Evaluation of the current evidence correlating clinical obstetric or neonatal problems with placental morphological change is highly problematic. Diagnostic criteria for specific clinical problems are very variable within the literature and occasionally clinical problems correlated to specific placental findings are referred to descriptively but not defined. There is a proliferation of non-standardised terminology and disease entities are often referred to without a clear statement as to whether it is the clinical or histological process under discussion.
1.8.1 Maternal/fetal chorioamnionitis
Preterm labour accounts for around 10% of all deliveries, having multiple well-recognised clinical and epidemiological associations, amongst which chorioamnionitis is clearly established (103-106). A small number of studies have examined the question of recurrent preterm birth and placental inflammation (107, 108). These studies are more difficult to place in context: the histological scoring systems used for the studies are variable, and fetal
Overwhelming maternal sepsis is occasionally but consistently reported as a complication of chorioamnionitis (109). It is a relatively rare occurrence, forming only a small
proportion of pregnancy-related intensive-care admissions; prognosis is generally good with appropriate treatment.
The associations between chorioamnionitis and stillbirths are controversial (110-113). In the specific group of preterm non-macerated stillborn infants with histological evidence of an established fetal inflammatory response (see below), it is reasonable to conclude that ascending infection was likely to be the underlying cause of the pregnancy loss, by precipitating delivery. This specific group accounts for only around 10-25% of all stillbirths (114), with the lower end of the range likely to be most applicable to Western populations (112).
The most important pathway relating chorioamnionitis to adverse neonatal outcome appears to be the fetal inflammatory response syndrome (115, 116). The data are, however, somewhat paradoxical. Histological chorioamnionitis is associated with improved survival in very preterm infants compared to gestationally age-matched cases with no inflammation (117), presumably as a consequence of the fact that preterm delivery is associated with ascending infections are otherwise normal infants, whereas those
delivered preterm for other indications will very likely have other complications such as fetal growth restriction.
Assessing the implications of chorioamnionitis for all liveborn infants, born preterm or term, continues to be problematic. A meta-analysis carried out 10 years ago (118)
reported significant associations between clinical chorioamnionitis and both cerebral palsy and periventricular leucomalacia in preterm infants and an association between histological chorioamnionitis and periventricular leucomalacia in preterm infants. For term infants, there was a positive association between clinical chorioamnionitis and cerebral palsy. A subsequent extended meta-analysis (119) reported an association between recorded clinical chorioamnionitis and cerebral palsy with a random effects model, and a more recent meta-analysis (120) reported associations between both clinical and histological
chorioamnionitis and cerebral palsy in studies predominantly, but not exclusively, of preterm infants.
1.8.2 Pregnancy-induced hypertension/pre-eclampsia
Both clinical and experimental studies have reported links between clinical pregnancy-induced hypertension, pre-eclampsia and eclampsia and placental morphology. A retrospective case series has reported correlation between the clinical severity of the maternal hypertensive disorder and the degree of placental infarction present: infarction involving ≥5% of placental tissue was found in 39.7% of severe pre-eclampsia, 17.1% of mild eclampsia and 5.1% of normal controls. When comparing placentas in severe pre-eclampsia, mild pre-eclampsia and normal mothers, there was an increase in the presence of any infarction and decidual arteriopathy (121).
A similar study, evaluating placentas from patients with severe pre-eclampsia with and without hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome has reported that infarction, intervillous thrombosis and abruption were more common in the pre-eclampsia group than in the HELLP group (122).
Analysis of placental microarchitecture of capillary loops in placentas from growth-restricted fetuses has shown a reduction in capillary loop number, with significantly increased length and fewer branches, compared to controls. It is suggested that these findings are consistent with an increase in fetoplacental vascular impedance at the capillary level and may account for impaired gas and nutrient exchanges in pre-eclampsia (95).
1.8.3 Placental abruption
Positive associations between chorioamnionitis and placental abruption in preterm and term births are reported within the literature (53, 55). The hypothesis is that localised inflammation processes disrupt normal placental attachment. It should, however, be acknowledged that many cases of abruption are associated with other, well validated, epidemiologically derived factors such as previous abruption, hypertension (as noted above), ethnicity, smoking and cocaine use (123-125).
1.8.4 Fetal growth restriction
Fetal growth restriction is most commonly defined as fetal growth < 10th centile for gestational age (126) , but growth below the 3rd centile has also been proposed as a more reliable indicator for associated perinatal morbidity (127). A number of authorities have
also noted that basing assessment of growth entirely on a population basis misclassifies a number of fetuses as either small or large for gestational age (128-130).
The most commonly reported specific placental lesions reported in association with fetal growth restriction include those lesions associated with maternal hypertension and also high-grade villitis of unknown etiology and chronic intervillous histiocytosis.
Early onset pre-eclampsia has been reported to be more strongly associated with specific placental lesions (infarction and decidual vasculopathy) than later onset pre-eclampsia (30, 131). Villitis of unknown etiology is repeatedly reported to be associated with growth restriction, albeit with lower grade lesions of more doubtful signficance (46, 132, 133).
Chronic intervillous histiocytosis has been reported in to be associated with growth restriction (27), although as discussed elsewhere this lesion may be more associated with recurrent pregnancy loss (49, 134).
1.9 CONCLUSIONS
Normal placental development is well understood. The end of the first trimester marks a shift from histiotrophic-fuelled growth and development to maternal perfusion-mediated growth and development.
The normal macroscopic appearances of the placenta are defined in terms of size, shape, weight and cord insertion site.
The normal microscopic appearances of the placenta are defined as micro-anatomical compartments: cord, free membranes, chorionic plate, intervillous space, chorionic villi and maternal decidua.
Macroscopic abnormalities of the placenta include infarction, intervillous thrombus formation and fetal thrombotic vasculopathy.
The significance of variations in placental shape (eccentricity) and centrality of cord insertion site is uncertain.
Microscopic abnormalities of placenta include chorioamnionitis and funisitis, impaired perfusion, villitis of unknown etiology, fetal thrombotic vasculopathy, placental abruption, chronic histiocytic intervillous inflammation, massive perivillous fibrin deposition and maternal floor infarction, intervillous thrombus, plasma cell deciduitis, eosinophilic inflammation and subacute chorionic plate inflammation.
Mechanisms of disease in placental disorders include acute and chronic inflammatory pathways, complement activation and impaired perfusion with subsequent oxidative stress.
Associations between placental lesions and adverse clinical outcomes have been reported in the context of both prospective and retrospective studies.
Findings are often confusing, conflicting and difficult to apply to clinical practice.