The association of umbilical cord blood neurofilament light with non-reassuring fetal status: a prospective observational study.

Abstract

Objective: Early detection of hypoxic-ischaemic 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.

Design: Prospective cohort study.

Setting: A single, large tertiary and quaternary referral hospital.

Patients: 108 maternal participants consenting to donate cord blood.

Intervention: Umbilical cord venous blood plasma NfL levels.

Main outcome measures: (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), NICU admission and length of stay; (3) Correlation of NfL with other cord biomarkers.

Results: 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 (OR = 2.29, 95%CI: 1.15 to 5.57), but not pH (OR = 0.78, 95%CI: 0.42 to 1.41), base excess (OR = 0.83, 95%CI: 0.37 to 1.86), or lactate (OR = 1.06, 95%CI: 0.51 to 2.12) was associated with non-reassuring fetal status. NfL levels were higher in neonates admitted to NICU (median (IQR): 11.3 (7) versus 8.5 (5.1)).

Conclusions: 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.

What is already known on this topic: Umbilical cord blood NfL is a promising biomarker of neuronal injury in neonates with overt HIE. Whether cord NfL may improve diagnosis of mild-moderate HIE via identification of in utero hypoxia is unknown.

What this study adds: We found that cord NfL is associated with non-reassuring fetal status, and outperforms other cord biomarkers.

How this study might affect research practice or policy: This study lays the groundwork for future research into the use of cord NfL for HIE diagnosis and risk stratification. It supports ongoing development of a point-of-care scalp NfL assay.