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

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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<.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. What is Already Known Increased sNfL levels are considered a marker of nervous system lesion. Elevated postpartum sNfL levels have been reported in most, but not all, women with MS or pre-eclampsia, without clear evidence of CNS injury. No data are currently available for healthy women with physiological pregnancies (HWwPP). Pregnancy induces significant neuroplasticity in the CNS What This Study Adds This study demonstrates a consistent postpartum increase in sNfL and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) levels in most, but not all, HWwPP. The transient increase of sNfL and sUHCL1 decreases with increasing parity. How This Study Might Affect Research, Practice, or Policy The postpartum increase in sNfL in women with MS not necessarily indicate new CNS lesions and MS disease activity. These findings suggest that the elevated postpartum sNfL and UCHL1 levels may reflect a physiological neuroplasticity induced by pregnancy. This study enables investigation of associations between biomarker levels and postpartum psychiatric disorders.

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