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Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Echocardiography | Research

Cardiac and obstetric outcomes of pregnancies for women after cardiotoxic therapy in childhood: a single center observational study

Authors: Julius C. Heemelaar, Steffie Heemelaar, Svenja N. Hertel, J. Wouter Jukema, Marieke Sueters, Marloes Louwerens, M. Louisa Antoni

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Childhood cancer survivors (CCS) are at increased risk of cardiomyopathy during pregnancy if they have prior cardiotoxic exposure. Currently, there is no consensus on the necessity, timing and modality of cardiac monitoring during and after pregnancy. Therefore, we examined cardiac function using contemporary echocardiographic parameters during pregnancy in CCS with cardiotoxic treatment exposure, and we observed obstetric outcomes in CCS, including in women without previous cardiotoxic treatment exposure.

Method

A single-center retrospective cohort study was conducted among 39 women enrolled in our institution’s cancer survivorship outpatient clinic. Information on potential cardiotoxic exposure in childhood, cancer diagnosis and outcomes of all pregnancies were collected through interviews and review of health records. Echocardiographic exams before and during pregnancy were retrospectively analyzed for left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) if available. The primary outcomes were (i) left ventricular dysfunction (LVD) during pregnancy, defined as LVEF < 50% or a decline of ≥ 10% in LVEF below normal (< 54%), and (ii) symptomatic heart failure (HF). Rate of obstetric and fetal complications was compared to the general population through the national perinatal registry (PERINED).

Results

All pregnancies (91) of 39 women were included in this study. The most common malignancy was leukemia (N = 17, 43.6%). In 22 patients, echocardiograms were retrospectively analyzed. LVEFbaseline was 55.4 ± 1.2% and pre-existing subnormal LVEF was common (7/22, 31.8/%). The minimum value of LVEF during pregnancy was 3.8% lower than baseline (p = 0.002). LVD occurred in 9/22 (40.9%) patients and HF was not observed. When GLS was normal at baseline (< -18.0%; N = 12), none of the women developed LVD. Nine of out ten women with abnormal GLS at baseline developed LVD later in pregnancy. In our cohort, the obstetric outcomes seemed comparable with the general population unless patients underwent abdominal irradiation (N = 5), where high rates of preterm birth (only 5/18 born at term) and miscarriage (6/18 pregnancies) were observed.

Conclusion

Our study suggests that women with prior cardiotoxic treatment have a low risk of LVD during pregnancy if GLS at baseline was normal. Pregnancy outcomes are similar to the healthy population except when patients underwent abdominal irradiation.
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Literature
1.
go back to reference Lipshultz SE, Adams MJ, Colan SD, et al. Long-term Cardiovascular toxicity in children, adolescents, and young adults who receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and research directions. Circulation. 2013;128:1927–95.CrossRef Lipshultz SE, Adams MJ, Colan SD, et al. Long-term Cardiovascular toxicity in children, adolescents, and young adults who receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and research directions. Circulation. 2013;128:1927–95.CrossRef
2.
go back to reference Chang WH, Katsoulis M, Tan YY, Mueller SH, Green K, Lai AG. Late effects of cancer in children, teenagers and young adults: Population-based study on the burden of 183 conditions, in-patient and critical care admissions and years of life lost. The Lancet Regional Health – Europe 2022;12. Chang WH, Katsoulis M, Tan YY, Mueller SH, Green K, Lai AG. Late effects of cancer in children, teenagers and young adults: Population-based study on the burden of 183 conditions, in-patient and critical care admissions and years of life lost. The Lancet Regional Health – Europe 2022;12.
3.
go back to reference Thouvenin-Doulet S, Berger C, Casagranda L, et al. Fecundity and quality of life of women treated for solid childhood tumors between 1948 and 1992 in France. J Adolesc Young Adult Oncol. 2018;7:415–23.CrossRef Thouvenin-Doulet S, Berger C, Casagranda L, et al. Fecundity and quality of life of women treated for solid childhood tumors between 1948 and 1992 in France. J Adolesc Young Adult Oncol. 2018;7:415–23.CrossRef
4.
go back to reference van der Kooi A-LLF, Mulder RL, Hudson MM, et al. Counseling and surveillance of obstetrical risks for female childhood, adolescent, and young adult cancer survivors: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Am J Obstet Gynecol. 2021;224:3–15.CrossRef van der Kooi A-LLF, Mulder RL, Hudson MM, et al. Counseling and surveillance of obstetrical risks for female childhood, adolescent, and young adult cancer survivors: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Am J Obstet Gynecol. 2021;224:3–15.CrossRef
5.
go back to reference Dorp Wv, Haupt R, Anderson RA, et al. Reproductive function and outcomes in female survivors of Childhood, adolescent, and Young Adult Cancer: a review. J Clin Oncol. 2018;36:2169–80.CrossRef Dorp Wv, Haupt R, Anderson RA, et al. Reproductive function and outcomes in female survivors of Childhood, adolescent, and Young Adult Cancer: a review. J Clin Oncol. 2018;36:2169–80.CrossRef
6.
go back to reference Group CsO. Long-Term Follow-Up Guidelines For Surviros of Childhood, Adolescent and Young Adult Cancers. 2018. Group CsO. Long-Term Follow-Up Guidelines For Surviros of Childhood, Adolescent and Young Adult Cancers. 2018.
7.
go back to reference SKION. Richtlijn follow-up na kinderkanker: meer dan 5 jaar na diagnose. Deel 1. Amsterdam, 2010. SKION. Richtlijn follow-up na kinderkanker: meer dan 5 jaar na diagnose. Deel 1. Amsterdam, 2010.
8.
go back to reference Rotz SJ, Ryan TD, Hlavaty J, George SA, El-Bietar J, Dandoy CE. Cardiotoxicity and cardiomyopathy in children and young adult survivors of hematopoietic stem cell transplant. Pediatr Blood Cancer. 2017;64:e26600.CrossRef Rotz SJ, Ryan TD, Hlavaty J, George SA, El-Bietar J, Dandoy CE. Cardiotoxicity and cardiomyopathy in children and young adult survivors of hematopoietic stem cell transplant. Pediatr Blood Cancer. 2017;64:e26600.CrossRef
9.
go back to reference Uderzo C, Pillon M, Corti P, et al. Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working parties. Bone Marrow Transplant. 2007;39:667–75.CrossRef Uderzo C, Pillon M, Corti P, et al. Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working parties. Bone Marrow Transplant. 2007;39:667–75.CrossRef
10.
go back to reference Nolan M, Oikonomou EK, Silversides CK, et al. Impact of Cancer Therapy-Related Cardiac Dysfunction on Risk of Heart failure in pregnancy. JACC: CardioOncology. 2020;2:153–62. Nolan M, Oikonomou EK, Silversides CK, et al. Impact of Cancer Therapy-Related Cardiac Dysfunction on Risk of Heart failure in pregnancy. JACC: CardioOncology. 2020;2:153–62.
11.
go back to reference Chow EJ, Chen Y, Kremer LC, et al. Individual prediction of heart failure among Childhood Cancer Survivors. J Clin Oncol. 2015;33:394–402.CrossRef Chow EJ, Chen Y, Kremer LC, et al. Individual prediction of heart failure among Childhood Cancer Survivors. J Clin Oncol. 2015;33:394–402.CrossRef
12.
go back to reference Oikonomou EK, Kokkinidis DG, Kampaktsis PN, et al. Assessment of Prognostic Value of Left Ventricular Global Longitudinal strain for early prediction of Chemotherapy-Induced cardiotoxicity: a systematic review and Meta-analysis. JAMA Cardiol. 2019;4:1007–18.CrossRef Oikonomou EK, Kokkinidis DG, Kampaktsis PN, et al. Assessment of Prognostic Value of Left Ventricular Global Longitudinal strain for early prediction of Chemotherapy-Induced cardiotoxicity: a systematic review and Meta-analysis. JAMA Cardiol. 2019;4:1007–18.CrossRef
13.
go back to reference Čelutkienė J, Pudil R, López-Fernández T, et al. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the heart failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020;22:1504–24.CrossRef Čelutkienė J, Pudil R, López-Fernández T, et al. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the heart failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020;22:1504–24.CrossRef
14.
go back to reference Asch FM, Miyoshi T, Addetia K, et al. Similarities and differences in left ventricular size and function among races and Nationalities: results of the World Alliance Societies of Echocardiography normal values study. J Am Soc Echocardiogr. 2019;32:1396–1406e2.CrossRef Asch FM, Miyoshi T, Addetia K, et al. Similarities and differences in left ventricular size and function among races and Nationalities: results of the World Alliance Societies of Echocardiography normal values study. J Am Soc Echocardiogr. 2019;32:1396–1406e2.CrossRef
15.
go back to reference NVOG. Hypertensive aandoeningen in de zwangerschap. 2012. NVOG. Hypertensive aandoeningen in de zwangerschap. 2012.
16.
go back to reference NVOG. Diabetes mellitus en zwangerschap. 2018. NVOG. Diabetes mellitus en zwangerschap. 2018.
18.
go back to reference Schannwell CM, Zimmermann T, Schneppenheim M, Plehn G, Marx R, Strauer BE. Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women. Cardiology. 2002;97:73–8.CrossRef Schannwell CM, Zimmermann T, Schneppenheim M, Plehn G, Marx R, Strauer BE. Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women. Cardiology. 2002;97:73–8.CrossRef
19.
go back to reference Melchiorre K, Sharma R, Khalil A, Thilaganathan B. Maternal Cardiovascular function in normal pregnancy. Hypertension. 2016;67:754–62.CrossRef Melchiorre K, Sharma R, Khalil A, Thilaganathan B. Maternal Cardiovascular function in normal pregnancy. Hypertension. 2016;67:754–62.CrossRef
20.
go back to reference Cong J, Fan T, Yang X, et al. Structural and functional changes in maternal left ventricle during pregnancy: a three-dimensional speckle-tracking echocardiography study. Cardiovasc Ultrasound. 2015;13:6.CrossRef Cong J, Fan T, Yang X, et al. Structural and functional changes in maternal left ventricle during pregnancy: a three-dimensional speckle-tracking echocardiography study. Cardiovasc Ultrasound. 2015;13:6.CrossRef
21.
go back to reference Kampman E, Valente MAE, van Melle J, et al. Cardiac adaption during pregnancy in women with congenital heart disease and healthy women. Heart. 2016;102:1302–8.CrossRef Kampman E, Valente MAE, van Melle J, et al. Cardiac adaption during pregnancy in women with congenital heart disease and healthy women. Heart. 2016;102:1302–8.CrossRef
22.
go back to reference Kimura Y, Kato T, Miyata H, et al. Left ventricular diastolic function during the normal Peripartum Period. Circ J. 2019;83:2265–70.CrossRef Kimura Y, Kato T, Miyata H, et al. Left ventricular diastolic function during the normal Peripartum Period. Circ J. 2019;83:2265–70.CrossRef
23.
go back to reference Chapman AB, Abraham WT, Zamudio S, et al. Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int. 1998;54:2056–63.CrossRef Chapman AB, Abraham WT, Zamudio S, et al. Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int. 1998;54:2056–63.CrossRef
24.
go back to reference Reulen RC, Bright CJ, Winter DL et al. Pregnancy and Labor Complications in Female Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study. J Natl Cancer Inst. 2017;109. Reulen RC, Bright CJ, Winter DL et al. Pregnancy and Labor Complications in Female Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study. J Natl Cancer Inst. 2017;109.
25.
go back to reference Teh WT, Stern C, Chander S, Hickey M. The impact of uterine radiation on subsequent fertility and pregnancy outcomes. Biomed Res Int. 2014;2014:482968–8.CrossRef Teh WT, Stern C, Chander S, Hickey M. The impact of uterine radiation on subsequent fertility and pregnancy outcomes. Biomed Res Int. 2014;2014:482968–8.CrossRef
26.
go back to reference Green DM, Peabody EM, Nan B, Peterson S, Kalapurakal JA, Breslow NE. Pregnancy outcome after treatment for Wilms Tumor: a Report from the National Wilms Tumor Study Group. J Clin Oncol. 2002;20:2506–13.CrossRef Green DM, Peabody EM, Nan B, Peterson S, Kalapurakal JA, Breslow NE. Pregnancy outcome after treatment for Wilms Tumor: a Report from the National Wilms Tumor Study Group. J Clin Oncol. 2002;20:2506–13.CrossRef
27.
go back to reference Sudour H, Chastagner P, Claude L, et al. Fertility and pregnancy outcome after abdominal irradiation that included or excluded the Pelvis in Childhood Tumor Survivors. Int J Radiation Oncology*Biology*Physics. 2010;76:867–73.CrossRef Sudour H, Chastagner P, Claude L, et al. Fertility and pregnancy outcome after abdominal irradiation that included or excluded the Pelvis in Childhood Tumor Survivors. Int J Radiation Oncology*Biology*Physics. 2010;76:867–73.CrossRef
28.
go back to reference Reulen RC, Zeegers MP, Wallace WHB et al. Pregnancy Outcomes among Adult Survivors of Childhood Cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiology Biomarkers & Prevention. 2009;18:2239–2247. Reulen RC, Zeegers MP, Wallace WHB et al. Pregnancy Outcomes among Adult Survivors of Childhood Cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiology Biomarkers & Prevention. 2009;18:2239–2247.
29.
go back to reference van de Loo LEXM, van den Berg MH, Overbeek A, et al. Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors. Fertil Steril. 2019;111:372–80.CrossRef van de Loo LEXM, van den Berg MH, Overbeek A, et al. Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors. Fertil Steril. 2019;111:372–80.CrossRef
30.
go back to reference Merz E, Miric-Tesanic D, Bahlmann F, Weber G, Wellek S. Sonographic size of uterus and ovaries in pre- and postmenopausal women. Ultrasound Obstet Gynecol. 1996;7:38–42.CrossRef Merz E, Miric-Tesanic D, Bahlmann F, Weber G, Wellek S. Sonographic size of uterus and ovaries in pre- and postmenopausal women. Ultrasound Obstet Gynecol. 1996;7:38–42.CrossRef
31.
go back to reference Huarte Ciganda M, Estaún Echavarren C, García Jiménez A, Huarte Sala I. Spontaneous uterine rupture in the second trimester in a patient with previous pelvic radiotherapy in Childhood: a Case Report. J Obstet Gynecol Can. 2020;42:84–7.CrossRef Huarte Ciganda M, Estaún Echavarren C, García Jiménez A, Huarte Sala I. Spontaneous uterine rupture in the second trimester in a patient with previous pelvic radiotherapy in Childhood: a Case Report. J Obstet Gynecol Can. 2020;42:84–7.CrossRef
32.
go back to reference Norwitz ER, Stern HM, Grier H, Lee-Parritz A. Placenta percreta and uterine rupture associated with prior whole body radiation therapy. Obstet Gynecol. 2001;98:929–31. Norwitz ER, Stern HM, Grier H, Lee-Parritz A. Placenta percreta and uterine rupture associated with prior whole body radiation therapy. Obstet Gynecol. 2001;98:929–31.
Metadata
Title
Cardiac and obstetric outcomes of pregnancies for women after cardiotoxic therapy in childhood: a single center observational study
Authors
Julius C. Heemelaar
Steffie Heemelaar
Svenja N. Hertel
J. Wouter Jukema
Marieke Sueters
Marloes Louwerens
M. Louisa Antoni
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10578-y

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