Risk factors for cytogenetically normal holoprosencephaly in California: Apopulation-based case-control study

Holoprosencephaly is a developmental field defect manifested by a spectrum of abnormalities of the forebrain and midface. Approximately 50% of holopro sencephaly cases are associated with a cytogenetic abnormality or a monogen ic syndrome. Suggested risk factors for the remaining 50% of cases have bee n described in case reports, but have not been confirmed in systematically conducted studies. We report the results of a population-based case-control study of holoprosencephaly. Live births, fetal deaths, and terminations wi th a diagnosis of cytogenetically normal holoprosencephaly were identified by the California Birth Defects Monitoring Program. Telephone interviews we re conducted with the mothers of 58 cases and 107 live born, nonmalformed c ontrols. Women were questioned about their health and reproductive historie s, family demographics, and exposures occurring during their pregnancies. A mong nonsyndromic cases, increased risks were observed for females (OR=1.8, 95% C.I. 0.9-3.9), foreign-born vs. U.S. or Mexico-born women (OR=3.1, 95% C.I. 1.1-8.6), and women with early menarche (OR=2.3,95% C.I. 0.9-5.7). Ma ternal periconceptional exposures associated with increased risks for nonsy ndromic holoprosencephaly included alcohol consumption (OR=2.0, 95% C.I. 0. 9-4.5), cigarette smoking (OR=4.1, 95% C.I. 1.4-12.0), and combined alcohol and smoking (OR=5.4, 95% C.I, 1.4-20.0), insulin-dependent diabetes (OR=10 .2, 95% C.I. 1.9-39.4), medications for respiratory illnesses (OR=2.3, 95% C.I. 0.9-6.0), and salicylate-containing medications (OR=2.5, 95% C.I. 0.8- 7.9). These findings are consistent with risk factors identified in some pr evious reports, and identify several new potential risk factors that requir e confirmation in future studies. (C) 2000 Wiley-Liss, Inc.