Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Nutrients

Feb 2020

DOI: 10.3390/nu12020491

Citations:187

Influential Citations:11

Systematic Reviews / Meta-Analyses

COI

Enhanced Details

Methods

Healthy pregnant women of any age and parity in LMICs; study designs included randomized controlled trials and quasi-experimental designs; data collected from 1995 onwards; trials conducted across East Asia and Pacific, Middle East and North Africa, sub-Saharan Africa, South Asia, Latin America and the Caribbean; 64 studies (439,649 women) in data analyses.

Intervention

MMN (UNIMMAP): daily prenatal supplement containing iron 30 mg and zinc 15 mg plus vitamins/minerals per UNIMMAP (A 800 µg, B1 1.4 mg, B2 1.4 mg, B6 1.9 mg, B12 2.6 mg, C 70 mg, D 200 IU, E 10 mg, niacin 18 mg, folic acid 400 µg, copper 2 mg, selenium 65 µg, iodine 150 µg); duration from enrollment to end of pregnancy. Iron–Folic Acid (IFA): daily elemental iron 50–60 mg with folic acid 400 µg; duration from enrollment to end of pregnancy (majority used 60 mg iron; some trials used 30 mg, 50 mg, or 100 mg). Lipid-Based Nutrient Supplements (LNS): lipid-based supplements providing the MMN vitamin/mineral profile plus protein, essential fatty acids and energy; duration from enrollment to end of pregnancy (or up to postpartum in some studies). Calcium: calcium supplementation during pregnancy (regimens varied; daily elemental calcium described in guidelines as 1.5–2.9 g). Vitamin A supplementation: dosing varied; administered during pregnancy in several studies. Vitamin D supplementation: dosing varied; administered during pregnancy in several studies. Zinc supplementation: dosing varied; administered during pregnancy in several studies. Supplements delivered orally as tablets, drops, syrup or powder from enrollment through pregnancy endpoints.

Results

MMN supplementation, vs IFA, reduced risk of low birthweight by 15% (RR 0.85; 95% CI 0.77–0.93), stillbirths by 9% (RR 0.91; 0.86–0.98), and small-for-gestational-age infants by 7% (RR 0.93; 0.88–0.98). Diarrhea incidence in children aged 6 months to <5 years declined by 16% (RR 0.84; 0.76–0.92); child retinol concentrations increased. Mortality outcomes were largely unchanged. LNS showed no clear advantages over MMN for most outcomes. IFA reduced maternal anemia (RR 0.53; 0.43–0.65) and LBW (RR 0.88; 0.78–0.99). Vitamin D alone may reduce preterm births (RR 0.64; 0.40–1.04; stronger effect when used without iron/folic acid; RR 0.33; 0.17–0.62). Calcium may reduce preeclampsia/eclampsia (RR 0.45; 0.19–1.06) but did not consistently affect LBW or stillbirth. Vitamin A increased maternal retinol; iron improved maternal hemoglobin and ferritin; zinc increased maternal zinc concentrations. Overall, MMN is supported as the preferred antenatal supplement in LMICs to improve birth outcomes; single-nutrient approaches yield limited or outcome-specific benefits; results support MMN over IFA in many settings, with ongoing need for more data on LNS and subgroup-specific effects.

Limitations

Heterogeneity in MMN formulations (UNIMMAP, adapted UNIMMAP, non-UNIMMAP); varying dosages and durations; limited data for several outcomes and populations (e.g., adolescent pregnancy, sex-disaggregated outcomes); few effectiveness trials; some analyses rely on outcomes with wide confidence intervals; incomplete disaggregation by baseline nutritional status and other modifiers; potential publication bias indicated by sensitivity analyses.

Abstract

Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included. Meta-analyses showed improvement in several key birth outcomes, such as preterm birth, small-for-gestational age (SGA) and low birthweight with MMN supplementation, compared to IFA. MMN also improved child outcomes, including diarrhea incidence and retinol concentration, which are findings not previously reported. Across all comparisons, micronutrient supplementation had little to no effect on mortality (maternal, neonatal, perinatal, and infant) outcomes, which is consistent with other systematic reviews. IFA supplementation showed notable improvement in maternal anemia and the reduction in low birthweight, whereas LNS supplementation had no apparent effect on outcomes; further research that compares LNS and MMN supplementation could help understand differences with these commodities. For single micronutrient supplementation, improvements were noted in only a few outcomes, mainly pre-eclampsia/eclampsia (calcium), maternal anemia (iron), preterm births (vitamin D), and maternal serum zinc concentration (zinc). These findings highlight that micronutrient-specific supplementation should be tailored to specific groups or needs for maximum benefit. In addition, they further contribute to the ongoing discourse of choosing antenatal MMN over IFA as the standard of care in LMICs. show less