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Histidine-Rich Glycoprotein as an Early Biomarker of Preeclampsia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Obstetrisk forskning/Axelsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Obstetrisk forskning/Axelsson)
2011 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 24, no 4, 496-501 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Prediction of preeclampsia is of great interest and the coagulation system as well as the angiogenic pathway is known to be dysfunctional in preeclampsia. Histidine-rich glycoprotein (HRG) is a protein interacting with both these biological systems and the purpose of this prospective, longitudinal cohort study was to analyze whether there is a difference in circulating levels of HRG during pregnancy in women developing preeclampsia compared to normal healthy pregnancies. We furthermore wanted to evaluate whether HRG has the potential of being an early biomarker of preeclampsia. METHODS: A cohort of healthy pregnant women (n = 469) was enrolled at gestational weeks 8-12. Plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37 and analyzed with an enzyme-linked immunosorbent assay. RESULTS: The levels of HRG decreased during pregnancy in all women, but the levels were significantly lower at gestational weeks 10, 25, and 28 in women who later developed preeclampsia than in normal pregnant women (P < 0.05, P < 0.05, and P < 0.05). CONCLUSION: Our data indicates that HRG levels in plasma might be a possible biomarker already in gestational week 10 for prediction of later onset of preeclampsia in a low risk population.

Place, publisher, year, edition, pages
2011. Vol. 24, no 4, 496-501 p.
Keyword [en]
angiogenesis, blood pressure, histidine-rich glycoprotein, hypertension, prediction, preeclampsia
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-144193DOI: 10.1038/ajh.2010.264ISI: 000288823200023PubMedID: 21252863OAI: oai:DiVA.org:uu-144193DiVA: diva2:392820
Available from: 2011-01-28 Created: 2011-01-28 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Pre-eclampsia – Possible to Predict?: A Biochemical and Epidemiological Study of Pre-eclampsia
Open this publication in new window or tab >>Pre-eclampsia – Possible to Predict?: A Biochemical and Epidemiological Study of Pre-eclampsia
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pre-eclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. A predictor of pre-eclampsia would enable intervention, close surveillance and timely delivery, and thereby reduce the negative consequences of the disorder.

The overall aim of this thesis was to study potential predictors of pre-eclampsia by biochemical and epidemiological methods.

Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are regulators of angiogenesis, which is important for placental development. In a prospective and longitudinal study of a low-risk population the Ang-1/Ang-2 ratio was evaluated. The Ang-1/Ang-2 ratio increased during pregnancy in all women but at gestational week 25 and 28 the ratios were significantly lower in women who later developed pre-eclampsia. The relevance of Histidine-rich glycoprotein (HRG), a protein with angiogenic properties, was furthermore evaluated. HRG levels decreased in all women, with significantly lower levels at gestational week 10, 25 and 28 in women who later developed pre-eclampsia. Thus both Ang-1/Ang-2 ratio and HRG may predict pre-eclampsia.

To evaluate the predictive value of HRG in combination with uterine artery Doppler early in pregnancy a study was performed in a high-risk population. The results revealed that the combination was better able to predict preterm pre-eclampsia than each marker individually, with a sensitivity of 91% at a specificity of 62%. 

A possible association between hyperemesis gravidarum and pre-eclampsia, as well as other placental dysfunctional disorders, was investigated. Hyperemesis gravidarum may be caused by high levels of human chorionic gonadotrophin (hCG) and increased levels of hCG in the second trimester is associated with later development of pre-eclampsia. A cohort of all pregnancies in the Swedish medical birth register between 1997 and 2009 was studied. After adjustment for confounding factors an association between hyperemesis gravidarum in the second trimester and preterm pre-eclampsia, placental abruption and infants born small for gestational age was demonstrated.

In conclusion, the ratio of Ang-1/Ang-2 as well as HRG in plasma may be potential predictors of pre-eclampsia. Combination with uterine artery Doppler further increases the predictive value of HRG for preterm pre-eclampsia. Hyperemesis gravidarum in the second trimester may be considered as a clinical risk predictor of pre-eclampsia and other placental dysfunctional disorders.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 835
Keyword
pre-eclampsia, angiopoietin, histidine-rich glycoprotein, hyperemesis gravidarum
National Category
Medical and Health Sciences
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-183394 (URN)978-91-554-8523-8 (ISBN)
Public defence
2012-12-14, Rosénsalen, Akademiska sjukhuset ingång 95, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-11-23 Created: 2012-10-25 Last updated: 2013-02-11Bibliographically approved

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Bolin, MarieÅkerud, Helena

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