# The association of umbilical cord blood neurofilament light with non‐reassuring fetal status: A prospective observational study

**Authors:** David Zalcberg, Kaitlin Kramer, Emma Payne, Thomas Payne, Shreeya Marathe, Neha Mahajan, Ashly Liu, Jessica Barry, Andrew Duckworth, Mitchell Brooks, Bradley de Vries, Fernando Gonzalez‐Ortiz, Kaj Blennow, Henrik Zetterberg, Adrienne Gordon, Benjamin Moran, Helen J. Manning, Robert D. Sanders

PMC · DOI: 10.1002/ijgo.70421 · International Journal of Gynaecology and Obstetrics · 2025-08-27

## TL;DR

This study explores whether measuring a specific protein in umbilical cord blood can help detect potential brain injuries in newborns.

## Contribution

The study demonstrates that umbilical cord blood neurofilament light (NfL) is a feasible and potentially useful biomarker for non-reassuring fetal status.

## Key findings

- Cord NfL levels were higher in preterm neonates and correlated with cord lactate, pH, and base excess.
- NfL was significantly associated with non-reassuring fetal status, while pH, base excess, and lactate were not.
- Neonates admitted to NICU had higher median NfL levels compared to those not admitted.

## Abstract

Early detection of hypoxic–ischemic encephalopathy (HIE) in neonates is critical. We conducted a pilot cohort study to determine the feasibility of collecting umbilical cord blood samples for neurofilament light (NfL) and to assess the association of NfL with non‐reassuring fetal status and other cord biomarkers. We aimed to address (1) Feasibility of cord NfL sample collection and analysis; (2) Association of NfL with non‐reassuring fetal status (CTG changes and/or documented non‐reassuring fetal status), neonatal intensive care unit (NICU) admission and length of stay; (3) Correlation of NfL with other cord biomarkers.

This was a prospective cohort study performed in a single, large tertiary and quaternary referral hospital. A total of 108 maternal participants consented to donate cord blood. Umbilical cord blood NfL levels were measured via single molecule array (Simoa) analysis.

Cord NfL was higher in preterm neonates and was correlated with cord lactate, pH, and base excess. After controlling for mode of delivery and gestational age, NfL (odds ratio [OR] = 2.29, 95% confidence interval [CI]: 1.15–5.57), but not pH (OR = 0.78, 95% CI: 0.42–1.41), base excess (OR = 0.83, 95% CI: 0.37–1.86), or lactate (OR = 1.06, 95% CI: 0.51–2.12) was associated with non‐reassuring fetal status. NfL levels were higher in neonates admitted to NICU (median [IQR]: 11.3 [7] vs 8.5 [5.1]).

Cord blood NfL analysis was feasible and provided correlates of adverse outcomes. Higher venous cord blood NfL levels were associated with non‐reassuring fetal status. Further research is needed to validate these findings and establish the role of NfL, if any, in clinical practice.

## Linked entities

- **Diseases:** hypoxic–ischemic encephalopathy (MONDO:0006663)

## Full-text entities

- **Genes:** NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}
- **Diseases:** HIE (MESH:D020925)
- **Chemicals:** lactate (MESH:D019344)

## Full text

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## Figures

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## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936647/full.md

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Source: https://tomesphere.com/paper/PMC12936647