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Review Article Placenta Accreta Spectrum: a Review of Pathology, Molecular Biology, and Biomarkers

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Review Article Placenta Accreta Spectrum: a Review of Pathology, Molecular Biology, and Biomarkers Placenta Accreta Spectrum: A Review of Pathology, Molecular Biology, and Biomarkers. Item Type Article Authors Bartels, Helena C;Postle, James D;Downey, Paul;Brennan, Donal J Citation Helena C. Bartels, James D. Postle, Paul Downey, and Donal J. Brennan, “Placenta Accreta Spectrum: A Review of Pathology, Molecular Biology, and Biomarkers,” Disease Markers, vol. 2018, Article ID 1507674, 11 pages, 2018. https:// doi.org/10.1155/2018/1507674. DOI 10.1155/2018/1507674 Publisher Hindawi Journal Disease Markers Rights Attribution-NonCommercial-NoDerivs 3.0 United States Download date 07/10/2021 06:20:50 Item License http://creativecommons.org/licenses/by-nc-nd/3.0/us/ Link to Item http://hdl.handle.net/10147/623961 Find this and similar works at - http://www.lenus.ie/hse Hindawi Disease Markers Volume 2018, Article ID 1507674, 11 pages https://doi.org/10.1155/2018/1507674 Review Article Placenta Accreta Spectrum: A Review of Pathology, Molecular Biology, and Biomarkers 1 1 1 1,2 Helena C. Bartels , James D. Postle, Paul Downey, and Donal J. Brennan 1National Maternity Hospital, Holles Street, Dublin 2, Ireland 2UCD School of Medicine, National Maternity Hospital, Holles Street, Dublin 2, Ireland Correspondence should be addressed to Donal J. Brennan; [email protected] Received 20 March 2018; Accepted 10 June 2018; Published 3 July 2018 Academic Editor: Irene Rebelo Copyright © 2018 Helena C. Bartels et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Placenta accreta spectrum (PAS) is a condition of abnormal placental invasion encompassing placenta accreta, increta, and percreta and is a major cause of severe maternal morbidity and mortality. The diagnosis of a PAS is made on the basis of histopathologic examination and characterised by an absence of decidua and chorionic villi are seen to directly adjacent to myometrial fibres. The underlying molecular biology of PAS is a complex process that requires further research; for ease, we have divided these processes into angiogenesis, proliferation, and inflammation/invasion. A number of diagnostic serum biomarkers have been investigated in PAS, including human chorionic gonadotropin (HCG), pregnancy-associated plasma protein-A (PAPP-A), and alpha-fetoprotein (AFP). They have shown variable reliability and variability of measurement depending on gestational age at sampling. At present, a sensitive serum biomarker for invasive placentation remains elusive. In summary, there are a limited number of studies that have contributed to our understanding of the molecular biology of PAS, and additional biomarkers are needed to aid diagnosis and disease stratification. 1. Introduction major obstetric haemorrhage and peripartum hysterectomy [5]. Mortality rates of up to 7% have been reported to be asso- Placenta accreta was first described in 1937 by Irving et al. as ciated with PAS [6]. The most recent confidential inquiry failure of separation of the placenta from the uterine wall fol- into maternal mortality in the United Kingdom lowing delivery of the human fetus leading to the often used (MMBRACE-UK, 2017) highlighted the continued high term morbid placental adherence [1]. The condition is char- maternal mortality associated with the condition [7]. acterised by invasive placentation which is associated with The most important antenatal risk factor for PAS is the catastrophic haemorrhage. Varied terminology has been number of previous caesarean sections. In the presence of applied to this condition; however, recent guidelines sug- low-lying placenta (placenta previa) and three previous cae- gested that placenta accreta spectrum (PAS), which includes sarean sections, a woman would have a 61% risk of PAS accreta, increta, and percreta (defined below), be used going [8]. Antenatal diagnosis is a key element to improving mater- forward [2]. The condition is unique to human pregnancy nal and perinatal outcome. Although dedicated ultrasound with no animal correlate reported in the literature [3]. and MRI having improved antenatal diagnosis, between The incidence of PAS has increased substantially from one half and two thirds of cases remain undiagnosed, result- 0.8 per 1000 deliveries in the 1980s to 3 per 1000 deliveries ing in poorer maternal outcomes [9, 10]. Hence, there is a in the past decade, a phenomenon attributed to a rising continued need to develop and study methods to improve global caesarean section rate [4]. PAS is associated with sig- the antenatal diagnosis of PAS, particularly in the first tri- nificant maternal morbidity and mortality, in particular, mester. This review aims to assess the existing evidence on 2 Disease Markers (a) (b) (c) (d) (e) (f) Figure 1: Histopathology of placenta accreta syndrome. (a) High-power picture of decidualised endometrium as a result of pregnancy. Stromal cells are large, pale, and polygonal. (b) Low-power image of decidualised endometrium on the surface with underlying congested myometrial blood vessels and myometrium. (c) Low-power image of PAS showing chorionic villi in direct contact with myometrium (no intervening decidua). (d) Chorionic villus with polar trophoblast invading myometrial muscle. (e) Nonadherent area of the same placenta where decidua is seen between villi (bottom right) and myometrium (top left). (f) PAS—chorionic villi in direct contact with muscle; a multinucleated extravillous trophoblast is seen in the top right. the pathology, molecular biology, and biomarkers associated most common component of PAS and accounts for 75% of with PAS. cases. Mild forms of PAS may present as retained placenta that may require manual removal. When PAS is identified, 2. Pathology the placentas are more often affected by chronic basal inflammation, changes of maternal vascular malperfusion, PAS refers to a spectrum of abnormal placental adherence and retromembranous and subchorionic/intervillous haem- ranging from the subclinical (often microscopic) finding of orrhage [16]. adherent myometrial fibres within the basal plate to a The diagnosis of a PAS is made on the basis of histo- dramatic presentation of placenta percreta, where there is pathologic examination and characterised by an absence of placental invasion through the uterus and the serosa into decidua and chorionic villi are seen to directly adjacent to the peritoneal cavity or bladder. myometrial fibres (Figure 1). Although not visible macro- Traditionally, PAS is thought to occur as a consequence scopically, microscopic examination of the placenta may of a localised uterine injury (e.g., previous caesarean section) confirm the presence of (placental) basal plate myometrial which can result in locally defective decidualisation/scarring fibres (Figure 1); although this finding can be seen in nor- and abnormal placental adherence in a subsequent preg- mal pregnancies, their presence is thought to indicate nancy. Although typically attributed to previous caesarean abnormal placental separation. Perhaps more importantly, delivery, even small disruptions to the lining of the uterus basal plate myometrial fibres are associated with an can result in subsequent placenta accreta [11]. While interac- increased risk of a morbidly adherent placenta in a subse- tions between the maternal-fetal interface may also play a quent placenta/pregnancy [14]. role in the pathogenesis of placenta accreta, this is beyond the scope of this article, and a number of studies describing 3. Molecular Biology the pathology of PAS in detail have been published [12–15]. Abnormal adherence of the placenta to the myometrium The development of PAS is a complex multifactorial process. is established in very early pregnancy and can be subdivided Normal placentae do not proceed beyond the inner third of into placenta accreta (where chorionic villi directly implant the myometrium through tight spatial and temporal regula- on to the myometrium), placenta increta (where chorionic tion; however, an invasive placenta proliferates and invades villi invade into the myometrium), and placenta percreta local structures in a similar fashion to a malignant tumour. (where chorionic villi invade through the myometrium and The underlying molecular mechanisms of invasive placenta- may involve surrounding structures). Placenta accreta is the tion are poorly understood; proposed hypotheses include a Disease Markers 3 Inducing Angiogenesis: Sustained proliferative (1) Upregulation of angiogenic signalling: growth factors: VEGF, Ang-2, (1) EGFR RLN, RXFPI (2) c-erB-2 oncogene (1) Suppressed antiangiogenic factors: sFlt-1 expression Enabling replicative Activating Invasion: immortality: (1) Persistent EMT throughout (1) Shortened telomeres pregnancy (2) Altered cellular senescence (2) Increased MMP-2, MMP-9 Placenta accreta spectrum Evading immune destruction: Resisting cell death (1) Increased: − FoxP3+ Tregs, Suppressed: CD25+ T-cells (1) INSL4 (2) Decreased: − CD4+ T cells, (2) microRNA-29a/b/c CD209+ DC, dNK, CD56+ upregulated MCL1 Reprogramming of energy Evading growth suppressors: metabolism: (1) p53 expression reduced (1) low levels of PAPP-A low insulin like growth factor Figure 2: Similarities between PAS and cancer. Figure showing the 8 hallmarks of cancer as described by Weinberg and Hannahan and the similarities to the molecular biology of PAS [18]. combination of primary absence of the decidua or basal plate, expression [22] as demonstrated by decreased expression
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