AbstractOBJECTIVE: To examine the association of craniosynostosis with maternal intake of folic acid–containing supplements and dietary nutrients. METHODS: The study included deliveries from 1997 to 2005 from the National Birth Defects Prevention Study. Nonsyndromic infants with craniosynostosis (n = 815) were compared to nonmalformed, population‐based liveborn control infants (n = 6789), by estimating adjusted odds ratios (AORs) and 95% confidence intervals (CIs) from logistic regression models that included mother's age, parity, race‐ethnicity, education, body mass index, smoking, alcohol, fertility treatments, plurality, and study center. We compared quartiles of intake and specified nutrients as continuous. RESULTS: Intake of folic acid–containing supplements was not associated with craniosynostosis (AORs were close to 1). Analyses of dietary nutrients were restricted to mothers who took supplements during the first trimester (i.e., most women). Based on continuous specifications of nutrients, sagittal synostosis risk was significantly lower among women with higher intake of riboflavin and vitamins B6, E, and C; metopic synostosis risk was significantly higher among women with higher intakes of choline and vitamin B12; and coronal synostosis risk was significantly lower among women with higher intake of methionine and vitamin C. As examples, AORs for sagittal synostosis among women with intakes of vitamin B6 and riboflavin in the highest versus lowest quartiles were 0.4 (95% CI, 0.2–0.6) and 0.5 (95% CI, 0.3–0.7), respectively. CONCLUSION: This analysis suggests that dietary intake of certain nutrients may be associated with craniosynostosis, and results may vary by suture type. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.