Refining current risk stratification guidelines for pregnant women with Fontan circulation: lessons from PROFAT registry

Magalie Ladouceur¹, Andrea Girnius², Dominica Zentner³, Anne Marie Valente⁴, Katherine E Economy⁵, Jolien Roos-Hesselink⁶, Carri Warshak⁷, Sara Partington⁸, Zhiqian Gao⁹, Nicholas J Ollberding¹⁰, Michelle Faust¹¹, Harald Kaemmerer¹², Teiji Akagi¹³, Jasmine Grewal¹⁴, Elisa A Bradley¹⁵, Jonathan Buber¹⁶, Joseph S Palumbo¹⁷, Niki Walker¹⁸, Jamil Aboulhosn¹⁹, Wendy Book²⁰, Petronella G Pieper²¹, Nicole Nagdyman¹², Scott Cohen²², Barbara J M Mulder²³, Erwin Oechslin²⁴, Helmut Baumgartner²⁵, Wesam Kurdi²⁶, Mary M Canobbio²⁷, Gruschen Veldtman²⁸

Affiliations

¹ Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland. Department of Cardiology, Adult congenital heart disease unit, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
² Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
³ Department of Cardiology and Department of Genomic Medicine, Royal Melbourne Hospital, Melbourne, Victoria, Australia. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Brigham and Women's Hospital, Department of Medicine, Division of Cardiovascular Disease, Department of Cardiology Harvard Medical School, Boston, Massachusetts, USA.
⁵ Brigham and Women's Hospital, Department of Obstetrics and Gynecology, Division Maternal and Fetal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁶ Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
⁷ Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁸ Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁹ The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁰ Department of Pediatrics, University of Cincinnati College of Medicine and Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹¹ Heart Institute Research Core, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹² Deutsches Herzzentrum München, Germany, Munich, Germany.
¹³ Cardiovascular Medicine, Okayama University, Okayama, Japan.
¹⁴ Cardiology, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada.
¹⁵ Adult Congenital Heart Disease, Pennsylvania State University, Hershey PA, USA.
¹⁶ Department of Medicine, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
¹⁷ Haematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁸ Scottish Adult Congenital Cardiac Service and University of Glasgow, Golden Jubilee National University Hospital, Glasgow, UK and Helen DeVos Children's Hospital, Corewell Health, Grand rapids, Michigan.
¹⁹ Ahmanson/UCLA ACHD Center, David Geffen School of Medicine at UCLA, Los Angeles,California, USA.
²⁰ Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, USA.
²¹ Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
²² Department of Cardiology, The Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
²³ Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
²⁴ Toronto Adult Congenital Heart Disease Program, Peter Munk Cardiac Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.
²⁵ Department of Cardiology III: Adult Congenital and Valvular Heart Disease, University Hospital Muenster, Muenster, Albert Schweitzer Campus 1, Building A1, 48149 Muenster, Germany.
²⁶ King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
²⁷ Ahmanson.UCLA ACHD Center, David Geffen School of Medicine School of Nursing, University of California Los Angeles, Los Angeles, California, USA.
²⁸ Scottish Adult Congenital Cardiac Service and University of Glasgow, Golden Jubilee National University Hospital, Glasgow, UK.

PMID: 40695560
DOI: 10.1093/eurjpc/zwaf456

Refining current risk stratification guidelines for pregnant women with Fontan circulation: lessons from PROFAT registry

Magalie Ladouceur et al. Eur J Prev Cardiol. 2025.

. 2025 Jul 22:zwaf456.

doi: 10.1093/eurjpc/zwaf456. Online ahead of print.

Authors

Affiliations

¹ Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland. Department of Cardiology, Adult congenital heart disease unit, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
² Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
³ Department of Cardiology and Department of Genomic Medicine, Royal Melbourne Hospital, Melbourne, Victoria, Australia. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Brigham and Women's Hospital, Department of Medicine, Division of Cardiovascular Disease, Department of Cardiology Harvard Medical School, Boston, Massachusetts, USA.
⁵ Brigham and Women's Hospital, Department of Obstetrics and Gynecology, Division Maternal and Fetal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁶ Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
⁷ Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁸ Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁹ The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁰ Department of Pediatrics, University of Cincinnati College of Medicine and Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹¹ Heart Institute Research Core, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹² Deutsches Herzzentrum München, Germany, Munich, Germany.
¹³ Cardiovascular Medicine, Okayama University, Okayama, Japan.
¹⁴ Cardiology, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada.
¹⁵ Adult Congenital Heart Disease, Pennsylvania State University, Hershey PA, USA.
¹⁶ Department of Medicine, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.
¹⁷ Haematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁸ Scottish Adult Congenital Cardiac Service and University of Glasgow, Golden Jubilee National University Hospital, Glasgow, UK and Helen DeVos Children's Hospital, Corewell Health, Grand rapids, Michigan.
¹⁹ Ahmanson/UCLA ACHD Center, David Geffen School of Medicine at UCLA, Los Angeles,California, USA.
²⁰ Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, USA.
²¹ Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
²² Department of Cardiology, The Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
²³ Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
²⁴ Toronto Adult Congenital Heart Disease Program, Peter Munk Cardiac Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.
²⁵ Department of Cardiology III: Adult Congenital and Valvular Heart Disease, University Hospital Muenster, Muenster, Albert Schweitzer Campus 1, Building A1, 48149 Muenster, Germany.
²⁶ King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
²⁷ Ahmanson.UCLA ACHD Center, David Geffen School of Medicine School of Nursing, University of California Los Angeles, Los Angeles, California, USA.
²⁸ Scottish Adult Congenital Cardiac Service and University of Glasgow, Golden Jubilee National University Hospital, Glasgow, UK.

PMID: 40695560
DOI: 10.1093/eurjpc/zwaf456

Abstract

Background: Pregnancy in women with a Fontan circulation carries increased risk. Given the relative evidence void, pregnancy counseling requires considerable nuance and experience.

Objectives: This study aimed to identify risk factors for maternal and fetal complications and to contrast risk estimates obtained from existing risk stratification tools, including the modified WHO, CARPREG II, and ZAHARA risk scores.

Methods: Pregnant women (>20 weeks of gestation) with a Fontan circulation were retrospectively included from 13 international centers. Univariate and multivariable analyses identified predictors of complications, and the performance of risk stratification tools was assessed.

Results: From 2006 to 2018, 84 women with Fontan physiology had 108 pregnancies, and form the basis of this investigation. Maternal cardiovascular complications occurred in 32 (30%) of all pregnancies including Fontan circulatory failure (17%), supraventricular tachycardia (7.4%), and thromboembolic events (3.7%). No maternal deaths occurred. Premature birth constituted 68% of neonatal complications, with a fetal and neonatal mortality of 13%. Multivariable analysis linked adverse maternal outcomes to pre-pregnancy oxygen saturation (adjusted OR 0.77; 95%CI 0.61-0.96; p=0.02). None of the risk models showed good discriminative ability. The modified WHO classification was the only risk model significantly associated with adverse fetal outcomes.

Conclusions: Pregnancy in women with Fontan circulation poses a significant cardiovascular risk for the mother and a high burden of fetal and neonatal complications. The existing predictive risk stratification models do not discriminate hazard between well-functioning patients with Fontan from those with additional hemodynamic burden. This underscores the necessity for large-scale studies to refine risk stratification.

Keywords: Fontan circulation; heart failure; pregnancy; risk classification; single ventricle.

Plain language summary

Women with a Fontan circulation—a unique surgical approach for complex congenital heart disease with a single ventricle—can experience successful pregnancies, but they face significant health risks. Our study analyzed outcomes from 108 pregnancies (>20 weeks of gestation) to identify risk factors and evaluate existing tools for predicting complications. Key findings are: Approximately one-third of pregnancies were complicated by maternal cardiovascular events, including Fontan failure, arrhythmias, and thromboembolic events, while two-thirds were associated with neonatal complications. Hypoxemia (oxygen saturation <92%) was a critical risk factor.Existing risk prediction models (CARPREG II, ZAHARA, and mWHO) showed poor accuracy in predicting maternal and fetal complications in this group, highlighting the need for improved risk assessment tools tailored to Fontan physiology. These findings emphasize the importance of specialized preconception counseling and multidisciplinary care for women with Fontan circulation to ensure informed decision-making and optimized management during pregnancy.

© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

PubMed Disclaimer

Comment in

The importance of an individualised approach to risk assessment in Fontan patients considering pregnancy.
Ratwatte S, Thorne SA, Rafiq I. Ratwatte S, et al. Eur J Prev Cardiol. 2025 Sep 2:zwaf571. doi: 10.1093/eurjpc/zwaf571. Online ahead of print. Eur J Prev Cardiol. 2025. PMID: 40892444 No abstract available.

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Silverchair Information Systems

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Refining current risk stratification guidelines for pregnant women with Fontan circulation: lessons from PROFAT registry

Affiliations

Refining current risk stratification guidelines for pregnant women with Fontan circulation: lessons from PROFAT registry

Authors

Affiliations

Abstract

Plain language summary

Comment in

LinkOut - more resources

Full Text Sources