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Antenatal steroids, prophylactic indomethacin, and the risk of spontaneous intestinal perforation
Laptook, A. R., Weydig, H., Brion, L. P., Wyckoff, M. H., Arnautovic, T. I., Younge, N., Oh, W., Chowdhury, D., Keszler, M., Das, A., & National Institute of Child Health and Human Development Neonatal Research Network (2023). Antenatal steroids, prophylactic indomethacin, and the risk of spontaneous intestinal perforation. The Journal of Pediatrics, 259, Article 113457. https://doi.org/10.1016/j.jpeds.2023.113457
OBJECTIVE: 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).
STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 grams, born between 1/1/2016 and 12/31/2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multi-level hierarchical generalized linear mixed model after covariate adjustment. This yielded adjusted odds ratios (aOR) and 95% confidence intervals.
RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6,393 infants (93.3%) and IndoD1 was given to 1,863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (p=0.10). 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=0.7). Indo-D1 but not ANS was associated with an increased odds of SIP (aOR 2.1, 1.51-2.91).
CONCLUSION: 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.
