Increased risk of small intestinal atresia among twins in the United States.

OBJECTIVE: To compare the prevalence of small intestinal atresia among twins and singletons in the United States. DESIGN: Descriptive analysis. MEASUREMENTS: The McDonnell Douglas Health Information System (MDHIS), a national registry of newborn diagnoses, 1982 through 1988; and the Metropolitan Atlanta Congenital Defects Program (MACDP), a registry of defects among infants in Atlanta, 1968 through 1989. PATIENTS: Live-born infants with small intestinal atresia. INTERVENTIONS: None. MAIN RESULTS: In both systems, the rate of small intestinal atresia was higher among twins than singletons (MDHIS: 5.5 per 10,000 vs 2.0, relative risk [RR] = 2.8, 95% confidence interval [CI] = 1.9 to 4.0; MACDP: 7.3 vs 2.5, RR = 2.9, 95% CI = 1.5 to 5.7). The increase was more notable among same-sex twins than opposite-sex twins, suggesting an increase among monozygotic twins. It was also more notable among twins with jejunoileal atresia than those with duodenal atresia, suggesting a vascular cause in many cases. CONCLUSION: Twins have a higher rate of small intestinal atresia than singletons, possibly due to vascular disruption in monozygotic twins.

Monitoring for new multiple congenital anomalies in the search for human teratogens.

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.

The changing epidemiology of neural tube defects. United States, 1968-1989.

OBJECTIVE: To describe the recent trends and epidemiologic characteristics of neural tube defects in the United States. RESEARCH DESIGN: Ongoing surveillance data. SETTING: Two birth defect surveillance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta (Ga) Congenital Defects Program for 1970 through 1989 and 1968 through 1989, respectively. PARTICIPANTS: Between 1970 and 1989, using discharge diagnoses of approximately 1 million live-born and stillborn infants per year, the Birth Defects Monitoring Program identified 15,503 cases of spina bifida and anencephaly. Between 1968 and 1989, using discharge diagnoses and clinical records until age 1 year of 38,000 infants per year, the Metropolitan Atlanta Congenital Defects Program identified 800 cases of spina bifida and anencephaly. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Nationwide, neural tube defect rates have declined from 1.3 per 1000 births in 1970 to 0.6 per 1000 births in 1989. In Atlanta, neural tube defect rates have declined from 2.0 per 1000 births in 1968 to 0.6 per 1000 births in 1989. Several changes in the epidemiologic characteristics of neural tube defects were observed: (1) the proportion of spina bifida cases has increased; (2) the proportion of neural tube defect cases compared with the proportion of other unrelated defects has increased; (3) the race ratio of whites to other races for isolated neural tube defect cases has declined in Atlanta; and (4) the rate of isolated neural tube defects in females has also decreased. CONCLUSIONS: The declining rates of neural tube defects can be partially explained by increased widespread prenatal diagnostic techniques, strongly suggesting the role of environmental factors in neural tube defects. In particular, the use of multivitamins and folic acid to prevent the occurrence of neural tube defects needs further evaluation. Nevertheless, the changing clinical and epidemiologic characteristics of cases over time points to the etiologic heterogeneity of these conditions.

Trends in rates of multiple vascular disruption defects, Atlanta, 1968-1989: is there evidence of a cocaine teratogenic epidemic?

Research suggests that, perhaps through mechanisms initiated by vasoconstriction and leading to vessel thrombosis or embolism, cocaine causes vascular disruption defects, and that frequent cocaine use during early pregnancy could disrupt multiple organ systems in the fetus. We hypothesized that if cocaine is an important cause of multiple vascular disruption defects, a rising prevalence of cocaine use by mothers during pregnancy should be accompanied by rising rates of these defects in their offspring. Using data from the Metropolitan Atlanta Congenital Defects Program, we identified all infants born in Atlanta from 1968 through 1989 who had nonsyndromic, provisional vascular disruption defects affecting more than one organ system: 61 infants (78%) had gastrointestinal and genitourinary defects, 7 (9%) had gastrointestinal and abdominal wall defects, 2 (3%) had gastrointestinal and limb reduction defects, 2 (3%) had limb reduction and abdominal wall defects, 2 (3%) had central nervous system and gastrointestinal defects, 2 (3%) had genitourinary and limb reduction defects, 1 (1%) had genitourinary and abdominal wall defects, and 1 (1%) had central nervous system and genitourinary defects. The prevalence of Atlanta infants with more than one vascular disruption defect is 0.13 per 1,000 live births. Chi-square analysis for trends showed no increase in prevalence during the study period. Our data are from one of the first population-based studies in which trends for defects potentially caused by maternal cocaine use are examined; the results of our study show no significant change in the prevalence of multiple vascular disruption defects over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns and trends of multiple congenital anomalies in birth defects surveillance systems.

Infants with multiple congenital anomalies (MCA) can provide important clues in the detection of teratogenic agents. Definition, classification, and ascertainment of MCA vary, however. We present comparative epidemiologic data on MCA from two U.S. surveillance systems: the Metropolitan Atlanta Congenital Defects Program, which ascertains major birth defects during the first year of life, and the Birth Defects Monitoring Program, a nationwide system that relies on newborn hospital-discharge diagnoses. This system has two components: the Commission on Public Hospitals Activities (CPHA) and the McDonnell Douglas Health Information System (MDHIS). Our analyses were based on over 600,000 births occurring in Atlanta, and over 5 million births occurring nationwide. Infants were classified as having MCA if they had two or more major defects from different categories (central nervous system, eye, orofacial, gastrointestinal, cardiovascular, genitourinary, and musculoskeletal). Additional analyses were also done on infants with three or more defects. Compared with the nationwide system, Atlanta showed 1) a much higher rate of MCA (16.2 per 10,000 births vs. 4.9 and 3.8 per 10,000 births in CPHA and MDHIS, respectively) and 2) a higher rate of MCA with chromosomal syndromes (2.0 per 10,000 births vs. 0.6 and 0.3 per 10,000 births in CPHA and MDHIS, respectively). Moreover, in Atlanta, the proportion of MCA with recorded chromosomal syndromes increased substantially during 20 years. These data point to differences in the ascertainment of MCAs in birth defects surveillance systems. More effort is needed to improve the ascertainment and comparability of MCA in surveillance systems, an important step toward better detection of human teratogens.

Are offspring of women with hereditary hematologic disorders at increased risk of congenital cardiovascular malformations?

Hereditary hematologic disorders (HHD) have been reported in excess among infants and families of infants with congenital cardiovascular malformations (CCM) compared with controls, suggesting possible common pathogenetic mechanisms. It is plausible that hemodynamic changes during pregnancy associated with HHD could affect cardiac morphogenesis. To investigate whether offspring of women with selected HHD have an excess risk of CCM, the authors examined data from a nationwide birth defects monitoring program (BDMP) covering about 2.9 million births in the United States between 1982 and 1988. The system ascertains major birth defects diagnosed in the newborn period. An anonymous linkage procedure linked maternal obstetric records with newborn records using demographic, diagnostic, and geographic variables. A total of 1,239 mothers were identified with selected HHD (47 hereditary spherocytosis, 575 thalassemias, 310 sickle cell anemia, 88 other hereditary hemolytic anemias, 159 von Willebrand disease, and 60 other congenital coagulopathies). In all, 14 infants received a newborn discharge diagnosis of CCM (expected number based on population rates of CCM from the same hospitals and time period is 7.74; P = 0.0268). No single CCM entity accounted for this excess. In contrast, 8 infants had major non-CCM defects (expected number 7.46; P = 0.466). These data suggest an excess risk of CCM among offspring of women with selected HHD. Further studies are needed to explore these findings and to evaluate the pathogenetic significance of this association.