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  • Clinical Research Article
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Adverse short- and long-term outcomes among infants with mild neonatal encephalopathy

Pediatric Research volume 94, pages 1003–1010 (2023)Cite this article

A Correction to this article was published on 28 November 2022

This article has been updated

Abstract

Background

Studies in newborns with mild neonatal encephalopathy (mNE) demonstrated normal outcomes, but recent literature suggests otherwise.

Methods

This retrospective cohort study examined inborn infants between 2014 and 2017. Biochemical and clinical characteristics determined the presence of NE and an encephalopathy score categorized infants as Definite or Possible mNE. An Unexposed control group consisted of newborns not meeting the inclusion criteria. Long-term outcomes assessed included cerebral palsy, seizures, developmental disorder, and motor and speech delay. The association of mNE with seizure disorder by 3 years of age was assessed with logistic regression and developmental disorders with Cox proportional hazards models.

Results

Of the 156,501 births, we identified 130 with Definite mNE and 445 with Possible mNE (0.8 and 2.8 per 1000 births, respectively). Both groups had significantly higher rates of any developmental disorder and motor and speech delay when compared to the Unexposed (p < 0.05, except for p = 0.07 for motor delay in the Possible NE group). The Definite mNE group had higher rates of developmental disorder and motor and speech delay when compared to the Unexposed with hazard ratios (95% CI) 2.0 (1.2–3.2), 3.7 (1.5–8.8), and 2.1 (1.3–3.5), respectively.

Conclusions

An estimate of short- and long-term consequences of mNE suggests that there may be a higher risk of adverse outcome.

Impact

  • Infants with mild NE are at significant risk for adverse short- and long-term outcomes. The risk of having an abnormal long-term outcome at 3 years of age were doubled in the mild NE group compared to the Unexposed group.

  • Randomized clinical trials are needed as neuroprotective strategies may mitigate these.

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Fig. 1: Enhanced infant neurologic exam for encephalopathy score (E-score) assessment.
Fig. 2: Criteria for subject classification,
Fig. 3: Consort flow diagram.

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Data availability

A deidentified analytic dataset with an accompanying data dictionary used in this study could be shared with qualified researchers who request the data to replicate the results shown in this article given approval by the Kaiser Foundation Research Institute Human Subjects Committee and by the Human Subjects Committee at the institutions requesting the data and a signed data sharing agreement.

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Acknowledgements

We would like to acknowledge the important contributions of Abhinav Kareddy, University of California, Los Angeles (Redcap Database set-up, statistical analysis, and review of manuscript). We would like to acknowledge the important contributions of William E Benitz MD Stanford University, Palo Alto.

Funding

This study was supported by Kaiser Permanente Northern California (KPNC) Central Research Committee Community Benefit Grant.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Kaiser Permanente East Bay, Walnut Creek, CA, USA

    Vishnu-Priya Akula

  2. Kaiser Permanente Northern California Residency Program, Oakland, CA, USA

    Achyuth Sriram & Matthew Cranshaw

  3. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    Sherian Xu, Eileen Walsh & Michael W. Kuzniewicz

  4. Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA

    Krisa Van Meurs

  5. Department of Pediatrics, Kaiser Permanente, San Francisco, CA, USA

    Michael W. Kuzniewicz

Authors
  1. Vishnu-Priya Akula
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Contributions

V.-P.A. designed the study, designed the data collection tool, and prepared and revised the manuscript. A.S. collected data, carried out the initial analyses, and reviewed the manuscript. E.W. study design and coordinated data collection. S.X. data analysis and collection tool. K.V.M. designed the study, reviewed, and revised the manuscript. M.C. data collection, analysis, reviewed and revised the manuscript. M.K. designed the study, data analysis, and reviewed and revised the manuscript.

Corresponding author

Correspondence to Vishnu-Priya Akula.

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The original online version of this article was revised: The author’s name Michael W. Kuzniewicz was incorrectly given as ‘Michael Kuzniwiecz’.

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Akula, VP., Sriram, A., Xu, S. et al. Adverse short- and long-term outcomes among infants with mild neonatal encephalopathy. Pediatr Res 94, 1003–1010 (2023). https://doi.org/10.1038/s41390-022-02249-8

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