Skip to main content
SpringerLink
Log in

Effects of Fetal Exposure to Maternal Chemotherapy

  • Current Opinion
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Approximately 1 in 1,000–2,000 pregnancies are complicated by cancer. Today, different treatment options are considered as safe during pregnancy: chemotherapy, radiotherapy, surgery, or a combination of these. Surgery is considered safe during all trimesters of pregnancy; radiotherapy can be administered during the first and the second trimester, and chemotherapy after the first trimester of pregnancy. The placenta, acting as a barrier between the mother and the fetus, plays a key role in the safe administration of chemotherapy during pregnancy. A few studies have investigated the short- as well as the long-term health, general development, and cognitive and cardiac outcomes on children exposed to chemotherapy in utero. In general, these results were reassuring. Nevertheless, better safety data are required. This means data with longer follow-up periods and comparison with appropriate control groups. Moreover, important biasing factors should be taken into account when interpreting these results. Firstly, a great proportion of children were born prematurely due to the maternal condition. Preterm birth in general has been associated with cognitive impairment. Secondly, cancer during pregnancy is clearly a stressful situation, and maternal stress is associated with attention deficits. In sum, we state that chemotherapy can be administered safely after the first trimester of pregnancy. Moreover, iatrogenic prematurity in order to start postpartum administration of chemotherapy should be avoided. Nonetheless, decisions concerning treatment in these specific cases should always be made in a multidisciplinary setting with internationally recognized expertise in the coexistence of cancer and pregnancy.

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

References

  1. Pavlidis NA. Coexistence of pregnancy and malignancy. Oncologist. 2002;7(4):279–87.

    PubMed  Google Scholar 

  2. Walton JR, Prasad MR. Obstetric and neonatal outcomes of cancer treated during pregnancy. Clin Obstet Gynecol. 2011;54(4):567–73.

    Article  PubMed  Google Scholar 

  3. Van Calsteren K, Heyns L, De Smet F, et al. Cancer during pregnancy: an analysis of 215 patients emphasizing the obstetrical and the neonatal outcomes. J Clin Oncol. 2010;28(4):683–9.

    Article  PubMed  Google Scholar 

  4. Luis SA, Christie DR, Kaminski A, et al. Pregnancy and radiotherapy: management options for minimising risk, case series and comprehensive literature review. J Med Imaging Radiat Oncol. 2009;53(6):559–68.

    Article  PubMed  CAS  Google Scholar 

  5. Van Calsteren K, Verbesselt R, Beijnen J, et al. Transplacental transfer of anthracyclines, vinblastine, and 4-hydroxy-cyclophosphamide in a baboon model. Gynecol Oncol. 2010;119(3):594–600.

    Article  PubMed  Google Scholar 

  6. Arnon J, Meirow D, Lewis-Roness H, et al. Genetic and teratogenic effects of cancer treatments on gametes and embryos. Hum Reprod Update. 2001;7(4):394–403.

    Article  PubMed  CAS  Google Scholar 

  7. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol. 2004;5(5):283–91.

    Article  PubMed  CAS  Google Scholar 

  8. Ebert U, Loffler H, Kirch W. Cytotoxic therapy and pregnancy. Pharmacol Ther. 1997;74(2):207–20.

    Article  PubMed  CAS  Google Scholar 

  9. De Santis M, Di Gianantoni E, Straface G, et al. Ionizing radiations in pregnancy and teratogenesis: a review of literature. Reprod Toxicol. 2005;20(3):323–9.

    Article  PubMed  Google Scholar 

  10. Kal HB, Struikmans H. Radiotherapy during pregnancy: fact and fiction. Lancet Oncol. 2005;6(5):328–33.

    Article  PubMed  Google Scholar 

  11. Amant F, Van Calsteren K, Halaska MJ, et al. Gynecologic cancers in pregnancy: guidelines of an international consensus meeting. Int J Gynecol Cancer. 2009;19(Suppl 1):S1–12.

    Article  PubMed  Google Scholar 

  12. Isaacs RJ, Hunter W, Clark K. Tamoxifen as systemic treatment of advanced breast cancer during pregnancy: case report and literature review. Gynecol Oncol. 2001;80(3):405–8.

    Article  PubMed  CAS  Google Scholar 

  13. Amant F, Loibl S, Neven P, et al. Breast cancer in pregnancy. Lancet. 2012;379(9815):570–9.

    Article  PubMed  Google Scholar 

  14. Rasmussen SA. Human teratogens update 2011: can we ensure safety during pregnancy? Birth Defects Res A Clin Mol Teratol. 2012;94(3):123–8.

    Article  PubMed  CAS  Google Scholar 

  15. Azim HA Jr, Azim H, Peccatori FA. Treatment of cancer during pregnancy with monoclonal antibodies: a real challenge. Expert Rev Clin Immunol. 2010;6(6):821–6.

    Article  PubMed  Google Scholar 

  16. Azim HA Jr, Metzger-Filho O, de Azambuja E, et al. Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the HERA trial (BIG 01-01). Breast Cancer Res Treat. 2012;133(1):387–91.

    Article  PubMed  CAS  Google Scholar 

  17. Makol A, Wright K, Amin S. Rheumatoid arthritis and pregnancy: safety considerations in pharmacological management. Drugs. 2011;71(15):1973–87.

    Article  PubMed  CAS  Google Scholar 

  18. Decker M, Rothermundt C, Hollander G, et al. Rituximab plus CHOP for treatment of diffuse large B-cell lymphoma during second trimester of pregnancy. Lancet Oncol. 2006;7(8):693–4.

    Article  PubMed  Google Scholar 

  19. Chakravarty EF, Murray ER, Kelman A, et al. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011;117(5):1499–506.

    Article  PubMed  CAS  Google Scholar 

  20. Shapira T, Pereg D, Lishner M. How I treat acute and chronic leukemia in pregnancy. Blood Rev. 2008;22(5):247–59.

    Article  PubMed  CAS  Google Scholar 

  21. Vandenbriele C, Vassou A, Pentheroudakis G, et al. Hematologic malignancies in pregnancy. In: Antica M, editor. Acute leukemia: the scientist’s perspective and challenge. New York: InTech; 2011. p. 371–90.

    Google Scholar 

  22. Eskander RN, Tarsa M, Herbst KD, et al. Chronic myelocytic leukemia in pregnancy: a case report describing successful treatment using multimodal therapy. J Obstet Gynaecol Res. 2011;37(11):1731–3.

    Article  PubMed  Google Scholar 

  23. Yazdani BP, Matok I, Garcia BF, et al. A systematic review of the fetal safety of interferon alpha. Reprod Toxicol. 2012;33(3):265–8.

    Article  Google Scholar 

  24. Gedeon C, Koren G. Designing pregnancy centered medications: drugs which do not cross the human placenta. Placenta. 2006;27(8):861–8.

    Article  PubMed  CAS  Google Scholar 

  25. Garland M. Pharmacology of drug transfer across the placenta. Obstet Gynecol Clin N Am. 1998;25(1):21–42.

    Article  CAS  Google Scholar 

  26. Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet. 2004;43(8):487–514.

    Article  PubMed  CAS  Google Scholar 

  27. Ceckova-Novotna M, Pavek P, Staud F. P-glycoprotein in the placenta: expression, localization, regulation and function. Reprod Toxicol. 2006;22(3):400–10.

    Article  PubMed  CAS  Google Scholar 

  28. Gaillard B, Leng JJ, Grellet J, et al. Transplacental passage of epirubicin [article in French]. J Gynecol Obstet Biol Reprod (Paris). 1995;24(1):63–8.

    CAS  Google Scholar 

  29. Grohard P, Akbaraly JP, Saux MC, et al. Transplacental passage of doxorubicin [article in French]. J Gynecol Obstet Biol Reprod (Paris). 1989;18(5):595–600.

    CAS  Google Scholar 

  30. Heyns L, Van Calsteren K, Han SN, et al. Review: chemotherapy during pregnancy. Belgian J Hematol. 2011;2(3):101–6.

    Google Scholar 

  31. Van Calsteren K, Verbesselt R, Van Bree R, et al. Substantial variation in transplacental transfer of chemotherapeutic agents in a mouse model. Reprod Sci. 2011;18(1):57–63.

    Article  PubMed  Google Scholar 

  32. Gralla RJ, Osoba D, Kris MG, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol. 1999;17(9):2971–94.

    PubMed  CAS  Google Scholar 

  33. Van Calsteren K, Verbesselt R, Ottevanger N, et al. Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study. Acta Obstet Gynecol Scand. 2010;89(10):1338–45.

    Article  PubMed  Google Scholar 

  34. Wapner RJ, Sorokin Y, Mele L, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. N Engl J Med. 2007;357(12):1190–8.

    Article  PubMed  CAS  Google Scholar 

  35. Avilés A, Neri N. Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero. Clin Lymphoma. 2001;2(3):173–7.

    Article  PubMed  Google Scholar 

  36. Hahn KM, Johnson PH, Gordon N, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer. 2006;107(6):1219–26.

    Article  PubMed  Google Scholar 

  37. Amant F, Van Calsteren K, Halaska MJ, et al. Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: an observational study. Lancet Oncol. 2012;9:256–64.

    Article  Google Scholar 

  38. Voigt B, Pietz J, Pauen S, et al. Cognitive development in very vs. moderately to late preterm and full-term children: can effortful control account for group differences in toddlerhood? Early Hum Dev. 2012;88(5):307–13.

    Article  PubMed  Google Scholar 

  39. van Baar AL, Vermaas J, Knots E, et al. Functioning at school age of moderately preterm children born at 32 to 36 weeks’ gestational age. Pediatrics. 2009;124(1):251–7.

    Article  PubMed  Google Scholar 

  40. Mulder EJ, Robles de Medina PG, Huizink AC, et al. Prenatal maternal stress: effects on pregnancy and the (unborn) child. Early Hum Dev. 2002;70(1–2):3–14.

    Article  PubMed  CAS  Google Scholar 

  41. Van den Bergh BR, Mennes M, Stevens V, et al. ADHD deficit as measured in adolescent boys with a continuous performance task is related to antenatal maternal anxiety. Pediatr Res. 2006;59(1):78–82.

    Article  PubMed  Google Scholar 

Download references

Funding

This article was funded by the Belgian Cancer Plan.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Lab of Experimental Gynaecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium

    Jana Dekrem & Frédéric Amant

  2. Obstetrics, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium

    Kristel Van Calsteren

  3. Gynaecologic Oncology, University Hospitals Leuven, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium

    Frédéric Amant

Authors
  1. Jana Dekrem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristel Van Calsteren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frédéric Amant
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frédéric Amant.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dekrem, J., Van Calsteren, K. & Amant, F. Effects of Fetal Exposure to Maternal Chemotherapy. Pediatr Drugs 15, 329–334 (2013). https://doi.org/10.1007/s40272-013-0040-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-013-0040-6

Keywords

Search

Navigation