Effect of a Fortified Balanced Energy-Protein Supplement on Birth Outcome and Child Growth in Houndé District, Burkina Faso. (MISAME-3)

The 2016 WHO antenatal care guidelines stated that pregnant women in undernourished populations should receive fortified balanced energy-protein (BEP) supplements to reduce the risk of stillbirth and small-for-gestational-age birth. However, acceptable supplements and delivery channels must be determined for different contexts.

The present proposal therefore will 1) perform a formative study to identify the most suitable (acceptability and utilization) BEP supplement for pregnant women in rural Burkina Faso (phase 1) and 2) evaluate the efficacy of this supplement to improve birth weight, fetal and infant growth (phase 2). The nutritional composition of the BEP supplement was established during an expert convening at the BMGF in September 2016. Private sector partners will prepare the supplements in the selected forms with the recommended nutrient composition.

Study Overview

• Status: Completed
• Conditions: Low Birth Weight; Prematurity; Small for Gestational Age at Delivery; Infant Malnutrition
• Intervention / Treatment: Dietary supplement: Fortified balanced energy-protein (BEP) supplement; Dietary supplement: Fe and folic acid supplement

Detailed Description

Pregnancy remains a challenging period in the life of many women in low- and middle-income countries. Maternal mortality remains high and many newborns suffer from premature delivery and /or gestational growth retardation both in length and in weight accumulation.

The 2016 WHO antenatal care guidelines stated that pregnant women in undernourished populations should receive fortified balanced energy-protein (BEP) supplements to reduce the risk of stillbirth and small-for-gestational-age birth. However, acceptable supplements and delivery channels must be determined for different contexts.

The purpose of this study is to assess the efficacy of a fortified BEP supplement for pregnant and lactating women to improve birth weight, fetal and infant growth.

This research includes 2 phases:

• Phase 1 - part 1: Formative research to identify preferred product types of a fortified BEP supplement;
• Phase 1 - part 2: Formative research with a 10-week home-feeding trial to determine the acceptability of a fortified BEP supplement for longer-term consumption.
• Phase 2: A community-based, individually randomized efficacy trial of the fortified BEP food supplement including 1,776 pregnant and lactating women aimed at testing 2 hypothesis: supplementing pregnant and lactating women with a fortified BEP supplement will improve fetal growth; improving fetal growth will have a positive effect on health and growth during infancy.

• Study Type: Interventional
• Enrollment (Actual): 1788
• Phase: Phase 4

Contacts and Locations

Study Locations

• Burkina Faso
  • Tuy
    • Houndé, Tuy, Burkina Faso
      • Houndé district

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 40 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participant age (15-40 years).
• Pregnant as determined by a pregnancy test and confirmed by ultrasound.
• Women who signed the informed consent form (in case of minors the parents or husband signs)

Exclusion Criteria:

• Women planning to leave the area before delivery.
• Women who plan to deliver outside the area.
• Pregnancies with a gestational age > 20 weeks at study inclusion.
• Women with multi-fetal gestation (exclusion from analysis).
• Women who are allergic to peanuts.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fortified BEP supplement; Intervention: Dietary Supplement: Fortified balanced energy-protein (BEP) supplement + iron and folic acid supplement.	Dietary supplement: Fortified balanced energy-protein (BEP) supplement; The product contains the following target nutrients: Total energy: 250-500 kcal per daily serving; Fat content: 10-60% of energy intake; Protein content: 16 g (range 14-18 g) with a Digestible Indispensable Amino Acid Score (DIAAS) of ≥ 0.9; Carbohydrate (CHO) Content: no specific recommendations, relative to fat and protein content.; Trans Fats: <1% energy intake Micronutrients include the following: A, D, E, K, B1 (thiamin), B2 (riboflavin), B3 (niacin), B6 (pyridoxine), B9 (folate), B12 and C; minerals: iron, zinc, iodine, calcium, phosphorous, copper, and selenium. The final composition of macro en micronutrients will be available after the acceptability testing (phase 1) and will be determined by 1) the product type and 2) the preferred taste.
ACTIVE_COMPARATOR: Fe and folic acid; Dietary Supplement: Fe and folic acid supplement.	Dietary supplement: Fe and folic acid supplement; Routine iron and folic acid supplementation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small-for-Gestational-age (SGA)	Incidence of Small-for-Gestational-age (SGA) defined as <10th centile of birthweight for gestational age standard, InterGrowth 21st reference.	within 72h after birth
Length-for-age Z-scores (LAZ)	Mean of Length-for-Age Z-scores (LAZ), WHO multi-country reference.	at 6 months (and 12 months on a subsample)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth weight		within 72h after birth
Birth length		within 72h after birth
Chest circumference		within 72h after birth
Head circumference		within 72h after birth
Mid-upper arm circumference		within 72h after birth
Gestational age		at delivery
Preterm birth	Incidence of preterm birth at <37 weeks of gestation	at delivery
Large-for-gestational age	Defined as a birth weight ≥90th centile intergrowth 21st reference	within 72h after birth
Ponderal or Rohrer's index'	Defined as birth weight/birth length3	within 72 hours after birth
Fetal loss	Fetal death at <24 completed weeks of gestational age	during pregnancy
Stillbirths	Fetal death at ≥ 24 weeks gestational age	during pregnancy
Neonatal mortality	(1) Early neonatal mortality: deaths between birth and ≤ 7 days of life; (2) Neonatal mortality: deaths between birth and ≤28 days of life; (3) Late neonatal mortality deaths between >7 days and ≤28 days of life	between birth and ≤ 28 days of life
Prenatal weight gain	Weight change between study inclusion until just before delivery: total and trimester specific	between study inclusion until just before delivery
Gestational weight change	Difference in maternal weight between maternal weight one month after delivery and maternal weight at study inclusion	between study inclusion until 1 month after delivery
Probable and possible maternal postnatal depression	Measured using the 10-item Edinburgh postnatal depression scale. Probable depression is defined as EPDS>12. Possible depression is defined as EPDS>9 .	(1) at 2 months of child age; (2) at 6 months of child age
Women's minimum and mean dietary diversity score	Measured biweekly using the 10 food group indicator as proposed by FAO. Minimum dietary diversity is defined as having consumed at least 5 food groups over the last 24 hours.	from study inclusion until delivery
Maternal anemia	Hemoglobin concentration <11g/dL	at the third antenatal consultation
Weight-for-Age Z-score	WAZ, calculated using the WHO growth reference	at 6 months of age
Weight-for-Length Z-score	WLZ, calculated using the WHO growth reference	at 6 months of age
Stunting	Length-for-Age Z-score (LAZ) <-2, calculated using the WHO growth reference	at 6 months of age
Wasting	Weight-for-Length Z-score (WLZ) <-2, calculated using the WHO growth reference	at 6 months of age
Underweight	Weight-for-Age Z-score (WAZ) <-2, calculated using the WHO growth reference	at 6 months of age
Incidence of child wasting		over first 6 months of life
Child weight gain	Monthly change in child weight	over first 6 months of life
Monthly change in LAZ		over first 6 months of life
Monthly change in WHZ		over first 6 months of life
Monthly change in WAZ		over first 6 months of life
Monthly change in head circumference		over first 6 months of life
Exclusive breastfeeding	Duration of exclusive breastfeeding	during the first 6 months of life
Child mortality		between birth and 6 months of age
Child morbidity symptoms	Signs include fever, vomiting, diarrhea, cough, difficult breathing, running nose	over first 6 months of life
Child anemia	Hemoglobin concentration <11g/dL	at 6 months of age
Hemoglobin concentration		at 6 months of age
Infant body composition	Sub-sample	first 3 months of life
Maternal body composition	Sub-sample	first 3 months after delivery
Breast milk composition	Sub-sample	between 1-2 and 3-4 months
Relative average telomere length	The umbilical cord blood will be analyzed to verify telomere length using qPCR on a sub-sample. Telomere lengths will be expressed as the ratio of telomere copy number to single-copy gene number (T/S) relative to the mean T/S ratio of the entire sample.	At birth

Collaborators and Investigators

• Sponsor: University Ghent
• Collaborators: University of California, Davis; Bill and Melinda Gates Foundation; Harvard School of Public Health (HSPH); Institut de Recherche en Sciences de la Sante, Burkina Faso; International Food Policy Research Institute; AfricSanté, Burkina Faso
• Investigators: Study Chair: Patrick Kolsteren, Prof. dr., University Ghent; Study Director: Carl Lachat, Prof. dr., University Ghent; Principal Investigator: Katrien W Vanslambrouck, MD, University Ghent; Principal Investigator: Brenda PH de Kok, MSc., University Ghent; Principal Investigator: Lieven F Huybregts, PhD, IFPRI; Principal Investigator: Laeticia Celine Toe, MD MSc., IRSS; Principal Investigator: Sheila Isanaka, Asst. Prof., Harvard School of Public Health (HSPH)

Publications and helpful links

General Publications

• Hanley-Cook G, Toe LC, Tesfamariam K, de Kok B, Argaw A, Compaore A, Ouedraogo M, Dailey-Chwalibog T, Kolsteren P, Lachat C, Huybregts L. Fortified Balanced Energy-Protein Supplementation, Maternal Anemia, and Gestational Weight Gain: A Randomized Controlled Efficacy Trial among Pregnant Women in Rural Burkina Faso. J Nutr. 2022 Oct 6;152(10):2277-2286. doi: 10.1093/jn/nxac171.
• de Kok B, Toe LC, Hanley-Cook G, Argaw A, Ouedraogo M, Compaore A, Vanslambrouck K, Dailey-Chwalibog T, Ganaba R, Kolsteren P, Huybregts L, Lachat C. Prenatal fortified balanced energy-protein supplementation and birth outcomes in rural Burkina Faso: A randomized controlled efficacy trial. PLoS Med. 2022 May 13;19(5):e1004002. doi: 10.1371/journal.pmed.1004002. eCollection 2022 May.
• Hanley-Cook GT, Argaw A, de Kok B, Toe LC, Dailey-Chwalibog T, Ouedraogo M, Kolsteren P, Huybregts L, Lachat C. Seasonality and Day-to-Day Variability of Dietary Diversity: Longitudinal Study of Pregnant Women Enrolled in a Randomized Controlled Efficacy Trial in Rural Burkina Faso. J Nutr. 2022 Sep 6;152(9):2145-2154. doi: 10.1093/jn/nxac104. Erratum In: J Nutr. 2022 Oct 6;152(10):2312.
• de Kok B, Argaw A, Hanley-Cook G, Toe LC, Ouedraogo M, Dailey-Chwalibog T, Diop L, Becquey E, Kolsteren P, Lachat C, Huybregts L. Fortified Balanced Energy-Protein Supplements Increase Nutrient Adequacy without Displacing Food Intake in Pregnant Women in Rural Burkina Faso. J Nutr. 2021 Dec 3;151(12):3831-3840. doi: 10.1093/jn/nxab289.
• Vanslambrouck K, de Kok B, Toe LC, De Cock N, Ouedraogo M, Dailey-Chwalibog T, Hanley-Cook G, Ganaba R, Lachat C, Huybregts L, Kolsteren P. Effect of balanced energy-protein supplementation during pregnancy and lactation on birth outcomes and infant growth in rural Burkina Faso: study protocol for a randomised controlled trial. BMJ Open. 2021 Mar 24;11(3):e038393. doi: 10.1136/bmjopen-2020-038393.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 30, 2019
• Primary Completion (ACTUAL): March 15, 2022
• Study Completion (ACTUAL): March 15, 2022

Study Registration Dates

• First Submitted: April 23, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (ACTUAL): May 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Body Weight; Birth Weight; Malnutrition; Infant Nutrition Disorders; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid
• Other Study ID Numbers: OPP1175213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Share study data with a similar study ongoing in Nepal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No