Skip to main content
SpringerLink
Log in

Temporal heterogeneity of placental segmental fetal vascular malperfusion: timing but not etiopathogenesis

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Clinicopathologic correlations of segmental villous avascularity and other histological lesions of segmental fetal vascular malperfusion (SFVM) were analyzed retrospectively to determine whether lesions of various durations reflect different etiopathogeneses. The frequencies of 25 independent clinical and 43 placental phenotypes were statistically compared by ANOVA or Chi-square among 3 groups containing a total of 378 placentas with SFVM: group 1 contained 44 cases of recent SFVM (endothelial fragmentation, villous hypovascularity by CD34 immunostain, and/or stromal vascular karyorrhexis); group 2 contained 264 cases of established SFVM (clusters of avascular villi); and group 3 contained 70 cases of remote SFVM (villous mineralization). Statistically significant differences among the three study groups (p Bonferroni < 0.002) were found in four clinical variables (gestational age, frequencies of macerated stillbirth, induction of labor, and cesarean section) and in five placental variables (frequencies of fetal vascular ectasia, stem vessel luminal vascular abnormalities, diffusely increased extracellular matrix in chorionic villi, chorionic disk extravillous trophoblast microcysts, and excessive extravillous trophoblasts in the chorionic disc). In summary, the absence of statistically significant differences between the study groups regarding the most common causes of SFVM (hypertensive conditions of pregnancy, diabetes mellitus, fetal anomalies, and clinical and pathological features of umbilical cord compromise) is evidence that the three types of SFVM reflect temporal heterogeneity rather than etiopathogenesis. This evidence can be used to date the onset of fetal vascular malperfusion before delivery or stillbirth. The coexistence of different SVFM lesions of various durations indicates ongoing or repeat occurrences of FVM rather than single episodes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Stanek J (2013) Hypoxic patterns of placental injury: a review. Arch Pathol Lab Med 137:706–720

    Article  PubMed  Google Scholar 

  2. Boyd TH, Roberts DJ, Heerema-McKenney A (2019) Fetal vascular malperfusion. In: Khong TY, Mooney EE, Nikkels PGJ, Morgan TH, Gordinj SJ (eds) Pathology of the Placenta. Springer, p 173

  3. Heider A (2017) Fetal vascular malperfusion. Arch Pathol Lab Med 141:1484–1489

    Article  PubMed  Google Scholar 

  4. Stanek J, Biesiada J (2016) Clustering and classical analysis of clinical and placental phenotypes in fetal growth restriction and constitutional fetal smallness. Placenta 42:93–105

    Article  PubMed  Google Scholar 

  5. Roberts DJ, Boyd TK, Kelehan P, Heerema-McKenney A (2019) Fetal vascular thrombosis. In: Khong TY, Mooney EE, Nikkels PGJ, Morgan TH, Gordinj SJ (eds) Pathology of the Placenta. Springer, p 91

  6. Redline RW, Wilson-Costello D, Borawski E, Fanaroff AA, Mack M (1998) Placental lesions associated with neurologic impairment and cerebral palsy in very low-birth-weight infants. Arch Pathol Lab Med 122:1091–1098

    CAS  PubMed  Google Scholar 

  7. Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler MA et al (2016) Sampling and definitions of placental lesions, Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med 140:698–713

    Article  PubMed  Google Scholar 

  8. Ernst L (2015) Distal villous lesions associated with fetal vascular occlusion. In: Heerema-McKenney A, Popek EJ, DePaepe ME (eds) Diagnostic pathology: placenta. Amirsys, Elsevier, Philadelphia II-6-8

    Google Scholar 

  9. Kingdom JC, Audette MC, Hobson SR, Windrim RC, Morgen E (2018) A placenta clinic approach to the diagnosis and management of fetal growth restriction. Am J Obstet Gynecol 218(2S):S803–S817

    Article  PubMed  Google Scholar 

  10. Genest DR (1992) Estimating the time of death in stillborn foetuses: II. Histologic evaluation of the placenta; a study of 71 stillborns. Obstet Gynecol 80:585–592

    CAS  PubMed  Google Scholar 

  11. Stanek J, Biesiada J (2012) Clustering of maternal/fetal clinical conditions and outcomes and placental lesions. Am J Obstet Gynecol 206:493.a1–493.a9

    Article  Google Scholar 

  12. Simcox LE, Ormesher L, Tower C, Greer IA (2015) Thrombophilia and pregnancy complications. Int J Mol Sci 16:28418–28428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Stanek J, Abdaljaleel M (2019) CD34 immunostain increases the sensitivity of placental diagnosis of fetal vascular malperfusion in stillbirth. Placenta 77:30–38

    Article  CAS  PubMed  Google Scholar 

  14. Stanek J (2018) Fetal vascular malperfusion. Arch Pathol Lab Med 142:679–680

    Article  PubMed  Google Scholar 

  15. Ariel I, Meir K (2019) Mineralization of trophoblast basement membrane. In: Khong TY, Mooney EE, Nikkels PGJ, Morgan TK, Gordinj SJ (eds) Pathology of the Placenta. Springer, p 143

  16. Stanek J (2010) Placental haemosiderosis. Pathology 42:499–501

    Article  PubMed  Google Scholar 

  17. Stanek J (2019) Segmental villous mineralization: a placental feature of fetal vascular malperfusion. Placenta 86:20–27

    Article  PubMed  Google Scholar 

  18. Stanek J (2020) Grading fetal vascular malperfusion in the placenta and short term perinatal outcome. Society for Pediatric Pathology Spring Meeting, Los Angeles, CA, February 28-March 1, 2020; Abstract #10

  19. Stanek J, Weng E (2007) Microscopic chorionic pseudocysts in placental membranes: a histologic lesion of in utero hypoxia. Pediatr Dev Pathol 10:192–198

    Article  PubMed  Google Scholar 

  20. Stanek J (2018) Placental examination in nonmacerated stillbirth versus neonatal mortality. J Perinat Med 46:323–331

    Article  PubMed  Google Scholar 

  21. Stanek J (2011) Chorionic disc extravillous trophoblasts in placental diagnosis. Am J Clin Pathol 136:540–547

    Article  PubMed  Google Scholar 

  22. Fox H, Sebire NJ (2007) Pathology of the placenta. Saunders, London

    Google Scholar 

  23. Muench MO, Kapidzic M, Gormley M, Gutierrez AG, Ponder KL, Fomin ME, Beyer AI, Stolp H, Qi Z, Fisher SJ, Bárcena A (2017) The human chorion contains definitive hematopoietic stem cells from fifteenth week of gestation. Development 144:1399–1411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. McDermott M, Gillan JE (1995) Trophoblast basement membrane haemosiderosis in the placental lesion of fetal artery thrombosis: a marker for disturbance of maternofetal transfer. Placenta 16:171–178

    Article  CAS  PubMed  Google Scholar 

  25. Pierce BT, Martin LS, Hume RF, Calhoun BC, Muir-Padilla J, Salafia CM (2002) Relationship between the extent of histologic villous mineralization and stillbirth in aneuploidy and euploid fetuses. J Soc Gynecol Investig 9:290–293

    Article  PubMed  Google Scholar 

  26. Korteweg FJ, Erwich JJHM, Timmer A, van der Meer J, Ravisé JM, Veedger NJGM et al (2012) Evaluation of 1025 fetal deaths: proposed diagnostic workup. Am J Obstet Gynecol 206:53.e1–53.12

    Article  Google Scholar 

  27. Opsjøn BE, Vogt C (2016) Explaining fetal death-what are the contributions of fetal autopsy and placenta examination? Pediatr Dev Pathol 19:24–30

    Article  PubMed  Google Scholar 

  28. Ptacek I, Sebire NJ, Man JA, Brownbill P, Heazell AEP (2014) Systematic review of placental pathology reported in association with stillbirth. Placenta 35:552–562

    Article  CAS  PubMed  Google Scholar 

  29. Gekas C, Dieterlen-Lièvre F, Orkin SH, Mikkola KA (2005) The placenta is a niche for hematopoietic stem cells. Dev Cell 8:365–375

    Article  CAS  PubMed  Google Scholar 

  30. Gao K, He S, Kumar P, Farmer D, Zhou J, Wang A (2020) Clonal isolation of endothelial colony-forming cells from early gestation chorionic villi of human placenta for fetal tissue regeneration. World J Stem Cells 12:123–138

    Article  PubMed  PubMed Central  Google Scholar 

  31. Liu H, Li Y, Zhang J, Rao M, Liang H, Liu G (2015) The defect of both angiogenesis and lymphangiogenesis is involved in preeclampsia. Placenta 36:279–286

    Article  CAS  PubMed  Google Scholar 

  32. Stanek J (2016) Association of coexisting morphological umbilical cord abnormality and clinical cord compromise with hypoxic and thrombotic placental histology. Virchows Arch 468:723–732

    Article  PubMed  Google Scholar 

  33. Baergen RN (2005) Manual of Benirschke and Kauffmann’s pathology of the human placenta. Springer, New York

    Google Scholar 

  34. Redline RW (2004) Clinical and pathological umbilical cord abnormalities in fetal thrombotic vasculopathy. Hum Pathol 325:1494–1498

    Article  CAS  Google Scholar 

  35. Chan JSY, Baergen RN (2012) Gross umbilical cord complications are associated with placental lesions of circulatory stasis and fetal hypoxia. Pediatr Dev Pathol 15:487–494

    Article  PubMed  Google Scholar 

  36. Faye-Petersen OM, Heller DS, Joshi VV (2006) Placental pathology. Taylor & Francis, London and New York

    Google Scholar 

  37. Saade GR, McLintock C (2002) Inherited thrombophilia and stillbirth. Semin Perinatol 26:51–69

    Article  PubMed  Google Scholar 

  38. Vern TZ, Alles AJ, Kowal-Vern A, Longtine J, Roberts DJ (2000) Frequency of factor V(Leiden) and prothrombin G20210A in placentas and their relationship with placental lesions. Hum Pathol 31:1036–1043

    Article  CAS  PubMed  Google Scholar 

  39. Stanek J (2019) Histological features of shallow placental implantation unify early onset and late onset preeclampsia. Pediatr Dev Pathol 22:112–122

    Article  PubMed  Google Scholar 

  40. Stanek J, Drummond Z (2007) Occult placenta accreta: the missing link in the diagnosis of abnormal `placentation. Pediatr Dev Pathol 10:266–273

    Article  PubMed  Google Scholar 

  41. Pinar H, Carpenter M (2010) Placenta and umbilical cord abnormalities seen with stillbirth. Clin Obstet Gynecol 53:656–672

    Article  PubMed  Google Scholar 

  42. Kingdom JC, Kaufmann P (1997) Oxygen and placental villous development: origins of fetal hypoxia. Placenta 18:613–621

    Article  CAS  PubMed  Google Scholar 

  43. Burton GJ, Jauniaux E (2018) Patophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol 218(2S):S745–S761

    Article  CAS  PubMed  Google Scholar 

  44. Paules C, Youssef L, Rovira C, Crovetto F, Nadal A, Peguero A, Figueras F, Eixarch E, Crispi F, Miranda J, Gratacós E (2019) Distinctive patterns of placental lesions in pre-eclampsia vs small-for-gestational age and their association with fetoplacental Doppler. Ultrasound Obstet Gynecol 54:609–616

    Article  CAS  PubMed  Google Scholar 

  45. Redline RW, Pappin A (1995) Fetal thrombotic vasculopathy: the clinical significance of extensive avascular villi. Hum Pathol 26:80–85

    Article  CAS  PubMed  Google Scholar 

  46. Lepais L, Gaillot-Durand L, Boutitie F, Lebreton F, Buffin R, Huissoud C, Massardier J, Guibaud L, Devouassoux-Shisheboran M, Allias F (2014) Fetal thrombotic vasculopathy is associated with thromboembolic events and adverse perinatal outcome but not with neurologic complications: a retrospective cohort study of 54 cases with a 3-year follow-up of children. Placenta 35:611–617

    Article  CAS  PubMed  Google Scholar 

  47. The Stillbirth Collaborative Research Network Writing Group (2011) Causes of death among stillbirths. JAMA 306:2459–2468

    Article  PubMed Central  Google Scholar 

  48. Stanek J (2019) Patterns of placental injury in congenital anomalies in second half of pregnancy. Pediatr Dev Pathol 22:513–522

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pathology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45255, USA

    Jerzy Stanek

Authors
  1. Jerzy Stanek
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The author is the only contributor.

Corresponding author

Correspondence to Jerzy Stanek.

Ethics declarations

Conflict of interest

The author declares that he has no conflict of interest.

Ethical approval

This study was approved by the institutional review board (IRB #2016-7942) and complies with ethical standards.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Quality in Pathology

Electronic supplementary material

ESM 1

(XLSX 81 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stanek, J. Temporal heterogeneity of placental segmental fetal vascular malperfusion: timing but not etiopathogenesis. Virchows Arch 478, 905–914 (2021). https://doi.org/10.1007/s00428-020-02916-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-020-02916-3

Keywords

Search

Navigation