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

Abstract

South Asia has >50% of the global burden of low birth weight (LBW). The objective was to determine the extent to which maternal nutrition interventions commenced before conception or in the 1st trimester improved fetal growth in this region. This was a secondary analysis of combined newborn anthropometric data for the South Asian sites (India and Pakistan) in the Women First Preconception Maternal Nutrition Trial. Participants were 972 newborn of mothers who were poor, rural, unselected on basis of nutritional status, and had been randomized to receive a daily lipid-based micronutrient supplement commencing ≥3 months prior to conception (Arm 1), in the 1st trimester (Arm 2), or not at all (Arm 3). An additional protein-energy supplement was provided if BMI <20 kg/m2 or gestational weight gain was less than guidelines. Gestational age was established in the 1st trimester and newborn anthropometry obtained <48-hours post-delivery. Mean differences at birth between Arm 1 vs. 3 were length +5.3mm and weight +89g. Effect sizes (ES) and relative risks (RR) with 95% CI for Arm 1 vs. 3 were: length-for-age Z-score (LAZ) +0.29 (0.11-0.46, p = 0.0011); weight-for-age Z-score (WAZ) +0.22 (0.07-0.37, p = 0.0043); weight-to-length-ratio-for-age Z-score (WLRAZ) +0.27 (0.06-0.48, p = 0.0133); LAZ<-2, 0.56 (0.38-0.82, p = 0.0032); WAZ <-2, 0.68 (0.53-0.88, p = 0.0028); WLRAZ <-2, 0.76 (0.64-0.89, p = 0.0011); small-for-gestational-age (SGA), 0.74 (0.66-0.83, p<0.0001); low birth weight 0.81 (0.66-1.00, p = 0.0461). For Arm 2 vs. 3, LAZ, 0.21 (0.04-0.38); WAZ <-2, 0.70 (0.53-0.92); and SGA, 0.88 (0.79-0.97) were only marginally different. ES or RR did not differ for preterm birth for either Arm 1 vs. 3 or 2 vs. 3. In conclusion, point estimates for both continuous and binary anthropometric outcomes were consistently more favorable when maternal nutrition supplements were commenced ≥3 months prior to conception indicating benefits to fetal growth of improving women's nutrition in this population.

Fig 1. Consort Diagram for Women First Preconception Maternal Nutrition Trial in South Asian region.

¹Excludes 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 prior to delivery. ²Gestational age (GA) at birth is defined as the age at the time of the ultrasound based on the ultrasound plus time until birth if the ultrasound was done between 6 weeks + 0 days to 13 weeks + 6 days and the GA at birth is between 24 weeks + 0 days and 42 weeks + 6 days. ³Primary outcome was obtained for live newborns with three length measurements taken within 48 hours of delivery. ⁴Length-for-age, weight-for-age, head circumference-for-age, and weight-length-ratio-for age Z-scores and percentiles based on measurements within 48 hours of age are calculated using the INTERGROWTH-21st International Standards for Newborn Size [37] and International Standards for Newborn Size for Very Preterm Infants [38] which provide Z-scores by sex and GA at birth for infants born between 33 weeks + 0 days to 42 weeks + 6 days GA at birth and between 24 weeks + 0 days to 32 weeks + 6 days GA at birth, respectively.

Fig 2. Women First Preconception Maternal Nutrition Trial: Effect sizes (95% confidence intervals) for continuous newborn continuous anthropometric outcomes in South Asian region.

Fig 3. Women First Preconception Maternal Nutrition Trial: Relative risks (95% confidence intervals) for binary newborn anthropometric outcomes in South Asian region.

LAZ, length-for-age Z-score; SGA, small-for-gestational age; WAZ, weight-for-age Z-score; WLRAZ, weight to length ratio-for-age Z-score.