Effects of early prenatal food supplementation and multiple micronutrients on under‐five survival, linear growth, metabolic markers and blood pressure up to 10 years of age. The MINIMat trial in rural Bangladesh

Abstract

Nutritional deficiencies in early life may have severe short‐ and long‐term consequences. Enhanced prenatal nutrition including macro‐ and micronutrient alternatives may prevent some of these unfavorable outcomes.In the MINIMat prenatal nutrition trial in Bangladesh (ISRCTN16581394) 4436 pregnant women were randomized into 6 equally sized groups; a double‐masked supplementation with either 30 mg Fe and 400 μg folic acid, or 60 mg Fe and 400 μg folic acid, or a multiple micronutrient supplement (MMS) containing a daily allowance of 15 micronutrients including 30 mg Fe and folic acid starting at around 14 weeks, was combined with a randomized early invitation (from around 9 weeks) or a usual invitation to start (from around 20 weeks) food supplementation (608 Kcal 6 days per week).These women had a median height of 150 cm, and 28% had a body mass index below 18.5. Among the 3625 live births the early timing of prenatal food supplementation combined with multiple micronutrients (vs. usual timing and 60 mg Fe‐folic acid) significantly reduced the under‐five mortality (HR 0.34; 95% CI 0.18–0.65). The early invitation to prenatal food supplementation resulted in less stunting 0–5 years (4.5 percent units), while prenatal multiple micronutrients was linked to more stunting (4.8 percent units) as well as to lower IGF‐1 levels. The early timing of prenatal food supplementation resulted in significantly lower cholesterol, LDL and ApoB levels at 4.5 years of age. Supplementation with MMS was associated with lower HDL and lower glucose levels. The higher dose of prenatal iron supplementation (60 mg) as compared to 30 mg iron or MMS was associated with significantly higher systolic and diastolic blood pressure at 10 years of age with effect sizes around 0.25 SD. The early invitation to food supplementation ameliorated that unfavourable effect. These prenatal nutrition interventions resulted in major improvement in child survival and effects on linear growth, metabolic markers and blood pressure. The combination of micronutrients with improved macronutrient nutrition in early pregnancy seems to be important in a population, where maternal undernutrition still is prevalent. These findings underline the need to analyze multiple and long‐term outcomes of prenatal nutrition interventions and to identify favorable as well as unfavorable effects in order to inform policy formation.Support or Funding InformationThe 4.5 and 10‐year follow‐up was funded by Swedish Research Council