Pregnancy Outcomes among Adult Survivors of Childhood Cancer in the British Childhood Cancer Survivor Study

Abstract

Purpose: We used data from the first large-scale overwhelmingly population-based study (a) to quantify the risk of adverse pregnancy outcomes in survivors of childhood cancer in relation to cancer type and treatment and (b) to assess live birth rates relative to the general population. Methods: A questionnaire, including questions inquiring about pregnancy outcomes, was completed by 10,483 survivors. A total of 7,300 pregnancies were reported. Odds ratios (OR) for live birth, miscarriage, termination, stillbirth, premature birth, and low birth weight were calculated for different types of childhood cancer and by whether initial treatment involved chemotherapy and abdominal or brain irradiation. For females, the observed number of live births was compared with that expected based on the general population of England and Wales. Results: Female survivors exposed to abdominal irradiation had a significantly increased OR of delivering preterm [OR, 3.2; 95% confidence interval (95% CI), 2.1-4.7] and producing offspring with a low birth weight (OR, 1.9; 95% CI, 1.1-3.2). An increased OR of miscarriage was also associated with abdominal radiotherapy (OR, 1.4; 95% CI, 1.0-1.9). The number of live births observed from all female survivors was two thirds of that expected (O/E, 0.64; 95% CI, 0.62-0.66) and lowest among survivors treated with brain (O/E, 0.52; 95% CI, 0.48-0.56) and abdominal radiotherapy (O/E, 0.55; 95% CI, 0.50-0.61). Conclusion: Female survivors of childhood cancer treated with abdominal radiotherapy are at 3-fold increased risk of delivering preterm, 2-fold increased risk of low birth weight, and a small increased risk of miscarriage. Overall, female survivors produce considerably fewer offspring than expected, particularly those treated with abdominal or brain radiotherapy.

Life beyond the disease: relationships, parenting, and quality of life among survivors of childhood cancer

“…8 The British Childhood Cancer Survivor Study reported only 31% of survivors having at least one child which is approximately two-thirds of what would be expected from British population statistics. 9 Just 3% of Dutch male and 15% of Dutch female survivors reported biological children. 10 Reports from the Childhood Cancer Survivor Study show 15% of men and 27% of women survivors with children.…”

“…However, prematurity and low-birth weights have been associated with abdominal radiation. [9][10][11][12] Pivetta et al use marriage and offspring as surrogate markers for the life-long impact of cancer therapy on the social and behavioral choices of adult survivors of childhood cancer. This raises important questions regarding measurement of QOL in this population.…”

Fertility Preservation in Reproductive-Age Women Facing Gonadotoxic Treatments

“…Youth is certainly a protective factor, but long-term follow-up of childhood cancer patients demonstrates clear effects on ovarian reserve and reproductive potential later in life [25][26][27][28][29][30][31] . Fortunately, chemotherapeutic agents do not appear to have long-term effects on the genetic competency of surviving oocytes or on the future pregnancies themselves 32 , but based on murine data, the risk of fetal malformation might be elevated for up to 6-12 months after exposure 33 .…”

“…Pelvic irradiation impairs fertility and is associated with poor pregnancy outcomes, including early and midtrimester loss, preterm birth, and low birthweight 41 . The pathophysiology appears to involve vascular, endometrial, and myometrial damage 31,42 . Exposure before completion of puberty impairs normal uterine development, with a resulting reduced adult uterine volume that is refractory to estrogen replacement therapy.…”

Lifestyle, distress, and pregnancy outcomes in the Childhood Cancer Survivor Study cohort

“…3 Previous studies have identified treatment-related risks, reporting an increased risk of preterm birth following ≥ 5 Gray (Gy) of uterine radiation, 3 stillbirth following ≥ 10 Gy of uterine and ovarian radiation, 4 and miscarriage following abdominal radiation. 5, 6 However, the influence of potentially modifiable prepregnancy lifestyle factors such as body mass index (BMI), smoking, heavy alcohol consumption, physical inactivity, and psychological distress on adverse pregnancy outcomes in childhood cancer survivors has not been evaluated.…”