Growth from Birth Through Six Months for Infants of Mothers in the "Women First" Preconception Maternal Nutrition Trial

Abstract

Objective: To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6 months postnatal age.

Study design: The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation initiated preconception (Arm 1) vs at ∼11 weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were in Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6 months. We fitted longitudinal models on growth from birth to 6 months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates.

Results: Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15-0.35; P < .001) and 0.19 (95% CI 0.09-0.28; P < .001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ <-2) were lower for Arms 1 and 2: 0.76 (0.66-0.87; P < .001) and 0.77 (0.67-0.88; P < .001), respectively.

Conclusions: Improved linear growth in early infancy observed for the 2 intervention arms supports the critical importance of maternal nutrition before conception and in the early phase of gestation.

Trial registration: ClinicalTrials.gov: NCT01883193.

Keywords: breastfeeding; infant growth; postnatal growth; small quantity-lipid nutrient supplement (SQ-LNS); stunting.

Figure 1.

Consort diagram: screening, randomization, and longitudinal 0- to 6-month analyses population by intervention arm. ^a Excludes women who became pregnant <3 months into the study. The women who had eligible pregnancies may have had delivery data obtained or they may have exited the study before delivery. ^bAfter excluding extreme invalid measurements as determined by expert internal review, the 0- to 6-month longitudinal analysis subset includes all live-born infants with birth length measurements measured by 7 days of age and at least 2 follow-up visits (1-month, 3-month, or 6-month).

Figure 2.

Longitudinal data for A, LAZ, B, WAZ; and C, BMI-for-age z score from birth to 6 months of age by intervention arm. Data are presented as mean ± SEM. Maternal participants in Arm 1 (N = 785 infants) started lipid-based nutrition supplements ≥3 months before conception; Arm 2 (N = 827 infants) started the same supplement at ~11 weeks of gestation; and Arm 3 (control, N = 809 infants) received no trial supplements. Different subscripts denote significant differences between arms when adjusted for site, cluster, maternal education, parity, and (for LAZ) site-by-arm interaction (P < .05).

Figure 3.

Progression of stunting from birth to 6 months of age by intervention arm. Data represent unadjusted means. Maternal participants in Arm 1 (N = 785 infants) started lipid-based nutrition supplements ≥3 months before conception; Arm 2 (N = 827 infants) started same supplement at ~11 weeks of gestation; and Arm 3 (control, N = 809 infants) received no trial supplements. Different superscripts denote significant differences between arms.