Preeclampsia is globally responsible for tens of thousands of maternal and neonatal deaths each year. Currently, there are no medical therapies to halt disease progression and expectant management and delivery remain the mainstay of treatment. An important step in the pathogenesis of preeclampsia is a poor placental invasion and the subsequent release of the anti-angiogenic factors soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng)into the maternal circulation. Given metformin and esomeprazole successfully mitigate key pathogenic features of preeclampsia, the investigator will study whether combining low-doses of metformin and esomeprazole may be additive or synergistic (or neither) in reducing sFlt-1 and sEng secretion, and mitigating endothelial dysfunction, compared to placebo.

This is a randomized double-blinded placebo-controlled intervention trial investigating preeclampsia, defined according to the International Society for the Study of Hypertension in Pregnancy (ISSHP). The population of interest involves pregnant women diagnosed with pre-eclampsia at a gestational age between 28 and 32 weeks at Aswan university hospital will be invited to participate. To be enrolled, the treating team needs to have determined after their initial assessment that delivery is unlikely to be required within 48 h. A starting point of 28 weeks has been chosen as this would be the earliest gestation that Aswan university hospital to be viable and are suitable to be offered expectant management The intervention involves randomization to oral esomeprazole tablets40 mg plus metformin tablets 1000 mg or identical placebo tablets from recruitment until delivery. Randomization is achieved using computational random allocation, and both participants and researchers will be blinded to the intervention given.

Inclusion Criteria:

• Pregnant women presenting at a Gestational age between 28 + 0 weeks and 32 + 0 weeks presented with preterm preeclampsia
• The patient will be managed with an expectant management
• Give written informed consent

Exclusion Criteria:

• Multiple pregnancies.

• Previous hypersensitivity reaction esomeprazole or metformin

• Contraindications to the use of esomeprazole or metformin

• The patient is unable or unwilling to give consent

• An established fetal compromise that necessitates delivery

• The presence of any of the following at presentation:

  • Eclampsia.
  • Severe hypertension.
  • A cerebrovascular event as an ischemic or hemorrhagic stroke.
  • Renal impairment.
  • Signs of left ventricular failure which include pulmonary edema.
  • Disseminated intravascular coagulation (DIC)
  • Haemolysis, elevated liver enzymes and low platelets (HELLP syndrome)

pregnant women with early-onset preeclampsia

both participants and researchers will be blinded to the intervention given