Human placentation is uniquely associated with physiological remodelling of the spiral arteries by the invading trophoblast to produce a low resistance uterine circulation. Defective placentation is associated with persistence of a high-resistance uterine circulation, impaired placental perfusion and a placental ‘stress’ response leading to the development of preeclampsia (PE). An imbalance of antigenic and antiangiogenic factors have the highest accuracy in predicting pregnancy complications associated with PE in late pregnancy. Despite these advances in delineating pathophysiology, the aetiology of preeclampsia is still largely unresolved – being labelled a “disease of theories”. According to the two-stage theory of preeclampsia, the maternal syndrome, hypertension and proteinuria, constitute the end-stage of a pathogenic cascade beginning earlier in pregnancy. The initial insult, a failure in trophoblast invasion, is localized to the placenta. It has been proposed that placental dysfunction disorders such as early onset PE comprise a disease entity, which is more or less distinct from late onset PE. The latter has been attributed as “maternal” preeclampsia, while the first has been dubbed as “fetal” preeclampsia. This dichotomy is rather simplistic. A systematic review of the literature does not demonstrate a strong association between placental villous and vascular histological lesions and PE. In fact, placental lesions are seen more frequently in normal pregnancies, which outnumber pathological pregnancies several-fold. Apparently characteristic placental lesions of PE appear neither specific nor sensitive for the condition (Falco et al., Ultrasound Obstet. Gynecol. 2017 Apr 23. doi: 10.1002/uog.17494). Additionally, impaired fetal growth is an expected consequence of poor placental development in preeclampsia. However, over 80% of PE cases occur at term, where the prevalence of SGA is only 15%, there is preponderance of LGA birth. Women with a history of PE also have an increased for cardiovascular diseases in later life, with the prevalence of hypertension being approximately 50% at 15 years after pregnancy – which is 3 to 4 times the risk found in women without PE. These inconsistencies with the placental origins hypothesis have been attributed to disease heterogeneity or the maternal form of PE – which are neither adequate nor actual explanations. An alternative explanation is that placental dysfunction is secondary to maternal cardiovascular maladaptation in pregnancy (TEDx talk: http://bit.ly/2i1SqDk). The concept that placental dysfunction is secondary to a maternal disorder is not new when one considers the clinical similarities between PE and gestational diabetes - both conditions that only develop in pregnancy and are cured by birth. It is accepted that gestational diabetes develops when the maternal pancreas is unable to manage the increasing glucose load of pregnancy. Similarly, pregnancy is known to present a substantial cardiovascular load on the maternal heart – which is an order of magnitude greater than observed in elite athletes and predisposes to cardiac dysfunction towards term (Melchiorre et al., Hypertension. 2016;67:754–762). Furthermore, PE is associated with substantial cardiac dysfunction, especially in early-onset PE where 20% of women exhibit biventricular systolic dysfunction (Melchiorre et al., Circulation.2014;130:703–714). As with PE and hypertension, there is a 50% risk of developing diabetes in the subsequent decade after gestational diabetes. The association of PE with adverse cardiovascular outcome postpartum is due largely to the fact that both environmental and genetic risk factors for PE overlap with those for cardiovascular disease (Buurma et al., Hum. Reprod. Update. 2013;19:289–303). Placental dysfunction is fundamental to the pathophysiology of pregnancy complications such as preeclampsia, but to date, the placenta has been considered in isolation without regard to the fact that it’s functioning is dependent on adequate perfusion by the maternal circulation. It would be churlish to disregard the evidence that failure of the maternal cardiovascular system to adapt to pregnancy may well be the primary mechanism leading to secondary placental dysfunction in PE.
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Feb 1, 2018
Alisse Hauspurg + 4
Open Access
