The effect of maternal micronutrient supplementation on early neonatal morbidity in rural Nepal: a randomised, controlled, community trial.

OBJECTIVE: Micronutrient deficiencies during pregnancy may be linked to poor newborn health and poor host defences against infection. We assessed newborn morbidity to determine the effect of four combinations of antenatal micronutrient supplements.

DESIGN: Cluster-randomised, double-masked, controlled trial.

SETTING: Rural community in Nepal.

INTERVENTIONS: Women received daily supplements from early pregnancy through to 3 months postpartum of vitamin A alone (control) or vitamin A with folic acid, folic acid plus iron, folic acid plus iron plus zinc or a multiple micronutrient supplement containing these and 11 other nutrients.

MAIN OUTCOME MEASURES: Infants were visited in their home at birth (n = 3927) and for each of 9 days thereafter to elicit a 24-h history of nine infant morbidity symptoms, measure infant respiratory rate and axial temperature, and assess the infant for chest indrawing. At 6 weeks of age, infants were visited again in their homes to elicit a 30-day and 7-day history of 10 morbidity symptoms using parental recall.

RESULTS: Maternal micronutrient supplementation had no effect on 10-day morbidity or morbidity 30-day and 7-day morbidity assessed at 6 weeks of age all relative risks were close to 1. Symptoms of birth asphyxia increased by about 60% (p<0.05) in infants of women who received the multiple micronutrient supplement compared with the control. Symptoms of combinations of sepsis, preterm and birth asphyxia were associated with 8- to 14-fold increased odds of 6-month infant mortality.

CONCLUSIONS: None of the combinations of antenatal micronutrient supplements tested improved symptoms of neonatal morbidity in the first 10 days of life or at 6 weeks of age. Further research is needed to elucidate the association and mechanism of increased risk of birth asphyxia following maternal multiple micronutrient supplementation.

TRIAL REGISTRATION NUMBERS: NCT00115271.