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Journal Article Ahead of print

PubMed: 42190850 DOI: 10.1016/j.bbi.2026.106831

Serum neurofilament light chain increases in healthy postpartum: is it subclinical brain damage or neuroplasticity?

Brain Behav Immun

Authors: Antonio Bertolotto, Paola Valentino, Cecilia Irene Bava, Serena Martire, Simona Malucchi, Lucia Giorgi, Carola Beltratti, Alessia Di Sapio, Luca Marozio

Affiliations

  • Percorso Sclerosi Multipla, Ospedale Koelliker, Corso Galileo Ferraris 245, Torino, Italy; Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, Orbassano, Italy.
  • Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, Orbassano, Italy; Department of Neurology, Regional Referral MS Center and BioBank, San Luigi Gonzaga University Hospital, Regione Gonzole 10, Orbassano (Turin), Italy.
  • Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, Orbassano, Italy.
  • Department of Neurology, Regional Referral MS Center and BioBank, San Luigi Gonzaga University Hospital, Regione Gonzole 10, Orbassano (Turin), Italy.
  • Department of Surgical Sciences, Gynecology and Obstetrics 1, Sant'Anna Hospital, University of Turin, Corso Spezia 60, Turin, Italy.

Abstract

BACKGROUND

Elevated serum neurofilament light chain (sNfL) levels occur postpartum in women with pre-eclampsia or multiple sclerosis (MS), though definitive central nervous system (CNS) injury remains unestablished. Data on sNfL levels in healthy women with physiological pregnancies (HWwPP) are lacking, whereas numerous MRI and histological studies have demonstrated pregnancy-induced neuroplasticity.

METHODS

We collected blood samples from 61 HHwPP at four peripartum time points (-1, +1, +2-5, +6-10 days), including nulliparous, primiparous, and multiparous women. Two additional control groups (19 healthy women at 20-180 days postpartum; 43 healthy women remote from delivery) were studied. Serum levels of NfL, Glial Fibrillary Acidic Protein (GFAP), Tubulin Associated Unit (TAU) protein, and Ubiquitin C-terminal Hydrolase L1 (UCHL1) were analyzed.

RESULTS

sNfL levels doubled on postpartum day 1 (median 19.84; range 5.02-66.19) versus pre-delivery (8.86; 1.88-34.62) (p < 0.001), increasing further at 6-10 days (28.18; 7.61-48.83). sNfL decreased significantly with increasing parity (linear mixed effect model: b = -0.74, 95% CI [-0.620, -0.872], p = 0.000642). This parity effect was also observed for sUCHL1, sGFAP, and sTAU. sUCHL1 increased sharply from median of 24.51 (1.58-170.63) before delivery to 153.69 (11.25-971.81) (p<.001) on postpartum day 1, returning to baseline by days 6-10.

CONCLUSION

HWwPP showed significant postpartum increase in sNfL and sUCHL1, most pronounced in the first pregnancy and diminishing with increasing parity. In women with MS, these elevations should not be attributed solely to new CNS lesions. Further studies must clarify whether this increase indicates subclinical CNS damage or reflects pregnancy-induced neuroplasticity.

MeSH

Pregnancy, Neuronal Plasticity, Serum, Brain, Psychoneuroimmunology, Parity, Postpartum Period