Cerebral biomarkers in neurologic complications of preeclampsia - 20/07/22
, Roxanne Hastie, PhD d, e, Emma Bokström-Rees, MD c, Henrik Zetterberg, MD f, g, h, i, j, Kaj Blennow, MD f, g, Sonja Schell a, Henrik Imberg k, l, Eduard Langenegger, PhD a, Ashley Moodley, MD a, Susan Walker, MD d, e, Stephen Tong, MD d, e, Catherine Cluver, MD a, d, eAbstract |
Background |
There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity.
Objective |
We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin.
Study Design |
In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The 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 with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64–2.88), 2.17-fold higher tau (95% confidence interval, 1.49–3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06–3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92–4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06–5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications (n=31). Moreover, angiogenic markers were higher, but to a lesser extent. Women with hemolysis, elevated liver enzymes, and low platelet count (n=20) demonstrated increased plasma concentrations of neurofilament light (1.64-fold higher; 95% confidence interval, 1.06–2.55), tau (4.44-fold higher; 95% confidence interval, 1.85–10.66), and glial fibrillary acidic protein (1.82-fold higher; 95% confidence interval, 1.32–2.50) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications. There was no difference shown in the angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications for any of the biomarkers. Plasma concentrations of tau and glial fibrillary acidic protein were increased in women with several neurologic complications compared with women with eclampsia only.
Conclusion |
Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preeclampsia.
Le texte complet de cet article est disponible en PDF.Key words : cerebral biomarkers, eclampsia, glial fibrillary acid protein, neurofilament light, prediction, preeclampsia, tau
Plan
| H.Z. has served at scientific advisory boards and/or as a consultant for AbbVie, Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, NervGen, AZTherapies, Cognition Therapeutics, and Red Abbey Labs and has given lectures in symposia sponsored by Cellectricon, Fujirebio, AlzeCure, and Biogen. Furthermore, H.Z. is a cofounder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program. K.B. has served as a consultant or has served at advisory boards for Abcam, Axon, Biogen, Lilly, MagQu, Novartis, and Roche Diagnostics. Furthermore, K.B. is a cofounder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program, all unrelated to the work presented in this article. L.B. is a part of a steering group in a study investigating first-trimester prediction of preeclampsia, where Roche Diagnostics, Thermo Fischer Scientific, and PerkinElmer provide free reagents for placental growth factor. The remaining authors report no conflict of interest. |
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| This study was supported by the Swedish Medical Society, Sweden, Märta Lundqvist Foundation, Sweden, Swedish Foundation for International Cooperation in Research and Higher Education, Sweden, Jane and Dan Olssons Foundation, Sweden, Mercy Perinatal, Australia, the Swedish Research Council (Vetenskapsrådet), Sweden, Center for Clinical Research Dalarna, Sweden, and the Preeclampsia Foundation, USA. L.B. is supported by the Swedish Society for Medical Research, Sweden and the Swedish state under the agreement between the Swedish government and the County Councils (ALF), Sweden. C.C. receives salary support from the Mercy Health Foundation, Australia. R.H. and S.T. receive salary support from the National Health and Medical Research Council of Australia, Australia. H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (grant number 2018-02532), Sweden, the European Research Council (grant number 681712), Europe, the Swedish State Support for Clinical Research (grant number ALFGBG-720931), Sweden, the Alzheimer Drug Discovery Foundation (ADDF; grant number 201809-2016862), USA, the AD Strategic Fund and the Alzheimer’s Association (grant numbers ADSF-21-831376-C, ADSF-21-831381-C, and ADSF-21-831377-C), USA, the Olav Thon Foundation, Sweden, the Erling-Persson Family Foundation, Sweden, the Stiftelsen för Gamla Tjänarinnor, Sweden, the Hjärnfonden (grant number FO2019-0228), Sweden, the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement number 860197 (MIRIADE), Europe, and the UK Dementia Research Institute at the University College London, United Kingdom. K.B. is supported by the Swedish Research Council (grant number 2017-00915), Sweden, the ADDF (grant number RDAPB-201809-2016615), USA, the Swedish Alzheimer Foundation (grant number AF-742881), Sweden, the Hjärnfonden (grant number FO2017-0243), Sweden, the ALF agreement (grant number ALFGBG-715986), Sweden, the European Union Joint Program for Neurodegenerative Disorders (grant number JPND2019-466-236), Europe, the National Institute of Health (grant number 1R01AG068398-01), USA, and the Alzheimer's Association 2021 Zenith Award (grant number ZEN-21-848495). |
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| Cite this article as: Bergman L, Hastie R, Bokström-Rees E, et al. Cerebral biomarkers in neurologic complications of preeclampsia. Am J Obstet Gynecol 2022;227:298.e1-10. |
Vol 227 - N° 2
P. 298.e1-298.e10 - août 2022 Retour au numéro
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