Evaluation and evolution during time of prenatal diagnosis of congenital heart diseases by routine fetal ultrasonographic examination

The objectives of this study were to evaluate routine prenatal diagnosis of congenital heart diseases (CHD) by fetal ultrasound examination in a well-defined population during the period 1994-1999 and to compare these results with the results from 1979 to 1993. This study included 80,076 consecutive pregnancies of known outcome from 1994 to 1999. CHD were classified as isolated or associated when at least one other major extra-cardiac malformation was present. Only 137 out of 688 malformed fetuses with CHD without chromosomal anomalies were detected (19.9%). The sensitivity of detection varied from 61.9% for malformations such as isolated hypoplastic left heart and single ventricle, to around 7-19% for atrial and ventricular septal defects. Prenatal detection rate of CHD was 11.4% for isolated cases, and 40.2% for multiple malformed with CHD. The gestational age at discovery varied from 16 to 36 weeks. There is no upper limit for termination of pregnancies in our country; 12.3% of all pregnancies were terminated after prenatal diagnosis. However, 62% of the pregnancies with a CHD detected prenatally were terminated. The detection rate of CHD increased during time from 9.2% during the period 1979-1988 to 13.7% during the period 1990-1993 and to 19.1% during the period 1994-1999. Our study shows large variation in the prenatal detection rate of CHD. Prenatal diagnosis of CHD is significantly higher when associated malformations are present. Cardiac defects affecting the size of the ventricles have the highest detection rate. Gestational age at discovery was 20-24 weeks for the majority of associated cardiac defects. The prenatal detection rate of CHD increased during time from 1979 to 1999.     

Evaluation of prenatal diagnosis of cleft lip/palate by foetal ultrasonographic examination

Ultrasound scans in the midtrimester of pregnancy are now a routine part of antenatal care in many countries. This type of screening procedure can detect serious foetal anomalies. Thanks to our registry of congenital anomalies a study was undertaken. The objective of the study was to evaluate prenatal detection of cleft lip (palate)(CL/P) by routine ultrasonographic examination of the foetus in 265679 consecutive pregnancies from 1979 to 1998. The percentage of prenatal detection of CL/P was low. For isolated malformation (foetuses with only CL/P) the detection rate was low: 17.8%; however, this detection rate increased from 5.3% during the period 1979-1988 to 26.5% during the period 1989-1998, for foetuses with associated malformations (foetuses with CL/P and one or more additional major malformations) these detection rates were 34.6, 13. 3 and 50.0%, respectively. In foetuses with associated malformations with CL/P this detection rate was higher for chromosomal abnormalities with CL/P and for non-syndromic, non-chromosomal multiply malformed children with CL/P than for non-chromosomal recognized syndromes with CL/P.     

Prenatal diagnosis, pregnancy terminations and prevalence of Down syndrome in Atlanta

BACKGROUND: The impact of prenatal diagnosis on the live birth prevalence of Down syndrome (trisomy 21) has been described. This study examines the prevalence of Down syndrome before (1990-1993) and after inclusion of prenatally diagnosed cases (1994-1999) in a population-based registry of birth defects in metropolitan Atlanta. METHODS: We identified infants and spontaneous fetal deaths with Down syndrome (n = 387), and pregnancies electively terminated after a prenatal diagnosis of Down syndrome (n = 139) from 1990 to 1999 among residents of metropolitan Atlanta from a population-based registry of birth defects, the Metropolitan Atlanta Congenital Defects Program (MACDP). Only diagnoses of full trisomy 21 were included. Denominator information on live births was derived from State of Georgia birth certificate data. We compared the prevalence of Down syndrome by calendar period (1990-1993, 1994-1999), maternal age (<35 years, 35+ years), and race/ethnicity (White, Black, other), using chi-square and Fisher's exact tests. RESULTS: During the period when case ascertainment was based only on hospitals (1990-1993), the prevalence of Down syndrome was 8.4 per 10,000 live births when pregnancy terminations were excluded and 8.8 per 10,000 when terminations were included. When case ascertainment also included perinatal offices (1994-1999), the prevalence of Down syndrome was 10.1 per 10,000 when terminations were excluded and 15.3 when terminations were included. During 1990-1993, the prevalence of Down syndrome was 24.7 per 10,000 among offspring to women 35+ years of age compared to 6.8 per 10,000 among offspring to women <35 years of age (rate ratio [RR] = 3.65, 95% confidence interval [CI] = 2.53-5.28). During 1994-1999, the prevalence of Down syndrome was 55.3 per 10,000 among offspring to women 35+ years compared to 8.5 per 10,000 among offspring to women <35 years (RR = 6.55, 95% CI = 5.36-7.99). There was no statistically significant variation in the prevalence of Down syndrome by race/ethnicity within maternal age and period of birth strata. During 1994-1999, the proportion of cases that were electively terminated was greater for women 35+ years compared to women <35 years (RR = 5.10, 95% CI = 3.14-8.28), and lower for Blacks compared to Whites among women 35+ years of age (RR = 0.33, 95% CI = 0.16-0.66). CONCLUSIONS: In recent years, perinatal offices have become an important source of cases of Down syndrome for MACDP, contributing at least 34% of cases among pregnancies in women 35+ years of age. Variation in the prevalence of Down syndrome by race/ethnicity, before or after inclusion of cases ascertained from perinatal offices, was not statistically significant. Among Down syndrome pregnancies in mothers 35+ years we found a lower proportion of elective termination among Black women compared to White women. We suggest that future reports on the prevalence of Down syndrome by race/ethnicity take into account possible variations in the frequency of prenatal diagnosis or elective termination by race/ethnicity.     

Associated malformations in cases with neural tube defects

Infants with neural tube defects (NTDs) may have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. The prevalences at birth of associated malformations in infants with NTDs were collected between 1979 and 2003 on all infants born in the area covered by the registry of congenital anomalies of Northeastern France in 334,262 consecutive births. Of the 360 infants with NTDs born during this period, 20.5 % had associated malformations. Associated malformations were more frequent in infants who had encephalocele (37.5 %) than in infants with anencephaly (11.8 %) or infants with spina bifida (23.7 %). Malformations in the face (oral clefts), in the musculoskeletal system, in the renal system, and in the cardiovascular system were the most common other anomalies. In conclusion the overall prevalence of malformations, which was one in five infants, emphasizes the need for a thorough investigation of infants with NTDs. A routine screening for other malformations especially facial clefts, musculoskeletal, renal and cardiac anomalies may need to be considered in infants with NTDs, and genetic counseling seems warranted in most of these complicated cases.     

Clinical anophthalmia: an epidemiological study in northeast Italy based on 368,256 consecutive births.

We describe an epidemiological and clinical study of Clinical Anophthalmia in a population of consecutive live and stillborns enrolled in a hospital based registry of congenital malformations in Northeast Italy during the period from 1981 to 1989; 22 cases were detected among 368,256 births yielding a birth prevalence of 0.60 per 10,000 (95% CI 0.34-0.84); 20 cases were associated with at least one other major malformation. Malformation syndrome, association, or sequence was diagnosed in 13, while a non-recognizable multiple defect pattern was observed in 7/20 (35%). A chromosomal anomaly was present in eight syndromic cases. No significant trend over time, nor space or time clusters, were detected. As most CAn cases are associated with other anomalies recognizable by ultrasound, a decreasing trend in its prevalence at birth is expected in the future.     

Prevalence of congenital anomalies at birth among offspring of women at risk for a genetic disorder and with a normal second-trimester ultrasound.

The goal of this study was to determine the prevalence and the nature of congenital anomalies found at birth in offspring of women who had a normal second-trimester ultrasound and/or amniocentesis. Two groups of women were studied in our prenatal diagnosis clinic between 1991-1997. Group 1 consisted of pregnant women who had an amniocentesis for advanced maternal age (AMA), or for familial chromosomal or monogenic disorders. Group 2 consisted of pregnant women attending the prenatal diagnosis clinic and who had no indication for amniocentesis. Those with an abnormal ultrasound and/or amniocentesis were excluded. At the time of delivery, a questionnaire was sent pertaining to perinatal complications and the anomalies detected during the neonatal period. From a total of 15, 370 questionnaires sent from 1991-1997, 10,823 (group 1, n = 8,877; group 2, n = 1,946) were returned (overall response rate, 70.4%). Mean maternal age was 36 years in group 1 and 29 years in group 2. The prevalence of perinatal complications was similar in the two groups. In each group, the prevalence of all unforeseen anomalies was 2.9%. In group 1, the distribution of those anomalies was: major anomalies, 67.7%; minor anomalies, 23.9%; and multiple congenital anomalies (MCA), 8.3%. In group 2, the distribution was: major anomalies, 70.7%; minor anomalies, 24.1%; and MCA, 5.2%. In patients at risk for a genetic disease and consulting in a prenatal diagnosis clinic, the prevalence of all anomalies diagnosed at birth was 2.9%, even if the second-trimester ultrasound and amniocentesis results were normal. Therefore, it is important to inform those couples of this remaining risk.     

Prevalence of neural tube defects in South Australia, 1966-91: effectiveness and impact of prenatal diagnosis.

OBJECTIVE--To determine trends in total prevalence of neural tube defects in South Australia during 1966-91, the impact of prenatal diagnosis on birth prevalence, and the effectiveness of prenatal screening for neural tube defects in 1986-91. DESIGN--All births and terminations of pregnancy affected by neural tube defects and information on prenatal screening were ascertained from multiple sources including the South Australian perinatal and abortion statistics collections, birth defects register, and state maternal serum alpha fetoprotein screening programme. SETTING--Southern Australia. SUBJECTS--All 1058 births and terminations of pregnancy affected by neural tube defects in 1966-91. MAIN OUTCOME MEASURES--Total prevalence and birth prevalence of individual and all neural tube defects. The proportion of screened cases detected prenatally. RESULTS--Total prevalence of neural tube defects during 1966-91 was 2.01/1000 births with no upward or downward trend. However, birth prevalence fell significantly (by 5.1% a year), with an 84% reduction from 2.29/1000 births in 1966 to 0.35/1000 in 1991 (relative risk = 0.16, 95% confidence interval 0.07 to 0.34). The fall was 96% for anencephaly and 82% for spina bifida. 85% of defects, both open and closed, were detected before 28 weeks'' gestation in women screened by serum alpha fetoprotein or mid-trimester ultrasonography, or both, in 1986-91 (99.0% for anencephaly and 75.7% for spina bifida). CONCLUSIONS--While the total prevalence of neural tube defects in South Australia remained stable, prenatal diagnosis and termination of pregnancy resulted in an 84% fall in birth prevalence during 1966-91. Screening detected over four fifths of cases in 1986-91.     

Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study.

OBJECTIVE: To monitor pregnancies in women with pre-existent insulin dependent diabetes for pregnancy loss, congenital malformations, and fetal growth in a geographically defined area of north west England. DESIGN: Population cohort study. SETTING: 10 maternity units in Cheshire, Lancashire, and Merseyside which had no regional guidelines for the management of pregnancy in diabetic women. SUBJECTS: 462 pregnancies in 355 women with insulin dependent diabetes from the 10 centres over five years (1990-4 inclusive). MAIN OUTCOME MEASURES: Numbers and rates of miscarriages, stillbirths, and neonatal and postneonatal deaths; prevalence of congenital malformations; birth weight in relation to gestational age. RESULTS: Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78 (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were terminated. Of the terminations, nine were for congenital malformation. The stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1) compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000 live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in the general population. When corrected for gestational age, mean birth weight in the sample was 1.3 standard deviations greater than that of infants of non-diabetic mothers. Infants with congenital malformations weighed less than those without. CONCLUSION: In an unselected population the infants of women with pre-existent insulin dependent diabetes mellitus have a 10-fold greater risk of a congenital malformation and a fivefold greater risk of being stillborn than infants in the general population. Further improvements in the management of pregnancy in diabetic women are needed if target of the St Vincent declaration of 1989 is to be met.     

Results of first year (1989) of a national register of Down's syndrome in England and Wales.

OBJECTIVE--To examine the feasibility of a national register of Down''s syndrome and its effectiveness in evaluating prenatal screening for the syndrome. DESIGN--Information for the register was obtained from all eligible cytogenetic laboratories on relevant cytogenetic diagnoses, including date and place of birth or termination, maternal age, indication for karyotyping, and type of diagnostic test used. SETTING--Cytogenetic laboratories in England and Wales. SUBJECTS--All fetuses with trisomy 21 diagnosed prenatally and live births with Down''s syndrome diagnosed at birth. MAIN OUTCOME MEASURES--Number of prenatal and postnatal diagnoses of Down''s syndrome. National and maternal age specific prevalence of Down''s syndrome. RESULTS--For 1989 there were 1060 registrations--323 prenatal diagnoses and 737 postnatal diagnoses--after exclusion of postnatally diagnosed miscarriages and stillbirths. The estimated national rate of affected births for mothers resident in England and Wales was 1.4/1000 live births, assuming no terminations of affected pregnancies and after correction for natural losses which would have occurred in the absence of termination. The corrected maternal age specific rates were close to those found in previous population based studies. The proportion of affected pregnancies diagnosed prenatally in mothers aged 35 to 39 was 44%, and for those aged 40 or more it was 71%. Abnormal findings on ultrasonography played an unexpectedly important part in initiating cytogenetic investigation (13% of the prenatal diagnoses). CONCLUSIONS--The findings establish the feasibility of a national Down''s syndrome register and its use in evaluating prenatal screening services. Together with information held by the Office of Population Censuses and Surveys on congenital malformations, data from the register will permit studies of environmental variables affecting the prevalence of the syndrome.     

Congenital malformations at birth in Central India: A rural medical college hospital based data

OBJECTIVE:

To study the incidence of congenital anomalies and the associated risk factors in Department of Pediatrics at Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, a rural medical college hospital in central Maharashtra.

MATERIALS AND METHODS:

All the intramural deliveries between 1 January 2005 and 31 July 2007 comprised 9386 births and their 9324 mothers (62 mothers gave birth to twin babies). The newborns were examined and assessed systematically for the presence of congenital anomalies, system wise distribution of anomalies and risk factors attributable.

RESULTS:

Out of the total 9386 deliveries, 9194 were live births and 192 were stillbirths. The total number of babies with congenital malformations was 179 (1.91%). Out of the 9262 singleton births, 177 (1.05%) were malformed, whereas 2 of the 62 pairs of twins had birth defects. Nine of the 179 malformed babies (5.02%) were still born. Prematurity, increased maternal age, increasing birth order and low birth weight were found to have a higher risk of congenital anomalies. Cardiovascular malformations were most common in live births, followed by musculoskeletal and genitourinary anomalies.

CONCLUSION:

Congenital anomalies are a major cause of stillbirths and infant mortality. Evaluation of cardiovascular system to rule out congenital heart disease in high-risk mothers’ babies is the important factor to be considered.     

Paper 1: The EUROCAT network--organization and processes

The European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe, funded by the European Union, which has been in operation for more than 30 years. It currently surveys more than 1.7 million births per year, including 31% of births in the European Union, and includes almost all population-based European congenital anomaly registries as its members. EUROCAT member registries collect data, ascertained from multiple sources, on all major structural congenital and chromosomal anomalies. EUROCAT surveillance relates to three areas: prevalence, primary prevention, and prenatal screening. This article describes the history of EUROCAT and gives an overview of the current methodology and work of EUROCAT covering the database content and management, coding and classification of anomalies, core surveillance, prevalence tables, statistical monitoring. The monitoring of new developments in prenatal diagnosis, medication during pregnancy, use of folic acid, and investigation of clusters and exposures are overseen by working groups responsible for organizing research and producing regular reports. The EUROCAT Web site includes current data on prevalence rates and prenatal detection rates-an example of information useful to clinicians, public health service managers, and patients.     

Trisomies 13 and 18: prenatal diagnosis and epidemiologic studies in Hawaii, 1986-1997

Using a birth defects registry, this study examined the influence of prenatal diagnosis and elective termination of pregnancy on trisomy 13 and trisomy 18 prevalence in Hawaii between 1986 and 1997. The investigation also evaluated the impact of various demographic factors on risk for the aneuploidies. Forty-seven cases of trisomy 13 and 116 cases of trisomy 18 were identified. The total prevalence of trisomy 13 was 1.91 per 10,000 births and of trisomy 18 was 4.71 per 10,000 births. Elective terminations accounted for 38.3% of trisomy 13 cases and 48.3% of trisomy 13 cases. The 1-year mortality rate for trisomy 13 was 89.5% and for trisomy 18 was 74.3%. Rates for both aneuploidies increased during the time period. The racial/ethnic group with the highest prevalence of both anomalies was Far East Asian. The aneuploidies were more common in metropolitan Honolulu than the rest of Hawaii. Demographic factors demonstrated differences in risk for trisomies 13 and 18, although most of these differences appeared to be due, at least in part, to differences in maternal age distribution. For the secular trend, increased prenatal diagnosis of the anomalies also contributed to the observed increase.     

The role of genomics in prevention or reducing the impact of congenital malformations

Congenital malformations (CMs) are permanent changes produced by abnormality of development in a body structure during prenatal life. Population based studies place the incidence of major malformations at about 2-3% of all live births. The etiology is mostly due multifactorial inheritance or unknown (50-80%). The continuum and gradual shift from genetics to genomics will offer new possibilities for diagnosis, treatment, prediction and prevention of congenital malformations. Genomics has many tools including pathogenomics, pharmacogenomics, nutrigenomics and bioinformatics. Pathogenomics will help to discover new genes or susceptibility genes and genetic variants with a role in the pathogenesis of CMs. Pharmacogenomics will identify genetic variants affecting the response to drugs and it should be applied to study drug induced birth defects. Nutrigenomics will determine the impact of diet on genome stability and how genotype determines nutritional requirements. Bioinformatics then will collect, store obtained data, which will facilitate analysis of systems biology questions involving relationships between genes, their variants and biological functions. This knowledge should be translated into more sensitive and specific genetic tests.     

High rates of neural tube defects in Ukraine

BACKGROUND: Oral consumption of synthetic folic acid can prevent neural tube defects (NTDs), which are some of the most severe congenital anomalies. The prevalence of NTDs in Ukraine and other countries of the former U.S.S.R. has not been well studied. We determined the prevalence of NTD-affected pregnancies in Northwestern Ukraine as background for policy decisions related to flour fortification in this country. METHODS: The Ukrainian-American Birth Defects Program was established in 1999 and conducts population- based surveillance of birth defects in several oblasts (states) of Ukraine. We determined the prevalence of NTDs in the Volyn and Rivne oblasts of Northwestern Ukraine for three years, 2000-2002. RESULTS: There were 75,928 births in the two oblasts in 2000-2002. There were 159 cases of NTDs among live births, stillbirths, and induced abortions. The prevalence of NTDs in the two oblasts in Northwestern Ukraine is 2.1 per 1000 births. CONCLUSIONS: The prevalence of NTD-affected pregnancies we found in Northwestern Ukraine is almost four times what it should be. This prevalence suggests that population folate deficiency is widespread in Ukraine. Universal folic acid fortification of flour milled in Ukraine is urgently needed to end this epidemic of birth defects. Such fortification would be expected to prevent folate deficiency anemia, heart attacks, and strokes.     

Births in Great Britain resulting from assisted conception, 1978-87. MRC Working Party on Children Conceived by In Vitro Fertilisation.

OBJECTIVE--To describe the characteristics at birth of children conceived by in vitro fertilisation (IVF) or by gamete intrafallopian transfer (GIFT) and to assess whether they differ from those of children conceived naturally. DESIGN--Survey of children resulting from IVF or GIFT and comparison of their characteristics at birth with national statistics. SETTING--England, Scotland, and Wales from 1978 to 1987. SUBJECTS--1267 Pregnancies conceived by IVF or GIFT, which resulted in 1581 liveborn or stillborn children. MAIN OUTCOME MEASURES--Sex ratio, multiplicity, gestational age at birth, birth weight, stillbirth rate, perinatal and infant mortality, and prevalence of congenital malformations. RESULTS--The ratio of male to female births was 1.07:1; 23% (249/1092) of the deliveries were multiple births compared with 1% for natural conceptions; 24% (278) of 1015 deliveries were preterm compared with 6% in England and Wales; 32% (406) of 1269 babies weighed less than 2500 g compared with 7% in England and Wales. The high percentage of preterm deliveries and of low birthweight babies was largely, but not entirely, due to the high frequency of multiple births. The rate of stillbirth, perinatal mortality, and infant mortality were twice the national average, these excesses being due to the high frequency of multiple births. One or more major congenital malformations were detected during the first week of life in 35 (2.2%) of 1581 babies. This figure is comparable with population based estimates of the prevalence of congenital malformations. The types of malformations reported varied, and the number of each specific type was small. The health of the children was not evaluated beyond the perinatal period. CONCLUSIONS--Multiple pregnancies often result from assisted conception and are the main determinant of the outcome of the pregnancies and of the health of the children at the time of birth. Congenital malformations are comparatively rare, so larger numbers of children need to be studied before firm conclusions can be drawn. The pooling of data from different countries is recommended.     

Comparative ultrasound and magnetic resonance diagnosis of fetal CNS malformations

The study was undertaken to optimize the diagnosis of fetal CNS and facial malformations, by using a complex of ultrasound (US) and magnetic resonance imaging (MRI) studies. A hundred and forty-four fetuses with suspected CNS and facial malformations were examined. The US study conducted by a specially developed protocol was supplemented by MRI (48 fetuses) also made by a specially developed protocol. Various fetal CNS malformations, such as neural tube defects, congenital endbrain malformations, cystic lesions, tumors, ventricular complex anomalies, defects of the face and eyes, multiple defects, including CNS and facial anomalies, were detected. With MRI, the diagnosis was changed in 33% of cases. The application of a complex of US and MRI studies enhances the efficiency of diagnosis of congenital CNS and facial malformations in the fetus. MRI in the diagnosis of fetal CNS and facial malformations has a number of advantages and should be used if there is some difficulty in establishing a diagnosis when an US study is performed.     

Congenital malformations in offspring of Vietnamese women in California, 1985-97

BACKGROUND: Little is known about reproductive outcome risks for Vietnamese women delivering infants and fetuses in the U.S. METHODS: Using data from a large population-based registry, we explored risks of selected congenital malformation phenotypes in offspring of Vietnamese women in California. Data were derived from the California Birth Defects Monitoring Program, a population-based active surveillance system for collecting information on infants and fetuses with congenital malformations using multiple source ascertainment. Approximately 3.4 million births (liveborn and stillborn) occurred during the ascertainment period, 1985-97. Information on maternal race/ethnic background was obtained from California birth certificate and fetal death files. Vietnamese women delivered 45,453 births and 1,257,853 births were delivered to non-Hispanic white women. RESULTS: The overall prevalence of structural congenital malformations was 1.92 among Vietnamese and 2.63 among non-Hispanic whites per 100 births and fetal deaths. Grouping by 20 3-digit malformation codes of the International Classification of Diseases-Ninth Revision revealed relative risks of 0.8 or less for spina bifida, eye, upper alimentary, genital, urinary, musculoskeletal, "other" limb, and "other" musculoskeletal anomalies, and relative risks of 1.3 or more for anencephaly and chromosomal anomalies. Grouping by the more specific 4-digit malformation codes revealed 50, among 178, malformation groupings with associated relative risks of >or=1.3 or 相似文献   

Maternal diabetes and congenital anomalies in South Australia 1986-2000: a population-based cohort study

BACKGROUND: This study examined the risk of congenital anomalies in infants born in South Australia to women with maternal diabetes in a population-based cohort study of births over a 15-year period, 1986-2000. Differences in the reporting, recording, and diagnosis of pre-existing diabetes mellitus, gestational diabetes mellitus, and impaired glucose tolerance make comparisons between studies difficult. In order to compare published research, details of research methods and analytic approaches are required to understand the potential confounding, bias, and effect modification that may occur. METHODS: Data on congenital anomalies from the South Australian Birth Defects Register were linked to birth data from the Pregnancy Outcome Statistics Unit of the South Australian Department of Health. This enabled information on congenital anomalies to be linked to pregnancy details, including diabetes status. RESULTS: Between 1986 and 2000, the prevalence of congenital anomalies in the infants of mothers with pre-existing diabetes mellitus, gestational diabetes mellitus, or impaired glucose tolerance was significantly higher than in the total population; relative risk = 2.01 (1.66-2.43) and 1.19 (1.08-1.31), respectively. This increased prevalence was not modified by adjustments for maternal age, ethnicity, or other demographic factors, nor did the rate change over the 15 years of the study period. CONCLUSIONS: The prevalence of congenital anomalies was found to be significantly higher in the infants of mothers with maternal diabetes. Larger population-based studies are needed to determine which anomalies are involved and how their occurrence can be reduced.