BACKGROUND: Findings from animal experiments suggest a link between poor maternal zinc status and increased risk of oral clefts in offspring; however, there are few human studies on this issue. METHODS: A case-control study was conducted using 74 case mothers of children with nonsyndromic cleft lip with or without cleft palate (CL/P, n = 57) or cleft palate alone (CP, n = 17), and 283 control mothers of unaffected children recruited in the Philippines in early 2003. Maternal zinc status was assessed by determining plasma zinc concentrations a mean of 5 years after delivery of the index child. Odds ratios (ORs) of estimates of the relative risk of oral clefts were calculated for quartiles of maternal plasma zinc concentrations. RESULTS: The mean plasma zinc concentration of CL/P case mothers (9.6 ± 1.2, SD μmol/l) was significantly lower than that in control mothers (10.1 ± 1.6 μmol/l; P < 0.05). Low plasma zinc concentrations (< 11.0 μmol/l) were found in 88% and 94% of CL/P and CP case mothers, respectively, and in 72% of controls (P < 0.05). The ORs for CL/P and CP combined, adjusted for potential confounding factors, decreased with increasing quartile of plasma zinc as follows: 1.0 (lowest quartile reference), 0.83 (95% confidence interval 0.37-1.89), 0.70 (0.31-1.68), and 0.26 (0.10-0.70) (P trend = 0.008). CONCLUSIONS: Low plasma zinc concentrations were common in Filipino women of reproductive age, and higher plasma zinc concentrations were associated with a lower risk for oral clefts in their children. © 2005 Wiley-Liss, Inc.