Increased Risk of Necrotizing Enterocolitis in Premature Infants with Patent Ductus Arteriosus Treated with Indomethacin

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Abstract
The authors evaluated the risk of necrotizing enterocolitis (NEC) in very low birth weight infants receiving indomethacin (INDO) to close patent ductus arteriosus (PDA). Controversy exists regarding the best method of managing very low birth weight infants with PDA and whether to employ medical management using INDO or surgical ligation of the ductus. Two hundred fifty-two premature infants with symptomatic PDA were given intravenously INDO 0.2 mg/kg every 12 hours x 3 in an attempt to close the ductus. Patients were evaluated for sex, birth weight, gestational age, ductus closure, occurrence of NEC, bowel perforation, and mortality. There were 135 boys and 117 girls. The PDA closed or became asymptomatic in 224 cases (89%), whereas 28 (11%) required surgical ligation. Ninety infants (35%) developed evidence of NEC after INDO therapy. Fifty-six were managed medically; surgical intervention was required in 34 of 90 cases (37.8%) or 13% of the entire PDA/INDO study group. Bowel perforation was noted in 27 cases (30%). Factors associated with the onset of NEC included gestational age < 28 weeks, birth weight < 1 kg, and prolonged ventilator support. The overall mortality rate was 25.5%, but was higher in infants with NEC versus those without. The highest mortality was noted in perforated NEC cases. The PDA/INDO patients were compared with a control group of 764 infants with similar sex distribution, birth weights, and gestational ages without PDA who did not receive INDO. Necrotizing enterocolitis occurred in 105 of 764 control patients (13.7%), including 13 (12.3%) with perforation. The overall mortality rate of controls was 25%, which was similar to the overall 25.5% mortality rate in the PDA/INDO study group. These data indicate that there is increased risk of NEC and bowel perforation in premature infants with PDA receiving INDO. Mortality was higher in the PDA/INDO group with NEC than those PDA/INDO infants without NEC.