Abstract
OBJECTIVE: Spontaneous intestinal perforation (SIP) occurs commonly in extremely low gestational age newborns (ELGANs; <30 weeks' GA). Early, concurrent neonatal use of indomethacin (Neo_IN) and hydrocortisone (Neo_HC) is a known risk for SIP. Mothers in premature labor often receive indomethacin (Mat_IN) for tocolysis and steroids (Mat_S) for fetal maturation. Coincidentally, ELGANs may receive Neo_IN or Neo_HC within the first week of life. There are limited data on the effect of combined exposures to maternal and neonatal medications. We hypothesized that proximity exposure to these medications may increase the risk of SIP. STUDY DESIGN: We reviewed the medical records of ELGANs from June 2014 to December 2019 at a single level III neonatal intensive care unit. We compared antenatal and postnatal indomethacin and steroid use between neonates with and without SIP. For analysis, chi-square, Student's t-test, Fisher's exact test, and Mann-Whitney U tests were used. RESULTS: Among 417 ELGANs, SIP was diagnosed in 23, predominantly in neonates < 26 weeks' GA (n = 21/126, 16.7%). Risk factors analysis focused on this GA cohort in which SIP was most prevalent. Mat_IN administration within 2 days of delivery increased SIP risk (odds ratio: 3; 95% confidence interval: 1.25-7.94; p = 0.036). Neo_HC was not independently associated with SIP (p = 0.38). A higher proportion of SIP group had close temporal exposure of Mat_IN and Neo_HC compared with the non-SIP group, though not statistically significant (14 vs. 7%, p = 0.24). CONCLUSION: Peripartum Mat_IN was associated with increased risk for SIP in this small study sample. Larger studies are needed to further delineate SIP risk from the interaction of peripartum maternal medication with early postnatal therapies and disease pathophysiology. KEY POINTS: · Perinatal indomethacin is associated with SIP in preterm infants born at less than 26 weeks.. · Temporal proximity of prenatal/postnatal medication exposure matters.. · Indomethacin and Hydrocortisone the risks, benefits, and timing related to SIP..