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  • Clinical Research Article
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The association of placental pathology and neurodevelopmental outcomes in patients with neonatal encephalopathy

Pediatric Research volume 94, pages 1696–1706 (2023)Cite this article

Abstract

Background

Studies conflict on how acute versus chronic placental pathology impacts outcomes after neonatal encephalopathy from presumed hypoxic-ischemic encephalopathy (HIE). We examine how outcomes after presumed HIE vary by placental pathology categories.

Methods

We performed retrospective chart review for neonates with presumed HIE, regardless of severity, focusing on 50 triads for whom placental specimens were available for re-review. Placentas were categorized as having only acute, any chronic, or no lesions. Primary outcomes included in-hospital morbidity/mortality and long-term neurodevelopmental symptoms. Secondary outcomes assessed neonatal MRI and EEG.

Results

Demographics did not differ between groups. Forty-seven neonates were treated with therapeutic hypothermia. Placental acuity category was not associated with primary or secondary outcomes, but clinical and/or histopathological chorioamnionitis was associated with abnormal EEG background and post-neonatal epilepsy (16.7%, n = 3 with chorioamnionitis versus 0%, n = 0 without chorioamnionitis, p = 0.04).

Conclusions

When grouped by acute, chronic, or absent placental lesions, we observed no association with in-hospital, neurodevelopmental, MRI, or EEG outcomes. When reanalyzed by the presence of chorioamnionitis, we found that chorioamnionitis appeared to be associated with a higher risk of EEG alterations and post-neonatal epilepsy. Despite our limited sample size, our results emphasize the critical role of placental examination for neuroprognostication in presumed HIE.

Impact

  • Neonatal encephalopathy presumed to result from impaired fetal cerebral oxygenation or blood flow is called hypoxic ischemic encephalopathy (HIE).

  • Prior studies link placental pathology to various outcomes after HIE but disagree on the impact of acute versus chronic pathology.

  • Our study determines that neurodevelopmental outcomes, in-hospital outcomes, injury on MRI, and EEG findings in patients with HIE are not differentially associated with acute versus chronic placental pathology.

  • Chorioamnionitis is associated with an increased risk of abnormal EEG patterns and post-neonatal epilepsy.

  • Histopathologic chorioamnionitis without clinical symptoms is common in HIE, emphasizing the crucial role of placental pathology for neuroprognostication.

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Fig. 1: Short-term, long-term, imaging findings, and EEG findings by placental pathology.
Fig. 2: EEG patterns and post-neonatal epilepsy in the presence or absence of chorioamnionitis.

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Data availability

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

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Acknowledgements

The authors would like to thank the study subjects for helping to advance our understanding of this field.

Funding

No targeted funding was obtained to support this study. J.B.R. is supported by NINDS grant 5K12NS098482-05 and a Duke University School of Medicine Strong Start Award.

Author information

Authors and Affiliations

  1. Pediatric Neurology Residency Program, Duke University Medical Center, Durham, NC, USA

    Alexa C. Stone

  2. Department of Pathology, Duke University Medical Center, Durham, NC, USA

    Kyle C. Strickland

  3. Division of Neonatology, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA

    David T. Tanaka

  4. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

    Jennifer B. Gilner

  5. Department of Pediatrics and Population Health Sciences, Duke University School of Medicine, Durham, NC, USA

    Monica E. Lemmon

  6. Division of Neurology, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA

    Jeffrey B. Russ

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Contributions

A.C.S.: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published. K.C.S.: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published. D.T.T.: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published. J.B.G.: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published. M.E.L.: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published. J.B.R.: Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published.

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Correspondence to Jeffrey B. Russ.

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The authors declare no competing interests.

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As determined by the Duke University Institutional Review Board, patient consent was not required for a retrospective chart review study utilizing deidentified patient data.

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Stone, A.C., Strickland, K.C., Tanaka, D.T. et al. The association of placental pathology and neurodevelopmental outcomes in patients with neonatal encephalopathy. Pediatr Res 94, 1696–1706 (2023). https://doi.org/10.1038/s41390-023-02737-5

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