Adjunctive mild controlled hypothermia for moderate necrotizing enterocolitis in very low birth weight infants: a...

Necrotizing enterocolitis (NEC) is a severe condition in preterm infants. Few therapies are available to slow disease progression or reduce the need for surgery. This study aims to assess if mild controlled hypothermia as an adjunctive treatment reduces surgical intervention in preterm infants with NEC. A single-center intervention was conducted from 2019 to 2023 and compared with an external, contemporaneous prospective cohort study. Infants weighing less than 1500 g with moderate NEC were enrolled. One center administered mild hypothermia and served as the intervention cohort. The other seven centers served as contemporaneous controls and provided standard care. The intervention group received mild controlled hypothermia. This targeted a core esophageal temperature of 35.5 °C (± 0.5 °C) for 48 h after NEC diagnosis, in addition to standard medical management. The control group received standard care and maintained normothermia. The primary outcome was the need for surgical intervention due to NEC. All-cause mortality was analyzed using subdistribution hazard ratios (SHR) for competing risks. Inverse probability of treatment weighting (IPTW) adjusted for baseline differences to strengthen causal inference. Among 285 preterm infants, 92 were in the intervention group. This group required fewer surgical interventions (14.13% vs. 46.11%; adjusted relative risk [aRR], 0.30; 95% confidence interval [CI], 0.17-0.53) and showed lower mortality risk (0.59; 95% CI, 0.38-0.93) compared to the control group (n = 193). The incidence of severe neurological outcomes was similar between groups; informative missingness was addressed using deterministic MNAR sensitivity analyses. Conditional inference tree analysis identified hypothermia as the primary protective factor against surgery.

Mild controlled hypothermia may reduce the need for surgical intervention and improve survival rates, indicating its potential as a promising adjunctive therapy.

• Necrotizing enterocolitis (NEC) affects preterm very low birth weight (VLBW) infants with sufficient severity to require surgical intervention. Mortality rates reach 50% in the most vulnerable subgroups. Current medical management has not demonstrated efficacy in halting disease progression or reducing the need for surgery. • Preclinical and pilot studies suggest that adjunctive mild hypothermia (35.5 °C) reduces intestinal inflammation and oxidative stress in NEC. However, no adequately powered multicenter trial has evaluated its clinical effectiveness as an adjunctive therapy.

• Adjunctive mild hypothermia was associated with decreased rates of surgical intervention and reduced all-cause mortality. • Exploratory analyses indicated that adjunctive mild hypothermia was the factor most strongly associated with avoidance of surgery.