Cardiac remodeling and exercise tolerance in small for gestational age: a follow-up cohort study from preadolescence into adolescence

Rommy H. Novoa^1,2Dora Fabijanovic^3,4Kilian Vellvé^1,2Filip Loncaric^3,4Merida Rodriguez-Lopez^1,2,5Alvaro Sepúlveda-Martínez^1,2,6Sebastian I Sarvari^3,7Brenda Valenzuela-Alcaraz¹Francesca Crovetto^1,2Rosa Faner^2,8,9Àlvar Agustí^2,8,9Marta Sitges^2,3,9Maja Cikes⁴Gabriel Bernardino^10,11,9Isabel Blanco^2,8,9Bart Bijnens^10,12,13Fàtima Crispi^1,2,9*

• ¹BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain
• ²Universitat de Barcelona, Barcelona, Spain
• ³Institut Clínic Cardiovascular, Hospital Clínic, Centre for Biomedical Research on CardioVascular Diseases (CIBERCV), Barcelona, Spain
• ⁴University of Zagreb School of Medicine, Department of Cardiovascular Diseases, University, Zagreb, Croatia
• ⁵Department of Public Health and Community Medicine, Universidad Icesi, Cali, Colombia
• ⁶Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Clínico de la Universidad de Chile, Santiago de Chile, Chile
• ⁷ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
• ⁸Department of Pulmonary Medicine, Respiratory Institute, Hospital Clínic Barcelona, Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Barcelona, Spain
• ⁹FRCB-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
• ¹⁰BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain
• ¹¹CREATIS, UMR 5220, U1294, F-69621, Univ Lyon, Université Claude Bernard Lyon 1, INSA-Lyon, CNRS, Inserm, Lyon, France
• ¹²Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Spain
• ¹³KU Leuven, Leuven, Belgium

Background. Being born small-for-gestational-age (SGA) affects 7-10% of newborns and is associated with increased cardiovascular risk and reduced exercise capacity in adulthood with unclear underlying mechanisms. Cardiac remodeling and dysfunction occur in fetuses and children born SGA, but it is uncertain whether and how these changes persist into adolescence. To assess resting cardiovascular morphology and function together with exercise tolerance in adolescents born SGA. Methods. Perinatal cohort including 30 adolescents born SGA (defined as birthweight below the 10th centile) and 28 normal birthweight controls in a Tertiary University Hospital in Spain. Participants were followed from preadolescence (7-12 years of age) into adolescence (12-17 years of age) with echocardiography and incremental cardio-pulmonary exercise test (CPET). Results. While signs of cardiac remodeling and dysfunction were evident in SGA preadolescents, no significant differences in left ventricular dimensions and deformation could be demonstrated in SGA adolescents. During the follow-up period, the SGA cohort had a significantly higher increase in left ventricular (LV) base-to-apex length (SGA mean 17.61 ± 6.78 vs. controls 13.44 ± 5.12, p=0.011), resulting in different change of LV sphericity (-0.07 ± 0.11 vs. -0.17 ± 0.14, p=0.010). Significant differences could be observed in SGA during exercise with reduced oxygen uptake (-0.07 L/min [-0.13 to -0.005], p=0.035), expired carbon dioxide (-0.08 L/min [-0.15 to -0.01], p=0.033), and peak expiratory flow rate (-0.11 L/s [-0.21 to -0.01], p=0.029). Conclusion. Changes in cardiac shape and function, described in children born SGA, seem to be ameliorated in adolescence related to compensatory growth as compared to healthy controls. However, SGA adolescents had markedly reduced exercise tolerance.