Treatment of poor placentation and the prevention of associated adverse outcomes – what does the future hold?

Abstract

Poor placentation, which manifests as pre-eclampsia and fetal growth restriction, is a major pregnancy complication. The underlying cause is a deficiency in normal trophoblast invasion of the spiral arteries, associated with placental inflammation, oxidative stress, and an antiangiogenic state. Peripartum therapies, such as prenatal maternal corticosteroids and magnesium sulphate, can prevent some of the adverse neonatal outcomes, but there is currently no treatment for poor placentation itself. Instead, management relies on identifying the consequences of poor placentation in the mother and fetus, with iatrogenic preterm delivery to minimise mortality and morbidity. Several promising therapies are currently under development to treat poor placentation, to improve fetal growth, and to prevent adverse neonatal outcomes. Interventions such as maternal nitric oxide donors, sildenafil citrate, vascular endothelial growth factor gene therapy, hydrogen sulphide donors, and statins address the underlying pathology, while maternal melatonin administration may provide fetal neuroprotection. In the future, these may provide a range of synergistic therapies for pre-eclampsia and fetal growth restriction, depending on the severity and gestation of onset.

Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study

“…Several metabolic pathways identified in this paper, and already tested in animal models as exerting control over fetal growth, could be tested in clinical trials to evaluate their safety and efficacy. Interestingly, melatonin, carnitine, and creatine are currently being tested for their anti-oxidant properties [40, 44, 45]. Due to the potent growth promoting effects of BCAAs in the third trimester, maternal protein supplementation in pregnancies at risk of FGR to improve fetal growth remains an attractive option.…”

Stillbirths

“…Fetal growth restriction due to placental insufficiency likely plays a more important role in these deaths, as does preeclampsia. 49,50 …”

“…Several other promising therapies are currently under investigation as a treatment of poor placentation, to improve fetal growth, and to prevent adverse fetal and neonatal outcomes. 49,50 These include maternal nitric oxide donors, sildenafil citrate, vascular endothelial growth factor gene therapy, hydrogen sulfide donors, and statins to address the underlying pathology. Except for aspirin, however, none of the other therapies has been recommended for routine clinical use.…”

A microphysiological model of the human placental barrier

“…This specialized barrier, which separates the maternal intervillous space and fetal circulation, is responsible for regulating the rate and selectivity of placental transport. Aberrant changes in its structure and function are implicated in various complications of pregnancy, such as preeclampsia and intrauterine growth restriction 8,9 . Our microsystem provides a novel platform to emulate this essential unit of the placenta by allowing human placental cells to grow and organize into a multilayered living tissue that replicates the native architecture of the maternal-fetal interface.…”