Preventing birth defects: The value of the NBDPS case-control approach

Birth Defect Registries provide a basis for epidemiological research into risk factors, thus facilitating a growing understanding of what causes congenital anomalies and how one might target preventive public health actions and reduce inequalities. The National Birth Defects Prevention Study (NBDPS) has used 10 U.S. registries as a basis for a large case-control study. This commentary reviews its methodology and selected areas of output. The strengths of NBDPS lie in the quality of diagnostic coding and classification of birth defects and its size. The sources of bias in NBDPS data relate particularly to retrospective exposure ascertainment entailing a long period of recall, incomplete ascertainment of terminations of pregnancy for fetal anomaly, and unknown bias in case selection. NBDPS results have shown the protective effect of healthy dietary patterns, but have not been as informative as expected in relation to furthering understanding of the protective effect of folic acid. NBDPS medication studies are making important contributions to addressing the gap in existing evidence systematically across a wide range of birth defects, but are challenged by the quality of information on exposure, dose and underlying disease condition, and the interpretation of results of multiple testing. Studies of environmental contaminants in collaboration with experts in exposure assessment have linked addresses to residential exposure measures, using the advantages of information on residential history and confounders, but are challenged by the need to consider exposure mixtures. NBDPS could increase its public health impact by placing more emphasis on socioeconomic inequalities.