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

Date Published: February 05, 2019

Publisher: Oxford University Press

Author(s): K Michael Hambidge, Jamie E Westcott, Ana Garcés, Lester Figueroa, Shivaprasad S Goudar, Sangappa M Dhaded, Omrana Pasha, Sumera A Ali, Antoinette Tshefu, Adrien Lokangaka, Richard J Derman, Robert L Goldenberg, Carl L Bose, Melissa Bauserman, Marion Koso-Thomas, Vanessa R Thorsten, Amaanti Sridhar, Kristen Stolka, Abhik Das, Elizabeth M McClure, Nancy F Krebs.


Reported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited.

This 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).

Women 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). A 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. In low-resource populations, benefits on fetal growth–related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester.

Partial Text

Linear growth restriction continues to be a major public health challenge globally for poor communities in low- and middle-income countries (1–3). Stunting before 2 y of age is prominent among the nutrition factors related to disease burden and mortality in early childhood (4, 5). Longer-term associations of early linear growth faltering include impairment of motor development, cognition, educational and economic achievement, chronic disease, and low offspring birth size (6). Fetal growth restriction is another major predictor of adverse outcomes beyond the neonatal period, including mortality, stunting, and impaired neurodevelopment (7–10). Recognition of the unique and compelling opportunities for optimizing the environment of both the fetus and young child has given prominence to the concept of “The First 1000 Days” (6, 11) and has prompted numerous trials directed either to early postnatal life or, by means of improving maternal nutrition, to life during gestation. The environmental factors underlying stunting and adverse birth outcomes are undoubtedly complex and potentially synergistic, but maternal undernutrition can clearly result in deficits of nutrients required for physical growth. Trials of maternal supplements, typically initiated during the second trimester of gestation, consisting of iron and folate, multimicronutrients with or without lipids, or protein-energy supplements, have frequently had some positive effect on offspring birth size, including length. However, the effect sizes of such maternal interventions have typically been quite modest (12–15).

The results of this 4-site trial add substantially to the evidence that poor fetal growth, including linear growth, in low-resource countries can be improved with maternal nutrition supplementation. Specifically, the intervention initiated before conception or late in the first trimester resulted in greater mean birth size (LAZ, WAZ, WLRAZ) and improved rates of stunting, underweight, wasting (WLRAZ < −2), and SGA in comparison with the control arm. Moreover, these benefits are evident in women who were selected without regard for anthropometric or biochemical evidence of malnutrition other than exclusion for severe anemia at baseline. Furthermore, overall improvements in fetal growth occurred despite the wide heterogeneity of the participating sites. With the exception of Guatemala, the mean effect sizes compare favorably with overall results of reported maternal nutrition interventions with either multimicronutrients alone, lipid-based nutrient supplement preparations, or a similar lipid-based protein-energy supplement commencing in mid-gestation (14, 15,35–38). However, starting the supplement before conception did not result in significantly greater newborn LAZ than starting the same intervention late in the first trimester.   Source:


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