Effect of Esomeprazole on Prolonging Gestation in Preterm Preeclampsia

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Esomeprazole is often used to relieve symptoms of gastroesophageal reflux during pregnancy.
Esomeprazole is often used to relieve symptoms of gastroesophageal reflux during pregnancy.

In women diagnosed with preterm preeclampsia at 26 to 32 weeks' gestation, esomeprazole 40 mg once daily did not extend gestation or reduce levels of soluble fms-like tyrosine kinase 1 (sFlt-1), a marker of preeclampsia, according to a study published in the American Journal of Obstetrics and Gynecology.

An international group of researchers conducted a double-blind, randomized controlled trial to assess the potential for prolongation of pregnancy with the use of esomeprazole in pregnant women with singleton pregnancies and a diagnosis of preterm preeclampsia. Pregnancies suspected of being associated with a major fetal anomaly or malformation were excluded from the study.

A total of 120 patients were recruited from January 2016 until April 2017. Median gestational age at randomization was 29 weeks 4 days for participants receiving esomeprazole and 29 weeks 5 days for those receiving placebo. The median time from randomization to delivery was 11.4 days for the esomeprazole group vs 8.3 for the placebo group.

Plasma samples to measure circulating preeclampsia and angiogenic biomarkers were collected at randomization and twice per week until delivery; placental tissue samples and umbilical artery cord blood were collected at delivery. Pharmacokinetics were performed and samples were drawn before after administration of esomeprazole. Maternal adherence was monitored daily.

After the trial was completed, measurements were collected for sFlt1, soluble endoglin, placental growth factor (PlGF), as well as markers of endothelial dysfunction: endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1).

No significant difference was found in median prolongation between treatment groups either unadjusted or adjusted for gestational age strata (3.0 vs .81). When adjusted for treatment group, no difference was found for prolongation between strata (median 3.0 days). The researchers did not find any difference in hazard of delivery (hazard ratio [HR] 1.13 for <29 weeks and HR 1.07 for ≥29 weeks).

No placental abruptions were found in the esomeprazole group (0/59) and 10% were identified in the placebo group (6/60); this finding was not significant. Circulating sFlt-1 and soluble endoglin concentrations were found to be high all among patients, and the researchers found no difference between the groups in concentrations on serial samples. Circulating levels of PlGF, endothelin 1, or VCAM-1 were not clinically different among either group.

Although the researchers reported that prior pharmacokinetic studies revealed esomeprazole to be present in the maternal circulation, the concentrations were considered too low to elicit a cell response. “This raises the possibility that higher doses may be effective.” However, the researchers conclude that “in women diagnosed with preterm preeclampsia at 26-32 weeks, a daily oral dose of 40mg of esomeprazole did not prolong pregnancies.”

Reference

Cluver CA, Hannan NJ, van Papendorp E, et al. Esomeprazole to treat women with preterm preeclampsia: a randomised placebo controlled trial [published online July 25, 2018]. Am J Obstet Gynecol. doi: 10.1016/j.ajog.2018.07.019

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