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: 1.15–5.57), 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) 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.

KB has served as a consultant and at advisory boards for Acumen, ALZPath, AriBio, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). The other authors have no conflicts of interest to declare.

The work is supported by US National Institutes of Health (NIH) grant R01 AG063849−01 (RDS). KB is supported by the Swedish Research Council (#2017−00915 and #2022−00732), the Swedish Alzheimer Foundation (#AF−930351, #AF−939721, #AF−968270, and #AF−994551), Hjärnfonden, Sweden (#FO2017−0243 and #ALZ2022−0006), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF−agreement (#ALFGBG−715986 and #ALFGBG−965240), the European Union Joint Program for Neurodegenerative Disorders (JPND2019−466−236), the Alzheimer′s Association 2021 Zenith Award (ZEN−21−848495), the Alzheimer′s Association 2022−2025 Grant (SG−23−1038904 QC), La Fondation Recherche Alzheimer (FRA), Paris, France, and the Kirsten and Freddy Johansen Foundation, Copenhagen, Denmark. HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023− 00356; #2022−01018 and #2019−02397), the European Union′s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG−71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809−2016862), the AD Strategic Fund and the Alzheimer′s Association (#ADSF−21−831376−C, #ADSF−21−831381−C, #ADSF−21−831377−C, and #ADSF−24−1284328−C), the Bluefield Project, Cure Alzheimer′s Fund, the Olav Thon Foundation, the Erling−Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022−0270), the European Union′s Horizon 2020 research and innovation programme under the Marie Skłodowska−Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme—Neurodegenerative Disease Research (JPND2021−00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI−1003).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Sydney Local Health District Human Research and Ethics Committee (approval number: 2022/ETH01100).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors