Abstract 28: Omeprazole Administration To Women With Preterm Preeclampsia: Effects On Circulating Soluble Fms-like Tyrosine Kinase-1, Placental Growth Factor And Endothelin-1 Secretion.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Rugina I Neuman ◽  
Willy Visser ◽  
Jan H Danser
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Gestational Age ◽  
Controlled Trial ◽  
Placental Growth Factor ◽  
Potential Treatment ◽  
Perinatal Complications ◽  
Longitudinal Course ◽  
The Difference ◽  
Circulating Levels

Low soluble Fms-like tyrosine kinase (sFlt-1) has been reported in women with suspected or confirmed preeclampsia (PE) coincidentally using proton pump inhibitors (PPIs), suggesting a role for these agents as potential treatment for PE. Here, we examined whether administration of omeprazole to women with PE could acutely reduce their circulating levels of sFlt-1 or enhance their placental growth factor (PlGF) concentrations. We performed a randomized controlled trial in which women (≥ 18 years) with confirmed preeclampsia and a gestational age between 20 +0 and 34 +6 weeks were allocated to receive 40mg omeprazole once daily or no omeprazole. Blood was collected at baseline and days 1,2,4,8 followed by twice-weekly until delivery. Primary outcome was specified as the difference in sFlt-1 or PlGF 4 days after omeprazole initiation compared to the non-omeprazole group. Secondary outcomes were defined as between-group differences in longitudinal course of sFlt-1 and PlGF and pregnancy outcomes. Between Dec 2018 and June 2021, 50 women with PE were randomized, of which 40 women remained pregnant after 4 days. Mean maternal age was 30 years, and median gestational age was 31 weeks. Baseline sFlt-1 levels did not differ between non-omeprazole (n=20) and omeprazole group (n=20) (10743 vs. 7110pg/mL, p=0.11), neither did the levels of PlGF (p=0.14). After 4 days, sFlt-1 levels remained similar in women receiving omeprazole compared to women not receiving omeprazole (8364 vs. 13017pg/mL, p=0.14), and the same was true for PlGF (90 vs. 55pg/mL, p=0.14). Using linear mixed models, no difference in longitudinal course of sFlt-1 or PlGF could be attributed to the treatment group, when adjusted for baseline values and GA at enrollment (p=0.47). Women receiving omeprazole had a similar length of pregnancy compared with those not receiving this drug (median 15 vs. 14 days, p=0.70). Except for a higher neonatal intubation rate in the non-omeprazole group (31% vs 4%, p=0.02) there were no differences in maternal/perinatal complications between the two groups. Our findings suggest that daily administration of 40mg in women with PE do not alter their circulating levels of sFlt-1 and PlGF, arguing against a role for this drug as a potential treatment for this syndrome.

scholarly journals Soluble fms-Like Tyrosine Kinase 1 Is Increased in Preeclampsia But Not in Normotensive Pregnancies with Small-for-Gestational-Age Neonates: Relationship to Circulating Placental Growth Factor

2005 ◽  
Vol 90 (8) ◽  
pp. 4895-4903 ◽  
Author(s):  
Eiji Shibata ◽  
Augustine Rajakumar ◽  
Robert W. Powers ◽  
Robert W. Larkin ◽  
Carol Gilmour ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Vascular Dysfunction ◽  
Normal Pregnancy ◽  
Maternal Serum ◽  
Placental Growth Factor ◽  
Gestational Age At Delivery ◽  
Placental Protein

Context: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease. Objective: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates. Study Design: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta). Results: sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ. Conclusions: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

Circulating soluble fms-like tyrosine kinase-1 and placental growth factor from 10 to 40 weeks’ pregnancy in normotensive women

2017 ◽  
Vol 45 (7) ◽  
Author(s):  
Tuangsit Wataganara ◽  
Busadee Pratumvinit ◽  
Piyaporn Lahfahroengron ◽  
Julaporn Pooliam ◽  
Pattarawalai Talungchit ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Gestational Age ◽  
Serum Levels ◽  
Reproductive Technologies ◽  
Placental Growth Factor ◽  
Low Risk ◽  
Placental Weight ◽  
Reference Ranges ◽  
Gestational Age At Delivery

AbstractIntroduction:Circulating soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are potential markers for preeclampsia. The objective was to construct and analyse the reference ranges of serum levels of sFlt-1 and PlGF throughout the course of pregnancy in low-risk Thai pregnant women.Methods:We enrolled 110 low-risk, Thai women singleton pregnancy from 10 to 40 gestational weeks. Serum concentrations of sFlt-1 and PlGF were measured with an automated assay. The reference ranges of serum levels of sFlt-1, PlGF and sFlt-1/PlGF ratio were constructed and assessed for possible correlations with gestational age, maternal factors [age, parity, tobacco use, artificial reproductive technologies (ARTS) and body mass index (BMI)], and pregnancy outcomes (gestational age at delivery, development of preeclampsia, neonatal birth weight and placental weight).Results:None of the subjects developed preeclampsia. Serum sFlt-1 concentrations significantly elevated from 20 to 40 gestational weeks (P=0.003). Significant elevation and dropping of serum PlGF levels and sFlt-1/PlGF ratios were observed at 10 to 29 and 30 to 40 weeks of gestation, respectively (P<0.001). There was an inversed correlation between serum PlGF levels at 20 to 29 gestational weeks and neonatal birth weights (r=−0.48, P<0.05). There were no associations between serum levels of sFlt-1, PlGF, or sFlt-1/PlGF ratios and maternal BMI, gestational age at delivery, or placental weight (P>0.05). Effects from parity, smoking and ARTS were inconclusive.Conclusion:Robust change of serum PlGF levels suggests for its broader clinical application compared to sFlt-1. Prediction of preeclampsia using serum analytes may be gestational period specific.

scholarly journals Pravastatin versus Placebo in Pregnancies at High Risk of Term Preeclampsia

Circulation ◽  
2021 ◽  
Author(s):  
Moritz Döbert ◽  
Anna Nektaria Varouxaki ◽  
An Chi Mu ◽  
Argyro Syngelaki ◽  
Anca Ciobanu ◽  
...  
Keyword(s):  
Growth Factor ◽  
High Risk ◽  
Tyrosine Kinase ◽  
Cox Regression ◽  
Gestational Hypertension ◽  
Controlled Trial ◽  
Placental Growth Factor ◽  
Adverse Outcomes ◽  
Double Blind ◽  
Clinical Trial Registration

Background: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with detection rate of about 75%, at screen positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. Methods: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1,120 women with singleton pregnancies at high-risk of term preeclampsia to receive pravastatin, at a dose of 20 mg per day, or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention-to-treat. Results: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80/548) participants in the pravastatin group and in 13.6% (74/543) in the placebo group. Allowing for the effect of risk at the time of screening and participating centre, the mixed effects Cox regression showed no evidence of an effect of pravastatin; hazard ratio (statin/placebo) 1.08 (95% confidence interval: 0.78, 1.49; p=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, previous pregnancy history, adherence and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization Adherence was good, with reported intake of 80% or more of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events. Conclusions: Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Clinical Trial Registration: URL: https://www.isrctn.com Unique Identifier ISRCTN16123934

Sign in / Sign up

Export Citation Format

Share Document