Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation

Abstract

To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286weeks or birth weight of 401-1000g, born between January 1, 2016 and December 31, 2019, and surviving >12hours. The primary outcome was SIP through 14days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169hours for durations >168hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5hours (6-81) vs 37.1hours (7-110) for infants with or without SIP, respectively (P=.10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P<.0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P=.7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.