Maternal Vitamin B-12 Status And Risk Of Cleft Lip And Cleft Palate Birth Defects In Tamil Nadu State, India

Background and Objective:The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B-12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL +/- P) in a case-control study in Tamil Nadu state, India.Methods:Case-mothers of CL +/- P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B-12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case-control status.Results:Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B-12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B-12 status (OR = 3.65 95% CI, 1.21-11.05). Case-control status was not consistently associated with folate or tHcy levels. Low vitamin B-12 status, when defined by a combination of both plasma vitamin B-12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09).Conclusions:Mothers of CL +/- P children in southern India were 6.5 times more likely to have poor vitamin B-12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B-12 or folate levels or their interactions are causally related to CL +/- P.