Effect of prophylactic indomethacin administration and early feeding on spontaneous intestinal perforation in extremely low-birth-weight infants

OBJECTIVE: To determine the effect of concomitant administration of prophylactic indomethacin and early enteral feeds on the risk of spontaneous intestinal perforation (SIP) in extremely low-birth-weight (ELBW) infants, and to describe the variation in prophylactic indomethacin use in Canada. STUDY DESIGN: A retrospective cohort study of 4268 ELBW infants born at < 30 weeks' gestation admitted to Canadian neonatal units between 2010 and 2014 was conducted. Prophylactic indomethacin (I+ or I-, administered within 24 h) and early feeding (E+ or E-, initiated in the first 2 days) exposures were studied concurrently and independently. The primary outcomes were SIP and death before discharge. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Compared with the I-/E+ reference group (n=1829), infants in I+/E+ (n=285; aOR 2.92, 95% CI 1.41 to 6.08) and I+/E (n=213; aOR 2.84, 95% CI 1.35 to 5.98) groups had higher odds of SIP, whereas those in the I-/E- group had similar odds (n=1941; aOR 1.37, 95% CI 0.88 to 2.14). Odds of SIP were higher in the indomethacin exposed group (I+) compared with the unexposed (I-) group when controlled for early feeding (aOR 2.43, 95% CI 1.41 to 4.19), but not in the early feeding group when controlled for indomethacin. The use of prophylactic indomethacin ranged from 0% usage in 13 sites to 78% use in one site. CONCLUSION: Prophylactic indomethacin was associated with increased odds of SIP independently from early feeding in this cohort; however, early enteral feeding was not associated with SIP. Marked variation in the use of prophylactic indomethacin was identified.