Maternal Health
Pre-eclampsia is a hypertensive disorder of pregnancy characterised by the onset of sustained high blood pressure and evidence of organ damage, most commonly proteinuria (kidney damage). By definition, it occurs after 20 weeks gestation, however the pathophysiological changes underpinning the disorder are known to start at very early stages of pregnancy.
Pre-eclampsia presents along a spectrum of symptoms, but can result in severe morbidity, including stroke, cardiac arrest, kidney or liver failure, foetal growth restriction and preterm birth. It is one of the leading causes of maternal and neonatal mortality and morbidity, affecting 2%-8% of all pregnancies worldwide. Women in LMICs are seven times more likely to develop pre-eclampsia than women in HICs, with rates as high as 16.7% in parts of Africa.
Preeclampsia and eclampsia are placental-mediated multisystem disorders that cause hypertension and organ dysfunction during pregnancy or post-partum, responsible for 10-15% of maternal deaths globally, with 99% occurring in LMICs. Current management relies on specialist healthcare: detection of elevated blood pressure and urinary protein assumes regular antenatal monitoring; measurement of biomarkers in urine or blood requires laboratory facilities; and definitive treatment – delivering the placenta – requires skilled obstetric care. Only one medicine – magnesium sulphate – is specifically indicated for PE&E (for eclamptic seizures) with safe administration requiring skilled healthcare practitioners. No other medicines are currently available for prevention or treatment, and none address the underlying aetiology. Low-dose aspirin and calcium supplementation are, however, recommended by the WHO for prevention in high-risk women; but identifying those at risk is challenging without expert medical assessment. Medicines based on improved understanding, and applicable to LMICs, are required. Since timely detection is essential, there is also an unmet need for diagnostics applicable to low-resource settings, especially point of care tests.
MZe786 is a novel hydrogen sulfide-releasing molecule with an aspirin structure ‘backbone’ being developed by MirZyme Therapeutics. The drug offers improved maternal and fetal outcomes over aspirin alone, and is intended to be taken once daily by women at risk of PE&E. It is the first pregnancy drug to be granted fast-track approval by the UK regulatory body (in 2022). The University of Technology Sydney has developed low-cost lateral flow assays targeting novel biomarkers for preeclampsia. Use on clinical samples demonstrated improved sensitivity and specificity over standard ELISA.