Pregnancy outcomes in correlation with placental histopathology in subsequent pregnancies complicated by fetal growth restriction
Introduction
Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality [1,2]. When “placental insufficiency” is the presumed cause of FGR, impaired placentation leads to placental vascular compromise and an increase in utero-placental malperfusion lesions constitute the main etiology of placental associated FGR [[3], [4], [5]].
In cases of growth restricted fetuses, as with most maternal and fetal conditions, careful evaluation of the placenta may help in the diagnosis of an underlying condition or pathophysiology [6,7]. As compared to appropriate for gestational age, placentas from FGR pregnancies are characterized by lower mean weight, lower fetal to placental weight ratio, increased thrombi or hematomas, villous infarction, and thickening of the villous trophoblastic basal membrane [7,8]. Existing evidence links specific placental lesions to FGR. According to Redline et al., the typical placental findings in cases of FGR include: global/partial maternal vascular malperfusion (MVM) lesions (accelerated maturation), villitis of unknown etiology (VUE) or chronic villitis, complete/segmental fetal vascular malperfusion (FVM) lesions (fetal thrombotic vasculopathy), fetal stromal-vascular developmental lesions, and perivillous fibrinoid deposition [3,8,9].
Salafia et al. studied placental lesions in 128 FGR cases. They found placental infarction, VUE, hemorrhagic endovasculitis, and placental vascular thromboses are more frequent in the FGR cases, compared to the non-FGR cases (55% versus 32%). Relationships of all placental lesions to FGR were independent of each other. In addition, FGR infants had multiple types of lesions in their placentas more frequently [10].
Placental-mediated complications, with FGR being the most common, are known to have a high recurrence rate in subsequent pregnancies [11].
The “Immune maladaptation theory” claims that the fetus and the placenta both act as the graft or foreign body while the mother, plays the role of the host. In the subsequent pregnancy, according to this theory, it would be reasonable to assume that the maternal immune system will recognize the fetus and therefore, the rejection reaction tends to be less severe [12]. We hypothesized that placental histopathology and neonatal outcome will differ between the first occurrence of FGR and the recurrent case of FGR in the same patient in a way that the former will be more severe than the later. In order to test our hypothesis, we compared the detailed placental histopathology reports and neonatal outcomes between subsequent pregnancies complicated by FGR in the same patient.
Section snippets
Patients selection
Our departmental protocol routinely performs a full placental analysis in all complicated pregnancies, as in cases of FGR pregnancies. The computerized files of all women who gave birth at 24–42 gestational weeks, to a singleton neonate with FGR, in our university affiliated tertiary centre, from January 2008 to November 2018, were reviewed. Exclusion criteria included pregnancies for which the placenta was not sent for pathological examination, pregnancy termination, pregnancies complicated by
Results
During the study period, 34,825 deliveries occurred. Of them 2786 (8%) were complicated by singleton FGR neonates, of whom only 1254 (45.0%) cases had placental pathology examination. Ninety-six patients had two subsequent singleton FGR pregnancies and met the inclusion criteria. The first FGR event constituted the 'first FGR group' (n = 96), and the subsequent FGR pregnancy constituted the 'subsequent FGR group' (n = 96). (Fig. 1).
Maternal and pregnancy characteristics of the first and
Discussion
This study aimed to compare pregnancy outcomes and placental histopathology in cases of first versus subsequent FGR occurrence, in the same woman. Our main findings were: 1) Placental MVM lesions were significantly more common in placentas from the first FGR group, as compared to the subsequent FGR group while there was no significant difference between the groups regarding the rate of FVM nor inflammatory lesions. 2) Adverse neonatal outcome was found to be more prevalent in the first
Disclosure
There is not any financial relationship with any organization or any conflict of interest to report.
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