Circulating angiogenic profiles and histo-morphological placental characteristics of uncomplicated post-date pregnancies

Abstract

Introduction: The objectives of this study were to describe the histo-morphology of post-date placentas in clinically uncomplicated pregnancies without adverse delivery outcomes and the association with maternal circulating pre-delivery Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), as well as the sFlt-1/PlGF ratio.

Methods: Post-date placentas (gestational week ≥40⁺², n = 87) were macroscopically and histo-morphologically assessed according to the international, standardized Amsterdam Workshop Consensus Group criteria. Inter-rater agreement was evaluated by percentage of agreement. PlGF and sFlt-1 concentrations were available from maternal serum sampled close to delivery, and were compared by Mann-Whitney U test. Linear regression analyses were adjusted for predefined potential confounders.

Results: The majority of the post-date placentas showed morphological signs of delayed maturation. About half of the placentas showed increased syncytial knotting and fibrin. In placentas with increased presence of intervillous fibrin, median maternal PlGF level was significantly lower (p = 0.004), median sFlt-1 level higher and sFlt-1/PlGF ratio significantly higher (p = 0.002) compared to those with normal fibrin amounts. Increased placental syncytial knotting was associated with lower levels of PlGF, higher sFlt-1 and higher sFlt-1/PlGF ratio compared to those with normal knotting.

Discussion: Our standardized morphological study of post-date placentas in clinically healthy women with uncomplicated pregnancies and delivery outcomes revealed delayed maturation in the majority of placentas. Increased pre-delivery circulating anti-angiogenic profile was associated with increased intervillous fibrin and syncytial knotting. We propose that circulating maternal angiogenic biomarkers may be of future use in clinical post-date pregnancy assessment, as they reflect important aspects of placental health and function.

Trial registration: ClinicalTrials.gov NCT03100084.

Keywords: Angiogenic factors; Delayed villous maturation; Placental growth factor; Post-date pregnancy; Soluble fms-like tyrosine kinase-1; Syncytial knotting.