Skip to main content
Log in

Placental pathology in pregnancies complicated by fetal growth restriction: recurrence vs. new onset

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

In an attempt to shed new light on the pathogenesis of fetal growth restriction (FGR), we aimed to study pregnancy characteristics, neonatal outcomes, and placental histopathological lesions of FGR pregnancies in two different subgroups: when developed after appropriate for gestational age (AGA) pregnancy and when developed after previous pregnancy with FGR.

Study design

Pregnancy and placental reports of all singleton pregnancies complicated by FGR (defined as actual birthweight below the 10th percentile according to local birthweight nomograms) between 2008 and 2018 were reviewed. Included were only cases with previous delivery. Maternal background, neonatal outcomes, and placental histopathology were compared between FGR that occurred after FGR (recurrent FGR group) and FGR that occurred after an AGA pregnancy (FGR after AGA group). Placental lesions were classified according to the current “Amsterdam” criteria. Continuous variables were compared using the Student’s t test or the Mann–Whitney test as appropriate. Categorical variables were compared using Chi-square or Fisher’s exact test as appropriate.

Results

A total of 334 FGR cases with a previous delivery were included in the study. Of them, 111 cases constituted the recurrent FGR group and 223 constituted the FGR after AGA group. The recurrent FGR group was characterized by higher rates of maternal diabetes during pregnancy and hypertensive diseases (9% versus 2.7%, p = 0.01 and 19.8% versus 11.6%, p = 0.04). The FGR after AGA group was characterized by a higher rate of fetal vascular malperfusion (FVM) lesions (29.6% versus 18.0%, p = 0.02), and by lower mean birthweight (1842 ± 424.9 versus 1977.4 ± 412.2, p = 0.005), as compared to the recurrent FGR group.

Conclusion

Recurrent FGR was associated with maternal background morbidities during pregnancy which represents a chronic repeated insult, while “new” FGR cases (those followed an AGA pregnancy) were characterized by a higher rate of FVM lesions and lower birthweight which probably represent an “accident” in placentation. These findings may suggest that different mechanisms of placental dysfunction exist in the two subgroups of FGR.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Brosens I, Pijnenborg R, Vercruysse L, Romero R (2011) The “great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol 204:193–201. https://doi.org/10.1016/j.ajog.2010.08.009

    Article  PubMed  Google Scholar 

  2. Kovo M, Schreiber L, Bar J (2013) Placental vascular pathology as a mechanism of disease in pregnancy complications. Thromb Res 131(Suppl):S18–21. https://doi.org/10.1016/S0049-38481370013-6

    Article  CAS  PubMed  Google Scholar 

  3. Ness RB, Sibai BM (2006) Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. Am J Obstet Gynecol 195:40–49. https://doi.org/10.1016/j.ajog.2005.07.049

    Article  PubMed  Google Scholar 

  4. Gerretsen G, Huisjes HJ, Elema JD (1981) Morphological changes of the spiral arteries in the placental bed in relation to pre-eclampsia and fetal growth retardation. Br J Obstet Gynaecol 88:876–881

    Article  CAS  Google Scholar 

  5. Redline RW, Heller D, Keating S, Kingdom J (2005) Placental diagnostic criteria and clinical correlation a workshop report. Placenta 26:S114–S117. https://doi.org/10.1016/j.placenta2005.02.009

    Article  PubMed  Google Scholar 

  6. Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler M-A, Derricott H, Evans MJ, Faye-Petersen OM, Gillan JE, Heazell AEP, Heller DS, Jacques SM, Keating S, Kelehan P, Maes A, McKay EM, Morgan TK, Nikkels PGJ, Parks WT, Redline RW, Scheimberg I, Schoots MH, Sebire NJ, Timmer A, Turowski G, van der Voorn JP, van Lijnschoten I, Gordijn SJ (2016) Sampling and definitions of placental lesions: amsterdam placental workshop group consensus statement. Arch Pathol Lab Med 140:698–713. https://doi.org/10.5858/arpa.2015-0225-CC

    Article  PubMed  Google Scholar 

  7. Sharma D, Shastri S, Sharma P (2016) Intrauterine growth restriction: antenatal and postnatal aspects. Clin Med Insights Pediatr 10:67–83. https://doi.org/10.4137/CMPed.S40070

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tyson RW, Staat BC (2008) The intrauterine growth-restricted fetus and placenta evaluation. Semin Perinatol 32:166–171. https://doi.org/10.1053/j.semperi.2008.02.005

    Article  PubMed  Google Scholar 

  9. Vedmedovska N, Rezeberga D, Teibe U, Melderis I, Donders GGG (2011) Placental pathology in fetal growth restriction. Eur J Obstet Gynecol Reprod Biol 155:36–40. https://doi.org/10.1016/j.ejogrb.2010.11.017

    Article  PubMed  Google Scholar 

  10. Levy M, Mizrachi Y, Leytes S, Weiner E, Bar J, Schreiber L, Kovo M (2018) Can placental histopathology lesions predict recurrence of small for gestational age neonates? Reprod Sci 25:1485–1491. https://doi.org/10.1177/1933719117749757

    Article  PubMed  Google Scholar 

  11. Levy M, Kovo M, Schreiber L, Kleiner I, Grinstein E, Koren L, Barda G, Bar J, Weiner E (2019) Pregnancy outcomes in correlation with placental histopathology in subsequent pregnancies complicated by fetal growth restriction. Placenta 80:36–41. https://doi.org/10.1016/j.placenta.2019.04.001

    Article  PubMed  Google Scholar 

  12. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon E (2001) Birth weight standards in the live-born population. Israel Med Assoc J 311:314

    Google Scholar 

  13. Hypertension in pregnancy (2013) Report of the American college of obstetricians and gynecologists’ task force on hypertension in pregnancy. Obstet Gynecol 122:1122–1131. https://doi.org/10.1097/01.AOG.0000437382.03963.88

    Article  Google Scholar 

  14. Roberge S, Nicolaides K et al (2016) The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obs Gynecol. 15:30783–30789. https://doi.org/10.1016/j.ajog.2016.09.076

    Article  CAS  Google Scholar 

  15. ACOG Practice Bulletin No (2013) 138: Inherited thrombophilias in pregnancy. Obstet Gynecol 122:706–717. https://doi.org/10.1097/01.AOG.0000433981.36184.4e

    Article  Google Scholar 

  16. ACOG Practice Bulletin No (2011) 118: Antiphospholipid syndrome. Obstet Gynecol 117:192–199. https://doi.org/10.1097/AOG.0b013e31820a61f9

    Article  Google Scholar 

  17. Redline RW (2015) Classification of placental lesions. Am J Obstet Gynecol 213:S21–S28. https://doi.org/10.1016/j.ajog.2015.05.056

    Article  PubMed  Google Scholar 

  18. Weiner E, Mizrachi Y, Grinstein E, Feldstein O, Rymer-Haskel N, Juravel E, Schreiber L, Bar J, Kovo M (2016) The role of placental histopathological lesions in predicting recurrence of preeclampsia. Prenat Diagn 36:953–960. https://doi.org/10.1002/pd.4918

    Article  CAS  PubMed  Google Scholar 

  19. Pinar H, Sung CJ, Oyer CE, Singer DB (1996) Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med J Soc Pediatr Pathol Affil with Int Paediatr Pathol Assoc 16:901–907

    CAS  Google Scholar 

  20. Fox GE, Van Wesep R, Resau JH, Sun CC (1991) The effect of immersion formaldehyde fixation on human placental weight. Arch Pathol Lab Med 115:726–728

    CAS  PubMed  Google Scholar 

  21. Strong THJ, Jarles DL, Vega JS, Feldman DB (1994) The umbilical coiling index. Am J Obstet Gynecol 170:29–32

    Article  Google Scholar 

  22. Gaudineau A (2013) Prevalence, risk factors, maternal and fetal morbidity and mortality of intrauterine growth restriction and small-for-gestational age. J Gynecol Obstet Biol Reprod (Paris) 42:895–910. https://doi.org/10.1016/j.jgyn.2013.09.013

    Article  CAS  Google Scholar 

  23. Vayssiere C, Sentilhes L, Ego A, Bernard C, Cambourieu D, Flamant C, Gascoin G, Gaudineau A, Grange G, Houfflin-Debarge V, Langer B, Malan V, Marcorelles P, Nizard J, Perrotin F, Salomon L, Senat M-V, Serry A, Tessier V, Truffert P, Tsatsaris V, Arnaud C, Carbonne B (2015) Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians. Eur J Obstet Gynecol Reprod Biol 193:10–18. https://doi.org/10.1016/j.ejogrb.2015.06.021

    Article  CAS  PubMed  Google Scholar 

  24. Hinkle SN, Albert PS, Mendola P, Sjaarda LA, Boghossian NS, Yeung E, Laughon SK (2014) Differences in risk factors for incident and recurrent small-for-gestational-age birthweight: a hospital based cohort study. BJOG discussion. https://doi.org/10.1111/1471-0528.12628

    Article  Google Scholar 

  25. Hooijschuur MCE, Ghossein-Doha C, Kroon AA, de Leeuw PW, Zandbergen AAM, van Kuijk SMJ, Spaanderman MEA (2018) Metabolic Syndrome and Preeclampsia. Ultrasound Obstet Gynecol 54:64–71. https://doi.org/10.1002/uog.20126

    Article  Google Scholar 

  26. Stekkinger E, Scholten RR, Heidema WM, Spaanderman MEA (2015) Recurrent pre-eclampsia in women with metabolic syndrome and low plasma volume: a retrospective cohort study. BJOG 122:1773–1780. https://doi.org/10.1111/1471-0528.13737

    Article  CAS  PubMed  Google Scholar 

  27. Kalafat E, Thilaganathan B (2017) Cardiovascular origins of preeclampsia. Curr Opin Obstet Gynecol 29:383–389. https://doi.org/10.1097/GCO.0000000000000419

    Article  PubMed  Google Scholar 

  28. Burton GJ, Jauniaux E (2018) Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol 218:S745–S761. https://doi.org/10.1016/j.ajog.2017.11.577

    Article  CAS  PubMed  Google Scholar 

  29. Boulanger H, Drouin D, Largilliere C, Lefevre G (2019) Intrauterine growth restriction, soluble fms-like tyrosine kinase-1 to placental growth factor ratio increase and preeclampsia. J Gynecol Obstet Hum Reprod 48:695–697. https://doi.org/10.1016/j.jogoh.2019.05.007

    Article  CAS  PubMed  Google Scholar 

  30. Yogev Y, Visser GHA (2009) Obesity, gestational diabetes and pregnancy outcome. Semin Fetal Neonatal Med 14:77–84. https://doi.org/10.1016/j.siny.2008.09.002

    Article  PubMed  Google Scholar 

  31. Ornoy A (2011) Prenatal origin of obesity and their complications: Gestational diabetes, maternal overweight and the paradoxical effects of fetal growth restriction and macrosomia. Reprod Toxicol 32:205–212. https://doi.org/10.1016/j.reprotox.2011.05.002

    Article  CAS  PubMed  Google Scholar 

  32. Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S, Forest J-C, Giguere Y (2010) Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 116:402–414. https://doi.org/10.1097/AOG.0b013e3181e9322a

    Article  PubMed  Google Scholar 

  33. Weiner E, Schreiber L, Grinstein E, Feldstein O, Rymer-Haskel N, Bar J, Kovo M (2016) The placental component and obstetric outcome in severe preeclampsia with and without HELLP syndrome. Placenta 47:99–104. https://doi.org/10.1016/j.placenta.2016.09.012

    Article  PubMed  Google Scholar 

  34. Redline RW, Ravishankar S (2018) Fetal vascular malperfusion, an update. APMIS 126:561–569. https://doi.org/10.1111/apm.12849

    Article  PubMed  Google Scholar 

  35. Heider A (2017) Fetal vascular malperfusion. Arch Pathol Lab Med 141:1484–1489. https://doi.org/10.5858/arpa.2017-0212-RA

    Article  PubMed  Google Scholar 

  36. Chisholm KM, Heerema-McKenney A (2015) Fetal thrombotic vasculopathy: significance in liveborn children using proposed society for pediatric pathology diagnostic criteria. Am J Surg Pathol 39:274–280. https://doi.org/10.1097/PAS.0000000000000334.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

M L: project development, data collection, manuscript writing, D A: data collection, M K: data analysis, L S: placental pathology analysis, E V: data analysis, L K: data collection, J B: manuscript editing, E W: project development, manuscript writing.

Corresponding author

Correspondence to Michal Levy.

Ethics declarations

Conflict of interest

There is not any financial relationship with any organization or any conflict of interest to report.

Informed consent

Because the retrospective nature of the study, informed consent was not required in accordance to a specific permission by the local ethics committee decision.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Levy, M., Alberti, D., Kovo, M. et al. Placental pathology in pregnancies complicated by fetal growth restriction: recurrence vs. new onset. Arch Gynecol Obstet 301, 1397–1404 (2020). https://doi.org/10.1007/s00404-020-05546-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05546-x

Keywords

Navigation