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Angiopoietin-1/angiopoietin-2 ratio for prediction of preeclampsia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Department of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Department of Obstetrics and Gynaecology, Karlstad, Sweden.
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2009 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 22, no 8, 891-895 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A number of different biophysical and biochemical markers have been proposed as predictors of preeclampsia. Factors involved in the angiogenic balance are suggested as candidate markers. The purpose of this prospective, longitudinal cohort study was to determine whether a ratio between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) can be used to predict preeclampsia in a low-risk population. METHODS: A cohort of healthy pregnant women (n = 469) were enrolled at gestational weeks 8-12. Plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. By using commercially available enzyme-linked immunosorbent assay kits Ang-1 and Ang-2 were analyzed. RESULTS: The median Ang-1/Ang-2 ratio increased during pregnancy in all women, but the ratios were significantly lower at gestational weeks 25 and 28 in women who later developed preeclampsia than in normal pregnant women (1.49 compared to 2.19 and 2.12 compared to 3.54, P < 0.05 and P < 0.05). CONCLUSION: Our data indicate that in a low-risk population of women the Ang-1/Ang-2 ratio in plasma constitutes a possible biomarker for prediction of later onset of preeclampsia.

Place, publisher, year, edition, pages
2009. Vol. 22, no 8, 891-895 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-120865DOI: 10.1038/ajh.2009.97ISI: 000268914800019PubMedID: 19478794OAI: oai:DiVA.org:uu-120865DiVA: diva2:304047
Available from: 2010-03-18 Created: 2010-03-16 Last updated: 2017-12-12Bibliographically 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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