Phenotypes of maternal vascular malperfusion placental pathology and adverse pregnancy outcomes: A retrospective cohort study.

Objective: To identify which components of maternal vascular malperfusion (MVM) pathology are associated with adverse pregnancy outcomes and to investigate the morphological phenotypes of MVM placental pathology and their relationship with distinct clinical presentations of pre-eclampsia and/or fetal growth restriction (FGR).

Design: Retrospective cohort study.

Setting: Tertiary care hospital in Toronto, Canada.

Population: Pregnant individuals with low circulating maternal placental growth factor (PlGF) levels (<100 pg/mL) and placental pathology analysis between March 2017 and December 2019.

Methods: Association between each pathological finding and the outcomes of interest were calculated using the chi-square test. Cluster analysis and logistic regression was used to identify phenotypic clusters, and their association with adverse pregnancy outcomes. Cluster analysis was performed using the K-modes unsupervised clustering algorithm.

Main Outcome Measures: Preterm delivery <34 weeks of gestation, early onset pre-eclampsia with delivery <34 weeks of gestation, birthweight <10th percentile (small for gestational age, SGA) and stillbirth.

Results: The diagnostic features of MVM most strongly associated with delivery <34 weeks of gestation were: infarction, accelerated villous maturation, distal villous hypoplasia and decidual vasculopathy. Two dominant phenotypic clusters of MVM pathology were identified. The largest cluster (n = 104) was characterised by both reduced placental mass and hypoxic ischaemic injury (infarction and accelerated villous maturation), and was associated with combined pre-eclampsia and SGA. The second dominant cluster (n = 59) was characterised by infarction and accelerated villous maturation alone, and was associated with pre-eclampsia and average birthweight for gestational age.

Conclusions: Patients with placental MVM disease are at high risk of pre-eclampsia and FGR, and distinct pathological findings correlate with different clinical phenotypes, suggestive of distinct subtypes of MVM disease.