Abstract
Placental pathological abnormalities are more frequently observed in complicated pregnancies than in healthy pregnancies. Infiltration of CD8+ T-cells into the placental villous tissue occurred in both fetal growth restriction and pre-eclampsia, whereas CD79α+ B-cell infiltration was only apparent with reduced fetal growth. Vascularization, fibrin depositions, macrophage and neutrophil infiltration in the placenta did not differ between healthy and complicated pregnancies. Fetal growth restriction (FGR) and pre-eclampsia are severe, adverse pregnancy outcomes. Alterations in placental histology are frequently reported in these pregnancy complications and are often based upon scoring by pathologists. However, many alterations are also observed in placenta from uncomplicated pregnancies. Moreover, knowledge of disease state may bias assessment. We sought to perform an objective comparison of placental microscopic appearance in normal and complicated pregnancies. Placental villous tissue (n=823) and edge biopsies (n=488) from 871 individual, singleton pregnancies were collected after delivery. Cases of small-for-gestational age (SGA) or pre-eclampsia were matched with healthy controls. A subset of the SGA cases displayed signs of FGR. Cases of preterm delivery were also included. Tissue sections were stained with haematoxylin and eosin or antibodies for CD8, CD14, CD31, CD79α and elastase. Images were scored by two experienced pathologists for pathological features or analysed by image analysis and stereology. Analyses were performed blind to case-control status and gestational age. Volume fraction of T-cells increased in placentas from pregnancies complicated by pre-eclampsia (adjusted odds ratio (aOR) 1.46, 95% CI: 1.12-1.90) and FGR (aOR 1.64, 95% CI: 1.11-2.43), whereas B-cells only increased in FGR (aOR 1.65, 95% CI: 1.05-2.60). Pathological abnormalities in villous tissue were reported in 21.4% (88/411) of complicated pregnancies and 14.3% (52/363) of controls (OR 1.62, 95% CI: 1.12-2.37). There were no differences in the fractions of endothelial cells, fibrin deposition, macrophages and neutrophils when comparing normal and complicated pregnancies. In conclusion, FGR and pre-eclampsia are associated with T-cell infiltration of the placenta and placental pathological abnormalities.
Highlights
Each year millions of pregnancies worldwide are complicated by fetal growth restriction (FGR) or pre-eclampsia
For the image analysis and stereology, we used four villous biopsies from 775 women stained with haematoxylin and eosin (H&E) and five different antibodies
The current examination by image analysis and stereology is based on quantification of over 18,000 different stained samples
Summary
Each year millions of pregnancies worldwide are complicated by fetal growth restriction (FGR) or pre-eclampsia. These pregnancy complications are associated with a higher risk of mortality and morbidity for both mother and baby (Lawn et al 2014; Salam et al 2014; Say et al 2014; Mol et al 2016). Villitis of unknown aetiology (VUE) is one of the key placental inflammatory lesions (Kim et al 2015). It has previously been shown in VUE that there is an infiltration of T-cells of maternal origin into villous tissue (Redline & Patterson, 1993; Kim et al 2008). Other placental changes reported in association with pregnancy complications include reduced surface area of fetal capillaries and terminal villi (Egbor et al 2006; Mayhew, 2009)
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