Histopathological examination of placenta in cases with adverse obstetric outcome is crucial. It provides valuable information to the obstetricians, neonatologists, and pediatricians. Sending a placenta to histopathology lab for evaluation must be correlated with the clinical condition.3 There are specific clinical situations that are suggested by experts to examine the placenta histopathologically.11,12 Studies have shown that presence of severe features of maternal vascular malperfusion lesions can carry 10–25% risk of recurrence in subsequent pregnancies.13 Same risk of recurrence is also found in spontaneous preterm birth with histological chorioamnionitis.14 This valuable information will assist the clinician to formulate appropriate plan of care in subsequent pregnancies. Although, ultrasound feature and abnormalities of the placenta is curical but we had to exclude it from our study as this information was not available for some of our patients as the ultrasound was done in another institution.
In our study, placenta histopathology was abnormal in 74% of cases presenting with various obstetric outcomes. A retrospective cohort study by Romero and others, aimed to determine the placental histopathologic lesions in a normal pregnancy outcome. Histopathological features of inflammatory or vascular lesions were present in 77.8% of cases. However, severe form of lesions was infrequent. Authors contributed the presence of these lesions in normal outcome pregnancies to tow possible reasons: 1) It could be associated with parturition process or 2) It didn’t affect course of pregnancy as it was mild and subclinical to cause any effect.15
Our study has shown that in cases of preterm labor, placenta histopathology was abnormal with placental inflammatory lesions being present in half of the cases and it was statistically significant. This result was in the line of multiple previous studies. Ogunyemi and others found that risk of preterm delivery and neonatal mortality increased significantly in presence of histological chorioamnionitis.6 Their study had shown also that risk of different prematurity complications including intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy and neonatal sepsis was increased in compared to preterm delivery cases without chorioamnionitis (OR: 2.2, 2, 1.8 and 2.5 respectively). Other two previous studies, aiming to assess placental pathology in cases with recurrent preterm delivery, had shown that inflammatory lesions were more associated with recurrent preterm delivery. 14,16 As per authors, this could be contributed to pre-pregnancy endometrial infection rather that ascending infection during pregnancy.16
With regards to FGR cases, with or without abnormal Doppler studies or oligohydramnios, our study found that placenta histopathology was abnormal in 65% of cases with statistically significant presence of maternal vascular under-perfusion and fetal thrombotic vasculopathy lesions. Ch et al., reported a similar figure of abnormal placental histopathology in FGR cases (66.7%).7 In a prospective case-control study, evaluating placental findings in small for gestation who delivered after 34 weeks of gestation and without Doppler signs of placental insufficiency, found that 21.8% of placentas were normal histologically and presence of maternal under-perfusion and fetal under-perfusion lesions were 64% and 15.5% respectively.17 Placenta weight in FGR cases was not evaluated in our study. However multiple previous studies showed that placenta weight was less than 10th percentile in at least half of those cases. 7,17 A study by Günyeli and others, identified two types of lesions that their presence is statistically significant in FGR cases: placental infarction and chorionic intravascular thrombi.18 To note, infarction is under the maternal vascular under-perfusion lesions, whilst chorionic intravascular thrombi is under fetal thrombotic vasculopathy lesions. Placental infarction should be more than 10–20% of the placental volume to cause an effect.19 These lesions represent features of defective extravillous trophoblast invasion which led to insufficiency in uteroplacental blood supply. 20,21
Presence of maternal vascular under-perfusion lesions in cases pre-eclampsia and its complications, eclampsia and HELLP syndrome, was statistically significant (50% of cases). Falco and others had published a systemic review and meta-analysis assessing placental histopathological lesions in pregnancies complicated by pre-eclampsia.9 They found that both placental villous and vascular histopathological lesions was four to seven-fold higher in pre-eclamptic than in normal pregnancies. They questioned whether these lesions are the cause of pre-eclampsia or it’s the effect of disease itself. Moreover, they concluded that these placental lesions are not specific to the diagnosis of pre-eclampsia and it is overestimated. They explain this by the unblinded methodology used in the studies included, and in fact that these placental lesions can also occur in other pregnancy complications like FGR and recurrent pregnancy loss. However, Orabona et al, reply to these queries through their retrospective cohort study, evaluating placenta histopathology in early-onset (< 34 weeks) and late-onset (> 34 weeks) pre-eclampsia cases.22 The incidence of placental histopathology abnormalities was more in early-onset group in compared to late-onset group. Interestingly, they found a significant relationship between uterine artery (UtA) Doppler velocimetry and different placenta histopathology lesions which are under maternal vascular malperfusion category, i.e., distal villous hypoplasia, decidual arteriolopathy, villous infarcts, syncytiotrophoblast knots, microcalcifications, perivillous fibrin deposition and placental hemorrhage, in which p < 0.05.22,23 This suggest that placenta pathology can be a strong contributor to pre-eclampsia cases.
Placenta histopathology was abnormal in 83.3% of cases with placental abruption found in our study. Maternal vascular under-perfusion lesions presented in nearly third of cases while inflammatory lesions presented in 11.1% of cases. Gonen et al, assessed placenta histopathology in early-onset (< 34 weeks) and late-onset (> 34 weeks) placental abruption cases. They found that maternal vascular malperfusion lesions, inflammatory lesions and placental hemorrhage were more frequent in early-onset group.24 Chen and others found that 58% of placental abruption cases was confirmed by placenta histopathological examination.25 Maternal surface indentation and intravillous hemorrhage were the most frequent lesions found, both are features of maternal vascular malperfusion. These findings confirming the causative association between uteroplacental insufficiency and placental abruption. Moreover, presence of inflammatory lesions noticed to be more in acute cases of placental abruption in compared to chronic cases.26
The etiopathogenesis of fetal thrombotic vasculopathy lesions in placenta is still not fully understood. Mostly explained as a result of what is called Virchow's triad, which includes: hypercoagulable state, endothelial cell injury and blood flow stasis.3 An interesting finding in our study, is the presence of fetal thrombotic vasculopathy lesions in FGR and placenta abruption cases with small percentage not exceeding 10% (5.4% and 7.4%. respectively) but it was of statistical significance. A similar pattern of results was demonstrated by Lepais et al, where they found higher frequency of fetal thrombotic vasculopathy lesions in obstetric complications, including FGR (OR 5.440), in compared to normal pregnancy.27 Leistra et al, also found an association between fetal thrombotic vasculopathy lesions in the placenta and neonatal thrombosis, beside its association with adverse obstetric outcome like pre-eclampsia and FGR.28
For IUFD, only 18 cases were included in our study. Placenta histopathology was abnormal in 83.3% of cases. A close figure was reported by a prospective study examining 27 placentas with fetal demise (74.1%).7 However, a systemic review by Ptacek and others, found a wide range of reported percentages of abnormal placenta in IUFD cases, 11 to 60%. This was interpreted by the variety of classification system used to describe placental lesions in which an idea of international consensus on terminology and criteria to classify placental lesions is suggested by authors.21 In another study, the cause of IUFD was primarily contributed to placenta pathology in 32% of cases.8 Maternal vascular malperfusion was the dominant placental abnormalities found especially massive perivillous fibrin deposition, which is similar to our results. Many IUFD cases remained unexplained despite the presence of. different lesions in placenta histopathology examination, as theses lesions were of uncertain significance, and it can overlap in cases with normal pregnancy outcome. 7,8
In our study, inflammatory lesions were present in almost two-third of second trimester pregnancy loss cases while one-third had maternal vascular underperfusion abnormalities. Srinivas et al, reported presence of stage 2–3 inflammatory response in 67% of cases with second trimester pregnancy loss.29 Similarly, Heller and others found that histologic acute chorioamnionitis present in 56.7% of cases with second trimester loss.30 Odendaal et al, assessed the placenta histopathology abnormalities in pregnancy losses before 22 weeks of gestation. Maternal vascular malperfusion came as the second most prevalent finding, after histologic abruption, followed by acute chorioamnionitis. 31, 32 The similarity in studies results confirms that placental inflammation and defective placentation plays an important role in the pathogenesis of second trimester pregnancy loss.