Association of Intrapartum Drugs with Spontaneous Intestinal Perforation: A Single-Center Retrospective Review

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.

Keywords

extremely low birth weight - spontaneous intestinal perforation - indomethacin - hydrocortisone - betamethasone - magnesium - neonate

Contributors' Statement

No outside honorarium, grant, or other forms of payment was provided to anyone to produce the manuscript. Drs. Mantle, Yang, Chan, and Yoder contributed to the conception and design of the study, data collection and analysis, and manuscript preparation; Dr. Judkins contributed to conception and design as well as manuscript review. Ms. Chanthavong contributed to data collection. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Ethical Considerations

The University of Utah institutional review board approved this study with a waiver of parental consent. Trained research staff abstracted the required maternal and neonatal data via electronic medical records. Information was stored on a dual encrypted, password-protected database for analysis.

Financial Disclosures

The authors have no relevant financial relationships to disclose.

Publication History

Received: 06 August 2020

Accepted: 06 October 2021

Publication Date:
19 October 2021 (online)

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