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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: In animal studies, some ortho-phthalates, including di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP), have been shown to be reproductive and developmental toxicants. Human studies show widespread population exposure to background levels of phthalates. Limited evidence suggests that particularly high exposure levels may result from orally ingested medicinal products containing phthalates as excipients (inactive ingredients)., Objective: In this study we aimed to identify and describe the scope of prescription (RX) and nonprescription (over-the-counter; OTC) medicinal products and dietary supplements marketed in the United States and Canada since 1995 that include phthalates as excipients., Methods: We used lists of modified-release drug products to identify potential drug products. Inclusion of phthalates was verified using available electronic databases, print references, published package inserts, product packages, and direct communication from manufacturers. Additional products were identified using Internet searches utilizing keywords for phthalates., Results: Based on labeling information, 6 RX drug products included DBP as an excipient, and 45 specified the use of diethyl phthalate (DEP). Phthalate polymers with no known toxicity--hypromellose phthalate (HMP), cellulose acetate phthalate (CAP), and polyvinyl acetate phthalate (PVAP)--were included in 75 RX products. Three OTC drug and dietary supplement products listed DBP, 64 listed DEP, and > 90 indicated inclusion of polymers., Conclusions: Numerous RX and OTC drug products and supplements from a wide range of therapeutic categories may use DBP or DEP as excipients in oral dosage forms. The potential effects of human exposure to these phthalates through medications are unknown and warrant further investigation.

Background: Evidence on the association of 5,10 methylentetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in women with gestational hypertension is inconsistent. It is also unknown whether the fetal genotype is relevant, or whether folic acid supplementation modifies this association., Methods: The study population was composed of U.S. and Canadian white women with nonmalformed infants participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery regarding multivitamin use in pregnancy and the occurrence of gestational hypertension, among other factors. DNA was extracted from cheek swabs and gene alleles determined by restriction fragment length polymorphism analysis. We compared the prevalence of the 677TT/CT and 1298CC/AC genotypes between cases with gestational hypertension (54 mothers and their 51 offspring) and controls (100 mothers and their 99 offspring). We also estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression to control for geographic region and calendar year., Results: The T allele was present in 69% of women with gestational hypertension versus 57% of control women (compared with 677CC, OR = 1.9; 95% CI = 0.9-4.0). The offspring of case and control women had a 677TT/CT genotype prevalence of 68% and 47%, respectively (2.4; 1.1-5.0). Among women supplemented with folic acid during the first 5 months of pregnancy, the ORs for maternal and fetal 677TT/CT genotypes were 0.9 (0.3-2.5) and 2.1 (0.7-6.0), respectively. Neither maternal nor fetal 1298CC/AC genotypes were associated with an increased risk of gestational hypertension., Conclusion: Maternal and fetal MTHFR C677T polymorphism may be associated with a moderately increased risk of gestational hypertension, and there is a suggestion that this association may be diminished among women receiving folate supplementation during pregnancy.

The authors investigated the association between folic acid supplementation and gestational hypertension. The study population included women with nonmalformed infants in the United States and Canada who were participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery about sociodemographic and medical factors, the occurrence of hypertension with or without preeclampsia, and multivitamin use in pregnancy. Relative risks, adjusted for weight, parity, twin pregnancy, diabetes, smoking, education, and family income, were estimated using Cox regression models. Of 2,100 women, 204 (9.7%) reported gestational hypertension (onset after the 20th week of gestation). The multivariate-adjusted relative risk of developing gestational hypertension during the month after folic acid supplementation, compared with not using folic acid during that same month, was 0.55 (95% confidence interval: 0.39, 0.79). This finding suggests that folic acid-containing multivitamins may reduce the risk of gestational hypertension.