J Hypertens. 2014 Jun;32(6):1194-6.

Can fetal vascular morphology at 30 weeks of gestation have impact on cardiovascular outcomes in childhood?

Kistner A.

Department of Molecular Medicine and Surgery, Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm bThe Sahlgrenska Center for Pediatric Ophthalmology Research, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.


Comment on: Third trimester fetal hemodynamics and cardiovascular outcomes in childhood: the Generation R study. [J Hypertens. 2014 Jun;32(6):1275-82.]


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.

PMID: 24682032



This editorial comment focuses on the results from a large study by Kooijman et al (1). Fetal hemodynamics from 917 ”normal” fetuses from gestational week 30 were examined by ultrasound and Doppler examinations and correlated with the cardiovascular outcomes in off-spring at 6 years of age.  There were certain correlations between cardiac hemodynamics in early third trimester and findings at six years of age. Trimester fetal aorta ascendens diameter (p<0.01) and fetal left cardiac (p<0.05) output were positively associated with childhood aortic root diameter, after adjustments for several possible confounding factors. Left ventricular mass at 6 years was inversely correlated with fetal umbilical artery pulsatility index (p<0.05), reflecting increased placental resistance or umbilical artery resistance. Also the fetal E/A ratio was inversely associated with childhood aortic root diameter (p<0.05). Regarding gender differences, in fetal life, boys had a lower pulse rate and a lower umbilical artery pulsatility index (p<0.01 for each) than girls and a larger diameter of ascending aorta (p=0.01). At follow-up, at 6 years of age, girls had slightly higher systolic and diastolic blood pressures whereas boys showed a larger aortic root diameter, left atrial diameter and left ventricular mass compared with girls. Thus differences between genders were larger at 6 years of age compared with fetal life. The authors conclude that third or early third trimester vascular resistance parameters were not associated with blood pressure or vascular resistance at 6 years of age whereas certain fetal cardiac hemodynamic measurements correlated with cardiac structural outcomes at 6 years of age.

In the discussion Kooijman and co-workers conclude that results from this large study do not exclude that late third trimester influences might affect cardiovascular structures later in life. During the last 10 weeks of fetal life body weight is doubled. One might speculate that periods with increased body growth such as late third trimester, the early months of life after term birth and pubertal years are windows of special importance for cardiovascular growth, affecting outcome in later life. Possible influences on cardiovascular structures such as left ventricular mass size during fetal life, childhood and adolescence are shown in figure 1. Is it possible to influence late fetal hemodynamics to minimize morbidity and improve future prognosis for some groups during? So far, we don’t know.




Figure 1. Critical windows of increased growth that might be of special importance for outcome of cardiovascular structure.



  1. Kooijman MN, de Jonge LL, Steegers EA, van Osch-Gevers L, Verburg BO, Hofman A, Helbing WA, Jaddoe VW 2014 Third trimester fetal hemodynamics and cardiovascular outcomes in childhood: the Generation R study J of Hyperten 2:1275-82



Anna Kistner, MD, PhD

Dept of Medicine, Sodersjukhuset Karolinska Institutet

118 40 Stockholm, Sweden

Tel: +46 8 6161000 Fax: +46 8 5177 36 58 Cell phone: +46 709 919181




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