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Knowledge that folic acid prevents spina bifida and anencephaly has existed for 25 years, yet only a small fraction of FAP SBA is being prevented worldwide. Several countries still have 5- to 20-fold epidemics of FAP SBA. Implementation of mandatory fortification with folic acid offers governments a proven and rapid way to prevent FAP SBA-associated disability and mortality, and to help achieve health-related Sustainable Development Goals. Birth Defects Research (Part A) 106:520-529, 2016. © 2016 Wiley Periodicals, Inc.

Background Our objective was to describe time trends in selected pregnancy exposures in the National Birth Defects Prevention Study (NBDPS). Methods We analyzed data from the NBDPS, a multi-site case-control study of major birth defects, for mothers of live-born infants without birth defects (controls), with an expected date of delivery (EDD) from 1998 –2011. Mothers from the 10 participating centers across the United States were interviewed by phone between six weeks and two years after the EDD. We focused on maternal race/ethnicity and five maternal risk factors: obesity, use of folic acid-containing multivitamins, opioid analgesics, selective serotonin reuptake inhibitors (SSRIs), and loratadine because of their prevalence of use and some reports of associations with major birth defects. Prevalence time trends were examined using the Kendall’s τβ test statistic. Results The exposure trend analysis included 11,724 control mothers with EDDs from 1998–2011. We observed a significant increase in obesity prevalence among control mothers, as well as use of SSRIs and loratadine. We also observed an increase in periconceptional use of folic acid-containing multivitamins. Some of the time trends varied by race/ethnicity. No remarkable trend in the overall use of opioid analgesics was observed. The racial/ethnic distribution of mothers changed slightly during the study period. Conclusions Long-term, population-based case-control studies continue to be an effective way to assess exposure-birth defects associations and provide guidance to health care providers. However, investigators examining rare outcomes covering many years of data collection need to be cognizant of time trends in exposures.