The great obstetrical syndromes and the placenta

Abstract

Although historically pre‐eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body of literature has demonstrated that the placenta and its development is the root cause of many cases of these conditions. This has led to the term ‘the great obstetrical syndromes’ being coined to reflect this common origin. Although these conditions mostly manifest in the second half of pregnancy, a failure to complete deep placentation (the transition from histiotrophic placentation to haemochorial placenta at 10–18 weeks of gestation via a second wave of extravillous trophoblast invasion), is understood to be key to the pathogenesis of the great obstetrical syndromes. While the reasons that the placenta fails to achieve deep placentation remain active areas of investigation, maternal inflammation and thrombosis have been clearly implicated. From a clinical standpoint these mechanisms provide a biological explanation of how low‐dose aspirin, which affects the COX‐1 receptor (thrombosis) and the COX‐2 receptor (inflammation), prevents not just pre‐eclampsia but all the components of the great obstetrical syndromes if initiated early in pregnancy. The optimal dose of low‐dose aspirin that is maximally effective in pregnancy remains a question open for further research. Additionally, other candidate medications have been identified that may also prevent pre‐eclampsia, and further study of them may offer therapeutic options beyond low‐dose aspirin. Interestingly, three of the eight identified compounds (hydroxychloroquine, metformin and pravastatin) are known to decrease inflammation.

Syncytiotrophoblast Markers Are Downregulated in Placentas from Idiopathic Stillbirths

“…Causal pathways for stillbirth frequently involve impaired placental function, either with foetal growth restriction (FGR), preterm labour, or both [6].…”

Improving maternal, neonatal and child health outcomes in low‐resource settings: Translating research evidence to practice – report from The Third International Conference on Maternal, Newborn and Child Health

“…Hoffman wrote an article on the ‘Great Obstetrical Syndromes’, which, among other points, emphasised the role of the placenta in the pathway to most of the important pregnancy outcomes. 1 He emphasised that placental malperfusion lesions, which generally have their origins in the first trimester, are at least partially responsible for stillbirth, preterm birth, pre-eclampsia, placental abruption and fetal growth restriction. This article arose in part from the ASPIRIN trial, which was led by the Research Unit at JNMC.…”

Prevention of Pregnancy Complications Using a Multimodal Lifestyle, Screening, and Medical Model

“…The combined impact of obstetric syndromes related to placental dysfunction make a significant contribution to global maternal and perinatal morbidity and mortality [1][2][3]. As a result, considerable international effort has been directed at understanding the pathogenesis and pathophysiology of these related conditions to inform prevention and management strategies.…”