Association of intrapartum drugs to spontaneous intestinal perforation: A single center retrospective review.

ABSTRACT Background: 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 is 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. Design: We reviewed the medical records of ELGANS from June 2014 to December 2019 at a single Level III NICU. We compared antenatal and postnatal indomethacin and steroid use between neonates with and without SIP. Chi-Square, Student’s t-test, Fisher’s Exact test, and Mann-Whitney U tests were used for analysis. Results: Among 417 ELGANs, SIP was diagnosed in 23; predominantly 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 two days of delivery increased SIP risk (OR 3.00, 95%Cl 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 to the non-SIP group, though not statistically significant (14% v. 7%, p=0.24). Conclusions: 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.