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Prophylactic indomethacin, antenatal betamethasone, and the risk of intestinal perforation in infants <28 weeks’ gestation

Journal of Perinatology volume 43, pages 1252–1261 (2023)Cite this article

Subjects

Abstract

Objective

To determine if intestinal perforations before 14 days (either spontaneous (SIP) or necrotizing enterocolitis-induced) are increased when infants who received antenatal betamethasone shortly before birth are treated with prophylactic indomethacin (PINDO).

Study design

Observational study of 475 infants <28 week’s gestation assigned to either a PINDO-protocol (n = 231) or expectant management protocol (n = 244) during consecutive protocol epochs.

Results

Intestinal perforations before 14 days occurred in 33/475 (7%). In unadjusted and adjusted models, we found no associations between PINDO-protocol and intestinal perforations. PINDO-protocol did not increase intestinal perforations or SIP-alone even when given to infants who received betamethasone <7 or <2 days before delivery. 213/231 (92%) PINDO-protocol infants actually received indomethacin. The results were unchanged when examined just in those who received indomethacin.

Conclusion

In our study, early intestinal perforations and SIP-alone were not increased when PINDO was used by protocol in infants who received antenatal betamethasone shortly before birth.

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Fig. 1: Flow diagram of patient distribution.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the neonatal and pediatric cardiology faculty, fellows, nurse practitioners, nurses, respiratory therapists and dieticians for their excellent care and their commitment to the nursery’s quality improvement projects and its consensus driven protocols.

Funding

This work was supported by a grant from U.S. Public Health Service NHLBI (HL109199) and by gifts from the Clyman Family Foundation. This work was supported by a grant from the U.S. Public Health Service National Heart, Lung, and Blood Institute (HL109199).

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Ronald I. Clyman

  2. Department of Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA

    Ronald I. Clyman

  3. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

    Nancy K. Hills

  4. Department of Neurology, University of California San Francisco, San Francisco, CA, USA

    Nancy K. Hills

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  1. Ronald I. Clyman
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Contributions

RC was the principal investigator of the overall study and was involved with the conceptualization and design of the study, study oversight, funding acquisition, data acquisition and formal analysis, writing of the first draft in addition to performing all 4 of the following tasks: (1) participated in the design of the study, acquired patient data, and submitted IRB proposal. (2) reviewed, revised and edited the manuscript. (3) gave approval to the final version of the manuscript. (4) agreed to be accountable for all aspects of the work. NKH performed the statistical consultation and analyses in addition to performing all 4 of the following tasks: (1) participated in the design of the original protocol and performed statistical analyses. (2) reviewed, revised and edited the manuscript. (3) gave approval to the final version of the manuscript. (4) agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Ronald I. Clyman.

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Competing interests

We have no conflict of interests. Neither of the authors has any potential conflict of interest, real or perceived; Neither of the authors has any financial agreement with any company whose product figures prominently in the manuscript. There are no “sponsors” of this project. And there are no “sponsors” who have had a role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. Dr. Clyman wrote the first draft of the manuscript and no honorarium, grant, or other form of payment was given to anyone to produce the manuscript.

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Clyman, R.I., Hills, N.K. Prophylactic indomethacin, antenatal betamethasone, and the risk of intestinal perforation in infants <28 weeks’ gestation. J Perinatol 43, 1252–1261 (2023). https://doi.org/10.1038/s41372-023-01653-0

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