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The “Great Obstetrical Syndromes” are associated with disorders of deep placentation
Open accessAbstract
Defective deep placentation has been associated with a spectrum of complications of pregnancy including preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. The disease of the placental vascular bed that underpins these complications is commonly investigated with targeted biopsies. In this review, we critically evaluate the biopsy technique to summarize the salient types of defective deep placentation, and propose criteria for the classification of defective deep placentation into 3 types based on the degree of restriction of remodeling and the presence of obstructive lesions in the myometrial segment of the spiral arteries.
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“Inadequate placentation is seen in several common obstetrical syn dromes, including fetal growth restriction, spontaneous second trimester miscarriages, placental abruption, preterm birth, and hyper tensive disorders in pregnancy (Brosens et al., 2011).”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Brosens et al., 2011
In the citing paper
“Failure of trophoblast invasion and arterial remodeling is associated with the 'Great Obstetrical Syndromes', including growth restriction, pre-eclampsia and late spontaneous abortion, due to impaired maternal perfusion (64).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [64]
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“Abnormal spiral artery remodeling is a common feature of placental dysfunction, resulting in impaired placental blood supply [3], which can affect fetal growth.”
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“…are directly associated with several pregnancy complications, such as preeclampsia, intrauterine growth restriction, preterm birth, and stillbirth (Brosens et al. 2011; Burton and Jauniaux 2018; Del Gobbo et al. 2020; Freedman et al. 2019; Hemberger and Dean 2023; Jauniaux et al. 2006; Kaufmann…”
Mone, F., Mulcahy, C., McParland, P., Downey, P., Culliton, M., Maguire, O. C., Mooney, E. E., Clarke, P. C., Fitzgerald, D., Tully, E. C., et al. (2019) · American Journal of Perinatology · doi:10.1055/s-0038-1677476 · Cited by 10
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“Destructive lesions later result during the second half of pregnancy from ischemic placental syndromes expressed as the great obstetrical syndromes.(7) Trimester-specific MPF triad diseases then negatively impact peripartum, neonatal, and pediatric outcomes.”
Engineered models for placental toxicology: Emerging approaches based on tissue decellularization
Parameshwar, P. K., Sagrillo‐Fagundes, L., Portilho, N. A., Pastor, W. A., Vaillancourt, C., & Moraes, C. (2022) · Reproductive Toxicology · doi:10.1016/j.reprotox.2022.07.003 · Cited by 10
Innervation of the placenta and uterus: Competition between cytotrophoblasts and nerves?
Nelson, P. G., & Nelson, K. B. (2013) · Placenta · doi:10.1016/j.placenta.2013.03.004 · Cited by 10
Placental Function in Maternofetal Exchange
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Brosens, I. A., Brosens, J. J., Muter, J., & Benagiano, G. (2020) · Placenta · doi:10.1016/j.placenta.2020.06.012 · Cited by 10
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“Reduced subpulmonary ventricular function before and during pregnancy is associated with impaired uteroplacental circulation [13, 23, 24], which, in turn, is associated with adverse maternal and neonatal outcome [25, 26].”
BackgroundExpression of DAB2IP in human trophoblast and its role in trophoblast invasion
Shan, N., Xiao, X., Chen, Y., Luo, X., Yin, N., Deng, Q., & Qi, H. (2015) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2014.1001974 · Cited by 10
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“Many common pregnancy complications, such as fetal growth restriction (FGR), pre-eclampsia, and stillbirth, are primarily associated with placental dysfunction [8].”
Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface
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“These examples highlight the importance of CXADR during critical periods of development and emphasize the relevance of our data in providing pivotal insights into the molecular regulation of trophoblast cell type-speci fi c differentiation pathways 1,73,74 .”
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Self-citationThe Chromosome 19 miRNA cluster guards trophoblasts against overacting innate immunity
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“Shallow invasion of the EVTs is associated with the pregnancy complications, such as pre-eclampsia, fetal growth restriction, and stillbirth 29 .”
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Paranavitana, L., Walker, M., Chandran, A. R., Milligan, N., Shinar, S., Whitehead, C. L., Hobson, S. R., Serghides, L., Parks, W. T., Baschat, A., et al. (2021) · Biology of Sex Differences · doi:10.1186/s13293-021-00362-7 · Cited by 9
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“The placenta plays an essential role in conceptus maintenance in the uterine environment, supplying oxygen, and nutrients and protecting it against harmful exogenous agents present in maternal blood flow [1].”
BackgroundUterus transplantation in the human: a complex surgical, medical and ethical challenge
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“Although the exact cause of pre-eclampsia (PE) is unknown, disordered placentation during early trophoblastic invasion of the maternal placental bed is a key feature [2].”
BackgroundPlacental Abruption Associated with Cerebral Palsy
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“The shift from a low to an increasingly normal physiological oxygen environment late in the first trimester [4] is a critical time in placental development, with deficiency in EVT invasion associated with complications ranging from miscarriage to preeclampsia [5,6].”
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Is there a role for placental histopathology in predicting the recurrence of preterm birth?
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“While the etiology of HDP is largely unknown it is considered to probably be multifactorial, including a role for endothelial damage in various organs and “defective deep placentation” [7].”
BackgroundSiegmund, A. S., Willems, T. P., Pieper, P. G., Bilardo, C. M., Gorter, T. M., Bouma, B. J., Jongbloed, M. R. M., Sieswerda, G. T., Roos‐Hesselink, J. W., van Dijk, A. P. J., et al. (2020) · Journal of Cardiovascular Magnetic Resonance · doi:10.1186/s12968-020-00645-9 · Cited by 9
Risk factors for third stage placental complications among primigravid women
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“…remodeling observed has been suggested to typically preserve the placental bed near the cord insertion while compromising vessels at the periphery [28, 29]; therefore, future study will focus on regional variation and histogram analysis This idea of regionalization is also supported by the…”
BackgroundXie, N., Wang, F., Chen, D., Zhou, J., Xu, J., & Qu, F. (2024) · PLoS ONE · doi:10.1371/journal.pone.0300461 · Cited by 8
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“Abnormal placentation is a key pathogenetic mechanism underlying various pregnancy complications, including preeclampsia (PE), intrauterine growth restriction, and placenta accreta spectrum (PAS) [1,2].”
Du, L., Zheng, R., Ren, W., Liu, Y., Zhu, X., Chang, S., & Yang, Z. (2025) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-025-01465-1 · Cited by 9
“However, UA hemodynamic abnormalities or inadequate SAR can lead to restricted placental perfusion, contributing to pregnancy complications such as FGR [21, 156], PE [15, 157], stillbirth, and RSA [12].”
Miller, E. C., Bello, N. A., Davis, R., Friedman, A. M., Elkind, M. S. V., Wapner, R. J., & Tom, S. E. (2021) · Journal of Women s Health · doi:10.1089/jwh.2021.0184 · Cited by 8
“38 Another possibility is that APOs may be associated with immunological intolerance and a heightened inflammatory state that portend adverse long-term consequences for the maternal vasculature.”
Kanninen, T. T., Jung, E., Gallo, D. M., Primera, R. J. D., Romero, R. J., Gotsch, F., Suksai, M., Bosco, M., & Chaiworapongsa, T. (2022) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2022.2153034 · Cited by 8
“an antiangiogenic state [1–19], defective deep placentation [20], uteroplacental ischemia [21,22], exaggerated intravascular inflammation [13,23–34], and endothelial cell dysfunction [35–40].”
BackgroundSelf-citationAssociation of polycystic ovary syndrome with multiple health factors and adverse pregnancy outcomes
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“Dis-ruptions in the remodeling of spiral arteries lead to placental dysfunction [15].”
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“There is evidence suggesting that disorders in deep placentation and failure in the physiological transformation of spiral arteries, leading to placental dysfunction, are also associated with spontaneous PTB in a substantial portion of cases [26].”
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“Although the specific pathogenesis of PE remains elusive, it is generally believed that reduced perfusion to the placental is the initial cause of PE [8, 9].”
Abruptio placentae in the baboon (Papio spp.)
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“Diminished placental perfusion may lead to placental insufficiency.(18) Of note, 40% of placentas in this cohort measured ≤10th percentile.”
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“For reasons not yet fully explored, there is frequently a failure of this deep trophoblast invasion in early pregnancy, which leads to premature blood flow to the placenta and placental stress of varying extent, resulting in miscarriages or obstetrical syndromes (Burton & Jauniaux, 2004; Brosens et al., 2011).”
BackgroundInfluentialCaries experience among children born after a complicated pregnancy
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“93% occurred in anemic patients; furthermore, significant obstetrical conditions, including preeclampsia, preterm labor, or birth, are related to biological and physiological immaturity of adolescents, which consists of impaired vascular adaptation of the maternal spiral arteries during the endovascular trophoblast in…”
BackgroundMaternal serum perlecan levels in women with preeclampsia
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Pathophysiology of Preeclampsia
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Reconstructing the human first trimester fetal–maternal interface using single cell transcriptomicsPreprint
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“Until recently, it has been increasingly recognized that obstetric complications affecting fetal outcomes are placenta-induced, proceeding to clinical manifestations, and may be causally related to clinical symptoms.(17) In this study, the placental modification of GDM in two gestational weeks (above 37 and below 37)…”
MethodEarly sonographic evaluation of the placenta in cases with IUGR: A pilot study
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“can also be a biomarker of shallow placentation [25].”
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Metabolomic prediction of severe maternal and newborn complications in preeclampsia
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Metadata
- Authors
- Brosens, I., Pijnenborg, R., Vercruysse, L., & Romero, R.
- Affiliations
- Leuven Institute for Fertility and Embryology (BE)
- Universitair Ziekenhuis Leuven (BE)
- National Institutes of Health (US)
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 204
- Issue
- 3
- Pages
- 193-201
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC3369813
- OpenAlex
- W2034492080
- Cited by
- 1,568
- References
- 82
- Citations by year
- 2026: 123 · 2025: 126 · 2024: 128 · 2023: 147 · 2022: 153 · 2021: 155 · 2020: 145 · 2019: 121 · 2018: 91 · 2017: 79 · 2016: 61 · 2015: 69 · 2014: 66 · 2013: 49 · 2012: 30
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institutes of Health
- U.S. Department of Health and Human Services
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Maternal and fetal healthcare
- Keywords
- great obstetrical syndromes, preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, miscarriage, placental abruption, spiral artery remodeling, placental biopsy
- MeSH terms
- Biopsy, Female, Humans, Placenta, Placenta Diseases, Pregnancy, Pregnancy Complications, Syndrome
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