Objectives Intrauterine growth restriction is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is not well‐documented. We evaluated longitudinally the association between cardiovascular remodeling in small‐for‐gestational‐age (SGA) fetuses and at 6 months of age. Methods A cohort of 80 SGA fetuses (defined by estimated fetal and birth weights < 10th centile) delivered > 34 weeks' gestation was compared with 80 normally grown age‐matched control fetuses, with follow‐up at 6 months of corrected age (i.e. 6 months from estimated date of delivery according to first‐trimester crown–rump length). Cardiovascular evaluation included a comprehensive echocardiographic assessment in both fetuses and infants and blood pressure and aortic intima–media thickness (aIMT) measurement in infants. Parameters were adjusted by linear regression analysis for gender, gestational age at delivery, pre‐eclampsia, prenatal glucocorticoid exposure, Cesarean delivery, admission to neonatal intensive care unit and body surface area. Results Both pre‐ and postnatally, when compared with controls, the SGA group showed a more globular cardiac shape (left sphericity index: controls 2.06 vs SGA 1.87 (P = 0.022) prenatally and 1.92 vs 1.67 (P = 0.007) postnatally), as well as signs of systolic longitudinal dysfunction (systolic annular peak velocity (S′): 7.2 vs 6.3 cm/s (P = 0.003) prenatally and 7.9 vs 6.4 cm/s (P < 0.001) postnatally; tricuspid annular plane systolic excursion: 7.2 vs 6.8 mm (P = 0.015) prenatally and 16.0 vs 14.2 mm (P < 0.001) postnatally) and diastolic dysfunction (left isovolumetric relaxation time: 46 vs 52 ms (P < 0.001) prenatally and 50 vs 57 ms (P = 0.034) postnatally). In addition, infants in the SGA group had increased mean blood pressure (mean: 61 vs 70 mmHg, P < 0.001) and maximum aIMT (0.57 vs 0.66 mm; P < 0.001). Conclusions Primary cardiovascular changes are already present in the SGA fetus and persist at 6 months of age. These data support prenatal cardiovascular remodeling as a mechanistic pathway of increased risk later in life in cases of SGA, regardless of Doppler abnormalities.

This work was supported by grants from Instituto de Salud Carlos III (grant numbers PI11/00051, PI12/00801, PI11/01709) and from the Ministerio de Economía y Competitividad (grant number SAF2012‐37196), and cofinanced by the Fondo Europeo de Desarrollo Regional de la Unión Europea ‘Una manera de hacer Europa’, Fundación Mutua Madrileña, Fundació Agrupació Premi Àmbit de la Infància (Spain) and Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK). B.V.A. was supported by Programa de Ayudas Postdoctorales FI Agaur (2013FI_B 00667). M.C.L. and B.V.A. wish to express their gratitude to the Mexican National Council of Science and Technology (CONACyT, Mexico City, Mexico) for partially supporting their predoctoral studies at Hospital Clínic, Barcelona, Spain.