Effects of Enteral Feeding Regimens on NEC, Mortality, and Neurodevelopment in Very Preterm Infants
The Effects of Different Enteral Feeding Regimens on Necrotizing Enterocolitis, Mortality, and Neurodevelopment in Very Preterm Infants: A Multicenter Double-Randomized Trial
1 other identifier
interventional
2,324
1 country
22
Brief Summary
The goal of this clinical trial is to evaluate whether supplementing with pasteurized donor human milk (pHDM) or preterm formula (PTF) when own mother's milk (OMM) is insufficient can improve outcomes in very preterm infants born before 29 weeks of gestation. It also aims to assess whether routine use of human milk fortifiers benefits this population. The main questions it aims to answer are: Does supplementing OMM with pHDM or PTF improve survival without surgery-requiring necrotizing enterocolitis (NEC) by 34 weeks corrected gestational age? Is routine fortification of human milk better than selective fortification based on growth faltering? Researchers will compare: pHDM vs. PTF to see which better supports survival without severe NEC. Routine fortification vs. selective fortification to assess the impact on growth and long-term neurodevelopment. Participants will: Be randomized twice:
- First, within the first week of life to receive either pHDM or PTF when OMM is insufficient
- Second, in the second week of life to receive either routine fortification or selective fortification only if growth faltering occurs Receive feeding and care as per standard clinical practice Complete neurodevelopmental assessment at 2 years corrected age using the PARCA-R tool (no additional study visits required) This multicenter, double-randomized, open-label randomized controlled trial is embedded in routine neonatal care and uses real-world data to assess both short- and long-term outcomes. COLLABORATE-China is being run in partnership with the UK-wide COLLABORATE trial sponsored by Imperial College London.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Mar 2026
Longer than P75 for not_applicable
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 17, 2025
CompletedFirst Posted
Study publicly available on registry
July 1, 2025
CompletedStudy Start
First participant enrolled
March 2, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2030
February 24, 2026
February 1, 2026
2.4 years
June 17, 2025
February 22, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Survival without surgical NEC
Survival to 34 weeks corrected gestational age without surgical necrotizing enterocolitis (NEC)
34 weeks corrected gestational age
Secondary Outcomes (16)
NEC requiring surgical intervention
34 weeks gestational age
Survival
28 days after birth
Survival that occurred during hospitalization
From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)
Medically treated NEC that occurred during hospitalization
From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)
Treated retinopathy of prematurity (ROP) that occurred during hospitalization
From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)
- +11 more secondary outcomes
Study Arms (2)
Pasteurized Donor Milk for Insufficient Breastfeeding
EXPERIMENTALParticipants receive pasteurized donor human milk (pHDM) as supplemental feeding when the clinician determines maternal milk supply is insufficient.
Preterm formula for Insufficient Breastfeeding
EXPERIMENTALParticipants receive preterm formula (PTF) as supplemental feeding when the clinician determines maternal milk supply is insufficient.
Interventions
Randomization 2 will be conducted when the total daily intake of human milk (including own mother's milk \[OMM\] and/or donor pasteurized human milk \[pHDM\] ) reaches between 60-120 mL/kg
Participants receive pasteurized donor human milk (pHDM) as supplemental feeding when the clinician determines maternal milk supply is insufficient. Randomization 1 will occur when the clinician determines that supplemental feeding is required due to insufficient breast milk supply.
Participants receive preterm formula (PTF) as supplemental feeding when the clinician determines maternal milk supply is insufficient. Randomization 1 will occur when the clinician determines that supplemental feeding is required due to insufficient breast milk supply.
Randomization 2 will be conducted: Add fortifiers when the infant meets predefined criteria for growth faltering (Preterm infants exhibit a sustained decline in growth velocity for weight, length, or head circumference, demonstrated by a downward crossing of centiles on growth curves, despite tolerating and consuming at least 180 mL/kg/day of breast milk or formula. Blood urea levels in these infants remain consistently below 1.5 mmol/L, and there are no severe complications such as active sepsis or the need for vasoactive medications to maintain circulatory stability. Chronic sodium depletion has also been ruled out, as this condition alone can lead to growth failure. Additionally, preterm infants are unable to tolerate high-volume feeding of 180 mL/kg/day due to specific reasons, such as severe gastroesophageal reflux or the presence of a high-output stoma following surgical procedures).
Eligibility Criteria
You may qualify if:
- Gestational age at birth less than 29 weeks;
- No contraindications to enteral feeding;
- Mother is willing to breastfeed.
You may not qualify if:
- For Randomization Group 1: If the infant has already received pasteurized human donor milk (pHDM), preterm formula (PTF), or nutritional fortifiers;
- For Randomization Group 2: If the infant is exclusively fed with preterm formula and the mother has no intention to express breast milk;
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
The First Affiliated Hospital of Guilin Medical University
Guilin, Guangxi, China
The Second Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, 530007, China
Yulin Maternity and Child Health Care Hospital, Guangxi
Yulin, Guangxi, 537000, China
The Affiliated Hospital of Guizhou Medical University
Guizhou, Guiyang, 550001, China
Nanyang Central Hospital
Nanyang, Henan, 473000, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
Yiyang Central Hospital
Yiyang, Hunan, China
Ganzhou Maternal and Child Health Hospital
Ganzhou, Jiangxi, China
Peking University First Hospital Ningxia Women and Children's Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital)
Yinchuan, Ningxia, China
Shandong Provincial Maternal and Child Health Care Hospital
Jinan, Shandong, China
Sichuan Provincial Maternal and Child Health Hospital
Chengdu, Sichuan, 610045, China
The Affiliated Hospital of Southwest Medical University
Luzhou, Sichuan, China
People's Hospital of Xinjiang Uygur Autonomous Region
Ürümqi, Xinjiang Uygur Autonomous Region, China
Yongkang Maternity and Child Health Care Hospital
Guli, Zhejiang, 321300, China
Children's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 0571, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Women's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310006, China
Hangzhou Women's Hospital
Hangzhou, Zhejiang, 310008, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016, China
Jiaxing Maternity and Child Health Care Hospital
Jiaxing, Zhejiang, 314000, China
Ningbo Women and Children's Hospital (The Affiliated Women and Children's Hospital of Ningbo University)
Ningbo, Zhejiang, 315012, China
Yiwu Maternity and Child Health Care Hospital (Yiwu Branch of The Children's Hospital, Zhejiang University School of Medicine)
Yiwu, Zhejiang, 322000, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr.
Study Record Dates
First Submitted
June 17, 2025
First Posted
July 1, 2025
Study Start
March 2, 2026
Primary Completion (Estimated)
July 31, 2028
Study Completion (Estimated)
July 31, 2030
Last Updated
February 24, 2026
Record last verified: 2026-02