Could Esomeprazole Prolong Pregnancy for Women with Preterm Preeclampsia?

BACKGROUND AND PURPOSE: 

• Esomeprazole, a proton pump inhibitor, is used in pregnancy (FDA category B) to treat gastric reflux 
• Other biologic effects include  
  • Decreases sFlt-1 and soluble endoglin production, which are angiogenic factors associated with abnormal maternal endothelial function and hypertension  
  • Dilates blood vessels  
• Cluver et al. (AJOG, 2018) examined whether esomeprazole could prolong pregnancy in women with preterm preeclampsia

METHODS: 

• Double blind, randomized controlled trial (RCT) 
• Participants 
  •  Women with preterm preeclampsia 
    • 26w0d- 31w6d 
  • Excluded if immediate delivery was indicated  
• Women either received 
  • 40 mg daily esomeprazole  
  • Placebo 
• Primary outcome: Prolongation of pregnancy of 5 days (based on power of the study)  
• Secondary outcomes  
  • Composite and individual maternal and neonatal outcomes 
• Circulating markers of endothelial dysfunction associated with preeclampsia were compared between groups  
• Pharmocokinetic studies were also completed

RESULTS: 

• 119 patients were included in the study  
  • 59 esomeprazole | 60 placebo  
  • Median gestation age at enrollment: 29w4d  
• There was no between-group differences in median time from randomization to delivery 
  •  11.4 days in the esomeprazole group 
  •  8.3 days in the placebo group  
  • 95% CI, -2·9-8·8 (P=0.31) 
• Abruption 
  • There were no placental abruptions in the esomeprazole group vs 10% in the placebo group, but not significant when adjusted for multiple comparisons for other secondary outcomes  (P=0.14 adjusted) 
• There were no differences in other maternal or neonatal outcomes, or markers of endothelial dysfunction 
• Esomeprazole and its metabolites were detected in maternal blood but only trace amounts in the umbilical cord blood

CONCLUSION: 

• 40 mg daily esomeprazole, the dose required to lower gastric pH, did not prolong gestation, decrease markers of endothelial dysfunction, or improve maternal or neonatal outcome 
• The study was powered for a 5 day prolongation and this study showed 3 days difference 
  • To confirm that 3 days difference was significant, >400 participants would be required in each group  
• Higher levels via higher dosing or IV route, may be required to alter sFlt-1 levels in maternal circulation  
• The authors also note that once a diagnosis of preeclampsia has been made, it may not be reversible 
  • Esomeprazole may be better suited to prevent preeclampsia  
  • Further clinical trials will be required to prove that hypothesis

Learn More – Primary Sources: 

Esomeprazole to treat women with preterm preeclampsia: a randomised placebo controlled trial