Fetal Growth Restriction Results in Remodeled and Less Efficient Hearts in Children -- Crispi et al., 10.1161/CIRCULATIONAHA.110.937995 -- Circulation

Submitted on September 22, 2009
Accepted on April 6, 2010

Fetal Growth Restriction Results in Remodeled and Less Efficient Hearts in Children

Fàtima Crispi MD, Bart Bijnens PhD, Francesc Figueras MD, Joaquim Bartrons MD, Elisenda Eixarch MD, Ferdinand Le Noble PhD, Asif Ahmed PhD, and Eduard Gratacós MD*

From the Department of Maternal-Fetal Medicine (Institut Clínic de Ginecologia, Obstetrícia i Neonatologia), Hospital Clinic-IDIBAPS, University of Barcelona, and Centro de Investigación Biomédica en Red en Enfermedades Raras (F.C., F.F., E.E., E.G.), Barcelona, Spain; ICREA-Universitat Pompeu Fabra (CISTIB) and Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (B.B.), Barcelona, Spain; Department of Pediatric Cardiovascular Surgery, University Hospital Sant Joan de Déu (J.B.), Esplugues de Llobregat, Barcelona, Spain; Laboratory for Angiogenesis and Cardiovascular Pathology, Max Delbrück Center for Molecular Medicine (F.L.N.), Berlin, Germany; Department of Reproductive and Vascular Biology (A.A.), Centre for Cardiovascular Sciences, Institute for Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and Gustav Born Centre for Vascular Biology and Centre for Cardiovascular Sciences (A.A.), Queen's Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom.


* To whom correspondence should be addressed. E-mail: egratacos@clinic.ub.es.


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/E' 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.

open here please:
Fetal Growth Restriction Results in Remodeled and Less Efficient Hearts in Children -- Crispi et al., 10.1161/CIRCULATIONAHA.110.937995 -- Circulation