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Third trimester fetal hemodynamics and cardiovascular outcomes in childhood: the Generation R study

Kooijman, Marjolein N.a,b,c; de Jonge, Layla L.a,b,c; Steegers, Eric A.P.d; van Osch-Gevers, Lenniec; Verburg, Bero O.d; Hofman, Albertb; Helbing, Willem A.c; Jaddoe, Vincent W.V.a,b,c

doi: 10.1097/HJH.0000000000000174
ORIGINAL PAPERS: Childhood hypertension

Objective: Low birth weight is associated with cardiovascular disease in adulthood. Hemodynamic adaptations related to fetal growth restriction may underlie these associations, through persistent influences on cardiovascular development. We examined the associations of third trimester fetal hemodynamics with cardiovascular outcomes in childhood.

Methods: In a prospective cohort study among 917 pregnant women and their children, we measured fetal growth, and fetal arterial and cardiac hemodynamic variables with ultrasound and Doppler examinations at a gestational age of 30.3 (95% range 28.8–32.3) weeks. At the age of 6 years, we measured blood pressure, carotid-femoral pulse wave velocity, and left cardiac structures and function.

Results: We observed that fetal hemodynamics were not associated with childhood blood pressure and carotid-femoral pulse wave velocity. The fetal aorta ascendens diameter and left cardiac output were positively associated with childhood aortic root diameter [0.14 standard deviation score (SDS), 95% confidence interval (CI) 0.07–0.22 and 0.08 SDS, 95% CI 0.01–0.15 per SDS change in diameter and output, respectively]. Fetal left ventricular diastolic filling pattern was inversely associated with aortic root diameter (−0.07 SDS, 95% CI −0.13 to 0.00 per SDS change in E/A ratio) at 6 years. Analyses adjusted and stratified for estimated fetal weight showed no differences in results.

Conclusion: Our results suggest that third trimester fetal vascular resistance parameters do not affect blood pressure or arterial stiffness in childhood. Fetal cardiac functional and structural measures are associated with cardiac outcomes in childhood. Whether these early adaptations lead to greater risks of cardiovascular disease should be further studied.

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aThe Generation R Study Group

bDepartment of Epidemiology

cDepartment of Pediatrics

dDepartment of Obstetrics and Gynaecology, Erasmus Medical Center, Rotterdam, the Netherlands

Correspondence to Vincent W.V. Jaddoe, MD, PhD, The Generation R Study Group (Na-2915), Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands. Tel: +31 0 10 7043405; fax: +31 0 10 4089382; e-mail:

Abbreviations: 95% CI, 95% confidence interval; IVSTD, interventricular end-diastolic septal thickness; LVM, left ventricular mass; LVEDD, left ventricular end-diastolic diameter; LVPWTD, left ventricular end-diastolic posterior wall thickness; PI, pulsatility index; PSV, peak systolic velocity; SDS, standard deviation score; TVI, time velocity integral; U/C, umbilical/cerebral

Received 21 October, 2013

Revised 24 December, 2013

Accepted 14 February, 2014

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