Maternal Nutrient Intake and Risks for Transverse and Longitudinal Limb Deficiencies: Data from the National Birth Defects Prevention Study, 1997-2003

BACKGROUND: The association between periconceptional intake of supplements containing folic acid with specific subtypes of limb deficiencies has been inconsistent. The objective was to investigate whether intake of nutrients involved in one-carbon metabolism (folate, vitamin B-6, vitamin B-12, riboflavin, choline, betaine, zinc, and methionine) through diet alone or in combination with a supplement containing folic acid influenced the risk for transverse limb deficiency (TLD) and longitudinal limb deficiency (LLD). METHODS: We analyzed 1997-2003 data from the National Birth Defects Prevention Study and included 324 case infants with TLD, 158 case infants with LLD, and 4982 nonmalformed control infants. A food frequency questionnaire was used to estimate nutrient intakes. Use of supplements containing folic acid 1 month before through 2 months after conception was recorded. RESULTS: Use of a supplement containing folic acid was not associated with LLD or TLD. For nonsupplement users, within (1) the lowest quartile of dietary folate intake or vitamin B-6 intake, adjusted odds ratios (aORs) for LLD were, respectively, 3.86 (95% confidence interval [CI]: 1.08-13.78) and 4.36 (95% CI: 0.93-20.48); and (2) the lowest quartile for riboflavin intake, the aOR for TLD was 2.94 (95% CI: 1.04-8.32). For supplement users within the lowest quartile of folate intake or riboflavin intake, the aORs for TLD were, respectively, 1.52 (95% CI: 0.91-2.54) and 1.54 (95% CI: 1.00-2.37). CONCLUSIONS: TLD and LLD were not associated with supplement use, but TLD was associated with low intakes of riboflavin from diet. Birth Defects Research (Part A) 85:773-779, 2009. (C) 2009 Wiley-Liss, Inc.