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Abstract. The relationship between congenital malformations and intrauterine growth retardation was investigated using data from the population-based Metropolitan Atlanta Congenital Defects Program. Between 1970 and 1984, the system ascertained 13,074 infants with major structural malformations diagnosed in the first year of life and born to metropolitan Atlanta residents. These infants were classified as having intrauterine growth retardation if their birth weight was below the race-, sex-, and gestational age-specific tenth percentile limits for all Atlanta births. Overall, the frequency of intrauterine growth retardation among malformed infants was 22.3% (relative risk 2.6). Of 48 defect categories evaluated, 46 were associated with excess intrauterine growth retardation, most notably chromosomal anomalies (eg, 83.7% for infants with trisomy 18, relative risk 46) and anencephaly (73.3%, relative risk 25). Only a few isolated defects (such as isolated polydactyly, pyloric stenosis, and congenital hip dislocation) were not associated with excess intrauterine growth retardation. Among infants with multiple malformations, the frequency of intrauterine growth retardation increased markedly with increasing number of defects--from 20% for infants with two defects to 60% for infants with nine or more defects. The relationship between malformations and intrauterine growth retardation can be explained by one or more of three mechanisms: (1) intrauterine growth retardation can be a secondary disturbance to the presence of malformations; (2) intrauterine growth retardation can predispose the fetus to malformations; and (3) intrauterine growth retardation can coexist with malformations because of common etiologic factors. Because the risk of a major... [ABSTRACT FROM AUTHOR]

Objectives. Although up to 2% of women undergo surgery during pregnancy, teratogenic effects of general anesthesia have not been adequately studied. Recently, and association between first-trimester operations and central nervous system defects has been described. This issue was explored in a population-based case-control study. Methods. Case patients included live-born and stillborn infants with central nervous system defects born to residents of metropolitan Atlanta, Ga, between 1968 and 1980. Control patients included normal babies frequency matched to case patients by race, birth hospital, and period of birth. Conditional logistic regression analysis was used to adjust for potential confounding factors. Results. Of 694 mothers of infants with central nervous system defects, 12 reported first-trimester anesthesia exposure; 34 of 2984 control mothers reported such exposure (odds ratio [OR] = 1.7, 95% confidence interval [CI]=0.8, 3.3). A striking association was observed between reported anesthesia exposure and hydrocephalus with another major defect (OR = 9.6, 95% CI=3.8, 24.6). The strongest association was that of anesthesia exposure with hydrocephalus and eye defects (OR = 39.6, 95% CI = 7.5% CI = 7.5, 209.2). Conclusions. An increased risk of hydrocephalus with other defects was found among offspring of mothers with reported first-trimester anesthesia. Further studies are needed to explore the possible teratogenic effects of general anesthesia. [ABSTRACT FROM AUTHOR]

Examines the impact of airport noise on teratogenesis in Atlanta, Georgia. Comparison of the rates of birth defects; Analysis of neural tube malformation; Correlation between spina bifida and hydrocephalus.

Background: Multivitamin use has been associated with lower risks for some birth defects. We evaluated whether multivitamin use modified birth defect risks associated with febrile illness, a common and possibly teratogenic exposure., Methods: From the population-based Atlanta Birth Defects Case-Control Study (1968-1980) we selected seven defects (neural tube defects, cleft lip and palate, cardiac outflow tract defects, ventricular septal defects, atrial septal defects, omphalocele, and limb deficiencies) because of their inverse relation with multivitamin supplement use documented in previous analyses. We defined four exposure categories from combinations of multivitamin use (periconceptional use compared with no use) and febrile illness (early pregnancy compared with no illness). The reference category was no multivitamin use and no illness., Results: Febrile illness with no multivitamin use was associated with generally increased risk for the seven defects and the combined group (odds ratio = 2.1, 1.7, 1.5, 1.9, 2.9, 4.4, 3.3, and 2.3, respectively). With multivitamin use, however, the risk estimates associated with febrile illness were generally lower (odds ratio = 0.6, 1.1, 0.0, 1.5, 0.0, 0.8, 0.0, and 0.8, respectively). Some of the associated 95% confidence intervals included one., Conclusions: The pattern of findings suggests that multivitamin use might decrease the risk associated with febrile illness.

We assessed the relation between febrile illness during pregnancy and cardiac defects in the offspring in a population-based case-control study in metropolitan Atlanta. Case infants (905) with cardiac defects were actively ascertained from multiple sources. Control infants (3,029) were infants without birth defects who were selected from birth certificates by stratified random sampling. We compared those whose mothers reported febrile illness from 1 month before pregnancy through the third month of pregnancy with those whose mothers reported no illness during the same period. Febrile illness was positively associated with the occurrence of heart defects in the offspring (odds ratio [OR] = 1.8; 95% confidence interval = 1.4-2.4). When influenzalike illness was the reported febrile illness, the OR was 2.1 (95% confidence interval = 0.8-5.5). The association with febrile illness was strongest for tricuspid atresia (OR = 5.2), left obstructive defects (OR = 2.7), transposition of the great arteries (OR = 1.9), and ventricular septal defects (OR = 1.8). These ORs were generally lower among mothers who used multivitamins during the periconceptional period.

Background: Documenting the prevalence and trends of congenital heart defects provides useful data for pediatric practice, health-care planning, and causal research. Yet, most population-based studies use data from the 1970s and 1980s. We sought to extend into more recent years the study of temporal and racial variations of heart defects occurrence in a well-defined population., Methods: We used data from the Metropolitan Atlanta Congenital Defects Program, a population-based registry with active case ascertainment from multiple sources. Heart defects were identified among liveborn infants up to 1 year old, among stillborn infants, and among pregnancy terminations to mothers residing in metropolitan Atlanta., Results: From 1968 through 1997, the registry ascertained 5813 major congenital heart defects among 937 195 infants, for a prevalence of 6.2 per 1000. The prevalence increased to 9.0 per 1000 births in 1995 through 1997. The prevalence of ventricular septal defects, tetralogy of Fallot, atrioventricular septal defects, and pulmonary stenosis increased, whereas that of transposition of the great arteries decreased. For some defects, prevalence and trends varied by race., Conclusions: The prevalence of congenital heart defects is increasing. Whereas most findings likely result from improved case ascertainment and reporting, others might be because of changes in the distribution of risk factors in the population. The basis of the racial variations is incompletely understood.

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.

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.

In the 1960s, thalidomide caused limb deficiencies in thousands of infants worldwide. The limb deficiencies were frequently of the intercalary type. As a result, numerous countries started birth defect surveillance programs. In 1967, the Centers for Disease Control (CDC) started the Metropolitan Atlanta Congenital Defects Program (MACDP), a population-based surveillance system, to provide early warning against new teratogens. Recent studies have shown that thalidomide may be beneficial for a range of conditions, including cancer and AIDS, and it may once again become widely available. Here, we examine the ability of MACDP to detect an increase in the birth prevalence of limb deficiency as an early warning of fetal exposure to thalidomide. We calculated base rates for all limb deficiencies, for bilateral nonsyndromic intercalary or preaxial deficiencies, and for all nonsyndromic intercalary limb deficiencies among Atlanta infants born from 1968 through 1993. We used relative risk estimates from previous studies and a range of pregnancy exposure rates for thalidomide. We tested the statistical power of MACDP to detect subtle changes in the birth prevalence of these defects using Poisson and cumulative sum (CUSUM) techniques. The base rates for all limb deficiencies, for bilateral intercalary or preaxial deficiencies, and for all intercalary limb deficiencies, were 0.53, 0.035, and 0.022/1,000, and the estimated relative risks were 175, 4,570, and 8,180, respectively. We varied the assumed rate of exposure to thalidomide from 1/10,000 to 5/100. With a 1/1,000 exposure rate, both Poisson and CUSUM techniques will detect a rate change in intercalary limb deficiency in about 6 months of monitoring, and a rate change in bilateral intercalary or preaxial deficiencies in about 12 months of monitoring. When monitoring all limb deficiencies, a pregnancy exposure rate of 3.5% or less would go unnoticed by the Poisson method and would take more than 50 years for the CUSUM method to signal an alarm with a 1/1,000 exposure rate. However, for rates of exposure less than 1/1,000, a progressively longer period of time or larger sample are needed to detect a rate change by both methods. Our findings highlight the importance of enlarging the monitored population and correct case classification in birth defects surveillance.

Several epidemiologic studies indicate that some paternal occupations are associated with an increased risk of birth defects in offspring. We evaluated this relation using data from a population-based case-control study. Cases are infants with a major birth defect registered with the Metropolitan Atlanta Congenital Defects Program between 1968 and 1980. We selected controls from livebirths in the Atlanta area using frequency matching for race, year, and hospital of birth. Case and control parents were interviewed to solicit information on several factors, including occupation. We classified paternal occupation according to the job held during the time from 6 months before until 1 month after the estimated date of conception. We compared fathers in one occupational category with fathers in all other categories combined. We identified a number of associations including: firemen with cleft lip [odds ratio (OR) = 13.3; 95% confidence interval (CI) = 4.0-44.4]; painters with atrial septal defect (OR = 2.7; 95% CI = 1.0-7.4); and farmers with cleft lip and palate (OR = 3.3; 95% CI = 0.9-11.9). This study, however, did not corroborate several associations found in previous studies, such as painters and neural tube defects. We identified several additional occupations as potential risk factors for some defects, including printers, electronic equipment operators, and vehicle manufacturers.

Agreement between the mother's and father's report of the father's occupation was assessed in a case-control study of paternal occupation and birth defects. Cases were identified from births registered with the Metropolitan Atlanta Congenital Defects Program between 1968 and 1980; controls were selected from liveborn infants without defects. Both parents were sought for interview, and each parent was asked about the father's job history for 2 years prior to the infant's death. This concordance analysis is based on 3,739 case infants and 2,279 control infants for whom both parents were interviewed. The authors considered the father's report of his occupation as correct, and they assessed the ability of the mother to report the same occupation(s) during a 7-month period around conception. The exact agreement between mother's and father's report of the father's occupation was 59%. Agreement improved slightly with increasing family income and when fathers were college graduates. Female partners were not accurate proxy respondents in this study of paternal occupation and birth defects, which suggests that investigators should interview both parents in studies of paternal exposures and reproductive outcomes, i.e., mothers for pregnancy history and maternal confounders and fathers for occupational history and paternal confounders.

Inferences regarding causes of birth defects in humans are often based on results of case-control studies conducted after birth. To address bias in these studies caused by potential differential recall of past exposures between case and control mothers, many investigators have advocated the use of affected controls (babies with birth defects other than the one of interest). To evaluate whether the use of affected controls is warranted for a wide range of scenarios, we analyzed data from a population-based case-control study of birth defects in Atlanta, in which there were 4,918 babies with serious defects ascertained in the first year of life and 3,029 babies without defects. We compared the magnitude of the odds ratios for 10 specific defects--risk factor associations between normal and affected controls. These associations included demographic factors (e.g., advanced maternal age and Down syndrome), chronic maternal illnesses (e.g., diabetes and cardiac defects), chronic exposures (e.g., multivitamins and neural tube defects), and acute exposures (e.g., flu and neural tube defects). In all instances, the use of affected controls did not change etiologic inferences derived from using normal controls and there were only moderate changes in odds ratios. On the basis of theoretical considerations, we show that recall bias can lead to spurious inferences only under extreme conditions. We conclude that concerns about recall bias are overrated in birth defects studies and that the use of normal controls is acceptable unless evidence of substantial recall bias exists.

The ability of birth defects monitoring to detect new human teratogenic and mutagenic agents may be limited if only isolated defects are monitored. Surveillance for "new" multiple congenital anomalies (MCA) may improve the detection of environmental agents associated with new defect patterns. To evaluate the feasibility of such monitoring, we examined data from two programs: 1) the Metropolitan Atlanta Congenital Defects Program (MACDP), which ascertains infants with serious defects diagnosed in the first year of life, and, 2) the Italian Multicenter Register for Congenital Malformations (IPIMC), which ascertains newborn infants with birth defects from many hospitals in Italy. We focused on 24 relatively serious defects and defect groups. For a baseline period (MACDP: 1968-1988, 581,000 births; IPIMC: 1986-1989, 448,000 births), we identified all possible combinations of defects occurring in the same baby. For a test period (MACDP: 1989-1990, 77,000 births; IPIMC: 1990, 91,500 births), we identified babies with "new" MCA (i.e., combinations of defects not observed before in the system). During this period in MACDP, of the 85 babies with two or more defects, 9 babies had new MCAs. In IPIMC, of the 54 babies with two or more defects, 10 babies had new MCAs. A review of the records of infants with new MCAs in MACDP and IPIMC did not identify commonalities in maternal characteristics. This analysis illustrates the feasibility of monitoring for new MCAs in surveillance systems. This approach, complemented by an evaluation of exposures, may be a powerful additional tool in searching for human teratogens and mutagens.

Several birth defects surveillance systems have shown an upward trend in the birth prevalence of several congenital cardiovascular malformations. Improvements in clinical ascertainment have been suggested as an explanation for this increase. For several decades, 40-50% of infants with Down's syndrome have been reported to have cardiac defects associated with the unbalanced genotype. Therefore, secular changes in the frequency of ascertained cardiovascular malformations among infants with Down's syndrome in surveillance systems could shed light on improvements in the ascertainment of these defects. The authors examined changes in the frequency of ascertained cardiovascular malformations among 532 cases of Down's syndrome recorded in the Metropolitan Atlanta Congenital Defects Program from 1968 through 1989. Overall, 33% of the cases have reported cardiovascular malformations. However, the frequency of these defects in Down's syndrome infants increased dramatically from about 20% in the early 1970s to more than 50% in the late 1980s (p = 0.0001). This upward trend was seen for all major categories of cardiac defects and persisted after the cases were stratified by race, sex, maternal age, hospital of birth, birth weight, and gestational age. These results show improvement in the ascertainment of cardiovascular malformations among Down's syndrome infants in a surveillance population. They are also consistent with the hypothesis that the increasing rates of cardiac defects are related, at least in part, to improved ascertainment of these defects in the population.

Although the manifestations of Down syndrome (DS) are well known, certain major birth defects such as duodenal atresia and endocardial cushion defects are present in some infants but not others, suggesting the possible role of other genetic or environmental factors interacting with the trisomy genotype. To explore the possible role of maternal factors in the presence of major defects among DS infants, we examined data from an epidemiologic study of DS conducted in metropolitan Atlanta. Of 219 DS infants born between 1968 and 1980, 50 had recorded cardiac defects, 9 had selected gastrointestinal atresias and 4 had oral clefts. We evaluated the association of these defects with several maternal factors including age, race, first trimester cigarette smoking, alcohol use, and fever. We found that different maternal factors were associated with several defects: (1) mother's race with cardiac defects (40% in blacks vs. 17% in whites, P less than 0.01), (2) mother's age with oral clefts (6% for less than 25 years, 1% for 25-34, and 0% for greater than 34, P less than 0.05), and (3) maternal first trimester fever with gastrointestinal defects (15% in infants with history of fever and 3% in infants without a history of fever, P less than 0.01). We also observed an inverse relationship between maternal alcohol use and the presence of ventricular septal defect. These findings suggest that maternal risk factors may influence the clinical manifestations of DS. In addition to searching for a genetic basis for the DS phenotype, we suggest that the role of environmental factors and maternal exposures be specifically explored in clarifying the genesis of various birth defects in Down syndrome.

Estimates of the Apert syndrome birth prevalence and the mutation rate are reported for Washington State, Nebraska, Denmark, Italy, Spain, Atlanta, and Northern California. Data were pooled to increase the number of Apert births (n = 57) and produce a more stable birth prevalence estimate. Birth prevalence of the Apert syndrome was calculated to be approximately 15.5/1,000,000 births, which is twice the rate determined in earlier studies. The major reason appears to be incomplete ascertainment in the earlier studies. The similarity of the point estimates and the narrow bounds of the confidence limits in the present study suggest that the birth prevalence of the Apert syndrome over different populations is fairly uniform. The mutation rate was calculated to be 7.8 x 10(-6) per gene per generation. Apert syndrome accounts for about 4.5% of all cases of craniosynostosis. The mortality rate appears to be increased compared to that experienced in the general population; however, further study of the problem is necessary.

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.

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)

The epidemiology of neural tube defects was reviewed, using data from two birth defects surveillance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta Congenital Defects Program, for 1970-1978 and 1968-1979, respectively. After excluding cases with recognized causes, neural tube defects were divided into two major groups: "singles" and "multiples," depending on the presence of associated major defects. Only singles, which accounted for the majority of cases, were shown to have the well-known epidemiologic characteristics of neural tube defects: marked predominance of females and whites, geographic variation with an east-to-west gradient, and decreasing rates over time. On the other hand, multiples had no excess of females and occurred less predominantly in whites; moreover, their rates showed no geographic variation and little or no downward trends over time. The presence of associated defects indicates that neural tube defects are epidemiologically and probably etiologically heterogeneous. It is suggested that analytic studies of neural tube defects may be more rewarding if they try to identify different risk factors associated with various subgroups. This approach to the study of birth defects may provide better clues to their etiology and pathogenesis.

The incidence of selected congenital malformations in areas with fluoride supplementation of public water supplies was compared with the incidence in areas where the water supply is deficient in fluoride. Comparison of the incidences of several common birth defects (including Down's syndrome) in fluoridated and nonfluoridated areas revealed no substantial or significant differences in which there was a consistent pattern for both sets of data.

Racial variation in the incidence of several common congenital malformations has been studied in Atlanta, Georgia. The white-to-black incidence ratios were substantially different from unity for single defects, while approximate equality of rates was noted for multiple defects. Amongst the specific malformations for which familial data were available, affected first- and second-degree relatives were found only in the families of probands with single defects. It is postulated that these findings may indicate a more prominent function of the environment in the genesis of multiple malformations than is the case for single defects, the occurrence of which may be more strongly affected by non-sporadic genetic factors.

The association between paternal age and the occurrence of birth defects was studied using data collected in Metropolitan Atlanta. Paternal-age information for babies born with defects was obtained from birth certificates, hospital records, and interviews with mothers; for babies born without defects, the information was obtained from birth certificates. Several statistical techniques were used to evaluate the paternal-age-birth-defects associations for 86 groups of defects. Logistic regression analysis that controlled for maternal age and race indicated that older fathers had a somewhat higher risk for having babies with defects, when all types of defects were combined; an equivalent association for older mothers was not found. Logistic regression analyses also indicated modestly higher risks for older fathers for having babies with ventricular septal defects and atrial septal defects and substantially higher risks for having babies with defects classified in the category chondrodystrophy (largely sporadic achondroplasia) and babies with situs inversus. An association between elevated paternal age and situs inversus has not been reported before; the magnitude of the estimated increased risk for situs inversus was about the same as that found in this study for chondrodystrophy.

Data from the population-based Metropolitan Atlanta Congenital Defects Program (MACDP) show that the overall rate of malformed infants, as well as the incidence of several specific defects, is higher for twins than for singletons. This elevated risk appears limited to same sex twins and, hence, is probably related to monozygosity. In addition to an 18-fold increase in risk of fetal death compared to singletons, twins have almost a 50% greater likelihood of congenital malformation.

We previously reported that among neural tube defects (NTDs) with no known causes the ones that occur alone (singles) have different epidemiologic characteristics from those that occur in combination with other defects (multiples), suggesting an underlying causal heterogeneity. In this study, we compared family histories of 223 single NTD cases and 66 multiple cases ascertained through the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1970 and 1979. Compared with siblings of multiples, siblings of singles had a higher precurrence rate for NTDs (2.0% vs. 0.0%) and for birth defects in general (10.9% vs. 3.0%). Furthermore, siblings of singles that were born within 2 years before the birth of the index case had a higher precurrence rate for NTDs (8.0% vs. 1.1%) and for major birth defects (20.0% vs. 2.9%) than had those born earlier. These results further suggest that NTDs are etiologically heterogeneous, depending on the presence of associated defects, and point to important environmental influences in the increased risk for birth defects among siblings of singles. Larger studies are needed to confirm these data and show that single and multiple NTDs have different recurrence rates, not only for NTDs but also for other birth defects.

The concepts of sensitivity, specificity, and predictive value can be used to assess patterns of birth defects associated with human teratogens. Although sensitivity of any single defect is generally low for many known teratogens, the presence of specific defect combinations is usually predictive of the teratogen. To evaluate the patterns of birth defects associated with diabetic embryopathy, a sensitivity-specificity analysis was performed on 4929 infants with major defects ascertained by the population-based Metropolitan Atlanta Congenital Defects Program between 1968 and 1980. By reviewing hospital records, maternal insulin-dependent diabetes mellitus was confirmed in 26 infants. Patterns of defects were evaluated among infants born to mothers with insulin-dependent diabetes mellitus and compared with the rest of the Metropolitan Atlanta Congenital Defects Program case population. Multiple logistic regression analysis was used to assess defect combinations that predict for insulin-dependent diabetes mellitus. Of 26 infants, 8 had multiple defects. However, most defects and their combinations were poorly sensitive and predictive for insulin-dependent diabetes mellitus. The predictive value for insulin-dependent diabetes mellitus was greatest for the combination of vertebral and cardiovascular anomalies (6.5%). Also, several pathogenetic mechanisms were noted among patients with insulin-dependent diabetes mellitus, such as cell migration defects, cell death events, deformations, and cardiac flow lesions. The inability to find a clear-cut phenotype for diabetic embryopathy may be due to several etiologic factors and mechanisms associated with diabetic embryopathy.

The epidemiological characteristics are presented of 46 children with small-bowel atresia, ascertained over a 6-year period by an active, population-based birth defect surveillance program in Atlanta, Georgia. The malformation occurred at a rate of 2.7/10,000 livebirths. The previously reported association of duodenal atresia and Down syndrome was confirmed was confirmed. No instances of familial association were noted, nor was any excessive prenatal exposure to drugs found. Thirty-two instances of isolated small-bowel atresia were analyzed in detail. The frequency of the isolated defect for blacks was twice that for whites because of a higher rate for black females. The isolated defect was commonest in the winter months. The relation between isolated small-bowel atresia, birth weight, and mortality was discussed. This small series cannot readily be subdivided into distinct epidemiological groups on the basis of the location of the atretic lesions along the length of the small bowel.

The crude incidence of Down's syndrome (DS) in the United States is currently about 1/1,000 births. Reduction in the proportion of births to women 35 years and older can account for a halving of the estimated percentage of DS births to this age group and a drop in the estimated crude incidence of DS from 1.33/1,000 births in 1960 to 0.99/1,000 births in 1978. Epidemiologic studies suggest that among women 35 years and older, the risk of having a child with DS has not changed. With the present distribution of maternal ages, prenatal diagnosis among women 35 years and older can result in no more than a 20% decrease in the crude incidence of DS. With continued use of prenatal diagnosis among older gravidas, upward of 80% of DS births will occur to younger mothers.