Periconceptional Use of Analgesics and Severity of Structural Birth Defects

Reports of associations between use of specific analgesic medications and specific structural birth defects are inconsistent and difficult to translate for clinical guidelines and informed decision-making. To overcome this challenge, this study examines associations between use of specific analgesics and severity of structural birth defects, using a novel approach based on survival rates. We recorded average 12-month survival rates reported in the literature for specific birth defects and applied those rates to birth defects in the National Birth Defects Prevention Study (1997-2011) to create severity groups: < 95% survival (n = 20,229), < 70% survival (n = 2936), and ≥ 95% survival (6911). Maternal uses of specific analgesic medications during the month before through the first 3 months of pregnancy (periconception) were compared between non-malformed controls (n = 11,614) and severity groups with odds ratios (aOR) and 95% confidence intervals (CI) adjusted for race/ethnicity, maternal education, pre-pregnancy body mass index, maternal periconceptional alcohol use, exposure to known teratogens, infant sex, and study site. Use of acetaminophen as a single component product or in combination with cough/cold agents was not associated with any of the birth defect severity groups. Elevated aORs in relation to risks of < 70% survival birth defects were observed for use of acetaminophen in combination with aspirin and caffeine, hydrocodone, codeine, or propoxyphene (aOR range: 1.46-2.00) and for hydrocodone alone (OR: 2.45). aORs remained elevated for the < 95% group except for acetaminophen plus codeine (OR 1.07). aORs for each severity group in association with use of acetaminophen combined with oxycodone approximated the null and those for ibuprofen, naproxen, and aspirin ranged between 1.15 and 1.28. In consideration of severity of birth defects, our findings indicate both safer and riskier analgesic medication options are available.