A multicountry randomized controlled trial of comprehensive maternal nutrition supplementation initiated before conception: the Women First trial

Abstract

BackgroundReported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited.ObjectivesThis study tested the effects on newborn size, especially length, of commencing nutrition supplements for women in low-resource populations ≥3 mo before conception (Arm 1), compared with the same supplement commenced late in the first trimester of pregnancy (Arm 2) or not at all (control Arm 3).MethodsWomen First was a 3-arm individualized randomized controlled trial (RCT). The intervention was a lipid-based micronutrient supplement; a protein-energy supplement was also provided if maternal body mass index (kg/m2) was <20 or gestational weight gain was less than recommendations. Study sites were in rural locations of the Democratic Republic of the Congo (DRC), Guatemala, India, and Pakistan. The primary outcome was length-for-age z score (LAZ), with all anthropometry obtained <48 h post delivery. Because gestational ages were unavailable in DRC, outcomes were determined for all 4 sites from WHO newborn standards (non-gestational-age-adjusted, NGAA) as well as INTERGROWTH-21st fetal standards (3 sites, gestational age-adjusted, GAA).ResultsA total of 7387 nonpregnant women were randomly assigned, yielding 2451 births with NGAA primary outcomes and 1465 with GAA outcomes. Mean LAZ and other outcomes did not differ between Arm 1 and Arm 2 using either NGAA or GAA. Mean LAZ (NGAA) for Arm 1 was greater than for Arm 3 (effect size: +0.19; 95% CI: 0.08, 0.30, P = 0.0008). For GAA outcomes, rates of stunting and small-for-gestational-age were lower in Arm 1 than in Arm 3 (RR: 0.69; 95% CI: 0.49, 0.98, P = 0.0361 and RR: 0.78; 95% CI: 0.70, 0.88, P < 0.001, respectively). Rates of preterm birth did not differ among arms.ConclusionsIn low-resource populations, benefits on fetal growth–related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester.This trial was registered at clinicaltrials.gov as NCT01883193.

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

“…Of these, a total of 72 unique studies, with 314 associated papers, were identified for inclusion based on our pre-defined inclusion and exclusion criteria ( Figure 1). Eight studies were included in the review, but did not contribute data to the meta-analyses for reasons including incomplete data and no reported outcomes of interest [48][49][50][51][52][53][54][55]. Subgroup analyses were conducted for the following comparisons: zinc vs. placebo, iron vs. placebo, and MMN vs. IFA supplementation.…”

“…Seven studies were conducted in Latin America and the Caribbean [48,[113][114][115][116][117][118], and only one trial was conducted in Europe and Central Asia (Turkey; [52]). Two trials were multi-country studies [55,119], conducted in countries representative of multiple geographical regions. A summary of study characteristics can be found in the Supplementary Materials, Table S2.…”

The impact of maternal supplementation during pregnancy and the first 6 months postpartum on the growth status of the next child born after the intervention period: Follow‐up results from Bangladesh and Ghana

“…Other available evidence, from three trials that started preconception maternal supplementation at least 3 months prior to conception, is mixed. A recent multicountry (Democratic Republic of the Congo, Guatemala, India, and Pakistan) randomized controlled trial showed no difference in birth outcomes in the group that received daily LNS starting at least 3 months before conception compared with the group that received LNS starting late in the first trimester of pregnancy, though birth outcomes in both LNS groups were improved relative to the control group that did not receive supplementation (Hambidge et al, 2019). An earlier food-based intervention in India showed no difference in birth weight among the infants of women who were provided with a nutrient-dense daily snack prior to conception and through pregnancy, compared with the infants of women provided a similar snack but with low micronutrient content (control; Potdar et al, 2014).…”

“…Thus, there is limited evidence on the impact of maternal nutrition interventions during the preconception period, including the importance of the specific timing and duration of the preconception intervention, on birth outcomes and child growth. A few studies have evaluated the effect of preconception nutrition interventions on birth outcomes (Hambidge et al, 2019;Nguyen et al, 2017;Potdar et al, 2014;Ramakrishnan et al, 2016). In the most recent trial, conducted in four low-and middle-income countries, maternal supplementation with a lipid-based nutrient supplement (LNS) starting at least 3 months before conception improved foetal growth, but the impact on foetal growth did not significantly differ from the impact observed when the supplement was started late in the first trimester (Hambidge et al, 2019).…”

Preconception nutrition intervention improved birth length and reduced stunting and wasting in newborns in South Asia: The Women First Randomized Controlled Trial

“…Here we report the newborn anthropometric data for the combined S. Asian sites participating in the Women First Preconception Maternal Nutrition Trial [30].…”