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

Abstract

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.

Fig 1. Trial flowchart of the MISAME-III study by the postnatal intervention arms.

BEP, balanced energy–protein supplementation; GA, gestational age; IFA, iron–folic acid tablets; MISAME, MIcronutriments pour la SAnté de la Mère et de l’Enfant.

Fig 2. Monthly changes in LAZ (upper panels) and WLZ (lower panels) by postnatal (left panels) and prenatal (right panels) intervention arms with the dashed lines representing the control group (IFA) and solid lines representing the intervention group (IFA + BEP).

Line graphs represent locally weighted scatterplot smoothing of observed values. Group differences were estimated using mixed-effects models with random intercepts for infant and random slopes for intervention time, with fixed effects including time, quadratic time (for LAZ), intervention group, and time × group interaction adjusted for allocation to the other intervention, clustering indicators (health center and randomization block), and a priori determined prognostic factors (maternal height, BMI, MUAC, hemoglobin, age and gestational age at inclusion, and parity). BEP, balanced energy–protein supplement; BMI, body mass index; CI, confidence interval; ES, regression coefficient; IFA, iron–folic acid; LAZ, length-for-age Z-score; MUAC, mid-upper arm circumference; WLZ, weight-for-length Z-score.

Fig 3. Monthly changes in WAZ (upper panels) and MUAC (lower panels) by postnatal (left panels) and prenatal (right panels) intervention arms with the dashed lines representing the control group (IFA) and solid lines representing the intervention group (IFA + BEP).

Line graphs represent locally weighted scatterplot smoothing of observed values. Group differences were estimated using mixed-effects models with random intercepts for infant and random slopes for intervention time, with fixed effects including time (for WAZ), time spline variables with 6 knots (for MUAC), intervention group, and time × group interaction adjusted for allocation to the other intervention, clustering indicators (health center and randomization block), and a priori determined prognostic factors (maternal height, BMI, MUAC, hemoglobin, age and gestational age at inclusion, and parity). For the spline model of MUAC, group difference was tested by likelihood ratio test comparing a model with and without time × group interaction terms. BEP, balanced energy–protein supplement; BMI, body mass index; CI, confidence interval; ES, regression coefficient; IFA, iron–folic acid; MUAC, mid-upper arm circumference; WAZ, weight-for-age Z-score.

Fig 4. Monthly changes in head circumference by postnatal (left panel) and prenatal (right panel) intervention arms with the dashed lines representing the control group (IFA) and solid lines representing the intervention group (IFA + BEP).

Line graphs represent locally weighted scatterplot smoothing of observed values. Group differences were estimated using mixed-effects models with random intercepts for infant and random slopes for intervention time, with fixed effects including time spline variables with 6 knots, intervention group, and time × group interaction terms adjusted for allocation to the other intervention, clustering indicators (health center and randomization block), and a priori determined prognostic factors (maternal height, BMI, MUAC, hemoglobin, age and gestational age at inclusion, and parity). Group difference was tested by likelihood ratio test comparing a model with and without time × group interaction terms. BEP, balanced energy–protein supplement; BMI, body mass index; IFA, iron–folic acid; MUAC, mid-upper arm circumference.