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Prophylactic indomethacin and the risk of serious pulmonary hemorrhages in preterm infants less than 28 weeks’ gestation

Journal of Perinatology (2024)Cite this article

Subjects

Abstract

Objective

To determine if prophylactic indomethacin (PINDO) decreases serious pulmonary hemorrhages in infants <28 weeks.

Study design

Intention-to-treat analysis of 615 consecutively admitted infants during four alternating protocol-driven epochs of PINDO or expectant patent ductus arteriosus (PDA) management.

Results

41/615 (6.7%) developed serious pulmonary hemorrhage at 2 (1, 3) days (median (IQR)). In unadjusted and adjusted multivariable models, infants born in a PINDO epoch had significantly lower incidences of pulmonary hemorrhage and pulmonary hemorrhage or death before 7 days. There were less moderate/large PDA during PINDO epochs. The associations between PINDO and pulmonary hemorrhage and pulmonary hemorrhage/death were no longer significant when presence of a PDA was included in the analyses. There was no apparent association between PINDO epochs and the incidence of serious intraventricular hemorrhages.

Conclusion

Even though PINDO no longer appears to affect the incidence of sIVH it still is associated with a lower incidence of pulmonary hemorrhage.

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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 Drs. Mark Cocalis, Michael Brook, Anita Moon-Grady, Shabnam Peyvandi, Hythem Nawaytou, and Nicole Cresalia for their expert help in reading and interpreting the echocardiograms, and to the neonatal faculty, fellows, nurses, respiratory therapists, and dieticians for their excellent care and their commitment to the nursery’s quality improvement projects and its consensus driven protocols. This work was supported by a grant from the U.S. Public Health Service National Heart, Lung, and Blood Institute (HL109199).

Funding

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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Contributions

Ronald Clyman 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. Nancy K. Hills 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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Clyman, R.I., Hills, N.K. Prophylactic indomethacin and the risk of serious pulmonary hemorrhages in preterm infants less than 28 weeks’ gestation. J Perinatol (2024). https://doi.org/10.1038/s41372-024-01971-x

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