Maternal exposure to prescription and non-prescription pharmaceuticals or drugs of abuse and risk of craniosynostosis.

Abstract

The pre- and peri-natal drug exposures reported by women participating in a case-control study of children in Colorado were examined for association with infant craniosynostosis. Mothers of case and control children underwent a standardized telephone interview and obstetric and newborn medical record review. The interview included questions on the use of prescription and non-prescription drugs, nutritional supplements, recreational and drugs of abuse. The mother's obstetric record was abstracted for information about pharmacologic agents taken before and during the antepartum period. There were no statistically significant risk ratios associating craniosynostosis with prenatal exposure to hydantoin, valproic acid, or cocaine. Mothers of four case children and one control child reported specific exposure to retinoic acid. There were no statistically significant increases in the odds ratio (OR) for any suture type among children exposed to hypoxigenic agents, sympathomimetic or parasympatholytic agents, or metal-containing agents. The OR was 1.87 (lower bound of the two-sided 95% test-based confidence interval (CI): 1.08) among children with sagittal/lambdoid suture synostosis who were exposed to nitrosatable drugs chlorpheniramine, chlordiazepoxide, and nitrofurantoin compared to controls. Certain nitrosatable drugs may be associated with increased risk of infant sagittal/lambdoid craniosynostosis. A possible mechanism related to ischaemia/reperfusion injury is suggested.