Abstract
Background
To develop a model for prediction of severe intracranial hemorrhage (ICH) or death based on variables from the first 12 h of age and to compare mortality and morbidities with and without exposure to early indomethacin.
Methods
This retrospective cohort study included extreme preterm (220/7−266/7 weeks) infants born at National Institute of Child Health and Human Development Neonatal Research Network sites. Primary outcome was a composite of severe ICH and/or death.
Results
Of 4624 infants, 1827 received early indomethacin. Lower gestation, lack of antenatal steroids exposure, lower 1-min Apgar, male sex, and receipt of epinephrine were associated with severe ICH or death. Early indomethacin was associated with a lower risk of patent ductus arteriosus, bronchopulmonary dysplasia, and higher risk of spontaneous intestinal perforation.
Conclusions
A model for early prediction of severe ICH/death was developed and validated. Early indomethacin was associated with a lower risk of patent ductus arteriosus and bronchopulmonary dysplasia and a higher risk of spontaneous intestinal perforation.
Clinical trial registration
Not applicable.
Impact
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Modern data on severe ICH and neonatal morbidities in relation to prophylactic indomethacin are scarce in the published literature.
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Prophylactic indomethacin was associated with a lower risk of patent ductus arteriosus and bronchopulmonary dysplasia and a higher risk of intestinal perforation.
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A risk estimator for severe intracranial hemorrhage/death was developed in a large cohort of extremely preterm infants.
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The risk estimator developed based on a large cohort of patients provides an estimate of severe intracranial bleeding for an individual infant.
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Funding
This study is supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
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Contributions
S.C.: Developed the protocol, created data collection form, reviewed analysis and drafted first version of the manuscript. G.N.: Contributed to the conception and design, reviewed the protocol, contributed to the analysis, and revised the manuscript critically. A.R.L.: Contributed to the conception and design, reviewed the protocol, contributed to the analysis, and revised the manuscript critically. D.C.: Reviewed the protocol, conducted the data analysis, and revised the manuscript critically. E.F.B.: Contributed to the conception and design, reviewed the protocol, contributed to the analysis, and revised the manuscript critically. N.A.; Contributed to the conception and design, reviewed the protocol, contributed to the analysis, and revised the manuscript critically. W.A.C.: Contributed to the conception and design, reviewed the protocol, contributed to the analysis, and revised the manuscript critically. M.G.: Reviewed the protocol, conducted the data analysis, and revised the manuscript critically. A.D.: Reviewed the protocol, supervised the analysis, and revised the manuscript critically. J.L.T.: Contributed to the conception and design, reviewed the protocol, contributed to the analysis, and revised the manuscript critically. H.H.: Contributed to the conception and design, reviewed the protocol, contributed to the analysis, and revised the manuscript critically. S.S.: Contributed to the conception and design, reviewed the protocol, contributed to the analysis and revised the manuscript critically. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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The Generic Database (GDB) data collection was approved by the institutional review board at each site, with waiver of consent granted at all except 3 sites, which required written or oral parental consent.
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Chawla, S., Natarajan, G., Laptook, A.R. et al. Model for severe intracranial hemorrhage and role of early indomethacin in extreme preterm infants. Pediatr Res 92, 1648–1656 (2022). https://doi.org/10.1038/s41390-022-02012-z
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DOI: https://doi.org/10.1038/s41390-022-02012-z
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