Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors

Abstract

Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early-onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0-19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95% CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95% C I 1.26-6.11; and 1965-1974: PR 1.55, 95% C I 0.94-2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades.

Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility

“…Male survivors who received high doses of alkylating drugs during childhood are especially less likely to father a child [64,65]. Offspring of survivors diagnosed in childhood do not appear to have a higher risk of congenital abnomalities, genetic diseases, and abnormal karyotypes compared with their siblings [66][67][68][69]. Moreover, no significant difference has been observed in the risk of hospitalization between children of paediatric cancer survivors and the overall population [69].…”

Fertility Preservation for Pediatric and Adolescent Patients With Cancer: Medical and Ethical Considerations

“…Many survivors of childhood cancer with intact fertility worry about the potential effects of previous cancer treatment on the health of their offspring. 17 Reassuringly, decades of cumulative experience have shown that naturally conceived biological children of survivors have no increased incidence of congenital malformations, [18][19][20][21][22] genetic or chromosomal anomalies, [23][24][25] or cancer compared with sibling controls and general population data. [26][27][28][29][30][31][32][33]…”

Perinatal complications in female survivors of cancer: a systematic review and meta-analysis

“…In the case of congenital abnormalities, the definition varies greatly -with large fluctuations in prevalence rates ranging from 1.4% [8] to 9.5% [12]. In the separate studies, only one of the twelve studies reporting on congenital abnormalities reported a higher prevalence in cancer survivors [18]. In that study, the unadjusted prevalence ratio was 1.21 (95% CI 1.03 -1.40) but after adjustment for maternal age at birth of child, parity, sex of child and birth decade of child, the adjusted prevalence ratio was 1.07 (95% CI 0.91 -1.25).…”

“…Some early studies suggested an increased relative risk of congenital abnormalities in the offspring of cancer survivors [15,16]. These findings have not been confirmed in more recent analyses [9,12,17,18]. Due to the low prevalence of both cancer in children and young adults and of some pregnancy and labor complications, evaluation of these data benefits from large number of subjects being involved, giving increased statistical power.…”