Atlanta Birth Defects Case-Control Study Research Articles

Maternal lifestyle factors and risk for ventricular septal defects.

Several studies have shown that the prevalence of ventricular septal defects (VSDs) has increased significantly in the United States in the past 30 years. This increase has been primarily attributed to increased detection through echocardiography. However, little is known about the etiology of VSD. This study sought to evaluate the association between maternal lifestyle exposures and the risk for VSD in offspring. The Atlanta Birth Defects Case-Control Study was used to identify 122 isolated simple VSD cases and 3029 control infants born during the period 1968 through 1980 in the metropolitan Atlanta area. Exposure data on alcohol, cigarette, and illicit drug use were obtained through standardized interviews with mothers and fathers. Associations between lifestyle factors and VSD were calculated using maternal self-reports; associations were also calculated using paternal proxy-reports of the mother's exposures. Maternal self-report of heavy alcohol consumption and paternal proxy-report of the mothers' moderate alcohol consumption were associated with isolated simple VSD. A two-fold increase in risk of isolated simple VSD was identified for maternal self- and paternal proxy-reported cannabis use. Risk of isolated simple VSD increased with regular (three or more days per week) cannabis use for both maternal self- and paternal proxy-report, although the association was significant only for maternal self-report. This is the first study to identify an association between maternal marijuana use and VSD in offspring. Further studies are needed to elucidate this association.

Do Multivitamin Supplements Attenuate the Risk for Diabetes-Associated Birth Defects?

To evaluate whether the risk for birth defects associated with maternal diabetes is attenuated by use of multivitamin supplements during the periconceptional period. In the population-based Atlanta Birth Defects Case-Control Study, we identified case infants who had nonsyndromic birth defects that were reported to be associated with diabetes (n = 3278) and were born during 1968-1980 to residents of metropolitan Atlanta. Controls were infants without birth defects (n = 3029). Maternal diabetes was defined as reported diabetes with onset before the date of birth of the index infant, and periconceptional use of multivitamins was defined as reported regular use of multivitamin supplements from 3 months before pregnancy through the first 3 months of pregnancy. Offspring of mothers with diabetes had an increased risk for selected birth defects. However, the increased risk was limited to offspring of mothers who had diabetes and had not taken multivitamins during the periconceptional period (odds ratio: 3.93; 95% confidence interval: 1.79-8.63). Offspring of mothers who had diabetes and had taken multivitamins during the periconceptional period had no increased risk for birth defects (odds ratio: 0.15; 95% confidence interval: 0.00-1.99). Periconceptional use of multivitamin supplements may reduce the risk for birth defects among offspring of mothers with diabetes.

Occurrence of Congenital Heart Defects in Relation to Maternal Multivitamin Use

Reports suggest that when prospective mothers take supplemental multivitamins containing folic acid during the periconceptional period, the risk of a neural tube defect declines and some types of congenital cardiac defects may be less frequent. This population-based case-control study examined the relation, if any, between maternal multivitamin use and the risk of cardiac defects. Data are from the Atlanta Birth Defects Case-Control Study, in which information was obtained from parents of infants with and without birth defects who were born between 1968 and 1980. The participation rate was 71%, leading to 958 case infants having nonsyndromic cardiac defects and 3029 control infants lacking birth defects of any kind. Infants whose defects were of known genetic or teratogenic origin were excluded. The data source was a stratified random sample of birth certificates. Septal defects, obstructive conditions, and outflow tract abnormalities were most prevalent. Mothers of control infants were more likely to be white and to have delivered in the earlier years of the period under study. Mothers of case infants were likelier to have had a chronic disorder of some kind around the time of conception. Regular use of multivitamins during the periconceptional period was reported by 14.2% of case mothers, whereas another 38.9% reported no such use. Periconceptional use of multivitamins seemed to lower the risk of all heart defects combined by 24% (odds ratio = 0.76, 95% confidence interval = 0.60–0.97). The major differences were a 54% reduction in outflow tract defects and 39% fewer ventricular septal defects. No protection was apparent when mothers started taking multivitamins in the second or third trimester. Should this apparent relationship prove to be causal, approximately one in four major cardiac defects might be prevented by making sure that prospective mothers take multivitamins during the periconceptional period.

Family history, maternal smoking, and clubfoot: an indication of a gene-environment interaction.

Although epidemiologic studies of some birth defects have suggested a gene-smoking interaction, the possibility of this interaction in clubfoot has not been examined. The authors analyzed risk factors among 346 infants with isolated clubfoot and 3,029 infants without defects from the Atlanta Birth Defects Case-Control Study. All infants were born during 1968-1980, and mothers were interviewed in 1982-1983. The authors examined the family history-smoking interaction as an indication of a gene-environment interaction. They defined "smoking" as smoking any time during the first 3 months of pregnancy and "family history" as having a first-degree relative with clubfoot. Conditional logistic regression (matching variables: race, birth hospital, and birth period) was used to obtain effect estimates. The adjusted odds ratios were 1.34 (95% confidence interval (CI): 1.04, 1.72) for smoking only, 6.52 (95% CI: 2.95, 14.41) for family history only, and 20.30 (95% CI: 7.90, 52.17) for a joint exposure of smoking and family history. The effect estimate for the joint exposure was higher than would be expected under either an additive or a multiplicative model of interaction and showed a statistically significant departure from additivity. This study confirms the importance of familial factors and smoking in the etiology of clubfoot and identifies a potentially important interaction.

Prenatal tea consumption and risks of anencephaly and spina bifida

PURPOSE: To evaluate the relationship between prenatal tea consumption and risk of anencephaly and spina bifida.METHODS: Data from the population-based Atlanta Birth Defects Case-Control Study were examined. Cases were infants with anencephaly (n = 122) or spina bifida (r = 154) and no other associated anomalies, and identified between 1968 and 1980. Controls were infants without birth defects (n = 3029) identified from birth certificates of the same birth cohort and frequency matched to cases by race, period of birth, and hospital of birth.RESULTS: Maternal tea consumption during the periconceptional period (3 months before through the first trimester of pregnancy) was reported at 82, 83.6, and 92.9% among controls, anencephaly, and spina bifida cases, respectively. With subjects whose mothers consumed no tea as a reference, odds ratios (OR) for tea consumption during the periconceptional period (adjusted for gender, race, period of birth, maternal age, education, alcohol consumption, smoking, and periconceptional multivitamins) were: anencephaly 0.9 (95% confidence limits (CI) 0.5–1.5); spina bifida 2.3 (CI 1.2–4.4). Odds ratios for spina bifida and number of cups of tea consumed/day were: 1–2 cups 2.1 (CI 1.1–4.0); 3+ cups 2.8 (CI 1.4–5.6). Consumption of other caffeinated beverages was not associated with risk for anencephaly or spina bifida.CONCLUSIONS: Further studies are warranted to corroborate and elucidate the observed association between tea consumption and spina bifida.

Occurrence of congenital heart defects in relation to maternal mulitivitamin use.

The purpose of this study was to assess the relation between maternal multivitamin use and risk for cardiac defects in the offspring, using a population-based approach. The Atlanta Birth Defects Case-Control study is a population-based case-control study of infants born between 1968 and 1980 to mothers residing in metropolitan Atlanta, Georgia. The 958 case infants with nonsyndromic cardiac defects were actively ascertained from multiple sources. The 3,029 infants without birth defects (control infants) were selected from birth certificates by stratified random sampling. Periconceptional multivitamin use, defined as reported regular use of multivitamins from 3 months before pregnancy through the first 3 months of pregnancy, was contrasted with no use during the same time period. Periconceptional multivitamin use was associated with a reduced risk for nonsyndromic cardiac defects in the offspring (odds ratio (OR) = 0.76; 95% confidence interval (Cl): 0.60, 0.97). The risk reduction was strongest for outflow tract defects (OR = 0.46; 95% Cl 0.24, 0.86) and ventricular septal defects (OR = 0.61; 95% Cl: 0.38, 0.99). No risk reduction was evident when multivitamin use was begun after the first month of pregnancy. If these associations are causal, the results suggest that approximately one in four major cardiac defects could be prevented by periconceptional multivitamin use.

Nausea during pregnancy and congenital heart defects: a population-based case-control study.

The authors investigated the possible association between a mother's nausea during pregnancy and her child's risk for a congenital heart defect using data from the population-based Atlanta Birth Defects Case-Control Study conducted in 1982-1983. Case infants (n = 998) had nonsyndromic congenital heart defects and control infants (n = 3,029) had no congenital defects. Nausea during pregnancy (NP) was graded in eight levels of "severity" based on its onset, frequency, and duration. Level 1, the most severe NP, was associated with a lower risk for a congenital heart defect in the child (odds ratio (OR) = 0.81, 95% confidence interval (CI) 0.67-0.99) compared with no nausea. The lower risk tended to disappear with less severe levels of nausea, and the trend was statistically significant. Overall, early NP (levels 1 to 4 combined) with use of antinausea medication, particularly Bendectin (doxylamine, dicyclomine (dropped from the formulation in 1976), pyridoxine (vitamin B6)), was associated with a lower risk for congenital heart defects compared with: 1) absence of nausea (OR = 0.67, 95% CI 0.50-0.92), and 2) nausea without medication use (OR = 0.70, 95% CI 0.50-0.94). The results suggest that pregnancy hormones and factors or, alternatively, a component of Bendectin (most probably pyridoxine) may be important for normal heart development. These findings outline potential areas for future research on and prevention of congenital heart defects.

Multivitamin supplementation and multiple births

It is well established that maternal multivitamin supplementation reduces the risk of neural tube defects and evidence suggests that it may be associated with other reproductive outcomes. The present study was prompted by a report from a randomized trial in Hungary which showed a 40% increase in multiple births among periconceptional vitamin users. Retrospectively collected data on multivitamin supplementation were obtained on multiple and singleton births from three separate studies: Atlanta Birth Defects Case-Control Study (ABDCCS) malformed and nonmalformed infants born 1968-1980, California Birth Defects Monitoring Program (CBDMP) malformed and nonmalformed infants born 1987-1989, and Boston University Slone Epidemiology Unit Birth Defects Study (SEU-BDS) malformed infants born 1987-1994. Supplementation was divided into three mutually exclusive categories based on timing: "periconceptional" use--before through at least the third month after conception; "early" use--beginning in the first month and continuing through at least the third month after conception; and "later" use--beginning in the second or third month after conception. For periconceptional use, four of five datasets showed a 30 to 60% greater prevalence of supplementation among mothers of multiple births. In contrast, this pattern was not evident for "early" and "later" use. Overall, the study findings are tentative, due to a lack of consistency across all five datasets and they should not alter recent recommendations related to folate supplementation for the prevention of neural tube defects.

Multivitamin supplementation and multiple births

It is well established that maternal multivitamin supplementation reduces the risk of neural tube defects and evidence suggests that it may be associated with other reproductive outcomes. The present study was prompted by a report from a randomized trial in Hungary which showed a 40% increase in multiple births among periconceptional vitamin users. Retrospectively collected data on multivitamin supplementation were obtained on multiple and singleton births from three separate studies: Atlanta Birth Defects Case-Control Study (ABDCCS) malformed and nonmalformed infants born 1968-1980, California Birth Defects Monitoring Program (CBDMP) malformed and nonmalformed infants born 1987-1989, and Boston University Slone Epidemiology Unit Birth Defects Study (SEU-BDS) malformed infants born 1987-1994. Supplementation was divided into three mutually exclusive categories based on timing: “periconceptional” use—before through at least the third month after conception; “early” use—beginning in the first month and continuing through at least the third month after conception; and “later” use—beginning in the second or third month after conception. For periconceptional use, four of five datasets showed a 30 to 60% greater prevalence of supplementation among mothers of multiple births. In contrast, this pattern was not evident for “early” and “later” use. Overall, the study findings are tentative, due to a lack of consistency across all five datasets and they should not alter recent recommendations related to folate supplementation for the prevention of neural tube defects. Am. J. Med. Genet. 71:93–96, 1997. © 1997 Wiley-Liss, Inc.

Periconceptional Multivitamin Use and the Occurrence of Conotruncal Heart Defects

Botto, Lorenzo D.; Khoury, Muin J.; Mulinare, Joseph; Erickson, J. David Author Information

Does Light-to-Moderate Alcohol Consumption During Pregnancy Increase the Risk for Renal Anomalies Among Offspring?

To determine the association between light-to-moderate prenatal alcohol exposure and congenital renal anomalies. Data from the population-based Atlanta Birth Defects Case-Control Study were used to examine the association between selected renal anomalies and self-reported maternal alcohol consumption during the period from 1 month before through 3 months after conception. Case infants were ascertained by a population-based birth defects registry with active case ascertainment; the case group consisted of 158 infants, born during 1968 through 1980 to metropolitan Atlanta residents, in whom these renal anomalies had been diagnosed. Two control groups were used. One had 3029 infants without birth defects, and the other had 4633 infants with birth defects exclusive of the urinary tract who were born during the same period. Overall, there was a moderate association between renal anomalies and moderate prenatal alcohol exposure (odds ratio, 1.5; 95% confidence interval, 1.0 to 2.3). When the renal anomalies were subclassified, moderate prenatal alcohol exposure was significantly associated only with renal agenesis or hypoplasia (odds ratio, 2.5; 95% confidence interval, 1.2 to 5.1), and within this group only infants with bilateral defects and other major anomalies in addition to renal agenesis or hypoplasia had significantly elevated risks. There were no significant associations between reported light consumption and any category of the selected renal anomalies. No conclusions could be reached for reported heavy consumption because of sparse data. Adjustments for potential confounding factors did not alter these results. This study suggests that moderate alcohol consumption during pregnancy may increase a woman's risk of giving birth to a child with renal agenesis or hypoplasia.

Does periconceptional multivitamin use reduce the risk for limb deficiency in offspring?

There is accumulating evidence that periconceptional multivitamin use may prevent the occurrence of some birth defects other than neural tube defects. Using data from the population-based Atlanta Birth Defects Case-Control Study, we investigated the possible association between periconceptional multivitamin use and the occurrence of limb deficiency. We examined the periconceptional use of multivitamins among mothers of 117 babies with nonsyndromic limb deficiency who were liveborn or stillborn to residents of metropolitan Atlanta from 1968 to 1980 and among mothers of 3,029 control babies born without birth defects who were randomly selected through birth certificates. We found that children whose mothers were periconceptional multivitamin users had a lower risk of having a limb deficiency [odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.23-0.97]. This protective effect, however, was mostly seen for transverse limb deficiency (OR = 0.30; 95% CI = 0.07-1.32) and not for longitudinal deficiency (including preaxial and postaxial deficiencies; OR = 1.03; 95% CI = 0.17-4.30). Adjustment for potential confounding factors did not change these findings. We found a trend of decreasing risk for all transverse limb deficiencies with earlier vitamin use. These data indicate that mothers' periconceptional multivitamin use may reduce the risk for some types of limb deficiency among their offspring. In addition, because we did not find the protective effect for all types of limb deficiency, the data may also indicate causal heterogeneity of limb deficiencies.

Periconceptional Multivitamin Use and the Occurrence of Conotruncal Heart Defects: Results From a Population-based, Case-Control Study

The preventive efficacy of the periconceptional use of multivitamins is well established for neural tube defects, much less so for other birth defects. We conducted a population-based, case-control study to assess the effects of multivitamin use on the risk for conotruncal defects, a group of severe heart defects that includes transposition of the great arteries, tetralogy of Fallot, and truncus arteriosus. From the population-based Atlanta Birth Defects Case-Control Study, we identified 158 case infants with conotruncal defects and 3026 unaffected, randomly chosen control infants, born from 1968 through 1980 to mothers residing in metropolitan Atlanta. Periconceptional multivitamin use was defined as reported regular use from 3 months before conception through the third month of pregnancy. We present the results of the crude analysis, because the multivariate model yielded essentially identical results. Mothers who reported periconceptional multivitamin use had a 43% lower risk of having infants with conotruncal defects (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.33 to 1.00) than did mothers who reported no use. The estimated relative risk was lowest for isolated conotruncal defects (OR, 0.41; 95% CI, 0.20 to 0.84) compared with those associated with noncardiac defects (OR, 0.91; 95% CI, 0.33 to 2.52) or a recognized syndrome (OR, 1.82; 95% CI, 0.31 to 10.67). Among anatomic subgroups of defects, transposition of the great arteries showed the greatest reduction in risk (OR, 0.36; 95% CI, 0.15 to 0.89). Periconceptional multivitamin use is associated with a reduced risk for conotruncal defects. These findings could have major implications for the prevention of these birth defects.

Cocaine and single ventricle: a population study.

A recent case report by Shepard et al. (Teratology 43:113-117, 1991) suggested that single ventricle may result from maternal cocaine ingestion by inducing coronary occlusion in the developing fetal heart. We used data from the Atlanta Birth Defects Case-Control Study and the Metropolitan Atlanta Congenital Defects Program (MACDP) to investigate the role of maternal cocaine ingestion in the induction of single ventricles. We identified through the MACDP 58 case infants with a single ventricle, 27 who were study subjects in the Atlanta Birth Defects Case-Control Study, and 31 who were not. We conducted a case-control study with the 27 Atlanta Birth Defects Case Control Study infants, frequency-matched to control infants by race, hospital of birth, and calendar quarter of birth. None of the 27 case infants were exposed to cocaine during early pregnancy, but 7 (0.43%) of the control infants were exposed during early pregnancy. Using MACDP data, we conducted an analysis of trends for prevalence of single ventricle in the metropolitan area. No upward trend in single ventricle was detected for 1968 through 1990. Our data suggest that even if maternal cocaine ingestion during pregnancy is a cause of single ventricle, most cases appear to be unrelated to this exposure.

Risk Factors for Birth Defects: Data From the Atlanta Birth Defects Case-Control Study

The Atlanta Birth Defects Case-Control Study data comprises information obtained from interviews with parents of 4,900 babies born with major birth defects and with the parents of 3,000 babies born without defects. The source of cases is the Centers for Disease Control's Metropolitan Atlanta Congenital Defects program; the case-control study is population-based. Birth defects are classified into 92 groups and cross-tabulated by 105 exposure/risk factor variables; data from selected cross-tabulations are presented. The associations of each of the 105 exposure variables with all types of defects combined are presented, as are the associations of each of the 92 defect groups with the specific exposure variable, maternal diabetes. These data can be used to evaluate hypotheses arising from other sources, and for the purpose of generating hypotheses. The data describing all 92 x 105 cross-tabulations are available to other investigators on floppy disk; write to Chief, Birth Defects and Genetic Diseases Branch, Centers for Disease Control, Atlanta, Georgia 30333.

Risk factors for birth defects: Data from the Atlanta Birth Defects Case‐Control Study

The Atlanta Birth Defects Case-Control Study data comprises information obtained from interviews with parents of 4,900 babies born with major birth defects and with the parents of 3,000 babies born without defects. The source of cases is the Centers for Disease Control's Metropolitan Atlanta Congenital Defects program; the case-control study is population-based. Birth defects are classified into 92 groups and cross-tabulated by 105 exposure/risk factor variables; data from selected cross-tabulations are presented. The associations of each of the 105 exposure variables with all types of defects combined are presented, as are the associations of each of the 92 defect groups with the specific exposure variable, maternal diabetes. These data can be used to evaluate hypotheses arising from other sources, and for the purpose of "generating" hypotheses. The data describing all 92 x 105 cross-tabulations are available to other investigators on floppy disk; write to Chief, Birth Defects and Genetic Diseases Branch, Centers for Disease Control, Atlanta, Georgia 30333.

Maternal cocaine use during early pregnancy as a risk factor for congenital urogenital anomalies

To study the association of maternal cocaine use during early pregnancy with the occurrence of congenital urogenital anomalies, we analyzed data from the population-based Atlanta Birth Defects Case-Control Study. We identified 276 and 791 case-babies with urinary and genital anomalies, respectively, who were live born and stillborn to residents of metropolitan Atlanta from 1968 through 1980. There were 2835 and 2973 respective control-babies born without birth defects randomly selected through birth certificates. Maternal cocaine use during early pregnancy was defined as reported use at any time from 1 month before the pregnancy began through the first 3 months of pregnancy. We found a statistically significant association of reported cocaine use with an increased risk for urinary tract defects (crude odds ratio, 4.39; 95% confidence interval, 1.12 to 17.24) and no statistically significant association with genital organ defects (odds ratio, 2.26; confidence interval, 0.67 to 7.62). The findings from this study were consistent with a previously reported association of maternal cocaine use and urinary tract anomalies in animal and clinical studies.

Diabetes Mellitus During Pregnancy and the Risks for Specific Birth Defects: A Population-Based Case-Control Study

Although the excess risk for birth defects among children of mothers with diabetes mellitus is well documented, there are few data concerning the risk for specific malformations. In the Atlanta Birth Defects Case-Control Study, those risks for malformations were evaluated. The population-based study included 4929 live and stillborn babies with major malformations ascertained by the Metropolitan Atlanta Congenital Defects Program in the first year of life born to residents of Metropolitan Atlanta between 1968 and 1980. The study also included 3029 nonmalformed live babies who were frequency-matched to case babies by race, period of birth, and hospital of birth. The relative risk for major malformations among infants of mothers with insulin-dependent diabetes mellitus (n = 28) was 7.9 (95% confidence interval [CI]1.9, 33.5) compared with infants of nondiabetic mothers. The relative risks for major central nervous system and cardiovascular system defects were 15.5 (95% CI = 3.3, 73.8) and 18.0 (95% CI = 3.9, 82.5), respectively. The absolute risks for major, central nervous system, and cardiovascular system malformations among infants of diabetic mothers were 18.4, 5.3, and 8.5 per 100 live births, respectively. Infants of mothers with gestational diabetes mellitus who required insulin during the third trimester of pregnancy were 20.6 (95% CI = 2.5, 168.5) times more likely to have major cardiovascular system defects than infants of nondiabetic mothers. The absolute risk for infants of this group of diabetic mothers was 9.7%. No statistically significant differences were found among infants of mothers with gestational diabetes mellitus who did not require insulin during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring?

To investigate the relationship between maternal cigarette smoking and the risk of oral clefts in offspring, we examined data from the Atlanta Birth Defects Case-Control Study, which included 238 cases of cleft lip with or without cleft palate and 107 cases of cleft palate ascertained by the Metropolitan Atlanta Congenital Defects Program from 1968 through 1980. In all, 2809 infants who served as controls were frequency matched to cases by race, period of birth, and hospital of birth. Maternal periconceptional exposures to smoking were investigated through use of a structured questionnaire. Smoking exposure was defined as reported maternal smoking during the periconceptional period (from 3 months before conception to 3 months after pregnancy began). Offspring of smoking mothers were 1.6 and 2.0 times more likely than offspring of nonsmoking mothers to have isolated cleft lip with or without cleft palate and cleft palate, respectively. On the other hand, offspring of smoking mothers were not at increased risk of having cleft palate or cleft lip with or without cleft palate that are associated with other defects. Adjustment for potential confounding variables did not alter these results. A relatively modest effect of smoking may be explained by the presence of underlying etiologic heterogeneity in oral clefts and differential susceptibility to smoking. Because of the inconsistencies in the literature on the relationship between smoking and oral clefts, these results suggest the need to refine oral clefts into more homogeneous subgroups in epidemiologic studies of these defects.

Periconceptional Use of Multivitamins and the Occurrence of Neural Tube Defects

We studied the association between multivitamin use during the periconceptional period and the occurrence of neural tube defects using data from the Atlanta Birth Defects Case-Control Study. There were 347 babies with neural tube defects who were live born or stillborn to residents of metropolitan Atlanta from 1968 through 1980. The 2829 control-babies born without birth defects were randomly selected through birth certificates. Periconceptional multivitamin use was defined as reported use for each of the three months before conception through the first three months of pregnancy. Mothers who reported not using multivitamins any time during the six-month period were defined as nonusers. Fourteen percent of mothers reported periconceptional multivitamin use and 40% reported nonuse. Multivitamin users were different from nonusers in a number of demographic, health-related, and life-style characteristics. We found an overall apparent protective effect of periconceptional multivitamin use on the occurrence of neural tube defects, with a crude estimated relative risk of 0.40 (95% confidence interval, 0.25 to 0.63). At this time, it is not possible to determine whether this apparently lower risk is the direct result of multivitamin use or the result of other characteristics of women who use multivitamins.