Maternal multiple micronutrient supplementation in rural Pakistan increased some milk micronutrient concentrations, but not infant growth, at three-months postpartum: a randomized controlled trial substudy

Background: In Pakistan, maternal micronutrient deficiencies are highly prevalent, and stunting affects 43% of infants by 6-mo postpartum. Human milk composition for some micronutrients can be negatively affected by suboptimal maternal nutrition; however, it is unknown whether this affects infant growth. Objectives: We aimed to determine whether mothers receiving multiple micronutrient supplements (MMSs) compared with standard of care had 1) greater concentrations of iodine, vitamins A, E, and B12, and folate in their milk at 3-mo postpartum; and 2) improved growth of their offspring. Associations between milk micronutrients and infant growth were also explored. Methods: This substudy was nested within a district-based, cluster-randomized, controlled trial (MaPPS Trial; 25,477 females) with the primary aim of evaluating whether maternal MMS (preconception: twice-weekly, pregnancy and postpartum: daily, to 6-mo postpartum) compared with the standard of care (preconception: no intervention; pregnancy and postpartum: daily iron and folic acid supplementation, to 6-mo postpartum) in rural Pakistan improved infant birthweight. Substudy mother-infant dyads (n = 186) were recruited if infants were term-born and predominantly or exclusively breastfed. Milk micronutrient concentrations were compared to reference values derived from mother's milk [mother's milk adequacy estimates (MAEs)]. Results: MMS increased milk iodine and vitamin A concentrations, but not vitamins B12 or E, nor folate. Importantly, few milk sample micronutrients in either arm were above existing MAEs. MMS compared to standard of care did not improve infant growth. Independent of allocation, having all 5 milk micronutrients below MAEs was associated with decreased infant length-for-age z-score (β: –0.39, 95% CI: –0.73, –0.04; P = 0.03). Conclusions: In a population with maternal micronutrient deficiencies, providing maternal MMS was not associated with milk micronutrient concentrations above MAEs; however, infants born to mothers with milk below MAEs for all investigated micronutrients appeared to experience poorer growth. Further research is needed to understand longer-term implications, if any. Clinical Trial Registry number and website: ClinlicalTrials.gov: NCT04451395 (https://clinicaltrials.gov/study/NCT04451395) and NCT03287882 (https://clinicaltrials.gov/study/NCT03287882).