Effects of Enteral Feeding Regimens on NEC, Mortality, and Neurodevelopment in Very Preterm Infants

Official title

The Effects of Different Enteral Feeding Regimens on Necrotizing Enterocolitis, Mortality, and Neurodevelopment in Very Preterm Infants: A Multicenter Double-Randomized Trial

Overview

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.

Interventions

• Dietary supplement Pasteurized Donor Milk for Insufficient Breastfeeding
  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.
• Dietary supplement Preterm Formula for Insufficient Breastfeeding
  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.
• Dietary supplement Routine fortification
  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
• Dietary supplement Rescue fortification
  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 sepsi

Primary outcome measures

• Survival without surgical NEC [Time frame: 34 weeks corrected gestational age]

Secondary outcome measures (12)

• NEC requiring surgical intervention [Time frame: 34 weeks gestational age]
• Survival [Time frame: 28 days after birth]
• Survival that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Medically treated NEC that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Treated retinopathy of prematurity (ROP) that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Hearing impairment that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Severe brain injury that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Length of hospital stay [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Number of episodes of bloodstream infection that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Events that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Number of days on parenteral nutrition that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]
• Number of days of NPO that occurred during hospitalization [Time frame: From birth until hospital discharge (up to approximately 44 weeks postmenstrual age)]

Eligibility criteria

Inclusion criteria

• Gestational age at birth less than 29 weeks;
• No contraindications to enteral feeding;
• Mother is willing to breastfeed.

Exclusion criteria

• 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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

China · 22 centers

• The First Affiliated Hospital of Guilin Medical University — Guilin
• The Second Affiliated Hospital of Guangxi Medical University — Nanning
• Yulin Maternity and Child Health Care Hospital, Guangxi — Yulin
• The Affiliated Hospital of Guizhou Medical University — Guizhou
• Nanyang Central Hospital — Nanyang
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou
• Yiyang Central Hospital — Yiyang
• Ganzhou Maternal and Child Health Hospital — Ganzhou
• … and 14 more centers

Identifiers

NCT: NCT07045844 · 2025-IRB-0232-P-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗