Preeclampsia, one of the hypertensive disorders of pregnancy, remains a leading cause of maternal death worldwide, with the majority of deaths occurring in developing countries. Preeclampsia is a multi-organ syndrome of pregnancy that manifests after 20 weeks' gestation with new-onset hypertension alongside maternal end-organ dysfunction and/or fetal growth restriction. Importantly, preeclampsia poses serious health risks for the baby, implicated in 12% of cases of fetal growth restriction, and is a known antecedent in up to 19% of preterm births. There is currently no effective treatment for preeclampsia except delivery of the baby, and as such, it remains a significant burden of disease for both mothers and their babies worldwide. Screening for women at risk of preeclampsia is an important part of antenatal care. Once women are identified as high risk, they can be targeted for more intensive antenatal surveillance and prophylactic interventions. Most current strategies for risk assessment are based on obstetric and medical history and clinical examination. However, there is surprisingly little reliable evidence on the actual risk associated with individual factors and how they might interact. Risk factors with a particularly high association with preeclampsia (more than one in ten risks) include maternal diabetes, chronic hypertension, and renal disease. Thrombophilia and autoimmune disease have a strong association with severe early-onset preeclampsia. Obstetric factors associated with high risk are multiple pregnancies, history of preeclampsia in a previous pregnancy especially if severe or early onset, and a current hydropic pregnancy. Other factors linked with preeclampsia but associated with a somewhat lower risk include first pregnancies, age less than 20 or more than 35 years, a family history of preeclampsia, and obesity. Proton pump inhibitors such as esomeprazole have long-term safety data about the treatment of gastric reflux in pregnancy. In vitro studies show proton pump inhibitors decrease soluble fems like tyrosine kinase -1 (sFlt-1) and soluble endoglin and improve markers of endothelial dysfunction . while esomeprazole reduces blood pressure in a preeclampsia transgenic mouse model that overexpresses sFlt-1.

This is a randomized double-blinded placebo-controlled intervention trial investigating preeclampsia, defined according to the National Institute of Clinical Excellence (NICE). The population of interest involves women attending the study hospital for antenatal care and delivery with a risk for developing preeclampsia. The intervention involves randomization to oral esomeprazole tablets40 mg or identical placebo tablet from recruitment until delivery. Randomization is achieved using computational random allocation, and both participants and researchers will be blinded to the intervention given. Calculation of the sample size considers that the incidence of preeclampsia is 10% in the population of interest. To detect a 50% reduction in incidence (with 80% power, two-sided p < 0.05), 450 women are required in each group with a 1:1 ratio.

Inclusion Criteria:

• Pregnant women presenting prior to 17+0 weeks' gestation.

  • Moderate to high risk of preeclampsia. One or more of the following: previous history of preeclampsia, antiphospholipid antibodies, pre-existing diabetes, pre-existing hypertension, pre-existing renal disease, autoimmune disease, nulliparity, family history of preeclampsia, elevated BMI > 25, and maternal age <20 or >35.

• Give written informed consent.

Exclusion Criteria:

• Multiple pregnancies.
• Current or previous esomeprazole ingestion within the last 6 weeks.
• Previous hypersensitivity reaction esomeprazole
• Contraindications to the use of a proton pump inhibitor

The population of interest involves women attending the study hospital for antenatal care and delivery

both participants and researchers will be blinded to the intervention given.