Maternal medicine: Morphometric placental villous and vascular abnormalities in early‐ and late‐onset pre‐eclampsia with and without fetal growth restriction

Abstract

Objective To evaluate placental morphology in pregnancies complicated by early-and late-onset pre-eclampsia (PET) with and without fetal growth restriction (FGR) using stereological techniques.Design A total of 69 pregnant women were studied. Twenty women had pregnancies complicated by PET, 17 by FGR and 16 by both PET and FUR; the remaining 16 were from gestationalage-matched controls. Each group was further classified into early onset (<34 weeks) and late onsets (>34 weeks) based on gestational ages.Setting NPIMR at Northwick Park and St Marks Hospital.Population placentae from pregnant women.Methods Formalin-fixed, wax-embedded sections stained with anti-CD34 antibodies and counterstained with haematoxylin.Main outcome measures Volumes, surface areas, lengths, diameters and shape factors of the villous tissues and fetal vasculature in the intermediate and terminal villi of all the groups studied.Results Terminal villi volume and surface area were compromised in early-onset PET cases, late-onset PET had no impact on peripheral villi or vasculature features. The morphology of the vascular and villous subcomponents in the intermediate and terminal villi was significantly influenced by late-onset FGR, whereas early-onset FGR caused a reduction in placental weight. Length estimates were not influenced by PET, FGR or age of onset. Intermediate arteriole shape factor was significantly reduced in late-onset FGR.Conclusions Isolated early-onset PET was associated with abnormal placental morphology, but placentas from late-onset PET were morphologically similar to placentas from gestational-age-matched controls, confirming the existence of two subsets of this condition and supporting the hypothesis that late-onset PET is a maternal disorder and not a placental disease.

Angiogenic Factors in Superimposed Preeclampsia

“…[22][23][24][25][26] It has also been suggested that women with chronic hypertension or diabetes mellitus develop PE in the context of smaller increments of sFlt and sEng, because there is already preexisting maternal endothelial cell dysfunction. 27 Our finding of more significant alterations in angiogenic factors in early versus late-onset SPE are consistent with reports that more severe placental dysfunction distinguishes early onset from late-onset SPE in women without preexisting hypertension.…”

Maternal serum insulin-like growth factor-binding protein-3 (IGFBP-3) at 11–13 weeks in preeclampsia

“…1,2 The underlying mechanism for early-PE, requiring delivery before 34 weeks, is thought to be impaired placentation because of inadequate trophoblastic invasion of the maternal spiral arteries, which has been documented by the findings of both histologic and Doppler ultrasound studies of the uterine arteries, [3][4][5][6][7][8] reduced maternal serum concentration of the placental product pregnancy-associated plasma protein-A (PAPP-A) 9 and impaired fetal growth. 10 In contrast late-PE, which is usually associated with normal placentation and fetal growth, 11,12 is thought to be a manifestation of an underlying metabolic disorder with increased insulin resistance. [13][14][15] Insulin-like growth factor-binding protein 3 (IGFBP-3) belongs to the family of IGFBPs, which determine the bioavailability and activity of the IGFs.…”

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia

“…In particular, microarray analysis has described the lower expression of at least two angiogenesis-associated transcripts (Egfl7 and Acvrl1) in EOPE compared to LOPE or agematched controls [15]. Therefore, reduced placental angiogenesis could be responsible for the impaired placental blood flow observed in EOPE, while the observed normal blood flow in LOPE could result from either no alterations or increased placental angiogenesis [3,6,13].…”

“…Specifically, Doppler studies reveal that impaired feto-placental blood flow is mainly evident in women with early-onset preeclampsia (EOPE) [8] rather than late-onset preeclampsia (LOPE) [9]. Moreover, EOPE exhibits placental histological changes related with reduced perfusion [10][11][12][13] as well as the anomalous structure of the peripheral villi and vasculature compared to respective controls identified by stereological analysis following EOPE, but not LOPE [13]. In addition, low placental levels of several pro-angiogenic factors have been reported in EOPE compared to LOPE or age-matched controls [14,15].…”