Plasma markers of neurological injury are elevated in preeclampsia

Preeclampsia, a medical complication of pregnancy, is associated with central nervous system (CNS) signs and symptoms, such as headache, hyperexcitability, hyperreflexia, visual disturbances, and seizures (referred to as eclampsia). We hypothesized that markers of neurological injury such as plasma neurofilaments comprising light chains (NfL) and phosphorylated heavy chains (pNfH), would be elevated in preeclampsia and could serve as biomarkers of severity of preeclampsia.

We first tested NfL and pNfH in nested case-control study from a third trimester plasma bank from patients who delivered at the Beth Israel Deaconess Medical Center (Boston Cohort, N = 288). We then validated the NfL and pNfH alterations in an independent cohort of women who were evaluated for preeclampsia at another tertiary care hospital in South Chicago (Chicago Cohort, N = 393). Data are presented as median (interquartile range) or proportion, and logistic regression was used to estimate risk ratios (RR) and 95 % confidence intervals (CI).

In the Boston cohort, plasma NfL concentrations were 10.8 (8.2, 15.0) pg/ml in normotensive controls versus 15.9 (10.1, 24.8) in preeclampsia (p = 0.002). Likewise, pNfH concentrations were 92.1 (55.6, 148) pg/ml in controls versus 141.5 (93.9, 212.0) in preeclampsia, respectively (p = 0.0004). The adjusted odds ratio (OR) for the risk of preeclampsia in the highest tertile of control NfL and pNfH concentrations, compared with lowest quartiles, was 3.72 (1.70, 8.17) and 3.99 (1.77, 9.03). Similar findings were replicated in the primarily African-American Chicago cohort (OR for NfL: 4.36 [2.46, 7.70] and pNfH: 2.91 [1.66, 5.13]). The risk of preeclampsia with severe features was highest among women who were in the highest quartile of the control distributions for both biomarkers but not for either biomarker alone (adjusted OR for Boston and Chicago cohorts were 7.56 and 5.78 respectively).

Markers of neurological injury are markedly elevated in preeclampsia in Caucasians and African Americans. Prospective studies are needed to evaluate whether these markers could herald the onset of eclampsia.