Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal.
BACKGROUND
We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15%.


OBJECTIVE
We examined the effect of daily maternal micronutrient supplementation on fetal loss and infant mortality.


METHODS
The study was a double-blind, cluster-randomized, controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal. In addition to vitamin A (1000 microg retinol equivalents), the intervention groups received either folic acid (FA; 400 microg), FA + iron (60 mg), FA + iron + zinc (30 mg), or multiple micronutrients (MNs; the foregoing plus 10 microg vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 2.2 mg vitamin B-6, 2.6 microg vitamin B-12, 100 mg vitamin C, 64 microg vitamin K, 20 mg niacin, 2 mg Cu, and 100 mg Mg). The control group received vitamin A only.


RESULTS
None of the supplements reduced fetal loss. Compared with control infants, infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15-20% lower 3-mo mortality; this pattern was not observed with MNs. The effect on mortality was restricted to preterm infants, among whom the relative risks (RRs) were 0.36 (95% CI: 0.18, 0.75) for FA, 0.53 (0.30, 0.92) for FA + iron, 0.77 (0.45, 1.32) for FA + iron + zinc, and 0.70 (0.41, 1.17) for MNs. Among term infants, the RR for mortality was close to 1 for all supplements except MNs (RR: 1.74; 95% CI: 1.00, 3.04).


CONCLUSIONS
Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality. Among preterm infants, FA alone or with iron reduced mortality in the first 3 mo of life. MNs may increase mortality risk among term infants, but this effect needs further evaluation.
Christian
Parul
P
Department of International Health, The Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Room 2041, Baltimore, MD 21205-2179, USA. pchristi@jhsph.edu
West
Keith P
KP
Khatry
Subarna K
SK
Leclerq
Steven C
SC
Pradhan
Elizabeth K
EK
Katz
Joanne
J
Shrestha
Sharada Ram
SR
Sommer
Alfred
A
D000328:Adult; D016000:Cluster Analysis; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005313:Fetal Death / Q000517:prevention & control*; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D007226:Infant Mortality; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007501:Iron / Q000008:administration & dosage; D018977:Micronutrients / Q000008:administration & dosage*; D009390:Nepal; D011247:Pregnancy; D011248:Pregnancy Complications / Q000517:prevention & control*; D011256:Pregnancy Outcome; D012307:Risk Factors; D012423:Rural Health; D014801:Vitamin A / Q000008:administration & dosage; D015032:Zinc / Q000008:administration & dosage
D018977:Micronutrients; D014801:Vitamin A; D005492:Folic Acid; D007501:Iron; D015032:Zinc