Formulating a Meaningful and Comprehensive Placental Phenotypic Classification

Introduction: While many placental lesions have been identified and defined, the significance of multiple overlapping lesions has not been addressed. The purpose of our analysis was to evaluate overlapping patterns of placental pathology and determine meaningful phenotypes associated with adverse birth outcomes. Methods: Placental pathology reports were obtained from a single hospital between 2009 and 2018. Placental lesions were grouped into four major categories: acute inflammation (AI), chronic inflammation (CI), maternal vascular malperfusion (MVM), and fetal vascular malperfusion (FVM). Within each category, lesions were classified as not present, low grade or high grade. Combinations of pathologies were evaluated in relation to preterm birth (<37 weeks) and small for gestational age (SGA) infant (birthweight <10th percentile). Results: During the study period, 19,027 placentas were reviewed by pathologists. Results from interaction models indicate that MVM and MVM in combination with CI and/or FVM are associated with the greatest odds of SGA infant and PTB. When incorporating grade, we identified 21 phenotype groups, each with characteristic associations with the SGA infant and patterns of PTB. Discussion: We have developed a comprehensive and meaningful placental phenotype that incorporates severity and multiplicity of placental lesions. We have also developed a web application to facilitate phenotype determination (https://placentaexpression.shinyapps.io/phenotype).