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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Dietary Supplement: Fortified balanced energy-protein (BEP) supplement
* Dietary Supplement: Fe and folic acid supplement


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fortified BEP supplement<br>Intervention: Dietary Supplement: Fortified balanced energy-protein (BEP) supplement + iron and folic acid supplement. | Dietary Supplement: Fortified balanced energy-protein (BEP) supplement<br>* 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.<br>|
| Active Comparator: Fe and folic acid<br>Dietary Supplement: Fe and folic acid supplement. | Dietary Supplement: Fe and folic acid supplement<br>* Routine iron and folic acid supplementation.<br>|

What is the study measuring?
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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 |