2005 © Oxford University Press
Parenthood in Survivors After Adulthood Cancer and Perinatal Health in Their Offspring: A Preliminary Report
Affiliations of authors: The Norwegian Radium Hospital, Department of Clinical Cancer Research, Oslo, Norway (SDF, HM, ABJ); The Medical Birth Registry of Norway, and Department of Public Health and Primary Health Care, University of Bergen, Norway (KM, RS); The Cancer Registry of Norway, Oslo, Norway (FL)
Correspondence to: S.D. Fosså, The Norwegian Radiumhospital, Department of Clinical Cancer Research, Montebello 0310 Oslo, Norway (e-mail: s.d.fossa{at}klinmed.uio.no).
 |
ABSTRACT |
|---|
 TopNotes Abstract IntroductionMETHODSRESULTSDISCUSSIONCONCLUSIONReferences |
|---|
Cancer survivors may fear infertility, obstetric problems, and genetic alterations in their offspring. After linkage of three registries the probability of post-treatment parenthood and the risk of obstetric and perinatal problems were estimated in cancer survivors compared to individuals without a cancer diagnosis. A total of 1531 of 13 817 patients had 2307 children after one parent's cancer diagnosis: 972 males had 1479 children and 559 females had 828. A total of 1217 patients (784 males and 433 females) became parents
9 months after the diagnosis (1899 births: 1221 to male cancer patients and 678 to female patients). The post-diagnosis parenthood probability was 8% at 5 years, and 14% at 10 years without further increase. Female cancer survivors gave birth to post-diagnosis infants with on average 130 grams lower birth weight and 6 days shorter gestations compared with infants in the non-cancer population. Infants fathered by male cancer survivors did not differ from control infants with respect to birth weight or gestational age. There was no increase in the prevalence of major congenital malformations in the offspring of cancer survivors as compared with the offspring of the non-cancer population. Multiple births and deliveries by cesarean sections were increased. Parenthood after cancer is possible in a significant number of patients, more so for males than females. The risk of major congenital malformations was not increased relative to the non-cancer population, nor was perinatal mortality increased. However, female cancer survivors delivered more preterm births and low-birth-weight infants than what was found in the non-cancer population.
|
INTRODUCTION |
|---|
|
TopNotesAbstractIntroductionMETHODSRESULTSDISCUSSIONCONCLUSIONReferences |
|---|
During the last two decades quality of life has become an important outcome parameter in oncology, including the possibility for cancer survivors to become parents of healthy children (1–3). An increase of malformations in the offspring of cancer survivors has not been documented compared with controls (1 ,4–6), though more data are needed to enable evidence-based counselling of cancer patients concerning future fertility and children's health.
The present preliminary report deals with the probability of parenthood after a cancer diagnosis and the risk of major congenital malformations in the offspring, together with obstetric and perinatal complications after one parent's first malignant diagnosis. Modern techniques of assisted fertilization (7–10) are not considered in the present report. The results are compared with those of a control group.
|
METHODS |
|---|
|
TopNotesAbstractIntroductionMETHODSRESULTSDISCUSSIONCONCLUSIONReferences |
|---|
Series Established by Linking Three Registries
Patient registry of the Norwegian Radium Hospital (NRH). The NRH is a comprehensive cancer center with about 300 beds. Starting in 1971 an electronic patient registry is available with information on the patients' cancer diagnosis (ICD-7) and summarized information on treatment and outcome.
Cancer registry of Norway (CRN). Cancer reporting to this registry has been compulsory for Norwegian hospitals and histopathological laboratories sine 1953 (date and type of diagnosis, extent of the disease, histology, date and cause of death).
Medical birth registry of Norway (MBRN). Since 1967 this population-based registry has collected information on all live births in Norway and on stillbirths of at least 16 weeks gestation. The midwife attending the birth reports demographic data of the parents, maternal health before and during pregnancy, previous reproductive history, complications during pregnancy and delivery, and pregnancy outcome, together with the results of the medical examination of the newborn. For the present study data were available for the time period 1967–1998 (about 1.8 million childbirths).
Linkage of person-identifiable records from these three registries is possible by means of the individual's unique identification number, given to each citizen living in Norway. Cases were selected based on the following eligibility criteria: a) patients aged 15–45 years at the first cancer diagnosis and at first referral to the NRH; b) hospitalized at the NRH between 1971 and 1997; c) histologically verified invasive malignancy, based on ICD-7 (140–207, except 189).
To estimate the probability of parenthood after a malignant diagnosis, we counted childbirths 9 months or more after the diagnosis of cancer. When evaluating perinatal outcome, we studied all deliveries after a parent's malignant diagnosis, independent of the length of the post-diagnostic interval, and compared the results with deliveries reported for all other individuals in the MBRN (controls).
Statistics
Common descriptive measures were used together with the Kaplan Meier procedure to estimate the probability of parenthood. Patients were censored at death or emigration or, for surviving patients, on January 1, 1999. Differences between curves were evaluated by the log-rank test. For categorical variables, we calculated crude odds ratios (ORs) with 95% confidence intervals, and we used logistic regression analyses to adjust for confounding factors (maternal age, parity, year of childbirth). A P value of 
0.05 was considered to be statistically significant.
|
RESULTS |
|---|
|
TopNotesAbstractIntroductionMETHODSRESULTSDISCUSSIONCONCLUSIONReferences |
|---|
We identified 13 817 eligible patients. About two-thirds of the patients were females (Table 1), and 57% had at least one child before the cancer diagnosis.
|
Post-diagnosis Parenthood (
9 Months)
A total of 1217 patients had at least 1 child 9 months after their cancer diagnosis, resulting in 1899 children (Table 2). Almost 90% of these 1217 patients had 1 or 2 children 9 months or later after the malignant diagnosis (Fig. 1). One patient had 7 children born after his treatment for testicular cancer. Post-treatment parenthood was significantly more frequent among males than among females (males: 784 fathers of 5183 patients versus females: 433 mothers of 8644 patients, P<0.01). The male cancer patients had a total of 1221 children, and the female cancer patients had 678 children. In general, 3–4.5 years elapsed from the diagnosis of cancer to the first post-treatment childbirth.
|
|
For all 13 817 patients the 5-year probability of first parenthood after at least 9 months was 8% and 14% at 5 and 10 years, respectively (Fig. 2, A). Being a male cancer survivor, age below 30 years at diagnosis, and being childless before the diagnosis of cancer favored post-diagnosis parenthood (Fig. 2, B–D).
|
Women with uterine choriocarcinoma displayed the highest 10-year probability of post-diagnosis parenthood (Fig. 3, A) followed by patients with malignant lymphoma, testicular cancer, and malignant melanoma (Fig. 3, B–D). The 10-year probability of post-diagnosis parenthood was only 5% for female patients with all other diagnoses (Fig. 3, E). After 1980 the 10-yearpost-diagnosis parenthood rate for male patients did not increase, whereas the 10-year post-diagnosis parenthood rate for female patients increased from 7.3% to 9.0% (P<0.05; Fig. 4). Overall the likelihood for motherhood was significantly lower than that of fatherhood for all strata examined.
|
|
Obstetric and Perinatal Outcome
When counting all births after a cancer diagnosis, independent of the post-diagnosis time interval, 972 male and 559 female cancer survivors were registered with at least one post-diagnosis birth in the MBRN, adding up to a total of 2307 post-diagnosis births (Table 2). The male cancer survivors were registered as fathers to a total of 1479 post-diagnosis infants, and the female cancer survivors delivered a total of 828 post-diagnosis infants (Table 2).
The mean age at post-diagnosis delivery for female cancer survivors was 29.8 years (95% confidence interval [CI] = 29.5; 30.1), whereas mean age for male cancer survivors at the time of post-diagnosis birth was 32.9 years (95% CI = 32.7; 33.2). This was significantly higher than the mean age at childbirth in the control population (mean maternal age 26.8 years [95% CI = 26.75; 26.77] and mean paternal age 30.4 years [95% CI = 30.40; 30.41]). Among post-diagnosis pregnancies, 35.9% were first pregnancies, 38.7% were second pregnancies, and 25.4% were of higher parities. Among pregnancies to women in the non-cancer population, 41.5% were first pregnancies, 34.6% were second pregnancies, and 23.9% were higher parity pregnancies.
Twins (3.2%) and triplets (0.4%) were significantly more common in post-diagnosis pregnancies than in control pregnancies (2.2% twins and 0.06% triplets), and also more common than in pregnancies to cancer patients before the cancer diagnosis (2.3% twins, no triplets). Male cancer survivors had the highest proportion of twins/triplets (Table 3). In addition, there was a marked time trend in the proportion of twins and triplets born after a cancer diagnosis over time (Fig. 5, A). This time trend was most marked for female cancer survivors, with an increase from no multiple births between 1971 and 1980 to 5.2% between 1991 and 1998. The time trend in the proportion of multiple births to male cancer survivors was similar to the time trend among control individuals, but the absolute proportion was higher throughout the time period (Fig. 5, A).
|
|
Compared with the control group, significantly more births in the cancer population were delivered by cesarean section, even when excluding multiple births (Fig. 5, B). The increased use of cesarean section was confined to female cancer survivors. In contrast to what was found among control individuals, the use of cesarean section in the female cancer population decreased over the time period of the study.
After excluding multiple births, the mean gestational age for infants delivered to female cancer survivors was 6 days shorter and the mean birth weight was 130 grams lower than that of infants delivered to control individuals. In line with this, there was a significant increase in preterm delivery (before 37 completed weeks) among female cancer survivors compared with the controls, which persisted after adjusting for maternal age, parity, and time period (Table 4). Likewise, the female cancer survivors had more than twice the risk of low-birth-weight delivery (birth weight below 2500 grams) than control individuals (Table 4). On the other hand, infants fathered by male cancer survivors did not differ significantly from infants in the control group with regards to gestational age or birth weight.
|
|
DISCUSSION |
|---|
|
TopNotesAbstractIntroductionMETHODSRESULTSDISCUSSIONCONCLUSIONReferences |
|---|
Overall, the cumulative 10-year probability of post-cancer parenthood was 14%, allowing the general view that a significant number of cancer survivors want to become parents and are successful in their attempt. The documented post-diagnosis pregnancies did in general not represent a major health risk for the mothers or the children. The chance of post-diagnosis fatherhood significantly exceeded that of motherhood, but the female cancer survivors' chances of having a child significantly increased after 1980.
In patients with gestational trophoblastic tumors it has been known for a long time that treatment with anti-metabolites does not lead to permanent ovarian failure (11). Today's treatment of malignant lymphoma and testicular cancer enables post-diagnosis parenthood at relatively high rates, in spite of frequent use of cytostatic drugs and irradiation. The introduction of ABVD chemotherapy (adriamycin, bleomycin, vinblastine, darcabazine) and the reduced use of pelvic radiotherapy after 1980 are probably the main reasons for this development (12,13). Recovery of spermatogenesis usually occurs after ABVD chemotherapy of Hodgkin lymphoma and after cisplatin-containing combination chemotherapy in patients with testicular cancer, thus allowing fatherhood in most patients with retained antegrade ejaculation (2,14,15). The introduction of pre-treatment sperm banking (16) along with improvement of assisted reproduction techniques (ART) overcome major infertility problems in men, though only about 20% ever use their banked semen (17). On the other hand, preservation of ovarian function implies many practical problems. Though cryopreservation of fertilized oocytes is possible and is in clinical use, cryopreservation of non-fertilized oocytes and ovarian tissue remains experimental (3,10).
Previous reports (1,6,18) have not been able to prove an increase of rate of congenital malformations in cancer survivors' offspring in spite of post-treatment chromatin alterations in sperm cells (4), even in men who have fathered a child. Neither has the present rather large series demonstrated an increase of major congenital malformations diagnosed during the perinatal period.
There was no increase of perinatal mortality for infants delivered to cancer survivors, though pregnancies to women with a cancer diagnosis more often resulted in pre-term delivery. It is not clear whether this latter risk is related to the malignancy itself or its treatment, such as scattered irradiation from abdominal radiotherapy. The combination of psychological and obstetric considerations has probably led to the high frequency of cesarean section. An increase of pre-term delivery together with the increased proportion of multiple births indicate that pregnancies in cancer survivors require a particularly high level of obstetric and perinatal health care.
Some limitations of the present report have to be mentioned. Thus far, specific treatments have not been taken into account in this preliminary report. Second, our cross-sectional calculations do not consider any sibling-related associations existing for birth weight, obstetric or perinatal complications, or malformations (19,20). Third, only those major malformations that were diagnosed during the perinatal period were considered, whereas minor malformations probably have remained undiagnosed.
|
CONCLUSION |
|---|
|
TopNotesAbstractIntroductionMETHODSRESULTSDISCUSSIONCONCLUSIONReferences |
|---|
Post-diagnosis parenthood is possible in a considerable proportion of cancer survivors (10-year cumulative rate of post-diagnosis parenthood: 14%). A slightly increased risk of pre-term births and an increased proportion of multiple pregnancies warrant particular obstetric and perinatal health care. No increase of major congenital malformations in cancer survivors' offspring was found.
|
NOTES |
|---|
This study was financially supported by a grant from the Lance Armstrong Foundation.
|
REFERENCES |
|---|
|
TopNotesAbstractIntroductionMETHODSRESULTSDISCUSSIONCONCLUSIONReferences |
|---|
(1) Byrne J, Rasmussen SA, Steinhorn SC, Connelly RR, Myers MH, Lynch CF, et al. Genetic disease in offspring of long-term survivors of childhood and adolescent cancer. Am J Hum Genet 1998;62:45–52.[CrossRef][ISI][Medline]
(2) Howell SJ, Shalet SM. Testicular function following chemotherapy. Hum Reprod Update 2001;7:363–9.
(3) Howell SJ, Shalet SM. Fertility preservation and management of gonadal failure associated with lymphoma therapy. Curr Oncol Rep 2002;4:443–52.[Medline]
(4) De Palma A, Vicari E, Palermo I, D'Agata R, Calogero AE. Effects of cancer and anti-neoplastic treatment on the human testicular function. J Endocrinol Invest 2000;23:690–6.[ISI][Medline]
(5) Morris ID. Sperm DNA damage and cancer treatment. Int J Androl 2002;25:255–61.[CrossRef][ISI][Medline]
(6) Swerdlow AJ, Jacobs PA, Marks A, Maher EJ, Young T, Barber JC, et al. Fertility, reproductive outcomes, and health of offspring, of patients treated for Hodgkin's disease: an investigation including chromosome examinations. Br J Cancer 1996;74:291–6.[ISI][Medline]
(7) Hovatta O. Cryopreservation of testicular tissue in young cancer patients. Hum Reprod Update 2001;7:378–83.
(8) Blumenfeld Z. Gynaecologic concerns for young women exposed to gonadotoxic chemotherapy. Curr Opin Obstet Gynecol 2003;15:359–70.[CrossRef][ISI][Medline]
(9) Wallace WH, Thomson AB. Preservation of fertility in children treated for cancer. Arch Dis Child 2003;88:493–6.
(10) Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol 2000;169:123–31.[CrossRef][ISI][Medline]
(11) Goldstein DP. Gestational trophoblastic neoplasia in the 1990s. Yale J Biol Med 1991;64:639–51.[ISI][Medline]
(12) Viviani S, Santoro A, Ragni G, Bonfante V, Bestetti O, Bonadonna G. Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD. Eur J Cancer Clin Oncol 1985;21:601–5.[CrossRef][ISI][Medline]
(13) Meistrich ML, Wilson G, Mathur K, Fuller LM, Rodriguez MA, McLaughlin P,et al. Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease. J Clin Oncol 1997;15:3488–95.
(14) Jacobsen KD, Ous S, Waehre H, Trasti H, Stenwig AE, Lien HH, et al. Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection. Br J Cancer 1999;80:249–55.[CrossRef][ISI][Medline]
(15) Pectasides D, Pectasides M, Farmakis D, Nikolaou M, Koumpou M,Kostopoulou V, et al. Testicular function in patients with testicular cancer treated with Bleomycin-Etoposide-Carboplatin (BEC90) combination chemotherapy. Eur Urol 2004;45:187–93.[CrossRef][ISI][Medline]
(16) Fossa SD, Aass N, Molne K. Is routine pre-treatment cryopreservation of semen worthwhile in the management of patients with testicular cancer? Br J Urol 1989;64:524–9.[ISI][Medline]
(17) Blackhall FH, Atkinson AD, Maaya MB, Ryder WD, Horne G, Brison DR, et al. Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease. Br J Cancer 2002;87:381–4.[CrossRef][ISI][Medline]
(18) Meistrich ML, Byrne J. Genetic disease in offspring of long-term survivors of childhood and adolescent cancer treated with potentially mutagenic therapies. Am J Hum Genet 2002;70:1069–71.[CrossRef][ISI][Medline]
(19) Skjaerven R, Wilcox AJ, Lie RT, Irgens LM. Selective fertility and the distortion of perinatal mortality. Am J Epidemiol 1988;128:1352–63.
(20) Skjaerven R, Wilcox AJ, Lie RT. A population-based study of survival and childbearing among female subjects with birth defects and the risk of recurrence in their children. N Engl J Med 1999;340:1057–62.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Geens, E. Goossens, G. De Block, L. Ning, D. Van Saen, and H. Tournaye Autologous spermatogonial stem cell transplantation in man: current obstacles for a future clinical application Hum. Reprod. Update, March 1, 2008; 14(2): 121 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Magelssen, K.K. Melve, R. Skjaerven, and S.D. Fossa Parenthood probability and pregnancy outcome in patients with a cancer diagnosis during adolescence and young adulthood Hum. Reprod., January 1, 2008; 23(1): 178 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hammond, J. R. Abrams, and K. L. Syrjala Fertility and Risk Factors for Elevated Infertility Concern in 10-Year Hematopoietic Cell Transplant Survivors and Case-Matched Controls J. Clin. Oncol., August 10, 2007; 25(23): 3511 - 3517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Lee, L. R. Schover, A. H. Partridge, P. Patrizio, W. H. Wallace, K. Hagerty, L. N. Beck, L. V. Brennan, and K. Oktay American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients J. Clin. Oncol., June 20, 2006; 24(18): 2917 - 2931. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||