Objective: To examine the role of indomethacin in neonatal gut injury.Study Design: Infants born at gestational age X23 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 ¼ 611) increased the odds of IIP (OR 4.17, CI, 1.24-14.08, P ¼ 0.02) but decreased the odds of NEC (OR 0.65, CI 0.43-0.97, P ¼ 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 ¼ 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.

OBJECTIVE Recent reports have posited a temporal association between blood transfusion with packed red blood cells (BT) and necrotizing enterocolitis (NEC). We evaluated the relationship between BT and NEC among infants at three hospitals who were consented at birth into a prospective observational study of NEC. STUDY DESIGN We used a case–control design to match each case of NEC in our study population of infants born at <33 weeks postmenstrual age (PMA) to one control infant using hospital of birth, PMA, birth weight and date of birth. RESULT The number of transfusions per infant did not differ between 42 NEC cases and their controls (4.0 ± 4.6 vs 5.4 ± 4.1, mean ± s.d., P = 0.063). A matched-pair analysis did not identify an association of transfusion with NEC in either the 48-h or 7-day time periods before the onset of NEC. Stratifying on matched-sets, the Cox proportional hazard model did not identify any difference in the total number of BTs between the two groups (hazard ratio 0.78, 95% confidence interval 0.57 to 1.07, P = 0.11). CONCLUSION In contrast to previous studies, our case–control study did not identify a significant temporal association between BT and NEC. Additional large prospective randomized studies are needed to clarify the relationship between BT and NEC.