Working towards a Reproducible Method for Quantifying Placental Syncytial Knots

Abstract

Prominent syncytial knots (SK) in placentas signal advanced gestation or placental malperfusion, reflecting exposures that adversely affect placental development and pregnancy outcomes. Molecular-level interrogations of syncytiotrophoblast have altered perceptions of and raised questions about the function and disposition of SK. Quantifying SK and achieving acceptable levels of interrater reliability have been challenging. Our objective was to develop a simple, reproducible protocol for counting SK and demonstrate interrater reliability overall and within 3 parameters, ie, preterm vs term delivery, presence vs absence of diffuse prominent SK (DPSK), and SK relationship with a lesion, all of which could influence measurement reproducibility and interpretation. Criteria for defining SK and a grid system drawn on glass slides were developed for counting percentage of villi with SK. One disc section each from 151 placentas, sampled from 8 groups defined by the 3 parameters, was assessed by 2 pretrained pathologists. The resulting weighted kappa statistic for overall interrater agreement was 0.60 (very good) and Spearman correlation coefficient for ranking quartiles was >0.70. Agreement was best for preterm placentas, kappa = 0.61, and those only showing DPSK associated with a lesion, kappa = 0.67. Agreement was low in the absence of DPSK, kappa = 0.22, or when DPSK was present in a placenta not associated with a lesion, kappa = 0.32. The proposed method offers a potentially reliable approach for categorizing SK counts as normal vs abnormal or providing continuous measure counts. More extensive pretraining, focused on placentas with few SK and those without an associated lesion, is recommended to improve agreement.