Dataset Information

Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).

ABSTRACT:

Background

Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors.

Methods

Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole.

Results

Mean maternal age was 30 years, and median gestational age was 30⁺³ weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%, P=0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio's 0.43-0.59), while only esomeprazole inhibited placental sFlt-1 release.

Conclusions

Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.

SUBMITTER: Neuman RI

PROVIDER: S-EPMC9093236 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).

Neuman Rugina I RI Baars Milan D MD Saleh Langeza L Broekhuizen Michelle M Nieboer Daan D Cornette Jérôme J Schoenmakers Sam S Verhoeven Michel M Koch Birgit C P BCP Russcher Henk H van den Berg Sjoerd A A SAA van den Meiracker Anton H AH Visser Willy W Danser A H Jan AHJ

Hypertension (Dallas, Tex. : 1979) 20220328 6

<h4>Background</h4>Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors.<h4>Methods</h4>Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT- ...[more]

PMID: 35341328

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Project description:Background: Aim of the study was a critical assessment of the clinical validity of the prenatal determination of sFlt-1/PlGF for preeclampsia (PE), pregnancy-induced hypertension (PIH), and proteinuria. Our analysis was based on a specificity of 95 % and a sensitivity of 82 % for the prediction of preeclampsia, as described by Elecsys (Roche). Methods: In this retrospective study the ratio of the prenatal antiangiogenic factor sFlt-1 (soluble fms-like tyrosine kinase-1) to the proangiogenic factor PIGF (placental growth factor) was analyzed using the electrochemiluminescence immunoassay of Elecsys (Roche Diagnostics, Mannheim, Germany) in 173 pregnant women. Sixty-three women with PE, 34 women with PIH and 6 women with proteinuria were compared to 72 controls. On average, the sFlt-1/PlGF ratio was determined 8 (controls), 2.4 (PE), 3.2 (PIH) and 4.1 (proteinuria) weeks before delivery. The PE and PIH cases were further subdivided into early (< 34 weeks of gestation) and late (≥ 34 weeks of gestation) onset groups. Statistical data analysis was done using the usual descriptive statistics and logistic regression analysis. ROC curves were calculated, and the sensitivity, specificity, and negative and positive predictive value (NPV, PPV) were estimated for a threshold of 85. Results: Although the specificity of the sFlt-1/PlGF ratio was high for PE, the sensitivity was low (only 59.4 %), thus giving unsatisfying results for PE. The sensitivity only increased to 62.5 % for the early-onset PE group. Intriguingly, a high ratio was detected for the combination of IUGR (intrauterine growth restriction) and PE in the early-onset PE group (8 cases). In the control group, 4 cases exceeded the cut-off value of 85 but showed no clinical signs of PE and the birth was unremarkable. In summary, we found that the sFlt-1/PIGF ratio could not be used as a predictive test for preeclampsia but rather as an indicator for the development and estimation of the severity of PE. Thus, the test is less suitable for the reliable exclusion of PE in routine clinical practice. Recommendation: The determination of the sFlT-1/PlGF ratio is only one element for PE diagnosis in addition to the measurement of blood pressure, proteinuria, ultrasound and Doppler.

Project description:Background There is little knowledge about the significance of extremely high values (>655) for the ratio of sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor). We aim to describe the time-to-delivery interval and maternal and perinatal outcomes when such values are demonstrated while assessing suspected or confirmed placental dysfunction based on clinical or sonographic criteria. Methods and Results A multicenter retrospective cohort study was performed on 237 singleton gestations between 20+0 and 37+0 weeks included at the time of first demonstrating a sFlt-1/PlGF ratio >655. Clinicians were aware of this result, but standard protocols were followed for delivery indication. Main outcomes were compared for women with and without preeclampsia at inclusion. In those with preeclampsia (n=185, of whom 77.3% had fetal growth restriction), severe preeclampsia features and fetal growth restriction in stages III or IV were present in 49.2% and 13.5% cases, respectively, at inclusion and in 77.3% and 28.6% cases, respectively, at delivery. In the group without preeclampsia (n=52, 82.7% had fetal growth restriction), these figures were 0% and 30.8%, respectively, at inclusion and 21.2% and 50%, respectively, at delivery. Interestingly, 28% of women without initial preeclampsia developed it later. The median time to delivery was 4 days (interquartile range: 1-6 days) and 7 days (interquartile range: 3-12 days), respectively (P<0.01). Overall, perinatal mortality was 62.1% before 24 weeks; severe morbidity surpassed 50% before 29 weeks but became absent from 34 weeks. Maternal serious morbidity was high at any gestational age. Conclusions An sFlt-1/PlGF ratio >655 is almost invariably associated with preeclampsia or fetal growth restriction that progresses rapidly. In our tertiary care settings, we observed that maternal adverse outcomes were high throughout gestation, whereas perinatal adverse outcomes diminished as pregnancy advanced.

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Dataset Information

Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).

Background

Methods

Results

Conclusions

Publications

Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1).

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