Early Life Growth, Adiposity and Cardiovascular Health in Childhood: The Generation R Study

Cardiovascular disease is a major public health problem worldwide and might originate in early life. Not only fetal life, but also early postnatal life is important for cardiovascular health. Common risk factors for cardiovascular disease, such as blood pressure, lipid levels and obesity track from childhood to adulthood. Both an adverse fetal environment and an affluent postnatal environment seem to adversely affect cardiovascular health from childhood to adulthood. Identifying the risk factors and the sensitive periods in early life and the mechanisms through which early life affects cardiovascular health are important for future preventive strategies to ensure cardiovascular health later in the life course. Therefore, studies presented in this thesis were designed to identify fetal, infant and childhood factors associated with cardiovascular health outcomes in childhood. The research is part of Generation R, a large and longitudinal cohort study on growth, development and health of 10.000 children from Rotterdam. Findings from this thesis suggest that early-life growth and adiposity related factors are associated with cardiac structure and adverse cardiovascular outcomes in children. Future studies should focus on how changes in cardiac structure and cardiovascular outcomes in childhood relate to cardiovascular disease risk in adulthood. Pr

Associations of Maternal Glycemia in the First Half of Pregnancy With Alterations in Cardiac Structure and Function in Childhood

OBJECTIVE: Gestational diabetes mellitus has been associated with offspring cardiac congenital malformations, ventricular hypertrophy, and diastolic dysfunction in large observational cohort studies and experimental animal models. We assessed the associations of maternal random glucose concentrations across the full range with childhood cardiac ventricular structure and function. RESEARCH DESIGN AND METHODS: In a population-based prospective cohort among 1,959 women and their offspring, maternal random glucose concentrations were measured at a median 13.1 weeks’ gestation (95% range 10.5–16.8 weeks). We obtained offspring cardiac outcomes, relative to body size, through cardiac MRI at 10 years. RESULTS: The mean maternal random glucose concentration was 4.4 mmol/L (SD 0.8). The highest quintile of maternal glucose concentrations, compared with the lowest quintile, was associated with a lower childhood left ventricular mass (–0.19 SD score [SDS]; 95% CI –0.31, –0.07) and left ventricular end-diastolic volume (–0.17 SDS; 95% –0.28, –0.05). Also, higher maternal glucose concentrations across the full range per 1 mmol/L increase were associated with a lower childhood left ventricular mass and left ventricular end-diastolic volume (P values ≤0.05). Adjustment for maternal prepregnancy BMI, gestational age, and weight at birth or childhood BMI and blood pressure did not influence the effect estimates. Maternal glucose concentrations were not significantly associated with childhood right ventricular end-diastolic volume or left and right ventricular ejection fraction. CONCLUSIONS: Higher maternal random glucose concentrations in the first half of pregnancy are associated with a lower childhood left ventricular mass and left ventricular end-diastolic volume, with the strongest associations for childhood left ventricular mass. These associations were not explained by maternal, birth, or childhood characteristics. Further studies are needed to replicate these findings using repeated maternal glucose measurements throughout pregnancy and offspring cardiac outcomes throughout childhood and adulthood

Tracking of structural and functional cardiac measures from infancy into school-age

Objective: Cardiac structure and function are important predictors for cardiovascular disease in adults. Not much is known about tracking of cardiac measures, other than left ventricular mass, from early life onwards. We examined whether and to what extent cardiac measures track from infancy into school-age. Methods: We performed a population-based prospective cohort study among 1072 children. Aortic root diameter, left atrial diameter, left ventricular mass, relative wall thickness and fractional shortening were measured repeatedly by echocardiography. We explored tracking between infancy (1.5, six and 24 months) and school-age (six and 10 years). Results: Of all cardiac measures, aortic root diameter, left atrial diameter and left ventricular mass were significantly correlated between infancy and school-age (r = 0.10–0.42, all p-values < 0.01), with the strongest correlations between 24 months and 10 years. Of the different structures, aortic root diameter showed the strongest correlations. Approximately 30% of children who were in the lowest or highest quartile of a measure at the age of 1.5 months remained in that quartile at the age of 10 years. When analysing the effects of the infant cardiac measures on the same outcomes at 10 years in conditional regression models, we observed effect estimates of the same size for the different age windows. Conclusion: Our results suggest moderate tracking of structural cardiac measures from early infancy until school-age, which become stronger at older ages, but not of relative wall thickness or fractional shortening. Moderate tracking of cardiac structures suggests that cardiac structures are at least partly determined in early life