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

• ClinicalTrials.gov Identifier: NCT03533712
• Recruitment Status: Completed
• First Posted: May 23, 2018
• Last Update Posted: March 22, 2022
• Sponsor: University Ghent
• Collaborators: Harvard School of Public Health (HSPH); Institut de Recherche en Sciences de la Sante, Burkina Faso; AfricSanté, Burkina Faso; International Food Policy Research Institute; University of California, Davis; Bill and Melinda Gates Foundation
• Information provided by (Responsible Party): VakgroepLevensmiddelentechnologieVoedselveiligheidGezondheid, University Ghent

Tracking Information

• First Submitted Date: April 23, 2018
• First Posted Date: May 23, 2018
• Last Update Posted Date: March 22, 2022
• Actual Study Start Date: October 30, 2019
• Actual Primary Completion Date: March 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 28, 2019)

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

Original Primary Outcome Measures (submitted: May 22, 2018)

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

Current Secondary Outcome Measures (submitted: February 15, 2021)

• Birth weight [ Time Frame: within 72h after birth ]
• Birth length [ Time Frame: within 72h after birth ]
• Chest circumference [ Time Frame: within 72h after birth ]
• Head circumference [ Time Frame: within 72h after birth ]
• Mid-upper arm circumference [ Time Frame: within 72h after birth ]
• Gestational age [ Time Frame: at delivery ]
• Preterm birth [ Time Frame: at delivery ]
  Incidence of preterm birth at <37 weeks of gestation
• Large-for-gestational age [ Time Frame: within 72h after birth ]
  Defined as a birth weight ≥90th centile intergrowth 21st reference
• Ponderal or Rohrer's index' [ Time Frame: within 72 hours after birth ]
  Defined as birth weight/birth length3
• Fetal loss [ Time Frame: during pregnancy ]
  Fetal death at <24 completed weeks of gestational age
• Stillbirths [ Time Frame: during pregnancy ]
  Fetal death at ≥ 24 weeks gestational age
• Neonatal mortality [ Time Frame: between birth and ≤ 28 days of life ]
  (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
• Prenatal weight gain [ Time Frame: between study inclusion until just before delivery ]
  Weight change between study inclusion until just before delivery: total and trimester specific
• Gestational weight change [ Time Frame: between study inclusion until 1 month after delivery ]
  Difference in maternal weight between maternal weight one month after delivery and maternal weight at study inclusion
• Probable and possible maternal postnatal depression [ Time Frame: (1) at 2 months of child age; (2) at 6 months of child age ]
  Measured using the 10-item Edinburgh postnatal depression scale. Probable depression is defined as EPDS>12. Possible depression is defined as EPDS>9 .
• Women's minimum and mean dietary diversity score [ Time Frame: from study inclusion until delivery ]
  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.
• Maternal anemia [ Time Frame: at the third antenatal consultation ]
  Hemoglobin concentration <11g/dL
• Weight-for-Age Z-score [ Time Frame: at 6 months of age ]
  WAZ, calculated using the WHO growth reference
• Weight-for-Length Z-score [ Time Frame: at 6 months of age ]
  WLZ, calculated using the WHO growth reference
• Stunting [ Time Frame: at 6 months of age ]
  Length-for-Age Z-score (LAZ) <-2, calculated using the WHO growth reference
• Wasting [ Time Frame: at 6 months of age ]
  Weight-for-Length Z-score (WLZ) <-2, calculated using the WHO growth reference
• Underweight [ Time Frame: at 6 months of age ]
  Weight-for-Age Z-score (WAZ) <-2, calculated using the WHO growth reference
• Incidence of child wasting [ Time Frame: over first 6 months of life ]
• Child weight gain [ Time Frame: over first 6 months of life ]
  Monthly change in child weight
• Monthly change in LAZ [ Time Frame: over first 6 months of life ]
• Monthly change in WHZ [ Time Frame: over first 6 months of life ]
• Monthly change in WAZ [ Time Frame: over first 6 months of life ]
• Monthly change in head circumference [ Time Frame: over first 6 months of life ]
• Exclusive breastfeeding [ Time Frame: during the first 6 months of life ]
  Duration of exclusive breastfeeding
• Child mortality [ Time Frame: between birth and 6 months of age ]
• Child morbidity symptoms [ Time Frame: over first 6 months of life ]
  Signs include fever, vomiting, diarrhea, cough, difficult breathing, running nose
• Child anemia [ Time Frame: at 6 months of age ]
  Hemoglobin concentration <11g/dL
• Hemoglobin concentration [ Time Frame: at 6 months of age ]
• Infant body composition [ Time Frame: first 3 months of life ]
  Sub-sample
• Maternal body composition [ Time Frame: first 3 months after delivery ]
  Sub-sample
• Breast milk composition [ Time Frame: between 1-2 and 3-4 months ]
  Sub-sample
• Relative average telomere length [ Time Frame: At birth ]
  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.

Original Secondary Outcome Measures (submitted: May 22, 2018)

• Birth length [ Time Frame: within 72h after birth ]
• Incidence of preterm birth [ Time Frame: at birth ]
  <37 weeks gestation
• Birth weight [ Time Frame: within 72h after birth ]
• Chest circumference [ Time Frame: within 72h after birth ]
• Head circumference [ Time Frame: within 72h after birth ]
• Weight-for-age Z-score [ Time Frame: at 6 months (and 12 months on a subsample) ]
• Weight-for-length Z-score [ Time Frame: at 6 months (and 12 months on a subsample) ]
• Infant body composition [ Time Frame: first 3 months of life ]
• Breast milk composition [ Time Frame: between 1-2 and 3-4 months ]
• Morbidity [ Time Frame: monthly, up to 6 months after delivery (and up to 9 or 12 months on a subsample) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of a Fortified Balanced Energy-Protein Supplement on Birth Outcome and Child Growth in Houndé District, Burkina Faso.
• Official Title: Effect of a Fortified Balanced Energy-Protein Supplement on Birth Outcome and Child Growth in Houndé District, Burkina Faso.

Brief Summary

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.

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
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:

The intervention study is a randomized controlled 2x2 factorial efficacy trial. At study inclusion, eligible pregnant women will be randomly assigned to the prenatal intervention or control group, and randomly assigned to a postnatal intervention or control group. The intervention group will receive daily a fortified BEP supplement to be consumed under supervision for the duration of pregnancy/lactation. Both control and intervention group will receive the standard iron and folic acid tablet through the regular ante natal care program.

Masking: None (Open Label)
Primary Purpose: Prevention

Condition

• Small for Gestational Age at Delivery
• Low Birth Weight
• Prematurity
• Infant Malnutrition

Intervention

• 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.

• Dietary Supplement: Fe and folic acid supplement
  Routine iron and folic acid supplementation.

Study Arms

• Experimental: Fortified BEP supplement
  Intervention: Dietary Supplement: Fortified balanced energy-protein (BEP) supplement + iron and folic acid supplement.
  Intervention: Dietary Supplement: Fortified balanced energy-protein (BEP) supplement
• Active Comparator: Fe and folic acid
  Dietary Supplement: Fe and folic acid supplement.
  Intervention: Dietary Supplement: Fe and folic acid supplement

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. J Nutr. 2022 Oct;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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 21, 2022): 1788
• Original Estimated Enrollment (submitted: May 22, 2018): 1776
• Actual Study Completion Date: March 15, 2022
• Actual Primary Completion Date: March 15, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 15 Years to 40 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Burkina Faso

Administrative Information

• NCT Number: NCT03533712
• Other Study ID Numbers: OPP1175213
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Share study data with a similar study ongoing in Nepal.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code

• Current Responsible Party: VakgroepLevensmiddelentechnologieVoedselveiligheidGezondheid, University Ghent
• Original Responsible Party: Department of Food Technology, Safety and Health, University Ghent, Prof. dr. Patrick Kolsteren
• Current Study Sponsor: University Ghent
• Original Study Sponsor: Same as current

Collaborators

• Harvard School of Public Health (HSPH)
• Institut de Recherche en Sciences de la Sante, Burkina Faso
• AfricSanté, Burkina Faso
• International Food Policy Research Institute
• University of California, Davis
• Bill and Melinda Gates Foundation

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)

• PRS Account: University Ghent
• Verification Date: March 2022