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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Association of Clomiphene and Assisted Reproductive Technologies With the Risk of Neural Tube Defects.

Authors: Benedum, Corey M; Yazdy, Mahsa M; Parker, Samantha E; Mitchell, Allen A; Werler, Martha M

Published In Am J Epidemiol, (2016 Jun 01)

Abstract: Clomiphene and assisted reproductive technologies (ART) are methods used to help subfertile couples become pregnant. ART has been reported to be associated with neural tube defects (NTDs) in offspring. To evaluate these associations, we studied mothers of 219 cases and 4,262 controls from the Slone Epidemiology Center Birth Defects Study (1993-2012) who were interviewed within 6 months after delivery about pregnancy events, including use of fertility treatments. We considered exposures to clomiphene (without ART) and ART during the periconceptional period. Logistic regression models were used to calculate adjusted odds ratios and 95% confidence intervals, controlling for education and study center. We observed elevated adjusted odds ratios of 2.1 (95% confidence interval: 0.9, 4.8) and 2.0 (95% confidence interval: 1.1, 3.6) for clomiphene and ART exposure, respectively. We performed a mediation analysis to assess whether the observed elevated NTD risk was mediated through multiple births. For clomiphene exposure without ART use, the direct effect estimate of the adjusted odds ratio (aORDE) was 1.7 and the indirect effect estimate (aORIE) was 1.4. Conversely, for ART exposure, the aORDE was 0.9 and the aORIE was 2.5. Our findings suggest that relatively little of the clomiphene-NTD association is mediated through the pathway of multiple births, while the ART-NTD association was explained by the multiple-births pathway.

PubMed ID: 27188944 Exiting the NIEHS site

MeSH Terms: Adult; Body Mass Index; Clomiphene/administration & dosage*; Female; Humans; Infertility, Female/drug therapy; Infertility, Female/epidemiology; Infertility, Female/therapy*; Logistic Models; Maternal Exposure/adverse effects*; Multiple Birth Offspring/statistics & numerical data*; Neural Tube Defects/chemically induced*; Odds Ratio; Pregnancy; Pregnancy Outcome/epidemiology; Reproductive History; Reproductive Techniques, Assisted/adverse effects*; Residence Characteristics; Socioeconomic Factors; Young Adult

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