABLE 2.3
Down syndrome international rates,* by region/country, 1998–2007
Region/country
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
CANADA†
14.2
14.5
15.1
13.3
14.1
15.0
13.4
14.9
13.8
13.0
Alberta, Canada
14.0
11.6
14.6
15.2
12.7
19.2
16.5
20.5
13.4
16.4
Atlanta, USA
11.5
12.0
11.1
13.2
12.5
13.0
13.0
12.9
10.9
13.1
Paris, France
10.5
5.2
7.9
7.8
6.2
4.7
5.3
9.1
7.1
8.7
Tuscany, Italy
6.3
6.1
4.9
5.7
3.8
4.0
4.1
4.1
4.6
4.8
11.3
10.0
11.8
14.2
14.2
12.3
12.2
11.7
14.2
14.0
Finland
Source: International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) Annual Report, 2009 (data from 2007)
†Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2007.
*Rate per 10,000 total births. Total births include live births and stillbirths.
Regional differences in maternal age-specific total
prevalence rates of DS are not available. Data from
the province of Alberta that include terminations of
pregnancy are outlined in Table 2.2. Mothers over
35 years of age had significantly higher DS
prevalence rates than mothers aged 25–29 years
during the combined years 2000–2009.
INTERNATIONAL COMPARISONS
In 2007, there were 1,430,697 DS births among
23 worldwide surveillance programs reporting to the
International Clearinghouse for Birth Defects
Surveillance and Research (ICBDSR).9 Canada
reported 483 cases through the Canadian
Congenital Anomalies Surveillance System (CCASS)
for that period. DS birth prevalence rates from 1998
to 2007 among a sample of ICBDSR registries are
presented in Table 2.3.
In a study including 20 ICBDSR registries between
1993 and 2004, the overall prevalence of DS
remained relatively stable at 8.3 per 10,000 total
births (live and stillbirths).10 During this time period,
however, the birth prevalence of DS decreased in
registries in France and Italy, and increased in others
including Israel, Norway and Alberta, Canada. The
mean termination rate of DS confirmed pregnancies
among the 20 registries increased from 4.8 per
10,000 total births in 1993 to 9.9 in 2004.
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TABLE 2.4
Percentage of mothers >35 years and Down syndrome terminations;
Down syndrome rate in live births, stillbirths and terminations, by region/country, 2007
Prevalence rate (per 10,000)
Region/Country
% of mothers >35 yr
% of terminations in
mother >35 yr
LB+SB
LB+SB+
terminations
Texas, USA
11.4
5.4
49.3
52.1
Alberta, Canada
15.5
40.0
51.5
85.9
Atlanta, USA
17.0
17.0
39.0
48.3
Sweden
21.7
73.2
18.2
67.6
Paris, France
28.6
83.1
8.0
47.5
Tuscany, Italy
32.1
70.6
10.1
34.2
Source: International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) Annual Report, 2009 (data from 2007).
LB—Live Birth, SB—Stillbirth
IMPACT OF PRENATAL DIAGNOSIS ON
BIRTH PREVALENCE OF DOWN SYNDROME
The impact of maternal age and prenatal diagnosis
on the DS prevalence rate, according to the ICBDSR
Collaborative Research Project,9 is presented in
Table 2.4. Improved access and performance of
prenatal screening are believed to have offset the
effect of increased rates in advanced maternal age
at birth throughout various jurisdictions. According
to this international study, the greatest termination
rates are in registries that show higher percentages
of advanced maternal age mothers.
The impact of prenatal diagnosis on the DS birth
prevalence rate in Canada requires provincial and
territorial termination data. With the exception of
Alberta, termination data are not currently reported
by provincial and territorial congenital anomalies
surveillance systems, nor are they captured
by CCASS.
For the combined years 1998–2007, age-specific
data from the Alberta Congenital Anomalies
Surveillance System did not demonstrate the
maternal age specific variation in termination rates
seen in 2007 by ICBDSR (Table 2.4). For the 10
years combined in Alberta, 52.4% of the total
confirmed DS pregnancies occurred among women
35 years of age or older; of these, 24% (range:
16.9% to 30.5%) were terminated, which was a
similar rate to that seen for women less than
35 years of age.
The Society of Obstetricians and Gynaecologists of
Canada (SOGC) published clinical care guidelines
for prenatal testing11 that advise against using
maternal age as the sole indication for invasive
prenatal diagnosis. They recommend that prenatal
screening for clinically significant fetal aneuploidies
be offered to all pregnant women. However, the
methods used for screening and their availability
vary between and even within provinces. Moreover,
the uptake of screening and utilization of prenatal
diagnosis is not captured within a single
national registry.
SUMMARY
Down syndrome remains the most frequently
occurring chromosome anomaly in Canada and has
an impact on infant morbidity and mortality as well
as childhood and adult morbidity. Despite the rising
rates of advanced maternal age at delivery, the
national birth prevalence rates have remained stable
over the 1998–2007 time period. This is most likely
due to increased access and utilization of prenatal
screening and testing and subsequent termination
of pregnancies affected with aneuploidy.
Continuing population-based surveillance and
research relating to the impact of prenatal testing
on the birth prevalence rates and the impact of
various pre- and postnatal factors that influence the
morbidity and mortality of babies born with DS is of
great public health importance in Canada.
24 | CONGENITAL ANOMALIES IN CANADA 2013
REFERENCES
1. Gardner RJM, Sutherland GR. Chromosome
Abnormalities and Genetic Counseling. 3rd Ed.
Toronto: Oxford University Press; 2004. p.
249-252.
7. Health Canada. Congenital Anomalies in
Canada — A Perinatal Health Report, 2002.
Ottawa: Minister of Public Works and
Government Services Canada, 2002.
2. World Health Organization. Birth Defects.
Report by the Secretariat. Sixty-Third World
Health Assembly. Provisional agenda item 11.7
[Internet]. 2010 Apr [cited 2011 Nov]. Available
from: http://apps.who.int/gb/ebwha/pdf_files/
WHA63/A63_10-en.pdf.
8. Statistics Canada. Births 2007. Ottawa: Minister
of Industry; 2009. Catalogue no. 84F0210X.
3. Boghassian NS, Hansen NI, Bell EF, et al.
Survival and morbidity outcomes for very low
birth weight infants with Down syndrome.
Pediatrics. 2010;126(6):1132-40.
4. Irving C, Basu A, Richmond S, et al.
Twenty-year trends in prevalence and
survival of Down syndrome. Eur J Hum Genet.
2008;16(11):1336-40.
5. Yang Q, Rasmussen SA, Friedman JM. Mortality
associated with Down’s syndrome in the USA
from 1983-1997: a population based study.
Lancet. 2002;359(9311):1019-25.
6.
Bull MJ, the Committee on Genetics. Clinical
Report - Health supervision for children with
Down syndrome. Pediatrics. 2011;128(2):393-406.
9. International Clearinghouse for Birth Defects
Surveillance and Research. Annual Report 2009
with data for 2007. Rome, Italy: International
Center on Birth Defects; 2009. Available from:
http://www.icbdsr.org/filebank/documents/
ar2005/Report2009.pdf.
10. Cocchi G, Gualdi S, Bower C, et al.
International trends of Down syndrome 19932004: births in relation to maternal age and
terminations of pregnancies. Birth Defects Res
A Clin Mol Teratol. 2010;88(6):474-479.
11. Chitayat D, Langlois S, Wilson RD; SOGC
Genetics Committee; CCMG Prenatal
Diagnosis Committee. Prenatal screening for
fetal aneuploidy in singleton pregnancies. Joint
SOGC-CCMG Clinical Practice Guideline 261.
J Obstet Gynaecol Can. 2011;33(7):736-50.
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CHAPTER 3
NEURAL TUBE DEFECTS
Nicolas L. Gilbert
Philippe De Wals
Juan Andrés León
Jane A. Evans
INTRODUCTION
Neural tube defects (NTDs) are a group of
heterogeneous anomalies of the central nervous
system caused by defective closure of the neural
tube during embryogenesis. The most common
NTDs are spina bifida, anencephaly, and
encephalocele. Anencephaly is lethal. Spina bifida
patients experience substantial morbidity
throughout life, and elevated mortality rates.1
RISK FACTORS
NTDs can occur in chromosomal disorders, genetic
syndromes and other patterns of multiple
malformations or be the result of an environmental
teratogen. In such cases, other congenital
malformations are often present. Most NTDs,
however, are isolated defects due to multifactorial
inheritance (i.e., the interaction of genetic and
environmental risk factors). In such cases, the
recurrence risk is 2–5% depending on baseline
population risk, but can be significantly reduced by
periconceptional folic acid supplementation.2
Folate deficiency3 is the most well established risk
factor for isolated NTDs. Inadequate intake of folic
acid from all sources (foods naturally rich in folate,
foods fortified with folic acid and folic acid
containing supplements) remains an important
modifiable risk factor in Canada and throughout
the world.
Fetuses of mothers who have the C677T variant of
the gene coding for 5,10-methylenetetrahydrofolate
reductase, an enzyme involved in folate metabolism,
are at increased risk for spina bifida4 and
anencephaly.5 Potentially other enzyme variants also
increase risk. Other risk factors whose association to
folate metabolism is less clear include certain ethnic
backgrounds (e.g., Celtic populations, Sikhs,
French Canadians, Hispanics),6 maternal obesity,7
pre-gestational diabetes8 and other forms of
hyperglycemia.9
Non-folate sensitive NTDs include some isolated
forms such as lipomyelomeningoceles,10 those due
to certain environmental exposures (e.g., valproic
acid,11 hyperthermia12 ), or suboptimal intake of
other micronutrients (e.g., vitamin B1213), as well as
those seen in patterns of multiple malformations.
Risks for these disorders would not be impacted by
food fortification with folic acid or supplementation
and thus they may be becoming proportionately
more common as causes of NTDs.
PREVALENCE RATE OF NEURAL TUBE
DEFECTS IN CANADA
The prevalence rate of all NTDs (including spina
bifida) in Canada declined between 1996 and 2007
(Figure 3.1). After falling sharply between 1997 and
1998, following the introduction of folic acidfortified flour on the North American market,14-16 the
prevalence of NTDs in general and spina bifida in
particular, continued to decline between 1999 and
2004, before leveling off. These trends are similar to
those observed by De Wals et al.,14 who noted a
decline in seven Canadian provinces postfortification. However, anomaly rates reported by
the Canadian Congenital Anomalies Surveillance
System (CCASS) are much lower than those from De
Wals’ study. This is due in large part to the exclusion
of terminations before 20 weeks by CCASS.
Based on the time course of population levels of
blood folate, it is assumed that births that occurred
before or during 1996 were conceived and had their
first gestational trimester in the pre-fortification
26 | CONGENITAL ANOMALIES IN CANADA 2013
period. Those that occurred in 1998 and 1999 were
conceived and had their first trimester while some
fortified food was available on the Canadian market
but before fortification became mandatory, and
those that occurred in 2001 were conceived in the
full fortification period.15 Compared to births from
the end of the pre-fortification era (i.e., 1996), those
from the early post-fortification era (i.e., 2001–2003),
had a 40% reduction in NTD prevalence and 46%
reduction in the prevalence of spina bifida. These
rates continued to decline in 2004–2007 (Table 3.1).
Other factors that may have contributed to the
decline of NTDs and spina bifida, in particular after
2001, include folic acid supplementation and
increased prenatal screening and diagnosis.
According to the Canadian Community Health
Survey, the proportion of Canadian mothers who
had taken folic acid supplements in the
periconceptional period increased from 47.2% to
57.8% between 2001 and 2005.17
FIGURE 3.1
Neural tube defect (NTD) rate, Canada, 1996–2007
NTD per 10,000 total births*
8
7
6
7.6
7.6
5.5
5.8
5.4
5
5.6
4.1
4
4.9
5.1
4.4
3.8
3.3
3.1
3
2
1.1
1
0
1.1
1996
1.5
0.9
0.9
0.7
1997
1998
4.4
4.0
1.2
1.2
0.9
0.8
0.8
1999
2000
2001
0.9
3.0
0.9
0.6
2002
2.9
1.0
0.7
2003
3.1
2.5
1.1
0.4
2004
4.1
4.6
3.5
2.4
0.9
0.7
2005
0.8
0.4
2006
2.7
Neural tube defects
Spina bifida
Anencephalus & similar
anomalies
Encephalocele
0.8
0.6
2007
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1996–2007
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1996–2007. Combined rates of specific NTD categories may not add up
to the total NTD rate because of rounding. *Total births include live births and stillbirths.
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TABLE 3.1
Prevalence of neural tube defects and relative risks compared to 1996, Canada, 1996–2007
Neural tube defects
Years
Number of
total births
Cases
Rate
per
10,000
total
births
RR
Spina bifida
95% CI
Cases
Rate
per
10,000
total
births
RR
200
5.5
1.00
95% CI
1996
(pre-fortification)
366,811
278
7.6
1.00
1998-1999
(partialfortification)
682,230
390
5.7
0.75
(0.68–0.83)
278
4.1
0.75
(0.66–0.84)
2001-2003
(post-fortification)
1,006,779
461
4.6
0.60
(0.55–0.66)
301
2.9
0.53
(0.49–0.61)
2004-2007
(post-fortification)
1,419,505
569
4.0
0.52
(0.49–0.57)
378
2.6
0.49
(0.44–0.54)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1996–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1996–2007.
RR—Relative Risk, CI—Confidence Interval
PROVINCIAL AND TERRITORIAL
PREVALENCE RATES
The analysis of provincial and territorial rates shows
that the decline in NTDs between 1998 and 2007
occurred across the country (Figure 3.2). The
significant differences that existed between
provinces prior to folic acid fortification were greatly
diminished after fortification. In 1991–1996, the
ratio of the highest to the lowest prevalence
(Newfoundland and Labrador to Québec) was 4.5.
In 2001–2007, the ratio of highest to lowest
prevalence (British Columbia to Québec) was only
1.8 (Figure 3.2).
28 | CONGENITAL ANOMALIES IN CANADA 2013
FIGURE 3.2
Neural tube defect (NTD) rate, by province/territory and time period, Canada, 1991–2007 combined
CANADA*
Newfoundland and Labrador
Prince Edward Island §
Nova Scotia**
New Brunswick
Québec
Ontario
1991–1996 (pre-fortification)
Manitoba
1997–2000 (partial-fortification)
Saskatchewan
2001–2007 (post-fortification)
Alberta
British Columbia
Territories §
0
10
20
30
40
NTD (95% CI) per 10,000 total births***
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1991–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1991–2007.
*Territorial data was unavailable because Nunavut was not established as a territory until 1999. Data on births in Nunavut were included within those
of the Northwest Territories.
**Nova Scotia data from 1991–1995 were excluded as they were not available to CCASS prior to 1996. Nova Scotia data are for 1996–2007.
***Total births include live births and stillbirths. § Rate suppressed due to small cell numbers (<5). CI—Confidence Interval
DATA LIMITATIONS
For provinces and territories other than Alberta, the
primary data source for CCASS is the hospital
discharge database. In Québec, an analysis of the
validity of hospital discharge summaries for the
identification of NTDs showed that this source has a
sensitivity of 92%, but a low predictive value due to
coding errors.18 Indeed, as mentioned earlier, the
rates measured by CCASS are much lower than
those measured by other researchers during the
same period,14 which indicates that CCASS is not
capturing all cases, leading to an underestimation of
rates. Moreover, comparison of provincial rates
between CCASS and De Wals et al. showed that,
while rates from CCASS data are consistently lower,
the under-reporting varies between provinces,
therefore comparisons between jurisdictions should
be interpreted with caution. Finally, a large
proportion of terminations of NTD-affected
pregnancies occur at a stage when stillbirth
registration is not required (i.e., gestational age
<20 weeks and weight <500 g).19
INTERNATIONAL COMPARISONS
In the United States, the birth prevalence of spina
bifida was determined separately for Hispanic,
non-Hispanic white people, and black people. In
these three subpopulations, the respective birth
prevalence rates of spina bifida were 6.5, 5.1, and
3.6 per 10,000 births in the pre-fortification period
(January 1995 – December 1996) and 4.2, 3.4 and
2.9 per 10,000 births in the mandatory fortification
period (October 1998 – December 2002).20 The
order of magnitude of these rates, as well as the
trends associated with folic acid fortification in
enriched grain products, are similar to those found
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in Canada. Much higher rates have been observed
in Europe in the absence of folic acid fortification in
food. In the European Union, the birth prevalence of
NTDs decreased from 10.5 per 10,000 total births in
2004 to 9.4 per 10,000 total births in 2008;21 in
England and Wales, the birth prevalence of NTDs
has remained stable and ranged between 14 and 18
per 10,000 total births in 1995–2004;22 and in
Sweden, the birth prevalence of spina bifida has
decreased from 5.5 per 10,000 in 1988-1992 to 4.4
per 10,000 births in 1993–1998 and 2.9 per 10,000
in 1999–2003, largely due to prenatal diagnosis and
termination of pregnancy.23
TABLE 3.2
Birth prevalence of neural tube defects (NTDs) in USA and Europe
Country /
Reference
Condition
Population
Hispanic
Spina bifida
Period
None
6.5
01/1997–09/1998
Optional
5.5
10/1998–12/2002
Mandatory
4.2
01/1995–12/1996
None
5.1
Optional
4.4
10/1998–12/2002
Mandatory
3.4
01/1995–12/1996
None
3.6
Optional
2.5
10/1998–12/2002
Mandatory
2.9
01/1995–12/1996
None
3.9
01/1997–09/1998
Optional
3.6
10/1998–12/2002
Mandatory
2.8
01/1995–12/1996
None
2.8
Optional
2.1
10/1998–12/2002
Mandatory
2.0
01/1995–12/1996
None
2.0
Optional
1.8
10/1998–12/2002
Mandatory
1.8
2004
None
10.5
2008
None
9.4
Non-Hispanic black 01/1997–09/1998
Hispanic
Anencephaly
Non-Hispanic white 01/1997–09/1998
Non-Hispanic black 01/1997–09/1998
Europe21
All NTDs
England and
Wales22
All NTDs
Sweden23
Spina bifida
Prevalence
(per 10,000
total births)
01/1995–12/1996
Non-Hispanic white 01/1997–09/1998
USA20
Folic acid
fortification
1995-1999
15.5
2000-2004
16.3
1993-1998
None
4.4
1999-2003
None
2.9
30 | CONGENITAL ANOMALIES IN CANADA 2013
IMPACT OF PRENATAL DIAGNOSIS
ON BIRTH PREVALENCE
All cases of anencephaly and a large proportion of
major spina bifida cases can be detected with
prenatal ultrasound at 18–20 weeks. However, it is
not possible to measure the impact of prenatal
diagnosis and subsequent termination of affected
pregnancies from CCASS data because only those
terminations taking place in or after the 20th week
of pregnancy, which are registered as stillbirths, are
included in the dataset. Nonetheless, a study in
British Columbia showed that 72.6% of pregnant
women chose to terminate their pregnancy
following a prenatal diagnosis of NTDs.19
PREVENTIVE MEASURES
Optimal folate status for all women of child bearing
age has been postulated to reduce the risk of NTDs
by as much as 70%. Folic acid supplementation is
especially important in women with a personal and
family history of NTDs as they have the highest
risk.24 It may also preferentially benefit those with
other risk factors such as polymorphisms in a variety
of genes involved in folate metabolism25 (e.g., the
C677T variant in the 5,10-methylenetetrahydrofolate
reductase gene).26 This includes those women on
medications that impair folate metabolism such as
certain anticonvulsants,27 since they are also at
increased risk for NTDs. As it is not feasible on a
population basis to identify all women who may be
inadequately protected against folate sensitive
NTDs, daily low dose (0.4 mg/day)
supplementation is recommended for all women of
child bearing potential.28
SUMMARY
The rate of NTDs declined between 1996 and 2007.
This decline is due to the introduction of folic acid
fortification in certain grain products, to an
increasing use of folic acid supplements among
women of child bearing age, and to an increase in
prenatal screening and diagnosis leading to
termination of affected pregnancies. The relative
contribution of these factors cannot be determined
with precision.
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REFERENCES
1. Padmanabhan R. Etiology, pathogenesis and
prevention of neural tube defects. Congenit
Anom (Kyoto). 2006;46(2):55-67.
2. MRC Vitamin Study Research Group.
Prevention of neural tube defects: results of the
Medical Research Council Vitamin Study.
Lancet. 1991;338(8760):131-7.
3. Oakley GP. The scientific basis for eliminating
folic acid-preventable spina bifida: a modern
miracle from epidemiology. Ann Epidemiol.
2009;19(4):226-30.
4. de Franchis R, Buoninconti A, Mandato C, et al.
The C677T mutation of the
5,10-methylenetetrahydrofolate reductase
gene is a moderate risk factor for spina bifida in
Italy. J Med Genet. 1998;35(12):1009-13.
5. Muñoz JB, Lacasaña M, Cavazos RG, et al.
Methylenetetrahydrofolate reductase gene
polymorphisms and the risk of anencephaly in
Mexico. Mol Hum Reprod. 2007;13(6):419-24.
6. Ray JG, Vermeulen MJ, Meier C, et al. Maternal
ethnicity and risk of neural tube defects: a
population-based study. CMAJ. 2004;171(4):
343-345.
7. Rasmussen SA, Chu SY, Kim SY, et al. Maternal
obesity and risk of neural tube defects: a
metaanalysis. Am J Obstet Gynecol.
2008;198(6):611-9.
8. Garne E, Loane M, Dolk H, et al. Spectrum of
congenital anomalies in pregnancies with
pregestational diabetes. Birth Defects Res A
Clin Mol Teratol. 2012;94(3):134-40.
9. Yazdy MM, Liu S, Mitchell AA, et al. Maternal
dietary glycemic intake and the risk of neural
tube defects. Am J Epidemiol. 2010;171(4):
407-414.
10. De Wals P, Van Allen MI, Lowry RB, et al.
Impact of folic acid food fortification on the
birth prevalence of lipomyelomeningocele in
Canada. Birth Defects Res A Clin Mol Teratol.
2008;82(2):106-9.
11. Jentink J, Bakker MK, Nijenhuis CM, et al. Does
folic acid use decrease the risk for spina bifida
after in utero exposure to valproic acid?
Pharmacoepidemiol Drug Saf. 2010;19(8):
803-7.
12. Shaw GM, Todoroff K, Velie EM, et al. Maternal
illness, including fever and medication use as
risk factors for neural tube defects. Teratology.
1998;57(1):1-7.
13. Ray JG, Wyatt PR, Thompson MD, et al.
Vitamin B12 and the risk of neural tube defects
in a folic-acid-fortified population.
Epidemiology. 2007;18(3):362-6.
14. De Wals P, Tairou F, Van Allen MI, et al.
Reduction in neural-tube defects after folic acid
fortification in Canada. N Engl J Med.
2007;357(2):135-42.
15. De Wals P, Tairou F, Van Allen MI, et al. Spina
bifida before and after folic acid fortification in
Canada. Birth Defects Res A Clin Mol Teratol.
2008;82(9):622-6.
16. Health Canada. Congenital Anomalies in
Canada — A Perinatal Health Report, 2002.
Ottawa: Minister of Public Works and
Government Services Canada, 2002.
17. Public Health Agency of Canada. Canadian
Perinatal Health Report, 2008 Edition. Ottawa
Minister of Health, 2008.
18. Tairou F, De Wals P, Bastide A. Validity of death
and stillbirth certificates and hospital discharge
summaries for the identification of neural tube
defects in Québec City. Chron Dis Can.
2006;27(3):131-41.
19. Van Allen MI, Boyle E, Thiessen P, et al. The
impact of prenatal diagnosis on neural tube
defect (NTD) pregnancy versus birth incidence
in British Columbia. J Appl Genet.
2006;47(2):151-8.
32 | CONGENITAL ANOMALIES IN CANADA 2013
20. Williams LJ, Rasmussen SA, Flores A, et al.
Decline in the prevalence of spina bifida and
anencephaly by race/ethnicity: 1995-2002.
Pediatrics. 2005;116(3):580-6.
25. van der Linden IJ, Afman LA, Heil SG, et al.
Genetic variation in genes of folate metabolism
and neural-tube defect risk. Proc Nutr Soc.
2006;65(2):204-15.
21. Khoshnood B, Greenlees R, Loane M, et al.
Paper 2: EUROCAT public health indicators for
congenital anomalies in Europe. Birth Defects
Res A Clin Mol Teratol. 2011;91(Suppl 1):
S16-22.
26. van der Put NM, Eskes TK, Blom HJ. Is the
common 677C-->T mutation in the
methylenetetrahydrofolate reductase gene a
risk factor for neural tube defects? A metaanalysis. QJM. 1997;90(2):111-5.
22. Morris JK, Wald NJ. Prevalence of neural tube
defect pregnancies in England and Wales from
1964 to 2004. J Med Screen. 2007;14(2):55-9.
27. Lambie DG, Johnson RH. Drugs and folate
metabolism. Drugs. 1985;30(2):145-55.
23. Nikkilä A, Rydhström H, Källén B. The incidence
of spina bifida in Sweden 1973-2003: The effect
of prenatal diagnosis. Eur J Public Health.
2006;16(6):660-2.
24. Grosse SD, Collins JS. Folic acid
supplementation and neural tube defect
recurrence prevention. Birth Defects Res A Clin
Mol Teratol. 2007;79(11):737-42.
28. Health Canada. Prenatal Nutrition Guidelines
for Health Professionals: Folate Contributes to
a Healthy Pregnancy [Internet]. 2009 [cited
2011 Sept]. Available from: http://www.hc-sc.
gc.ca/fn-an/pubs/nutrition/folate-eng.php.
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CHAPTER 4
CONGENITAL HEART DEFECTS
KS Joseph
Shiliang Liu
INTRODUCTION
Congenital heart defects (CHDs) are defined as
“gross structural abnormalities of the heart or
intra-thoracic vessels that are actually or potentially
of functional significance”.1 They constitute the
most common congenital anomaly among
newborns, with a birth prevalence ranging from
50 to 150 per 10,000 total births.2,3 CHDs remain
one of the most important causes of infant
morbidity and mortality and also constitute an
important cause of disability and death in youth and
adult life.4 Although various potentially modifiable
and non-modifiable risk factors for CHDs have been
identified in recent years, it is unclear if awareness
of risk factors has resulted in a change in the
frequency of such malformations. For instance, one
study5 from Québec showed a decline in the birth
prevalence of severe CHDs from 1998 to 2005
(following the introduction of food fortification with
folic acid). However, another study from Northern
England,6 where food is not fortified with folic acid,
documented a substantial increase in such defects.
RISK FACTORS
There is a large body of evidence on the genetic
and non-genetic risk factors for CHDs.7,8 The
genetic causes of CHDs include chromosomal
syndromes and single gene disorders. Down
syndrome is associated with congenital heart
disease in approximately 45% of cases, although no
single gene on chromosome 21 has yet been
identified as responsible for heart defects.9
DiGeorge syndrome (typically characterized by
22q11 deletion) and Williams-Beuren syndrome
(typically characterized by a 7q11.23 microdeletion)
are other examples of chromosomal disorders, while
Alagille syndrome (commonly caused by mutations
of the gene JAG1), Noonan syndrome (due to
mutations in PTPN11, SOS1, or KRAS), and HoltOram syndrome (with mutations in TBX5) are
examples of single gene defects.7 Family history of
CHDs sometimes helps in the prenatal identification
of such heritable defects.
Recent studies have also implicated various
modifiable non-inherited risk factors,8 though the
evidence is less consistent in some instances and
more definitive in others. Modifiable determinants
of CHDs include maternal rubella during pregnancy,
use of multivitamin/folic acid supplements,
medications (e.g., anti-epileptics, thalidomide,
isotretinoin and lithium), glycemic control for
diabetes mellitus and dietary modification for
maternal phenylketonuria. Other possible causes
include maternal illnesses (e.g., influenza, HIV
infection, and systemic lupus erythematosus),
therapeutic drug exposure (e.g., anti-virals and
antifungal agents), non-therapeutic drug exposure
(e.g., cocaine, marijuana and cigarette smoking),
environmental exposures (e.g., organic solvents,
herbicides, and pesticides) and socio-demographic
and lifestyle characteristics (e.g., race/ethnicity and
maternal age). Paternal determinants such as age
and cocaine, or marijuana use have also been
implicated as potential causes.8
PREVALENCE RATE OF CONGENITAL
HEART DEFECTS IN CANADA
Estimates of the prevalence of CHDs in Canada vary
somewhat depending on the data source used to
ascertain rates. Canadian Congenital Anomalies
Surveillance System (CCASS) data using Discharge
Abstract Data (DAD) provide the most recent
information and show that rates of CHDs (as
ascertained up to 30 days of age) decreased by
21% from 107.1 per 10,000 total births in 1998 to
85.1 per 10,000 total births in 2009 (Figure 4.1).
34 | CONGENITAL ANOMALIES IN CANADA 2013
FIGURE 4.1
Congenital heart defect (CHD) rate, Canada (excluding Québec),* 1998–2009
CHD per 10,000 total births**
140
120
107.1
112.2
106.0
108.5
103.3
99.0
100
94.8
93.7
98.6
90.8
94.6
85.1
2008
2009
80
60
40
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
Note: Data quality issues pertaining to these birth prevalence estimates are discussed in the text.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths.
FIGURE 4.2
Rate of selected congenital heart defects (CHDs), Canada (excluding Québec),* 1998–2009
7
Rate per 10,000 total births**
6
TGV
5
TOF
ECD
4
HLHS
3
CV
CT
2
1
0
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
CT: Common truncus (P value for trend <0.0001)
TGV: Transposition of great vessels (P value for trend <0.05)
TOF: Tetralogy of Fallot (P value for trend <0.0001)
CV: Common ventricle (P value for trend <0.0001)
ECD: Endocardial cushion defects (P value for trend <0.05)
HLHS: Hypoplastic left heart syndrome (P value for trend <0.001)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths.
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Figure 4.2 shows the birth prevalence rates of selected
CHDs in Canada (excluding Québec) between 1998
and 2009. Rates of common truncus, tetralogy of
Fallot and common ventricle showed a decrease in
frequency between 1998 and 2007, whereas rates of
transposition of the great vessels were stable and
endocardial cushion defects increased.
Table 4.1 shows rates of some specific CHDs as
estimated by the CCASS and the Alberta
Congenital Anomalies Surveillance System (ACASS)
and provides some insight into how different data
collection methods affect rates (even if estimates
apply to different regions and different periods).
Rates of common truncus, endocardial cushion
defects and hypoplastic left heart syndrome were
not significantly different in Alberta, 2000–2009, as
estimated by ACASS, and Canada (excluding
Québec), 1998–2009 as estimated by CCASS.
However, the approximately similar frequency of
CHDs in the different databases does not
necessarily imply equal accuracy of case
identification or case-by-case correspondence
between the different databases. The two data
sources have the following features:
1. The inclusion of information from pregnancy
terminations, use of rigorous case definitions,
hierarchical classification and standard data
verification procedures makes ACASS data the
most accurate information on CHDs in Canada.
2. Underestimation of cases in CCASS is likely
offset by overestimation due to coding
problems (e.g., tetralogy of Fallot coded as
both the tetralogy and as a ventricular septal
defect) and lack of data verification. For
instance, infants with patent ductus arteriosus
and patent foramen ovale who are <37 weeks
gestation or <2,500 g birth weight may be
coded as cases in CCASS, while in ACASS such
cases are only coded in full term infants.
TABLE 4.1
Rates of specific congenital heart defects,* Alberta and Canada (excluding Québec), 2000–2009 and 1998–2009
Diagnostic category
Rate (95% CI) in Alberta
2000–2009
Rate (95% CI) in Canada
1998–2009
Common truncus
0.6(0.4–0.9)
0.9 (0.8–1.0)
Transposition of great vessels
3.5(3.0–4.1)
5.0 (4.8–5.2)
Tetralogy of Fallot
3.4(2.9–4.0)
4.1 (3.9–4.3)
Ventricular septal defect
31.2(29.5–32.9)
35.0(34.3–35.6)
Atrial septal defect
19.6(18.3–21.0)
46.9(46.1–47.6)
Endocardial cushion defect
4.5(3.9–5.2)
3.6 (3.4–3.8)
Hypoplastic left heart syndrome
3.1(2.6–3.7)
2.8 (2.6–3.0)
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 2000–2009.
Source of Canadian data: Canadian Congenital Anomalies Surveillance System, 1998–2009; and the Canadian Institute for Health Information,
1998–2009.
Note: Data quality issues pertaining to these prevalence estimates are discussed in the text.
*Per 10,000 total births. Total births include live births and stillbirths. CI—Confidence Interval
36 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE 4.2
Congenital heart defect (CHD) international rates, by region/country, 2000-2005 combined
Country/Region
Rate of CHDs*
Styria, Austria
153.4
Hainaut, Belgium
66.6
Zagreb, Croatia
53.9
Odense, Denmark
89.1
Paris, France
83.8
Mainz, Germany
119.0
Emilia Romagna, Italy
68.6
Malta
152.5
Northern, Netherlands
60.8
Norway
102.7
Ukraine
77.8
Source: Special Report: Congenital Heart Defects in Europe, 2000-2005 EUROCAT 2009.
*Rate numerators include CHDs among live births, fetal deaths and terminations of pregnancy and; rates are expressed per 10,000 total births
(live births plus fetal deaths).
3
TABLE 4.3
Prevalence of specific subtypes of non-chromosomal congenital heart defects, EUROCAT Registry, 2000–2005
Diagnostic category
Prevalence per 10,000 total births*
Common truncus
0.9
Transposition of great vessels
3.5
Tetralogy of Fallot
2.8
Ventricular septal defect
30.6
Atrial septal defect
20.5
Hypoplastic left heart syndrome
2.6
Source: Special Report: Congenital Heart Defects in Europe, 2000-2005 EUROCAT, 2009.3
*Rate numerators include CHDs among live births, fetal deaths and terminations of pregnancy and; rates are expressed per 10,000 total births
(live births plus fetal deaths).
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PROVINCIAL AND TERRITORIAL
PREVALENCE RATES
availability and uptake of prenatal diagnosis and
subsequent pregnancy terminations prior to
20 weeks gestation.
Figure 4.3A shows birth prevalence rates of CHDs in
each province and territory for 2000–2009 based on
the DAD (estimate for Québec, 1998–2007, based
on MED-ÉCHO). Rates of CHDs in Newfoundland
and Labrador, Québec, Alberta and Nunavut were
higher than the Canadian average while rates in
Nova Scotia, New Brunswick, Manitoba,
Saskatchewan and British Columbia were lower
(Figure 4.3B). These differences in prevalence rates
could represent true differences in rates of CHDs or
differences in case identification (diagnosis) during
the birth hospitalization. True differences in rates
may arise from population differences in genetic
and other risk factors or differences in the
INTERNATIONAL COMPARISONS
Table 4.2 shows rates of CHDs in several European
registries in 2000–05.3 Birth prevalence ranged from
53.9 per 10,000 total births in Croatia to 153.4 per
10,000 total births in Austria. Registries included live
births, stillbirths and terminations of pregnancy;
however, terminations did not occur in some
countries, but were frequent in others e.g., France.
Table 4.3 shows the birth prevalence of specific
congenital heart defect subtypes; rates were similar
to those documented in Canada, especially rates
estimated by ACASS that also capture terminations
(Table 4.1).
FIGURE 4.3A
Congenital heart defect (CHD) rate, by province/territory, Canada, 2000–2009 (Quèbec 1998–2007) combined
CANADA
Newfoundland and Labrador
Prince Edward Island
Nova Scotia
New Brunswick
Québec*
Ontario
Manitoba
Saskatchewan
Alberta
British Columbia
Yukon
Northwest Territories
Nunavut
0
50
100
150
200
250
300
CHD (95% CI) per 10,000 total births**
Source: Discharge Abstract database of the Canadian Institute for Health Information, 2011.
Source for Québec: Estimated from the Canadian Congenital Anomalies Surveillance System database, 1998–2007.
*Québec data shows the combined rate for the 10-year period 1998–2007.
**Data quality issues pertaining to these birth prevalence estimates are discussed in the text. Total births include live births and stillbirths.
CI—Confidence Interval
38 | CONGENITAL ANOMALIES IN CANADA 2013
FIGURE 4.3B
Ratio of provincial/territorial congenital heart defect rate to national rate,**
Canada, 2000–2009, (Québec 1998–2007) combined
Birth Prevalance Ratios
> 1.50
1.26 - 1.50
1.01 - 1.25
0.76 - 1.00
<0.76
No Cases or Suppressed
*
Statistical Significance
YT
NT
BC*
AB*
NU*
NL*
SK*
MB*
ON
NL*
QC*
PE
NB
NS*
Source: Canadian Congenital Anomalies Surveillance System database, 1998–2009 (Québec 1998–2007).
**This ratio calculates the birth prevalence rate per 10,000 total births of each individual province/territory to the birth prevalence rate for Canada
during the specified time period. The birth prevalence for Canada includes cases for which province/territory is unknown.
IMPACT OF PRENATAL DIAGNOSIS ON
BIRTH PREVALENCE OF CONGENITAL
HEART DEFECTS
It is unclear if the live birth prevalence of CHDs has
declined in recent years as prenatal diagnosis of
such conditions has improved.5,6 However, Canadian
studies10,11 have shown that congenital anomalyrelated fetal deaths have increased at very early
gestation and declined at late gestation, and
congenital anomaly-related infant deaths have
decreased in recent decades. Between 1981–85 and
1994–98, CHDs related fetal deaths at 20-25 weeks
gestation increased from 0.02 to 0.3 per 10,000
fetuses at risk,* CHDs related fetal deaths at 26–44
weeks decreased from 0.5 to 0.4 per 10,000 fetuses
at risk and CHDs related infant deaths decreased
from 10.2 to 5.6 per 10,000 live births.11 The change
in congenital anomaly-related fetal death rates is
likely an effect of prenatal diagnosis and pregnancy
termination, whereas the decline in congenital
anomaly-related infant deaths probably represents
the combined effect of prenatal diagnosis and
pregnancy termination and improvements in the
postnatal management of CHDs.
* The fetuses at risk model estimates gestational age-specific stillbirth
rates as an incidence, with stillbirths at any gestation in the numerator
and all fetuses at risk of stillbirth in the denominator i.e., the
denominator includes all live births and stillbirths that occur at the
gestation of interest and beyond.
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Studies show that approximately one-third of all
CHDs and 60–80% of severe heart anomalies are
diagnosed prenatally,12,13 though such estimates vary
across populations and will continue to increase
with wider access to health services. The proportion
of prenatally diagnosed cases that are terminated
also varies widely, ranging from 30% to 60%.12-15
Termination of pregnancy is more common when
the heart defects are associated with chromosomal
anomalies or other syndromes or with multiple
anomalies. A study16 from a single Canadian
institution showed that 19% of cases of tetralogy of
Fallot were diagnosed prenatally between 1998 and
2006. Of the 15% that were terminated, over half
had other congenital anomalies such as
omphalocele, talipes, pentalogy of Cantrell and
trisomy 18. Some estimates suggest that prenatal
screening and pregnancy termination has led to a
21% reduction in birth prevalence of congenital
heart disease.17,18 However, recent improvements in
the management of isolated heart defects mean
that parents increasingly opt for attempts at
postnatal surgical correction over pregnancy
termination.
PREVENTIVE MEASURES
Food fortification with folic acid and
periconceptional supplementation with
multivitamins are potential preventive measures.5,8
Antenatal assessment of rubella immunoglobulin
titres can identify seronegative women who could
be offered immunization postnatally. The Canadian
Immunization Guide19 recommends that women not
immunized in childhood (e.g., immigrant women
from countries where rubella vaccination is not
routine), should be offered one dose of mumpsmeasles-rubella vaccination sufficiently prior to
pregnancy. Avoidance of exposures to illnesses,
drugs and environmental contaminants would be
advisable for women planning a pregnancy. Such
avoidance can be challenging when the medication
in question is strongly indicated (e.g., for psychosis
or epilepsy), though alternative medication with
lesser teratogenic potential may be an option. On
the other hand, Health Canada recommends that
medications such as isotretinoin, used for severe
acne, should only be prescribed to women of
reproductive age in accordance with standard
guidelines.20 A family history of CHDs disease can
be used for referral to a genetic counsellor and may
facilitate the early prenatal detection of cases.
Finally, prenatal diagnosis and the option and
availability of termination of pregnancies for severe
CHDs can reduce the birth prevalence, if identified
early in gestation.
SUMMARY
CHDs are important congenital anomalies, in terms
of both frequency and the severity of associated
morbidity. The birth prevalence of CHDs in Canada
has declined by about 18% in recent years.
However, this finding needs to be investigated
further as potential problems in contemporary data
sources do not permit a robust inference. Provincial
and territorial rates show wide variation in birth
prevalence, although the significance of observed
differences is not entirely clear. International
comparisons show that rates of CHDs in Canada are
similar to those in European countries.
40 | CONGENITAL ANOMALIES IN CANADA 2013
REFERENCES
1. Mitchell SC, Korones SB, Berendes HW.
Congenital heart disease in 56,109 births.
Incidence and natural history. Circulation.
1971;43(3):323-32.
2. Oyen N, Poulsen G, Boyd HA, et al. National
time trends in congenital heart defects,
Denmark, 1977-2005. Am Heart J.
2009;157(3):467-73.
3. EUROCAT. Special Report: Congenital Heart
Defects in Europe, 2000–2005 [Internet]. 2009
[cited 2012 Jan]. Available from: http://www.
eurocat-network.eu/content/Special-ReportCHDs.pdf.
4. van der Bom T, Zomer AC, Zwinderman AH, et
al. The changing epidemiology of congenital
heart disease. Nat Rev Cardiol. 2011;8(1):50–60.
5. Ionescu-Ittu R, Marelli AJ, Mackie AS, et al.
Prevalence of severe congenital heart disease
after folic acid fortification of grain products:
time trend analysis in Québec, Canada. BMJ.
2009;338:b1673.
6. Dadvand P, Rankin J, Shirley MD, et al.
Descriptive epidemiology of congenital heart
disease in Northern England. Paediatr Perinat
Epidemiol. 2009;23(1):58-65.
7. Pierpont ME, Basson CT, Benson DW Jr, et al.
Genetic basis for congenital heart defects:
current knowledge: a scientific statement from
the American Heart Association Congenital
Cardiac Defects Committee, Council on
Cardiovascular Disease in the Young: endorsed
by the American Academy of Pediatrics.
Circulation. 2007;115(23):3015-38.
8. Jenkins KJ, Correa A, Feinstein JA, et al.
Noninherited risk factors and congenital
cardiovascular defects: current knowledge: a
scientific statement from the American Heart
Association Council on Cardiovascular Disease
in the Young: endorsed by the American
Academy of Pediatrics. Circulation.
2007;115(23):2995-3014.
9. Vis JC, Duffels MGJ, Winter MM, et al. Down
syndrome: a cardiovascular perspective.
J Intellect Disabil Res. 2009;53(5):419-25.
10. Liu S, Joseph KS, Kramer MS, et al. Relationship
of prenatal diagnosis and pregnancy termination
to overall infant mortality in Canada. JAMA.
2002;287:1561-7.
11. Liu S, Joseph KS, Wen SW. Trends in fetal and
infant deaths due to congenital anomalies.
Semin Perinatol. 2002;26(4):268-76.
12. Tegnander E, Williams W, Johansen JO, et al.
Prenatal detection of heart defects in a nonselected population of 30,149 fetuses —
detection rates and outcome. Ultrasound
Obstet Gynecol. 2006;27(3):252-65.
13. Tomek V, Marek J, Jicínská H, et al. Fetal
cardiology in the Czech Republic: current
management of prenatally diagnosed
congenital heart diseases and arrhythmias.
Physiol Res. 2009;58(S2):S159–66.
14. Fesslova V, Nava S, Villa L. Evolution and long
term outcome in cases with fetal diagnosis of
congenital heart disease: Italian multicenter
study. Fetal Cardiology Study. Group of the
Italian Society of Pediatric Cardiology. Heart.
1999;82(5):594–9.
15. Paladini D, Russo M, Teodoro A, et al. Prenatal
diagnosis of congenital heart disease in the
Naples area during the years 1994-1999 — the
experience of a joint fetal-pediatric cardiology
unit. Prenat Diagn. 2002;22(7):545–52.
16. Hirji A, Bernasconi A, McCrindle BW, et al.
Outcomes of prenatally diagnosed tetralogy of
Fallot: Implications for valve-sparing repair
versus transannular patch. Can J Cardiol.
2010;26(1):e1-6.
17. Bull C. Current and potential impact of fetal
diagnosis on prevalence and spectrum of
serious congenital heart disease at term in the
UK. British Pediatric Cardiac Association. Lancet.
1999;354(9186):1242–7.
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CONGENITAL ANOMALIES
IN CANADA
2013 | 41
18. Germanakis I, Sifakis S. The impact of fetal
echocardiography on the prevalence of liveborn
congenital heart disease. Pediatr Cardiol.
2006;27(4):465-72.
19. Public Health Agency of Canada. Canadian
Immunization Guide [Internet]. 2008 [cited 2012
Dec]. Available from: http://www.phac-aspc.gc.
ca/publicat/cig-gci/index-eng.php#toc.
20. Health Canada. Therapeutic Products
Directorate. Important safety information on
Accutane. 2001 [cited 2012 Dec]. Available
from: http://www.hc-sc.gc.ca/dhp-mps/medeff/
advisories-avis/prof/_2001/accutane_hpc-cpseng.php.
42 | CONGENITAL ANOMALIES IN CANADA 2013
CHAPTER 5
OROFACIAL CLEFTS
Julian Little
Chantal Nelson
INTRODUCTION
Every year, approximately 600 babies are born with
orofacial clefts (OFCs) in Canada.1 Affected children
need multidisciplinary surgical and nonsurgical care
from birth until adulthood and they and their
families may suffer psychological effects.2 Increased
perinatal mortality has been observed even in the
absence of associated anomalies and the risk of
death remains higher than expected throughout
childhood and adulthood.3 The causes of OFCs
remain largely unknown; therefore, in the absence
of information on which to base primary prevention
strategies, these congenital anomalies (CA) continue
to pose major challenges in terms of morbidity,
health care, and social and employment exclusion
for affected individuals, their families and society.1
On the basis of their distinct developmental origins,
and the observation that under most circumstances
cleft lip with or without cleft primary palate (CL±CP)
and isolated cleft secondary palate (CP) do not
segregate in the same family, OFCs are usually
subdivided into these two categories (primary and
secondary).2 Disruption in any of the processes of
cell proliferation, migration, adhesion, differentiation
and apoptosis involved in the highly coordinated
growth and fusion of the facial processes and palatal
shelves before the end of the sixth week of
development can result in clefts of the lip and
primary palate; between the sixth and tenth weeks,
they cause clefts of the secondary palate.
PREVALENCE RATE OF OROFACIAL
CLEFTS IN CANADA
The overall prevalence at birth of OFCs in Canada
from 1998–2007 was 16.3 per 10,000 total births
(live births and stillbirths). The prevalence at birth of
CL±CP was 9.4 per 10,000 and of CP 7.0 per
10,000. There appeared to be a small decline in the
prevalence at birth of OFCs but not CP (Figure 5.1).
Of a total of 5,599 births with OFCs, 95 were
stillborn of which 70 had an additional anomaly. The
majority of babies born with orofacial clefts do not
have additional anomalies, but the precise ratio of
isolated to complex cases cannot be determined
from CCASS data alone.
PROVINCIAL AND TERRITORIAL
PREVALENCE RATES
There is marked variation in the prevalence of OFCs
at birth in Canada (Figures 5.2A and B). For the
overall period 1998 to 2007, the rates ranged from
14.1 (95% CI: 11.5–17.2) per 10,000 in New
Brunswick to 38.2 (95% CI: 21.8–62.1) per 10,000 in
Nunavut. However, the high extreme of this
distribution was from Nunavut where the number of
births was less than 5,000. In jurisdictions with over
10,000 births, the variation was less pronounced.
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FIGURE 5.1
Total orofacial cleft (OFC) rate, Canada, 1998–2007
20
OFC per 10,000 total births*
18
17.9
18.6
17.1
16
16.2
16.5
10.7
10
4
2
0
10.5
10.3
9.4
9.4
14.2
6.7
7.3
2.9
2.9
1998
1999
3.5
2000
6.8
3.0
2001
7.3
Cleft lip
9.5
3.1
2002
6.9
Orofacial Clefts
15.0
Cleft lip±cleft palate
8.9
8.3
8.0
8
6
16.3
15.1
14
12
16.3
6.8
Cleft palate
8.6
8.2
6.6
7.5
6.3
3.0
2.7
2003
2004
2.9
2.9
2005
2006
3.2
2007
Source: Public Health Agency of Canada, Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
Note: Rates that do not add up exactly may be due to rounding.
*Total births include live births and stillbirths.
FIGURE 5.2A
Orofacial cleft (OFC) rate, by province/territory, Canada, 1998–2007 combined
CANADA
Newfoundland and Labrador
Prince Edward Island
Nova Scotia
New Brunswick
Québec
Ontario
Manitoba
Saskatchewan
Alberta
British Columbia
Yukon §
Northwest Territoires
Nunavut
0
10
20
30
40
50
60
OFC (95% CI) per 10,000 total births*
Source: Public Health Agency of Canada, Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. § Rate suppressed due to small cell numbers (<5). CI—Confidence Interval
70
44 | CONGENITAL ANOMALIES IN CANADA 2013
INTERNATIONAL COMPARISONS
A review of peer-reviewed literature and
supplemental data obtained from the European
Surveillance of Congenital Anomalies (EUROCAT)
and the National Birth Defects Prevention Network
(NBDPN, USA) registries found that, from 1958–
1998, there was approximately an eightfold variation
in the prevalence at birth of CL±CP with a range
from 0.3 (USA) to 2.3 (India) per 1,000 births
internationally.4 This is consistent with 2000–2005
data from registries in 30 countries during the
period which also suggested about an eightfold
variation of CL±CP in birth prevalence.5 Numerous
methodological issues affect the comparability of
published data from different jurisdictions including
the source population of births considered, the
length of data collection, types and numbers of
sources of ascertainment, inclusion/exclusion
criteria, clinical classification and sampling
fluctuation.5 Moreover, little or no information on
the frequency of OFCs is available for many parts
of the world, notably parts of Africa, Asia and
Eastern Europe. See Table 5.1 for a list of selected
international comparisons.
IMPACT OF PRENATAL DIAGNOSIS ON
BIRTH PREVALENCE OF OROFACIAL CLEFTS
According to 2000–2005 data from registries that
record terminations of pregnancy, the proportion of
cases of CL±CP accounted for by fetuses from
terminated pregnancies was less than 5%.5 In the
National Birth Defects Prevention Study, US, which
included OFCs cases without chromosomal
abnormalities or single gene disorders in live births,
stillbirths and pregnancy terminations, the proportions
of prenatally diagnosed cases were 33.3% for cleft lip
with cleft palate, 20.3% for cleft lip alone and 0.3% for
cleft palate alone.6 Prenatal detection rates are higher
for OFCs associated with malformations in other
systems than for isolated clefts,7 and terminations of
pregnancy are more common when the cleft is
associated with other anomalies.8
FIGURE 5.2B
Ratio of provincial/territorial orofacial cleft rate to national rate,** Canada, 1998–2007 combined
Birth Prevalance Ratios
> 1.50
1.26 - 1.50
1.01 - 1.25
0.76 - 1.00
<0.76
No Cases or Suppressed
*
Statistical Significance
YT
NT
BC*
AB
NU*
NL
SK*
MB*
ON*
NL
QC*
PE
NB
NS*
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
**This ratio calculates the birth prevalence rate per 10,000 total births of each individual province/territory to the birth prevalence rate for Canada
during the specified time period. The birth prevalence for Canada includes cases for which province/territory is unknown.
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TABLE 5.1
Cleft lip with or without cleft palate international rate,* by region/country, 2007
Country/Region
Rate of cleft lip with or without cleft
palate (CL±CP)
Rate of cleft palate (CP)
8.6
6.6
16.6
5.3
8.6
3.5
Texas, USA
11.0
5.2
Utah, USA
12.3
7.6
Victoria, Australia
11.9
5.4
Western Australia
12.6
7.0
9.0
4.1
Japan
21.2
4.5
Norway
13.1
6.2
South America
14.5
4.0
Wales, UK
12.7
9.0
Finland
11.9
12.1
Strasbourg, France
8.5
7.6
Emilia Romagna, Italy
5.9
6.6
CANADA†
Alberta, Canada
Atlanta, USA
Hungary
Source: International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) Annual Report, 2009 (data from 2007).
†Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2007.
*Per 10,000 total births.
RISK FACTORS
Approximately 70% of cases of CL±CP and 50% of
cases of CP are considered to be multifactorial, i.e.,
due to the interaction of genetic predisposition and
environmental factors.9 The remaining cases have
syndromes associated with known teratogens,
chromosomal anomalies or one of over 500 single
gene syndromes.9 For isolated cases, there is
debate about the effects of the anatomical severity
of the cleft in the index child on the recurrence risk
in first-degree relatives.10 As would be expected for
a multifactorial condition, a large Danish study
showed that the recurrence risk declined sharply by
degree of relationship: 2.7%–3.5% (depending on
the type of defect in the index case) for first-degree,
0.7%–0.8% for second-degree and 0.3%–0.6% for
third-degree relatives.11 Little information is
available on ethnic differences in cleft frequency in
Canada, but Aboriginal populations may be at
increased risk.12,13
In Greater Glasgow (Scotland) in 1974–1985, the
highest rates of OFCs were observed in areas with
high proportions of local authority (public) housing,
high unemployment and a preponderance of
unskilled workers, whereas the lowest rates were
found in affluent areas with high proportions of
professional and non-manual workers with largely
owner occupied or high-quality housing.14 Similar
findings have been reported in other parts of the
UK.1 Variation by ethnic group may also reflect
socioeconomic status SES differences. Maternal
smoking during pregnancy has been linked
consistently with increased risk of both CL±CP and
CP,15 with a population-attributable risk as high as
20%,16 Moreover, the impact of tobacco may have
been underestimated because maternal exposure
to environmental tobacco smoke (passive smoking),
which some studies suggest is positively
associated with OFCs,17 has not been assessed
in most investigations.
46 | CONGENITAL ANOMALIES IN CANADA 2013
While some studies suggest that heavy maternal
alcohol consumption during early pregnancy
increases the risk of OFCs, the evidence as to
the effects of moderate maternal alcohol use
is inconsistent.1
Both maternal obesity18 and underweightedness19
have been found to be associated with CL±CP. In a
meta-analysis of observational studies, maternal use
of multivitamin supplements in early pregnancy was
associated with a decreased risk of OFCs, but with
heterogeneity between studies.20 The combined
effect estimates indicated risk reductions of 25%
and 12% for CL±CP and CP respectively.20 It is not
possible to determine from these studies which of
the nutrients in the multivitamins are protective and
whether or not other healthy behaviours of
multivitamin users confound these results. Similarly,
the effect of dietary or supplemental intake of folic
acid on OFCs is uncertain. In North America, where
there has been mandatory fortification of grains with
folic acid since November 1998, there is some
evidence of a subsequent decline in the prevalence
at birth of CL±CP.21 For all clefts combined, there
was a decrease after the introduction of fortification
in the United States, but not in Canada, Argentina,
Brazil or Chile.21 Additional risk factors are
presented in Table 5.2.
TABLE 5.2
Additional risk factors for orofacial clefts (OFCs)
Vitamin deficiencies
Lower vitamin B-6 (pyridoxine and related compounds)22 and zinc levels23 have been
associated with an increased risk of OFCs.
Medication use
Certain anti-convulsant medications, notably diazepam, phenytoin and phenobarbital24
and possibly lamotrigene25 increase the risk of OFCs.
Valproic acid monotherapy was associated with an increased risk of CP,26 but
carbamazepine did not appear to increase the risk of CL±CP.27
Infection and febrile illness in early pregnancy may increase the risk of a cleft.28 Reported
use of acetaminophen in the first trimester, other than in combination products, was not
associated with OFCs, and appeared to reduce the risk of CL±CP in women who
reported concomitant febrile illness.29
Occupational and
environmental exposures
Maternal occupational exposures to organic solvents,30 maternal exposure to ambient air
pollutants31 and parental exposure to agricultural chemicals32 have been inconsistently
associated with OFCs.
Gene-environment
interactions
Although many potential gene-environment interactions in the etiology of OFCs have
been investigated,33 results have been inconclusive.2
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PREVENTIVE MEASURES
SUMMARY
Identification of modifiable risk factors is the first
step towards primary prevention. Modifiable risk
factors include smoking tobacco and obesity, as
both are consistently associated with OFCs.
OFCs continue to be an important cause of
morbidity among Canadian children. Evidence is
increasing that smoking and obesity increase risk of
occurrence, which reinforces the need to strengthen
public health efforts relating to reduction of these
factors. Multivitamin supplementation is associated
with reduced risk of CL±CP and perhaps CP, but
there is a need for better understanding of this
relationship in order to inform primary prevention
efforts. The development of enhanced surveillance
of CL±CP and CP, together with focused interdisciplinary research, is required to identify
additional modifiable risk factors. In addition,
surveillance of outcomes for children with OFCs will
be important in terms of maximizing the success of
tertiary prevention efforts.
Multivitamin supplements are associated with a
reduced risk for CL±CP and perhaps CP. There are
reported adverse effects of prolonged use of
supplements containing antioxidant vitamins and it
is important to clarify the specific nutrients and/or
minerals that account for this apparent inverse
association.2
With regard to tertiary prevention, OFCs have
health consequences in the longer term that are not
directly related to the presence of the cleft and the
interventions used to manage it. There is a need not
only for surveillance of the occurrence of OFCs, but
also of later effects, with a view to maximizing the
effectiveness of both primary prevention efforts and
therapeutic interventions.
48 | CONGENITAL ANOMALIES IN CANADA 2013
REFERENCES
1. Mossey PA, Shaw WC, Munger RG, et al.
Global oral health inequalities: challenges in
the prevention and management of orofacial
clefts and potential solutions. Adv Dent Res.
2011;23(2):247-58.
10. Sivertsen A, Wilcox AJ, Skjaerven R, et al.
Familial risk of oral clefts by morphological type
and severity: population based cohort study of
first degree relatives. BMJ. 2008;336
(7641):432-4.
2. Mossey PA, Little J, Munger RG, et al. Cleft lip
and palate. Lancet. 2009;374(9703):1773-85.
11. Grosen D, Chevrier C, Skytthe A, et al. A cohort
study of recurrence patterns among more than
54,000 relatives of oral cleft cases in Denmark:
support for the multifactorial threshold model
of inheritance. J Med Genet. 2010;47(3):162-8.
3. Christensen K, Juel K, Herskind AM, et al. Long
term follow up study of survival associated with
cleft lip and palate at birth. BMJ. 2004;328
(7453):1405.
4. Mossey PA, Little J. Epidemiology of Oral
Clefts: An International Perspective. In:
Wyszynski DF, editor. Cleft Lip and Palate: From
Origin to Treatment. New York: Oxford
University Press; 2002. p. 127-58.
5. Prevalence at Birth of Cleft Lip With or Without
Cleft Palate: Data From the International
Perinatal Database of Typical Oral Clefts
(IPDTOC). Cleft Palate. Craniofac J.
2011;48(1):66-81.
6. Johnson CY, Honein MA, Hobbs CA, et al.
National Birth Defects Prevention Study.
Prenatal diagnosis of orofacial clefts, National
Birth Defects Prevention Study, 1998-2004.
Prenat Diagn. 2009;29(9):833-9.
7. Offerdal K, Jebens N, Syvertsen T, et al.
Prenatal ultrasound detection of facial clefts: a
prospective study of 49,314 deliveries in a
non-selected population in Norway. Ultrasound
Obstet Gynecol. 2008;31(6):639-46.
8. da Silva Dalben G. Termination of pregnancy
after prenatal diagnosis of cleft lip and palate—
possible influence on reports of prevalence.
Oral Surg Oral Med Oral Pathol Oral Radiol
Endod. 2009;107(6):759-62.
9. Dixon MJ, Marazita ML, Beaty TH, et al. Cleft
lip and palate: understanding genetic and
environmental influences. Nat Rev Genet.
2011;12(3):167-78.
12. Coddington DA, Hisnanick JJ. Midline
congenital anomalies: the estimated
occurrence among American Indian and Alaska
Native infants. Clin Genet. 1996;50(2):74-7.
13. Lowry RB, Thunem NY, Silver M. Congenital
anomalies in American Indians of British
Columbia. Genet Epidemiol. 1986;3(6):455-67.
14. Womersley J, Stone DH. Epidemiology of facial
clefts. Arch Dis Child. 1987;62(7):717-20.
15. Little J, Cardy A, Munger RG. Tobacco smoking
and oral clefts: a meta-analysis. Bull World
Health Organ. 2004;82(3):213-8.
16. Little J, Cardy A, Arslan MT, et al. United
Kingdom-based case-control study. Smoking
and orofacial clefts: a United Kingdom-based
case-control study. Cleft Palate Craniofac J.
2004;41(4):381-6.
17. Chevrier C, Bahuau M, Perret C, et al. Genetic
susceptibilities in the association between
maternal exposure to tobacco smoke and the
risk of nonsyndromic oral cleft. Am J Med
Genet A. 2008;146A(18):2396-406.
18. Stothard KJ, Tennant PW, Bell R, et al. Maternal
overweight and obesity and the risk of
congenital anomalies: a systematic review and
meta-analysis. JAMA. 2009;301(6):636-50.
19. Waller DK, Shaw GM, Rasmussen SA, et al.
Prepregnancy obesity as a risk factor for
structural birth defects. Arch Pediatr Adolesc
Med. 2007;161(8):745-50.
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CONGENITAL ANOMALIES
IN CANADA
2013 | 49
20. Johnson CY, Little J. Folate intake, markers
of folate status and oral clefts: is the
evidence converging? Int J Epidemiol.
2008;37(5):1041-58.
27. Jentink J, Dolk H, Loane MA, et al. Intrauterine
exposure to carbamazepine and specific
congenital malformations: systematic review
and case-control study. BMJ. 2010;341:c6581.
21. Wehby GL, Murray JC. Folic acid and orofacial
clefts: a review of the evidence. Oral Dis.
2010;16(1):11-9.
28. Metneki J, Puho E, Czeizel AE. Maternal
diseases and isolated orofacial clefts in
Hungary. Birth Defects Res A Clin Mol Teratol.
2005;73(9):617-23.
22. Munger RG, Sauberlich HE, Corcoran C, et al.
Maternal vitamin B-6 and folate status and risk
of oral cleft birth defects in the Philippines.
Birth Defects Res A Clin Mol Teratol. 2004;
70 (7):464-71.
23. Tamura T, Munger RG, Corcoran C, et al.
Plasma zinc concentrations of mothers and the
risk of nonsyndromic oral clefts in their children:
a case-control study in the Philippines. Birth
Defects Res A Clin Mol Teratol. 2005;73(9):
612-6.
24. Dansky LV, Finnell RH. Parental epilepsy,
anticonvulsant drugs and reproductive
outcome: epidemiologic and experimental
findings spanning three decades; 2: human
studies. Reprod Toxicol. 1991;5(4):301-35.
25. Nguyen HT, Sharma V, McIntyre RS.
Teratogenesis associated with antibipolar
agents. Adv Ther. 2009;26(3):281-94.
26. Jentink J, Loane MA, Dolk H, et al. Valproic
acid monotherapy in pregnancy and major
congenital malformations. N Engl J Med.
2010;362(23):2185-93.
29. Feldkamp ML, Meyer RE, Krikov S, et al.
Acetaminophen use in pregnancy and risk of
birth defects: findings from the National Birth
Defects Prevention Study. Obstet Gynecol.
2010;115(1):109-15.
30. Holmberg PC, Hernberg S, Kurppa K, et al.
Oral clefts and organic solvent exposure during
pregnancy. Int Arch Occup Environ Health
1982;50(4):371-6.
31. Marshall EG, Harris G, Wartenberg D. Oral cleft
defects and maternal exposure to ambient air
pollutants in New Jersey. Birth Defects Res A
Clin Mol Teratol. 2010;88(4):205-15.
32. Garcia AM, Fletcher T, Benavides FG, et al.
Parental agricultural work and selected
congenital malformations. Am J Epidemiol.
1999;149(1):64-74.
33. Beaty TH, Ruczinski I, Murray JC, et al.
Evidence for gene-environment interaction in a
genome wide study of nonsyndromic cleft
palate. Genet Epidemiol. 2011;35(6):469-78.
50 | CONGENITAL ANOMALIES IN CANADA 2013
CHAPTER 6
LIMB DEFICIENCY DEFECTS
Alison M. Elliott
Jocelyn Rouleau
Jane A. Evans
INTRODUCTION
Limb Deficiency Defects (LDDs), also known as limb
reduction defects, are conspicuous anomalies that
are highly variable in their presentation. They can be
characterized by total or partial absence of a limb,
or can involve a smaller portion, such as a missing
finger or toe.1 LDDs can occur as isolated
malformations or be found in association with other
anomalies. Although they are relatively uncommon,
the surveillance of these anomalies is important as
their occurrence can contribute to the identification
of teratogens. Indeed, surveillance of congenital
anomalies in many jurisdictions was introduced
following the identification of the embryopathy
associated with thalidomide exposure in the late
1950s and early 1960s.
LDDs are a heterogeneous group of limb
malformations. Three to eight infants per 10,000 live
births are affected with an LDD1-4 and in at least 30%
of these the LDD is associated with other congenital
malformations.5,6 The most common cause of limb
deficiency relates to vascular disruption (2.2 per
10,000),3 although the precise pathogenetic
mechanisms involved in this remain unclear.
Mortality is increased when the malformation is
found in association with severe anomalies of other
systems, such as cardiac defects.
The most severe LDD is Amelia — absence of a
limb, while partial absences are often classified
based on the affected segment. Intercalary defects
refer to the absence or hypoplasia of a long bone
(e.g., femur or humerus) with more normal structures
distally. Terminal transverse defects have absence of
distal structures perpendicular to the limb. Some
transverse defects can be complete (e.g., total
absence of a forearm or foot or just involve certain
digits).3 Longitudinal defects are defined as the
absence or hypoplasia of bones parallel to the
longitudinal axis and can be characterized as
central, preaxial (thumb/radial side) or postaxial (fifth
ray/ulnar side) depending on the affected
developmental field.
Limb development is a complex process involving
multiple molecular networks. Limb differentiation
occurs sequentially with the upper limb developing
24 hours before the lower and is first recognized as
a small limb bud at the 26th day after fertilization.7
There are three different axes on which the limb
develops. Certain genes are necessary for limb
outgrowth, (e.g., TBX5 for the upper limb).8
Classifications of limb defects can be anatomic,
molecular, etiological or embryologic. Swanson
proposed a classification of limb malformations
based on patterns of deficiencies according to the
parts that have been primarily affected by certain
embryological failures.9 Although intended for use
with hand changes, it can be extrapolated to
include the foot and entire upper and lower limbs.
Category I refers to failure of formation of parts
(arrest of development) while V refers to
undergrowth (hypoplasia) and VI refers to congenital
constriction band syndrome (also known as amniotic
band syndrome). Each general category can be
further classified (e.g., Category I can be complete
or partial; transverse or longitudinal). Gold and
colleagues have proposed a classification based on
the anatomy and etiology of the defect.3
Challenges in the surveillance of LDDs result from
inconsistent classification systems. Definitions based
on embryologic involvement have been utilized, but
are not universally accepted and do not necessarily
translate into the International Classification of
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Diseases (ICD) codes.10 Furthermore, the transition
from ICD9 to ICD10 involved classification changes
that did not capture all defects consistently (e.g.,
central ray deficiency/split hand-foot malformation).
The International Clearinghouse for Birth Defects
Surveillance and Research proposed a descriptive
classification system, and distinguishes anomalies
into three general types: deficiencies,
supernumerary and fusion/separation defects.11,12
RISK FACTORS
In addition to known single gene disorders, LDDs
can be due to chromosomal causes, early chorionic
villous sampling13 and other environmental insults
including the medications thalidomide14 and
misoprostol.15 Thalidomide is the most well known
teratogen with respect to limb development. The
critical period of sensitivity to thalidomide
embryopathy is between 20 and 36 days post
conception.16 Approximately 20% of pregnancies
exposed during this gestational window will result in
affected children who have a wide variety of LDDs in
addition to other congenital malformations.16,17
Recently, it has been shown that infants born after in
vitro fertilization show an increased risk for limb
reduction defects.18
Altered homocysteine metabolism has been
associated with an increased risk of neural tube
defects. Maternal homozygosity for the common
methylenetetrahydrofolate reductase mutation,
C677T, a known contributor to neural tube defects
has also been suggested as a potential risk factor
for limb defects.19 While the protective effect of folic
acid for neural tube defects is well established, data
with respect to LDDs is conflicting. Bower et al.
showed that neither folic acid supplements nor
dietary folate prevented LDDs.20 Robitaille et al.
showed that LDD rates were not associated with
supplement use, but that transverse limb
deficiencies were associated with low intakes of
riboflavin from diet.21 Ethnicity can also play a role.
Werler and colleagues showed that Hispanic women
had an increased risk for terminal limb deficiencies.
These researchers also demonstrated that maternal
cigarette smoking and aspirin use both increased
the risk of these malformations.22 Drug exposures
associated with a potential increase risk for LDDs
include valproic acid, amniopterin, methotrexate,
hydantoin and isotretinoin.17,23-25 Pregestational
maternal diabetes has also been associated with
limb deficiency.26-28 Maternal obesity has been
implicated as well, but the literature is
inconsistent.29-32
PREVALENCE RATE OF LIMB DEFICIENCY
DEFECTS IN CANADA
In 1998 in Canada, the rate of LDDs in live births
and stillbirths (including pregnancy terminations
over 20 weeks gestation occurring in hospitals) was
4.5 per 10,000 total births compared to 3.5 per
10,000 in 2007 (Figure 6.1). A decrease in risk
factors, such as cigarette smoking and an increase in
preventive measures, such as food fortification with
folic acid, may help to explain the downward trend.
However, it may also be a reflection of increased
uptake of prenatal diagnosis and termination of
affected pregnancies.
52 | CONGENITAL ANOMALIES IN CANADA 2013
FIGURE 6.1
Limb deficiency defect (LDD) rate, Canada, 1998–2007
5.0
LDD per 10,000 total births*
4.8
4.6
4.5
4.4
4.2
4.1
4.1
4.0
3.8
3.8
3.8
3.7
3.7
3.6
3.5
3.5
3.4
3.3
3.2
3.0
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007. *Total births include live births and stillbirths.
FIGURE 6.2A
Limb deficiency defect (LDD) rate, by province/territory, Canada, 1998–2007 combined
CANADA
Newfoundland and Labrador
Prince Edward Island §
Nova Scotia
New Brunswick
Québec
Ontario
Manitoba
Saskatchewan
Alberta
British Columbia
Yukon §
Northwest Territories §
Nunavut §
0
1
2
3
4
5
6
7
LDD (95% CI) per 10,000 total births*
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. §Rate suppressed due to small cell counts (<5). CI—Confidence Interval
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FIGURE 6.2B
Ratio of provincial/territorial limb deficiency defect rate to national rate,** Canada, 1998–2007 combined
Birth Prevalance Ratios
> 1.50
1.26 - 1.50
1.01 - 1.25
0.76 - 1.00
<0.76
No Cases or Suppressed
*
Statistical Significance
YT
NT
BC
AB*
NU
NL
SK*
MB
ON*
NL
QC*
PE
NB
NS
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
**This ratio calculates the birth prevalence rate per 10,000 total births of each individual province/territory to the birth prevalence rate for Canada
during the specified time period. The birth prevalence for Canada includes cases for which province/territory is unknown.
PROVINCIAL AND TERRITORIAL
PREVALENCE RATES
Provincial and territorial rates from 1998–2007 are
shown in Figure 6.2A. The LDD rate varied among
Canadian provinces and territories (Figure 6.2B).
This variation may be due in part to differing data
sources (CIHI, ACASS, MED-ÉCHO) and coding
practices. Uptake of prenatal diagnosis and the
likelihood of termination of affected pregnancies
are also factors that may influence rate differences.
Identification of specific genetic or environmental
risk factors that could be contributing to regional
variation would require more detailed
epidemiological evaluation.
INTERNATIONAL COMPARISONS
The data presented in Table 6.1 are from
surveillance programs that, like the Canadian
Congenital Anomalies Surveillance System (CCASS),
include live births and stillbirths, but not early
terminations of pregnancy.11 Canada’s rate is similar
to those of Ireland, Slovak Republic, Spain and
Japan. Data from Chilean and South American
registries indicate the highest rate (9.7 per 10,000
and 9.3 per 10,000 total births, respectively). These
increased rates potentially reflect limited access to
prenatal diagnosis and termination of pregnancy. In
Brazil, for example, where terminations of
pregnancy are illegal, the use of misoprostol, an
abortifacient, could have increased rates.15,33 An
additional factor potentially contributing to the high
rates in Brazil could be the continued use of
thalidomide to treat conditions such as leprosy.34
Diet, nutrition, environmental exposures (e.g.,
tobacco smoke and other forms of air pollution),
altitude and inherent ethnic differences22 may also
contribute to these differences in rates.
54 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE 6.1
Limb deficiency defect (LDD) international rate, by region/country, 2007
Country/Region
Rate of LDD*
CANADA†
3.5
Japan
3.0
Ukraine
5.1
Slovak Republic
2.8
Spain
4.6
Dublin, Ireland
3.4
Mexico
6.1
Maule, Chile
9.7
South America
9.3
Source: International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) Annual Report, 2009 (data from 2007).
†Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2007. *Per 10,000 total births.
IMPACT OF PRENATAL DIAGNOSIS
ON BIRTH PREVALENCE OF LDD
Major limb defects can be diagnosed prenatally by
second trimester ultrasound. Depending upon the
type of LDD, the presence of other malformations
and ultrasound screening policies, the reported
detection rate for isolated LDDs varies from 20%–
64%.35 As noted, prenatal diagnosis potentially
influences rates both nationally and internationally.
PREVENTIVE MEASURES
The avoidance of risk factors, such as certain
medications and smoking, will help to reduce
prevalence of LDDs. The potential protective effect
of nutritional factors will require further study.
Ongoing surveillance of LDDs in Canada will be
necessary to examine the impact of risk factors and
effectiveness of risk reduction strategies.
SUMMARY
LDDs are a complex and highly variable group of
congenital limb malformations. The thalidomide
tragedy highlighted the importance of birth defects
surveillance and more specifically for these defects.
Since that time, a variety of environmental risk
factors have been proposed to be associated with
LDDs. Ongoing surveillance combined with
epidemiological analysis is essential in order to
establish true prevalence rates and the importance
of specific risk factors.
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villus sampling: a distinctive teratogenic effect
on fingers? Birth Defects Res A Clin Mol
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19. Shashi V, Rickheim A, Pettenati MJ. Maternal
homozygosity for the common MTHFR
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11. International Clearinghouse for Birth Defects
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21. Robitaille J, Carmichael SL, Shaw GM, et al.
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22. Werler MM, Bosco JL, Shapira SK. Maternal
vasoactive exposures, amniotic bands, and
terminal transverse limb defects. Birth Defects
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23. Alessandri JL, Isidor B, David A, et al. Tibial
developmental field defect in valproic acid
embryopathy: report on three cases. Am J Med
Genet A. 2010;152A(11):2805-9.
24. Honein MA, Paulozzi LJ, Erickson JD.
Continued occurrence of Accutane-exposed
pregnancies. Teratology. 2001;64(3):142-7.
25. Evermann D. Hands and Feet. In: Stevenson
RE, Hall JG, editors. Human Malformations and
Related Anomalies. New York: Oxford
University Press; 2006. p. 935-96.
26. Aberg A, Westbom L, Kallen B. Congenital
malformations among infants whose mothers
had gestational diabetes or preexisting
diabetes. Early Hum Dev. 2001;61(2):85-95.
27. Correa A, Gilboa SM, Besser LM, et al.
Diabetes mellitus and birth defects. Am J
Obstet Gynecol. 2008;199(3):237-9.
28. Van Allen MI, Jackson JC, Knopp RH, et al. In
utero thrombosis and neonatal gangrene in an
infant of a diabetic mother. Am J Med Genet.
1989;33(3):323-7.
29. Moore LL, Singer MR, Bradlee ML, et al. A
prospective study of the risk of congenital
defects associated with maternal obesity and
diabetes mellitus. Epidemiology.
2000;11(6):689-94.
30. Shaw GM, Todoroff K, Schaffer DM, et al.
Maternal height and prepregnancy body mass
index as risk factors for selected congenital
anomalies. Paediatr Perinat Epidemiol.
2000;14(3):234-39.
31. Waller DK, Shaw GM, Rasmussen SA, et al.
Prepregnancy obesity as a risk factor for
structural birth defects. Arch Pediatr Adolesc
Med. 2007;161(8):745-50.
32. Watkins ML, Rasmussen SA, Honein MA, et al.
Maternal obesity and risk for birth defects.
Pediatrics. 2003;111(5 Part 2):1152-8.
33. Gonzalez CH, Vargas FR, Perez AB, et al. Limb
deficiency with or without Mobius sequence in
seven Brazilian children associated with
misoprostol use in the first trimester of
pregnancy. Am J Med Genet. 1993;47(1):59-64.
34. Vianna FS, Lopez-Camelo JS, Leite JC, et al.
Epidemiological surveillance of birth defects
compatible with thalidomide embryopathy in
Brazil. PloS One. 2011;6(7):e21735.
35. Stoll C, Wiesel A, Queisser-Luft A, et al.
Evaluation of the prenatal diagnosis of limb
reduction deficiencies. EUROSCAN Study
Group. Prenat Diagn. 2000;20(10):811-8.
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CHAPTER 7
GASTROSCHISIS
Aideen Moore
Jocelyn Rouleau
Erik Skarsgard
INTRODUCTION
Gastroschisis is a defect of the abdominal wall of
the develop­­ing fetus resulting in extrusion of the
intestines into the amniotic space. The defect is
typically located to the right of the umbilicus and
can usually be detected during pregnancy by a
combination of maternal serum screening and
ultrasound. Unlike omphalocele, which is frequently
associated with other anomalies, gastroschisis is
usually an isolated defect. Treatment consists of
either urgent surgical closure or delayed closure
after gradual reduction of herniated viscera using a
preformed silo, which is placed over the bowel and
through the defect. Survival in gastroschisis exceeds
90%,36 however, babies suffer variable degrees of
morbidity related to the severity of bowel injury
present at birth. A temporal increase in the
incidence of gastroschisis has been observed in
many countries, including Canada. The reason for
this increase is unclear, but is the focus of
epidemiologic studies worldwide.
RISK FACTORS
The cause of gastroschisis is unknown, but is
presumed to be due to multiple factors. The most
widely accepted hypothesis is that of vascular
disruption, either of the right umbilical vein1 or the
right vitelline artery,2 which predisposes to focal
weakness and disruption of the paraumbilical
abdominal wall. Most cases are sporadic. Although
it is generally accepted that additional
malformations are uncommon, recent Canadian
data suggest that such defects may be responsible
for stillbirths and early neonatal deaths that might
not otherwise have been attributed to associated
anomalies, suggesting a “hidden mortality” due to
associated anomalies.3
The most consistently observed epidemiologic
phenomenon of gastroschisis is the inverse
relationship between maternal age and birth
prevalence. A population based study of 395 cases
from Florida identified an adjusted relative risk (RR)
of 3.4 in the under 20 year of age cohort, and of 1.9
in the 20–24 year cohort compared to the reference
group of 25–29 years.4 Aggregate data (936 cases)
from EUROCAT reported an RR of 7.0 in the under
20 year, and of 2.4 in the 20–24 year group
compared to the 25–29 year reference group.5 This
phenomenon has been consistently observed in the
majority of studies.6-8 It is not clear whether the
observed temporal increase is due exclusively to
increased prevalence within the teenage mother
population,9 or whether the overall prevalence
increase is attributable to increased prevalence at
birth in all age groups.10,11
Studies of risk related to paternal age (adjusted for
young maternal age), suggests that young paternal
age may be an independent risk factor. One study
reports a 1.6 fold increase in risk per 10 year
reduction in paternal age,11 while a second
suggests a 1.5 fold increased risk of affected
offspring in a 20–24 year group compared to the
25–29 year group.12
Among teenage mothers and those aged
20–24 years, whites appear to be at increased risk
compared with blacks and “other” ethnicities.13
However, in another study in which ethnicity
categories were adjusted for maternal age, mothers
of Hispanic ethnicity were more likely to have an
affected infant than those who were white.14
58 | CONGENITAL ANOMALIES IN CANADA 2013
Measures of socioeconomic status (SES) have also
been examined. In an analysis controlled for
maternal age, an annual family income of less than
$10,000 was associated with an increased likelihood
of gastroschisis compared to a referent family
income of $50,000 or more (RR=4.5).7 However,
other factors frequently reflective of SES, such as
maternal education level, have not been found to
confer increased risk.7,15
The association between cigarette smoking and
gastroschisis has been widely studied, with most
studies suggesting a moderate risk increase among
mothers who smoke during pregnancy, with RR
adjusted for maternal age ranging from 1.5–2.0.16-18
One study suggested a dose-response relationship
with higher rates among mothers who smoked 20 or
more cigarettes per day.19 Studies of maternal
alcohol consumption have shown a relationship
between first trimester alcohol consumption
(including binge drinking) and the risk for
gastroschisis, with an observed two to three fold
increase in incidence.7,15 Maternal exposure to illicit
drugs is another postulated risk factor, with most
studies relying on self-reporting as the method by
which exposure is documented. Among drugs
evaluated in age-matched controlled studies, the
strongest associations emerge with cocaine: odds
ratio (OR)=1.7–4.6, marijuana (OR=3.0) and
methamphetamines (OR=0.9–1.8).7,18,19 In addition
to increasing risk of gastroschisis, non-therapeutic
exposures are also associated with poorer functional
outcomes, as well as more severe bowel injury
noted at birth. In one Canadian study, infants of
mothers who had smoked took significantly more
days to recover before they were able to tolerate
enteral nutrition20 and, in a second study, cocaine
use was associated with a higher severity of bowel
injury (e.g., perforation, necrosis or atresia) detected
at birth.21 A study from Washington State has shown
an association with month of birth that persisted on
multivariate analysis, suggesting that infants born in
January, February or March are twice as likely to
have gastroschisis as infants born in other months.22
This finding raises the possibility that infection might
be playing a role in causation. Another study
supportive of an infectious contribution suggests
that gastroschisis is more common in infants of
women who had a genitourinary infection in the
month preceding pregnancy or during the first
trimester. Women who reported both a urinary tract
infection and a sexually transmitted disease had a
significantly increased risk.23 Environmental
exposure data from the Washington State study
linked maternal residence distance to high surface
water herbicide (e.g., atrazine) concentrations to an
increased risk.24 In this same study, spring
conception (coinciding with herbicide spraying) was
also associated with a higher birth prevalence,
raising the concern that controllable environmental
exposures may contribute to risk.
Recent data suggest a relationship with prepregnancy body mass index (BMI). One study
observed a higher rate in underweight compared to
normal weight mothers, with an OR adjusted for age
and ethnicity of 3.0.25 Two other studies have
demonstrated a lower risk in mothers who are
overweight or obese, compared to those of
normal weight.26,27
Dietary markers of good and poor nutrition were
correlated with gastroschisis occurrence in an
age-matched case control study.28 Dietary intake
data for the three months preceding conception
were recorded and diets were classified as either
low or adequate for a-carotene and glutathione
(both anti-oxidants), and normal or high nitrosamine.
This study identified associations on multivariate
analysis between low a-carotene, low total
glutathione and high nitrosamines and gastroschisis.
Another dietary study considered the relationship
with dietary fats, based on a hypothesized
relationship between dietary fat and
vasoconstriction leading to fetal vascular
disruption.29 This case-control study looked at
dietary fat intake in the year prior to conception and
found that there was an association, albeit weak,
between total fat intake in the middle and high
centiles and the occurrence of gastroschisis.
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A number of studies have looked at the effect of
prenatal exposure to therapeutic medications.
Evidence supporting increased risks among women
using aspirin, ibuprofen or acetaminophen is weak
overall, but strongest for aspirin with OR on
multivariate analysis ranging from 2.7–20.4.18,30
Studies looking at maternal decongestant use are
inconsistently associated with increased risk.15,31
PREVALENCE RATE OF GASTROSCHISIS
IN CANADA
Based on aggregate data from 2002 to 2009 from
the Canadian Congenital Anomalies Surveillance
System (CCASS), the prevalence rate of
gastroschisis in Canada is 3.7 per 10,000 total
births. Over this time period there has been a
gradual increase in prevalence (Figure 7.1), similar
to reports from many other countries. Specifically,
the rate of gastroschisis in Canada (excluding the
province of Québec) increased from 3.1 per 10,000
total births (i.e., live births and stillbirths) in 2002 to
4.4 per 10,000 total births in 2009, which
corresponded to 129 individual cases for 2009. This
represents an increase of 43.8% (P=0.015). The
reason for this rise in prevalence is unknown.
The rates presented in this report were restricted to
2002–2009 because prior to 2002 CCASS used the
International Classification of Diseases (ICD)-9
codes where gastroschisis and omphalocele
(and prune belly syndrome) could not be
differentiated, as they were all under one
code (756.7). ICD-10 gave them separate codes.
The province of Alberta used the British Pediatric
Association expansion of the ICD-9, which did
differentiate them.
FIGURE 7.1
Gastroschisis rate, Canada, 2002–2009*
Gastroschisis per 10,000 total births**
5.0
4.2
3.4
3.1
3.0
2002
2003
3.5
3.5
2004
2005
3.6
4.4
4.4
2008
2009
3.8
2.6
1.8
1.0
2006
2007
Source: Public Health Agency of Canada, Canadian Congenital Anomalies Surveillance System, 2002–2009.
*Some provincial data were only available for certain years: New Brunswick (2004–2009), Québec (2006–2007) and Manitoba (2005–2009).
All others were available for the full period (2002–2009). **Total births include live births and stillbirths.
60 | CONGENITAL ANOMALIES IN CANADA 2013
PROVINCIAL AND TERRITORIAL
PREVALENCE RATES
The birth prevalence of gastroschisis varies
considerably across Canada (Figures 7.2A and B). In
2002–2009, the rates ranged from 19.6 (95% CI
9.4–36.1) per 10,000 total births in Nunavut to 1.6
(95% CI 1.1–2.4) in Québec. Although small
changes in case numbers could markedly influence
rates in areas with few births, maternal age
differences may explain some of this difference as
the age specific fertility rate for 10–19 year olds in
2004 was 59.2 (95% CI 51.1–68.1) per 1,000 females
in Nunavut compared to 5.1 (95% CI 4.9–5.3) per
1,000 females in Québec.32 Rates of smoking in
pregnancy also show geographic differences with
Nunavut again having very high rates.32
FIGURE 7.2A
Gastroschisis rate, by province/territory, Canada, 2002–2009* combined
CANADA
Newfoundland and Labrador
Prince Edward Island
Nova Scotia
New Brunswick
Québec
Ontario
Manitoba
Saskatchewan
Alberta
British Columbia
Yukon §
Northwest Territories §
Nunavut
0
5
10
15
20
25
30
35
40
Gastroschisis (95% CI) per 10,000 total births**
Source: Public Health Agency of Canada, Canadian Congenital Anomalies Surveillance System, 2002-2009.
*New Brunswick 2004-2009, Manitoba 2005-2009 and Québec 2006-2007. **Total births include live births and stillbirths.
§ Rate suppressed due to small cell numbers (<5). CI—Confidence Interval
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FIGURE 7.2B
Ratio of provincial/territorial gastroschisis rate to national rate,** Canada, 2000–2009 combined
Birth Prevalance Ratios
> 1.50
1.26 - 1.50
1.01 - 1.25
0.76 - 1.00
<0.76
No Cases or Suppressed
*
Statistical Significance
YT
NT
BC
AB*
NU*
NL
SK
MB*
ON*
NL
QC*
PE
NB
NS*
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2000–2009.
**This ratio calculates the birth prevalence rate per 10,000 total births of each individual province/territory to the birth prevalence rate for Canada
combined for the eight-year period 2002–2009, with the exception of New Brunswick 2004–2009, Manitoba 2005–2009 and Québec 2006–2007.
The birth prevalence for Canada includes cases for which province/territory is unknown.
INTERNATIONAL COMPARISONS
Table 7.1 illustrates the variation in prevalence of
gastroschisis worldwide. Prevalence rates for 2007
range from a low of 0.7 cases per 10,000 births in
Campania-Italy to a high of 9.4 cases per 10,000
births in South America. Geographical differences in
prevalence have also been reported within Europe
by EUROCAT, with higher rates of gastroschisis in
the United Kingdom and lower rates in more
southerly countries such as Italy, even after adjusting
for maternal age.10 In the United States, the state of
Texas reported a 5.1% annual increase in prevalence
during 1999–200733 and North Carolina reported a
130% increase from 1997 to 2000, a shift from 2.0
to 4.5 per 10,000 live births, primarily due to lower
maternal age.34 Similar to the Canadian data, most
registries reporting to the International
Clearinghouse for Birth Defects Surveillance and
Research showed higher prevalence rates in 2007
compared to previous periods.35
IMPACT OF PRENATAL DIAGNOSIS ON
BIRTH PREVALENCE OF GASTROSCHISIS
Most cases of gastroschisis are now diagnosed
antenatally; the British Isles Network of Congenital
Anomaly Registrars registry for the United Kingdom
showed 97% of cases being diagnosed antenatally,36
while Canadian figures showed that 94% were
diagnosed antenatally.37 Less than 10% of cases are
associated with other congenital anomalies and
terminations for isolated defects are infrequent.
Hence, prenatal diagnosis appears to have had little
impact on the prevalence at birth of gastroschisis.
62 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE 7.1
Gastroschisis international rate, by region/country, 2007
Country/ Registry
Rate of gastroschisis*
CANADA†
3.8
Alberta, Canada
4.9
British Columbia, Canada
5.0
Victoria, Australia
1.9
Western, Australia
3.7
Chile
2.2
Finland
3.7
Campania, Italy
0.7
Japan
1.9
South America
9.4
Sweden
1.7
Wessex, United Kingdom
4.8
Wales, United Kingdom
3.8
Atlanta, USA
5.9
Texas, USA **
5.1
Utah, USA
5.1
Source: International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) Annual Report, 2009 (data from 2007)
*Per 10,000 total births. **Source: Texas, 2006 data.
†Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2007.
PREVENTIVE MEASURES
SUMMARY
The strong association with young maternal age
and also the observed relationship with maternal
undernutrition25,28 indicate that reduction in teenage
pregnancy rates and ensuring good maternal
nutrition may help reduce risk, as would avoidance
of maternal smoking, alcohol use and other high risk
behaviours. Ongoing epidemiological studies may
identify other modifiable risk factors.
4-11
Gastroschisis is one of the more serious congenital
anomalies, requiring urgent surgical and medical
intervention at birth. The mortality rate is
approximately 5%37 and morbidity with prolonged
hospital stay and occasionally intestinal failure is
significant.37,38 It is vital that continued surveillance
efforts are directed towards monitoring the
increasing prevalence in Canada and its
regional variability, as well as identifying the
factors—environmental, pharmacological
or otherwise—that may be contributing to
this increase.
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REFERENCES
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The vascular pathogenesis of gastroschisis:
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gastroschisis in Europe 1980-2002: a
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Paediatr Perinat Epidemiol. 2007;21:363-9.
11. Kazaura MR, Lie RT, Irgens LM, et al. Increasing
risk of gastroschisis in Norway: an age-periodcohort analysis. Am J Epidemiol. 2004;159(4):
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3. Akhtar J, Skarsgard ED. Associated
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gastroschisis. J Pediatr Surg. 2012;47(5):911-6.
12. Archer NP, Langlois PH, Suarez L, et al.
Association of paternal age with prevalence of
selected birth defects. Birth Defects Res A Clin
Mol Teratol. 2007;79(1):27-34.
4. Salemi JL, Pierre M, Tanner JP, et al. Maternal
nativity as a risk factor for gastroschisis: a
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Clin Mol Teratol. 2009;85(1):890-6.
13. Williams LJ, Kucik JE, Alverson CJ, et al.
Epidemiology of gastroschisis in metropolitan
Atlanta, 1968 through 2000. Birth Defects Res
A Clin Mol Teratol. 2005;73(3):177-83.
5. Castilla EE, Mastroiacovo P, Orioli IM.
Gastroschisis: international epidemiology and
public health perspectives. Am J Med Genet C
Semin Med Genet. 2008;148C(3):162-79.
14. Salihu HM, Pierre-Louis BJ, Druschel CM, et al.
Omphalocele and gastroschisis in the State of
New York, 1992-1999. Birth Defects Res A Clin
Mol Teratol. 2003;67(9):630-6.
6. Reefhuis J, Honein MA. Maternal age and
non-chromosomal birth defects, Atlanta —
1968-2000: teenager or thirty-something, who
is at risk? Birth Defects Res A Clin Mol Teratol.
2004;70(9):572-9.
15. Werler MM, Mitchell AA, Shapiro S.
Demographic, reproductive, medical, and
environmental factors in relation to
gastroschisis. Teratology. 1992;45(4):353-60.
7. Torfs CP, Velie EM, Oechsli FW, et al. A
population-based study of gastroschisis:
demographic, pregnancy, and lifestyle risk
factors. Teratology. 1994;50(1):44-53.
8. Rittler M, Castilla EE, Chambers C, et al. Risk
for gastroschisis in primigravidity, length of
sexual cohabitation, and change in paternity.
Birth Defects Res A Clin Mol Teratol.
2007;79(6):483-7.
9. Nichols CR, Dickinson JE, Pemberton PJ. Rising
incidence of gastroschisis in teenage
pregnancies. J Matern Fetal Med.
1997;6(4):225-9.
10. Loane M, Dolk H, Bradbury I ; EUROCAT
Working Group. Increasing prevalence of
16. Haddow JE, Palomaki GE, Holman MS. Young
maternal age and smoking during pregnancy
as risk factors for gastroschisis. Teratology.
1993;47(3):225-28.
17. Martinez-Frias ML, Rodriguez-Pinilla E, Prieto L.
Prenatal exposure to salicylates and
gastroschisis: a case-control study. Teratology.
1997;56(4):241-43.
18. Draper ES, Rankin J, Tonks AM, et al.
Recreational drug use: a major risk factor for
gastroschisis? Am J Epidemiol. 2008;167(4):
485-91.
19. Werler MM, Sheehan JE, Mitchell AA.
Association of vasoconstrictive exposures with
risks of gastroschisis and small intestinal atresia.
Epidemiology. 2003;14(3):349-54.
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20. Weinsheimer RL, Yanchar NL; Canadian
Pediatric Surgical Network. Impact of maternal
substance abuse and smoking on children with
gastroschisis. J Pediatr Surg. 2008;43(5):879-83.
30. Werler MM, Sheehan JE, Mitchell AA. Maternal
medication use and risks of gastroschisis and
small intestinal atresia. Am J Epidemiol.
2002;155(1):26-31.
21. Brindle ME, Wales PW, Flageole H; Canadian
Pediatric Surgery Network. Influence of
maternal factors on health outcomes in
gastroschisis: a Canadian population-based
study. Neonatology. 2012;102(1):45-52.
31. Torfs CP, Katz EA, Bateson TF, et al. Maternal
medications and environmental exposures as
risk factors for gastroschisis. Teratology.
1996;54(2):84-92.
22. Goldbaum G, Daling J, Milham S. Risk factors for
gastroschisis. Teratology. 1990;42(4):397-403.
23. Feldkamp ML, Reefhuis J, Kucik J, et al. Casecontrol study of self reported genitourinary
infections and risk of gastroschisis: findings from
the national birth defects prevention study,
1997-2003. BMJ. 2008;336(7658):1420-3.
24. Waller SA, Paul K, Peterson SE, et al.
Agricultural-related chemical exposures, season
of conception, and risk of gastroschisis in
Washington State. Am J Obstet Gynecol.
2010;202(3):241.e1-241.
25. Lam PK, Torfs CP, Brand RJ. A low pregnancy
body mass index is a risk factor for an offspring
with gastroschisis. Epidemiology. 1999;10(6):
717-21.
26. Waller DK, Shaw GM, Rasmussen SA, et al.
Prepregnancy obesity as a risk factor for
structural birth defects. Arch Pediatr Adolesc
Med. 2007;161(8):745-50.
27. Stothard KJ, Tennant PW, Bell R, et al. Maternal
overweight and obesity and the risk of
congenital anomalies: a systematic review and
meta-analysis. JAMA. 2009;301(6):636-50.
28. Torfs CP, Lam PK, Schaffer DM, et al.
Association between mothers’ nutrient intake
and their offspring’s risk of gastroschisis.
Teratology. 1998;58(6):241-50.
29. Siega-Riz AM, Olshan AF, Werler MM, et al. Fat
intake and the risk of gastroschisis. Birth Defects
Res A Clin Mol Teratol. 2006;76(4):241-5.
32. Public Health Agency of Canada. Canadian
Perinatal Health Report, 2008 Edition.
Ottawa: Minister of Health, 2008.
33. Langlois PH, Mareng LK, Canfield MA. Time
trends in the prevalence of birth defects in Texas
1999-2007: real or artifactual? Birth Defects Res
A Clin Mol Teratol. 2011;91(10):902-17.
34. Laughon M, Meyer R, Bose C, et al. Rising birth
prevalence of gastroschisis. J Perinatol.
2003;23(4):291-3.
35. International Clearinghouse for Birth Defects
Surveillance and Research. Annual Report 2009
with data for 2007. Rome, Italy: International
Center on Birth Defects; 2009. Available from:
http://www.icbdsr.org/filebank/documents/
ar2005/Report2009.pdf.
36. Boyd PA, Tonks AM, Rankin J, et al. Monitoring
the prenatal detection of structural fetal
congenital anomalies in England and
Wales: register-based study. J Med Screen.
2011;18(1):2-7.
37. Baird R, Eeson G, Safavi A, et al. Institutional
practice and outcome variation in the
management of congenital diaphragmatic
hernia and gastroschisis in Canada. J Pediatr
Surg. 2011;46(5):801-7.
38. Wales PW, de Silva N, Kim JH, et al. Neonatal
short bowel syndrome: a cohort study. J Pediatr
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CHAPTER 8
PRIMARY PREVENTION: MODIFIABLE RISK FACTORS
Michiel Van den Hof
Amanda MacFarlane
Paromita Deb-Rinker
Rachel McMillan
Wei Luo
Prevention involves avoidance of disease through
deliberate strategies that take into consideration
knowledge of risk factors and their pathophysiologic
influences. Avoiding fetal/neonatal disease is likely
to be cost effective given the emotional, economic
and health services resources needed to deal with
lifelong morbidity. The in utero environment is
influenced by maternal exposures such as
medication use, lifestyle and environmental risk
factors, all of which are also influenced by
socioeconomic status (SES). Nutrition also influences
fetal development. Correcting nutrient deficiencies
is important with the caveat that over-correction
may have its own inherent risks. In addition,
maternal demographics are changing and these
changes also have the potential to alter fetal
outcome. Genetic risk from advanced and very
young maternal age or chronic maternal
medical conditions can negatively impact fetal/
neonatal outcomes.
Primary prevention issues for congenital anomalies
have been arbitrarily categorized into: (1) maternal
environmental/SES factors; (2) nutritional factors;
and (3) the influences of maternal age along with
common chronic medical diseases.
MATERNAL ENVIRONMENT AND
SOCIOECONOMIC FACTORS
SES is closely related to health outcomes, including
perinatal and infant health. SES is measured using a
combination of indicators such as education,
occupation and individual/family income since these
factors are often closely interrelated.1 Low social
status is a well-established risk indicator for adverse
perinatal and infant outcomes such as low birth
weight, preterm birth, stillbirth and perinatal,
neonatal or post neonatal mortality.2 More
socioeconomically deprived groups have higher
non-chromosomal congenital anomaly rates, part of
which may be explained by differences in nutritional
status. Higher risks of neural tube defects (including
spina bifida and anencephaly) have been reported
in populations with lower SES.3 Trends towards
higher risks in lower social classes have also been
reported for orofacial clefts4 and possibly for
selected congenital heart defects.3 Among residents
of more socioeconomically deprived areas, both
higher and lower birth prevalence rates of Down
syndrome have been reported.5 Average age at first
delivery usually increases with social status thus, in
Down syndrome and similar trisomies that are
associated with higher maternal age, there is a
greater risk with higher social status. It is important
to note that while SES inequalities in rates of
anomalies in utero differ with type of anomaly, there
are also socioeconomic variations in access to
prenatal diagnosis and screening and in termination
of pregnancy rates. This can lead to a widening of
SES inequalities in the rate of live births and
neonatal deaths associated with both chromosomal
and non-chromosomal anomalies.2
Several studies suggest that maternal smoking
during pregnancy is associated with an increased
risk of defects of the cardiovascular, orofacial clefts,
musculoskeletal and gastrointestinal systems.6
These specific defects should be included in public
health educational information to encourage more
women to stop smoking before or in early
66 | CONGENITAL ANOMALIES IN CANADA 2013
pregnancy; in particular, younger women and those
from lower socioeconomic groups, in which smoking
prevalence is greatest, should be targeted.
Alcohol exposure during pregnancy can have many
adverse effects on the developing fetus, resulting in
a spectrum of birth defects that can negatively
affect a child’s growth, cognition, physical
appearance and behaviour. This spectrum of
disorders is referred to as fetal alcohol spectrum
disorders (FASD). Fetal alcohol syndrome (FAS) is
the most serious disorder within this spectrum and is
one of the leading causes of preventable birth
defects and mental handicap. Several maternal risk
factors, including advanced maternal age, illicit drug
use, history of previous pregnancy with FASD, lower
SES and malnutrition in combination with fetal
exposure to alcohol are associated with a higher risk
of FASD.7,8
The use of medications during pregnancy poses a
potential risk to both the mother and fetus. The
effect of many medications on the outcome of
pregnancy are unknown, therefore the safest
pregnancy-related option is to take as few
medications as possible. However, almost every
pregnant woman is exposed to some type of
medication during pregnancy.9 Women with a
history of psychiatric, seizure-related or hematologic
illnesses frequently require medication throughout
pregnancy. In such patients, care must be taken to
select the safest drug from the relevant class of
medication. An estimated less than 1% of birth
defects may be caused by pharmaceutical drugs.10
Among the commonly used over-the-counter
medications, acetaminophen, chlorpheniramine,
kaolin and pectin preparations, and most antacids
have a good safety record. With all medications
used during pregnancy, the benefit of the drug
should outweigh the risk to the fetus, being that less
than 1% of pharmaceuticals are considered to pose
no human teratogenic risk.9
According to the Public Health Agency of Canada’s
Maternity Experiences Survey, 7% of Canadian
women reported having used recreational drugs in
the three months prior to pregnancy and 1%
reported recreational drug use during pregnancy.
Women living in low-income households and
younger mothers were more likely to report having
used illicit drugs both prior to and during
pregnancy.11 Recreational drug use during
pregnancy is associated with low birth weight,
preterm birth, developmental and behavioural
issues during childhood, gastroschisis and
neuroblastoma.11–13
Environmental risk factors such as residence near
industrial sites or socioeconomically deprived areas
have also been studied in association with
congenital anomalies. Increases in risk of adverse
health effects (low birth weight, birth defects and
certain types of cancers) have been reported near
individual landfill sites. Typically, people of lower
SES are more highly exposed to pollution, either
because housing prices are lowest near landfills and
other potentially hazardous locations, have less
power or advocacy skills to prevent exposure, have
less access to environmental health information, or
because aspects of lifestyle associated with greater
deprivation (such as inability to buy bottled water)
lead to higher exposure.14
Embryonic and fetal infections, including
cytomegalovirus, varicella, rubella and
toxoplasmosis infections are also considered
causes/suspected causes for certain congenital
anomalies.15 Vaccination for rubella is an example of
successful primary prevention of congenital
anomalies due to a known viral teratogen.
Cytomegalovirus and toxoplasmosis are now the
most common known infectious teratogens.
Research is needed to determine population
incidence and options for screening/diagnosis, as
well as treatment for these potential fetal threats.
NUTRITION
Good nutrition is critical for appropriate fetal
development and an overall healthy pregnancy. A
number of specific nutrients have been thought to
be associated with risk for congenital anomalies.
The best studied example is folic acid, for which
suboptimal status is associated with increased risk
for neural tube defects (NTDs). Two key randomized
clinical trials in the 1990’s clearly demonstrated that
folic acid supplementation in the periconceptional
period prevented the primary occurrence and
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secondary recurrence of NTDs by approximately
70%.16,17 As such, it is recommended that women of
childbearing age who could become pregnant take
a daily multivitamin supplement containing 0.4 mg
(400 µg) folic acid.18 In addition, since November
1998, the Government of Canada has mandated
folic acid fortification of white flour, pasta and some
other cereal-based products to increase folic acid
intake by approximately 150 µg per day among
women of childbearing age. As a result, the
incidence of NTDs in Canada has declined by
approximately 45%.19
While the weight of evidence for other nutrients
does not equate to that for folic acid and NTDs,
observational and case-control studies have
indicated that achieving an adequate intake of
many nutrients could prevent a number of
anomalies (Table 8.1). The associations reported
between specific nutrients and various congenital
anomalies are not always consistent. However, the
use of multivitamin supplements during pregnancy
is associated with reduced risk for a number of
congenital anomalies such as those noted in Table
8.1.20 Also, deficiency for many nutrients has been
associated with pregnancy complications, such as
preterm delivery, pregnancy-associated anemia,
small-for-gestational-age and preeclampsia. The
evidence therefore emphasises the need for women
to achieve adequate intakes of all nutrients through
a well-balanced diet and a multivitamin supplement
for a healthy pregnancy.18,21 For folic acid in
particular, the Public Health Agency of Canada
recommends that supplements be started prior
to pregnancy.
Women should be cautioned against overconsuming supplemental vitamin A as it has
teratogenic effects and is associated with increased
risk for limb and heart defects.38,39
TABLE 8.1
Low nutrient intake/status as potential risk factors for congenital anomalies
Congenital anomaly
Nutrient(s)
Neural tube defects
Folate/folic acid, vitamin B12, vitamin B6, riboflavin, choline, vitamin C,
vitamin E, vitamin A, beta-carotene, iron, niacin, magnesium and lutein
Congenital heart defects25–27
Folate/folic acid, vitamin B12, riboflavin and nicotinamide
Cleft lip with or without palate28–31
Folate/folic acid, thiamine, niacin, vitamin A, vitamin C, iron, vitamin E,
magnesium and vitamin B6
Limb deficiencies32
Folate/folic acid, vitamin B6 and riboflavin intakes
Hypospadias33
Choline, methionine and vitamin B12
Congenital diaphragmatic hernia34
Folate/folic acid, choline, thiamine, riboflavin, vitamin B6, vitamin B12,
calcium, iron, magnesium, zinc and vitamin E
Fetal bone mineral accrual and
bone morphology35
Vitamin D
Eye development36
Vitamin A
Neurodevelopment and cognitive
development37
Omega-3 fatty acids
22–24
68 | CONGENITAL ANOMALIES IN CANADA 2013
MATERNAL CHRONIC DISEASE
Many maternal chronic diseases are associated with
an increased risk of fetal congenital anomalies or
post-natal developmental abnormalities. For some
pregnant women, a number of these medical
conditions may co-exist and all increase in
prevalence with advanced maternal age. Age
demographics for pregnant women continue to
change with increasing numbers of women choosing
to delay childbearing. Age-specific fertility statistics
show that, for women aged 40–44 years, the fertility
rate has more than doubled between 1986 and
2008 (from 3.4 to 8.4 per 1,000 births).40 The
percentage of pregnant women over the age of 35
years also continues to increase, from 13.4% in 1996
to 18.1% in 2008.41,42 In addition to the known
genetic risks for the fetus, these older mothers are
at higher risk of having or developing chronic
medical conditions that can impact fetal and
newborn health. Some common maternal medical
conditions that are known to influence fetal
outcome are obesity, hypertension, diabetes and
thyroid disease. Older women also tend to have
older partners and there are independent factors
associated with late paternal age, especially
increased risks for de novo genetic mutations.
Maternal obesity has been associated with an
increased risk of many congenital anomalies,
including neural tube defects, congenital heart
defects, orofacial clefts, hydrocephalus, anorectal
atresia and limb reduction abnormalities.43,44 There
appears to be a relationship to severity of obesity.45
Although it is accepted that obesity likely is an
independent risk factor for congenital anomalies,
other co-existing factors such as diabetes may
account for some of the increased risk. In addition,
antenatal congenital anomaly detection rates are
lower in obese women, leading to an increased rate
for neonatal congenital anomalies.46 The rate of
maternal obesity has increased dramatically. In
North America, the rate of obesity among 20 to
39-year-old females has gone from 9.3% in 1986–92
to 20.9% in 2007–2008.47 Maternal obesity can also
develop in pregnancy, particularly among women of
low SES. According to the 2006 Maternity
Experiences Survey, women who are young,
primiparous, less educated or Aboriginal tend to
gain more weight than is recommended during
pregnancy.48 This, in turn, has been shown to be
associated with postpartum weight retention and
places these individuals at higher risk in subsequent
pregnancies.48
The prevalence of diabetes is increasing and this is
likely related to sedentary lifestyle and obesity.
Between 2000 and 2010, the prevalence of diabetes
in the entire Canadian population has increased
103% and is currently at 7.6%. Pre-diabetes within
the population is 21.8%.49 Diabetes in pregnancy
has also increased. Pre-gestational diabetes has
more than doubled between 1999 and 2005 (0.8%
to 1.8%) as shown in a study in USA.50. In 2008/09,
close to 2.4 million Canadians aged one year and
older were living with diagnosed diabetes (either
type 1 or type 2), which represented approximately
6.8% of the population.51 There is a direct
relationship between age and incidence of diabetes.
For all men and women aged 18–34 years, it was
0.9%; for those aged 35–44 years, it was 2%.52 With
pre-gestational diabetes, the risk of both
spontaneous abortion and congenital anomalies is
increased. The risks are directly related to glycemic
control in early pregnancy (less than nine weeks
menstrual dating). Among these women, the overall
risk for congenital anomalies is approximately 6%,
which is double that in the non-diabetic
population.53 Other fetal effects include fetal growth
abnormalities. Accelerated fetal growth can be
initiated by poor early glycemic control. Larger
infants are at increased risk for birth injury and
hypoxia due to shoulder dystocia. Postnatally, they
are at higher risk to develop obesity, diabetes and
attention disorder.54 Maternal diabetes, particularly
with vascular complications, can also be associated
with fetal growth restriction. These infants are at
higher risk for neurodevelopmental delay.55
Maternal thyroid disease and thyroid medication
use have been linked to selected birth defects such
as congenital heart disease, hydrocephaly,
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hypospadias and isolated anorectal atresia.56 In
addition, both hypo- and hyperthyroidism are
associated with other adverse perinatal outcomes.
Hyperthyroidism is linked to low birth weight and
pre-term birth and, on rare occasions, to fetal/
neonatal goitre.57,58 Neonatal hypothyroidism results
in severe mental handicap, but overt maternal
hypothyroidism is also associated with postnatal
neuropsychological and cognitive impairment.
There is also an increased risk for postnatal
neurocognitive dysfunction with maternal subclinical
hypothyroidism, but it is unclear whether this is an
independent risk factor or due to the increased rate
of preterm birth with this condition. The risk of
thyroid disease in pregnancy is related to age,
obesity and family history. Approximately 1% of
pregnant women have overt thyroid dysfunction;
2–3% have subclinical hypothyroidism and 10–15%
are antibody positive.59
SUMMARY
Primary prevention avoids the suffering and cost
associated with congenital anomalies. This chapter
has outlined many factors that increase congenital
anomaly occurrence, but are amenable to
prevention strategies. There have been prior
successes such as the fetal benefits of adequate
nutrient intakes—particularly dramatic with folic acid
food fortification. SES, many environmental factors,
obesity and chronic diseases are recognized as
having widespread importance for public health, in
addition to specifically consequences for the
developing fetus. Nutritional factors require public
education, ready access to good nutrition for
expectant mothers, as well as research on the need
for proper nutrient supplements or additives.
Finally, the public requires ongoing education on
the risks inherent with the age extremes of
reproductive potential.
70 | CONGENITAL ANOMALIES IN CANADA 2013
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CHAPTER 9
SECONDARY PREVENTION: PRENATAL SCREENING
AND DIAGNOSIS
R. Douglas Wilson
INTRODUCTION
Primary prevention is a strategy designed to avoid
the initial occurrence of a disease or condition.
Secondary preventive measures are used for the
early identification, treatment and/or management
of an existing disorder for the purpose of reducing
or preventing morbidity. The distinction between
primary and secondary prevention as it relates to
congenital anomalies (CAs) is less clear. Prenatal
diagnosis and, in some cases, subsequent
termination of pregnancies with a CA is considered
one method of secondary prevention in that it
reduces birth prevalence, but other strategies can
be used to ameliorate the impact of existing
disease. These include prenatal detection,
ultrasound monitoring and early intervention to
reduce associated co-morbidities either before birth
or soon after. A multidisciplinary maternal, fetal and
neonatology team approach to determining the
most effective time, place and means of delivery of
an affected infant supports early intervention and
treatment. Genetic counselling (including provision
of recurrence risks and methods to reduce them) of
the parents and other individuals at risk can also be
an effective means of secondary prevention.
This review is focussed on the six types of anomalies
highlighted in this report: Down syndrome, neural
tube defects, congenital heart defects, orofacial
clefts, limb deficiency defects and gastroschisis.
Prenatal screening and diagnosis take different
approaches based on the congenital anomaly. The
previous Congenital Anomalies Report1 provided a
basic summary for prenatal screening and testing.
Over the last decade, there have been major
screening and diagnostic advances beyond fetal
aneuploidy and neural tube defects. Major fetal
CAs, identified during pregnancy, are estimated to
be 1–3%.2 Follow up in the neonatal population
usually increases the congenital anomaly incidence
(see Chapter 1 on overall prevalence) and
emphasizes that only some structural defects (e.g.,
malformation, deformation, disruptive categories)
are identified prenatally by the screening imaging
techniques.
SCREENING/DIAGNOSTIC TECHNIQUES
Fetal CA screening uses the systematic application
of a test (e.g., ultrasound, maternal serum analytes)
in order to identify fetuses at sufficient risk of a
specific disorder to warrant further investigation
such as amniocentesis. These screening tests usually
involve fetal surveillance in the first and/or second
trimester by ultrasound and maternal serum
screening (e.g., biochemical analytes, quantitative
protein levels, fetal molecular sequences). The
biological effects and safety of obstetrical
ultrasound have been reviewed by Bly et al.3
Prenatal diagnosis usually involves an invasive
diagnostic test using fetal-related tissues such as
placental specimen by chorionic villus, fetal cells by
amniocentesis, fetal blood cells or serum by
cordocentesis or direct fetal biopsy of skin or
muscle. Diagnostic fetoscopy has been used on a
limited basis due to improving imaging technology,
which has rendered fetoscopy less warranted. These
invasive procedures have an increased risk of fetal
loss or damage above the background risk when no
procedure is undertaken.
Additional imaging such as Magnetic Resonance
Imaging (MRI) (e.g., central nervous system, lungs,
heart, abdomen/renal, limbs)4–6 or low radiation
computed tomography (CT) scan (e.g., skeletal
dysplasia/anomalies)7–10 usually functions as second
tier screening, assisting in triaging, or directing the
74 | CONGENITAL ANOMALIES IN CANADA 2013
differential diagnosis for invasive testing, after which
molecular diagnostic testing can be confirmatory. At
times, such imaging can be diagnostic if
pathognomonic features are present.
a second tier screen prior to invasive prenatal
testing, until large scale clinical testing provides
accurate data on true sensitivity, specificity and cost
within prenatal assessment.12 In a cohort of 4,664
“high risk” women, who were also undergoing
invasive diagnostic testing by traditional
biochemical analyte and ultrasound screening
criteria, the reported trisomy 21 detection rate using
maternal serum was 98.6%, the false positive rate
was 0.2% and the test failed in 0.8%.12 Similar
detection rates based on maternal serum screening
were seen for trisomies 13 and 18 in a later study of
the same sample cohort.13
If a pregnancy with an anomaly is terminated or
ends spontaneously an autopsy is recommended,
especially when there is no definite diagnosis as this
allows for more accurate parental counselling and
estimation of recurrence risk. If there is an increased
risk of recurrence for the CA, planning for prenatal
diagnosis in a subsequent pregnancy and/or other
family studies can be considered.
Though not without significant ethical, legal and
practical implications,11 it is now feasible to
sequence the fetal genome from maternal blood.
For Down syndrome, it is likely that
deoxyribonucleic acid (DNA) sequencing of
maternal plasma (combined DNA 90% maternal and
10% fetal) will remain as a screening test, possibly as
Table 9.1 summarizes screening and diagnostic
factors used in prenatal testing, during each
trimester, while Table 9.2 summarizes characteristics
of ultrasound-guided diagnostic procedures and
their associated risks and accuracy.
TABLE 9.1
Summary of screening and diagnostic factors used in prenatal testing, by trimester
Screening/Diagnostic
Factor
1st Trimester
2nd Trimester
3rd Trimester
Timing of ultrasound
screening 4,33-39
increasing opportunity
standard of care
fetal growth, AF volume,
physiology
Timing of diagnostic
procedure
(singleton, twins)19,32
CVS
CVS
amniocentesis
cordocentesis
CVS
amniocentesis
cordocentesis
Neural tube defect
diagnosis5,6,11
ultrasound opportunity
ultrasound 100%
MSAFP 95%
_
Molecular trisomy
screening12,13
MS at >7 weeks
_
_
Other imaging
techniques5,7-10,40
_
MRI >20 wks
low dose CT >18 wks
_
AF—amniotic fluid, CVS — chorionic villus sampling (placental biopsy), MSAFP—maternal serum alpha fetoprotein, MS—maternal serum, MRI—
magnetic resonance imaging, CT—computer tomography
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TABLE 9.2
Summary of ultrasound-guided diagnostic procedures, associated risks and accuracy
CVS
Amniocentesis
Cordocentesis
Fetal tissue to be
analyzed41,42
placenta
amniotic fluid
blood
Timing of procedure41,42
1st, 2nd,3rd trimester
2nd, 3rd trimester
2nd, 3rd trimester
Testing results41,42
chromosomes
molecular
chromosomes
molecular
chromosomes
molecular
Pregnancy loss risk
in addition to background
loss rate41,42
TA 1–2%
TC 2–6%
TA 0.5–1.0%
TA 2–3%
Testing accuracy
accurate with 1–2% CPM
accurate
accurate
CVS—chorionic villus sampling, TA—transabdominal approach, TC—transcervical approach, CPM—confined placental mosaicism
FETAL THERAPY
A review of fetal therapy indication, techniques and
outcomes has been recently published.14 The option
of fetal therapy could increase the prevalence
among live births of certain congenital anomalies
such as myelomeningocele, diaphragmatic hernia,
pulmonary anomalies (e.g., congenital cystic
adenomatoid malformation, bronchopulmonary
sequestration, pleural effusion), and urinary tract
obstructive anomalies.
IMPACT OF PRENATAL TESTING
Previous publications have looked at the impact of
prenatal screening and diagnosis on the
epidemiology of structural congenital anomalies.
Chi et al.15 reported on abdominal wall defects,
renal agenesis/dysgenesis, and limb reduction
defects. They found that marked increases in
prenatal diagnosis occurred over the study period,
but not in the proportions of pregnancies
terminated, concluding that for these CAs, prenatal
testing had made little impact on their prevalence.
More recent monitoring of prenatal detection of
structural fetal congenital anomalies in England and
Wales identified 2,883 births with congenital
anomalies from a cohort of 601,545 live births and
stillbirths.16 The congenital anomalies evaluated
included anencephaly, spina bifida, serious cardiac
anomalies, diaphragmatic hernia, gastroschisis,
omphalocele, bilateral renal agenesis, severe/lethal
skeletal dysplasia and cleft lip with or without cleft
palate. The most frequently reported CAs were
serious cardiac defects (14.1 per 10,000 total births)
and cleft lip with or without palate (9.7 per 10,000
total births). The least reported anomalies were
bilateral renal agenesis and lethal/severe skeletal
dysplasia at <1.5 per 10,000 total births. Prenatal
diagnosis varied from 53.1% for serious cardiac
anomalies to 99.6% for anencephaly. The least
variation in prenatal diagnosis rates was seen for
anencephaly and gastroschisis and the greatest
for serious cardiac defects and lethal/severe
skeletal dysplasia.
76 | CONGENITAL ANOMALIES IN CANADA 2013
PRENATAL DIAGNOSIS REVIEW
DOWN SYNDROME: PRESENT SCREENING
PERFORMANCE AND ASSESSMENT
The present performance of aneuploidy screening
for trisomy 21 has a detection rate of 90–95% with
a false positive/screen positive rate of 2–5%.17
Chitayat et al.18 reviewed currently available
screening options and their performance. Timing
accuracy of prenatal screening options and
approaches are provided in Table 9.3. These
include maternal serum and first trimester
ultrasound aneuploidy screening. Ultrasound
second trimester markers (most common) for the
detection of fetal trisomy 2119 include cardiac—
structural defects, extra cardiac focus; central
nervous system (CNS)—cerebral ventriculomegaly;
gastrointestinal—duodenal atresia after 22 weeks
gestation, hyperechogenic bowel; fetal non-immune
hydrops; thickened nuchal (neck) fold; skeletal—
absent/short nasal bone, short femur/humerus and
renal—pyelectasis.
TABLE 9.3
Summary of prenatal screening options19
Trimester
Detection
rate (DR) %
False positive rate
(FPR) %
Odds of being
affected for
positive result
(OAPR)
FTS (MA, hCG, PAPPA, NT)
1st
83
5.0
1:27
Quad (MA, AFP, hCG, Inhibin A)
2nd
77
5.2
1:50
IPS (MA, PAPPA, AFP, hCG, uE3,
Inhibin A, NT)
1st/ 2nd
87
1.9
1:10
IPS minus Inhibin A
1st / 2nd
88
3.0
1:20
IPS minus NT (serum only)
1st / 2nd
85
4.4
1:26
FTS— first trimester screening, MA— maternal age, NT— nuchal translucency, AFP—alpha-fetoprotein, hCG— human chorionic gonadotropin,
PAPPA— pregnancy associated plasma protein A, uE3— unconjugated estriol 3, DR— detection rate, FPR— false positive rate, OAPR— odds of
being affected for a screen positive result, IPS— Integrated Prenatal Screen
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NEURAL TUBE DEFECTS:
PRESENT SCREENING PERFORMANCE5
Screening for neural tube defects (NTDs) includes
ultrasound and maternal serum screening with alpha
feto-protein (MSAFP). Ultrasound will identify almost
all cases of anencephaly and cranial anomalies.5,6,20
Careful assessment using the posterior fossa
Arnold-Chiari malformation in association with
imaging of the spine to identify the level of the
myelomeningocele defect allows 95% identification
of spina bifida.
MSAFP screening for NTDs started in the 1970s
with the first population-based screening beginning
in Canada in 1985. MSAFP multiples of the
gestational age-specific median (MOM) at 16 weeks
of gestation are 3.8 MOM and 6.5 MOM for open
spina bifida and anencephaly respectively. The
typical screen positive cut-off for NTDs screening is
2.0–2.5 MOM. The detection rate using 2.0 MOM is
90%.20 Positive screens identify women who can be
offered fetal assessment with ultrasound, followed
by amniocentesis and measurement of amniotic
fluid AFP and acetylcholinesterase in equivocal
cases. Increased MSAFP values are seen in many
other situations such as multiple pregnancy, fetal
death, oligohydramnios, placental anomalies,
intrauterine growth restriction and pre-eclampsia as
well as with other CA including gastroschisis and
omphalocele.20 MSAFP remains a useful screening
tool for NTDs and abdominal wall defects, including
gastroschisis, especially in those jurisdictions where
timely examination by skilled ultrasonographers is
not available for all women or if fetal imaging is
difficult because of maternal obesity.
CONGENITAL HEART DISEASE:
PRESENT SCREENING PERFORMANCE
The American Institute for Ultrasound in Medicine
(AIUM) Practice Guideline for the Performance of
Fetal Echocardiography was published in January
2011.21 Maternal indications included autoimmune
antibodies, familial inherited disorders, a first
degree relative with congenital heart defect (CHDs),
in vitro fertilization, metabolic disease and
teratogen exposure with cardiac implications. Fetal
indications were abnormal cardiac screen, abnormal
heart rate/rhythm, fetal chromosomal anomaly,
extracardiac anomaly, hydrops, increased nuchal
translucency, monochorionic twins and unexplained
severe polyhydramnios. Further reviews document
the historical and clinical role of fetal
echocardiography (ECG),22 fetal ECG at 11–13
weeks by transabdominal high frequency
ultrasound,23 and an audit of 10 years of referrals for
fetal ECG.24
Experts in fetal cardiology viewing videoclips of
fetal cardiac assessments at 11–13 weeks in 886
fetuses suspected a cardiac anomaly in 100. The
obstetricians performing the initial scans detected
95% of these, with a correct diagnosis in 84% as
confirmed by the “gold standard” of fetal ECG at
18–22 weeks. The defect was classified as major in
54 cases and minor in 46. A normal cardiac scan was
identified in 767 (86.6%) cases and inadequate
cardiac views were seen in 2%.23
In a 10-year audit of 623 fetuses referred for fetal
ECG in the Netherlands, 301 (48%) had some form
of cardiac pathology. CHDs, usually severe, were
seen in 81%, 26% of which had chromosomal
abnormalities. In the CHD cases with normal
karyotypes, 23% had extracardiac anomalies. There
were terminations of pregnancy in 24% and a
further 19% were intrauterine or postnatal deaths.
The termination of pregnancy rate was 24.9% for all
cardiac pathology and was 29.6% for the severe
CHD group. Once first trimester nuchal translucency
screening as an indication for increased cardiac risk
was introduced in this Dutch population, referral for
fetal ECG increased. Severe CHD was found in 34%
(81/239) of fetuses with an increased nuchal
translucency.24
OROFACIAL CLEFTS:
PRESENT SCREENING PERFORMANCE
Although the majority of orofacial clefts (OFCs) are
not detected prenatally, routine and enhanced
ultrasound techniques can be valuable for assessing
fetuses at risk. Sommerlad et al.25 used a
conventional 2D ultrasound combined with an
enhanced 3D technique to evaluate fetal lips,
78 | CONGENITAL ANOMALIES IN CANADA 2013
alveolar ridge, and secondary palate in 100 fetuses
suspected of having an isolated OFC on standard
ultrasound. The sensitivity for cleft lip diagnosis was
95% with a false positive rate (FPR) of 7.7%; for
alveolar ridge clefts, sensitivity was 4.5% with a FPR
of 7.2% and for hard palate clefts, sensitivity was
89.7% with a FPR of 15.6%. The authors concluded
that this ultrasound technique was feasible in 90%
of patients and correctly identified the nature of the
OFC in 90% of cases.
Mailath-Pokorny et al.26 studied the added value of
MRI in prenatal diagnosis of OFCs. Thirty-four
women had a fetal MRI at a mean of 26 weeks
gestation (range 19–34 weeks) after ultrasound had
identified either a facial cleft (N=29) or other
malformation (N=5). MRI successfully visualized
OFCs in both primary and secondary palates and
allowed classifications that correlated with postnatal
examination in all 34. Ultrasound imaging had
missed five OFCs and misclassified 15 others.
LIMB ANOMALIES:
PRESENT SCREENING PERFORMANCE
Although careful ultrasound examination of the
limbs can detect deficiency defects, most are not
routinely identified prenatally (approximately 25% of
isolated cases and roughly 45% with other CAs).27
With respect to multiple contractures (i.e.,
arthrogryposis), prenatal evaluation including
imaging (e.g., ultrasound, MRI), cytogenetic and
molecular/microarray testing and serial fetal
surveillance for hydrops and polyhydramnios can be
helpful.28 Delivery planning can be assisted by using
MRI and ultrasound to predict pulmonary hypoplasia
(e.g., secondary to kyphosis and/or scoliosis) or
potential problems for resuscitation or intubation
(e.g., secondary to jaw or spinal features).
Ultrasound features that aid early evaluation for
skeletal dysplasia include increased nuchal
translucency, short femora, abnormal skull shape or
mineralization, facial profile and chest shape.
Assessment is problematic before the second
trimester. In fifteen cases where a diagnosis of
skeletal dysplasia had been suspected by 14 weeks
gestation, retrospective evaluation determined that
accurate prenatal diagnosis was made only in those
cases with positive family history and in single de
novo cases of thanatophoric dysplasia and
Roberts syndrome.7
Fetal talipes (i.e., club foot) is a relatively common
finding on ultrasound. Sharma et al.29 reviewed 174
prenatally diagnosed cases of talipes equinovarus
and classified them as isolated (47.7%) or complex
with other CAs (52.3%). Outcomes were poor when
other anomalies were present and a high frequency
of cases had CNS anomalies and/or abnormal
karyotypes. The isolated cases did better, but the
preterm birth rate was high (18%), potentially due to
the high proportion of multiple pregnancies (19%).
GASTROSCHISIS / ABDOMINAL WALL DEFECTS:
PRESENT SCREENING PERFORMANCE
A retrospective review of 113 cases determined that
prenatal ultrasound diagnosis tends to be more
accurate for omphalocele (91%) than for
gastroschisis (79%).30 In gastroschisis, there is usually
an isolated defect and increased MSAFP.
Omphalocele cases are more likely to have other
CAs such as cardiac defects (18–24%), chromosomal
anomalies (more typical with smaller defects),
pulmonary hypoplasia (associated with “giant”
omphaloceles), Central Nervous System (CNS)
anomalies and atypical VACTERL association.
SUMMARY
Prenatal identification of congenital anomalies uses
maternal evaluation (e.g., whole blood, serum,
molecular analysis, carrier screening, genetic
molecular mutation analysis, fetal molecular analysis)
and fetal imaging (e.g., ultrasound, MRI, CT scan)
for evaluation of the conceptus and its
development. Major CAs amenable to prenatal
diagnosis include aneuploidy, NTDs and other
CNS defects, CHDs, respiratory anomalies,
abdominal wall defects, renal anomalies, limb
anomalies, OFCs and pathology secondary to
monochorionic twinning.
Fetal therapy has a place for improving fetal
mortality and neonatal morbidity, but complete
amelioration of the anomaly and its effects has not
been reported. Maternal transfer for optimal fetal/
neonatal care at designated tertiary centres for
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further investigation, as well as counselling and
ongoing expectant management and delivery
should be considered as prenatal diagnosis can
optimize outcomes after neonatal surgery for CAs
such as congenital lung malformations,
sacrococcygeal teratoma, myelomeningocele, giant
fetal neck masses, diaphragmatic hernia and
congenital heart defects.31 After prenatal diagnosis
of congenital anomalies, some parents will opt for
termination of pregnancy. Regardless of the
outcome, identification of an affected fetus and
subsequent investigations into cause can allow for
genetic counselling and facilitate plans for future
pregnancy, including planned prenatal assessment
or use of assisted reproductive technology.
Evaluation of prenatal testing in Canada indicates
that many healthcare systems have limitations in
providing state-of-the-art screening and diagnosis
services due to cost. Issues with respect to the need
for genetic counselling and informed consent,
language barriers and distance from tertiary centres
increases the barriers to access and availability.
Despite these drawbacks, prenatal diagnosis and
screening tests have clear economic benefit.
Current standards of care dictate that such tests
should be offered to all pregnant women to assess
their risk of having a baby with a CA or genetic
disorder.19,31,32
80 | CONGENITAL ANOMALIES IN CANADA 2013
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1. Health Canada. Congenital Anomalies in
Canada — A Perinatal Health Report, 2002.
Ottawa: Minister of Public Works and
Government Services Canada, 2002.
2. Twining P, McHugo JM, Pilling DW. Textbook of
Fetal Abnormalities. Second Edition.
Philadelphia. USA: Churchill Livingstone
Elsevier; 2007 p. 10-20.
3. Bly S, Van den Hof MC, Lewthwaite B, et al.
Obstetric ultrasound biological effects and
safety. J Obstet Gynaecol Can. 2005;27(6):
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4. Gagnon A, Wilson RD, Allen VM, et al.
Evaluation of prenatally diagnosed structural
congenital anomalies. J Obstet Gynaecol Can.
2009;31(9):875-81.
5. Kline-Fath BM, Calvo-Garcia MA. Prenatal
imaging of congenital malformations of the
brain. Semin Ultrasound CT MR.
2011;32(3):167-88.
6. Liptak GS, Dosas NP. Myelomeningocele.
Pediatr Rev. 2010;31(11):443-50.
7. Cassart M. Suspected fetal skeletal
malformations or bone diseases: how to
explore. Pediatr Radiol. 2010;40(6):1046-51.
8. Khalil A, Pajkrt E, Chitty LS. Early prenatal
diagnosis of skeletal anomalies. Prenat Diagn.
2011;31(1):115-24.
9. Krakow D, Lachman RS, Romoin DL. Guidelines
for the prenatal diagnosis of fetal skeletal
dysplasias. Genet Med. 2009;11(2):127-33.
10. Victoria T, Epelman M, Bebbington M, et al.
Low-dose fetal CT for evaluation of severe
congenital skeletal anomalies: preliminary
experience. Pediatr Radiol. 2012;42(Suppl
1):S142-9.
11. Greely HT. Get ready for the flood of fetal gene
screening. Nature. 2011;469(7330):289-91.
12. Palomaki GE, Kooza EM, Lambert-Messerlian
GM, et al. DNA sequencing of maternal plasma
to detect Down syndrome: an international
clinical validation study. Genet Med.
2011;13(11):913-20.
13. Palomaki GE, Deciu C, Kloza EM, et al. DNA
sequencing of maternal plasma reliably
identifies trisomy 18 and trisomy 13 as well as
Down syndrome: an international collaborative
study. Genet Med. 2012;14(3):296-305.
14. Wilson RD. Fetal Therapy: Maternal Fetal
Surgery and Percutaneous Ultrasound Guided
Fetal Therapy Techniques for Congenital
Anomalies. In: Fleisher AC, Toy EC, Lee W, et
al., editors. Sonography in Obstetrics and
Gynecology: Principles and Practice, Seventh
edition. New York: McGraw-Hill Medical; 2011.
p. 793-814.
15. Chi LH, Stone DH, Gilmour WH. Impact of
prenatal screening and diagnosis on the
epidemiology of structural congenital
anomalies. J Med Screen. 1994;2(2):67-70.
16. Boyd PA, Tonks AM, Rankin J, et al. Monitoring
the prenatal detection of structural fetal
congenital anomalies in England and Wales:
register-based study. J Med Screen.
2011;18(1):2-7.
17. Canick J. Prenatal screening for trisomy 21:
recent advances and guidelines. Clin Chem Lab
Med. 2011;50(6):1003-8.
18. Chitayat D, Langlois S, Wilson RD, et al.
Prenatal screening for fetal aneuploidy in
singleton pregnancies. J Obstet Gynaecol Can.
2011;33(7):736-50.
19. Benacerraf BR. The history of the secondtrimester sonographic markers for detecting
fetal Down syndrome, and their current role in
obstetric practice. Prenat Diagn. 2010;30(7):
644-52.
20. Krantz DA, Hallahan TW, Sherwin JE. Screening
for open neural tube defects. Clin Lab Med.
2010;30(3):721-5.
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2013 | 81
21. Lee W, Drose J, Wax J, et al. AIUM practice
guideline for the performance of fetal
echocardiography. J Ultrasound Med.
2011;30(1):127-36.
31. Izquierdo LA, Berkshire S. Access, quality and
costs of prenatal diagnosis. Bol Asoc Med P R.
2010;102(4):25-9.
22. Devore GR. Genetic sonography: the historical
and clinical role of fetal echocardiography.
Ultrasound Obstet Gynecol. 2010;30(1):509-21.
32. Audibert F, Gagnon A, Wilson RD, et al.
Prenatal screening for and diagnosis of
aneuploidy in twin pregnancies. J Obstet
Gynaecol Can. 2011;33(7):754-67.
23. Persico N, Moratalla J, Lombardi CM, et al. Fetal
echocardiography at 11-13 weeks by
transabdominal high-frequency ultrasound.
Ultrasound Obstet Gynecol. 2011;37(3):296-301.
33. Cargill Y, Morin L, Bly S, et al. Content of a
complete routine second trimester obstetrical
ultrasound examination and report. J Obstet
Gynaecol Can. 2009;31(3):272-5.
24. Clur SA, Van Brussel PM, Mathijssen IB, et al.
Audit of 10 years of referrals for fetal
echocardiography. Prenat Diagn.
2011;31(12):1134-40.
34. Chitty LS, Lau TK. First trimester screening –
new directions for antenatal care? Prenat
Diagn. 2011;31(1):1-2.
25. Sommerlad M, Patel N, Vijayalakshmi, B, et al.
Detection of lip, alveolar ridge and hard palate
abnormalities using two-dimensional
ultrasound enhanced with the threedimensional reverse-face view. Ultrasound
Obstet Gynecol. 2010;36(4):596-600.
26. Mailath-Pokorny M, Worda C, KrampleBettelheim E, et al. What does magnetic
resonance imaging add to the prenatal
ultrasound diagnosis of facial clefts? Ultrasound
Obstet Gynecol. 2010;36(4):445-51.
27. Stoll C, Wiesel A, Queisser-Luft A, et al.
Evaluation of the prenatal diagnosis of limb
reduction deficiencies. EUROSCAN Study
Group. Prenat Diagn. 2000;20(10):811-18.
28. Rink BD. Arthrogryposis: a review and approach
to prenatal diagnosis. Obstet Gynecol Surv.
2011;66(6):369-77.
29. Sharma R, Stone S, Alzouebi A, et al. Perinatal
outcome of prenatally diagnosed congenital
talipes equinovarus. Prenat Diagn.
2011;31(2):142-5.
30. Joó JG, Csatlós E, Rigó J Jr. Abdominal wall
malformations in a 15 year fetopathological
study: accuracy of prenatal ultrasonography
diagnosis. Prenat Diagn. 2010;30(11):1015-8.
35. Demianczuk NN, Van den Hof MC. The use of
first trimester ultrasound. J Obstet Gynaecol
Can. 2003;25(10):864-9.
36. Eik-Nes SH. The 18-week fetal examination and
detection of anomalies. Prenat Diagn.
2010;30(7):624-30.
37. Morin L, Lim K, Bly S, et al. Ultrasound in twin
pregnancies. J Obstet Gynaecol Can.
2011;33(6):643-56. 38. Robson S. Fetal ultrasound screening and
diagnosis 10 years hence. Prenat Diagn.
2010;30(7):696-8. 39. Van den Hof MC, Wilson RD, Bly S, et al. Fetal
soft markers in obstetric ultrasound. J Obstet
Gynaecol Can. 2005;27(6):592-612.
40. Santos XM, Papanna R, Johnson A, et al. The
use of combined ultrasound and magnetic
resonance imaging in the detection of fetal
anomalies. Prenat Diagn. 2010;30(5):403-7.
41. Wilson RD, Langlois S, Johnson JA, et al.
Mid-trimester amniocentesis fetal loss rate. J
Obstet Gynaecol Can. 2007;27(6):586-90.
42. Wilson RD, Davies G, Gagnon A, et al.
Amended Canadian guideline for prenatal
diagnosis (2005) change to 2005-techniques for
prenatal diagnosis. J Obstet Gynaecol Can.
2005;27(11):1048-54.
82 | CONGENITAL ANOMALIES IN CANADA 2013
CHAPTER 10
MANAGEMENT AND OUTCOMES IN OROFACIAL CLEFTS,
DOWN SYNDROME AND SPINA BIFIDA
Albert E. Chudley
R. Brian Lowry
This chapter deals with three common congenital
anomalies, namely orofacial clefts, Down sydrome
and spina bifida. We present some of the relevant
points of management, prognosis and quality of
life issues that affected individuals experience
after birth.
OROFACIAL CLEFTS
Most orofacial clefts (OFCs) fall into two main
groups: cleft lip with or without cleft palate (CL±CP),
of which isolated cleft lip (CL) and cleft lip with cleft
palate (CLP) are subgroups and cleft palate alone
(CP). OFCs may be seen in isolation or associated
with a syndrome, chromosomal anomaly or other
malformation. The prognosis and management for
each group will be very different depending on
whether the cleft is an isolated anomaly or belongs
to one of the other groups. Here we discuss the
problems and issues related to the isolated
examples of CL, CLP and CP. It is important to
remember that a person with an isolated cleft may
in fact belong to a less obvious syndrome group
such as 22q11 deletion. Etiologic heterogeneity is a
major factor in OFCs.
The major pediatric medical issues, including early
feeding problems, recurrent ear infections often
requiring insertion of tubes in the middle ear,
conductive hearing loss, speech and language
problems and complex dental problems, are well
known and are covered very fully by Smyth.1 He also
discusses the pros and cons of different surgical
methods or techniques and the timing of these,
noting that surgery is best done with a team
approach in a major centre. In Canada, most
provinces will have such a team in place, but smaller
provinces and the territories will likely require the
services of adjoining provinces. Dental and
orthodontic care may not be available through the
Canadian universal healthcare system, especially
after age 18.
QUALITY OF LIFE
There is increasing interest and concern regarding
quality of life (QOL) and health related quality (HRQ)
issues for persons living with congenital anomalies,
especially when defects are visible. The latter can
cause stigmatization, lack of self-esteem and
psychosocial issues, especially in elementary school
where conformity and sameness are important, but
many of these same issues are still a problem for
adults with OFCs.
Marcusson et al.2 evaluated QOL in 68 adults with
repaired CLP by means of a self-administered
questionnaire, and compared them to 66 adults
without clefting, matched for gender and age. The
CLP group felt that their handicap had a marked
effect on their lives, particularly on their overall
well-being and social life. Mani et al.3 studied 86
adults with unilateral CLP for a mean follow up time
of 35 years and compared selected HRQ issues with
normative data matched for age and gender. The
patient group had lower values in the mental health
category, but were similar to the controls in many
other areas, indicating that most of the affected
adults in their study appeared to cope well with
their malformation. Ramstad et al.4 investigated 233
Norwegian adults with a mean age of 28 years
(range 20–35 years) with repaired CLP and
compared them to a large control sample of similar
age. Common psychological and medical problems
among the CLP subjects were appearance, dentition
and speech. Questions that yielded significant
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differences between controls and persons with CLP
were related to work, friendship and geographic
mobility. Men seem to adjust less well than women
indicating a need for psychologic counselling and
psychiatric care from the craniofacial team. A
follow-up study of 6,464 patients with clefting in
Denmark (born 1936–1987)5 found that 284 (4.4%)
were hospitalized at some time for psychiatric
disease, largely because of mental handicap and
substance abuse. This increase in risk was not due
to associated malformations or anomaly syndromes.
The risk for schizophrenia and bipolar disorder
was not significantly different from that of the
general population.
Providing a syndromic form of CLP or CP has been
excluded, the risk for the offspring of an affected
person is in the 2–5% range (2% for CP, 2–5% for
CL±CP with some evidence to suggest the higher
risk for the offspring of a person with bilateral CLP
and a lower one for unilateral CL). The risks may be
higher if there is a positive family history for CLP or
CP and genetic counselling advice should be
sought. Prevention as a result of folic acid
fortification or by pre- or post conceptional
ingestion of multivitamins and folic acid has not
been proven to change either first occurrence or
recurrence. Prenatal diagnosis by ultrasound
examination can be achieved (see Chapter 9).
MORTALITY
Early studies6,7 found a higher infant mortality,
especially when there were associated anomalies.
However, even in isolated defects, the death rate
was four times higher for CL±CP and 1.5 times
higher for CP compared to that for infants with no
anomalies.7 In Denmark, a long term survival study8
was conducted involving 5,331 persons with
isolated CLP, who were born between 1943 and
1987 and followed to 1998. The expected number
of deaths was 259, but 402 occurred, corresponding
to a Standardized Mortality Ratio (SMR) of 1.4 for
males and 1.8 for females. The increased risk of
mortality was nearly constant for the three age
intervals: first year of life, 1–17 years, 18–55 years.
Death from cancer was only marginally increased,
but the risk of suicide was significantly higher in
both sexes. Accidents, which in some cases may be
suicides, were not increased. About 50% of the
overall deaths were attributed to causes other than
the malformation. Deaths in the first year of life
were due to prematurity, pneumonia, operative
complications, asphyxia, aspiration, sepsis and an
unknown group. For all other age groups, all but
diseases of the central nervous system (CNS)
showed moderate but non-significant increases in
SMR. Mortality due to diseases of the CNS showed
a significant increase for females. Stratifying for CL,
CLP and CP, there was a significant risk for CLP and
CP as compared to CL where there was only a slight
risk of increased mortality.
COGNITIVE/LEARNING
Children with non-syndromic OFCs have been
shown to have cognitive difficulties compared with
matched controls, with many having language
disabilities.9,10 A study from Sweden11 compared the
intelligence of 17–19 year-old men with CL±CP
(N=307) or CP (N=81) being evaluated for military
service, with controls (N=272,879). Both groups
were non-syndromic. Those with CL±CP showed no
significant difference compared with the control
group, but the CP group had significantly lower
general intellectual scores. A quantitative MRI
analysis of brain structure12 found significant
abnormalities in the brain morphology in adult
males with non-syndromic CL±CP compared to a
matched healthy control group. The abnormalities
were: abnormally enlarged anterior regions of the
cerebrum; decreased volume of the posterior
cerebrum and cerebellum, with the left temporal
lobe being severely affected. The structural
abnormalities were directly related to cognitive
function.
SUMMARY
Wherever possible, care and management for
persons with OFCs is best managed by a
comprehensive team in a major setting and should
84 | CONGENITAL ANOMALIES IN CANADA 2013
extend beyond the pediatric age group.
Psychological care—comprehensively reviewed by
Kapp-Simon13—is an important part of the team to
help such individuals adjust to life with their
disability, particularly those with a visible defect.
Unfortunately, appropriately specialized
psychological care may not always be available.
Accessing orthodontic and dental care may present
a further challenge for adults, due to the fact that
it is generally not covered for people over the
age of 18.
Clearly, further research is needed to study the
problems of brain abnormality and function. The
decreased longevity, even in the absence of other
anomalies, remains unexplained.
DOWN SYNDROME
Down syndrome (DS) results from extra chromosome
21 material in the genome.14,15 DS is most often due
to a non-familial chromosome imbalance as a result
of maternal meiotic non-disjunction leading to
trisomy 21. In about 5% of cases, it is the result of a
translocation, usually involving a Robertsonian
translocation with fusion between two acrocentric
chromosomes; a chromosome 21 and most
commonly a chromosome 14. About half of these
are inherited translocations. Approximately 2% of
persons with DS may have two cell lines (mosaicism);
a normal cell line and a trisomy 21 cell line in various
proportions. This usually results in a less severe
phenotype and often a better outcome. Testing
persons suspected of having DS involves taking a
blood specimen for chromosome analysis; these
tests are available in most major medical centres in
Canada. Prenatal screening and diagnosis for DS is
available in most major medical centres. This topic is
covered in the chapter on prenatal diagnosis (see
Chapter 9).
A variety of congenital anomalies and medical
complications are more common in persons with DS
(Table 10.1). There are anticipatory guidelines and
health supervision guidelines by age categories that
care givers can use to monitor health in persons
affected by DS.16 Resources and support for parents
of children with DS are available through provincial
and national DS support groups or associations and
through various web sites.
TABLE 10.1
Common health concerns in children with Down syndrome*
Condition
% Affected
Hearing loss
75
Visual impairment
60
Sleep apnea
50–75
Congenital heart disease
40–50
Transient myeloproliferative disorder
10
Gastrointestinal atresia
12
Thyroid disease
4–18
Seizures
1–13
Coeliac disease
5
Atlantoaxial instability
1–2
Autism
1
Hirschsprung disease
<1
Leukemia
1
* Modified from Bull, 201116
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Telling new parents about the diagnosis of DS is a
sensitive issue and one that requires knowledge,
skill, sensitivity and compassion.17,18 For future
pregnancies, affected parents should be advised
that the recurrence risk of DS is higher than in the
general population. They should also be referred for
genetic counselling. Precise risk calculation will
depend on the mother’s age in previously-affected
and subsequent pregnancies. For translocation
carriers, the risk is higher if the mother is a carrier
than if the father carries the translocation (10–15%
vs. 1–2%).19,20
INTERVENTIONS AND QUALITY OF LIFE
Medical complications do not usually dominate care
and, barring major medical issues such as
congenital heart defects, caring for a child with
Down syndrome is not much different from caring
for any other child. Persons with DS need love, care
and respect like any other person. A balanced
perspective, with hope and encouragement, and
discussion of positive aspects can promote parents’
adaptation to the diagnosis and encourage an
attitude and perspective of acceptance and
normalization.
Since most children with DS are delayed in reaching
most developmental milestones, early intervention
that includes speech therapy, occupational therapy,
and physical therapy is recommended. There is
evidence that these interventions can optimize longterm outcomes.21,22 At school age, individualized
education plans can be tailored to the child’s needs,
which typically involve a special education
classroom setting. Inclusion in school can result in
improved social skills, speech and language,
literacy, daily living skills and behaviour. 23 Older
children with DS have a lower QOL and HRQ when
compared to children at the same age.24 This often
manifests as emotional and behavioural problems
and significantly lower gross motor skills, autonomy,
social functioning and cognitive functioning.25
People with DS have wide ranges of abilities,
ranging from nonverbal individuals to those who are
high-functioning. They require different levels of
support as adults. Higher-functioning adults with DS
can participate in social, physical, educational, and
vocational activities.26 Some of these young adults
are able to live outside of the primary household,
obtain a driver’s license, get married and be
gainfully employed. Individuals with mild intellectual
disability may go on to attend post-secondary
schooling. Fertility is reduced in adults with DS.
Males are almost always infertile due to defects in
spermatogenesis. However, there are a few reports
of males with DS fathering a child. Women with DS
are at increased risk of having offspring with DS.
The risk is less than the theoretical risk of 50% due
to the higher loss rate of trisomic embryos and
fetuses. Prenatal diagnosis has been discussed in
Chapter 9.
Mental illness occurs in approximately 30% of all
adults with DS with depression being the most
frequent. Common symptoms of depression in DS
include sleep and behaviour disturbances, apathy,
and weight change.27 Other health issues common
to adults with DS include obesity, osteoporosis, and
lower cardiovascular fitness.25 Exercise programs
appear to positively affect the overall health of
adults with DS, thereby increasing the quality of life
and years of healthy life for these individuals.26
Almost all adults with DS over 40 years of age
display neuropathology consistent with Alzheimer
disease. Prevalence rates for Alzheimer disease
among adults with DS increase with age, with rates
of 10% at 30–39 years, up to 55% at 50–59 years
and almost 75% at 60–65 years.28
MORTALITY
Many persons with DS are living longer due to
medical interventions and improvements in
treatment of congenital anomalies. The estimated
life expectancy of people with DS in developed
countries has increased from an average of 12 years
in the 1940s to a current average of 57.8 years for
women and 61.1 years for men.29,30
Data from Western Australia indicate that 6.5% of
infants with DS born between 1980–2004 died
within the first year. However, while the infant
mortality rate between 1980–1984 was 13%, this
had dropped to 4% by 2000–2004. There is a strong
correlation between the presence of congenital
heart defects and death during the first 10 years of
life, with improved survival correlated with earlier
86 | CONGENITAL ANOMALIES IN CANADA 2013
surgical correction of the congenital heart disease.29
In adults over 40 years, pneumonia and other
respiratory infections were the most common causes
of death (39.6%), followed by coronary artery
disease (9.9%), cardiac, renal, and respiratory
failure (9%), cerebrovascular accident (6.3%),
and cancers (5.4%).29
CLASSIFICATION
SUMMARY
MANAGEMENT, COMPLICATIONS AND
QUALITY OF LIFE
DS remains a common condition that is associated
with a high morbidity and mortality. Improved care
and intervention has resulted in an improved quality
of life and enhanced survival with increasing
longevity for many persons affected by DS. Despite
these improvements, the burden of this
chromosomal imbalance does remain substantial in
terms of physical and mental health challenges,
both to those affected and those caring for these
vulnerable members of our society.
SPINA BIFIDA
The prevalence of spina bifida congenita (SBC) and
all forms of neural tube defects has decreased in the
past 20 to 30 years likely because of
periconceptional folic acid supplementation, food
fortification in several countries, and prenatal
screening for fetal anomalies. SBC results from the
failure of closure of the neural tube between 21 and
28 days post conception. The reasons for this are
unclear, but most of these defects are due to
multifactorial inheritance in which both genetic and
environmental factors are operating. One important
environmental factor is folic acid which has been
shown to substantially, but not completely, reduce
the risk of occurrence of SBC and related neural
tube defects. Optimal use of preconceptional folic
acid, decreases recurrence risks from 3.5% to 1%, an
over 70% reduction. SBC can be a feature of a child
with multiple anomalies (syndromic forms) or can
occur as an isolated birth defect. Syndromic forms
include chromosomal disorders (e.g., trisomy 13 or
18), teratogenic conditions (e.g., valproic acid
embryopathy, diabetic embryopathy), and other
genetic (e.g., Currarino syndrome) or multiple
congenital anomalies disorders (e.g., OEIS complex,
pentalogy of Cantrell). This discussion will be
restricted to non-syndromic forms of SBC.
SBC and other forms of spinal dysraphism can be
open or closed defects. The clinical effects of SBC
depend in part on the severity of the lesion and the
location. The reader is referred to an excellent
review article on classification and imaging
characteristics of SBC.31
Although there is no clear evidence from the
neurosurgical perspective to favour caesarean
section in the absence of gross hydrocephalus,
breech presentation or other obstetric indications,32
many children with a prenatal diagnosis of SBC are
delivered in this way. Optimally, the back lesion
should be closed within 72 hours after birth. Doing
so further decreases the risk of CNS infection and
possibly improves neurological outcome.
Prophylactic antibiotics may be associated with a
lower risk of ventriculitis. Surgical treatment will not
be addressed further here and readers are referred
to a review article for more details.32
Approximately 80–90% of individuals with SBC will
develop hydrocephaly. Many are shunted at the
time of meningomyelocele repair. In the absence of
obvious hydrocephalus, monitoring of ventricular
size is common practice. Where there is only
moderate enlargement the decision to shunt may
be deferred. Placement of a shunt imposes a
significant burden to children with the risk of
ventriculitis and need for shunt revision. Shunt
dependent hydrocephalus and shunt related
complications are not only detrimental to
cognitive outcome, but are strongly related to
reduced survival.33
Urinary tract infections are common in SBC. They
are more frequent in lumbosacral level lesions than
in other locations. The introduction of clean
intermittent catheterization, the use of
anticholinergic drugs to improve bladder capacity
and aggressive management of constipation have
significantly improved the urological prognosis both
in terms of reducing the risk of renal damage and
reduction in the number of infections.34, 35 Many
patients can be managed with clean intermittent
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catheterization, but some will require incontinent
urinary diversion, such as vesicostomy,
ileovesicostomy or ileal conduit creation.34
Children born with SBC have reduced life
expectancy and suffer significant cognitive and
physical disability, remaining wholly or partially
dependent on the care of others into adult life.35,36
Spinal deformities and scoliosis are also seen in a
minority of adolescent and adult patients with SBC
and sometimes require surgical treatment with
spinal fusion.37
Tethered spinal cord may be a primary defect in
some forms of spinal dysraphism or can occur after
surgical repair of the spinal defect. Following the
initial surgery, the terminal spinal cord remains low
in the spinal canal, commonly imbedded in scar
tissue. As spinal growth continues, traction is
exerted on the spinal cord and nerve roots leading
to ischaemic injury, and secondary neurological
deterioration including pain, decreased motor
function and foot deformities. Once recognized,
surgical repair can reverse this process.
Severe developmental delay is seen in about 15% of
patients with SBC.31 Otherwise, the prospects for
independent mobility are strongly related to the
neurological level of the lesion. For low lumbar and
sacral lesions, independent mobility is expected.
For lesions above the second lumbar vertebra, loss
of quadriceps and iliopsoas muscle function means
that independent mobility is unlikely and will result
in reliance on a wheel chair.38 Approximately 70% of
patients with SBC will have an IQ of 80 or more.39
What limited data are available on adult
survivors suggest that between 25–38% will be
gainfully employed.40
Most males and females with SBC are fertile. Males
may have more difficulty fathering children due to
problems achieving erection and ejaculation rather
than lack of fertility. The recurrence risk to offspring
born to a parent with SBC is in the 3-4% range
regardless of the gender of the affected parent, but
can be significantly reduced by preconception folic
acid supplementation. Prevention and prenatal
diagnosis have been discussed fully in Chapters
8 and 9. SURVIVAL
In the absence of additional serious congenital
anomalies, individuals born with SBC are now likely
to survive for an average of 30 years.41,42 Ventriculitis
and shunt related complications were the prime
causes of death during infancy in the past; however,
brainstem dysfunction (due to Chiari II
malformation) leading to respiratory impairment
and swallowing dysfunction now explains the
majority of early deaths.43,44
SUMMARY
Spina bifida is considered one of the most complex
birth defects compatible with life. Individuals with
SBC suffer from brain complications, spinal cord
injury and compromised renal function. Children
and adults with SBC need multiple specialists,
generalists who can address health promotion, and
an integrated system to deliver this complex care.
Improved care has resulted in improved QOL and
survival; better preventive strategies have reduced
the number of children born with this complex
condition.45,46
88 | CONGENITAL ANOMALIES IN CANADA 2013
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Pediatric Surgery and Urology: Long-term
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11. Persson M, Becker M, Svensson H. General
intellectual capacity of young men with cleft lip
with or without cleft palate and cleft palate
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2. Marcusson A, Akerlind I, Paulin G. Quality of
life in adults with repaired complete cleft lip
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12. Nopoulos P, Berg S, Canady J, et al. Structural
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3. Mani M, Carlsson M, Marcusson A. Quality of
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4. Ramstad T, Ottem E, Shaw WC. Psychosocial
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5. Christensen K, Mortensen PB. Facial clefting
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6. Mackeprang M, Hay S. Cleft lip and palate
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7. Hujoel PP, Bollen AM, Mueller BA. First-year
mortality among infants with facial clefts. Cleft
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8. Christensen K, Juel K, Herskind AM, et al. Long
term follow up study of survival associated with
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9. Richman LC. Cognitive pattern and learning
disabilities in cleft palate children with
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10. Hentges F, Hill J, Bishop DVM, et al. The effect
of cleft lip on cognitive development in schoolaged children: a paradigm for examining
sensitive period effects. J Child Psychol
Psychiatry. 2011;52(6):704-12.
13. Kapp-Simon KA. Psychological care of children
with cleft lip and palate in the family. In:
Wyszynski DF, editor. Cleft Lip and Palate. New
York: Oxford University Press; 2002. p. 412-423.
14. Schieve L, Boulet S, Boyle C, et al. Health of
children 3 to 17 years of age with Down
syndrome in the 1997–2005 national
health interview survey. Pediatrics.
2009;123(2);e253-60.
15. Roizen NJ, Patterson D. Down’s syndrome.
Lancet. 2003;361(9365):1281-9.
16. Bull MJ; Committee on Genetics. Health
supervision for children with Down syndrome.
Pediatrics. 2011;128(2):393-406.
17. Sheets KB, Crissman BG, Feist CD, et al.
Practice guidelines for communicating a
prenatal or postnatal diagnosis of Down
syndrome: recommendations of the national
society of genetic counsellors. J Genet Couns.
2011;20(5):432-41.
18. Skotko BG, Capone GT, Kishnani PS, et al.
Postnatal diagnosis of Down syndrome:
synthesis of the evidence on how to
best deliver the news. Pediatrics.
2009;124(4):e751-8.
19. Gardner RJM, Sutherland GR. Chromosome
Abnormalities and Genetic Counselling.
Third edition. New York: Oxford University
Press, Inc.; 2004.
20. De Souza E, Halliday J, Chan A, et al.
Recurrence risks for trisomies 13, 18, and 21.
Am J Med Genet A. 2009;149A(12):2716-22.
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21. Davidson MA. Primary care for children and
adolescents with Down syndrome. Pediatr Clin
North Am. 2008;55(5):1099-111.
22. Rihtman T, Tekuzner E, Parush S, et al. Are the
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Med Child Neurol. 2010;52(1):72-8.
23. Buckley S, Bird G, Sacks B, et al. A comparison
of mainstream and special education for
teenagers with Down syndrome: implications
for parents and teachers. Downs Syndr Res
Pract. 2006;9(3):54-67.
24. Brown R, Taylor J, Matthews B. Quality of life
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25. van Gameren-Oosterom HB, Fekkes M,
Buitendijk SE, et al. Development, problem
behavior, and quality of life in a population
based sample of eight-year-old children with
Down syndrome. PLoS One. 2011;6(7):e21879.
26. Barnhart RC, Connolly B. Aging and Down
syndrome: implications for physical therapy.
Phys Ther. 2007;87(10):1399-406.
27. Finesilver C. A new age for childhood diseases.
Down syndrome. RN. 2002;65(11):43- 8.
28. Shamas-Ud-Din S. Genetics of Down’s
syndrome and Alzheimer’s disease. Br J
Psychiatry. 2002;181:167-8.
29. Bittles AH, Bower C, Hussain R, et al. The four
ages of Down syndrome. Eur J Public Health.
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30. Glasson EJ, Sullivan SG, Hussain R, et al.
Comparative survival advantage of males with
Down syndrome. Am J Hum Biol. 2003;
15(2):192-5.
31. Rossi A, Gandolfo C, Morana G, et al. Current
classification and imaging of congenital spinal
abnormalities. Semin Roentgenol.
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32. Bowman RM, McLone DG. Neurosurgical
management of spina bifida: research issues.
Dev Disabil Res Rev. 2010;16(1):82-7.
33. Barf HA, Verhoef M, Jennekens-Schinkel A,
et al. Cognitive status of young adults with
spina bifida. Dev Med Child Neurol.
2003;45(12):813-20.
34. Lapides J, Diokno AC, Silber SJ, et al. Clean,
intermittent self-catheterization in the
treatment of urinary tract disease. J Urol.
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35. Metcalfe P, Gray D, Kiddoo D. Management of
the urinary tract in spina bifida cases varies with
lesion level and shunt presence. J Urol.
2011;185(6)(Suppl):2547-51.
36. Dicianno BE, Kurowski BG, Yang JM, et al.
Rehabilitation and medical management of the
adult with spina bifida. Am J Phys Med Rehabil.
2008;87(12):1027-50.
37. McDonald CM, Jaffe KM, Mosca VS, et al.
Ambulatory outcome of children with
myelomeningocele: effect of lower extremity
muscle strength. Dev Med Child Neurol.
1991;33(6):482-90.
38. Seitzberg A, Lind M, Biering-Sorensen F.
Ambulation in adults with myelomeningocele.
Is it possible to predict the level of ambulation
in early life? Childs Nerv Syst. 2008;24(2):231-7.
39. Oakeshott P, Hunt GM. Long-term outcome in
open spina bifida. Br J Gen Pract.
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40. Valtonen K, Karlsson AK, Alaranta H, et al.
Work participation among persons with
traumatic spinal cord injury and
meningomyelocele1. J Rehabil Med.
2006;38(3):192-200.
41. Hunt GM. The median survival time in open
spina bifida. Dev Med Child Neurol.
1997;39(8):568.
42. Davis BE, Daley CM, Shurtleff DB, et al. Longterm survival of individuals with
myelomeningocele. Pediatr Neurosurg.
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43. Bowman RM, McLone DG, Grant JA, et al.
Spina bifida outcome: a 25-year prospective.
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44. Stevenson KL. Chiari Type II malformation: past,
present, and future. Neurosurg Focus.
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45. Thompson DN. Postnatal management and
outcome for neural tube defects including
spina bifida and encephalocoeles. Prenat
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CONCLUSION
PRECONCEPTION HEALTH AND CONGENITAL
ANOMALIES SURVEILLANCE IN CANADA:
MEETING CANADA’S FUTURE HEALTH NEEDS
Ruth Kohut
R. Brian Lowry
Neel Rancourt
One of the main goals of public health is to improve
the health and well-being of populations by means
of health promotion and primary prevention. As a
perinatal health outcome, congenital anomalies
impact 3–5% of infants in Canada, and are a major
contributor to infant mortality, premature births and
childhood morbidity. Moreover, they often continue
to have an impact on health and longevity well into
adulthood. Thus, concerted efforts to promote
preconception health across all levels of public
health would yield dividends in protecting and
improving population health.
Health promotion and prevention
of adverse perinatal health
outcomes are most effective
before conception.
Preconception interventions and practices have
been described throughout this report and include:
- Optimal nutrition, including folic acid fortification
and supplementation;
- Maintenance of healthy preconception weight;
- Avoidance of alcohol, tobacco, street drugs and
other known teratogens;
- Preconception control of maternal chronic
diseases such as epilepsy and diabetes mellitus;
- Full immunization coverage; and,
- Avoidance, or reduction of medication use and
exposure to suspected environmental teratogens.
In current dollars, total annual health expenditures
in Canada are approaching 200 billion dollars; of
which hospitals costs make up the largest category.1
Limiting our attention to acute management and
treatment of congenital anomalies would simply
contribute to these costs and place increasing
pressure on our healthcare system in the long term.
A primary prevention approach focusing on early
intervention to offset the economic burden of these
conditions makes sense. The introduction of
mandatory folic acid fortification in 1998 by the
Canadian government and the subsequent 46%
reduction in the prevalence of neural tube defects
nationwide represents the most notable
preconception primary prevention strategy.2 Thus, a
new era of opportunities in preconception health
promotion and primary prevention is upon us.
Shifting population demographics, chronic disease
patterns, emerging genetic and reproductive
technologies, and changes in the physical
environment are variably influencing occurrence
patterns of congenital anomalies in Canada and
worldwide. These and other factors will continue to
re-shape our understanding of congenital anomalies
and prompt us to adapt our existing public health
strategies accordingly. A broadened view of
perinatal health considering determinants,
outcomes and preconception health promotion,
particularly for vulnerable populations in Canada,
will remain important if we are to further elucidate
the complex etiology of these conditions and
successfully prevent them.
92 | CONGENITAL ANOMALIES IN CANADA 2013
For these reasons, congenital anomalies are an
important public health issue both nationally
and internationally. In this respect, the World
Health Organization (WHO) has urged member
countries to:
- record surveillance data on birth defects as part of
national health information systems;
- develop expertise and build capacity in the
prevention of birth defects and care of children
with birth defects;
- strengthen research and studies on etiology,
diagnosis and prevention of major birth defects
and promote international cooperation in
combating them and,
- collaborate with the International Clearinghouse
for Birth Defects Surveillance and Research in
order to improve collection of data on the
global burden of mortality and morbidity
due to birth defects.3
The above WHO priorities align implicitly with the
ongoing work of the Public Health Agency of
Canada and its Canadian Congenital Anomalies
Surveillance Network.
To meet Canada’s future health needs in this area,
there will be a continued requirement for national,
provincial and territorial organizations involved in
reproductive, maternal and infant health to ensure
that public health strategies and programs are
evidence-based and determined by appropriate
priorities. This report serves to support that function
and underscores the importance of integrating
congenital anomalies surveillance and reproductive/
preconception health promotion within the public
health spectrum of priority setting, programming,
practice and evaluation.
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REFERENCES
1. Canadian Institute for Health Information.
National Health Expenditure Trends. 1975-2010.
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http://www.cihi.ca.
2. De Wals P, Tairou F, Van Allen MI, et al.
Reduction in neural-tube defects after folic acid
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3. World Health Organization. Resolutions and
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int/gb/ebwha/pdf_files/WHA63-REC1/WHA63_
REC1-en.pdf.
94 | CONGENITAL ANOMALIES IN CANADA 2013
APPENDIX A
HOW DATA FOR THE CANADIAN CONGENITAL ANOMALIES
SURVEILLANCE SYSTEM (CCASS) ARE DERIVED
Jocelyn Rouleau
R. Brian Lowry
SOURCES OF DATA
The majority of Canada’s acute care hospitals
forward data on all transfers, discharges or deaths to
the Canadian Institute for Health Information (CIHI).
This data are kept in CIHI’s Discharge Abstract
Database (DAD), which accounts for most hospital
inpatient discharges in Canada. The province of
Québec does not participate in the DAD, but their
congenital anomalis (CAs) data are available via
their Système de maintenance et d’exploitation des
données pour l’étude de la clientèle hospitalière
(MED-ÉCHO), which is very similar to the DAD.
The MED-ÉCHO system does not include stillbirths,
requiring the Québec system to rely on vital
statistics data to capture stillbirths with CAs. These
only capture the cause of death, which limits the
incidence of congenital anomalies in stillbirths as
the cause of death is often not recorded as due to a
CA, even when one is present. The DAD can also
report several CAs in stillbirths while Vital Statistics
is only able to report one. Up to 2007, data from
Alberta were available to CCASS directly from the
Alberta Congenital Anomalies Surveillance System
(ACASS), a province-wide registry with multiple
sources of ascertainment. Because more recent
Alberta data are available through ACASS and the
DAD (up to 2009), this report utilized these data
sources. Authors selected the source according to
the analysis needs for their chapters.
Each DAD data file contains demographic, health
services and diagnoses information. Diagnosis
information is managed using the International
Classification of Diseases (ICD) codes (ICD-9 CM
(Clinical Modification), or ICD-9 prior to 2001, and
ICD-10-CA (Canadian Enhancement) from 2001
onwards. The implementation of ICD-10-CA across
Canadian jurisdictions was completed in 2006.
Demographic information includes variables such as
province of residence, scrambled health insurance
number, three-digit postal code, residence code,
year of birth, gender, admission date, discharge
date, date of death, birth weight, live birth or
stillbirth, and 25 ICD codes.
MED-ÉCHO and ACASS data are merged with the
CIHI-derived DAD data by the Maternal and Infant
Health Section, Public Health Agency of Canada to
create the final CCASS database.
ASCERTAINMENT
The CCASS data are limited to live births and
stillbirths. The length of ascertainment
changed from one year to 30 days in 2001 for
all data derived from the DAD, due to
administrative reasons.
The CCASS data using DAD depend on a melding
process to group the admission of the same infant
into one record to avoid duplication of CAs. This is a
two-step approach. The first step is based on the
melding of infant records using the scrambled
health insurance number provided in the DAD, the
second step involves a probabilistic method using
CA codes, province of residence, birth date (only
available for an infant up to 30 days), gender,threedigit postal code and a residence code that
identifies the area in which the patient resides. Such
codes are defined by the provincial and territorial
Ministries of Health and may reflect city,
municipality, health region, etc.
CODING OF CONGENITAL ANOMALIES
Categorization of congenital anomalies in CCASS
includes summary by individual ICD codes, 59
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standard categories and 14 major categories, see
Table A.1. Minor CAs may fall under these codes,
but are not included in the statistics. Anomalies
which are not reported in major categories include:
congenital anomalies of eyelids, lacrimal system,
and orbit (743.6/Q10.0–Q10.6); certain
musculoskeletal deformities of skull, face and jaw
(754.0/Q67.0–Q67.4); other anomalies of larynx,
trachea, and bronchus (748.3/Q31–Q32); other
anomalies of intestine (751.5/ Q43.4–Q43.9); atresia
and stenosis of urethra and bladder neck (753.6/
Q64.2–Q64.3); undescended testicle (752.5/Q53);
other specified anomalies of skin (757.3/Q81,
Q82.1–Q82.8); tongue tie (750.0/Q38.1). Individual
counts of these codes can be obtained.
A CA category is defined by a list of one or more
ICD codes. The CA category includes every infant
with one or more of the codes listed within a given
category. For example, an infant with an upper limb
deficiency and a lower limb deficiency is counted as
one case of limb deficiency. However, the upper
and lower limb anomalies can also be reported as
two separate categories, when needed, because
they have two distinct ICD codes. Similarly, infants
with more than one anomaly involving different
categories will be counted in each of those
categories as a case. For instance, an infant with
cleft lip and palate and an atrioventriculoseptal
defect will be counted as one case in each category.
Counting is straight forward when an anomaly and a
case are one and the same, (e.g., gastroschisis,
Down syndrome, cleft palate). However, when
organs are paired, information is lost by grouping
them under one category. For example, an infant
with microphthalmia in one eye and glaucoma in
the other (i.e., anomalies in two different sections of
the eye), will only be counted once as a case of eye
anomalies in CCASS. However, because
microphthalmia (ICD-Q11.2) and glaucoma (ICD
Q15.0) have separate ICD codes the two conditions
can be reported separately, when the major
categories are expanded.
Neural tube defects (NTDs) are a special case. Many
systems such as the ACASS code only the highest
level lesion, thus anencephaly will usually trump all
other lesions; if two NTDs are present, a hierarchical
decision is made by the ACASS coders (e.g., an
infant has anencephaly and spina bifida, only
anencephaly is coded and counted). The CCASS
does not use this approach with respect to NTDs.
This is not a problem when reporting NTDs as a
category but could have an impact on the rates of
anencephaly, encephalocele and spina bifida when
reported separately.
STRENGTHS
• The CCASS provides national coverage.
• The timing of the availability of the DAD data
continues to improve.
• The CCASS makes a very efficient use of
available resources.
• Gestational age is available for the data
reported in the DAD using the ICD-10-CA.
Gestational age was not used in this report
because this information is incomplete or
non-existent prior to 2007.
• Since the use of ICD-10-CA data, the
DAD allows for maternal and newborn
linkage, which makes possible to include
other important maternal variables (e.g.,
smoking, diabetes, hypertension, obesity and
maternal age).
DATA LIMITATIONS
• Data from ACASS and MED-ÉCHO are ICD
code-based and are processed in the same
manner as CIHI DAD data by CCASS. Despite
being processed in the same manner, certain
rules may differ between systems as noted in
the NTDs the rule of the highest level lesion
example above.
• Coding is dependent on hospital coders
who may utilize different coding protocols
and who may have differing degrees of
knowledge and skill concerning CA coding.
• Two specific issues relate to coding. First,
because gestational age is not available,
there may be grossly exaggerated rates
of patent ductus arteriosus, patent
foramen ovale, pulmonary hypoplasia and
undescended testes. Although, as mentioned
earlier, undescended testes are omitted as a
96 | CONGENITAL ANOMALIES IN CANADA 2013
minor anomaly, data on them as an individual
CA can be tabulated. Second, coding the
individual components of a tetralogy of
Fallot (e.g., pulmonary stenosis, VSD, and
dextroposed aorta), will artificially inflate the
rates of these CAs if they are considered
individually. This would not represent an
issue if this combination is reduced to a
single category.
• The lack of information on terminations of
pregnancy for CAs before 20 weeks gestation
is a major weakness.
• Other limitations include lack of verification of
diagnosis, no follow-up on apparent clusters,
inability to totally eliminate duplications and
lack of information on maternal or paternal
risk factors.
TABLE A.1
Canadian Congenital Anomalies Surveillance System Routine Analysis Categories
Categories
ICD-9 Codes
ICD-10 Codes
Anencephalus & similar anomalies
740.0–740.2
Q00.0–Q00.2
Spina bifida
741.0–741.9
Q05.0–Q05.9, Q07.0
Encephalocele
742.0
Q01.0–Q01.2, Q01.8, Q01.9
Anencephalus & similar anomalies
740.0–740.2
Q00.0–Q00.2
Spina bifida
741.0–741.9
Q05.0–Q05.9, Q07.0
Encephalocele
742.0
Q01.0–Q01.2,Q01.8,Q01.9
Microcephalus & brain reduction
742.1–742.2
Q02, Q04.0–Q04.3
Congenital hydrocephalus
742.3
Q03.0, Q03.1, Q03.8, Q03.9
Other specified & unspecified
CNS anomalies
742.4–742.9
Q04.4–Q04.6, Q04.8, Q04.9, Q06.0–Q06.4,
Q06.8, Q06.9, Q07.8, Q07.9
Anophthalmos, microphthalmos
743.0–743.1
Q11.0–Q11.2
Other eye anomalies
743.2–743.9
Q10.0–Q10.7, Q11.3, Q12.0–Q12.4, Q12.8–
Q13.5, Q13.8–Q14.3, Q14.8–Q15.0, Q15.8,
Q15.9
Anomalies of ear causing impairment
744.0
Q16.0, Q16.1, Q16.3–Q16.5, Q16.9
Other ear anomalies
744.1–744.3
Q16.2, Q17.0–Q17.5, Q17.8, Q17.9
Anomalies of face & neck
744.4–744.9
Q18.0–Q18.9
Common truncus
745.0
Q20.0, Q21.4
Transposition of great vessels
745.1
Q20.1–Q20.3, Q20.5
Tetralogy of Fallot
745.2
Q21.3
Births
Stillbirths
Neural tube defects
Central nervous system anomalies
Eye anomalies
Ear face & neck anomalies
Congenital heart defects
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Categories
ICD-9 Codes
ICD-10 Codes
Common ventricle
745.3
Q20.4
Ventricular septal defect
745.4
Q21.0, Q21.8
Atrial septal defect
745.5
Q21.1
Endocardial cushion defects
745.6
Q21.2
Other septal closure defects
745.7–745.9
Q21.9
Heart valve anomalies
746.0–746.6
Q22.0–Q22.5, Q23.0–Q23.3
Hypoplastic left heart syndrome
746.7
Q23.4
Other heart anomalies
746.8–746.9
Q20.6, Q20.8, Q20.9, Q22.6, Q22.8, Q22.9,
Q23.8–Q24.6, Q24.8, Q24.9
Coarctation of aorta
747.1
Q25.1
Other anomalies of aorta
747.2
Q25.2–Q25.4
Pulmonary artery anomalies
747.3
Q25.5–Q25.7
Other circulatory system anomalies
747.4–747.9
Q25.8–Q26.6, Q26.8–Q27.4, Q27.8–Q28.3,
Q28.8, Q28.9
Nose anomalies
748.0, 748.1
Q30.0–Q30.3, Q30.8, Q30.9
Lung agenesis & hypoplasia
748.5
Q33.2, Q33.3, Q33.6
Other respiratory system anomalies
748.2–748.4, 748.6,
748.8, 748.9
Q31.0–Q31.4, Q31.8–Q32.4, Q33.0, Q33.1,
Q33.4, Q33.5, Q33.8–Q34.1, Q34.8, Q34.9
Cleft palate
749.0
Q35.0–Q35.9
Cleft lip
749.1
Q36, Q36.0, Q36.1, Q36.9
Cleft palate with cleft lip
749.2
Q37, Q37.0–Q37.5, Q37.8, Q37.9
750.3
Q39.0–Q39.4, Q39.8
Circulatory system anomalies
Respiratory system anomalies
Orofacial clefts
Digestive system anomalies
T-E fistula, esophageal atresia
& stenosis
Other upper alimentary tract anomalies 750.1, 750.2, 750.4–
750.9
Q38.0, Q38.2–Q38.8, Q39.5, Q39.6, Q39.9,
Q40.0–Q40.3, Q40.8, Q40.9
Intestinal, anorectal atresia & stenosis
751.2
Q42.0–Q42.3, Q42.8, Q42.9
Other digestive system anomalies
751.0, 751.1, 751.3–
751.9
Q41.0–Q41.2, Q41.8, Q41.9, Q43.0–Q44.7,
Q45.0–Q45.3, Q45.8, Q45.9
Hypospadias, epispadias
752.6
Q54.0–Q54.4, Q54.8, Q54.9, Q64.0
Other genital organ anomalies
752.0–752.5, 752.7–
752.9
Q50.0–Q50.6, Q51.0–Q53.2, Q53.9, Q55.0–
Q55.6, Q55.8–Q56.4
Renal agenesis & dysgenesis
753.0
Q60.0–Q60.6
Cystic kidney disease
753.1
Q61.0–Q61.5, Q61.8, Q61.9
Other urinary system anomalies
753.2–753.9
Q62.0–Q62.8, Q63.0–Q63.3, Q63.8, Q63.9,
Q64.1–Q64.9
Genital organ anomalies
Urinary system anomalies
98 | CONGENITAL ANOMALIES IN CANADA 2013
Categories
ICD-9 Codes
ICD-10 Codes
Certain musculoskeletal anomalies
754.0–754.2, 754.4,
754.8
Q67.0–Q67.7, Q68.0–Q68.5, Q76.3
Congenital dislocation of hip
754.3
Q65.0–Q65.6, Q65.8
Clubfoot
754.5–754.7
Q66.0–Q66.9
Polydactyly, syndactyly
755.0–755.1
Q69.0–Q69.2, Q69.9–Q70.4, Q70.9
Limb deficiency defects
755.2–755.4
Q71.0–Q71.4, Q71.5, Q71.8–Q73.1, Q73.8
Other, unspecified limb anomalies
755.5–755.9
Q65.9, Q68.8, Q71.6, Q74.0–Q74.3, Q74.8,
Q74.9
Anomalies of abdominal wall
756.7
Q79.2–Q79.5
Other musculoskeletal anomalies
756.0–756.6, 756.8,
756.9
Q67.8, Q75.0–Q75.5, Q75.8–Q76.2, Q76.4–
Q78.6, Q78.8–Q79.1, Q79.6, Q79.8, Q79.9
Musculoskeletal anomalies
Gastroschisis*
Q79.3
Anomalies of integument
757.0–757.9
Q80.0–Q80.4, Q80.8–Q81.2, Q81.8–Q82.5,
Q82.8–Q83.3, Q83.8–Q84.6, Q84.8, Q84.9
Down syndrome
758.0
Q90.0–Q90.2, Q90.9
Trisomy 13
758.1
Q91.4–Q91.7
Trisomy 18
758.2
Q91.0–Q91.3
Autosomal syndromes
758.3–758.5
Q92.0–Q93.9, Q95.0–Q95.5, Q95.8, Q95.9
Sex chromosome conditions
Other chromosomal anomalies
758.6–758.8
Q96.0–Q96.4, Q96.8–Q97.3, Q97.8–Q99.2
Other & unspecified anomalies
758.9, 759.0–759.9
Q85.0, Q85.1, Q85.8–Q86.2, Q86.8, Q87.0–
Q87.5, Q87.8, Q89.0–Q89.4, Q89.7–Q89.9,
Q99.8, Q99.9
Fetal alcohol syndrome
Not reportable
Q86.0
Cases
All anomalies
Source: Canadian Congenital Anomaly Surveillance System.
*Gastrochisis was not included as a separate condition in routine CCASS analysis using ICD-9.
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APPENDIX B
DATA TABLES
TABLE B1.1
Total congenital anomaly (CA) rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI)
per 10,000 total births
Year
Total births**
Number of cases
1998
269,079
12,140
451.2 (443.2–459.3)
1999
265,746
11,909
448.1 (440.1–456.3)
2000
258,667
11,428
441.8 (433.7–450.0)
2001
263,350
12,126
460.5 (452.3–468.7)
2002
259,505
11,207
431.9 (423.9–439.9)
2003
264,981
10,994
414.9 (407.2–422.7)
2004
266,277
10,830
406.7 (399.1–414.5)
2005
269,530
10,837
402.1 (394.5–409.7)
2006
275,737
10,564
383.1 (375.8–390.5)
2007
286,098
10,799
377.5 (370.4–384.6)
2008
290,725
11,203
385.3 (378.2–392.5)
2009
292,312
11,260
385.2 (378.1–392.4)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths.
CI—Confidence Interval
100 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B1.2
Total congenital anomaly (CA) rate in live births, Canada (excluding Québec),* 1998–2009
Year
Live births
Number of cases
Prevalence rate (95% CI)
per 10,000 live births
1998
267,386
11,804
441.5 (433.5–449.5)
1999
263,932
11,484
435.1 (427.2–443.1)
2000
256,943
11,053
430.2 (422.2–438.3)
2001
261,524
11,735
448.7 (440.6–456.9)
2002
257,634
10,802
419.3 (411.4–427.3)
2003
263,051
10,569
401.8 (394.2–409.5)
2004
264,305
10,446
395.2 (387.7–402.9)
2005
267,465
10,422
389.7 (382.2–397.2)
2006
273,680
10,114
369.6 (362.4–376.8)
2007
283,871
10,283
362.2 (355.3–369.3)
2008
288,458
10,691
370.6 (363.6–377.7)
2009
290,067
10,763
371.1 (364.1–378.1)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. CI—Confidence Interval
TABLE B1.3
Total congenital anomaly (CA) rate in stillbirths, Canada (excluding Québec),* 1998–2009
Year
Total stillbirths
Number of cases
Prevalence rate (95% CI)
per 10,000 total stillbirths
1998
1,693
336
1,984.6(1778.1–2208.6)
1999
1,814
389
2,144.4(1936.6–2368.5)
2000
1,724
368
2,134.6(1922.0–2364.2)
2001
1,826
392
2,146.8(1939.5–2370.2)
2002
1,871
404
2,159.3(1953.8–2380.5)
2003
1,930
425
2,202.1(1997.7–2421.7)
2004
1,972
384
1,947.3(1757.3–2152.1)
2005
2,065
415
2,009.7(1821.0–2212.7)
2006
2,057
450
2,187.7(1990.2–2399.4)
2007
2,227
516
2,317.0(2121.4–2525.8)
2008
2,267
512
2,258.5(2067.1–2462.9)
2009
2,245
497
2,213.8(2023.4–2417.3)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. CI—Confidence Interval
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TABLE B1.4
Percentage of stillborn congenital anomaly (CA) cases <750 g, Canada (excluding Québec),* 1998–2009
Year
Total stillborn
cases
Total stillborn
cases with known
birth weight
Number of
stillborn cases
<750 g
Percentage of
total stillborn
cases <750 g
Percentage of
total stillborn
cases with known
birth weight
<750 g
1998
336
320
212
63.1%
66.3%
1999
389
377
276
71.0%
73.2%
2000
368
349
257
69.8%
73.6%
2001
392
378
259
66.1%
68.5%
2002
404
353
252
62.4%
71.4%
2003
425
368
279
65.6%
75.8%
2004
384
342
258
67.2%
75.4%
2005
415
370
286
68.9%
77.3%
2006
450
356
288
64.0%
80.9%
2007
516
387
286
55.4%
73.9%
2008
512
382
278
54.3%
72.8%
2009
497
383
285
57.3%
74.4%
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
TABLE B1.5A/B
Total congenital anomaly (CA) rate, by province/territory, Canada (excluding Québec),* 2000–2009 combined
Province/territory
Total births**
Number of cases
Prevalence rate (95% CI)
per 10,000 total births
46,294
2,880
622.1 (599.6–645.3)
Prince Edward Island
14,039
589
419.5 (386.3–454.8)
Nova Scotia
88,046
3,174
360.5 (348.1–373.3)
New Brunswick
70,791
3,148
444.7 (429.3–460.5)
1,368,360
52,836
386.1 (382.8–389.4)
Manitoba
143,598
4,994
347.8 (338.2–357.6)
Saskatchewan
124,584
4,899
393.2 (382.3–404.4)
Alberta
430,089
20,168
468.9 (462.5–475.4)
British Columbia
409,270
16,806
410.6 (404.4–416.9)
Yukon
3,912
178
455.0 (390.6–527.0)
Northwest Territories
6,984
268
383.7 (339.2–432.5)
Nunavut
5,529
328
593.2 (530.8–661.0)
2,727,182
111,248
407.9 (405.5–410.3)
Newfoundland and Labrador
Ontario
CANADA‡
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2000–2009.
* Québec was excluded because data were not available for all years. ** Total births include live births and stillbirths.
‡ Includes data for unknown provinces/territories. CI—Confidence Interval
102 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B1.6
Total congenital anomaly (CA) rate, by gender, Canada (excluding Québec),* 1998–2009
Males
Year
Total
births**
Number
of cases
1998
269,079
6,909
256.8
1999
265,746
6,629
2000
258,667
2001
Females
Prevalence rate (95% CI)
per 10,000 total births
Number of
cases
Prevalence rate (95% CI)
per 10,000 total births
(250.7–262.9)
5,209
193.6 (188.4–198.9)
249.4
(243.5–255.5)
5,227
196.7 (191.4–202.1)
6,492
251.0
(244.9–257.2)
4,922
190.3 (185.0–195.7)
263,350
6,734
255.7
(249.6–261.9)
5,383
204.4 (199.0–209.9)
2002
259,505
6,288
242.3
(236.4–248.4)
4,907
189.1 (183.8–194.5)
2003
264,981
6,187
233.5
(227.1–239.4)
4,794
180.9 (175.8–186.1)
2004
266,277
6,174
231.9
(226.1–237.7)
4,639
174.2 (169.2–179.3)
2005
269,530
6,118
227.0
(221.3–232.7)
4,693
174.1 (169.2–179.2)
2006
275,737
6,025
218.5
(213.0–224.1)
4,513
163.7 (158.9–168.5)
2007
286,098
6,071
212.2
(206.9–217.6)
4,682
163.7 (159.0–168.4)
2008
290,725
6,445
221.7
(216.3–227.2)
4,711
162.0 (157.4–166.7)
2009
292,312
6,532
223.5
(218.1–228.9)
4,678
160.0 (155.5–164.7)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths.
CI—Confidence Interval
TABLE B1.7
Ratio of total male to total female congenital anomaly cases (CA), Canada (excluding Québec),* 1998–2009
Year
Number of male cases
Number of female cases
Ratio of male to female cases
1998
6,909
5,209
1.33
1999
6,629
5,227
1.27
2000
6,492
4,922
1.32
2001
6,734
5,383
1.25
2002
6,288
4,907
1.28
2003
6,187
4,794
1.29
2004
6,174
4,639
1.33
2005
6,118
4,693
1.30
2006
6,025
4,513
1.34
2007
6,071
4,682
1.30
2008
6,445
4,711
1.37
2009
6,532
4,678
1.40
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
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TABLE B2.1
Down syndrome (DS) rate, Canada, 1998–2007
Year
Total births*
Number of cases
Prevalence rate (95% CI) per
10,000 total births
1998
343,823
487
14.2 (12.9–15.5)
1999
338,407
492
14.5 (13.3–15.9)
2000
330,398
500
15.1 (13.8–16.5)
2001
336,835
449
13.3 (12.1–14.6)
2002
331,527
469
14.1 (12.9–15.5)
2003
338,417
507
15.0 (13.7–16.3)
2004
339,687
455
13.4 (12.2–14.7)
2005
347,476
517
14.9 (13.6–16.2)
2006
359,618
496
13.8 (12.6–15.1)
2007
372,724
483
13.0 (11.8–14.2)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
TABLE B2.2A/B
Down syndrome (DS) rate, by province/territory, Canada, 1998–2007 combined
Province/territory
Total births*
Prevalence rate (95% CI) per
10,000 total births
Number of cases
Newfoundland and Labrador
46,644
74
15.9 (12.5–19.9)
Prince Edward Island
14,078
24
17.0 (10.9–25.4)
Nova Scotia
89,344
171
19.1 (16.4–22.2)
New Brunswick
72,161
105
14.6 (11.9–17.6)
Québec
748,444
838
11.2 (10.5–12.0)
Ontario
1,354,028
1,923
14.2 (13.6–14.9)
Manitoba
141,087
208
14.7 (12.8–16.9)
Saskatchewan
122,222
185
15.1 (13.0–17.5)
Alberta
416,281
556
13.4 (12.3–14.5)
British Columbia
406,580
715
17.6 (16.3–18.9)
Yukon
3,938
§
Northwest Territories
7,434
18
Nunavut
4,186
9
3,438,912
4,855
CANADA‡
§
24.2 (14.3–38.3)
21.5(9.8–40.8)
14.1 (13.7–14.5)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. § Rate suppressed due to small cell counts (<5).
‡Includes data for unknown provinces/territories. CI—Confidence Interval
104 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B3.1A
Neural tube defect (NTD) rate, Canada, 1996–2007
Year
Total births*
Number of cases
Prevalence rate (95% CI) per
10,000 total births
1996
366,811
278
7.6 (6.7–8.5)
1997
351,139
267
7.6 (6.7–8.6)
1998
343,823
194
5.6 (4.9–6.5)
1999
338,407
196
5.8 (5.0–6.7)
2000
330,398
170
5.1 (4.4–6.0)
2001
336,835
166
4.9 (4.2–5.7)
2002
331,527
145
4.4 (3.7–5.1)
2003
338,417
150
4.4 (3.8–5.2)
2004
339,687
130
3.8 (3.2–4.5)
2005
347,476
159
4.6 (3.9–5.3)
2006
359,618
126
3.5 (2.9–4.2)
2007
372,724
154
4.1 (3.5–4.8)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1996–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1996–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
TABLE B3.1B
Spina bifida congenita (SBC) rate, Canada, 1996–2007
Year
Total births*
Number of cases
Prevalence rate (95% CI)
per 10,000 total births
1996
366,811
200
5.5 (4.7–6.3)
1997
351,139
188
5.4 (4.6–6.2)
1998
343,823
142
4.1 (3.5–4.9)
1999
338,407
136
4.0 (3.4–4.8)
2000
330,398
110
3.3 (2.7–4.0)
2001
336,835
104
3.1 (2.5–3.7)
2002
331,527
98
3.0 (2.4–3.6)
2003
338,417
99
2.9 (2.4–3.6)
2004
339,687
84
2.5 (2.0–3.1)
2005
347,476
106
3.1 (2.5–3.7)
2006
359,618
86
2.4 (1.9–3.0)
2007
372,724
102
2.7 (2.2–3.3)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1996–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1996–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
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TABLE B3.1C
Anencephalus & similar anomalies rate, Canada, 1996–2007
Year
Total births*
Number of cases
Prevalence rate (95% CI)
per 10,000 total births
1996
366,811
42
1.1 (0.8–1.5)
1997
351,139
54
1.5 (1.2–2.0)
1998
343,823
31
0.9 (0.6–1.3)
1999
338,407
31
0.9 (0.6–1.3)
2000
330,398
38
1.2 (0.8–1.6)
2001
336,835
39
1.2 (0.8–1.6)
2002
331,527
29
0.9 (0.6–1.3)
2003
338,417
33
1.0 (0.7–1.4)
2004
339,687
36
1.1 (0.7–1.5)
2005
347,476
33
0.9 (0.7–1.3)
2006
359,618
28
0.8 (0.5–1.1)
2007
372,724
30
0.8 (0.5–1.1)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
TABLE B3.1D
Encephalocele rate, Canada, 1996–2007
Year
Total births*
Number of cases
Prevalence rate (95% CI) per
10,000 total births
1996
366,811
40
1.1 (0.8–1.5)
1997
351,139
33
0.9 (0.6–1.3)
1998
343,823
23
0.7 (0.4–1.0)
1999
338,407
31
0.9 (0.6–1.3)
2000
330,398
25
0.8 (0.5–1.1)
2001
336,835
26
0.8 (0.5–1.1)
2002
331,527
20
0.6 (0.4–0.9)
2003
338,417
25
0.7 (0.5–1.1)
2004
339,687
12
0.4 (0.2–0.6)
2005
347,476
25
0.7 (0.5–1.1)
2006
359,618
13
0.4 (0.2–0.6)
2007
372,724
23
0.6 (0.4–0.9)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1996–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1996–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
106 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B3.2A
Neural tube defect (NTD) rate, by province/territory, Canada, 1991–1996 combined
Province/territory
Prevalence rate (95% CI) per 10,000
total births
Total births*
Number of cases
Newfoundland and Labrador
37,383
114
30.5(25.2–36.6)
Prince Edward Island
10,172
10
9.8(4.7–18.1)
Nova Scotia**
10,623
21
19.8(12.2–30.2)
New Brunswick
55,154
86
15.6(12.5–19.3)
Québec
541,446
371
6.9(6.2–7.6)
Ontario
897,664
849
9.5(8.8–10.1)
Manitoba
98,184
98
10.0(8.1–12.2)
Saskatchewan
80,865
96
11.9(9.6–14.5)
Alberta
243,150
190
7.8(6.7–9.0)
British Columbia
277,204
245
8.8(7.8–10.0)
Yukon
2,717
§
§
Northwest Territories
7,633
§
§
Nunavut***
N/A
N/A
N/A
CANADA‡
2,251,572
2,063
9.2(8.8–9.6)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1991–1996.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1991–1996.
*Total births include live births and stillbirths.
**Nova Scotia data from 1991–1995 were excluded as they were not available to CCASS prior to 1996.
***Territorial data was unavailable because Nunavut was not established as a territory until 1999. Data on births in Nunavut were included within
those of the Northwest Territories. §Rate suppressed due to small cell counts (<5). ‡Includes data for unknown provinces/territories.
CI—Confidence Interval
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TABLE B3.2B
Neural tube defect (NTD) rate, by province/territory, Canada, 1997–2000 combined
Province/territory
Newfoundland and Labrador
Prince Edward Island
Total births*
20,426
Prevalence rate (95% CI)
per 10,000 total births
Number of cases
17
8.3(4.8–13.3)
5,973
§
Nova Scotia
38,512
37
9.6(6.8–13.2)
§
New Brunswick
31,591
23
7.3(4.6–10.9)
Québec
295,660
161
5.4(4.6–6.4)
Ontario
536,421
329
6.1(5.5–6.8)
Manitoba
57,456
45
7.8(5.7–10.5)
Saskatchewan
50,110
29
5.8(3.9–8.3)
Alberta
151,960
71
4.7(3.6–5.9)
British Columbia
169,658
115
6.8(5.6–8.1)
Yukon
1,576
§
§
Northwest Territories
3,826
§
§
Nunavut**
598
§
§
CANADA‡
1,325,255
827
6.1(5.7–6.5)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1997–2000.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1997–2000.
*Total births include live births and stillbirths.
**The rate for Nunavut is a combined rate for the 2-year period of 1999–2000 because Nunavut was not established as a territory until 1999.
§Rate suppressed due to low cell numbers (<5). ‡Includes data for unknown provinces/territories. CI—Confidence Interval
TABLE B3.2C
Neural tube defect (NTD) rate, by province/territory, Canada, 2001–2007 combined
Province/territory
Newfoundland and Labrador
Total births*
Number of cases
Prevalence rate (95% CI) per
10,000 total births
4.7(2.6–7.8)
31,660
15
9,675
§
Nova Scotia
60,849
31
5.1(3.5–7.2)
New Brunswick
48,716
17
3.5(2.0–5.6)
Québec
531,165
173
3.3(2.8–3.8)
Ontario
954,653
386
4.0(3.6–4.5)
98,386
54
5.5(4.1–7.2)
Prince Edward Island
Manitoba
Saskatchewan
§
84,577
42
5.0(3.6–6.7)
Alberta
301,475
126
4.2(3.5–5.0)
British Columbia
281,500
168
6.0(5.1–6.9)
Yukon
2,817
§
§
Northwest Territories
4,738
§
§
Nunavut
3,588
§
§
CANADA‡
2,426,284
1,030
4.2(4.0–4.5)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2001–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 2001–2007.
*Total births include live births and stillbirths.
§Rate suppressed due to small cell counts (<5). ‡Includes data for unknown provinces/territories. CI—Confidence Interval
108 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B4.1
Congenital heart defect (CHD) rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
1998
269,079
2,883
107.1(103.3–111.1)
1999
265,746
2,816
106.0(102.1–110.0)
2000
258,667
2,902
112.2(108.1–116.3)
2001
263,350
2,858
108.5(104.6–112.6)
2002
259,505
2,681
103.3(99.4–107.3)
2003
264,981
2,513
94.8(91.2–98.6)
2004
266,277
2,626
98.6(94.9–102.5)
2005
269,530
2,668
99.0(95.3–102.8)
2006
275,737
2,583
93.7(90.1–97.4)
2007
286,098
2,599
90.8(87.4–94.4)
2008
290,725
2,751
94.6(91.1–98.2)
2009
292,312
2,487
85.1(81.8–88.5)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
**Total births include live births and stillbirths. CI—Confidence Interval
TABLE B4.2A
Common truncus (CT) defect rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
1998
269,079
39
1.4(1.0–2.0)
1999
265,746
37
1.4(1.0–1.9)
2000
258,667
33
1.3(0.9–1.8)
2001
263,350
27
1.0(0.7–1.5)
2002
259,505
17
0.7(0.4–1.0)
2003
264,981
26
1.0(0.6–1.4)
2004
266,277
13
0.5(0.3–0.8)
2005
269,530
21
0.8(0.5–1.2)
2006
275,737
17
0.6(0.4–1.0)
2007
286,098
26
0.9(0.6–1.3)
2008
290,725
27
0.9(0.6–1.4)
2009
292,312
9
0.3(0.1–0.6)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
**Total births include live births and stillbirths. CI—Confidence Interval
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TABLE B4.2B
Transposition of great vessels (TGV) rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
1998
269,079
151
5.6(4.8–6.6)
1999
265,746
167
6.3(5.4–7.3)
2000
258,667
154
6.0(5.1–7.0)
2001
263,350
116
4.4(3.6–5.3)
2002
259,505
120
4.6(3.8–5.5)
2003
264,981
112
4.2(3.5–5.1)
2004
266,277
123
4.6(3.8–5.5)
2005
269,530
135
5.0(4.2–5.9)
2006
275,737
129
4.7(3.9–5.6)
2007
286,098
130
4.5(3.8–5.4)
2008
290,725
143
4.9(4.1–5.8)
2009
292,312
149
5.1(4.3–6.0)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
**Total births include live births and stillbirths.
CI—Confidence Interval
TABLE B4.2C
Tetralogy of Fallot (TOF) rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
1998
269,079
143
5.3(4.5–6.3)
1999
265,746
130
4.9(4.1–5.8)
2000
258,667
159
6.1(5.2–7.2)
2001
263,350
105
4.0(3.3–4.8)
2002
259,505
103
4.0(3.2–4.8)
2003
264,981
96
3.6(2.9–4.4)
2004
266,277
79
3.0(2.3–3.7)
2005
269,530
118
4.4(3.6–5.2)
2006
275,737
99
3.6(2.9–4.4)
2007
286,098
102
3.6(2.9–4.3)
2008
290,725
107
3.7(3.0–4.4)
2009
292,312
93
3.2(2.6–3.9)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years.
**Total births include live births and stillbirths. CI—Confidence Interval
110 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B4.2D
Endocardial cushion defect (ECD) rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
1998
269,079
87
3.2(2.6–4.0)
1999
265,746
87
3.3(2.6–4.0)
2000
258,667
91
3.5(2.8–4.3)
2001
263,350
65
2.5(1.9–3.1)
2002
259,505
93
3.6(2.9–4.4)
2003
264,981
94
3.5(2.9–4.3)
2004
266,277
110
4.1(3.4–5.0)
2005
269,530
110
4.1(3.4–4.9)
2006
275,737
103
3.7(3.0–4.5)
2007
286,098
101
3.5(2.9–4.3)
2008
290,725
120
4.1(3.4–4.9)
2009
292,312
121
4.1(3.4–4.9)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. CI—Confidence Interval ** Total births include live births and stillbirths.
TABLE B4.2E
Hypoplastic left heart syndrome (HLHS) rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
1998
269,079
88
3.3(2.6–4.0)
1999
265,746
78
2.9(2.3–3.7)
2000
258,667
92
3.6(2.9–4.4)
2001
263,350
90
3.4(2.7–4.2)
2002
259,505
68
2.6(2.0–3.3)
2003
264,981
62
2.3(1.8–3.0)
2004
266,277
75
2.8(2.2–3.5)
2005
269,530
74
2.7(2.2–3.4)
2006
275,737
54
2.0(1.5–2.6)
2007
286,098
76
2.7(2.1–3.3)
2008
290,725
74
2.5(2.0–3.2)
2009
292,312
70
2.4(1.9–3.0)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths. CI—Confidence Interval
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TABLE B4.2F
Common ventricle (CV) defect rate, Canada (excluding Québec),* 1998–2009
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
1998
269,079
30
1.1(0.8–1.6)
1999
265,746
33
1.2(0.9–1.7)
2000
258,667
34
1.3(0.9–1.8)
2001
263,350
16
0.6(0.3–1.0)
2002
259,505
22
0.8(0.5–1.3)
2003
264,981
14
0.5(0.3–0.9)
2004
266,277
12
0.5(0.2–0.8)
2005
269,530
11
0.4(0.2–0.7)
2006
275,737
18
0.7(0.4–1.0)
2007
286,098
18
0.6(0.4–1.0)
2008
290,725
21
0.7(0.4–1.1)
2009
292,312
16
0.5(0.3–0.9)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2009.
*Québec was excluded because data were not available for all years. **Total births include live births and stillbirths. CI—Confidence Interval
TABLE B4.3A/B
Congenital heart defect (CHD) rate, by province/territory, Canada (excluding Québec),* 2000–2009 combined
Province/territory
Total births**
Prevalence rate (95% CI) per
10,000 total births
Number of cases
Newfoundland and Labrador
46,294
704
152.1(141.0–163.7)
Prince Edward Island
14,039
142
101.2(85.2–119.2)
Nova Scotia
88,046
743
84.4(78.4–90.7)
New Brunswick
70,791
678
95.8(88.7–103.3)
1,368,360
13,530
98.9(97.2–100.6)
Manitoba
143,598
1,242
86.5(81.7–91.4)
Saskatchewan
124,584
1,133
90.9(85.7–96.4)
Alberta
430,089
4,752
British Columbia
409,270
3,225
78.8(76.1–81.6)
Yukon
3,912
45
115.0(83.9–153.9)
Northwest Territories
6,984
76
108.8(85.7–136.2)
5,529
130
235.1(196.4–279.2)
2,727,182
26,668
Ontario
Nunavut
CANADA‡
110.5(107.4–113.7)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2000–2009.
*Québec was excluded because data were not available for all years.
**Total births include live births and stillbirths.
‡Includes data for unknown provinces/territories. CI—Confidence Interval
97.8(96.6–99.0)
112 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B5.1
Total orofacial clefts (OFCs) and cleft palate (CP) rates, Canada, 1998–2007
Orofacial clefts (OFCs)
Cleft palate (CP)
Year
Total
births*
1998
343,823
617
17.9(16.6–19.4)
250
7.3(6.4–8.2)
1999
338,407
628
18.6(17.1–20.1)
272
8.0(7.1–9.1)
2000
330,398
564
17.1(15.7–18.5)
223
6.7(5.9–7.7)
2001
336,835
544
16.2(14.8–17.6)
229
6.8(5.9–7.7)
2002
331,527
547
16.5(15.1–17.9)
241
7.3(6.4–8.2)
2003
338,417
511
15.1(13.8–16.5)
234
6.9(6.1–7.9)
2004
339,687
553
16.3(15.0–17.7)
232
6.8(6.0–7.8)
2005
347,476
565
16.3(14.9–17.7)
260
7.5(6.6–8.4)
2006
359,618
511
14.2(13.0–15.5)
227
6.3(5.5–7.2)
2007
372,724
559
15.0(13.8–16.3)
247
6.6(5.8–7.5)
Number of
cases
Prevalence rate (95% CI)
per 10,000 total births
Number of
cases
Prevalence rate (95% CI)
per 10,000 total births
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
TABLE B5.1A
Cleft lip (CL) and cleft lip with or without cleft palate (CL±CP) rates, Canada, 1998–2007
Cleft lip (CL)
(CL±CP)
Year
Total
births*
1998
343,823
98
2.9(2.3–3.5)
367
10.7(9.6–11.8)
1999
338,407
97
2.9(2.3–3.5)
356
10.5(9.5–11.7)
2000
330,398
114
3.5 (2.8 –4.1)
341
10.3(9.3–11.5)
2001
336,835
102
3.0(2.5–3.7)
315
9.4(8.3–10.4)
2002
331,527
103
3.1(2.5–3.8)
310
9.4(8.3–10.5)
2003
338,417
91
2.7(2.2–3.3)
280
8.3(7.3–9.3)
2004
339,687
102
3.0(2.4–3.6)
323
9.5(8.5–10.6)
2005
347,476
101
2.9(2.4–3.5)
309
8.9(7.9–9.9)
2006
359,618
103
2.9(2.3–3.5)
294
8.2(7.3–9.2)
2007
372,724
118
3.2(2.6–3.8)
322
8.6(7.7–9.6)
Number of
cases
Prevalence rate (95% CI)
per 10,000 total births
Number of
cases
Prevalence rate (95% CI)
per 10,000 total births
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
REPORT TITLE
GOES HERE
CONGENITAL ANOMALIES
IN CANADA
2013 | 113
TABLE B5.2A/B
Orofacial cleft (OFC) rate, by province/territory, Canada, 1998–2007 combined
Province/territory
Total births*
Prevalence rate (95% CI) per
10,000 total births
Number of cases
Newfoundland and Labrador
46,644
93
19.9(16.1–24.4)
Prince Edward Island
14,078
21
14.9(9.2–22.8)
Nova Scotia
89,344
177
19.8(17.0–23.0)
New Brunswick
72,161
102
14.1(11.5–17.2)
Québec
748,444
1,092
14.6(13.7–15.5)
Ontario
1,354,028
1,978
14.6(14.0–15.6)
Manitoba
141,087
293
20.8(18.5–23.3)
Saskatchewan
122,222
273
22.3(19.8–25.1)
Alberta
416,281
712
17.1(15.9–18.4)
British Columbia
406,580
809
19.9(18.5–25.3)
Yukon
3,938
§
Northwest Territories
7,434
13
17.5(9.3–29.9)
Nunavut
4,186
16
38.2(21.8–62.1)
3,438,912
5,599
16.3(15.9–16.7)
CANADA‡
§
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. §Rate suppressed due to small cell counts (<5).
‡Includes data for unknown provinces/territories. CI—Confidence Interval
TABLE B6.1
Limb deficiency defect (LDD) rate, Canada, 1998–2007
Prevalence rate (95% CI) per
10,000 total births
Year
Total births*
Number of cases
1998
343,823
156
4.5(3.9–5.3)
1999
338,407
127
3.8(3.1–4.5)
2000
330,398
123
3.7(3.1–4.4)
2001
336,835
138
4.1(3.4–4.8)
2002
331,527
137
4.1(3.5–4.9)
2003
338,417
127
3.8(3.1–4.5)
2004
339,687
119
3.5(2.9–4.2)
2005
347,476
129
3.7(3.1–4.4)
2006
359,618
117
3.3(2.7–3.9)
2007
372,724
129
3.5(2.9–4.1)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. CI—Confidence Interval
114 | CONGENITAL ANOMALIES IN CANADA 2013
TABLE B6.2A/B
Limb deficiency defect (LDD) rate, by province/territory, Canada, 1998–2007 combined
Province/territory
Total births*
Prevalence rate (95% CI) per
10,000 total births
Number of cases
3.4(2.0–5.6)
Newfoundland and Labrador
46,644
16
Prince Edward Island
14,078
§
Nova Scotia
89,344
29
3.3(2.2–4.7)
New Brunswick
72,161
18
2.5(1.5–3.9)
Québec
748,444
354
4.7(4.2-5.2)
Ontario
1,354,028
401
3.0(2.7–3.3)
Manitoba
141,087
62
4.4(3.4–5.6)
Saskatchewan
122,222
63
5.2(4.0–6.6)
Alberta
416,281
202
4.9(4.2–5.6)
British Columbia
406,580
147
3.6(3.1–4.2)
§
Yukon
3,938
§
§
Northwest Territories
7,434
§
§
Nunavut
4,186
§
§
CANADA‡
3,438,912
1,302
3.8(3.6–4.0)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 1998–2007.
Source of Alberta data: Alberta Congenital Anomalies Surveillance System, 1998–2007.
*Total births include live births and stillbirths. ‡Includes data for unknown provinces/territories.
§Rate suppressed due to small cell counts (<5). CI—Confidence Interval
TABLE B7.1
Gastroschisis rate, Canada, 2002–2009*
Prevalence rate (95% CI) per
10,000 total births
Year
Total births**
Number of cases
2002
236,492
73
3.1(2.4–3.9)
2003
241,824
72
3.0(2.3–3.7)
2004
251,727
87
3.5(2.8–4.3)
2005
267,658
95
3.5(2.9–4.3)
2006
356,541
130
3.6(3.0–4.3)
2007
369,701
139
3.8(3.2–4.4)
2008
289,172
128
4.4(3.7–5.3)
2009
290,664
129
4.4(3.7–5.3)
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2002–2009.
*Some provincial data were only available for certain years: New Brunswick (2004–2009), Québec (2006–2007) and Manitoba (2005–2009). All others
were available for the full period (2002–2009)
**Total births include live births and stillbirths. CI—Confidence Interval
REPORT TITLE
GOES HERE
CONGENITAL ANOMALIES
IN CANADA
2013 | 115
TABLE B7.2A/B
Gastroschisis rate, by province/territory, Canada, 2002–2009 combined*
Province/territory
Total births**
Prevalence rate (95% CI) per
10,000 total births
Number of cases
Newfoundland and Labrador
36807
15
4.1(2.3–6.7)
Prince Edward Island
11244
9
8.0(3.7–15.2)
Nova Scotia
69993
40
5.7(4.1–7.8)
New Brunswick
41999
15
3.6(2.0–5.9)
Québec‍‍‍‍
167104
27
1.6(1.1–2.4)
Ontario
1103527
307
2.8(2.5–3.1)
74502
53
7.1(5.3–9.3)
Saskatchewan
100331
46
4.6(3.4–6.1)
Alberta
355671
182
5.1(4.4–5.9)
British Columbia
329083
143
4.3(3.7–5.1)
Manitoba
Yukon
2819
§
§
Northwest Territories
5600
§
§
Nunavut
5099
10
19.6(9.4–36.1)
2,303,779
853
3.7(3.5–4.0)
CANADA‡
Source: Public Health Agency of Canada. Canadian Congenital Anomalies Surveillance System, 2002–2009.
*Combined rate for the eight-year period 2002–2009, with the exception of New Brunswick 2004–2009, Manitoba 2005–2009
and Québec 2006–2007
**Total births include live births and stillbirths. §Rate suppressed due to small cell counts (<5).
‡Includes data for unknown provinces/territories. CI—Confidence Interval
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