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Cerebral biomarkers in women with preeclampsia
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. (Obstetrik)ORCID-id: 0000-0001-5202-9428
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.

This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).

In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.

In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).

In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.

In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2017. , s. 98
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1364
Nyckelord [en]
preeclampsia, eclampsia, biomarkers, S100B, NSE, PRES
Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Forskningsämne
Obstetrik och gynekologi
Identifikatorer
URN: urn:nbn:se:uu:diva-322780ISBN: 978-91-513-0057-3 (tryckt)OAI: oai:DiVA.org:uu-322780DiVA, id: diva2:1137872
Disputation
2017-10-20, Gustavianum, Auditorium Minus, Akademigatan 3, 753 10 Uppsala, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2017-09-28 Skapad: 2017-09-01 Senast uppdaterad: 2025-02-11
Delarbeten
1. Plasma levels of S100B during pregnancy in women developing pre-eclampsia
Öppna denna publikation i ny flik eller fönster >>Plasma levels of S100B during pregnancy in women developing pre-eclampsia
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2012 (Engelska)Ingår i: Pregnancy Hypertension, ISSN 2210-7789, E-ISSN 2210-7797, Vol. 2, nr 4, s. 398-402Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective

S100B is suggested to be a peripheral biomarker of central nervous system injury with increased blood–brain barrier permeability. The aim of this study was to investigate if there is a difference in plasma levels of S100B throughout pregnancy between women developing pre-eclampsia and those who did not.

Study design

A nested case-control study within a longitudinal study cohort was performed. Healthy pregnant women were enrolled and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Levels of S100B throughout pregnancy were analyzed with an ELISA assay.

Results

The levels of S100B did not change between gestational weeks 10 and 37 (0.047 vs. 0.052; p = 0.71) in the healthy controls, but the S100B levels increased between corresponding weeks in women who developed pre-eclampsia (0.052 vs. 0.075; p < 0.05). In gestational weeks 33 and 37 women who developed pre-eclampsia had higher levels of S100B than the controls (p = 0.047 and p = 0.010, respectively).

Conclusion

S100B levels increase during pregnancy in women who develop pre-eclampsia and there is an increased S100B level in women who develop pre-eclampsia compared with healthy pregnancies several weeks before clinical symptoms of the disease. The increased amount of plasma S100B in women developing pre-eclampsia might be secondary to cerebral vascular damage and S100B is a potential peripheral biomarker reflecting cerebral involvement in pre-eclampsia.

Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Identifikatorer
urn:nbn:se:uu:diva-185093 (URN)10.1016/j.preghy.2012.03.001 (DOI)000209446000010 ()26105610 (PubMedID)
Forskningsfinansiär
Svenska läkaresällskapetStiftelsen Olle Engkvist Byggmästare
Tillgänglig från: 2012-11-20 Skapad: 2012-11-20 Senast uppdaterad: 2025-02-11Bibliografiskt granskad
2. Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects
Öppna denna publikation i ny flik eller fönster >>Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects
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2014 (Engelska)Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 27, nr 8, s. 1105-1111Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND:

S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.

METHODS:

A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.

RESULTS:

Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).

CONCLUSIONS:

S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.

Nationell ämneskategori
Kardiologi och kardiovaskulära sjukdomar
Identifikatorer
urn:nbn:se:uu:diva-221882 (URN)10.1093/ajh/hpu020 (DOI)000342237900022 ()24610883 (PubMedID)
Tillgänglig från: 2014-04-07 Skapad: 2014-04-07 Senast uppdaterad: 2025-02-10Bibliografiskt granskad
3. Plasma Levels of the Cerebral Biomarker, Neuron-Specific Enolase, are Elevated During Pregnancy in Women Developing Preeclampsia
Öppna denna publikation i ny flik eller fönster >>Plasma Levels of the Cerebral Biomarker, Neuron-Specific Enolase, are Elevated During Pregnancy in Women Developing Preeclampsia
2016 (Engelska)Ingår i: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 23, nr 3, s. 395-400Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objectives: Neuron-specific enolase (NSE) is considered to be a peripheral biomarker of central nervous system injury. The aim of this study was to compare levels of NSE throughout pregnancy, in healthy pregnant women and in women developing preeclampsia. Methods: A nested case-control study within a longitudinal study cohort was performed. Four hundred sixty nine healthy pregnant women were enrolled, and plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. Levels of NSE were analyzed in 16 women with preeclampsia and 36 controls throughout pregnancy with an enzyme-linked immunosorbent assay. Results: In gestational week 37, women who developed preeclampsia had significantly higher plasma levels of NSE than healthy pregnant controls (P < .001). The levels of NSE did not change between gestational weeks 10 and 37 in women who developed preeclampsia, but the levels decreased significantly in healthy pregnant controls (P < .001). Conclusion: In pregnant women developing preeclampsia, the levels of NSE remained high throughout pregnancy, whereas in healthy women, these tended to decline over time, especially at the 2 last time points. The result might be confounded in early pregnancy by extracerebral sources of NSE, such as the corpus luteum. Findings need to be confirmed in a larger prospective study.

Nyckelord
eclampsia, NSE, preeclampsia
Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Identifikatorer
urn:nbn:se:uu:diva-281488 (URN)10.1177/1933719115604732 (DOI)000370719100015 ()26355117 (PubMedID)
Tillgänglig från: 2016-03-30 Skapad: 2016-03-24 Senast uppdaterad: 2025-02-11Bibliografiskt granskad
4. Cerebral Biomarkers in Women With Preeclampsia Are Still Elevated 1 Year Postpartum
Öppna denna publikation i ny flik eller fönster >>Cerebral Biomarkers in Women With Preeclampsia Are Still Elevated 1 Year Postpartum
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2016 (Engelska)Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 29, nr 12, s. 1374-1379Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND There is evidence of cerebral involvement among women with preeclampsia. Levels of the cerebral biomarkers neuron-specific enolase (NSE) and S100B are elevated during pregnancy in women developing preeclampsia. It is although not known if these biomarkers return to normal range postpartum. The aim with this study was to compare levels of S100B and NSE during pregnancy and 1 year postpartum in women who have had preeclampsia to women with normal pregnancies. METHODS This study was a longitudinal study of cases (n = 53) with preeclampsia and controls (n = 58) consisted of normal pregnant women in matched gestational weeks. Plasma samples were collected at inclusion during pregnancy and 1 year postpartum. Plasma samples were analyzed for levels of S100B and NSE by enzyme-linked immunosorbent assays kits. RESULTS Levels of NSE and S100B in women with preeclampsia were higher during pregnancy than in women with normal pregnancies. One year postpartum, women who have had preeclampsia still had a higher median level of both NSE (5.07 vs. 4.28 mu g/l, P < 0.05) and S100B (0.07 vs. 0.06 mu g/l, P < 0.05) compared to women with previous normal pregnancies. High levels of NSE and S100B postpartum remained associated with previous preeclampsia after adjustment for confounding factors. Levels of NSE correlated to S100B during pregnancy and postpartum. CONCLUSIONS Levels of NSE and S100B are still elevated 1 year postpartum in women who have had preeclampsia in contrast to women with previous normal pregnancies. We hypothesize that there might be a persistent cerebral involvement among women with preeclampsia even 1 year postpartum.

Nyckelord
blood pressure, hypertension, Neurological dysfunction, NSE, preeclampsia, S100B
Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Identifikatorer
urn:nbn:se:uu:diva-316434 (URN)10.1093/ajh/hpw097 (DOI)000392732700009 ()27653032 (PubMedID)
Forskningsfinansiär
Svenska läkaresällskapetVetenskapsrådet, 2014-3561 D0277901
Tillgänglig från: 2017-03-01 Skapad: 2017-03-01 Senast uppdaterad: 2025-02-11Bibliografiskt granskad
5. Effect of Experimental Preeclampsia, Seizure and MgSO4 Treatment in a Rat Model on Serum Levels of S100B and Neuron Specific Enolase
Öppna denna publikation i ny flik eller fönster >>Effect of Experimental Preeclampsia, Seizure and MgSO4 Treatment in a Rat Model on Serum Levels of S100B and Neuron Specific Enolase
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nyckelord
eclampsia; neurological dysfunction; neuron specific enolase; preeclampsia; S100B
Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Forskningsämne
Obstetrik och gynekologi
Identifikatorer
urn:nbn:se:uu:diva-328757 (URN)
Konferens
RCOG world congress 2017 20th-22nd of March 2017
Tillgänglig från: 2017-08-31 Skapad: 2017-08-31 Senast uppdaterad: 2025-02-11

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