Common strategies to decide whether a variable is a confounder that should be adjusted for in the analysis rely mostly on statistical criteria. The authors present findings from the Slone Epidemiology Unit Birth Defects Study, 1992-1997, a case-control study on folic acid supplementation and risk of neural tube defects. When statistical strategies for confounding evaluation are used, the adjusted odds ratio is 0.80 (95% confidence interval: 0.62, 1.21). However, the consideration of a priori causal knowledge suggests that the crude odds ratio of 0.65 (95% confidence interval: 0.46, 0.94) should be used because the adjusted odds ratio is invalid. Causal diagrams are used to encode qualitative a priori subject matter knowledge.

Objective To provide information on overall medication use throughout pregnancy, with particular focus on the first trimester and specific prescription medications. Study Design The Slone Epidemiology Center Birth Defects Study (BDS), 1976 to 2008, and the National Birth Defects Prevention Study (NBDPS), 1997 to 2003, which together interviewed over 30,000 women about their antenatal medication use. Results Over the last three decades, first trimester use of prescription medication increased by over 60%, and use of four or more medications more than tripled. By 2008, approximately 50% of women reported taking at least 1 medication. Use of some specific medications markedly decreased or increased. Prescription medication use increased with maternal age and education, was highest for non-Hispanic whites, and varied by state. Conclusion These data reflect the widespread and growing use of medications by pregnant women and reinforce the need to study their respective fetal risks and safety.

These data support an association between the maternal use of SSRIs in late pregnancy and PPHN in the offspring; further study of this association is warranted. These findings should be taken into account in decisions as to whether to continue the use of SSRIs during pregnancy.

Folic acid antagonists, which include such common drugs as trimethoprim, triamterene, carbamazepine, phenytoin, phenobarbital, and primidone, may increase the risk not only of neural-tube defects, but also of cardiovascular defects, oral clefts, and urinary tract defects. The folic acid component of multivitamins may reduce the risks of these defects.

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