Effect of prenatal micronutrient-fortified balanced energy-protein supplementation on maternal and newborn body composition: A sub-study from the MISAME-III randomized controlled efficacy trial in rural Burkina Faso
Authors: Argaw Alemayehu , Toe Laeticia Celine , Hanley-Cook Giles , Dailey-Chwalibóg Trenton , de Kok Brenda , Ouédraogo Lionel , Compaoré Anderson , Ouédraogo Moctar , Sawadogo Amadi , Ganaba Rasmané , Vanslambrouck Katrien , Kolsteren Patrick , Lachat Carl , Huybregts Lieven 
Published: July 2023

Background
Micronutrient-fortified balanced energy-protein (BEP) supplements are promising interventions to prevent intrauterine growth retardation in low- and middle-income countries. On the other hand, one concern with blanket prenatal supplementation programs using energy-dense supplements is that they could lead to more maternal and/or infant overweight. However, evidence is lacking on the potential effect of BEP on maternal and offspring body composition. This study evaluates the effects of micronutrient-fortified BEP supplementation during pregnancy on body composition of mothers and their newborns in rural Burkina Faso.

Methods and findings
The MISAME-III study is an open label individually randomized controlled trial where pregnant women (n = 1,897) of gestational age <21 weeks received either a combination of micronutrient-fortified BEP and iron-folic acid (IFA) tablets (i.e., intervention) or IFA alone (i.e., control). The prenatal phase of the MISAME-III study was conducted between the first enrollment in October 2019 and the last delivery in August 2021. In a sub-study nested under the MISAME-III trial, we evaluated anthropometry and body composition in newborns who were born starting from 17 November 2020 (n: control = 368 and intervention = 352) and their mothers (n: control = 185 and intervention = 186). Primary study outcomes were newborn and maternal fat-free mass (FFMI) and fat-mass (FMI) indices. We used the deuterium dilution method to determine FFMI and FMI and %FFM and %FM of total body weight within 1 month postpartum. Our main analysis followed a modified intention-to-treat approach by analyzing all subjects with body composition data available. Univariable and multivariable linear regression models were fitted to compare the intervention and control arms, with adjusted models included baseline maternal age, height, arm fat index, hemoglobin concentration and primiparity, household size, wealth and food security indices, and newborn age (days). At study enrollment, the mean ± SD maternal age was 24.8 ± 6.13 years and body mass index (BMI) was 22.1 ± 3.02 kg/m2 with 7.05% of the mothers were underweight and 11.5% were overweight. Prenatal micronutrient-fortified BEP supplementation resulted in a significantly higher FFMI in mothers (MD (mean difference): 0.45; 95% CI (confidence interval): 0.05, 0.84; P = 0.026) and newborns (MD: 0.28; 95% CI: 0.06, 0.50; P = 0.012), whereas no statistically significant effects were found on FMI. The effect of micronutrient-fortified BEP on maternal FFMI was greater among mothers from food secure households and among those with a better nutritional status (BMI ≥21.0 kg/m2 or mid-upper arm circumference (MUAC) ≥23 cm). Key limitations of the study are the relatively high degree of missing data (approximately 18%), the lack of baseline maternal body composition values, and the lack of follow-up body composition measurements to evaluate any long-term effects.

Conclusions
Micronutrient-fortified BEP supplementation during pregnancy can increase maternal and newborn FFMI, without significant effects on FMI.

Trial registration
ClinicalTrials.gov with identifier NCT03533712.