Background— Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. We evaluated whether prenatal cardiovascular changes previously demonstrated in FGR persist into preadolescence. Methods and Results— A cohort study of 58 FGR (defined as birth weight below 10th centile) and 94 normally grown fetuses identified in utero and followed-up into preadolescence (8–12 years of age) by echocardiography and 3-dimensional shape computational analysis. Compared with controls, FGR preadolescents had a different cardiac shape, with more spherical and smaller hearts. Left ventricular ejection fraction was similar among groups, whereas FGR had decreased longitudinal motion (decreased mitral annular systolic peak velocities: control median, 0.11 m/s [interquartile range, 0.09–0.12] versus FGR median 0.09 m/s [interquartile range, 0.09–0.10]; P <0.01) and impaired relaxation (isovolumic relaxation time: control, 0.21 ms [interquartile range, 0.12–0.35] versus FGR, 0.35 ms [interquartile range, 0.20–0.46]; P =0.04). Global longitudinal strain was decreased (control mean, −22.4% [SD, 1.37] versus FGR mean, −21.5% [SD, 1.16]; P <0.001) compensated by an increased circumferential strain and with a higher prevalence of postsystolic shortening in FGR as compared with controls. These differences persisted after adjustment for parental ethnicity and smoking, prenatal glucocorticoid administration, preeclampsia, gestational age at delivery, days in intensive care unit, sex, age, and body surface area at evaluation. Conclusions— This study provides evidence that cardiac remodeling induced by FGR persists until preadolescence with findings similar to those reported in their prenatal life and childhood. The findings support the hypothesis of primary cardiac programming in FGR for explaining the association between low birth weight and cardiovascular risk in adulthood.

Fetal growth restriction (FGR) because of placental insufficiency affects 5% to 7% of pregnancies and represents one of the leading causes of perinatal morbidity and mortality.1 Numerous historical cohort studies 2 and animal models 3 have demonstrated that FGR has a strong association not only with metabolic but also with primary cardiovascular remodeling that lead to long-term adverse consequences in later life. The rapid cell proliferation and differentiation during fetal growth are sensitive to any of the even smallest changes damaging the environment that can lead to permanent alterations in structural and functional constitution, which may persist into the adult life. 2 The heart is a central organ in the prenatal adaptation to placental insufficiency and fetal hypoxia. Previous studies have demonstrated remodeled hearts (more globular) with signs of systolic and diastolic dysfunction and preserved ejection fraction. [4][5][6] FGR cases are associated with prenatal adverse cardiac remodeling 4,5 that persists postnatally, 6 and low birth weight was linked to increased cardiovascular mortality in adulthood.2 Chronic pressure/volume overload together with hypoxia in utero have been postulated as the potential underlying mechanistic pathway of prenatal cardiovascular remodeling in FGR. 5,6 Editorial see p 759 Clinical Perspective on p 787Although evaluation of cardiac function with echocardiography has traditionally been limited to volume-based assessment, recent developments in cardiac ultrasound allow the noninvasive measurement of cardiac deformation with direct assessment of myocardial muscle by assessing regional Background-Fetal growth restriction (FGR) is associated with global adverse cardiac remodeling in utero and increased cardiovascular mortality in adulthood. Prenatal myocardial deformation has not been evaluated in FGR to date. We aimed to evaluate prenatal cardiac remodeling comprehensively in FGR including myocardial deformation imaging. Methods and Results-Echocardiography was performed in 37 consecutive FGR (defined as birthweight <10th centile) and 37 normally grown fetuses. A comprehensive fetal echocardiography was performed including tissue Doppler and 2-dimensional-derived strain and strain rate. Postnatal blood pressure measurement at 6 months of age was also performed. FGR cases showed signs of more globular hearts with decreased longitudinal motion (left systolic annular peak velocity: controls mean 6 cm/s [SD myocardial strain and strain rate. [7][8][9] Strain is defined as change in length/thickness of a segment of myocardium relative to its resting length and is expressed as a percentage; strain rate is the velocity of this deformation.7-9 Myocardial deformation imaging has demonstrated a high sensitivity for detecting preclinical myocardial dysfunction in various pathological conditions characterized by myocardial dysfunction, despite preserved ejection fraction, such as asymptomatic carriers of hypertrophic cardiomyopathy, sarcomeric mutations, Fabry disease, or myocardial ste...