Zinc supplementation initiated prior to or during pregnancy modestly impacted maternal status and high prevalence of hypozincemia in pregnancy and lactation: the Women First Preconception Maternal Nutrition Trial.

BACKGROUND: Data regarding effects of small quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited.

OBJECTIVES: Evaluate the effect of preconception vs prenatal zinc supplementation (vs control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low resource settings, and to assess associations with birth anthropometry.

METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, Pakistan) of the Women First Preconception Nutrition trial, we compared SZC at 12- and 34-weeks gestation (n=651 and 838, respectively) and 3-months postpartum (n=742) in women randomized to daily SQ-LNS containing 15 mg zinc from ≥3 months prior to conception (preconception, Arm 1), from ∼12 weeks gestation through delivery (early pregnancy, Arm 2) or not at all (control, Arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.

RESULTS: At 12-weeks gestation and 3-months postpartum, no statistical differences in mean SZC were observed among arms. At 34-weeks, mean SZC for Arms 1 and 2 were significantly higher than Arm 3 (50.3, 50.8, 47.8 μg/dL respectively; P=0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-weeks (<56 μg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 weeks (<50 μg/dL) 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-months postpartum (<66 μg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-weeks was associated with lower birth length-for-age Z-scores (all sites P=0.013, Pakistan P=0.008) and weight-for-age Z-scores (all sites P=0.017, Pakistan P=0.022).

CONCLUSIONS: Despite daily zinc supplementation for ≥7 months, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings.

CLINICAL TRIAL REGISTRATION: The study protocol is registered at ClinicalTrials.gov #NCT01883193 at https://clinicaltrials.gov/ct2/show/NCT01883193?term=01883193&rank=1 and the protocol is available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000057/.