Grading placental fetal vascular malperfusion and short-term perinatal outcome

Abstract

This retrospective analysis was performed to seek possible associations of the global fetal vascular malperfusion (GFVM) and grade of segmental fetal vascular malperfusion (SFVM) with early perinatal outcome. Clinical associations of 538 consecutive cases of placental fetal vascular malperfusion (FVM), including 374 cases of SFVM (group 1: 308 low-grade, group 2: 66 high-grade), and 65 cases of GFVM without segmental villous changes (group 3), were statistically compared. Histological SFVM was graded on HE (Subgroups 1A and 2A) and on CD34 or histochemistry stains (segmental endothelial fragmentation, segmental hypovascularity and/or mineralization) (subgroups 1B and 2B). The short term neonatal outcome as evaluated by NICU stay and neurological complications was statistically significantly more frequently complicated in association with high-grade SFVM than in low-grade SFVM and GFVM in general, and equally frequently in high-grade SFVM diagnosed on HE slides only and on CD34 immunostain and/or mineralization histochemistry only (about 61% of cases each). High-grade SFVM portends a more complicated short-term perinatal outcome than low-grade SFVM or GFVM. CD34 immunohistochemistry and/or mineralization histochemistry diagnosed/upgraded high-grade SFVM has the same short-term prognostic significance as high-grade SFVM diagnosed on HE only, thus increasing the sensitivity of placental examination for FVM by these methods.

Placental recent/on-going foetal vascular malperfusion with endothelial fragmentation is diagnostically equivalent to established distal villous lesions of foetal vascular malperfusion

“…In postnatal complications, FVM seems to be a less sensitive tool for the prediction of complications [38]. The NICU stay in the infants analysed here was around 70% in all groups (Table I), but high-grade distal FVM is associated with complicated short-term perinatal outcome, no matter if remote or recent [3]. CD34 immunohistochemistry and/or mineralization histochemistry diagnosed/upgraded to high-grade FVM has the same short-term prog-nostic significance as high-grade segmental FVM diagnosed by H&E only [3], but not global FVM, which was also confirmed by this analysis (Table II).…”

“…In the latter application, the immunostaining increased the sensitivity of placental FVM diagnosis in stillbirth, was capable of upgrading low-grade FVM to high grade by increasing the number of involved distal chorionic villi (not seen on H&E staining) [11], and of disclosing temporal heterogeneity of FVM lesions by adding more recent lesions with clustered endothelial fragmentation (2 days) to other established lesions of FVM: clustered stromal vascular karyorrhexis (3 days), clusters of hypovascular distal villi (several days), clusters of sclerotic chorionic villi (2 weeks), or mineralized chorionic villi (> 2 weeks) [12,13]. We also showed that distal villous lesions of FVM are clinically more relevant than proximal large-vessel FVM lesions [14] and that high-grade FVM is associated with adverse short-term perinatal outcome whether diagnosed by H&E, immunohistochemistry, or histochemistry staining [3].…”

“…Neonatal complications may manifest with end-organ thrombi, decreased platelets, foetal death, neonatal encephalopathy, foetal stroke, cerebral palsy, and mild fetal growth restriction (FGR) [1]. Those neonatal complications were more often seen in segmental and high-grade than in global and low-grade FVM [3]. Mild FVM can also occur in pregnancies with a normal/ uncomplicated outcome (19.7%), thus representing a subclinical pathological process, but high-burden lesions were reported in only 0.7% of placentas [4].…”

Placental CD34 immunohistochemistry in fetal vascular malperfusion in stillbirth

“…The cases identified using immunohistochemistry showed less abnormal clinical and placental phenotypes that those identified using hematoxilin‐eosin staining alone, likely because the former had a duration that was shorter than that required to bediagnosable using hematoxilin‐eosin staining. Previously we proved that high‐grade segmental FVM diagnosed by or upgraded by CD34 immunostain portends the same poor outcome for the fetus as when diagnosed using hematoxilin‐eosin staining 34 . Therefore, the CD34 immunostaining may be either diagnostic or contributory in explaining the cause of the otherwise inexplicable stillbirths without high‐grade FVM according to hematoxilin‐eosin staining alone.…”

“…Previously we proved that high-grade segmental FVM diagnosed by or upgraded by CD34 immunostain portends the same poor outcome for the fetus as when diagnosed using hematoxilin-eosin staining. 34 Therefore, the CD34 immunostaining may be either diagnostic or contributory in explaining the cause of the otherwise inexplicable stillbirths without high-grade FVM according to hematoxilin-eosin staining alone.…”