Necrotizing Enterocolitis (NEC), Very Preterm Infant
Conditions
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.
Interventions
DIETARY_SUPPLEMENTPasteurized 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_SUPPLEMENTPreterm 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_SUPPLEMENTRoutine 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_SUPPLEMENTRescue 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 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).
Sponsors
The Children's Hospital of Zhejiang University School of Medicine
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 14 Days
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival without surgical NEC | 34 weeks corrected gestational age | Survival to 34 weeks corrected gestational age without surgical necrotizing enterocolitis (NEC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Survival: Survival outcome indicators measure the success of enduring life-threatening conditions, eg. survival rate. |
| Medically treated NEC that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Medically treated NEC: Diagnosis of necrotizing enterocolitis that required medical (non-surgical) treatment, such as bowel rest and antibiotic therapy. |
| Treated retinopathy of prematurity (ROP) that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Treated retinopathy of prematurity (ROP): ROP that progressed to a stage requiring medical or surgical intervention, including laser therapy or intravitreal injections. |
| Hearing impairment that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Hearing impairment: Documented hearing loss identified through newborn hearing screening or diagnostic audiology tests, potentially requiring follow-up or intervention. |
| Severe brain injury that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Severe brain injury: Presence of significant brain injury such as Grade III or IV intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) as diagnosed by cranial imaging. |
| Length of hospital stay | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Length of hospital stay: Total number of days from birth until discharge from the hospital. |
| Number of episodes of bloodstream infection that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Number of episodes of bloodstream infection: Total number of confirmed bloodstream infections (positive blood cultures) during the hospital stay. |
| Events that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Number of days of antibiotic treatment: Cumulative number of days the infant received systemic antibiotic therapy during hospitalization. |
| Number of days on parenteral nutrition that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Number of days on parenteral nutrition: Total number of days the infant received intravenous nutritional support due to inability to tolerate full enteral feeds. |
| Number of days of NPO that occurred during hospitalization | From birth until hospital discharge (up to approximately 44 weeks postmenstrual age) | Number of days of NPO: Total number of days the infant was designated "nil per os" (NPO), meaning no enteral feeding was given. |
| Body weight | From birth until 2 years corrected age. | Growth parameters (weight): Measurements of the infant's body weight at 2 years corrected age. |
| Body length | From birth until 2 years corrected age. | Body length: Measurements of the infant's body length at 2 years corrected age. |
| Head circumference | From birth until 2 years corrected age. | Head circumference: Measurements of the infant's head circumference at 2 years corrected age. |
| Parent Report of Children's Abilities-Revised (PARCA-R) assessment | At 2 years corrected age | Survival without moderate to severe cognitive or language impairment. PARCA-R stands for Parent Report of Children's Abilities-Revised. It is a parent completed questionnaire that can be used to assess children's cognitive and language development at 24 months of age. |
Countries
China
Contacts
CONTACTYanping Xu
Outcome results
None listed