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(Circulation. 2008;117:649-659.)
© 2008 American Heart Association, Inc.

Pediatric Cardiology

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; 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.

Correspondence to Professor E.A.P. Steegers, Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, the Netherlands. E-mail e.a.p.steegers{at}erasmusmc.nl

Received April 17, 2007; accepted November 28, 2007.

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.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2008 117: 589-591. [Full Text]