The Characteristic Histopathological Findings Suggestive of Placental VascuIar Malperfusion Observed in Meconium Obstruction of Prematurity in the Context of Early Preterm Fetal Growth Restriction; Knob-like Syncytial Knots and Extreme Distal Villous Hypoplasia

초록

Objectives: There is a paucity of information about the role of placental-pathology in the development of meconium-obstruction of prematurity(MOP), a rare-form of neonatal intestinal-obstruction, in the context of fetal-growth-restriction(FGR). We examined whether specific placental-lesions in placental-vascular-malperfusion(PVM) are associated with MOP in the context of early-preterm FGR. Methods: This study is a secondary-analysis of a prospectively-conducted study investigating the association between prenatal and/or postnatal Doppler-ultrasound findings and MOP in pregnancies complicated by FGR(<10th percentile). Study-population included 27 preterm-FGR neonates(i.e., 7neonates with MOP vs. 20neonates without MOP) delivered before GA 33.9weeks from May 2018 until Jan 2022 in SNU Hospital. We analyzed placental-histopathology using the standard ‘Amsterdam-Placental-Workshop-Group-criteria’, with additional-assessment of lesions such as extreme-distal-villous-hypoplasia(EDVH, defined in the presence of sparse, slender terminal-villi occupying >50% of the lower two-thirds of the parenchyma) and knob-like syncytial-knots(KSK, defined in the presence of ≥3 clusters showing ‘a hobnail-like configuration, featuring a narrow-neck and often exhibiting a bulbous-protrusion from the villous-surface’ per high-power field[HPF] in at-least three distinct-foci) according-to the presence or absence of MOP. MOP was diagnosed based-on clinical-signs of bowel-obstruction and feeding-intolerance, with resolution following the passage of inspissated-meconium after a contrast-enema or surgical-intervention. Results: The standard histopathological-features of whole maternal-vascular-malperfusion(MVM, G2) and fetal-vascular-malperfusion(FVM, G3) as defined-by ‘Amsterdam-Placental-Workshop-Group-criteria’ were not significantly different between placentas with and without MOP. However, targeted-analysis revealed that EDVH(85.7%[6/7]vs25.0%[5/20], p=0.009) and KSK(100%[7/7]vs50%[10/20], p=0.026) were significantly more-common in the placentas with MOP than those without MOP. Conclusion: In early-preterm neonates with FGR, MOP was associated with specific-lesions(i.e., EDVH and KSK) in PVM, which are not identified by the standard ‘Amsterdam-Placental-Workshop-Group criteria’. This finding suggests that targeted-analysis of EDVH and KSK, alongside the standard ‘Amsterdam-Placental-Workshop-Group-criteria’ may improve the prediction of MOP-development in the setting of early-preterm FGR.