Congenital Anomalies in Canada: A Perinatal Health Report, 2002

Congenital Anomalies in Canada: A Perinatal Health Report, 2002
87 Pages - (670 KB) in PDF Format

Table of Contents

Foreword

Contributors

Introduction

Chapter 1: Down Syndrome (Trisomy 21)

Risk Factors
Prevalence Rate of Down Syndrome in Canada
Provincial and Territorial Prevalence Rates
International Comparisons
Impact of Prenatal Diagnosis on Birth Prevalence of Down Syndrome
Preventive Measures
Summary
References

Chapter 2: Neural Tube Defects

Risk Factors
Prevalence Rate of Neural Tube Defects in Canada
Provincial and Territorial Prevalence Rates
International Comparisons
Impact of Prenatal Diagnosis on Birth Prevalence of Neural Tube Defects
Preventive Measures
Summary
References

Chapter 3: Congenital Heart Defects

Risk Factors
Prevalence Rate of Congenital Heart Defects in Canada
Provincial and Territorial Prevalence Rates
International Comparisons
Impact of Prenatal Diagnosis on Birth Prevalence of Congenital Heart Defects
Preventive Measures
Summary
References

Chapter 4: Oral Facial Clefts

Risk Factors
Prevalence Rate of Oral Facial Clefts in Canada
Provincial and Territorial Prevalence Rates
International Comparisons
Impact of Prenatal Diagnosis on Birth Prevalence of Oral Facial Clefts
Preventive Measures
Summary
References

Chapter 5: Limb Reduction Defects

Risk Factors
Prevalence Rate of Limb Reduction Defects in Canada
Provincial and Territorial Prevalence Rates
International Comparisons
Impact of Prenatal Diagnosis on Birth Prevalence of Limb Reduction Defects
Preventive Measures
Summary
References

Chapter 6: Prenatal Testing

Prenatal Screening
Prenatal Diagnosis
Impact of Prenatal Diagnosis on Birth Prevalence of Congenital Anomalies
Report on Prenatal Testing Practices in Canada
References

Bibliography

Appendices

Appendix A: Data Sources and Methods
Appendix B: ICD-9 Codes for Congenital Anomalies Listed in this Report
Appendix C: List of Acronyms
Appendix D: Data Tables

List of Figures and Tables

Figures

Figure 1.1: Down syndrome (DS) rate, Canada (excluding Nova Scotia), 1989-1999

Figure 1.2: Down syndrome (DS) rate, by province/territory, Canada, 1997-1999

Figure 2.1: Neural tube defect (NTD) rate, Canada (excluding Nova Scotia), 1989-1999

Figure 2.2: Neural tube defect (NTD) rate, by province/territory, Canada, 1997-1999

Figure 3.1: Congenital heart defect (CHD) rate, Canada (excluding Nova Scotia), 1989-1999

Figure 3.2: Hypoplastic left heart syndrome (HLHS) rate, Canada (excluding Nova Scotia), 1989-1999

Figure 3.3: Hypoplastic left heart syndrome (HLHS) rate, by province/territory, Canada, 1997-1999

Figure 4.1: Cleft lip with or without cleft palate (CL/P) rate, Canada (excluding Nova Scotia), 1989-1999

Figure 4.2: Cleft palate (CP) rate, Canada (excluding Nova Scotia), 1989-1999

Figure 4.3: Cleft lip with or without cleft palate (CL/P) rate, by province/territory,
Canada, 1997-1999

Figure 4.4: Cleft palate (CP) rate, by province/territory, Canada, 1997-1999

Figure 5.1: Limb reduction defect (LRD) rate, Canada (excluding Nova Scotia), 1989-1999

Figure 5.2: Limb reduction defect (LRD) rate, by province/territory, Canada, 1997-1999

Tables

Table 1.1: Down syndrome (DS) rate and number of cases, by maternal age, Alberta, 1990-1998

Table 1.2: Percent of live births to older mothers (30-39 years), Canada, selected years

Table 1.3: Down syndrome (DS) international rate, by country/registry, 1999

Table 2.1: Anencephaly and spina bifida international rates, by country/registry,
1999

Table 3.1: Congenital heart defect (CHD) rate, by maternal age, California, 1995

Table 3.2: Hypoplastic left heart syndrome (HLHS) international rate, by country/
registry, 1999

Table 4.1: Epidemiology of oral facial clefts

Table 4.2: Oral facial clefts international rate, by country/registry, 1999

Table 5.1: Limb reduction defect (LRD) international rate, by country/registry, 1999

Table 6.1: Summary of prenatal diagnostic tests available in Canada

Table 6.2: Proportion of terminations of pregnancy (TOP) among total number of neural tube defect (NTD) cases recorded, by country/registry, 1997-1998  

Foreword

Congenital anomalies contribute a significant proportion of infant morbidity and mortality, as well as fetal mortality. As a consequence, it is essential to have basic epidemiological information on these anomalies. Initially, in the wake of the thalidomide tragedy of 1958-1962, congenital anomaly registries and/or surveillance systems were set up in the hope that they would detect new teratogens. For the most part, this has not proved successful. One exception is valproic acid, which was identified as a teratogen by Dr. Elisabeth Robert in the Rhône region of France, who noted an association between maternal ingestion of valproic acid and spina bifida. Undoubtedly, a rare defect like thalidomide embryopathy would be ascertained from registry systems because of its unique pattern of anomalies and previously rare occurrence. If a teratogen caused a common anomaly like cleft lip or palate or congenital heart defect, it would be very difficult to pinpoint the cause based on most registry systems. Most teratogenic agents which cause malformations are ascertained by astute clinical observations. Despite the fact that registries will not likely detect a new teratogen, it is of vital importance to collect good statistics to note unusual changes in the baseline rate. If a significant cluster is identified, then an ad hoc investigation should take place. Congenital anomaly rates can also be used for planning health services.

The advent of preventive measures, such as the use of folic acid in the prevention of neural tube defects, has brought a new interest in having good baseline statistics on congenital anomalies. Without these data, it would be very difficult to evaluate the effects of such preventive actions. Folic acid may well be an important agent in preventing other congenital anomalies, such as cleft lip and palate and certain types of congenital heart defects. Prenatal diagnosis followed by selective pregnancy termination will also change the birth prevalence of a number of congenital anomalies; hence the need for registries and surveillance systems to enhance ascertainment of fetal anomalies.

The Canadian Congenital Anomalies Surveillance System (CCASS) was established in 1966, prompted by the thalidomide events. Eight years later, Canada was one of the founding members of the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). Unfortunately, there was a hiatus in CCASS's membership in ICBDMS in the early 1990s, but membership was reinstated in 1996. Currently, CCASS is managed by the Division of Health Surveillance and Epidemiology in the Centre for Healthy Human Development at Health Canada.

In the year 2000, Health Canada brought together participants from all provinces and territories to discuss ways of enhancing the surveillance of congenital anomalies in Canada. In addition to increased reporting of CCASS data, as exemplified by this report, Health Canada agreed to establish and support a formal network for congenital anomalies surveillance. The primary goal of the Canadian Congenital Anomalies Surveillance Network is to increase the quantity and quality of congenital anomalies surveillance activities in Canada. The plan is to develop a working coalition between the various provinces and territories and Health Canada, and to support standardized collection of congenital anomaly data, as well as collaborative surveillance efforts. An important step forward is the development of a website and a newsletter and the production of educational materials. In addition, the first annual scientific meeting of this network will be held in Ottawa in September 2002. As one who has worked in this field for nearly 40 years, I am delighted at the initiative that Health Canada is showing.

R. Brian Lowry, MD, DSc, FRCPC
Medical Consultant
Alberta Congenital Anomalies Surveillance System
Calgary, Alberta  

Introduction

Of the approximately 350,000 children born in Canada each year, most are born healthy and at term. However, 2%-3% of these babies will be born with a serious congenital anomaly.¹ More commonly, these babies are born to women with no family history and no known risk factors for congenital anomalies. Infant mortality due to major congenital anomalies has decreased significantly in Canada, from 3.1 per 1,000 live births in 1981 to 1.9 per 1,000 live births in 1995.² Nevertheless, major congenital anomalies remain a leading cause of death among Canadian infants in both the neonatal and postneonatal periods. The case fatality rates for the most severe anomalies, such as anencephaly, trisomies 13 and 18, and severe congenital heart defects, are virtually 100% by the child's first birthday.¹ Although less severe birth defects are often correctable, the emotional and economic burden on the family and society is considerable and invariably leaves families and health care providers with unanswered questions regarding the causes, recurrence risks and preventive measures.

A congenital anomaly is an abnormality of structure, function or body metabolism that is present at birth (even if not diagnosed until later in life) and results in physical or mental disability, or is fatal.3 A congenital anomaly is considered to be multifactorial (or polygenic) in origin when there is a combined influence of (a number of) genes and environmental factors that interfere with normal embryologic development. Multifactorial inheritance is considered when there appears to be a genetic component but there is no clear Mendelian pattern of inheritance. Multifactorial inheritance is the underlying etiology of most of the common congenital anomalies.

Causes of Congenital Anomalies

In spite of the frequency of congenital anomalies, the underlying causes for most remain obscure. It has been estimated that around 15%-25% are due to recognized genetic conditions (chromosome and single gene causes), 8%-12% are due to environmental factors (maternal-related conditions, drug or chemical exposures) and 20%-25% are due to multifactorial inheritance. The majority, 40%-60% of congenital anomalies, have unexplained causes.^4,5

Genetic causes of congenital anomalies include Mendelian-inherited and chromosomal disorders. In Mendelian-inherited conditions, the child inherits a genetic disease or an at-risk gene from one or both parents, or is affected as a result of a new mutation. Cystic fibrosis, Tay-Sachs disease and hemoglobinopathies are examples of relatively common Mendelian conditions. Chromosome abnormalities, the most common being Down syndrome (DS) or trisomy 21, come about as a result of a change in the number or structure of chromosomes, giving rise to the associated physical and mental problems. When chromosomal disorders and Mendelian inheritance are clinically excluded, most of the common congenital anomalies are believed to be multifactorial in origin, wherein environmental and genetic factors have a joint role in causation.

A teratogen is a factor that has an adverse effect on an embryo or a fetus between fertilization and birth.6

The teratogenic risks associated with most maternal environmental exposures are not well-established. Even less understood are the effects of paternal environmental exposures.⁷ For the most part, environmental exposures involve multiple agents and other confounding elements, creating difficulty in identifying the underlying cause(s). The essential principles for determining a cause and effect relationship between environmental exposures and congenital anomalies are: an assessment of the strength of the association; evidence for biologic credibility; consistency of the findings with other studies; specificity of the association; and evidence of both time-exposure and dose-response relationships.⁸ Proving an exposure is teratogenic requires well-designed epidemiologic research using high quality population-based surveillance data.

Examples of infectious agents that can be transmitted to the fetus and have an adverse effect include rubella, cytomegalovirus, varicella and toxoplasma. A number of drugs have clearly been shown to be teratogenic. The global epidemic of thalidomide-induced limb defects seen in the 1960s resulted in today's practice of monitoring for congenital anomalies worldwide. Other examples of teratogenic agents include folic acid antagonists, anticonvulsants (Dilantin, Tegretol), coumarin derivatives and retinoids (Accutane). The most commonly used teratogenic agent is alcohol. Fetal alcohol syndrome (FAS) has been recognized in Canada as one of the leading causes of preventable birth defects and developmental delay in children.^9,10 A wide spectrum of effects of alcohol on the fetus has been demonstrated. Although these relationships are not fully understood, the magnitude of the risk and the nature of harm to the fetus are dependent on the amount of alcohol intake, the gestational age at exposure and the maternal/fetal genetic predisposition. An estimate of the incidence of fetal alcohol syndrome is 1:1,000 births.¹¹

Despite public concerns regarding exposures from the physical environment, actual evidence for the human teratogenic effects from these exposures is limited. Recent research has reported increased risks for structural birth defects and chromosomal abnormalities with air pollution and proximity to hazardous waste sites, respectively;^12,13 however, further studies are required to interpret these findings. Other physical environmental factors with inconclusive findings include maternal pesticide exposure,¹⁴ trihalomethane by-products in public water supplies,^15,16 and industrial areas heavily polluted with lead.¹⁷

Maternal age is a risk factor for congenital anomalies, specifically chromosome problems. Maternal health conditions that contribute to increased risks for congenital anomalies include obesity, epilepsy controlled with anticonvulsant medications, and insulin-dependent diabetes. More recent but somewhat contradictory research has implicated maternal thyroid disease, even when treated, as increasing the risk for congenital anomaly-affected pregnancies.¹⁸

Prevention of Congenital Anomalies

Reducing the birth prevalence and associated infant mortality and morbidity attributed to congenital anomalies in Canada is an attainable goal. Primary preventive efforts are clearly the optimal approach for ensuring the healthiest possible pregnancy outcomes for Canadian women. Food fortification with folic acid, promoting folic acid-containing multivitamin use in the periconceptional period, pre-pregnancy immunization against rubella, and interventions to reduce alcohol and drug use in pregnancy are examples of important primary preventive efforts.

Prenatal diagnosis and subsequent termination of affected pregnancies, as well as in-utero treatment of prenatally detected congenital anomalies, are two secondary preventive strategies. As the scope of in-utero treatment remains limited, secondary prevention is mainly achieved through selective abortion. Prenatal diagnosis also contributes to tertiary prevention in cases where an early prenatal diagnosis improves postnatal management and reduces or avoids neonatal complications. Advances in prenatal testing in Canada are presented in detail in chapter 6 of this report.

Surveillance of Congenital Anomalies in Canada

Accurate surveillance contributes to our knowledge of the possible causative factors and impact of preventive measures on the burden of congenital anomalies in Canada.

Uses of Congenital Anomalies Surveillance Data to provide accurate data on the burden of congenital anomalies in Canada to track trends and identify significant temporal or geographic variation in the occurrence of congenital anomalies to evaluate preventive measures to provide the evidence base for maternal health program and policy development

Canadian Congenital Anomalies Surveillance System

The Canadian Congenital Anomalies Surveillance System (CCASS) is an essential component of congenital anomaly surveillance in Canada. Established by Health Canada in 1966, CCASS was a founding member of the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). This database is managed by the Division of Health Surveillance and Epidemiology in the Centre for Healthy Human Development at Health Canada. CCASS provides birth prevalence rates for selected congenital anomalies in Canada. Live births up to one year of age, and registered stillbirths are captured by CCASS. Data are primarily collected from the Canadian Institute for Health Information (CIHI) acute in-patient abstract file "Discharge Abstract Database" (DAD). Manitoba and Québec submit data to Health Canada from systems similar to the DAD — the Manitoba hospitalization database and Système de maintenance et d'exploitation des données pour l'étude de la clientèle hospitalière (Med-Écho), respectively. Data from Alberta come from the Alberta Congenital Anomalies Surveillance System (ACASS). (See Appendix A for a description of the data sources.) CCASS data are coded according to the International Classification of Diseases, Ninth Edition (ICD-9).

The birth prevalence of congenital anomalies is defined as the number of individual live born and stillborn infants with the congenital anomaly in question (in the numerator), expressed as a proportion of the total number of live births and stillbirths (in the denominator), in a given place and time. "Birth prevalence" is used rather than "incidence," as affected pregnancies that end in early spontaneous abortion or pregnancy termination are not captured.

Strengths and limitations of Canadian Congenital Anomalies Surveillance System data

CCASS is the only ongoing population-based congenital anomaly surveillance database that is able to estimate the Canadian birth prevalence of specific congenital anomalies. CCASS also provides temporal trends at the national level, in addition to provincial/territorial and international comparisons.

One of the most significant limitations is the inability to monitor the impact of prenatal diagnosis on the birth prevalence of selected congenital anomalies. Affected pregnancies that are terminated prior to meeting the jurisdictional criteria for a stillbirth are not captured in CCASS data. This directly limits an assessment of primary and secondary preventive strategies. Further strengths and limitations of CCASS are outlined in Appendix A.

Provincial and Territorial Congenital Anomalies Surveillance Activities

Alberta Congenital Anomalies Surveillance System (ACASS)

ACASS was first established in 1966 as the Registry for Handicapped Children in Alberta, along with similar systems in British Columbia, Manitoba and New Brunswick. In 1980, it was reorganized as a surveillance system for congenital anomalies of infants born in the province of Alberta. ACASS captures cases from early in pregnancy up to 1 year of age using multiple sources of data for case ascertainment. (A database containing pregnancy terminations for the indication of congenital anomalies has been in operation since 1997.) Although this program is considered a passive system, a medical consultant is available to review questionable diagnoses and actively pursue a confirmation of diagnosis from the ascertainment source or attending physician. ACASS regularly publishes a report (Alberta Congenital Anomalies Surveillance System Report), with support from Alberta Health and Wellness, Health Surveillance and Alberta Vital Statistics. ACASS is also an associate member of ICBDMS.

British Columbia Health Status Registry

The Health Status Registry (HSR) in British Columbia operates an independent comprehensive database on congenital anomalies, other genetic conditions, as well as selected disabilities and handicapping conditions. First established in 1952 as the Crippled Children's Registry, the name was changed to the Health Status Registry in 1992 with a legal mandate under the Health Act. The HSR is managed by the British Columbia Vital Statistics Agency. Ascertainment of cases is done through multiple sources and registration is not age limited; however, registration of persons with selected disabilities and specific handicapping conditions is limited to those under 20 years of age. Within the HSR, procedures for registering medically terminated pregnancies due to congenital anomalies began in late 1998, with ongoing efforts to improve provincial ascertainment of this information. A regular congenital anomalies report based on the HSR is published annually, providing statistics on more than a dozen specific categories of congenital anomalies by health region. About 9,000 new cases with more than 12,000 diagnoses are reported annually. At the end of 2001, HSR had a total caseload of approximately 215,000. British Columbia is a full member in ICBDMS.

Reproductive Care Program of Nova Scotia

The Reproductive Care Program of Nova Scotia manages the Nova Scotia Atlee Perinatal Database (NSAPD) which contains population-based data from 1988 onwards. Variables include maternal and infant demographics, and information about procedures, interventions, diagnoses and outcomes for women and newborns. The NSAPD is used for ongoing clinical audit, peer review, surveillance, and epidemiologic and clinical research. The Reproductive Care Program reports on a number of variables related to perinatal care and perinatal outcome, including the birth prevalence of congenital anomalies in live births and stillbirths within the province.

In addition to the NSAPD, a fetal anomalies database established in 1992 is managed by the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, IWK Grace Health Centre. This database captures all pregnancies with a prenatally diagnosed fetal anomaly referred to the centre from Nova Scotia, Prince Edward Island or New Brunswick.

Other provincial programs

In addition to these established provincial systems, plans are also under way for a pilot study of congenital anomaly data collection in Ontario. At one time, Manitoba also had a congenital anomaly surveillance program but, due to difficulties with funding, the program was unable to maintain its infrastructure. However, interest remains strong in re-establishing Manitoba's provincial surveillance system.

Surveillance of exposures related to congenital anomalies

Many regional maternal and prenatal genetic centres across Canada offer information and guidance to pregnant women and their health care providers regarding the potential teratogenic risks associated with a specific exposure in question. The Motherisk program, a multidisciplinary centre affiliated with the University of Toronto, is renowned for its work in the field of teratology. The program's mandate is to provide authoritative evidence-based information on drug, chemical, infection, disease and radiation exposure(s) during pregnancy. A similar program, Info-médicaments en allaitement et grossesse (IMAGe), which is designed to provide health professionals with teratogen risk information, is operated by the Hôpital Ste-Justine in Montréal.

Greater integration of teratology and other exposure databases with congenital anomalies surveillance databases is required. To that end, the Centre for Surveillance Coordination (CSC) in Health Canada has recently become a partner with these two teratogen information services in a pilot project called MotherNet. The proposed system would include a minimum dataset of risk variables, including maternal health and exposures, and pregnancy outcome variables.

The National Children's Study

The National Institute of Child Health and Human Development, along with a consortium of federal agencies in the United States, has been authorized to conduct a 21-year longitudinal study to "investigate basic mechanisms of developmental disorders and environmental factors, both risk and protective, that influence health and developmental processes."19 Background information is available through the National Institute of Child Health and Human Development web page. A database has been prepared for the analysis of determinants of congenital anomalies. As the study is intended to include 100,000 children, following them during prenatal development, through birth, childhood and on into adulthood, it may provide further insight into the etiologies of the more common congenital anomalies.

New initiatives in the Canadian surveillance of congenital anomalies

In May 2000, Health Canada held a national workshop on the surveillance of congenital anomalies with key stakeholders from the provinces and territories, as well as a number of international congenital anomalies surveillance experts. This workshop presented an update on current Canadian congenital anomaly surveillance activities and provided a forum for discussion of provincial and territorial initiatives and issues relating to congenital anomaly surveillance. From the discussions at the workshop, a number of tasks appropriate to the federal level were identified. One such task was to produce a congenital anomalies surveillance report that would highlight this important issue in the Canadian setting. An additional important federal role identified at the workshop was to support a formal network of provinces, territories and other stakeholders to enhance congenital anomaly surveillance at all levels in Canada. Health Canada will formally launch the Canadian Congenital Anomalies Surveillance Network (CCASN) in the fall of 2002. The goals of the CCASN will include:

• increasing the quantity and quality of congenital anomalies surveillance activities in Canada

• developing minimum data sets and common definitions in order to attain quality and consistency in surveillance activities in Canada

• being a resource for professional support — e.g., epidemiology, medical genetics and others — for new and developing surveillance activities

• facilitating collaborative congenital anomalies surveillance and research efforts among provinces and territories

• facilitating the communication of information related to congenital anomalies for both health professionals and the Canadian public

• fostering educational opportunities in congenital anomalies surveillance and research

More information about the CCASN is available at http://www.hc-sc.gc.ca/pphb-dgspsp/rhs-ssg/index.html

Outline of the Report

Congenital Anomalies in Canada provides a concise overview of five important categories of congenital anomalies in Canada. Background information on each category is followed by a review of the known risk factors, national-level birth prevalence data, and provincial/territorial and international comparisons. The impact of prenatal diagnosis on the surveillance of the specific anomalies and prevention opportunities are also discussed. The final chapter of the report is devoted to the important topic of prenatal testing in Canada. This report will provide readers with an appreciation of the burden of specific congenital anomalies, as well as the importance of accurate surveillance in addressing this issue in Canada.

References

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3. March of Dimes Resource Center. Birth Defects. 1998. (Available www.modimes.org).

4. Stevenson RE. The Genetic Basis of Human Anomalies. In: Stevenson RE, Hall JG, Goodman RM (Eds.), Human Malformations and Related Anomalies. Vol. 1. New York: Oxford University Press, 1993: 115.

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10. Reprotox: An Information System on Environmental Hazards to Human Reproduction and Development. Alcohol, RTC 1127. 2001. (Available: http://reprotox.org/).

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12. Ritz B, Yu F, Fruin S, Chapa G, Shaw GM, Harris JA. Ambient air pollution and risk of birth defects in Southern California. Am J Epidemiol 2002; 155: 17-25.

13. Vrijheid M et al. Chromosomal congenital anomalies and residence near hazardous waste landfill sites. Lancet 2002; 359: 320-2.

14. Shaw GM, Wasserman CR, O'Malley CD, Nelson V, Jackson RJ. Maternal pesticide exposure from multiple sources and selected congenital anomalies. Epidemiology 1999; 10: 60-6.

15. Dodds L, King WD. Relation between trihalomethane compounds and birth defects. Occup Environ Med 2001; 7: 443-6.

16. Graves CG, Matanoski GM, Tardiff RG. Weight of evidence for an association between adverse reproductive effects and exposure to disinfection by-products: a critical review. Regul Toxicol Pharmacol 2001; 2: 103-24.

17. Vinceti M et al. Risk of birth defects in a population exposed to environmental lead pollution. Sci Total Environ 2001; 278: 23-30.

18. Wolfberg AJ, Nagey DA. Thyroid disease during pregnancy and subsequent congenital anomalies, Abstract #274. Society for Maternal-Fetal Medicine Annual Meeting, New Orleans, 2002.

19. National Institute of Child Health and Human Development. The National Children's Study. 2002. (Available: http://nationalchildrens study.gov/about/overview.cfm).

Congenital Anomalies in Canada: A Perinatal Health Report, 2002
87 Pages - (670 KB) in PDF Format