Association of co-exposure of antenatal steroid and prophylactic Indomethacin with spontaneous intestinal perforation

1. Among preterm and extremely low birth weight neonates, the co-exposure to antenatal steroids and postnatal indomethacin was associated with an increased risk of spontaneous intestinal perforation.

Evidence Level Rating: 2 (Good)

Both antenatal steroids (ANS) and postnatal indomethacin (PI) are utilized in neonatology to reduce the morbidity and mortality associated with intraventricular hemorrhage (IVH) as well as reduce the incidence of severe IVH (sIVH) and patent ductus arteriosus (PDA), respectively, among preterm and extremely low weight neonates. However, there is a concern that exposure to both drugs increases the risk of spontaneous intestinal perforation (SIP). Both sIVH and SIP are quite dangerous. As such, the objective of this study was to evaluate the association between ANS and PI co-exposure and the incidence of SIP among neonates of < 26 weeks gestational age or < 750 g birth weight. 4,720 infants were included for analysis, 87% of whom received ANS and 22.1% of whom received PI. The overall incidence of PI was 4.2%. Among those exposed to ANS, infants who also received PI had higher odds of SIP (aOR 1.61, 95% CI 1.14 to 2.28) compared with no exposure to PI. In a subgroup analysis, recent ANS exposure (≤ 7 days before birth) with PI co-exposure was associated with significantly higher odds of SIP (aOR 1.67, 95% CI 1.15 to 2.43) while latent ANS exposure (> 7 days before delivery) with PI co-exposure was not (aOR 1.24, 95% CI 0.48 to 3.21). Among those receiving latent ANS, there were no differences in the risk of SIP, sIVH, or mortality regardless of PI exposure. Finally, among those not exposed to ANS, receipt of PI was associated with a lower mortality (aOR 0.45, 95% CI 0.28 to 0.73) compared with no receipt of PI. In all, this study suggests that co-exposure of ANS and PI – especially if ANS was received within 7 days before birth – was associated with higher odds of SIP among neonates born at < 26 weeks gestational age or < 750 g birth weight. These data may support the development of personalized approaches for the administration of PI based on whether ANS was received and when.

Click to read the study in the Journal of Pediatrics

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