Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines

• Published in: Birth defects research. A Clinical and molecular teratology 2004-07, Vol.70 (7), p.464-471
• Main Authors: Munger, Ronald G., Sauberlich, Howerde E., Corcoran, Christopher, Nepomuceno, Buena, Daack-Hirsch, Sandra, Solon, Florentino S.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; birth defects; Case-Control Studies; cleft lip; Cleft Lip - metabolism; Cleft Palate - metabolism; Embryology: invertebrates and vertebrates. Teratology; epidemiology; Female; folate; folic acid; Folic Acid - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Male; Mothers; nutrition; oral clefts; Philippines; Philippines - epidemiology; pyridoxine; Risk Factors; Teratology. Teratogens; Vitamin B 6 - metabolism; vitamin B-6
• ISSN: 1542-0752; 1542-0760
• DOI: 10.1002/bdra.20037

BACKGROUND Vitamin deficiencies induce oral clefts in animal experiments, but the role of specific nutrients in human oral clefts is uncertain. METHODS Associations between maternal vitamin B‐6 and folate status and risk of nonsyndromic cleft lip, with or without cleft palate (CL/P), were examined in case–control studies at two sites in the Philippines—Negros Occidental and Davao. Cases were mothers of affected children and control mothers were those who had no children with oral clefts. RESULTS The risk of having a CL/P‐affected child increased with increasing tertile of vitamin B‐6 deficiency in both Negros Occidental and Davao (odds ratios [ORs] and 95% confidence intervals [CIs] for sites combined = 1.0 [reference], OR, 2.94; 95% CI, 1.51–5.73; OR, 4.98; 95% CI, 2.56–9.67). Poor B‐6 status had a stronger association with CL/P among mothers with lower versus higher plasma folate levels. Increasing tertiles of plasma folate were marginally associated with an increased risk of clefts in both sites combined (1.0 [reference]; OR, 1.58; 95% CI, 0.93–2.68; OR, 1.59; 95% CI, 0.94–2.70). Increasing tertiles of erythrocyte folate were associated with a decreased risk of CL/P in Negros Occidental (1.0 [reference]; OR, 0.34; 95% CI, 0.13–0.90; OR, 0.46; 95% CI, 0.20–1.09) and an increased risk in Davao (1.0 [reference]; OR, 1.23; 95% CI, 0.54–2.81; OR, 4.85; 95% CI, 2.24–10.50). The inconsistent associations between folate status and CL/P risk appeared to be a result of statistical interaction between folate, vitamin B‐6, and case–control status that produced different results in study areas of higher versus lower prevalence of vitamin B‐6 deficiency. CONCLUSIONS Poor maternal vitamin B‐6 status was consistently associated with an increased risk of CL/P at two sites in the Philippines. Folate‐CL/P associations were inconsistent and may be related to the vitamin B‐6 status or other characteristics of the populations under study. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.