Skip to main content
SpringerLink
Log in

Is advanced maternal age associated with placental vascular malperfusion? A prospective study from a single tertiary center

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

Abstract

Purpose

Pregnancy at advanced maternal age (AMA) has become more common. There has been concern regarding the adverse effect deferring pregnancy might have on pregnancy outcomes. We aimed to prospectively study the effect of AMA on placental pathology.

Methods

A prospective case–control study was performed in a single university center. Placental histopathology, maternal demographics, labor characteristics, and neonatal outcomes of pregnancies with AMA were collected and compared to matched controls. We defined AMA as maternal age > 35 years at delivery. In attempt to isolate the effect of maternal age, we excluded cases complicated by preterm birth, hypertensive disorders, diabetes mellitus, small for gestational age, and congenital/genetic anomalies.

Results

The study group included 110 AMA patients that were matched with controls. The groups did not differ in maternal demographics, but the AMA group had a higher rate of assisted reproductive technologies (ART) as compared to the control group (p < 0.001). Placentas in the AMA group were characterized by a higher rate of maternal vascular lesions (MVM) (39.1% vs. 24.5%, p = 0.003), but not fetal vascular malperfusion lesions (p = 0.576). In multivariable analysis maternal age was associated with placental MVM lesions independent of all other maternal demographics (aOR 1.18 95% CI 1.06–3.17). Neonatal outcomes did not significantly differ between the groups.

Conclusions

After excluding all background morbidities—AMA was associated with a higher rate of placental MVM lesions vs. controls. These findings suggest an independent effect of AMA on placental function. Large prospective trials are needed to study the clinical importance of these findings.

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

Similar content being viewed by others

Data statement

Data available on request due to privacy/ethical restrictions.

References

  1. Martin JA, Hamilton BE, Osterman MJK (2018) Births in the United States, 2017. NCHS Data Brief

  2. Yogev Y, Melamed N, Bardin R, Tenenbaum-Gavish K, Ben-Shitrit G, Ben-Haroush A (2010) Pregnancy outcome at extremely advanced maternal age. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2010.07.039

    Article  PubMed  Google Scholar 

  3. Jackson S, Hong C, Wang ET, Alexander C, Gregory KD, Pisarska MD (2015) Pregnancy outcomes in very advanced maternal age pregnancies: the impact of assisted reproductive technology. Fertil Steril. https://doi.org/10.1016/j.fertnstert.2014.09.037

    Article  PubMed  Google Scholar 

  4. Khalil A, Syngelaki A, Maiz N, Zinevich Y, Nicolaides KH (2013) Maternal age and adverse pregnancy outcome: a cohort study. Ultrasound Obstet Gynecol. https://doi.org/10.1002/uog.12494

    Article  PubMed  Google Scholar 

  5. Bayrampour H, Heaman M (2010) Advanced maternal age and the risk of cesarean birth: a systematic review. Birth. https://doi.org/10.1111/j.1523-536X.2010.00409.x

    Article  PubMed  Google Scholar 

  6. Kenny LC, Lavender T, McNamee R, O’Neill SM, Mills T, Khashan AS (2013) Advanced maternal age and adverse pregnancy outcome: evidence from a large contemporary cohort. PLoS One. https://doi.org/10.1371/journal.pone.0056583

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jacobsson B, Ladfors L, Milsom I (2004) Advanced maternal age and adverse perinatal outcome. Obstet Gynecol. https://doi.org/10.1097/01.AOG.0000140682.63746.be

    Article  PubMed  Google Scholar 

  8. Salem Yaniv S, Levy A, Wiznitzer A, Holcberg G, Mazor M, Sheiner E (2011) A significant linear association exists between advanced maternal age and adverse perinatal outcome. Arch Gynecol Obstet. https://doi.org/10.1007/s00404-010-1459-4

    Article  PubMed  Google Scholar 

  9. Schimmel MS, Bromiker R, Hammerman C, Chertman L, Ioscovich A, Granovsky-Grisaru S, Samueloff A, Elstein D (2015) The effects of maternal age and parity on maternal and neonatal outcome. Arch Gynecol Obstet. https://doi.org/10.1007/s00404-014-3469-0

    Article  PubMed  Google Scholar 

  10. Reddy UM, Ko CW, Willinger M (2006) Maternal age and the risk of stillbirth throughout pregnancy in the United States. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2006.06.019

    Article  PubMed  Google Scholar 

  11. Rosenstein MG, Cheng YW, Snowden JM, Nicholson JM, Caughey AB (2012) Risk of stillbirth and infant death stratified by gestational age. Obstet Gynecol. https://doi.org/10.1097/AOG.0b013e31825bd286

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sheen JJ, Wright JD, Goffman D, Kern-Goldberger AR, Booker W, Siddiq Z, D’Alton ME, Friedman AM (2018) Maternal age and risk for adverse outcomes. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2018.08.034

    Article  PubMed  Google Scholar 

  13. Kahveci B, Melekoglu R, Evruke IC, Cetin C (2018) The effect of advanced maternal age on perinatal outcomes in nulliparous singleton pregnancies. BMC Pregnancy Childbirth. https://doi.org/10.1186/s12884-018-1984-x

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wu Y, Chen Y, Shen M, Guo Y, Wen SW, Lanes A, White RR, Adanlawo A, Walker M, Hua X (2019) Adverse maternal and neonatal outcomes among singleton pregnancies in women of very advanced maternal age: a retrospective cohort study. BMC Pregnancy Childbirth 19:1–9

    Article  Google Scholar 

  15. Maoz-Halevy E, Pariente G, Sheiner E, Wainstock T (2020) Perinatal outcomes of women aged 50 years and above. Am J Perinatol. https://doi.org/10.1055/s-0039-1700859

    Article  PubMed  Google Scholar 

  16. Woods L, Perez-Garcia V, Kieckbusch J, Wang X, Demayo F, Colucci F, Hemberger M (2017) Decidualisation and placentation defects are a major cause of age-related reproductive decline. Nat Commun. https://doi.org/10.1038/s41467-017-00308-x

    Article  PubMed  PubMed Central  Google Scholar 

  17. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon ES (2005) Birthweight standards in the live-born population in Israel. Isr Med Assoc J 7:311–314

    Google Scholar 

  18. Weiner E, Barber E, Feldstein O, Schreiber L, Dekalo A, Mizrachi Y, Bar J, Kovo M (2018) The placental component and neonatal outcome in singleton vs. twin pregnancies complicated by gestational diabetes mellitus. Placenta. https://doi.org/10.1016/j.placenta.2018.01.010

    Article  PubMed  Google Scholar 

  19. Miremberg H, Gindes L, Schreiber L, Raucher Sternfeld A, Bar J, Kovo M (2019) The association between severe fetal congenital heart defects and placental vascular malperfusion lesions. Prenat Diagn. https://doi.org/10.1002/pd.5515

    Article  PubMed  Google Scholar 

  20. Khong TY, Mooney EE, Ariel I et al (2016) Sampling and definitions of placental lesions Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med. https://doi.org/10.5858/arpa.2015-0225-CC

    Article  PubMed  Google Scholar 

  21. Redline RW (2015) Classification of placental lesions. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2015.05.056

    Article  PubMed  PubMed Central  Google Scholar 

  22. Pinar H, Sung CJ, Oyer CE, Singer DB (1996) Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med. https://doi.org/10.1080/15513819609168713

    Article  PubMed  Google Scholar 

  23. Strong TH, Jarles DL, Vega JS, Feldman DB (1994) The umbilical coiling index. Am J Obstet Gynecol. https://doi.org/10.1016/S0002-9378(94)70378-7

    Article  PubMed  Google Scholar 

  24. Bar J, Schreiber L, Golan A, Kovo M (2012) Placental factor in spontaneous term labor in uncomplicated pregnancy. J Matern Neonatal Med. https://doi.org/10.3109/14767058.2012.704450

    Article  Google Scholar 

  25. Fragouli E, Alfarawati S, Spath K, Jaroudi S, Sarasa J, Enciso M, Wells D (2013) The origin and impact of embryonic aneuploidy. Hum Genet. https://doi.org/10.1007/s00439-013-1309-0

    Article  PubMed  Google Scholar 

  26. Menken J, Trussell J, Larsen U (1986) Age and infertility. Science (80-) 78:89. https://doi.org/10.1126/science.3755843

    Article  Google Scholar 

  27. Impact S, No P (2013) Induction of labour at term in older mothers: RCOG scientific impact paper number 34

  28. Johnson JA, Tough S (2017) No-271-Delayed child-bearing. J Obstet Gynaecol 39:e500–e515

    Google Scholar 

  29. Redline RW (2008) Placental pathology: a systematic approach with clinical correlations. Placenta. https://doi.org/10.1016/j.placenta.2007.09.003

    Article  PubMed  Google Scholar 

  30. Khong Y, Brosens I (2011) Defective deep placentation. Best Pract Res Clin Obstet Gynaecol. https://doi.org/10.1016/j.bpobgyn.2010.10.012

    Article  PubMed  Google Scholar 

  31. Stanek J (2014) Comparison of placental pathology in preterm, late-preterm, near-term, and term births. Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2013.10.015

    Article  PubMed  Google Scholar 

  32. Erez O, Yeo L, Jung EJ et al (2018) The frequency and type of placental histologic lesions in term pregnancies with normal outcome. J Perinat Med 46:613–630

    Article  Google Scholar 

  33. Conrad KP, Rabaglino MB, Post Uiterweer ED (2017) Emerging role for dysregulated decidualization in the genesis of preeclampsia. Placenta. https://doi.org/10.1016/j.placenta.2017.06.005

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Departments of Obstetrics and Gynecology, The Edith Wolfson Medical Center, P.O Box 5, 58100, Holon, Israel

    Hadas Miremerg, Omry Frig, Shiran Rona, Hadas Ganer Herman, Yossi Mizrachi, Jacob Bar, Michal Kovo & Eran Weiner

  2. Departments of Pathology, The Edith Wolfson Medical Center, Holon, Israel

    Letizia Schreiber

  3. Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Hadas Miremerg, Omry Frig, Shiran Rona, Hadas Ganer Herman, Yossi Mizrachi, Letizia Schreiber, Jacob Bar, Michal Kovo & Eran Weiner

Authors
  1. Hadas Miremerg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Omry Frig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shiran Rona
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hadas Ganer Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yossi Mizrachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Letizia Schreiber
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jacob Bar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michal Kovo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eran Weiner
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HM and EW: Protocol development and methodology, Manuscript writing and editing; OF and SR: Data collection and management; HGH and YM: Data analysis; LS: Data management; JB and MK: Manuscript writing.

Corresponding author

Correspondence to Hadas Miremerg.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Approval was obtained from the local ethics committee (decision number 0006-19-WOMC).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent to publish

Patients signed informed consent regarding publishing their data.

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

Miremerg, H., Frig, O., Rona, S. et al. Is advanced maternal age associated with placental vascular malperfusion? A prospective study from a single tertiary center. Arch Gynecol Obstet 301, 1441–1447 (2020). https://doi.org/10.1007/s00404-020-05562-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05562-x

Keywords

Search

Navigation