Background Cardiovascular autonomic nervous functions (CANF) exert important homeostatic mechanisms to prevent major arterial blood pressure fluctuations by adjusting heart rate (HR), cardiac contractility, and peripheral vascular tone. Children conceived by assisted reproductive technologies (ART) are at risk of increased carotid intima-media thickness, insulin resistance, arterial stiffness, and hypertension. CANF is impaired in children with obesity and diabetes mellitus, and conductance artery stiffness is documented to influence CANF. CANF may therefore be hypothetized to be impaired in children conceived by ART. Purpose This is the first study to investigate whether children conceived by ART have impaired CANF as compared to naturally conceived children. Method CANF was studied in 105 singletons aged 7–12 years conceived naturally (NC, N=33) or by ART (frozen embryo transfer (FET, N=34) and fresh embryo transfer (Fresh ET, N=38)). CANF was evaluated with continuous non-invasive hemodynamic measurements (Finapres®) by the HR and blood pressure changes seen relative to rest during active standing, deep breathing and Valsalva, respectively. Results The descriptive data showed no difference in CANF measurements between our study groups (Table 1). In the multivariate analysis, only the Valsalva HR-ratio to rest was significantly higher in children conceived by FET as compared to NC children after adjustments for age, sex, BMI and maternal age at delivery (Figure 1). For all meaures, the effect size (Hedges d) ranged from 0.02 to 0.48. Conclusion In this study only the Valsalva HR-response between FET and NC groups were statistically significant after adjustment for confounders, and in general effect sizes were small. Our study suggests that children conceived by ART do not have a significantly impaired cardiovascular autonomic nervous function as compared to naturally conceived children. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation
Background Epigenetics may alter the cardiovascular system of children conceived after assisted reproductive technology (ART). Singletons born after frozen embryo transfer (FET) are more likely to be large for gestational age and fresh embryo transfer (ET) are at risk of being small for gestational age. Children conceived after ART may have endothelial dysfunction, and high body mass index and arterial blood pressure (ABP). Such changes may be associated with cardiac diastolic dysfunction. Purpose We investigate whether children conceived after fresh ET and FET are at risk of cardiac changes including left ventricular (LV) diastolic dysfunction. Methods 150 9-year-old singletons have been recruited in a cardiac magnetic resonance imaging study (all scanned by April 2020). 50 children were born after natural conception (NC); 50 children after FET; and 50 children after fresh ET. Left atrium (LA) maximal volume, LA early emptying fraction (LAEEF), LV peak filling rates (PFR) and the peak ejection rate (PER)/PFR ratio are reported to assess the diastolic function. Results Preliminary data analyzed in a blinded manner from 59 children show no differences in ambulatory ABP, LV and right ventricular ejection fraction, end-diastolic and end-systolic volumes, stroke volumes and LV mass between the groups. With respect to LV diastolic function, no differences were seen in LA maximal volume and LAEEF; but the Fresh ET group tended to have lower PFR with a resultant PER/PFR ratio now increasing above unity compared to the other groups. Conclusion Preliminary data suggest a possible trend towards diastolic dysfunction in children born after fresh ET. If the lack of significant difference in heart function between NC and FET can be ascertained in the full cohort, this is reassuring. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk Foundation
Background Increased vascular stiffness in adults is associated with symptomatic cardiovascular disease independently of other risk factors. From puberty and onwards, men have higher aortic pulse-wave velocity than women explaining part of the male overrepresentation of early cardiovascular disease. It is not known if the stiff male arterial system is related to adult life-style or develops under the influence of male hormones, or if it is already present before puberty. According to the hyperbolic Bramwell-Hill relation, early changes must be expected to become detectable in aortic distensibility before influencing aortic pulse-wave velocity. Purpose The objective of this study was to quantitate sex-related differences in aortic distensibility and pulse-wave velocity in pre-pubertal children. Methods 150 children aged 8–9 years (75 girls and 75 boys) were recruited to a cardiovascular magnetic resonance imaging (CMR) study of the importance of in vitro fertilization (IVF) for aortic distensibility. Data did not show differences related to the mode of conception (natural vs. IVF), and pooled data are reported here. Conductance artery stiffness was determined from ascending, descending and abdominal aorta distensibility and from arch and abdominal aorta pulse-wave velocity (PWV). Data were analyzed blinded to child sex and mode of conception and related to left heart function as determined from flow and volumetric CMR data. The effects of sex on ascending aorta distensibility and total aortic PWV were examined in four linear regression models by stepwise adjustment for potential confounders. Results Systolic and diastolic blood pressures, cardiac output and total peripheral resistance did not differ between the sexes. Pulse pressure, however, was a mean of 2 mmHg lower and heart rate 7 bpm higher in girls (Table 1), and corresponding to the lower heart rate, left ventricle (LV) end-diastolic volume index and left ventricle stroke volume were 7 mL and 5 mL, respectively, higher in boys. LV peak-filling rate indexed to LV end-diastolic volume was 0.5 s-1 lower in boys, but in general LV filling and left atrium emptying parameters were equal. Distensibility of the ascending and descending aorta were both significantly higher in girls as compared to boys, whereas boys and girls had equal abdominal aortic distensibility and equal aortic pulse-wave velocities. Distensibility of the ascending aorta remained statistically significant after adjustment for potential confounders (Table 2). Conclusion Without yet significantly affecting pulse wave velocity or left ventricle function, pre-pubertal boys had significantly lower distensibility of the ascending aorta and the aortic arch than pre-pubertal girls. This is the part of the aorta primarily responsible for the aortic Windkessel function, and it seems that the stiffer arterial system seen in adult men as compared to adult women may already be present in childhood well before puberty. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Table 1 Table 2
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