Skip to main content
SpringerLink
Log in

Placental fetal vascular malperfusion in congenital diaphragmatic hernia

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

Abstract

The success of in-utero or intrapartum treatment for congenital diaphragmatic hernia (CDH) can be impacted by poor placental function; however, this relationship has not yet been studied. To analyze placental histomorphology in CDH, the frequencies of 24 independent clinical and 48 placental phenotypes were compared. Slides from 103 CDH placentas (group 1) and 133 clinical umbilical cord (UC) compromise/anatomical UC abnormality placentas without CDH (group 2) were subjected to hematoxylin/eosin staining and CD34 immunostaining and then examined. CD34 immunostaining was performed to identify clustered distal villi with endothelial fragmentation of recent fetal vascular malperfusion (FVM). Cesarean delivery and ex utero intrapartum treatment were more common in group 1, but group 2 showed a higher frequency of statistically significant increases in other clinical phenotypes. The frequencies of large vessels and distal villous FVMs (clustered endothelial fragmentation by CD34 immunostaining, stromal vascular karyorrhexis, avascular, or mineralized villi) did not differ between the groups, but low-grade distal villous FVMs were statistically significantly more common in group 1 than in group 2, while high-grade distal villous FVMs were significantly more common in group 2 than group 1. Large vessel and distal villous FVMs were manyfold more common in both the CDH and UC compromise groups than in the general population. However, CDH placentas were more likely to show low-grade distal villous FVMs and less likely to show high-grade distal villous FVMs in UC compromise placentas. FVM of CDH may therefore be caused by a similar pathomechanism as that of UC compromise, resulting in impaired placental fetal blood outflow.

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. DeKoninck P, Richter J, Van Mieghem T, Van Schoubroeck D, Allegaert K, De Catte L, Deprest JA (2014) Cardiac assessment in fetuses with right-sided congenital diaphragmatic hernia: case-control study. Ultrasound Obstet Gynecol 43:432–436

    Article  PubMed  CAS  Google Scholar 

  2. Allan LD, Irish MS, Glick PL (1996) The fetal heart in diaphragmatic hernia. Clin Perinatol 23:795–812

    Article  PubMed  CAS  Google Scholar 

  3. Van Mieghem T, Gucciardo I, Done E, Van Schoubroeck D, Graatsma EM, Visser GHA, Verghaeghe J, Deprest J (2009) Left ventricular cardiac function in fetuses with congenital diaphragmatic hernia and the effect of fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol 34:424–429

    Article  PubMed  Google Scholar 

  4. Rudman HA, Stott MC, Loh MY, Clark EC (2018) Rectal varices due to chronic inferior mesenteric vein thrombosis caused by external compression in a large hiatus hernia containing the pancreas. Ann R Coll Surg Engl 100:e171–e173

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Wcislo KM, Hall CE, Abbassi-Ghadi N (2020) Acute Budd-Chiari syndrome causes by inferior vena cava compression from a congenital diaphragmatic hernia. Ann R Coll Surg Engl 102:e202–e204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Gilbert Barness E, Debich-Spicer DE (2005) Handbook of Pediatric Autopsy Pathology. Humana Press, Totowa, pp 258–259 and 267

    Book  Google Scholar 

  7. Cuniff C, Jones KL, Jones MC (1990) Patterns of malformations in children with congenital diaphragmatic defects. J Pediatr 116:258

    Article  Google Scholar 

  8. Bianchi DW, Crombleholme TM, D’Alton ME, Malone FD (2010) Fetology. Diagnosis and management of fetal patients, 2nd edn. McGraw Hill Medical, New York, pp 278–290

    Google Scholar 

  9. Thébaud B, Azanmcot A, de Lagaussie P, Vuillard E, Ferkadji L, Benali K, Beaufils F (1997) Congenital diaphragmatic hernia: antenatal prognostic factors. Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia? Intensive Care Med 23:10062–10069

    Article  PubMed  Google Scholar 

  10. Stevenson RE, Hall JG (eds) (2006) Human malformations and related anomalies. Oxford University Press, pp 214–217

    Google Scholar 

  11. Howe DT, Kilby MD, Sirry H et al (1996) Structural chromosome abnormalities in congenital diaphragmatic hernia. Prenat Diagn 16:1003

    Article  PubMed  CAS  Google Scholar 

  12. Enns GM, Cox VA, Goldstein RB et al (1998) Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: a retrospective study of 60 patients and literature review. Am J Med Genet 79:215

    Article  PubMed  CAS  Google Scholar 

  13. Datin-Dorriere V, Rouzies S, Taupin P, Walter-Nicolet E, Benachi A, Sonigo P, Mitanchez D (2008) Prenatal diagnosis in isolated congenital diaphragmatic hernia. Am J Obstet Gynecol 198:80.e1–80.e5

    Article  PubMed  Google Scholar 

  14. 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 

  15. Stanek J (2022) Patterns of placental injury in various types of fetal congenital heart disease. J Perinat Med 2022(51):704–711

    Google Scholar 

  16. Baptista MJ, Vaz T, Barreira JL, Martins A, Moreira J (2002) Acute aortic thrombosis in a newborn with congenital diaphragmatic hernia masquerading as coarctation of the aorta. Rev Port Cardiol 21:351–353

    PubMed  Google Scholar 

  17. Gu H, Devine M, Hedrick HI, Rintoul NE, Thom CS (2022) High rate of extreme thrombocytosis indicates bone marrow hyperactivity and splenic dysfunction among congenital diaphragmatic hernia patients. Platelets 33:787–789

    Article  PubMed  CAS  Google Scholar 

  18. Yonekura T, Kubota A, Hoki M, Asano S, Nakayama T, Kato M, Oyanagi H (1998) Intermittent obstruction of the inferior vena cava by congenital anteromedial diaphragmatic hernia: an extremely rare case of Budd-Chiari syndrome in an infant. Surgery 124:109–111

    Article  PubMed  CAS  Google Scholar 

  19. Stanek J (2022) Umbilical cord compromise versus other clinical conditions predisposing to placental fetal vascular malperfusion. Placenta 127:8–11

    Article  PubMed  Google Scholar 

  20. Redline RW (2008) Cerebral palsy in term infants: a clinicopathologic analysis of 158 medicolegal case reviews. Pediatr Dev Pathol 11:456–464

    Article  PubMed  Google Scholar 

  21. Redline RW, Ravishankar S, Bagby CM, Saab ST, Zarei S (2021) Four major patterns of placental injury: a stepwise guide for understanding and implementing the 2016 Amsterdam consensus. Modern Pathol 34:1074–1092

    Article  Google Scholar 

  22. 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 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  25. Roberts DJ, Polizzano C (2021) Atlas of placental pathology. American Registry of Pathology, Arlington, Virginia, pp 224–231

    Book  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Stanek J (2021) Temporal heterogeneity of placental segmental fetal vascular malperfusion: timing but not etiopathogenesis. Virchows Arch 478:905–9214

    Article  PubMed  CAS  Google Scholar 

  28. 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 

  29. Ariel I, Meir K (2019) Mineralization of trophoblast basement membrane. In: Khong TY et al (eds) Pathology of the Placenta. Springer Nature Switzerland AG, pp 143–146

    Chapter  Google Scholar 

  30. 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

    PubMed  CAS  Google Scholar 

  31. Ernst LM (2015) Fetal vascular malperfusion. In: Heerema-McKenney A, Popek EJ, De Paepe ME (eds) Diagnostic pathology: placenta. Amirsys, Elsevier, Philadelphia, PA, pp 174–185

    Google Scholar 

  32. Baergen RN (2007) Cord abnormalities, structural lesions, and cord “accidents”. Sem Diagn Pathol 24:23–32

    Article  Google Scholar 

  33. Jessop FA, Lees CC, Pathak S, Hook CE, Sebire NJ (2014) Umbilical cord coiling: clinical outcomes in an unselected population and systematic review. Virchows Arch 464:105–112

    Article  PubMed  CAS  Google Scholar 

  34. Redline RW (2004) Clinical and pathological umbilical cord abnormalities in fetal thrombotic vasculopathy. Hum Pathol 35:1494–1498

    Article  PubMed  CAS  Google Scholar 

  35. Luo G, Redline RW (2013) Peripheral insertion of umbilical cord. Pediatr Dev Pathol 16:399–404

    Article  PubMed  Google Scholar 

  36. Boyd TK, Roberts DJ, Heerema-McKenney A. Fetal vascular malperfusion, in: Khong TY, Mooney EE, Nikkels PGJ, Morgan TK, Gordinj SJ, eds. Pathology of the Placenta, Springer 2019, 173-182

    Chapter  Google Scholar 

  37. Zimmermann N, Stanek J (2017) Perinatal case of fatal Simpson-Golabi-Behmel syndrome with hyperplasia of seminiferous tubules. Am J Case Rep 18:649–655

    Article  PubMed  PubMed Central  Google Scholar 

  38. Stanek J, Sheridan RM, Le LD, Crombleholme TM (2011) Placental fetal thrombotic vasculopathy in severe congenital anomalies prompting EXIT procedure. Placenta 32:373–379

    Article  PubMed  CAS  Google Scholar 

  39. Stanek J (2021) CD34 immunostain increases sensitivity of the diagnosis of fetal vascular malperfusion in placentas from ex-utero intrapartum treatment. J Perinat Med 49:203–208

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pathology, Cincinnati Children’s Hospital Medical Center, and Department of Pathology, University of Cincinnati Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, 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

Ethical approval

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

Conflict of interest

The author declares no competing interests.

Additional information

Publisher’s note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stanek, J. Placental fetal vascular malperfusion in congenital diaphragmatic hernia. Virchows Arch 484, 83–91 (2024). https://doi.org/10.1007/s00428-023-03600-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-023-03600-y

Keywords

Search

Navigation