Mortality and Extrauterine Growth Restriction of Necrotizing Enterocolitis in Very Preterm Infants with Heart Disease: A Multi-Center Cohort Study

Abstract

OBJECTIVE. Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. PATIENTS AND METHODS. This was an observational cohort study that enrolled VPIs (born between 24^+ 0 and 31^+ 6 weeks) admitted to 97 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. RESULTS. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD, 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, death or EUGR were more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20–3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17–1.94) than those without heart diseases. While no significant increased risks in NEC related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41–2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82–1.87), increased risks in EUGR was identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31–4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16–2.01) in survivors. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC. CONCLUSIONS. In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR.