Associations of maternal angiogenic factors during pregnancy with childhood carotid intima-media thickness and blood pressure

BACKGROUND AND AIMS: Reduced maternal placental growth factor (PlGF) and higher soluble fms-like tyrosine kinase (sFlt-1) concentrations in pregnancy may have persistent effects on offspring vasculature. We hypothesized that suboptimal maternal angiogenic factors in pregnancy may adversely affect fetal vascular development, leading to an increased risk of adverse atheriosclerotic adaptations and higher blood pressure in offspring. METHODS: In a population-based prospective cohort among 4565 women and their offspring, we examined the associations of maternal serum PlGF and sFlt-1 concentrations in the first half of pregnancy with offspring vascular development. We measured childhood blood pressure and obtained childhood carotid intima media thickness and carotid distensibility through ultrasonography at 9 years. RESULTS: After adjustment for maternal sociodemographic and lifestyle characteristics, no associations were present of maternal first and second trimester angiogenic factors with childhood blood pressure, carotid intima media thickness (IMT) or distensibility in the total population. In preterm born children only, higher maternal second trimester PlGF concentrations, but not sFlt-1 concentrations, were associated with a lower childhood diastolic blood pressure (difference: -0.16 SDS (95% CI -0.30, –0.03) per SDS increase in maternal second trimester PlGF concentration). No associations among children born small-for-gestational age were present. CONCLUSIONS: In a low-risk population, maternal angiogenic factors in the first half of pregnancy are not associated with childhood blood pressure, carotid IMT or carotid distensibility after considering maternal socio-demographic and lifestyle factors. Only in children born preterm, lower maternal second trimester PlGF concentrations are associated with higher childhood diastolic blood pressure, but not with other vascular outcomes

The Cardiovascular Stress Response as Early Life Marker of Cardiovascular Health: Applications in Population-Based Pediatric Studies—A Narrative Review

Stress inducement by physical exercise requires major cardiovascular adaptations in both adults and children to maintain an adequate perfusion of the body. As physical exercise causes a stress situation for the cardiovascular system, cardiovascular exercise stress tests are widely used in clinical practice to reveal subtle cardiovascular pathology in adult and childhood populatio

Physical exercise and cardiovascular response:design and implementation of a pediatric CMR cohort study

To examine feasibility and reproducibility and to evaluate the cardiovascular response to an isometric handgrip exercise in low-risk pediatric population using Cardiovascular Magnetic Resonance measurements. In a subgroup of 207 children with a mean age of 16 years participating in a population-based prospective cohort study, children performed an isometric handgrip exercise. During rest and exercise, continuous heart rate and blood pressure were measured. Cardiovascular magnetic resonance (CMR) measurements included left ventricular mass, aortic distensibility and pulse wave velocity at rest and left ventricular end-diastolic and end-systolic volumes, ejection fraction, stroke volume and cardiac output during rest and exercise. 207 children had successful CMR measurements in rest and 184 during exercise. We observed good reproducibility for all cardiac measurements. Heart rate increased with a mean ± standard deviation of 42.6% ± 20.0 and blood pressure with 6.4% ± 7.0, 5.4% ± 6.1 and 11.0% ± 8.3 for systolic, diastolic and mean arterial blood pressure respectively (p-values &lt; 0.05). During exercise, left ventricular end-diastolic and end-systolic volumes and cardiac output increased, whereas left ventricular ejection fraction slightly decreased (p-values &lt; 0.05). Stroke volume did not change significantly. A sustained handgrip exercise of 7 min at 30-40% maximal voluntary contraction is a feasible exercise-test during CMR in a healthy pediatric population, which leads to significant changes in heart rate, blood pressure and functional measurements of the left ventricle in response to exercise. This approach offers great novel opportunities to detect subtle differences in cardiovascular health.</p

Associations of maternal angiogenic factors during pregnancy with alterations in cardiac development in childhood at 10 years of age

Aim: To examine whether maternal angiogenic factors in the first half of pregnancy are associated with offspring left and right cardiac development. Methods: In a population-based prospective cohort among 2,415 women and their offspring, maternal first and second trimester plasma PlGF and sFlt-1 concentrations were measured. Cardiac MRI was performed in their offspring at 10 years. Results: Maternal angiogenic factors were not associated with childhood cardiac outcomes in the total population. In children born small-for-their-gestational-age, higher maternal first trimester PlGF concentrations were associated with a lower childhood left ventricular mass (-0.24 SDS [95%CI -0.42, -0.05 per SDS increase in maternal PlGF]), whereas higher sFlt-1 concentrations were associated with higher childhood left ventricular mass (0.22 SDS [95%CI 0.09, 0.34 per SDS increase in maternal sFlt-1]). Higher second trimester maternal sFlt-1 concentrations were also associated with higher childhood left ventricular mass (P-value <.05). In preterm born children, higher maternal first and second trimester sFlt-1/PlGF ratio were associated with higher childhood left ventricular mass (0.30 SDS [95%CI 0.01, 0.60], 0.22 SDS [95%CI -0.03, 0.40]) per SDS increase in maternal sFlt-1/PlGF ratio in first and second trimester respectively). No effects on other childhood cardiac outcomes were present within these higher-risk children. Conclusions: In a low-risk population, maternal angiogenic factors are not associated with childhood cardiac ventricular structure, and function within the normal range. In children born small for their gestational age or preterm, an imbalance in maternal angiogenic factors in the first half of pregnancy was associated with higher childhood left ventricular mass only