BACKGROUND: We report that inadequate vitamin B-6 status of Filipino mothers, assessed by erythrocyte aspartate aminotransferase activity coefficient (EAST-AC), is associated with an increased risk for isolated cleft lip with or without cleft palate (CL/P) in their children. Its association with the status assessed by plasma pyridoxal-5′-phosphate (PLP) concentrations is unknown. METHODS: In a case-control study in the Philippines including 46 cases (mothers of a child with CL/P) and 392 controls (mothers of an unaffected child), we evaluated the association between the risk for CL/P and maternal vitamin B-6 status assessed by PLP and EAST-AC. RESULTS: The ORs of CL/P were estimated by classifying mothers by PLP (>30, 20-30, and <20 nmol/L). Using the highest PLP group as the reference, ORs (95% CIs) were 1.03 (0.45-2.37) and 2.66 (1.30-5.50) for the middle and lowest groups, respectively (p trend = .01). In multivariate models controlling for various covariates including folate, the risk for CL/P was approximately 12 times higher in mothers with inadequate vitamin B-6 status, assessed by both PLP and EAST-AC values, compared to those with adequate status by both values. CONCLUSIONS: Inadequate vitamin B-6 status assessed by maternal PLP and EAST-AC values independently and both combined was associated with an increased risk for CL/P. The association was highest when both values were considered, suggesting that the measurement of both PLP and EAST-AC provides better assessment of vitamin B-6 status than either measurement alone. © 2007 Wiley-Liss, Inc.