Objective: To identify the presence of different cardiac phenotypes among FGR. Study Design: Fetal echocardiography was performed in 126 FGR (defined as birth weight <10th centile) and 64 adequate for gestational age (AGA). Principal component and cluster analyses were performed to identify different cardiac phenotypes among FGR cases. Results: Three different cardiac phenotypes were identified within FGR: globular, elongated and hypertrophic. Most FGR cases (54%) were characterized by a ‘globular’ heart with the lowest left ventricular sphericity index (controls: median 1.78 (interquartile range 1.62-1.97), FGR-elongated: 1.92 (1.78-2.09), FGR-globular 1.44 (1.36-1.52) and FGR-hypertrophic 1.65 (1.42-1.77), P=0.001), while 29% of the cases showed an ‘elongated’ left ventricle with nearly normal cardiac dimensions. Finally, 17% of the FGR showed a ‘hypertrophic’ phenotype with the highest values in left ventricular wall thickness (controls: 1.22 mm/kg (1.1-1.67), FGR-elongated: 1.52 (1.28-1.86), FGR-globular 1.65 (1.39-1.99) and FGR-hypertrophic 3.68 (3.45-4.71), P=0.001) and cardiac dimensions. The globular and elongated phenotype showed fetoplacental profile of late-onset FGR while the hypertrophic phenotype showed signs of early-onset FGR The hypertrophic cluster also showed the worst perinatal results presenting the lowest birthweight centile, gestational age at birth, Apgar score, and the highest postnatal blood pressure and carotid intima media thickness. Conclusions: FGR induces at least 3 different cardiac phenotypes, with early-onset FGR cases associated with a hypertrophic response and worse perinatal outcomes. This cardiac phenotypic classification may improve identification of those FGR cases with the highest perinatal and long-term cardiovascular risk.

This work was supported by the Erasmus+ Programme of the European Union (grant number 2013‐0040) (this publication reflects the views of only the authors and the Commission cannot be held responsible for any use which may be made of the information contained herein); Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (grant numbers PI12/00801, PI14/00226, SAF2012‐37196 and TIN2014‐52923‐R), cofinanciado por el Fondo Europeo de Desarrollo Regional de la Unión Europea ‘Una manera de hacer Europa’. The research leading to these results has received funding from ‘la Caixa’ Foundation, Cerebra Foundation for the Brain Injured Child and Agència de Gestió d'Ajuts Universitaris i de Recerca (grant number SGR_928). B.V.A. was supported by Programa de Ayudas Postdoctorales from Agència de Gestió d'Ajuts Universitaris i de Recerca (grant number: 2013FI_B 00667) and wishes to express her gratitude to the Mexican National Council of Science and Technology (CONACyT, Mexico City, Mexico) for partially supporting her predoctoral stay at Hospital Clínic, Barcelona, Spain.