Author + information
- Kara A. Thompson, MD∗ (, )
- Michelle A.T. Hildebrandt, PhD and
- Joann L. Ater, MD
- ↵∗Department of Cardiology, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1451, Houston, Texas 77030
We evaluated the cardiac outcomes of M.D. Anderson Cancer Center childhood cancer survivors who were pregnant and who were previously exposed to anthracyclines and/or chest radiation. We identified 337 women between ages 16 and 55 years and who had been diagnosed with cancer at <20 years and treated with anthracyclines and/or chest radiation. Patients were followed up for ≥10 years from the time of diagnosis unless pregnancy occurred prior to 10 years. Echocardiographic screenings were conducted every 1 year to 5 years as recommended by the risk-based Children’s Oncology Group survivorship guidelines (1). Exclusion criteria included a history of abortion or miscarriage without live birth, having Down’s syndrome, and death from disease without adequate follow-up off treatment. Of the 337 women, 58 had at least 1 pregnancy and gave birth to 86 children. The median follow-up time was 20 years. A control group of 80 women survivors without pregnancies who had similar anthracycline doses and follow-up times was identified. Characteristics for pregnancy patients with adverse cardiac conditions were compared to those without and compared to the control group of women survivors who did not have pregnancies (Table 1).
Of the 80 women in the control group, 12 (15%) had an adverse cardiac event defined as ejection fraction <50% on at least 2 echocardiograms or coronary artery disease. Of the 58 women who had ≥1 pregnancy, 17 (29.3%) had an adverse cardiac event. Three were diagnosed with cardiac disease prior to pregnancy, 9 were diagnosed during pregnancy, and 5 were diagnosed after pregnancy. The peripartum period was defined as during pregnancy or 1 year after delivery. Of these 17 patients with adverse cardiac events, at the time of last follow-up, 8 (47.1%) had recovered, 7 (41.2%) had not recovered, and 2 (11.8%) had died. We found subgroups of pregnant patients with increased risk of adverse cardiac outcomes. Older age at the time of cancer diagnosis was significantly associated with a 14% reduction in risk (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76-0.97; p = 0.011). Longer time to first pregnancy was associated with a significant increase in risk (OR: 1.13; 95% CI: 1.03-1.25). Together, these findings suggest increased risk of cardiotoxicity with increased length of time between exposure to anthracyclines and time to first pregnancy. And, higher anthracycline dose was also associated with an increase in risk (OR: 1.01; 95% CI: 1.00-1.01; p = 0.014).
Pregnancy was associated with a 2.35-fold increase in risk (95% CI: 1.02-5.41; p = 0.045) of cardiotoxicity in the overall study population (N = 138). This effect increased in significance after adjusting for anthracycline dose (OR: 2.80; 95% CI: 1.14-6.86; p = 0.025) and remained borderline significant when including follow-up time into the model (OR: 2.48; 95% CI: 0.995 to 6.22; p = 0.051).
There is limited data on cardiac outcomes of childhood cancer survivors who had pregnancies and were previously exposed to cardiotoxic agents. In 1 study, 37 childhood cancer survivors were followed prospectively throughout pregnancy. All received a cumulative dose of doxorubicin of <500 mg/m2. This study suggested a favorable outcome in patients with fractional shortening >30% and did not find pregnancy to be a contributing factor to worse cardiac function after anthracyclines (2). In another study, 53 women who had childhood cancer and pregnancies were reviewed. None of these women developed clinical signs or symptoms of heart failure, although echocardiograms were not performed to conclusively rule out development of heart failure. Although encouraging, this study was not adequately powered to assess cardiac risk (3). More recently, Hines et al. (4) presented findings from a cohort of 847 women treated at St. Jude Children’s Research Hospital and reported a low (0.3%) incidence of pregnancy-associated cardiomyopathy. However, these findings were based on self-reported development of cardiac events and not on echocardiographic changes.
In our study of high-risk pregnant patients, we identified subgroups with an increased risk of adverse cardiac outcomes: younger age at cancer diagnosis, longer time from cancer treatment to first pregnancy, and higher total anthracycline dose. Pregnancy was an independent risk for cardiotoxicity. These patients require more vigilant monitoring than the general population.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- ↵Children's Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer, 2013. Available at: http://www.survivorshipguidelines.org/pdf/LTFUGuidelines_40.pdf. Accessed on January 15, 2016.
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