High folate and low vitamin B-12 intakes during pregnancy are associated with small-for-gestational age infants in South Indian women: a prospective observational cohort study.

Folic acid supplementation in those with a low vitamin B-12 intake or status may have adverse effects. These effects are unknown with regard to birth outcome in pregnant Indian women who are routinely supplemented with high doses of folic acid. The objective was to examine the association of unbalanced vitamin B-12 and total folate (folic acid supplement + dietary folate) intakes during pregnancy with outcomes in small-for-gestational-age (SGA) infants. This was a prospective observational cohort study of 1838 pregnant women in South India. Low intake of dietary vitamin B-12 in the presence of high total folate intake was examined as the ratio of vitamin B-12 intake to total folate intake. The inadequacy of vitamin B-12 intake (<1.2 μg/d) assessed by a food-frequency questionnaire in the first, second, and third trimesters of pregnancy was 25%, 11%, and 10%, respectively. Multivariate log binomial regression showed that low vitamin B-12 and folate intakes in the first trimester were independently associated with a higher risk of SGA. In a subgroup of women with high supplemental folic acid intakes in the second trimester, those with the lowest tertile of vitamin B-12:folate ratio had a higher risk of SGA outcome than did those in the highest tertile (adjusted RR: 2.73; 95% CI: 1.17, 6.37). A similar trend was observed in the analysis of blood micronutrient status in a random subset (n = 316) of the sample. These findings suggest that, in addition to vitamin B-12 and folate deficiencies alone, there may be adverse birth outcomes associated with unbalanced vitamin B-12 and folate intakes or status during pregnancy. These findings have important implications for the antenatal B vitamin supplementation policy in India. This trial was registered at the Clinical Trial Registry of India as 2013/07/005342.