Background-Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood. Methods and Results-Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/EЈ ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction. Conclusions-These findings suggest that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. If these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR. (Circulation. 2010;121:2427-2436.)Key Words: remodeling Ⅲ pregnancy Ⅲ pediatrics Ⅲ cardiomyopathy Ⅲ hypoxia C ardiovascular disease is the main cause of death in adults. Most factors that lead to chronic cardiovascular disease are already present in childhood. 1,2 Epidemiological evidence has long suggested a link between low birth weight and increased cardiovascular mortality in adulthood. 3 This association is essentially mediated through fetal growth restriction (FGR), 4 a condition defined as a birth weight below the 10th percentile for gestational age that affects 5% to 10% of all newborns. 5 The mechanistic pathways underlying the relationship between FGR and cardiovascular risk are poorly understood. 6 A number of studies support that it might be explained in part by fetal metabolic programming leading to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension 6 ; however, it remains unclear whether FGR induces primary changes in the heart that might predispose to cardiovascular dysfunction later in life. Clinical Perspective on p 2436It has long been known that intrauterine growth retardation is associated with dilated ...

A ssisted reproductive technologies (ARTs), mainly standard in vitro fertilization or intracytoplasmic sperm injection, permit childbirth in many infertile couples and nowadays represent 1% to 4% of births in developed countries.1 Although these technologies are generally considered safe, the potential association of ART with poorer pregnancy outcomes has long been investigated. There is evidence that ART is associated with increased risk for adverse perinatal outcome and congenital malformations.2 This notwithstanding, it is not possible to separate ART-related risks from those secondary to the underlying reproductive pathology of the infertile couple. [3][4][5] In this scenario, preliminary evidence has recently suggested that ART could be associated with long-term cardiovascular changes. Ceelen et al 6 first suggested the presence of increased blood pressure in late childhood after ART conception. More recently, another study demonstrated the presence of signs of systemic and pulmonary vascular dysfunction in 12-year-old children conceived by ART. Editorial see p 1398 Clinical Perspective on p 1450Background-Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. Methods and Results-This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies.ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.