Use of clomiphene citrate and birth defects, National Birth Defects Prevention Study, 1997-2005.
BACKGROUND
Clomiphene citrate (CC) is the first line drug for subfertility treatment. Studies assessing the association between CC and birth defects have been inconclusive.


METHODS
We used data from the National Birth Defects Prevention Study, a population-based, multi-site case-control study of major birth defects. Women from 10 US regions with deliveries affected by at least one of >30 birth defects (cases) and mothers of live born infants without a major birth defect (controls) who delivered October 1997-December 2005 were interviewed. The exposure of interest was reported CC use in the period from 2 months before conception through the first month of pregnancy. Women who conceived using assisted reproductive technology were excluded. Thirty-six birth defect categories with at least three exposed cases were studied. Multiple logistic regression was used to control for potential confounders.


RESULTS
CC use was reported by 1.4% of control mothers (94/6500). Among 36 case-groups assessed, increased adjusted odds ratios (aOR) were found [all: aOR, 95% confidence interval (CI)] for anencephaly (2.3, 1.1-4.7), Dandy-Walker malformation (4.4, 1.7-11.6), septal heart defects (1.6, 1.1-2.2), muscular ventricular septal defect (4.9, 1.4-16.8), coarctation of aorta (1.8, 1.1-3.0), esophageal atresia (2.3, 1.3-4.0), cloacal exstrophy (5.4, 1.6-19.3), craniosynostosis (1.9, 1.2-3.0) and omphalocele (2.2, 1.1-4.5).


CONCLUSIONS
Several associations between CC use and birth defects were observed. However, because of the small number of cases, inconsistency of some findings with previous reports, and the fact that we cannot assess the CC effect separately from that of the subfertility, these associations should be interpreted cautiously.
Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, 1600 Clifton Road NE MS E-86, Atlanta, GA 30333, USA. nzr5@cdc.gov
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J
Reefhuis
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Honein
L A
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Schieve
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Rasmussen
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000757:Anencephaly / Q000453:epidemiology; D016022:Case-Control Studies; D002996:Clomiphene / Q000009:adverse effects*; D003398:Craniosynostoses / Q000453:epidemiology; D003616:Dandy-Walker Syndrome / Q000453:epidemiology; D005260:Female; D006330:Heart Defects, Congenital / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016015:Logistic Models; D011247:Pregnancy; D014481:United States / Q000453:epidemiology
D002996:Clomiphene