Impact of Hindmilk on Weight Gain Among Moderate to Very Preterm Infants in Zambia

The primary hypothesis is that very preterm infants between 28 0/7 to 31 6/7 weeks with a birth weight from 1000-1999 grams allocated to the HV breastmilk group (200-240 mL/kg/day) until hospital discharge or 40 weeks' post-menstrual age (PMA), whichever comes first, will have increased growth velocity compared to those given UV breastmilk (140-180 mL/kg/day).

Study Overview

• Status: Completed
• Conditions: Postnatal Growth Restriction
• Intervention / Treatment: Other: High-volume breastmilk

Detailed Description

The proposed study is a non-blinded randomized controlled trial with a 1:1 parallel allocation of infants to higher-volume feedings (200-240 ml/kg/day) or usual-volume feedings (140-180 ml/kg/day) using computer-generated random-block sequences. The study will enrol a total of 214 study participants including 190 preterm infants randomized controlled trial of HV feedings and 24 mothers of enrolled infants and healthcare workers for in-depth interviews. We will also screen mothers to study participants for postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) screening tool.

Study aims are:

Aim 1: To evaluate the impact of high volume (HV) feedings using additionally expressed milk at the end of feeding (hind-milk) vs usual volume (UV) feedings on growth velocity from birth to discharge or 40 weeks' PMA, whichever comes first, among very preterm infants.

Through a 1:1 randomization, the study will enrol 190 preterm infants weighing between 1,000g - 1,999g in both study arms and follow them until hospital discharge or 40 weeks' PMA, whichever comes first.

Aim 2: To evaluate the impact of HV vs UV breastfeeding until 40 weeks' PMA on all-cause neonatal mortality and morbidity (including sepsis, NEC, intestinal perforation, and hypoglycaemia).

All study participants (n=190) will be until 40 weeks' PMA to estimate its impact on all-cause neonatal mortality and morbidity.

Aim 3: To characterize the acceptability, feasibility, and feeding tolerance among HV breastfeeding women and their infants at the hospital and its feasibility by healthcare workers.

A total of 24 mothers and healthcare workers will be interviewed through in-depth interviews (IDIs) to better understand the acceptability of this intervention by the feeding mothers, the feeding tolerance by their newborns, and the feasibility of the same by the healthcare workers.

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Zambia
  • Lusaka, Zambia, 10101
    • University Teaching Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Between 28 0/7 to 31 6/7 weeks of age or weighing between 1000-1999 grams,
• Admitted to the UTH NICU within 24 hours after birth, and
• Infants who have reached feeding volume ≥120 mL/kg/day at time of randomization

Exclusion Criteria:

• Who are deemed unstable by the neonatologist,
• With necrotizing enterocolitis or intestinal perforation
• Known gastrointestinal malformations,
• Major malformations or congenital anomalies, and
• Whose parents do not provide informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Usual-volume breastfeeding (UV Group); Infants will receive cup-feeding (to standardize the volume at each feeding) per standard of care guidelines (SOC: 140-180 mL/kg/day) with volumes adjusted for weight and infant age.
EXPERIMENTAL: High-volume breastfeeding (HV Group); Along with SOC volume provided via cup-feeding, the mother will continue to express and feed the baby hind-milk reaching 240 mL/kg/day with volumes adjusted for weight and infant age (200-240 ml/kg/day).	Other: High-volume breastmilk; Preterm infants will be given high-volume breastmilk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight gain	Average change in weight between enrolment (baseline) up to 40 weeks post-menstrual age (PMA) or hospital discharge, whichever comes first.	Baseline up to 40 weeks PMA.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Head circumference	Average change in head circumference (in centimetres using measuring tape) between enrolment (baseline) and 40 weeks post-menstrual age (PMA) or hospital discharge, whichever comes first.	Baseline up to 40 weeks PMA.
Mid-arm circumference	Average change in mid-arm circumference (in centimetres using measuring tape) between enrolment (baseline) and 40 weeks post-menstrual age (PMA) or hospital discharge, whichever comes first.	Baseline up to 40 weeks PMA.
Length	Average change in length (in centimetres using measuring tape) between enrolment (baseline) and 40 weeks post-menstrual age (PMA) or hospital discharge, whichever comes first.	Baseline up to 40 weeks PMA.
Length of hospital stay	Average change in length of hospital stay between enrolment (baseline) and 40 weeks post-menstrual age (PMA) or hospital discharge, whichever comes first.	Baseline up to 40 weeks PMA.
Characterise acceptability, feasibility, and feeding tolerance by breastfeeding women and their infants	To characterize the acceptability, feasibility, and feeding tolerance among HV breastfeeding women and their infants at the hospital.	Through study completion, on average 8 weeks after enrolment
Characterise feasibility of HV breastfeeding by healthcare workers (HCWs)	To characterize the feasibility of HV breastmilk by mothers to the infants (patients) by HCWs	Through study completion, on average 8 weeks after enrolment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal mortality	Newborn status at 28 days after birth	28 days after birth
Weight at 40 weeks PMA	For infants discharged prior to 40 weeks PMA, their birthweight will be taken at 40 weeks PMA during study exit.	40 weeks PMA
Postpartum Depression	Maternal postpartum depression at at 6-8 weeks postnatally using Edinburgh Postnatal Depression Scale screening tool (scale ranges from 0-30, with 11+ indicative of depressive symptoms)	6-8 weeks postnatal

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Centre for Infectious Disease Research in Zambia; Chiesi Foundation

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 13, 2022
• Primary Completion (ACTUAL): December 28, 2022
• Study Completion (ACTUAL): February 10, 2023

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (ACTUAL): June 3, 2022

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 11, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: preterm; breastmilk; hindmilk; high-volume breastfeeding; postnatal growth restriction
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain
• Other Study ID Numbers: IRB-300007476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study data will be shared upon a reasonable request to the study PI.
• IPD Sharing Time Frame: Data will be available for sharing following publication of study findings (or during submission for publication if requested by the journal)
• IPD Sharing Access Criteria: Following a reasonable request to the study PI.
• 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