Laura J. Williams

Decline in the Prevalence of Spina Bifida and Anencephaly by Race/Ethnicity: 1995–2002

Objective. In an effort to reduce the occurrence of neural tube defects (NTDs), folic acid fortification of US enriched grain products was authorized by the Food and Drug Administration in March 1996 and required by January 1998. Fortification has been shown to result in an important decline in the prevalence of spina bifida and anencephaly in the general US population; however, fortifications impact on specific racial/ethnic groups has not been well described. We sought to characterize the decline in the prevalence of spina bifida and anencephaly among specific racial/ethnic groups during the transition to mandatory folic acid fortification in the United States. Methods. Data from 21 population-based birth defects surveillance systems were used to examine trends in prevalence of spina bifida and anencephaly for specific racial/ethnic groups for the years 1995–2002. These years were divided into 3 periods: prefortification, optional fortification, and mandatory fortification. Race/ethnicity was defined as Hispanic, non-Hispanic white, and non-Hispanic black. Prevalence ratios were calculated for each racial/ethnic group by dividing the prevalence from the mandatory fortification period by the prevalence in the prefortification period. Results. The study included data on 4468 cases of spina bifida and 2625 cases of anencephaly. The prevalence of spina bifida and anencephaly was highest among Hispanic births, followed by non-Hispanic white births, with the lowest prevalence among non-Hispanic black births. Significant declines in spina bifida and anencephaly were observed among Hispanic births and non-Hispanic white births. The prevalence ratio for non-Hispanic black births was of borderline significance for spina bifida and was not significant for anencephaly. Conclusions. The results of this study suggest that folic acid fortification is associated with significant decreases in the prevalence of spina bifida and anencephaly among non-Hispanic white and Hispanic births. The magnitude of the reduction was similar between these 2 groups and was more pronounced for spina bifida than for anencephaly. The decline in the prevalence of spina bifida and anencephaly among non-Hispanic black births did not reach statistical significance. Efforts to increase folic acid consumption for the prevention of NTDs in pregnancies among women of all races/ethnicities should be continued, and studies to identify and elucidate other risk factors for NTDs are warranted.

Genetic Association Studies of Cleft Lip and/or Palate With Hypodontia Outside the Cleft Region

OBJECTIVE The purpose of this study was to determine whether the candidate genes previously studied in subjects with cleft lip, cleft palate, or both are associated with hypodontia outside the region of the cleft. SUBJECTS One hundred twenty subjects from the Iowa Craniofacial Anomalies Research Center were selected based on the availability of both dental records and genotype information. METHOD The type of orofacial clefting and type and location of dental anomalies (missing teeth, supernumerary teeth, or peg laterals) were assessed by dental chart review and radiographic examination. Genotype analysis of candidate genes was performed using polymerase chain reaction/single-strand conformation polymorphism analysis. RESULTS The prevalence of hypodontia in this sample was 47.5%, with 30.0% of subjects having missing teeth outside the cleft. There was a positive association between subjects with cleft lip or cleft lip and palate who had hypodontia outside the cleft region (compared with noncleft controls) and both muscle segment homeo box homolog 1 (MSX1) (p =.029) and transforming growth factor beta 3 (TGFB3) (p =.024). It was not possible in this analysis to determine whether this association was specifically associated with orofacial clefting combined with hypodontia or whether it was due primarily to the clefting phenotype. CONCLUSIONS In this sample, there was a significantly greater incidence of hypodontia outside the cleft region in subjects with cleft lip and palate, compared with cleft lip only or cleft palate only. Cleft lip and/or palate with hypodontia outside the cleft region was positively associated with both TGFB3 and MSX1, compared with noncleft controls.

Using active birth defects surveillance programs to supplement data on fetal death reports: Improving surveillance data on stillbirths

BACKGROUND Surveillance of stillbirths using fetal death reports (FDRs) has been challenging because of under-reporting of fetal deaths and missing data on the FDRs. Using active case finding and chart abstraction within the infrastructure of established birth defect surveillance programs could potentially enhance the data from FDRs. The data collection form for the Metropolitan Atlanta Congenital Defects Program, an active, population-based birth defects surveillance system, was modified to collect additional information on stillbirths from medical records. METHODS The study population was a 25% simple random sample of stillbirths recorded on FDRs in 2004 (n = 125) by residents in the five central counties of metropolitan Atlanta. Stillbirth was defined as a fetal death at > or =20 weeks gestation or > or =350 g if age was unknown. Data on demographic characteristics and risk factors collected from the two sources were compared for completeness and agreement, as well as causes of and conditions associated with the fetal death. RESULTS Combining data sources provided more information. Demographic and risk factor variables in the two data sources showed strong agreement (categorical variable, kappa range = 0.79-1.00; continuous variable, correlation coefficient range = 0.61-1.00). The actively ascertained data provided more complete information for causes and conditions of fetal death. Data from the FDRs yielded 42% of cases with no listed cause of death or associated condition compared with 10% using Metropolitan Atlanta Congenital Defects Program data. CONCLUSIONS Expanding the potential of existing active birth defects surveillance programs to include stillbirth surveillance could potentially improve the quantity and quality of available data on fetal deaths. Ongoing studies are needed to corroborate these findings and to assess completeness of case ascertainment.

Birth Defects Cluster Study: A national approach to birth defects cluster investigations†‡

BACKGROUND Investigations of clusters of birth defects have been challenging endeavors that have had only modest success identifying causes or risk factors. Some of the challenges to individual cluster investigations have been small sample size and limited data collection. We describe a novel approach for investigating and analyzing pooled information from a series of birth defects cluster investigations. METHODS The Birth Defects Cluster Study uses a case-control study design with standardized methods, including a case definition, control selection, data collection methods, and data collected (e.g., maternal interviews, blood samples, and environmental samples). Analyses of pooled data from several clusters of the same defect are conducted for specific hypotheses once a sufficient sample size has been achieved. The feasibility of conducting individual birth defect investigations was evaluated on a cluster of gastroschisis. RESULTS The pilot investigation of a cluster of gastroschisis demonstrated success in recruiting participants and in collecting data and specimens for eventual inclusion in a pooled analysis. CONCLUSIONS The Birth Defects Cluster Study offers a unique and effective approach to cluster investigations that improves the likelihood of identifying genetic and environmental causes of birth defects and provides a model for cluster investigations of other noninfectious health outcomes.