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.