SummaryBackgroundChildhood stunting can start in the womb and continue for two years. Therefore, the first 1000 days of life between a woman's pregnancy and her child's 2nd birthday offer a unique window of opportunity to build healthier and more prosperous futures. Therefore, we aimed to assess the effectiveness of nutritional supplementation during the first 1000-days to reduce the prevalence of stunting in children at 24 months of age.MethodsIn this cluster randomized controlled trial, we enrolled women during their pregnancy from two rural districts of Sindh, Pakistan. A cluster was one union council with a population of ∼25000 residents. Out of 29 clusters, we randomly allocated 6 clusters to the intervention and control groups each. Pregnant women received a monthly supply of 5 kg (i.e., 165 grams/day) of wheat soya blend plus (WSB+) during pregnancy and the first six months of their lactation period. In addition, their children received lipid-based nutrient supplement - medium-quantity (LNS-MQ) between 6-23 months of age. The primary outcome was a reduction in the prevalence of stunting in children at 24 months of age. Analysis was an intention to treat. The trial is registered on ClinicalTrial.gov, number NCT02422953.FindingsTwo thousand thirty pregnant women (1017 in the intervention group and 1013 in the control group) were enrolled between August 30, 2014, and May 25, 2016. Monthly follow-ups were conducted between October 1, 2014, and October 25, 2018. At 24 months of age, we captured data from 699 (78%) of 892 live births in the intervention group and 653 (76%) of 853 live births in the control group. There was a significant difference in mean length (49.4 cm vs 48.9 cm,p =0.027), weight (3.1 kg vs 3.0 kg,p =0.013), length for age z-scores (-1.2 vs -1.5,p =0.004) and weight for age z-scores (-1.2 vs -1.5,p =0.015) among infants in the intervention compared to control group. At 24 months of age, a significant difference in the prevalence of stunting (absolute difference, 10.2%, 95% CI 18.2 to 2.3,p =0.017) and underweight (absolute difference, 13.7%, 95% CI 20.3 to 7.0,p =0.001) were observed in the intervention as compared to the control group. The prevalence of wasting was not significantly different between the intervention and control groups (absolute difference, 6.9%, 95% CI 14.1 to 0.3,p =0.057).InterpretationProvision of WSB+ and LNS-MQ during the first 1000-days of life improved child linear growth and reduced stunting in children at 24 months. This study can be scaled-up in similar settings to lower the prevalence of stunting in children under two years of age.FundingWorld Food Programme, Pakistan