Small Study: Clomiphene Linked to NTDs


LOS ANGELES — Maternal exposure to clomiphene was independently associated with spinal neural tube defects in a case-control study nested within a live-birth cohort, Yvonne Wu, M.D., reported.

Although several studies have examined the possibility of a link between the ovulation-stimulating drug and neural tube defects, the results to date have been mixed, Dr. Wu said in a presentation at the annual meeting of the Child Neurology Society.

Dr. Wu stressed that her study is too limited in size and scope to make definitive statements about the association. “The data linking infertility treatment and neural tube defects have been inconsistent, and our results do not really shift the balance yet,” she said. “Our study was an offshoot of an existing [investigation] of cerebral palsy and was not even designed to look at this question.”

Given the study's limitations, the findings should not impact clinical decision-making. Instead, they should be the impetus for larger, better-defined studies, she said.

In the current study, Dr. Wu and colleagues from the University of California, San Francisco, electronically reviewed the medical charts of 110,624 mothers and their full-term singleton infants born at Kaiser Permanente Northern California between 1994 and 1997 to identify history of infertility exposure and cases of neural tube defects of the spine. For the purposes of the study, infertility exposure was defined as evaluation at an infertility clinic within Kaiser Permanente, physician diagnosis of infertility, or infertility medication prescribed within 60 days of conception. Information on infertility medication and diagnosis was obtained from electronic databases.

Of the full cohort, 18 infants were diagnosed with neural tube defects, including 12 with spina bifida cystica, 4 with tethered cord syndrome associated with sacral lipoma, and 2 with dermal sinus tracts.

Using multivariate logistic regression analysis, the investigators compared the 18 case mothers with 1,610 randomly selected controls from the same cohort. The mothers of babies born with neural tube defects were more likely to be Hispanic, have had a history of infertility, and have been prescribed clomiphene within 60 days of conception. After adjusting for maternal age, ethnicity, gestational age, and birth weight, exposure to clomiphene was the only independent association with neural tube defects of the spine, according to Dr. Wu.

To authoritatively confirm or dismiss the association between clomiphene and neural tube defects, “we need studies that include comprehensive infertility data on all cases of neural tube defects in a population, including those that resulted in pregnancy termination,” she said.

A better understanding of the underlying pathogenesis of neural tube defects and the mechanism of action of clomiphene, both of which are poorly understood, could provide important insight into the possible association between the two as well, Dr. Wu concluded.

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