Preventing Infant Malnutrition With Early Supplementation

Study Overview
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Brief Summary
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Background: Worldwide, more than 50 million children under 5 years of age are wasted (weight-for-length/height Z-score (WLZ) <-2) and over 150 million children under 5 are stunted (length/height-for-age Z-score (LAZ) <-2); such wasting and stunting often begin during infancy.1 Optimal nutrition can prevent wasting and stunting. Exclusive breastfeeding (EBF) is widely recommended by community health workers, doctors and nurses and provides optimal nutrition for most infants. However, early growth faltering is common for infants in low and middle income countries (LMIC) and can both increase an infant's risk of early mortality and also lead to deficits in attained height and weight throughout childhood. Thus research is needed to determine the most efficacious strategy to promote healthy early growth in LMIC. Objective: The proposed study will test the efficacy of early small-volume supplementation (ESVS) for increasing weight-for-age z-score (WAZ) at 1 month of age. Methodology: The PRIMES pilot (Study 3) will be a randomized clinical trial enrolling infants in Guinea-Bissau and Uganda weighing ≥2000g at birth. Infants weighing 2000-2499g at <6 hours of age (n=144; 72 per site) will be randomized on enrollment to one of two groups: 1) Early Small-Volume Supplementation (ESVS intervention group), which consists of up to 59 mL formula administered daily after breastfeeding through 30 days of age followed by EBF through 6 months of age; or 2) frequent exclusive breastfeeding without any food or fluid other than vitamins, minerals and medications (control) through 6 months of age. Infants weighing 2500-3300g at <6 hours of age will be weighed again at 4 days of age; those weighing <2600g at 4 days of age (n=180; 90 per site) will be randomized to the same intervention and control groups. Weight will be measured on all enrolled babies at birth on Day 1 and at 4, 14, 30, 60 and 180 days of age and additional measures including height, MUAC, skinfolds, and hemoglobin will be assessed at other time points. The study's primary outcome will be WAZ at 1 month of age. Secondary outcomes will include WLZ at 1 month of age; WAZ, WLZ and LAZ through 6 months of age; breastfeeding duration and infant intestinal microbiota.

Official Title
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Preventing Infant Malnutrition With Early Supplementation, Aim 3

Conditions
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Wasting, Underweight, Stunting, Breastfeeding, Microbial Colonization

Intervention / Treatment
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* Other: ESVS
* Other: Exclusive breastfeeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infant < 6 hours old Infant birth weight 2000-2885g Mother intends to breastfeed Mother with negative HIV test Mother lives in study catchment area and anticipates availability for all study visits Mother ≥18 years old Exclusion Criteria: Twins and other multiples Infant with known major congenital anomalies including orofacial clefts, neural tube defects or congenital heart defects Infant with WHO newborn and respiratory danger signs present: Not feeding well Convulsions Very fast breathing ≥60 breaths/minute Severe chest indrawing No spontaneous movement Lethargic or unconscious Raised temperature > 37.5 degrees Celsius Hypothermia <35.5 degrees Celsius Any jaundice in first 24 hours of life or yellow palms or soles at any age Head nodding, nasal flaring or grunting Maternal psychiatric or psychosocial barrier to enrollment: Contraindication to breastfeeding at each site as determined by a site's national or sub-national health authorities Mothers unable or unwilling to complete all aspects of the protocol Infant enrolled in another study Mother has had another infant enrolled in PRIMES

Ages Eligible for Study
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Minimum Age: 0 Hours
Maximum Age: 24 Hours

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early, Small-Volume Supplementation (ESVS)<br>Breastfeeding with up to 59 mL formula daily until 30 days of age, followed by recommendation to breastfeed exclusively through 6 months of age | Other: ESVS<br>* Breastfeeding with up to 59-mL formula daily for the first 30 days, followed by exclusive breastfeeding through 6 months of age<br>|
| Active Comparator: Exclusive Breastfeeding<br>Recommendation to breastfeed exclusively for 6 months without any other food or fluid except vitamins, minerals and medications | Other: Exclusive breastfeeding<br>* Breastfeeding exclusively without any other food or fluid except vitamins, minerals and medications through 6 months of age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight-for-age z-score (WAZ) at 30 days of age | WAZ calculated according to WHO Child Growth Standards | 30 days of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight-for-length z-score (WLZ) at 30 days of age | WLZ calculated according to WHO Child Growth Standards | 30 days of age | 
| Weight-for-length z-score (WLZ) at 180 days of age | WLZ calculated according to WHO Child Growth Standards | 180 days of age | 
| Weight-for-length z-score (WLZ) at 365 days of age | WLZ calculated according to WHO Child Growth Standards | 365 days of age | 
| Weight-for-age z-score (WLZ) at 180 days of age | WAZ calculated according to WHO Child Growth Standards | 180 days of age | 
| Weight-for-age z-score (WLZ) at 365 days of age | WAZ calculated according to WHO Child Growth Standards | 365 days of age | 
| Length-for-age z-score (LAZ) at 180 days of age | LAZ calculated according to WHO Child Growth Standards | 180 days of age | 
| Length-for-age z-score (LAZ) at 365 days of age | LAZ calculated according to WHO Child Growth Standards | 365 days of age | 
| Whether or not breastfeeding continues at 180 days of age | Continuation of breastfeeding | 180 days of age | 
| Abundance of B.infantis in intestinal microbiota | Microbiota will be collected in DNA/RNA Shield Fecal Collection Tube containers (Zymo Research, Irvine, CA) and analyzed using 16S rRNA gene profiling | 30 days of age | 
| Abundance of B.infantis in intestinal microbiota | Microbiota will be collected in DNA/RNA Shield Fecal Collection Tube containers (Zymo Research, Irvine, CA) and analyzed using 16S rRNA gene profiling | 180 days of age | 
| Neurodevelopment | Bayley Scales of Infant and Toddler Development, 3rd Edition | 180 days of age | 
| Neurodevelopment | Bayley Scales of Infant and Toddler Development, 3rd Edition | 365 days of age | 
| Brain volume | Low-field MRI | 90 days of age | 
| Brain volume | Low-field MRI | 180 days of age | 
| Brain volume | Low-field MRI | 365 days of age | 
| White matter volume | Conventional MRI | 365 days of age |