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Obstetric and offspring risks of women’s morbid conditions linked to prior anticancer treatments

Abstract

Background

Literature shows the effects of type of cancer and/or anticancer treatment on live birth percentages and/or pregnancy and neonatal complications in female cancer survivors. However, studies analyzing the obstetric and offspring risks of the morbid conditions associated with previous anti-cancer treatments are missing. The present review aims to uncover these risks.

Methods

A literature search based on publications up to March 2016 identified by PubMed and references cited in relevant articles.

Results

The morbid conditions associated with prior anticancer treatments including chemotherapy, radiotherapy, surgery, and/or hematopoietic stem-cell transplant may induce not only obstetric and neonatal complications but also long-term effects on offspring. Whereas some risks are predominantly evidenced in untreated women others are observed in both treated and untreated women. These risks may be superimposed on those induced by the current women’s trend in Western societies to postpone maternity.

Conclusions

Medical professionals should be aware and inform female cancer survivors wishing to have a child not only of the short- and long-term risks to themselves and their prospective offspring of previous anticancer treatments, fertility-preservation technologies, and pregnancy itself, but also of those risks linked to the morbid conditions induced by prior anticancer treatments. Once female cancer survivors wishing to have a child have been properly informed about the risks of reproduction, they will be best placed to make decisions of whether or not to have a biological or donor-conceived child. In addition, when medical professionals be aware of these risks, they will be also best placed to provide appropriate treatments before/during pregnancy in order to prevent or alleviate the impact of these morbid conditions on maternal and offspring health.

Background

The recent advances in anticancer treatments including chemotherapy, radiotherapy, surgery, and/or hematopoietic stem-cell transplant have increased percentages of remission and survival after treatment (for review, see Tschudin and Bitzer [1]). Despite these improvements, anticancer treatments still represent an immediate threat to health as well as later health complications clinically evidenced years or even decades after completion of therapy. In fact, it is estimated that approximately two thirds of childhood cancer survivors experience at least one chronic medical problem. The other one third suffers from severe or life-threatening complications 30 years after diagnosis of their primary cancer, mostly due to adverse cardiovascular events, pulmonary dysfunction, or second malignancies including leukemias and a variety of solid tumors involving the thyroid gland, breast, cervix, corpus of the uterus, and ovaries (for reviews, see Barnes and Chemaitilly [2] and Travis et al. [3]).

Another important issue linked to anticancer treatments is the temporary or permanent loss of fertility (for review, see Knopman et al. [4]). We should note that most female cancer survivors desire to have biological children and many of them, especially childless women, may feel cancer-related infertility as an emotionally distressing and devastating health problem [5]. This distress, however, may be attenuated if female cancer patients were properly informed about the risks to fertility of anticancer therapies and offered fertility preservation options prior starting any treatment [6]. Indeed, a number of medical approaches to preserve fertility before treatment begins are being currently developed and implemented. These approaches include the use of gonadotropin releasing hormone analogs (GnRHas) for ovarian suppression during chemotherapy, fertility-sparing surgery, transvaginal immature oocyte retrieval and subsequent in-vitro maturation, oocyte cryopreservation for future in-vitro fertilization (IVF), cryopreservation of embryos after either IVF or intracytoplasmic sperm injection, and ovarian tissue banking for future orthotopic or heterotopic auto-transplantation, xeno-transplantation into immunodeficient animals, or in-vitro follicular maturation and IVF (for reviews, see West et al. [7], Dittrich et al. [8], Smyth et al. [9], and Lambertini et al. [10]). Of note, some of these procedures including ovarian tissue cryopreservation [11], in-vitro maturation [12], and ovarian suppression during chemotherapy with GnRHas [13] are still nowadays classified as experimental/investigational. Consequently, they should not be represented or marketed to patients as established or routine medical procedures [14]. They should be offered to patients only in a research setting with institutional review board oversight [15].

In addition to the risk to fertility, female cancer patients should be informed before starting any anticancer treatment about the potential short- and long-term risks of anticancer therapy and fertility-preservation practices including the risk posed by fertility treatment and the possibility of reintroducing malignant tumors cells after transplantation of cryopreserved ovarian tissue [15]. Cancer patients should know that chemotherapy and radiotherapy have the potential to induce germ cell mutations that may lead to congenital anomalies and/or genetic disease in the next generation, particularly in those cancer survivors who have not undergone a previous fertility preservation procedure. They should be informed about this possibility despite literature shows that neither chemotherapy nor radiotherapy is associated with (1) germline minisatellite mutations in survivors of childhood and young adult cancer [16]; and (2) single gene disorders, chromosomal defects, mitochondrial DNA mutations, altered sex ratio (suggesting no increased incidence of X-linked mutations), congenital abnormalities or adventitious cancer in offspring [1719] (for reviews, see Knopman et al. [4], Hudson [20], Lawrenz et al. [21], and Nakamura et al. [22]). Cancer patients should know that the reported absence of effect of anticancer therapies on offspring genetic/chromosomal/congenital anomalies is likely due, at least in part, to the strong selection against most of the common chromosomal abnormalities present during pre- and post-implantation embryo/fetal development [23]. Accordingly, most embryos/fetuses with chromosomal anomalies may be lost before or shortly after implantation, even before women are aware that they are pregnant. Not surprisingly, literature shows that female cancer survivors without a prior fertility preservation procedure are substantially less likely to achieve a pregnancy and to have live births than their siblings or the general population (for reviews, see Knopman et al. [4] and Lawrenz et al. [21]). In addition, most birth defects are multifactorial in origin with clear interactions among genetics, epigenetics, maternal hormonal levels, and environmental exposures (e.g., medications, folate levels, nutrition, obesity, smoking, alcohol, pollutants, etc.) (for review, see Webber et al. [24]). This multifactorial origin of birth defects may dilute any existing association of anticancer therapies on offspring congenital anomalies. Notwithstanding, circumstantial evidence suggests that human immature resting oocytes compared with mouse oocytes are relatively resistant to radiation, not only in terms of cell killing but also in terms of induction of mutations (for review, see Nakamura et al. [22]).

After treatment and remission, female survivors wishing to have a child should be aware of other biological risks not only to themselves but also to their prospective offspring before making the decision to reproduce, irrespectively of whether they previously used fertility-preservation technologies or not. In particular, the potential risks posed by pregnancy on cancer recurrence (especially in breast cancer, endometrial cancer, and malignant melanoma), the difficulty in detecting cancer during pregnancy (particularly in breast cancer and endometrial cancer), and transmission of hereditary cancer syndromes (for review, see Matthews et al. [25]).

Although literature evidences the effects of type of cancer and/or anticancer treatment on live birth percentages and/or pregnancy and neonatal complications (for reviews, see Knopman et al. [4], Hudson [20], and Lawrenz et al. [21]), studies showing the obstetric and offspring risks of the morbid conditions associated with previous anti-cancer treatments are missing. In order to fill this gap, the present review aims to uncover and highlight the obstetric and offspring risks of the morbid conditions associated with previous anti-cancer treatments.

Methods

A literature search based on publications up to March 2016 identified by PubMed database searches using the following search terms: female cancer survivors, obstetric and neonatal risks, long-term risks, offspring, hyperprolactinemia, hypopituitarism, hypothyroidism, hyperthyroidism, primary ovarian insufficiency, obesity, overweight, hyperglycemia, insulin resistance, metabolic syndrome, diabetes mellitus, cardiovascular disease, obstructive lung disease, restrictive lung disease, decreased pulmonary diffusion capacity, chronic kidney disease, chronic hypertension, uterine damage, and low bone mineral density. In addition, a hand search was done to explore the references cited in the primary articles. Only articles (whenever possible systematic reviews and meta-analyses) published in English were included.

Results

Table 1 shows the potential obstetric and offspring risks of morbid conditions associated with prior anticancer treatment. Note that whereas some risks are predominantly evidenced in untreated women others are observed in both treated and untreated women. For instance, the increased risk of seizure (neonatal seizure, febrile seizure, and epilepsy), autism spectrum disorders, and attention-deficit hyperactivity disorder in offspring associated with maternal hypothyroidism or hyperthyroidism is mainly observed when the mother is first time diagnosed and treated for thyroid dysfunction after birth of the child, not before/during pregnancy (for review, see Andersen et al. [26]). Such a circumstance suggests that diagnosis and treatment of thyroid dysfunction before/during pregnancy may prevent or alleviate the effects of maternal thyroid disease on early brain development (for review, see Andersen et al. [26]). Likewise, (1) untreated hyperprolactinemia may be a risk factor for ectopical pregnancy [27]; (2) uncontrolled overt hyperthyroidism is associated with increased risk of thyroid storm, maternal congestive heart failure, miscarriage, stillbirth, preterm delivery, pre-eclampsia, low birth weight, intrauterine growth restriction, and fetal/neonatal thyroid dysfunction (for review, see Pearce [28]); (3) untreated euthyroid pregnant women with detectable thyroid autoantibodies display higher risks of miscarriage and preterm delivery than treated women (for systematic review, see Thangaratinam et al. [29]); and (4) tight glycemic control as well as dietary antioxidant supplementation during the preconception period and during the first trimester of pregnancy can prevent diabetes-associated birth defects and pregnancy complications (for review, see Ornoy et al. [30]). Notwithstanding, the level of glycemic control and glycemic threshold in pregnancy for preventing offspring complications later in life is still unknown (for review, see Hiersch and Yogev [31]).

Table 1 Potential obstetric and offspring risks of morbid conditions associated with prior anticancer treatments including chemotherapy, radiotherapy, surgery, and/or hematopoietic stem-cell transplant

On the contrary, chronic hypertension is associated with increased risk of adverse obstetrical and neonatal outcomes including pre-eclampsia, placental disorders, gestational diabetes, threatened abortion, preterm delivery, low birth weight, and congenital malformations, irrespectively of whether women are treated or not during pregnancy (for reviews, see Czeizel and Bánhidy [32] and Batemanet al. [33]). Of note, pregnant women suffering from chronic hypertension treated with antihypertensive drugs display ORs as high as 6.0 for pre-eclampsia, 2.3 for placental disorders, and 2.2 for gestational diabetes compared with control pregnant women without any type of hypertension (for review, see Czeizel and Bánhidy [32]). In addition, there are morbid conditions associated with prior anticancer therapies displaying problematic, controversial, or no treatment at all. For instance, obesity, restrictive lung disease, decreased pulmonary diffusion capacity, and uterine damage are not easily managed in clinical practice. Furthermore, many drugs prescribed for heart disease have teratogenic effects. Therefore, medication should be reviewed prior to pregnancy (for review, see Emmanuel and Thorne [34]).

Finally, we cannot ignore that maternal age at childbirth is steadily rising in many Western populations, and female cancer survivors are not an exception to this general trend [35]. The resulting obstetric and offspring risks associated with postponed maternity (for reviews, see Usta and Nassar [36], Nassar and Usta [37], and Sauer [38]) may be superimposed on those already present in cancer survivors. Importantly, the extra risks posed by delayed motherhood may not be prevented by applying fertility preservation strategies such as oocyte/embryo/ovarian tissue cryopreservation at younger ages. In fact, reciprocal ovarian transplants between young and old female mice show that the risk of congenital heart disease associated with advanced maternal age is not conferred by oocytes, but by the mother’s age [39]. Interestingly, this risk is modified by the mother’s genetic background and can be mitigated (but not eliminated entirely) by maternal voluntary (ad libitum) exercise beyond a threshold number of days before birth date, whether exercise begins at a young age or later in life [39].

Conclusions

The present review shows that the morbid conditions associated with prior anticancer treatments including chemotherapy, radiotherapy, surgery, and/or hematopoietic stem-cell transplant may induce obstetric and neonatal complications as well as long-term effects on offspring. Of note, whereas some risks are predominantly evidenced in untreated women others are observed in both treated and untreated women. These risks may be superimposed on those induced by the current women’s trend in Western societies to postpone maternity. Medical professionals should be aware and inform female cancer survivors wishing to have a child of the short- and long-term risks to themselves and their prospective offspring irrespectively of whether they previously used fertility-preservation technologies or not. These risks not only include those associated with previous anticancer treatments, fertility-preservation technologies, and pregnancy itself, but also those linked to the morbid conditions induced by prior anticancer treatments. Once female cancer survivors wishing to have a child have been properly informed about the risks of reproduction, they will be best placed to make decisions of whether or not to have a biological or donor-conceived child. In addition, when medical professionals be aware of these risks, they will be also best placed to provide appropriate treatments before/during pregnancy in order to prevent or alleviate the impact of these morbid conditions on maternal and offspring health.

Abbreviations

ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; BMI, body mass index; CI, confidence interval; FSH, follicle-stimulating hormone; GH, growth hormone; GnRHa, gonadotropin releasing hormone analog; HR, hazard ratio; IVF, in-vitro fertilization; LH, luteinizing hormone; OR, odds ratio; POI, primary ovarian insufficiency; PR, prevalence ratio; RR, relative risk; T4, thyroxine; TPOAb, thyroid peroxidase autoantibody; TSH, thyroid stimulating hormone

References

  1. 1.

    Tschudin S, Bitzer J. Psychological aspects of fertility preservation in men and women affected by cancer and other life-threatening diseases. Hum Reprod Update. 2009;15:587–97.

    Article  PubMed  Google Scholar 

  2. 2.

    Barnes N, Chemaitilly W. Endocrinopathies in survivors of childhood neoplasia. Front Pediatr. 2014;2:101.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Travis LB, Ng AK, Allan JM, Pui CH, Kennedy AR, Xu XG, et al. Second malignant neoplasms and cardiovascular disease following radiotherapy. Health Phys. 2014;106:229–46.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Knopman JM, Papadopoulos EB, Grifo JA, Fino ME, Noyes N. Surviving childhood and reproductive-age malignancy: effects on fertility and future parenthood. Lancet Oncol. 2010;11:490–98.

    Article  PubMed  Google Scholar 

  5. 5.

    Canada AL, Schover LR. The psychosocial impact of interrupted childbearing in long-term female cancer survivors. Psychooncology. 2012;21:134–43.

    Article  PubMed  Google Scholar 

  6. 6.

    Armuand GM, Wettergren L, Rodriguez-Wallberg KA, Lampic C. Women more vulnerable than men when facing risk for treatment-induced infertility: a qualitative study of young adults newly diagnosed with cancer. Acta Oncol. 2015;54:243–52.

    Article  PubMed  Google Scholar 

  7. 7.

    West ER, Zelinski MB, Kondapalli LA, Gracia C, Chang J, Coutifaris C, et al. Preserving female fertility following cancer treatment: current options and future possibilities. Pediatr Blood Cancer. 2009;53:289–95.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Dittrich R, Maltaris T, Hoffmann I, Oppelt PG, Beckmann MW, Mueller A. Fertility preservation in cancer patients. Minerva Ginecol. 2010;62:63–80.

    CAS  PubMed  Google Scholar 

  9. 9.

    Smyth C, Robertson I, Higgins L, Memeh K, O’Leary M, Keane M, et al. Fertility preservation in young females with non-gynaecologic malignancy: an emerging speciality. Ir J Med Sci. 2014;183:33–8.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Lambertini M, Ginsburg ES, Partridge AH. Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy. Curr Opin Obstet Gynecol. 2015;27:98–107.

    Article  PubMed  Google Scholar 

  11. 11.

    Practice Committee of American Society for Reproductive Medicine. Ovarian tissue cryopreservation: a committee opinion. Fertil Steril. 2014;101:1237–43.

    Article  Google Scholar 

  12. 12.

    Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. In vitro maturation: a committee opinion. Fertil Steril. 2013;99:663–6.

    Article  Google Scholar 

  13. 13.

    Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2013;100:1214–23.

    Article  Google Scholar 

  14. 14.

    Practice Committee of the American Society for Reproductive Medicine. Definition of experimental procedures: a committee opinion. Fertil Steril. 2013;99:1197–8.

    Article  Google Scholar 

  15. 15.

    Ethics Committee of American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: a committee opinion. Fertil Steril. 2013;100:1224–31.

    Article  Google Scholar 

  16. 16.

    Tawn EJ, Rees GS, Leith C, Winther JF, Curwen GB, Stovall M, et al. Germline minisatellite mutations in survivors of childhood and young adult cancer treated with radiation. Int J Radiat Biol. 2011;87:330–40.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Green DM, Lange JM, Peabody EM, Grigorieva NN, Peterson SM, Kalapurakal JA, et al. Pregnancy outcome after treatment for Wilms tumor: a report from the national Wilms tumor long-term follow-up study. J Clin Oncol. 2010;28:2824–30.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Guo Y, Cai Q, Samuels DC, Ye F, Long J, Li CI, et al. The use of next generation sequencing technology to study the effect of radiation therapy on mitochondrial DNA mutation. Mutat Res. 2012;744:154–60.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Winther JF, Olsen JH, Wu H, Shyr Y, Mulvihill JJ, Stovall M, et al. Genetic disease in the children of Danish survivors of childhood and adolescent cancer. J Clin Oncol. 2012;30:27–33.

    Article  PubMed  Google Scholar 

  20. 20.

    Hudson MM. Reproductive outcomes for survivors of childhood cancer. Obstet Gynecol. 2010;116:1171–83.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Lawrenz B, Henes M, Neunhoeffer E, Fehm T, Huebner S, Kanz L, et al. Pregnancy after successful cancer treatment: what needs to be considered? Onkologie. 2012;35:128–32.

    Article  PubMed  Google Scholar 

  22. 22.

    Nakamura N, Suyama A, Noda A, Kodama Y. Radiation effects on human heredity. Annu Rev Genet. 2013;47:33–50.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Rubio C, Rodrigo L, Mercader A, Mateu E, Buendía P, Pehlivan T, et al. Impact of chromosomal abnormalities on preimplantation embryo development. Prenat Diagn. 2007;27:748–56.

    Article  PubMed  Google Scholar 

  24. 24.

    Webber DM, MacLeod SL, Bamshad MJ, Shaw GM, Finnell RH, Shete SS, et al. Developments in our understanding of the genetic basis of birth defects. Birth Defects Res A Clin Mol Teratol. 2015;103:680–91.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Matthews ML, Hurst BS, Marshburn PB, Usadi RS, Papadakis MA, Sarantou T. Cancer, fertility preservation, and future pregnancy: a comprehensive review. Obstet Gynecol Int. 2012;2012:953937.

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Andersen SL, Olsen J, Laurberg P. Foetal programming by maternal thyroid disease. Clin Endocrinol (Oxf). 2015;83:751–8.

    Article  Google Scholar 

  27. 27.

    Rossi AM, Vilska S, Heinonen PK. Outcome of pregnancies in women with treated or untreated hyperprolactinemia. Eur J Obstet Gynecol Reprod Biol. 1995;63:143–6.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Pearce EN. Thyroid disorders during pregnancy and postpartum. Best Pract Res Clin Obstet Gynaecol. 2015;29:700–6.

    Article  PubMed  Google Scholar 

  29. 29.

    Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Ornoy A, Reece EA, Pavlinkova G, Kappen C, Miller RK. Effect of maternal diabetes on the embryo, fetus, and children: congenital anomalies, genetic and epigenetic changes and developmental outcomes. Birth Defects Res C Embryo Today. 2015;105:53–72.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Hiersch L, Yogev Y. Impact of gestational hyperglycemia on maternal and child health. Curr Opin Clin Nutr Metab Care. 2014;17:255–60.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Czeizel AE, Bánhidy F. Chronic hypertension in pregnancy. Curr Opin Obstet Gynecol. 2011;23:76–81.

    Article  PubMed  Google Scholar 

  33. 33.

    Bateman BT, Huybrechts KF, Fischer MA, Seely EW, Ecker JL, Oberg AS, et al. Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study. Am J Obstet Gynecol. 2015;212:337.e1–e14.

    Article  Google Scholar 

  34. 34.

    Emmanuel Y, Thorne SA. Heart disease in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2015;29:579–97.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Goldrat O, Kroman N, Peccatori FA, Cordoba O, Pistilli B, Lidegaard O, et al. Pregnancy following breast cancer using assisted reproduction and its effect on long-term outcome. Eur J Cancer. 2015;51:1490–6.

    Article  PubMed  Google Scholar 

  36. 36.

    Usta IM, Nassar AH. Advanced maternal age. Part I: obstetric complications. Am J Perinatol. 2008;25:521–34.

    Article  PubMed  Google Scholar 

  37. 37.

    Nassar AH, Usta IM. Advanced maternal age. Part II: long-term consequences. Am J Perinatol. 2009;26:107–12.

    Article  PubMed  Google Scholar 

  38. 38.

    Sauer MV. Reproduction at an advanced maternal age and maternal health. Fertil Steril. 2015;103:1136–43.

    Article  PubMed  Google Scholar 

  39. 39.

    Schulkey CE, Regmi SD, Magnan RA, Danzo MT, Luther H, Hutchinson AK, et al. The maternal-age-associated risk of congenital heart disease is modifiable. Nature. 2015;520:230–3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Du X, Yuan Q, Yao Y, Li Z, Zhang H. Hypopituitarism and successful pregnancy. Int J Clin Exp Med. 2014;7:4660–5.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Tarín JJ, García-Pérez MA, Hamatani T, Cano A. Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases. Reprod Biol Endocrinol. 2015;13:31.

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Khalak R, Cummings J, Dexter S. Maternal obesity: significance on the preterm neonate. Int J Obes (Lond). 2015;39:1433–6.

    CAS  Google Scholar 

  43. 43.

    Marchi J, Berg M, Dencker A, Olander EK, Begley C. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews. Obes Rev. 2015;16:621–38.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Cyganek K, Hebda-Szydlo A, Skupien J, Katra B, Janas I, Borodako A, et al. Glycemic control and pregnancy outcomes in women with type 2 diabetes from Poland. The impact of pregnancy planning and a comparison with type 1 diabetes subjects. Endocrine. 2011;40:243–9.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Gutaj P, Sawicka-Gutaj N, Brazert M, Wender-Ozegowska E. Insulin resistance in pregnancy complicated by type 1 diabetes mellitus. Do we know enough? Ginekol Pol. 2015;86:219–23.

    Article  PubMed  Google Scholar 

  46. 46.

    Vinceti M, Malagoli C, Rothman KJ, Rodolfi R, Astolfi G, Calzolari E, et al. Risk of birth defects associated with maternal pregestational diabetes. Eur J Epidemiol. 2014;29:411–8.

    Article  PubMed  Google Scholar 

  47. 47.

    Malek A. The impact of metabolic disease associated with metabolic syndrome on human pregnancy. Curr Pharm Biotechnol. 2014;15:3–12.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Kvetny J, Poulsen H. Transient hyperthyroxinemia in newborns from women with autoimmune thyroid disease and raised levels of thyroid peroxidase antibodies. J Matern Fetal Neonatal Med. 2006;19:817–22.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Dallas JS. Autoimmune thyroid disease and pregnancy: relevance for the child. Autoimmunity. 2003;36:339–50.

    Article  PubMed  Google Scholar 

  50. 50.

    Svensson J, Lindberg B, Ericsson UB, Olofsson P, Jonsson B, Ivarsson SA. Thyroid autoantibodies in cord blood sera from children and adolescents with autoimmune thyroiditis. Thyroid. 2006;16:79–83.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Wilson RM, Messaoudi I. The impact of maternal obesity during pregnancy on offspring immunity. Mol Cell Endocrinol. 2015;418(Pt 2):134–42.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments. Nat Rev Cardiol. 2015;12:547–58.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Armenian SH, Landier W, Francisco L, Herrera C, Mills G, Siyahian A, et al. Long-term pulmonary function in survivors of childhood cancer. J Clin Oncol. 2015;33:1592–600.

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Lapinsky SE, Tram C, Mehta S, Maxwell CV. Restrictive lung disease in pregnancy. Chest. 2014;145:394–8.

    Article  PubMed  Google Scholar 

  55. 55.

    McAuliffe F, Kametas N, Rafferty GF, Greenough A, Nicolaides K. Pulmonary diffusing capacity in pregnancy at sea level and at high altitude. Respir Physiol Neurobiol. 2003;134:85–92.

    Article  PubMed  Google Scholar 

  56. 56.

    Giussani DA, Niu Y, Herrera EA, Richter HG, Camm EJ, Thakor AS, et al. Heart disease link to fetal hypoxia and oxidative stress. Adv Exp Med Biol. 2014;814:77–87.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Knijnenburg SL, Mulder RL, Schouten-Van Meeteren AY, Bökenkamp A, Blufpand H, van Dulmen-den Broeder E, et al. Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst Rev. 2013;10:CD008944.

    PubMed  Google Scholar 

  58. 58.

    Porta C, Cosmai L, Gallieni M, Pedrazzoli P, Malberti F. Renal effects of targeted anticancer therapies. Nat Rev Nephrol. 2015;11:354–70.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Gyamlani G, Geraci SA. Kidney disease in pregnancy: (Women’s Health Series). South Med J. 2013;106:519–25.

    Article  PubMed  Google Scholar 

  60. 60.

    Wo JY, Viswanathan AN. Impact of radiotherapy on fertility, pregnancy, and neonatal outcomes in female cancer patients. Int J Radiat Oncol Biol Phys. 2009;73:1304–12.

    Article  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Wallace WH, Critchley HO, Anderson RA. Optimizing reproductive outcome in children and young people with cancer. J Clin Oncol. 2012;30:3–5.

    Article  PubMed  Google Scholar 

  62. 62.

    Teh WT, Stern C, Chander S, Hickey M. The impact of uterine radiation on subsequent fertility and pregnancy outcomes. Biomed Res Int. 2014;2014:482968.

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Wasilewski-Masker K, Kaste SC, Hudson MM, Esiashvili N, Mattano LA, Meacham LR. Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature. Pediatrics. 2008;121:e705–13.

    Article  PubMed  Google Scholar 

  64. 64.

    Wissing MD. Chemotherapy- and irradiation-induced bone loss in adults with solid tumors. Curr Osteoporos Rep. 2015;13:140–5.

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Kovacs CS et al. Calcium metabolism during pregnancy and lactation. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, editors. Endotext [Internet] (MDText.com, Inc.; 2000-: South Dartmouth (MA). 2015. Available from http://www.ncbi.nlm.nih.gov/books/NBK279173/). Accessed 10 March 2015.

    Google Scholar 

  66. 66.

    Done SL. Fetal and neonatal bone health: update on bone growth and manifestations in health and disease. Pediatr Radiol. 2012;42 Suppl 1:S158–76.

    Article  PubMed  Google Scholar 

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JJT has been involved in conception and design, acquisition, analysis and interpretation of data, drafting the article and final approval of the version to be published. MAGP and AC have been involved in analysis and interpretation of data, revising the article critically for important intellectual content and final approval of the version to be published.

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Tarín, J.J., García-Pérez, M.A. & Cano, A. Obstetric and offspring risks of women’s morbid conditions linked to prior anticancer treatments. Reprod Biol Endocrinol 14, 37 (2016). https://doi.org/10.1186/s12958-016-0169-6

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Keywords

  • Fertility
  • Gestation
  • Gynecology
  • Pregnancy
  • Pregnancy complications