Objectives Prior studies have reported increased risks of congenital heart defects (CHD) and pyloric stenosis (PS) after prenatal exposure to macrolide antibiotics. We sought to assess the association between maternal use of erythromycin and non-erythromycin macrolides and the risks of CHD and PS. Study Design Among participants in the Slone Epidemiology Center Birth Defects Study from 1994 to 2008, we identified 4132 infants with CHD and 735 with PS as cases, and 6952 infants without any malformation as controls. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with use of erythromycin or non-erythromycin macrolides in each trimester using conditional logistic regression and adjusting for risk factors for CHD and PS, fever, specific types of infections, and their associated treatments. Results During the first trimester, 0.4% and 0.7% of control women had used erythromycin and non-erythromycin macrolides, respectively. Compared to non-use during pregnancy, first-trimester exposure to erythromycin was not associated with an increased risk of CHD (OR, 1.3; 95% CI, 0.6–2.6) or PS (OR, 0.9; 95% CI, 0.3–3.0). The corresponding ORs for non-erythromycin macrolides were 0.7 (95% CI, 0.4–1.3) for CHD and 1.7 (95% CI, 0.6–4.6) for PS. We found no association between third-trimester exposure to erythromycin or non-erythromycin macrolides and the risk of PS. Hypothesis generation analyses did not identify appreciable associations between maternal use of macrolides and other common specific birth defects. Conclusions We found no meaningful associations between the risks of CHD, PS, and other common malformations in relation to use of macrolides in pregnancy.

Previous studies suggested that early pregnancy exposure to specific oral decongestants increases the risks of several birth defects. Using January 1993-January 2010 data from the Slone Epidemiology Center Birth Defects Study, we tested those hypotheses among 12,734 infants with malformations (cases) and 7,606 nonmalformed control infants in the United States and Canada. Adjusted odds ratios and 95% confidence intervals were estimated for specific birth defects, with controlling for potential confounders. Findings did not replicate several hypotheses but did support 3 previously reported associations: phenylephrine and endocardial cushion defect (odds ratio = 8.0; 95% confidence interval: 2.5, 25.3; 4 exposed cases), phenylpropanolamine and ear defects (odds ratio = 7.8; 95% confidence interval: 2.2, 27.2; 4 exposed cases), and phenylpropanolamine and pyloric stenosis (odds ratio = 3.2; 95% confidence interval: 1.1, 8.8; 6 exposed cases). Hypothesis-generating analyses involving multiple comparisons identified a small number of associations with oral and intranasal decongestants. Accumulating evidence supports associations between first-trimester use of specific oral and possibly intranasal decongestants and the risk of some infrequent specific birth defects.

Background Prior studies have suggested an increased risk of oral clefts after exposure to amoxicillin in early pregnancy, but findings have been inconsistent. Methods Among participants in the Slone Epidemiology Center Birth Defects Study from 1994 to 2008, we identified 877 infants with cleft lip with/without cleft palate (CL/P) and 471 with cleft palate alone (CP). Controls included 6952 non-malformed infants. Mothers were interviewed about demographic, reproductive and medical factors, and details of medication use. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with use of amoxicillin in the first trimester using conditional logistic regression and adjusting for known risk factors for oral clefts, as well as for infections, fever, and concomitant treatments. Results In the control group, 3% of women had used amoxicillin in the first trimester. Maternal use of amoxicillin was associated with an increased risk of CL/P (adjusted OR= 2.0 [95% CI= 1.0–4.1]), with an OR of 4.3 (1.4–13.0) for third-gestational-month use. Risks were not elevated for use of other penicillins or cephalosporins. For CP, the OR for first-trimester amoxicillin was 1.0 (0.4–2.3), with an OR of 7.1 (1.4–36.4) for third-gestational-month use. Conclusions Amoxicillin use in early pregnancy may be associated with an increased risk of oral clefts.

Background Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects. Objective To test 16 previously-hypothesized associations between specific antihistamines and specific birth defects, and identify possible new associations. Methods We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within six months of delivery about demographic, reproductive, medical, and behavioral factors, and details on use of prescription and non-prescription medications. We compared 1st trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6,982 non-malformed controls, using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use. Results Overall, 13.7% of controls were exposed to antihistamines during the 1st trimester. The most commonly-used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). Where estimates were stable, none supported the previously-hypothesized associations. Among over 100 exploratory comparisons of other specific antihistamine/defect pairs, 14 had ORs ≥1.5 of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons. Conclusion Our findings do not provide meaningful support for previously-posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation which may also apply to our new findings.