Exploring the Antecedents of Neonatal Bowel Perforation

Background: Spontaneous intestinal perforation (SIP) occurs in 3-8% of preterm neonates before they reach two weeks of age. Early, concurrent neonatal use of Indocin and Hydrocortisone is a known association of SIP. Mothers in premature labor often receive Indocin as a tocolytic therapy for early labor. Mothers also receive steroids for the maturation of the fetus before delivery. There is limited data on combined exposures to these medications shortly before birth, and subsequently, in early postnatal life on the effect, these may have on SIP in the infant. Methods: A retrospective review of neonates admitted to a Level III NICU with a birth gestational age < 30 weeks from June 2014 to June 2019 was performed. Data collected included maternal and neonatal demographics, medications, and clinical outcomes. A comparison of proximate prenatal/postnatal Indocin and steroid use between neonates with SIP and those without SIP was examined. Analysis of other potential confounding medication exposure was also considered, including antenatal magnesium, postnatal ibuprofen, and dopamine. Fisher's exact and Student's t-test were used for categorical and continuous variables, respectively.Results: Initial analysis revealed 18 of 354 or approximately 5% of neonates who were born at 30 weeks or less gestational age had SIP. The neonates diagnosed with SIP had a lower gestation and birth weight than those who didn't develop SIP (24±1 vs. 27±2 weeks, p <.0001; 709±162 vs. 980±306 grams, p=.0002). The combined use of maternal Indocin administration (Mat_IN) given within two days of delivery and the administration of neonatal Hydrocortisone (Neo_HC) given in the infant's first week of life was associated with a 12.5 fold increased risk for SIP (see table 1). As 94% of all the infants diagnosed with SIP were less than 26 weeks gestation, a secondary analysis was performed. For all infants less than 26 weeks gestation, 17 of 111 or approximately 15% of neonates had SIP. The combined use of Mat_IN within 48 hours before delivery and the administration of Neo_HC also showed an increase in SIP in this subgroup, 18% vs. 5%. However, this did not reach statistical significance (p >.10). All other confounding medications evaluated did not show an association for SIP (see table 2).Conclusion: Close temporal exposure of antenatal Indocin and postnatal HC was associated with an increased risk of SIP. This association was not significant in the subgroup analysis of <26 weeks GA, but we suggest caution with early postnatal HC use if recent antenatal Indocin was given. Further study into this matter with a larger sample size is necessary.