NCT06908239

Milk Temperature Control and Necrotizing Enterocolitis Risk in Extremely Preterm Infants

Milk Temperature Control and Necrotizing Enterocolitis Risk in Extremely Preterm Infants: a Randomized Trial

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 250 (estimated)
• Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University · Academic / Other
• Sex: All
• Age: 24 Weeks – 31 Weeks
• Healthy volunteers: Not accepted

Summary

Necrotizing enterocolitis (NEC) is one of the most common and severe gastrointestinal emergencies during the neonatal period, especially among preterm infants. In high-income countries such as Finland and the USA, the prevalence of NEC ranges from 2% to 16.58% among very preterm infants (VPIs) and from 6.8% to 10.0% among extremely preterm infants (EPIs). According to the 2022 Annual Report of the China Newborn Collaboration Network (CHNN) from 89 tertiary hospitals, the prevalence of NEC was reported at 14.2% among VPIs and EPIs. Up to half of NEC cases in infants require surgical intervention, with 39.1% of VPIs and 44.5% of EPIs needing surgery. Consequently, NEC-related mortality rates vary significantly, ranging from 21.9% to 42.3% in preterm infants weighing less than 1500 grams (equivalent to VPIs) and from 33.0% to 50.5% in those weighing 500-1000 grams (equivalent to EPIs).

Detailed description

Although the pathophysiology of NEC is not fully understood, epidemiological studies strongly suggest a multifactorial cause, involving infection and inflammation, premature birth, hypoxic-ischemia, improper feeding, and cold exposure. As for cold exposure, it encompasses inhaling cold air through the respiratory tract, contact with cold environments through the skin, and consuming cold food through the digestive tract. Such exposure increases the risks of cardiovascular hospitalization, temperature-related mortality, allergic diseases including asthma and atopic dermatitis, and neonatal death. A recent study by Lyu et al. suggested that admission hypothermia is associated with an increased incidence of NEC. However, no research has systematically explored how preventing cold exposure, such as through milk feeding via the digestive tract, could potentially reduce the development of NEC among EPIs/VPIs. Covariates collected using medical records throughout study conduction included maternal age, neonatal sex, birthweight and gestational age at delivery, and weekly weight until discharged. Gestational diabetes mellitus was diagnosed based on a 2-hour 75g three-time-point oral glucose tolerance test was performed at the clinic according to the International Association of Diabetes and Pregnancy Study (IADPSG) criteria adopted by Chinese Obstetrics and Gynecology guidelines between 24 and 28 weeks of gestation. The investigators collected information on clinical diagnosis of hypertension disorders during pregnancy (HDP) from medical records, which was defined by systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥ 90 mm Hg, with positive proteinuria, at any timepoints between week 20 and delivery.Other pregnancy outcomes or complications were also retrieved from the medical databased, such as the admission of antenatal corticoids, placenta previa, premature rupture of the membrane, and intrahepatic cholestasis of pregnancy that were diagnosed based on national guidelines. As for infants, neonatal critical case score (NCIS) were assessed within 24 hours of admission and divided into non-critical group (\>90), critical group (70-90) and extremely critical group (\<70) according to the Chinese Pediatric guidelines. Others neonatal medical conditions during hospitalization were also recorded if diagnosed based on international guidelines, namely small-for-gestational age (SGA), respiratory distress syndrome (RDS) and early onset of sepsis (EOS) within three days after birth. In addition, the days to diagnosis of NEC, length of stay during hospitalization, and cases of surgery among NEC cases were collected from thermostatic feeding and standard feeding groups.

Conditions

• Necrotizing Enterocolitis
• Preterm

Interventions

Type	Name	Description
OTHER	thermostatic feeding	In the thermostatic feeding group (intervention arm), milk or formula was delivered directly into the stomach via an infusion pump (Model 8713030CN, Shenzhen Shengnuo Medical Equipment Co., Ltd., Shenzhen, Guangdong, China) located within the incubator. The initial temperature of the milk was set at 38°C, and naturally decreased to match that of the incubator, maintaining a stable, thermostatic environment until the completion of feeding, as well as the setting and adjustment of the temperature of incubator according to the Chinese Medical Association guidelines
OTHER	control	In the control arm, standard feeding involved delivering breast milk or formula directly into the stomach using an infusion pump (Model 8713030CN) placed on an infusion stand. The initial temperature of the milk or formula was set at 38°C, and the temperature was allowed to naturally decrease to match the ambient air temperature of the NICU until feeding was completed. For both groups, the feeding volume and speed were managed in accordance with the clinical application guidelines for neonatal nutrition support in China.

Timeline

• Start date: 2024-09-01
• Primary completion: 2029-12-31
• Completion: 2029-12-31
• First posted: 2025-04-03
• Last updated: 2025-04-03

Locations

1 site across 1 country: China