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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Postnatal Growth Restriction

Intervention / Treatment
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* Other: High-volume breastmilk


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 7 Days

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
Interventional Model 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual-volume breastfeeding (UV Group)<br>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)<br>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<br>* Preterm infants will be given high-volume breastmilk<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breastmilk, hindmilk, high-volume breastfeeding, postnatal growth restriction, preterm