Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia

Pre-eclampsia (PE) is a condition in pregnancy, identified by a combination of high blood pressure and protein in the urine. It affects 3-5% pregnancies. Women with preterm PE (pPE; delivery before 37 weeks) frequently develop abnormal heart function after pregnancy, which increases their risk of heart disease in later life. Subtle changes in heart function have also been shown to increase the chance of a woman getting PE again in her next pregnancy. Despite this, research to date has focused on the pregnancy and relatively little is known about what happens after pregnancy and whether outcomes can be improved with treatment. sFlt is a protein that prevents blood vessel growth and causes blood vessel constriction. sFlt levels are raised in pPE and correlate with the degree of abnormal heart function. In animal studies, sFlt has been shown to directly cause injury to the heart and it is therefore possible that sFlt mediates pPE associated heart damage. Angiotensin converting enzyme (ACE) inhibitors are commonly used to protect against heart damage following myocardial infarction, but their use has never been tested following pPE.

Objectives:

• To characterise abnormal heart function following pPE
• To determine if this can be modified by treatment with enalapril.

Study design:

Women who have had pPE, will be randomly allocated to enalapril or placebo from delivery for 6 months. Heart function will be assessed using blood tests and ultrasound scans (echocardiography). This will allow us to learn more about how pPE affects the heart (from the placebo group) and measure the protective effect of enalapril on the heart. Recruitment rates and acceptability of the intervention will also be assessed in this feasibility study.

Inclusion criteria

• Diagnosis of pPE in this pregnancy requiring delivery < 37 weeks gestation: new or worsening hypertension >20 weeks with proteinuria or other features suggestive of PE (abnormal haematological, biochemical parameters, fetal growth restriction (FGR) and/or abnormal sFlt:PlGF (>85)).
• Biochemical / haematological cut-offs:
• Platelet count <100 x109/L
• Alanine amino transferase > 50units/L
• Creatinine >90mmol/L
• FGR:
• Abdominal circumference (AC) / estimated fetal weight (EFW) <3rd centile
• Or 2 of the following:
• AC/EFW <10th centile
• AC/EFW crossing centiles by >2 quartiles
• Cerebroplacental ratio <5th centile
• Umbilical artery PI >95th centile
• At time of randomisation:
• Postpartum, within 3 days of delivery
• Aged 18 years or over
• Able to provide informed consent
• Serum creatinine <100 mmol/l

Exclusion criteria

• Inability to consent
• Known cardiac disease
• Contraindication to ACE inhibitors
• Renal artery stenosis