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

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 &lt;26 weeks of gestation or &lt;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 (&gt;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 &lt;26 weeks of gestation or birth weight &lt;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.</p