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

Kandraju, Hemasree, Kanungo, Jaideep, Lee, Kyong-Soon, Daspal, Sibasis, Adie, Mohammad Amin, Dorling, Jon, Ye, Xiang Y., Lee, Shoo K. and Shah, Prakesh S. , Canadian Neonatal Network (CNN) and Canadian Preterm Birth Network (CPTBN) Investigators (2021) Association of co-exposure of antenatal steroid and prophylactic indomethacin with spontaneous intestinal perforation. Journal of Pediatrics, 235, 34-41.e1. (doi:10.1016/j.jpeds.2021.03.012).

Abstract

Objective: to evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at <26 weeks of gestation or <750 g birth weight.

Study design: we conducted a retrospective study of preterm infants admitted to Canadian Neonatal Network units between 2010 and 2018. Infants were classified into 2 groups based on receipt of antenatal steroids; the latter subgrouped as recent (≤7 days before birth) or latent (>7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs.

Results: among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin.

Conclusions: in preterm neonates of <26 weeks of gestation or birth weight <750 g, co-exposure of antenatal steroids and prophylactic indomethacin was associated with SIP, especially if antenatal steroids was received within 7 days before birth. Among those unexposed to antenatal steroids, prophylactic indomethacin was associated with lower odds of mortality.

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Contributors

Author: Jon Dorling

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