Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal

Background: Previously we showed that women in rural Nepal experience multiple micronutrient deficiencies in early pregnancy. Objective: This study examined the effects of daily antenatal micronutrient supplementation on changes in the biochemical status of several micronutrients during pregnancy. Design: In Nepal, we conducted a randomized controlled trial in which 4 combinations of micronutrients (folic acid, folic acid + iron, folic acid + iron + zinc, and a multiple micronutrient supplement containing folic acid, iron, zinc, and 11 other nutrients) plus vitamin A, or vitamin A alone as a control, were given daily during pregnancy. In a subsample of subjects (n = 740), blood was collected both before supplementation and at ≈32 wk of gestation. Results: In the control group, serum concentrations of zinc, riboflavin, and vitamins B-12 and B-6 decreased, whereas those of copper and α-tocopherol increased, from the first to the third trimester. Concentrations of serum folate, 25-hydroxyvitamin D, and undercarboxylated prothrombin remained unchanged. Supplementation with folic acid alone or folic acid + iron decreased folate deficiency. However, the addition of zinc failed to increase serum folate, which suggests a negative inhibition; multiple micronutrient supplementation increased serum folate. Folic acid + iron + zinc failed to improve zinc status but reduced subclinical infection. Multiple micronutrient supplementation decreased the prevalence of serum riboflavin, vitamin B-6, vitamin B-12, folate, and vitamin D deficiencies but had no effect on infection. Conclusions: In rural Nepal, antenatal supplementation with multiple micronutrients can ameliorate, to some extent, the burden of deficiency. The implications of such biochemical improvements in the absence of functional and health benefits remain unclear.