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  • Clinical Research Article
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Fetal inflammatory response severity on placental histology identifies neonates at risk for meconium aspiration syndrome

Pediatric Research (2025)Cite this article

Abstract

Background

While fetal hypoxia-ischemia is a known trigger for meconium aspiration syndrome (MAS), many infants develop MAS without it, suggesting other risk factors. We examined the association between MAS and the presence and severity of fetal inflammatory response (FIR) on placental histopathology.

Methods/Study design

A single-center retrospective cohort study of term infants with meconium-stained amniotic fluid (MSAF) born at Parkland Hospital (2010–2018). Maternal and infant demographics and clinical data were recorded. Placental histopathologic evidence of FIR was classified per Amsterdam criteria. MAS was defined as respiratory distress in an infant with MSAF requiring NICU admission and ≥48 hours of respiratory support and/or radiographic findings of MAS.

Results

Among 1,696 term neonates with MSAF, 118 (6.9%) developed MAS. Univariate analysis showed that MAS was associated with post-term delivery, non-reassuring fetal heart patterns, cesarean delivery, thick meconium, low Apgar scores, severe acidosis, and presence of FIR (all P < 0.001). On multivariate analysis, FIR remained significant (adjusted OR 2.50, 95% CI 1.41–4.82). Moderate to severe FIR conferred 5-times higher odds for developing MAS (adjusted OR 5.43, 95% CI 2.83–10.40).

Conclusion

FIR, particularly its severity, is an independent predictor of MAS, highlighting intrauterine inflammation as a key mechanism alongside hypoxia-ischemia.

Impact

  • Fetal Inflammatory Response (FIR) is independently associated with Meconium Aspiration Syndrome (MAS)

  • Increasing severity of FIR confers progressively higher risk of MAS.

  • This is the first study to demonstrate a dose-response relationship between FIR severity on MAS.

  • These observations highlight the role of intrauterine inflammation in MAS pathogenesis and provide new insight into its impact on term neonates.

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Fig. 1
Fig. 2: Severity of fetal inflammatory response is associated with increased incidence of meconium aspiration syndrome.

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Acknowledgements

We wish to thank several people who participated in data collection: Patti J Burchfield, RN, and Pollieanna M Sepulveda, RN.

Funding

This work was supported by Children’s Clinical Research Advisory Council (CCRAC) grant awarded to Dr. Imran N. Mir.

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Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Roberto Gonzalez, Julide Sisman, Manahil Firdaus, Zehra Yusuf, Lina Chalak, Vishal Kapadia & Imran Mir

  2. Parkland Health and Hospital System, Dallas, TX, USA

    Steven Brown

Authors
  1. Roberto Gonzalez
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  2. Steven Brown
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  3. Julide Sisman
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  4. Manahil Firdaus
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  5. Zehra Yusuf
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  6. Lina Chalak
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  7. Vishal Kapadia
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  8. Imran Mir
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Contributions

Imran N. Mir wrote the first version of the manuscript. Steven Brown performed statistical analyses. All authors participated in the study design, data collection, data interpretation, and revision and approval of the final version of the manuscript.

Corresponding author

Correspondence to Imran Mir.

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Competing interests

The authors declare no competing interests.

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The Institutional Review Board of University of Texas Southwestern Medical Center and Parkland Health approved the study and waived the need for individual consent.

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Gonzalez, R., Brown, S., Sisman, J. et al. Fetal inflammatory response severity on placental histology identifies neonates at risk for meconium aspiration syndrome. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04657-y

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