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Circulation
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on January 22, 2008

Circulation. 2008
Published online before print January 22, 2008, doi: 10.1161/CIRCULATIONAHA.107.709717
A more recent version of this article appeared on February 5, 2008
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Submitted on April 17, 2007
Accepted on November 28, 2007

Fetal Hemodynamic Adaptive Changes Related to Intrauterine Growth. The Generation R Study

Bero O. Verburg MD, PhD, Vincent W.V. Jaddoe MD, PhD, Juriy W. Wladimiroff MD, PhD, Albert Hofman MD, PhD, Jacqueline C.M. Witteman PhD, and Eric A.P. Steegers MD, PhD*

From The Generation R Study Group (B.O.V., V.W.V.J.), Department of Epidemiology and Biostatistics (B.O.V., V.W.V.J., A.H., J.C.M.W.), Department of Obstetrics and Gynecology (B.O.V., J.W.W., E.A.P.S.), and Department of Pediatrics (V.W.V.J.), Erasmus Medical Center, Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.

* To whom correspondence should be addressed. E-mail: e.a.p.steegers{at}erasmusmc.nl.

Background—It has been suggested that an adverse fetal environment increases susceptibility to hypertension and cardiovascular disease in adult life. This increased risk may result from suboptimal development of the heart and main arteries in utero and from adaptive cardiovascular changes in conditions of reduced fetal growth. The aim of the present study was to evaluate whether reduced fetal growth is associated with fetal circulatory changes and cardiac dysfunction.

Methods and Results—This study was embedded in a population-based, prospective cohort study starting in early fetal life. Fetal growth characteristics and fetal circulation variables were assessed with ultrasound and Doppler examinations in 1215 healthy women. The fetal circulation was examined in relation to estimated fetal weight. Higher placental resistance indices were strongly associated with decreased fetal growth. Cerebral resistance showed a gradual decline with reduced fetal growth. Cardiac output, peak systolic velocity of the outflow tracts, and cardiac compliance showed a gradual reduction with diminished fetal growth, whereas intraventricular pressure gradually increased.

Conclusions—Decreased fetal growth is associated with adaptive fetal cardiovascular changes. Cardiac remodeling and cardiac output changes are consistent with a gradual increase in afterload and compromised arterial compliance in conditions of decreased fetal growth. These changes have already begun to occur before the stage of clinically apparent fetal growth restriction and may contribute to the increased risk of cardiovascular disease in later life.


Key words: physiology • circulation, fetoplacental • fetal development • epidemiology • echocardiography • cardiovascular diseases




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