Serum hypoxia-inducible factor-1α and uterine artery Doppler ultrasound during the first trimester for prediction of preeclampsia

Abstract

The objective of this study was to determine the predictive value of serum hypoxia-inducible factor-1α (HIF-1α) combined with uterine artery Doppler in singleton pregnancy during 11–13+6 weeks of gestation for preeclampsia. This prospective observational study was conducted in singleton pregnant women at 11–13+6 weeks of gestation who visited the King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University for antenatal care between February 2019 and May 2020. Serum HIF-1α levels and uterine artery Doppler ultrasound were performed. Pregnancy outcomes were recorded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these tests at the optimal cut-off values were determined to predict preeclampsia. A total of 385 participants were analyzed. Of these, 31 cases had preeclampsia (8.1%), and 6 cases of them had early-onset preeclampsia (1.6%). Preeclamptic women had significantly higher serum HIF-1α levels than normal pregnant women (median 1315.2 pg/ml vs. 699.5 pg/ml, p < 0.001). There was no difference in the mean pulsatility (PI) of the uterine artery. Serum HIF-1α levels were higher than 1.45 multiple of median for the gestational age as a cut-off value for predicting preeclampsia; the sensitivity, specificity, PPV, and NPV were 66.7%, 71.5%, 17.2%, and 96.2%, respectively. When a combination of abnormal serum HIF-1α levels and abnormal uterine artery Doppler PI (above the 95th percentile) were used as a predictive value to predict preeclampsia, the sensitivity, specificity, PPV, and NPV were 74.2%, 67.2%, 16.6%, and 96.8%, respectively. This study showed that the serum HIF-1α levels with or without uterine artery Doppler at 11–13+6 weeks of gestation were effective in predicting preeclampsia.

Early increase in circulating carbonic anhydrase IX: A potential new predictive biomarker of preeclampsia

“…CAIX was significantly increased ( p < .001) in women at risk who later on (within 2–7 weeks) developed the disease starting from the 28th gestational week. These data are consistent with those that have been already described by our and other groups, suggesting hypoxia may play an important role in PE pathogenesis ( Galbiati et al, 2015 ; Brandão Tenório et al, 2019 ; Tianthong and Phupong, 2021 ). Indeed, in our previous study, increased HIF1A mRNA was the earliest marker found in association with the PE development even before the 28th gestational week ( Galbiati et al, 2015 ).…”

“…The inability of the trophoblasts to reach uterine arteries in women who will develop PE generates hypoxia-induced oxidative stress ( Hu and Zhang, 2021 ) and imbalance of angiogenic factors. Upregulation of HIF1A has been reported in the PE pathogenesis as a main regulator of the cells in response to low oxygen levels ( Tianthong and Phupong, 2021 ; Valsecchi et al, 2022 ). In normoxic conditions, HIF1A is inactivated and degraded; however, in hypoxic conditions, HIF1A regulates the expression of several genes (among which VEGF and CAIX) by binding to the hypoxia-responsive element at the 5′ end to their transcriptional start site with consequent hypoxic upregulation of these genes ( Tianthong and Phupong, 2021 ).…”

“…Upregulation of HIF1A has been reported in the PE pathogenesis as a main regulator of the cells in response to low oxygen levels ( Tianthong and Phupong, 2021 ; Valsecchi et al, 2022 ). In normoxic conditions, HIF1A is inactivated and degraded; however, in hypoxic conditions, HIF1A regulates the expression of several genes (among which VEGF and CAIX) by binding to the hypoxia-responsive element at the 5′ end to their transcriptional start site with consequent hypoxic upregulation of these genes ( Tianthong and Phupong, 2021 ). In this study, we have investigated the relationship between the expression of CAIX and preeclampsia.…”

Defective Uteroplacental Vascular Remodeling in Preeclampsia: Key Molecular Factors Leading to Long Term Cardiovascular Disease

“…Therefore, the efficacy of using maternal serum level of HIF-1α as a predictive marker for preeclampsia has been questioned. A recent prospective study showed that high serum HIF-1α level (above 1.45 MoM) in the first trimester of pregnancy (11–13 +6 weeks of gestation) was related to development of preeclampsia, which requires further confirmation with large-scaled studies [ 82 ].…”

Second-trimester serum high mobility group box-1 and uterine artery Doppler to predict preeclampsia

“…Preeclampsia and poor pregnancy outcomes have been associated with an increase uterine artery Doppler impedance flow or early-diastolic notching waveforms 10 , 11 . However, uterine artery Doppler as a single marker has limited sensitivity and accuracy in predicting preeclampsia, thus, various maternal biochemical markers were combined with uterine artery Doppler to improve diagnostic yields 12 – 15 .…”