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Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis. J Perinatol 2010 Dec;30(12):786-93



Pubmed ID





OBJECTIVE: To examine the role of indomethacin in neonatal gut injury.

STUDY DESIGN: Infants born at gestational age 23 weeks and with birth weights 400-1200 g were included in this prospective prevalence study of neonatal gut injury. Infants with isolated intestinal perforation (IIP) confirmed at laparotomy or at autopsy or with necrotizing enterocolitis (NEC) were identified. Data were abstracted bi-weekly.

RESULT: Among 992 study infants, 58 infants exposed solely to prenatal indomethacin did not show an increased rate of neonatal gut injury. Any postnatal indomethacin exposure (n=611) increased the odds of IIP (OR 4.17, CI, 1.24-14.08, P=0.02) but decreased the odds of NEC (OR 0.65, CI 0.43-0.97, P=0.04). There was a negative association between the timing of indomethacin-exposure and the odds of developing IIP (OR 0.30, CI 0.11-0.83, P=0.02). Compared with NEC, IIP occurred at an earlier age (P<0.05) and was more common (P<0.05) among infants who received early indomethacin (first dose at <12 h of age) to prevent intraventricular hemorrhage than among infants who were treated with late indomethacin for closure of a patent ductus arteriosus (PDA). Unlike the classic hemorrhagic ischemic lesions of NEC in which large areas of tissue were inflamed or necrotic, the IIP lesions were small and discrete.

CONCLUSION: Early (<12 h) postnatal indomethacin exposure was associated with an increased odds of IIP in very low birth weight infants whereas its later use for closure of a PDA appeared to provide protection against NEC. The paradoxical effect of the timing of indomethacin on IIP versus on NEC may be related to the different pathogeneses of the two diseases. Our findings also suggest that PDA may contribute to NEC.

Author List

Sharma R, Hudak ML, Tepas JJ 3rd, Wludyka PS, Teng RJ, Hastings LK, Renfro WH, Marvin WJ Jr


Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anti-Inflammatory Agents, Non-Steroidal
Cerebral Hemorrhage
Cerebral Ventricles
Drug Administration Schedule
Ductus Arteriosus, Patent
Enterocolitis, Necrotizing
Infant, Extremely Low Birth Weight
Infant, Newborn
Infant, Very Low Birth Weight
Intensive Care Units, Neonatal
Intestinal Perforation
Milk, Human
Odds Ratio
Prenatal Care
Risk Factors
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00