Preventing Infant Malnutrition With Early Supplementation (PRIMES)

Preventing Infant Malnutrition With Early Supplementation, Aim 3

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.

Study Overview

• Status: Completed
• Conditions: Microbial Colonization; Wasting; Stunting; Breastfeeding; Underweight
• Intervention / Treatment: Other: ESVS; Other: Exclusive breastfeeding

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Guinea-Bissau
  • Bissau, Guinea-Bissau
    • International Partnership for Human Development
• Uganda
  • Kampala, Uganda
    • Makerere University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 day (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: University of California, Davis; Bill and Melinda Gates Foundation; Makerere University; University of Aberdeen; International Partnership for Human Development

Publications and helpful links

General Publications

• Ginsburg AS, Braima de Sa A, Nankabirwa V, Co R, Murungi J, Kim MO, Brim R, Namiiro F, Namugga O, Hartigan-O'Connor DJ, Roberts SB, Flaherman V. Randomized controlled trial of early, small-volume formula supplementation among newborns: A study protocol. PLoS One. 2022 Feb 4;17(2):e0263129. doi: 10.1371/journal.pone.0263129. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 28, 2021
• Primary Completion (ACTUAL): January 14, 2022
• Study Completion (ACTUAL): January 31, 2023

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (ACTUAL): January 11, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Nutrition Disorders; Body Weight; Infections; Communicable Diseases; Malnutrition; Thinness; Infant Nutrition Disorders
• Other Study ID Numbers: 19-29405

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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