Among the 815 cases, 438 (54%) involved the sagittal suture, 145 (18%) the metopic suture, 137 (17%) the coronal suture, 27 (3%) the lambdoid suture, and 66 (8%) multiple sutures. Mothers of cases tended to be more likely than controls to be non-Hispanic white, have higher education, and be older ().
Descriptive Characteristics of 815 Infants with Craniosynostosis (Cases) and 6789 Liveborn Infants with No Major Birth Defects (Controls), National Birth Defects Prevention Study, 1997–2005
Analyses of supplement intake included 757 cases and 5946 controls with data on this variable and the covariates. AORs for supplement intake and overall craniosynostosis tended to be relatively weak (i.e., >0.7 and <1.5), and the confidence intervals included 1 (). For example, the AOR for craniosynostosis overall was 0.9 (CI 95%, 0.6, 1.3) for supplement intake during the second or third trimester of pregnancy and 1.2 (0.8, 1.7) for no intake during pregnancy, compared to intake during the first trimester. AORs comparing women who started taking supplements in the month before or the month after conception (i.e., very early users) to women who started taking them in the second or third month after conception were close to 1 (data not shown). Unadjusted ORs were similar to the AORs presented in , with the exception of the ORs for intake in the second or third trimester for all cases (unadjusted OR, 0.6; 95% CI, 0.4, 0.8, vs. AOR of 0.9) and for sagittal cases (unadjusted OR, 0.5; 95% CI, 0.3, 0.8, vs. AOR of 0.8), demonstrating substantial confounding was present for these particular associations.
Adjusted Odd Ratios for the Association of Intake of Folic Acid–Containing Supplements with Craniosynostosisa
Analyses of dietary nutrients were restricted to mothers who took folic acid–containing supplements during the first trimester (few women did not take supplements and were therefore excluded) and who had complete dietary intake data, and to cases of sagittal, metopic, or coronal synostosis (given the small numbers of lambdoid and multiple suture synostosis), that is, mothers of 591 cases and 5152 controls. For sagittal synostosis, AORs comparing highest to lowest quartiles of intake were ≤0.7 for folate, choline, methionine, riboflavin, glycemic load, and vitamins B6, B12, E, and C; however, only confidence intervals for riboflavin and vitamins B6 and E excluded 1 (). Specifically, the AORs were 0.5 (0.3, 0.7) for riboflavin, 0.4 (0.2, 0.6) for vitamin B6, and 0.6 (0.4, 0.9) for vitamin E. AORs were closer to 1 for other nutrients (i.e., betaine and beta-carotene). In addition, results supported a linear association with riboflavin and vitamins B6, E, and C; that is, the p values for the linear specification of these nutrients were <0.05.
Adjusted Odds Ratios for the Association between Craniosynostosis and Maternal Dietary Intake of Selected Nutrients, among Women Who Took Folic Acid–Containing Supplements during the First Trimester of Pregnancya
For metopic synostosis, AORs comparing highest to lowest quartiles of intake were ≤0.7 for vitamin C and ≥1.4 for choline, methionine, beta-carotene, and vitamin E, but none of the confidence intervals excluded 1 (). The continuous specification of the nutrients suggested a significant positive association with choline (p = 0.03) and vitamin B12 (p < 0.01).
For coronal synostosis, AORs comparing highest to lowest quartiles of intake were ≤0.7 for folate, choline, methionine, and vitamins B6, B12, C, and E and ≥1.4 for glycemic load; only the confidence interval for methionine excluded 1 (). The continuous specification of the nutrients suggested a significant negative association with methionine (p = 0.01) and vitamin C (p = 0.02).
For analyses of each suture type, models that included the nutrients specified as continuous, plus quadratic terms, provided no evidence of nonlinearity of the associations with nutrients; that is, p values for the quadratic terms were all >0.10 (data not shown).
For results related to the nutrient scores, higher values of the one-carbon nutrient score, which reflects the number of relevant nutrients for which intake was greater than the lowest quartile, were associated with lower risk of sagittal synostosis (AOR, 0.92; 95% CI, 0.87, 0.98) (). That is, a one-unit change in the score corresponded to an 8% reduction in risk; a seven-unit change in the score (the maximum change possible, given that seven nutrients comprised the score) corresponded to a 44% reduction (1.0 – [0.92]7 = 0.44).
Adjusted Odds Ratios for the Association between Craniosynostosis and Maternal Nutrient Scores, among Women Who Took Folic Acid–Containing Supplements during the First Trimester of Pregnancya
After removing subjects with a family history of craniosynostosis (24 cases, 5 controls) and 79 nonisolated cases, the pattern of results was essentially unchanged (data not shown).