Pathologic placental lesions in early and late fetal growth restriction

Abstract

Introduction The purpose of the study was to evaluate the differences in individual histopathologic placental lesions in pregnancies complicated by early‐onset (<32 weeks at diagnosis) and late‐onset (≥32 weeks at diagnosis) fetal growth restriction (FGR). Material and methods A cohort study of 440 singleton pregnancies complicated by FGR, diagnosed according to standard ultrasonographic criteria, followed up and delivered at the same institution between 2010 and 2016. Placental lesions were classified according to the Amsterdam Placental Workshop Consensus Criteria. Pathologic examination of placentas from 113 healthy singleton term pregnancies served as controls. Binary and multinomial logistic regression models were used to evaluate the independent association of placental lesions with the type of FGR. Results In our cohort the prevalences of early and late FGR were 37.3% (164/440) and 62.7% (276/440), respectively. The overall rates of preeclampsia (69/164 vs 59/276, P < 0.01) and absent/reversed umbilical artery pulsatility indices (61/164 vs 14/276, P < 0.001) were higher among early FGR than late FGR. Placental characteristics from early and late FGR pregnancies differed mainly in regard to maternal vascular malperfusion scores rather than fetal scores, with preeclampsia found to be a cofactor modulating the rates and severity of associated lesions. In the binary logistic analysis, recent infarcts (OR 2.44, 95% CI 1.2‐5), distal villous hypoplasia (OR 1.8, 95% CI 1.0‐3.2), atherosis (OR 2.71, 95% CI 1.35‐5.47), persistent endovascular trophoblasts (OR 1.67, 95% CI 1.03‐2.7), and a reduced fetal/placental weight score (OR 0.27, 95% CI 0.2‐0.38) were independently associated with an increased likelihood of early FGR compared with late FGR. The sensitivity, specificity, and area under the curve of the model were 60% (95% CI 51.2‐66.2), 89.1% (95% CI 84.9‐92.3), and 0.81 (95% CI 0.77‐0.85), respectively, suggesting a fair to good predictive value. Conclusions Individual placental lesions suggestive of increased rates of ischemia, defective remodeling of spiral arteries, peripheral hypoxia interfering with villus development, and reduced placental efficiency were significantly more common in early FGR than late FGR.

Can information regarding the index stillbirth determine risk of adverse outcome in a subsequent pregnancy? Findings from a single‐center cohort study

“…Unfortunately, only a small proportion of placentas were sent for histopathological analysis after subsequent pregnancy, which meant that the recurrence of maternal or fetal vascular malperfusion, and their relation to iatrogenic preterm birth, cannot be determined. However, as preterm fetal growth restriction, preeclampsia, and antepartum hemorrhage are closely related to placental disease, 18 particularly in preterm disease, it is plausible that this pathology underpins the increased incidence of preterm birth in this population. Further research, comparing the histopathological phenotype of index stillbirth and subsequent pregnancies, is needed to address this question.…”

Characterization of Placental Microvascular Architecture by MV‐Flow Imaging in Normal and Fetal Growth–Restricted Pregnancies

“…It is important to note that abnormalities at different locations within the placenta are associated with different forms of disease. 28 Lesions from the maternal-side microvasculature are associated with early onset of preeclampsia, whereas lesions of the stem villi from the fetal side are more closely related to FGR. Thus, detailed localization of structural abnormalities within the placenta can be helpful for the differential diagnosis.…”

The potential role of the E SRRG pathway in placental dysfunction

“…Placental dysfunction describes when the placenta fails to develop and/or function adequately to support the nutritional demands of the fetus, and is central to the development of both fetal growth restriction (FGR) and preeclampsia (Redman 1991, Spinillo et al 2019. FGR describes a fetus that does not reach its genetic growth potential.…”

“…True FGR affects 5%-10% of fetuses and is associated with both short-term and longterm complications including stillbirth, neonatal death, abnormal neurodevelopment, and cardiovascular and metabolic disorders in later life (Bernstein et al 2000, Gardosi et al 2005, Crispi et al 2010, Ramirez-Velez et al 2017, Pels et al 2019). The majority of cases of FGR are mediated by abnormal placental structure and function (Spinillo et al 2019). FGR may also co-exist with preeclampsia, which is defined as an elevation of maternal blood pressure with proteinuria occurring after 20 weeks' gestation (Brown et al 2018).…”