Bergman, Lina; Hastie, Roxanne; Bokström-Rees, Emma; Zetterberg, Henrik; Blennow, Kaj; Schell, Sonja; Imberg, Henrik; ... Cluver, Catherine; + view all Bergman, Lina; Hastie, Roxanne; Bokström-Rees, Emma; Zetterberg, Henrik; Blennow, Kaj; Schell, Sonja; Imberg, Henrik; Langenegger, Eduard; Moodley, Ashley; Walker, Susan; Tong, Stephen; Cluver, Catherine; - view fewer (2022) Cerebral biomarkers in neurological complications of preeclampsia. American Journal of Obstetrics and Gynecology 10.1016/j.ajog.2022.02.036. (In press).

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Abstract

BACKGROUND AND OBJECTIVES: There are no tools to accurately predict who is at risk of developing neurological complications of preeclampsia and no objective methods to determine disease severity. We assessed whether plasma levels of the cerebral biomarkers neurofilament light (NfL), tau and glial fibrillary acidic protein (GFAP) could reflect disease severity in various phenotypes of preeclampsia and compared them to the angiogenic biomarkers soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng) . STUDY DESIGN: In this observational study, we included women from the South African PROVE biobank. Plasma samples taken at diagnosis (preeclampsia cases) or at admission for delivery (normotensive controls) were analyzed for concentrations of NfL, tau, GFAP, PlGF, sFlt-1 and sEng. Cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age and parity. RESULTS: Compared to 28 normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of NfL (95% CI 1.64-2.88), 2.17-fold higher tau (1.49-3.16) and 2.77-fold higher GFAP (2.06-3.72). In total 72 women with neurological complications (eclampsia, cortical blindness and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher, 95% CI 1.92-4.65) and GFAP (3.22-fold higher, 95% CI 2.06-5.02) compared to women with preeclampsia without pulmonary edema, HELLP or neurological complications (n=31). Angiogenic markers were also higher but to a lesser extent. Women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (n=20) demonstrated increased plasma concentrations of NfL (1.64-fold higher, 95% CI 1.06-2.55), tau (4.44-fold higher, 95% CI 1.85-10.66) and GFAP (1.82-fold higher, 95% CI 1.32-2.50) compared to women with preeclampsia without pulmonary edema, HELLP or neurological complications . No difference was shown in angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema, HELLP or neurological complications for any of the biomarkers. Plasma concentrations of tau and GFAP were increased in women with several neurological complications vs eclampsia only. CONCLUSIONS: Plasma NfL, GFAP and tau are candidate biomarkers for diagnosis and possibly prediction of cerebral complications of preeclampsia.

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