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

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.

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.

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.

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.