Work

Predicting pre-eclampsia : Angiogenic factors and various forms of human chorionic gonadotropin

Year: 2014
Type: dissertation
Study design: Observational Study
Abstract: Pre-eclampsia, defined as hypertension and proteinuria, causes significant maternal and perinatal complications. It affects about 2-8% of all pregnancies and there is no curative medication. If women at risk could be identified, prevention or, at least, reduction of the complications of pre-eclampsia might be possible. When serum biochemical markers and clinical characteristics have been combined, the prediction of pre-eclampsia has improved. We studied whether hyperglycosylated human chorionic gonadotropin (hCG-h) is useful for identifying women at risk of pre-eclampsia already in the first or second trimester of pregnancy. Concentrations of hCG, hCG-h, pregnancy-associated plasma protein-A (PAPP-A) and the free beta subunit of hCG (hCGβ) in the serum in the first trimester and of placental growth factor (PlGF), soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) and of the angiogenetic factors, angiopoietin-1 (Ang-1), -2 (Ang-2) and their common soluble endothelial cell-specific tyrosine kinase receptor Tie-2 (sTie-2) in the second trimester were studied as predictors of pre-eclampsia. For first trimester screening, 158 women who subsequently developed preeclampsia, 41 with gestational hypertension, 81 with small-for-gestational age (SGA) infants and 427 controls were selected among 12,615 pregnant women who attended for first trimester screening for Down's syndrome. For second trimester screening we used serum samples from 55 women who subsequently developed pre-eclampsia, 21 with gestational hypertension, 30 who were normotensive and gave birth to SGA infants, and 83 controls. For analysis of Ang-1, -2 and sTie-2 at 12-15 and 16-20 weeks of pregnancy, 49 women who subsequently developed preeclampsia, 16 with intrauterine growth restriction (IUGR) and 59 healthy controls were recruited among 3240 pregnant women attending for first trimester screening for Down's syndrome. Another 20 healthy women were recruited at term pregnancy for examination of the concentrations of these markers in maternal and fetal circulation and urine and the amniotic fluid before and after delivery. The proportion of hCG-h out of total hCG(%hCG-h) was lower in the first but not in second trimester in women who subsequently developed pre-eclampsia as compared to controls. In the first trimester, %hCG-h was predictive of pre-eclampsia, especially of early-onset pre-eclampsia (diagnosed before 34 weeks of pregnancy). The predictive power improved when PAPP-A, the mean arterial blood pressure and parity were combined with %hCG-h. When these four variables were used together, 69% of the women who were to develop early-onset pre-eclampsia were identified with a specificity of 90%. The concentrations of circulating Ang-2 during the second trimester were higher and those of PlGF were lower in women who later developed pre-eclampsia. Ang-2 was only 20% sensitive and at 90% specific for predicting pre-eclampsia, but PlGF performed well and was 53% sensitive and 90% specific for predicting early-onset pre-eclampsia. %hCG-h did not provide independent prognostic value in the second trimester. In conclusion, hCG-h is a promising first trimester marker of early-onset preeclampsia. In line with the earlier observations, PlGF is a useful second trimester predictive marker of early-onset pre-eclampsia.
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W1504482061
Cites: 210
Cited by: 1
Related to: 10