A Multi-Omics and Human Biomonitoring Approach to Assessing the Effectiveness of Fortified Balanced Energy-Protein Supplementation on Maternal and Newborn Health in Burkina Faso: A Study Protocol.

Fortified balanced energy-protein (BEP) supplementation is a promising intervention for improving maternal health, birth outcomes and infant growth in low- and middle-income countries. This nested biospecimen sub-study aimed to evaluate the physiological effect of multi-micronutrient-fortified BEP supplementation on pregnant and lactating women and their infants. Pregnant women (15-40 years) received either fortified BEP and iron-folic acid (IFA) (intervention) or IFA only (control) throughout pregnancy. The same women were concurrently randomized to receive either a fortified BEP supplement during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention) or the postnatal standard of care, which comprised IFA alone for 6 weeks postpartum (i.e., control). Biological specimens were collected at different timepoints. Multi-omics profiles will be characterized to assess the mediating effect of BEP supplementation on the different trial arms and its effect on maternal health, as well as birth and infant growth outcomes. The mediating effect of the exposome in the relationship between BEP supplementation and maternal health, birth outcomes and infant growth were characterized via biomonitoring markers of air pollution, mycotoxins and environmental contaminants. The results will provide holistic insight into the granular physiological effects of prenatal and postnatal BEP supplementation.

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.

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.

Correction: Fortified balanced energy-protein supplementation during pregnancy and lactation and infant growth in rural Burkina Faso: A 2 × 2 factorial individually randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pmed.1004186.].

Fortified balanced energy-protein supplementation during pregnancy and lactation and infant growth in rural Burkina Faso: A 2 × 2 factorial individually randomized controlled trial.

BACKGROUND: Optimal nutrition is crucial during the critical period of the first 1,000 days from conception to 2 years after birth. Prenatal and postnatal supplementation of mothers with multimicronutrient-fortified balanced energy-protein (BEP) supplements is a potential nutritional intervention. However, evidence on the long-term effects of BEP supplementation on child growth is inconsistent. We evaluated the efficacy of daily fortified BEP supplementation during pregnancy and lactation on infant growth in rural Burkina Faso. METHODS AND FINDINGS: A 2 × 2 factorial individually randomized controlled trial (MISAME-III) was implemented in 6 health center catchment areas in Houndé district under the Hauts-Bassins region. From October 2019 to December 2020, 1,897 pregnant women aged 15 to 40 years with gestational age <21 completed weeks were enrolled. Women were randomly assigned to the prenatal intervention arms receiving either fortified BEP supplements and iron-folic acid (IFA) tablets (i.e., intervention) or IFA alone (i.e., control), which is the standard of care during pregnancy. The same women were concurrently randomized to receive either of the postnatal intervention, which comprised fortified BEP supplementation during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention), or the postnatal control, which comprised IFA alone for 6 weeks postpartum (i.e., control). Supplements were provided by trained village-based project workers under direct observation during daily home visits. We previously reported the effect of prenatal BEP supplementation on birth outcomes. The primary postnatal study outcome was length-for-age z-score (LAZ) at 6 months of age. Secondary outcomes were anthropometric indices of growth (weight-for length and weight-for-age z-scores, and arm and head circumferences) and nutritional status (prevalence rates of stunting, wasting, underweight, anemia, and hemoglobin concentration) at 6 months. Additionally, the longitudinal prevalence of common childhood morbidities, incidence of wasting, number of months of exclusive breastfeeding, and trajectories of anthropometric indices from birth to 12 months were evaluated. Prenatal BEP supplementation resulted in a significantly higher LAZ (0.11 standard deviation (SD), 95% confidence interval (CI) [0.01 to 0.21], p = 0.032) and lower stunting prevalence (-3.18 percentage points (pp), 95% CI [-5.86 to -0.51], p = 0.020) at 6 months of age, whereas the postnatal BEP supplementation did not have statistically significant effects on LAZ or stunting at 6 months. On the other hand, postnatal BEP supplementation did modestly improve the rate of monthly LAZ increment during the first 12 months postpartum (0.01 z-score/month, 95% CI [0.00 to 0.02], p = 0.030), whereas no differences in growth trajectories were detected between the prenatal study arms. Furthermore, except for the trend towards a lower prevalence of underweight found for the prenatal BEP intervention at 6 months (-2.74 pp, 95% CI [-5.65 to 1.17], p = 0.065), no other secondary outcome was significantly affected by the pre- or postnatal BEP supplementation. CONCLUSIONS: This study provides evidence that the benefits obtained from prenatal BEP supplementation on size at birth are sustained during infancy in terms of linear growth. Maternal BEP supplementation during lactation may lead to a slightly better linear growth towards the second half of infancy. These findings suggest that BEP supplementation during pregnancy can contribute to the efforts to reduce the high burden of child growth faltering in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03533712.

Fortified Balanced Energy-Protein Supplementation, Maternal Anemia, and Gestational Weight Gain: A Randomized Controlled Efficacy Trial among Pregnant Women in Rural Burkina Faso.

BACKGROUND: Anemia and suboptimal gestational weight gain (GWG) are associated with adverse maternal and birth outcomes. Limited research indicates that balanced energy-protein (BEP) supplements reduce the incidence of inadequate GWG. OBJECTIVES: We assessed the efficacy of a micronutrient-fortified BEP supplement on the secondary outcomes of anemia, GWG, GWG rate, and GWG in relation to the Institute of Medicine (IOM)'s recommendations, as compared with an iron-folic acid (IFA) tablet. METHODS: We conducted a randomized controlled trial in Burkina Faso, among pregnant women (15-40 y old) enrolled at <21 weeks of gestation. Women received either BEP and IFA (intervention) or IFA (control). Hemoglobin (g/dL) concentrations were measured at baseline and the third antenatal care visit (ANC), whereas maternal weight was measured at baseline and all subsequent ∼7-weekly ANCs. GWG (kg) was calculated as a woman's last weight measurement (at ∼36 weeks of gestation) minus weight at enrollment, whereas GWG rate (kg/wk) was GWG divided by the time between the first and last weight measurements. GWG adequacy (%) was computed as GWG divided by the IOM's recommendation. Binary outcomes included severely inadequate, inadequate, and excessive GWG. Statistical analyses followed the intention-to-treat principle. Linear regression and probability models were fitted for the continuous and binary outcomes, respectively, adjusting for baseline measurements. RESULTS: Women in the BEP group tended to have higher, but nonsignificantly different, GWG (0.28 kg; 95% CI: -0.05, 0.58 kg; P = 0.099). Furthermore, there were no significant differences in prenatal anemia prevalence, GWG rate, GWG adequacy, or incidence of inadequate or excessive GWG. Findings were robust to model adjustments and complete case and per protocol analyses. CONCLUSIONS: This trial does not provide evidence that fortified BEP supplementation reduces maternal anemia or increases GWG, as compared with IFA. In conjunction with the small, but positive, effects of maternal BEP supplementation on birth outcomes, our findings warrant the investigation of additional biochemical and postnatal outcomes.This trial was registered at clinicaltrials.gov as NCT03533712.

Prenatal fortified balanced energy-protein supplementation and birth outcomes in rural Burkina Faso: A randomized controlled efficacy trial.

BACKGROUND: Providing balanced energy-protein (BEP) supplements is a promising intervention to improve birth outcomes in low- and middle-income countries (LMICs); however, evidence is limited. We aimed to assess the efficacy of fortified BEP supplementation during pregnancy to improve birth outcomes, as compared to iron-folic acid (IFA) tablets, the standard of care. METHODS AND FINDINGS: We conducted an individually randomized controlled efficacy trial (MIcronutriments pour la SAnté de la Mère et de l'Enfant [MISAME]-III) in 6 health center catchment areas in rural Burkina Faso. Pregnant women, aged 15 to 40 years with gestational age (GA) <21 completed weeks, were randomly assigned to receive either fortified BEP supplements and IFA (intervention) or IFA (control). Supplements were provided during home visits, and intake was supervised on a daily basis by trained village-based project workers. The primary outcome was prevalence of small-for-gestational age (SGA) and secondary outcomes included large-for-gestational age (LGA), low birth weight (LBW), preterm birth (PTB), gestational duration, birth weight, birth length, Rohrer's ponderal index, head circumference, thoracic circumference, arm circumference, fetal loss, and stillbirth. Statistical analyses followed the intention-to-treat (ITT) principle. From October 2019 to December 2020, 1,897 pregnant women were randomized (960 control and 937 intervention). The last child was born in August 2021, and birth anthropometry was analyzed from 1,708 pregnancies (872 control and 836 intervention). A total of 22 women were lost to follow-up in the control group and 27 women in the intervention group. BEP supplementation led to a mean 3.1 percentage points (pp) reduction in SGA with a 95% confidence interval (CI) of -7.39 to 1.16 (P = 0.151), indicating a wide range of plausible true treatment efficacy. Adjusting for prognostic factors of SGA, and conducting complete cases (1,659/1,708, 97%) and per-protocol analysis among women with an observed BEP adherence ≥75% (1,481/1,708, 87%), did not change the results. The intervention significantly improved the duration of gestation (+0.20 weeks, 95% CI 0.05 to 0.36, P = 0.010), birth weight (50.1 g, 8.11 to 92.0, P = 0.019), birth length (0.20 cm, 0.01 to 0.40, P = 0.044), thoracic circumference (0.20 cm, 0.04 to 0.37, P = 0.016), arm circumference (0.86 mm, 0.11 to 1.62, P = 0.025), and decreased LBW prevalence (-3.95 pp, -6.83 to -1.06, P = 0.007) as secondary outcomes measures. No differences in serious adverse events [SAEs; fetal loss (21 control and 26 intervention) and stillbirth (16 control and 17 intervention)] between the study groups were found. Key limitations are the nonblinded administration of supplements and the lack of information on other prognostic factors (e.g., infection, inflammation, stress, and physical activity) to determine to which extent these might have influenced the effect on nutrient availability and birth outcomes. CONCLUSIONS: The MISAME-III trial did not provide evidence that fortified BEP supplementation is efficacious in reducing SGA prevalence. However, the intervention had a small positive effect on other birth outcomes. Additional maternal and biochemical outcomes need to be investigated to provide further evidence on the overall clinical relevance of BEP supplementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03533712.