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A history of cesarean section and future maternal long-term risk for neoplasms: a population-based cohort study

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

Abstract

Objective

Mode of delivery has long-term implications on the mother, including recent data regarding the level of transmission of fetal microchimeric cells (FMc) and their possible effect on cancer development. We aimed to evaluate the association between cesarean section (CS) and future risk for neoplasms.

Study design

A population-based cohort analysis comparing the long-term risk for neoplasms between patients that delivered only by CS to those that delivered only vaginally (VD). Neoplasms were pre-defined based on ICD-9 codes. Deliveries occurred between the years 1991–2017 in a tertiary medical center. Kaplan–Meier survival curves were used to compare the cumulative incidence of neoplasms and Cox proportional hazards models were constructed to control for confounders.

Results

During the study period 105,992 patients met the inclusion criteria; 14150 (13.4%) of patients had only CS and 91842 (86.6%) had VD (comparison group). The CS group had significantly higher incidence of benign and malignant neoplasms (4.73 per 1000 patient-years versus 3.88 per 1000 patient-years, OR = 1.26, 95% CI 1.16–1.37; p = 0.001; 2.19 per 1000 patient-years of follow up versus 1.93 per 1000 patient-years, OR = 1.16, 95% CI 1.03–1.31; p = 0.013). Specifically, the CS group had higher incidence of uterine cancer (1.2 versus 0.06 per 1000 patient-years, OR = 1.97, 95% CI 1.14–3.39; p = 0.013). The cumulative incidence of benign, malignant and uterine neoplasms was significantly higher in the CS group (Log rank test p = 0.001; 0.036 and 0.014; respectively). Importantly, no significant association was found with breast and ovarian malignancies.”

When performing a Cox regression model controlling for confounders, the risk for malignancy-related hospitalizations remained significant (adjusted HR = 1.22, 95% CI 1.01–1.48; p = 0.031) but not for uterine cancer (adjusted HR = 1.6, 95% CI 0.9–2.8; p = 0.103).

Conclusion

Our findings provide support to linkage between delivery by cesarean section and future maternal malignancy.

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References

  1. Adams Waldorf KM, Gammill HS, Lucas J, Aydelotte TM, Leisenring WM, Lambert NC et al (2010) Dynamic changes in fetal microchimerism in maternal peripheral blood mononuclear cells, CD4+ and CD8+ cells in normal pregnancy. Placenta 31(7):589–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Maloney S, Smith A, Furst DE, Myerson D, Rupert K, Evans PC et al (1999) Microchimerism of maternal origin persists into adult life. J Clin Invest 104(1):41–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA (1996) Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci U S A 93(2):705–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Koopmans M, Kremer Hovinga IC, Baelde HJ, Harvey MS, de Heer E, Bruijn JA et al (2008) Chimerism occurs in thyroid, lung, skin and lymph nodes of women with sons. J Reprod Immunol 78(1):68–75

    Article  CAS  PubMed  Google Scholar 

  5. Feitsma AL, Worthington J, van der Helm-van Mil AH, Plant D, Thomson W, Ursum J et al (2007) Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development. Proc Natl Acad Sci USA 104(50):19966–19970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Guthrie KA, Dugowson CE, Voigt LF, Koepsell TD, Nelson JL (2010) Does pregnancy provide vaccine-like protection against rheumatoid arthritis? Arthritis Rheum 62(7):1842–1848

    PubMed  PubMed Central  Google Scholar 

  7. Stevens AM (2006) Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders? Lupus 15(11):820–826

    Article  CAS  PubMed  Google Scholar 

  8. Zeng XX, Tan KH, Yeo A, Sasajala P, Tan X, Xiao ZC et al (2010) Pregnancy-associated progenitor cells differentiate and mature into neurons in the maternal brain. Stem Cells Dev 19(12):1819–1830

    Article  PubMed  Google Scholar 

  9. Khosrotehrani K, Reyes RR, Johnson KL, Freeman RB, Salomon RN, Peter I et al (2007) Fetal cells participate over time in the response to specific types of murine maternal hepatic injury. Hum Reprod 22(3):654–661

    Article  CAS  PubMed  Google Scholar 

  10. Gadi VK, Nelson JL (2007) Fetal microchimerism in women with breast cancer. Cancer Res 67(19):9035–9038

    Article  CAS  PubMed  Google Scholar 

  11. Fugazzola L, Cirello V, Beck-Peccoz P (2010) Fetal cell microchimerism in human cancers. Cancer Lett 287(2):136–141

    Article  CAS  PubMed  Google Scholar 

  12. Dubernard G, Aractingi S, Oster M, Rouzier R, Mathieu MC, Uzan S et al (2008) Breast cancer stroma frequently recruits fetal derived cells during pregnancy. Breast Cancer Res 10(1):R14

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hromadnikova I, Kotlabova K, Pirkova P, Libalova P, Vernerova Z, Svoboda B et al (2014) The occurrence of fetal microchimeric cells in endometrial tissues is a very common phenomenon in benign uterine disorders, and the lower prevalence of fetal microchimerism is associated with better uterine cancer prognoses. DNA Cell Biol 33(1):40–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fuchs O, Sheiner E, Meirovitz M, Davidson E, Sergienko R, Kessous R (2017) The association between a history of gestational diabetes mellitus and future risk for female malignancies. Arch Gynecol Obstet 295(3):731–736

    Article  PubMed  Google Scholar 

  15. El Hajj N, Schneider E, Lehnen H, Haaf T (2014) Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment. Reproduction 148(6):R111–R120

    Article  PubMed  PubMed Central  Google Scholar 

  16. Argyraki M, Damdimopoulou P, Chatzimeletiou K, Grimbizis GF, Tarlatzis BC, Syrrou M et al (2019) In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health. Hum Reprod Update 25(6):777–801

    Article  CAS  PubMed  Google Scholar 

  17. Kessous R, Sergienko R, Sheiner E (2020) Tubal ligation during cesarean delivery and future risk for ovarian cancer: a population-based cohort study. Arch Gynecol Obstet 301(6):1473–1477

    Article  PubMed  Google Scholar 

  18. Betrán AP, Ye J, Moller AB, Zhang J, Gülmezoglu AM, Torloni MR (2016) The increasing trend in caesarean section rates: global, regional and national estimates: 1990–2014. PLoS ONE 11(2):e0148343

    Article  PubMed  PubMed Central  Google Scholar 

  19. Martin JA, Hamilton BE, Osterman MJK (2017) Births in the United States, 2016. NCHS Data Brief 287:1–8

    Google Scholar 

  20. Shree R, Harrington WE, Kanaan SB, Forsyth A, Cousin E, Lopez A et al (2019) Fetal microchimerism by mode of delivery: a prospective cohort study. BJOG 126(1):24–31

    Article  CAS  PubMed  Google Scholar 

  21. Cho HW, Ouh YT, Lee KM, Han SW, Lee JK, Cho GJ et al (2019) Long-term effect of pregnancy-related factors on the development of endometrial neoplasia: a nationwide retrospective cohort study. PLoS ONE 14(3):e0214600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gadi VK, Malone KE, Guthrie KA, Porter PL, Nelson JL (2008) Case-control study of fetal microchimerism and breast cancer. PLoS ONE 3(3):e1706

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gadi VK (2010) Fetal microchimerism in breast from women with and without breast cancer. Breast Cancer Res Treat 121(1):241–244

    Article  PubMed  Google Scholar 

  24. Cha D, Khosrotehrani K, Kim Y, Stroh H, Bianchi DW, Johnson KL (2003) Cervical cancer and microchimerism. Obstet Gynecol 102(4):774–781

    PubMed  Google Scholar 

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Authors

Contributions

Dr. PS, Conceptualization, Methodology, Investigation, Writing—Original Draft; Review & Editing. Prof. ES, Investigation, Review & Editing; Mr. RS, Methodology, Formal analysis, Writing—Review & Editing; Dr. RK, Methodology, Investigation, Writing—Original Draft; Review & Editing.

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Correspondence to P. Schwarzman.

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The authors declare no conflicts of interest relevant to this article. We confirm that no honorarium, grant, or other form of payment was given to any of the authors to produce the manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Schwarzman, P., Sheiner, E., Sergienko, R. et al. A history of cesarean section and future maternal long-term risk for neoplasms: a population-based cohort study. Arch Gynecol Obstet 308, 499–505 (2023). https://doi.org/10.1007/s00404-022-06698-8

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  • DOI: https://doi.org/10.1007/s00404-022-06698-8

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