A three-dimensional atlas of child's cardiac anatomy and the unique morphological alterations associated with obesity.

AIMS: Statistical shape models (SSMs) of cardiac anatomy provide a new approach for analysis of cardiac anatomy. In adults, specific cardiac morphologies associate with cardiovascular risk factors and early disease stages. However, the relationships between morphology and risk factors in children remain unknown. We propose an SSM of the paediatric left ventricle to describe its morphological variability, examine its relationship with biometric parameters and identify adverse anatomical remodelling associated with obesity. METHODS AND RESULTS: This cohort includes 2631 children (age 10.2 ± 0.6 years), mostly Western European (68.3%) with a balanced sex distribution (51.3% girls) from Generation R study. Cardiac magnetic resonance short-axis cine scans were segmented. Three-dimensional left ventricular (LV) meshes are automatically fitted to the segmentations to reconstruct the anatomies. We analyse the relationships between the LV anatomical features and participants' body surface area (BSA), age, and sex, and search for features uniquely related to obesity based on body mass index (BMI). In the SSM, 19 modes described over 90% of the population's LV shape variability. Main modes of variation were related to cardiac size, sphericity, and apical tilting. BSA, age, and sex were mostly correlated with modes describing LV size and sphericity. The modes correlated uniquely with BMI suggested that obese children present with septo-lateral tilting (R2 = 4.0%), compression in the antero-posterior direction (R2 = 3.3%), and decreased eccentricity (R2 = 2.0%). CONCLUSIONS: We describe the variability of the paediatric heart morphology and identify anatomical features related to childhood obesity that could aid in risk stratification. Web service is released to provide access to the new shape parameters.

Pericardial adipose tissue, cardiac structures, and cardiovascular risk factors in school-age children.

AIMS: We examined the associations of pericardial adipose tissue with cardiac structures and cardiovascular risk factors in children. METHODS AND RESULTS: We performed a cross-sectional analysis in a population-based cohort study among 2892 children aged 10 years (2404 normal weight and 488 overweight/obese). Pericardial adipose tissue mass was estimated by magnetic resonance imaging (MRI) and indexed on height3. Left ventricular mass (LVM) and left ventricular mass-to-volume ratio (LMVR) were estimated by cardiac MRI. Cardiovascular risk factors included android adipose tissue percentage obtained by Dual-energy X-ray absorptiometry, blood pressure and glucose, insulin, cholesterol, and triglycerides concentrations. Adverse outcomes were defined as values above the 75 percentile. Median pericardial adipose tissue index was 3.6 (95% range 1.6-7.1) among normal weight and 4.7 (95% range 2.0-8.9) among overweight children. A one standard deviation (1 SD) higher pericardial adipose tissue index was associated with higher LMVR [0.06 standard deviation scores, 95% confidence interval (CI) 0.02-0.09], increased odds of high android adipose tissue [odd ratio (OR) 2.08, 95% CI 1.89-2.29], high insulin concentrations (OR 1.17, 95% CI 1.06-1.30), an atherogenic lipid profile (OR 1.22, 95% CI 1.11-1.33), and clustering of cardiovascular risk factors (OR 1.56, 95% CI 1.36-1.79). Pericardial adipose tissue index was not associated with LVM, blood pressure, and glucose concentrations. The associations showed largely the same directions but tended to be weaker among normal weight than among overweight children. CONCLUSION: Pericardial adipose tissue is associated with cardiac adaptations and cardiovascular risk factors already in childhood in both normal weight and overweight children.

Ethnic differences in childhood right and left cardiac structure and function assessed by cardiac magnetic resonance imaging.

Ethnic differences in cardiovascular risk factors and disease are well-known and may originate in early-life. We examined the ethnic differences in cardiac structure and function in children using cardiac magnetic resonance imaging in a European migrant population, and whether any difference was explained by early life factors. We used a prospective population-based cohort study among 2317 children in Rotterdam, the Netherlands. We compared children from Dutch (73%), Cape Verdean (3.5%), Dutch Antillean (3.3%), Moroccan (6.1%), Surinamese-Creoles (3.9%), Surinamese-Hindustani (3.4%), and Turkish (6.4%) background. Main outcomes were cMRI-measured cardiac structures and function. Cardiac outcomes were standardized on body surface area. Cape Verdean, Surinamese-Hindustani, and Turkish children had smaller right ventricular end-diastolic volume and left ventricular end-diastolic volume relative to their body size than Dutch children (p < 0.05). These results were not fully explained by fetal and childhood factors. Right ventricular ejection fraction and left ventricular ejection fraction did not differ between ethnicities after adjustment for fetal and childhood factors.Conclusion: Right ventricular end-diastolic volume and left ventricular end-diastolic volume differ between ethnic subgroups in childhood, without affecting ejection fraction. Follow-up studies are needed to investigate whether these differences lead to ethnic differences in cardiac disease in adulthood. What is Known: • Ethnic differences in cardiovascular risk factors and disease are well-known and may originate in early-life. • The prevalence of cardiovascular disease differs between ethnic groups. What is New: • We examined ethnic differences in left and right cardiac structure and function in children using cMRI. • Right and left cardiac dimensions differ between ethnic groups in childhood and are only partly explained by fetal and childhood factors.

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.

Body Fat Distribution, Overweight, and Cardiac Structures in School-Age Children: A Population-Based Cardiac Magnetic Resonance Imaging Study.

Background Adiposity is associated with larger left ventricular mass in children and adults. The role of body fat distribution in these associations is not clear. We examined the associations of body fat distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school-age children. Methods and Results In a population-based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual-energy X-ray absorptiometry, and magnetic resonance imaging to collect information on body mass index, lean mass index, fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end-diastolic volume, left ventricular mass, and mass-to-volume ratio as a marker for concentricity. All body fat measures were positively associated with right and left ventricular end-diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P<0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94-1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14-0.57) higher left ventricular mass-to-volume ratio than normal weight children. Conditional on body mass index, higher lean mass index was associated with higher right and left ventricular end-diastolic volume and left ventricular mass, whereas higher fat mass measures were inversely associated with these cardiac measures (all P<0.05). Conclusions Higher childhood body mass index is associated with a larger right and left ventricular size. This association is influenced by higher lean mass. In childhood, lean mass may be a stronger determinant of heart growth than fat mass. Fat mass may influence cardiac structures at older ages.

Fetal and infant growth patterns and left and right ventricular measures in childhood assessed by cardiac MRI.

OBJECTIVES: Early life is critical for cardiac development. We examined the associations of longitudinal fetal and childhood growth patterns with childhood right and left ventricular structures measured by cardiac magnetic resonance imaging. METHODS: In a population-based prospective cohort study among 2827 children, we measured growth at 20 and 30 weeks of pregnancy, at birth, 0.5, 1, 2, 6 and 10 years. At 10 years, we measured right ventricular end-diastolic volume, left ventricular end-diastolic volume, left ventricular mass and left ventricular mass-to-volume ratio by cardiac magnetic resonance imaging. RESULTS: Small size for gestational age at birth was associated with smaller right and left ventricular end-diastolic volume relative to current body surface area, but with larger left ventricular mass-to-volume ratio (P < 0.05). Children in the upper 25% of right and left ventricular end-diastolic volume and left ventricular mass at age 10 years were larger at birth and became taller and leaner in childhood (P < 0.05). In contrast, children in the lower 25% of right and left ventricular end-diastolic volume and left ventricular mass were smaller at birth and became shorter and heavier in childhood (P < 0.05). Both fetal and childhood growth were independently of each other associated with childhood right and left ventricular end-diastolic volume and left ventricular mass. CONCLUSION: Children who are larger at birth and grow taller and leaner in childhood have larger hearts relative to body surface area. Small size at birth children, who grow shorter and heavier in childhood, have relatively smaller hearts with larger left ventricular mass-to-volume ratio. Both fetal and childhood growth are important for the development of cardiac dimensions.

Third Trimester Fetal Cardiac Blood Flow and Cardiac Outcomes in School-Age Children Assessed By Magnetic Resonance Imaging.

Background An adverse fetal environment leads to fetal hemodynamic adaptations with cardiac flow alterations that may subsequently affect cardiac development. We examined the associations of third trimester placental and fetal cardiac hemodynamics with cardiac outcomes in school-age children. Methods and Results We performed a population-based prospective cohort study among 547 mothers and their children. At a gestational age of 30.4 (95% range 28.4-32.7) weeks, we measured umbilical and cerebral artery resistance, cardiac output, and tricuspid and mitral E/A waves with Doppler. At the median age of 10.0 years (95% range 9.4-11.7) we measured cardiac outcomes with cardiac magnetic resonance imaging. Cardiac outcomes included right ventricular end-diastolic volume) and right ventricular ejection fraction, left ventricular end diastolic volume and left ventricular ejection fraction, left ventricular mass, and left ventricular mass-to-volume ratio as left ventricular mass/left ventricular end diastolic volume. Higher third-trimester umbilical artery resistance was associated with higher childhood right ventricular ejection fraction (P value <0.05), but not with other cardiac outcomes. The third-trimester umbilical artery-cerebral artery pulsatility index ratio was not associated with childhood cardiac outcomes. Higher third-trimester fetal left cardiac output was associated with lower childhood left ventricular ejection fraction and higher left ventricular mass-to-volume ratio (P value <0.05). Third-trimester fetal right cardiac output was not associated with childhood cardiac outcomes. A higher third-trimester fetal tricuspid valve E/A ratio was associated with higher childhood right ventricular ejection fraction (P value <0.05). Conclusions Our findings suggest that fetal cardiac fetal blood flow redistribution may have long-term effects on cardiac structure and function. These results should be considered as hypothesis generating and need further replication.

Associations of Fetal and Infant Weight Change With General, Visceral, and Organ Adiposity at School Age.

Importance: Both fetal and infant growth influence obesity later in life. The association of longitudinal fetal and infant growth patterns with organ fat is unknown. Objective: To examine the associations of fetal and infant weight change with general, visceral, and organ adiposity at school age. Design, Setting, and Participants: This cohort study was embedded in the Generation R Study, a population-based prospective cohort study in Rotterdam, the Netherlands. Pregnant women with a delivery date between April 2002 and January 2006 were eligible to participate. Follow-up measurements were performed for 3205 children. Data analysis of this population was performed from July 26, 2018, to February 7, 2019. Exposures: Fetal weight was estimated in the second and third trimester of pregnancy. Infant weight was measured at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in standard deviation scores greater than 0.67 between 2 ages. Main Outcomes and Measures: Visceral fat index, pericardial fat index, and liver fat fraction were measured by magnetic resonance imaging. Results: The sample consisted of 3205 children (1632 girls [50.9%]; mean [SD] age, 9.8 [0.3] years). Children born small for gestational age had the lowest median body mass index compared with children born appropriate for gestational age and large for gestational age (16.4 [90% range, 14.1-23.6] vs 16.9 [90% range, 14.4-22.8] vs 17.4 [90% range, 14.9-22.7]). Compared with children with normal fetal and infant growth (533 of 2370 [22.5%]), those with fetal weight deceleration followed by infant weight acceleration (263 of 2370 [11.1%]) had the highest visceral fat index (standard deviation scores, 0.18; 95% CI, 0.03-0.33; P = .02) and liver fat fraction (standard deviation scores, 0.34; 95% CI, 0.20-0.48; P < .001). Conclusions and Relevance: Fetal and infant weight change patterns were both associated with childhood body fat, but weight change patterns in infancy tended to have larger effects. Fetal growth restriction followed by infant growth acceleration was associated with increased visceral and liver fat.

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.

Early Infant Growth Velocity Patterns and Cardiovascular and Metabolic Outcomes in Childhood.

OBJECTIVE: To evaluate the impact of infant growth on childhood health by examining the associations of detailed longitudinal infant weight velocity patterns with childhood cardiovascular and metabolic outcomes. STUDY DESIGN: In a population-based prospective cohort study of 4649 children, we used repeated growth measurements at age 0-3 years to derive peak weight velocity (PWV), age at adiposity peak (AGEAP), and body mass index at adiposity peak (BMIAP). At age 6 years, we measured blood pressure, left ventricular mass, and cholesterol, triglyceride, and insulin concentrations and defined children with clusters of risk factors. We assessed associations using 2 multivariable linear regression models. RESULTS: A 1-SDS-higher infant PWV was associated with higher diastolic blood pressure (0.05 SDS; 95% CI, 0.02-0.09) and lower left ventricular mass (-0.05 SDS; 95% CI, -0.09 to -0.01), independent of body size. A 1-SDS-higher BMIAP was associated with higher systolic (0.12; 95% CI, 0.09-0.16) and diastolic (0.05; 95% CI, 0.01-0.08) blood pressure, but these associations were explained by childhood BMI. We did not observe any associations of PWV, BMIAP, and AGEAP with cholesterol and insulin concentrations. Higher PWV and AGEAP were associated with elevated risk of clustering of cardiovascular risk factors in childhood (P < .05). CONCLUSION: Infant weight velocity patterns are associated with cardiovascular outcomes. Further studies are needed to explore the associations with metabolic outcomes and long-term consequences.

Longitudinal growth during fetal life and infancy and cardiovascular outcomes at school-age.

OBJECTIVE: Low birth weight is associated with cardiovascular disease. We examined the effects of fetal and infant growth patterns on cardiovascular outcomes in children. METHODS: In a population-based prospective cohort study among 6239 children, we estimated fetal-femur length and weight by 20 and 30 weeks ultrasound, and child length and weight at birth, 0.5, 1, 2 and 6 years. We measured blood pressure (BP), carotid-femoral pulse wave velocity, aortic root diameter, left ventricular mass and fractional shortening at 6 years. We used regression analyses to identify longitudinal growth patterns associated with height-standardized vascular outcomes and body-surface-area-standardized cardiac outcomes. RESULTS: Younger gestational age and lower birth weight were associated with higher BP, smaller aortic root diameter and lower left ventricular mass in childhood (all P values <0.05). Children with decelerated or normal fetal growth followed by accelerated infant growth had higher BP, whereas those with decelerated growth during both fetal life and infancy had a relatively larger left ventricular mass. Longitudinal growth analyses showed that children with increased BP tended to be smaller during third trimester of fetal life, but of normal size during infancy, than children with normal BP. Children with increased aortic root diameter or left ventricular mass tended to be larger during fetal life, but of similar size during infancy. CONCLUSION: Specific fetal and infant growth patterns are associated with different cardiovascular outcomes in children. Further studies are needed to identify the underlying mechanisms and the long-term cardiovascular consequences.

Associations between physical growth and general cognitive functioning in international adoptees from Eastern Europe at 30 months post-arrival.

BACKGROUND: Internationally adopted children have often experienced early adversity and growth suppression as a consequence of institutional care. Furthermore, these children are at risk for impaired cognitive development due to their early adverse experiences. This study examined the association between physical growth, the growth hormone (GH) system, and general cognitive functioning post-adoption. Based on previous research, we expected to find that a child's initial physical growth status and normalization of the growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis would be positive predictors of general cognitive functioning. METHODS: Post-institutionalized children (n = 46) adopted from Eastern Europe were seen approximately 1 month after their arrival into the USA to determine baseline measurements. They were seen again 6 and 30 months later for two follow-up sessions. Measures included anthropometry, insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), Mullen Scales of Early Learning, and Stanford-Binet Intelligence Scales. Information about parental education was also collected. RESULTS: We found that a child's general cognitive functioning at 30 months post-adoption was predicted by their general developmental scores at 6 months post-adoption, their initial height status, and markers of the growth hormone system. Children with lower initial IGFBP-3 standard deviation (SD) scores had higher verbal IQ scores at 30 months. Furthermore, a child's initial height was found to be a significant positive predictor of non-verbal IQ. CONCLUSIONS: These results suggest an association between a child's suppressed physical growth in response to early adversity and alterations in GH system functioning and subsequent recovery in cognitive functioning.

Predictors of developmental status in young children living in institutional care in Kazakhstan.

The main objective of this study was to assess the developmental status of children living in the severely adverse environment of institutional care and the examination of risk factors with regard to developmental status, including degree of stunting and emotional-behavioral and anemia status. The Bayley Scales of Infant Development were used to assess development status in 103 children aged 14.9 months (SD = 6.8) in six Kazakh institutions. The Behavioral Rating Scales were used to assess emotional-behavioral regulation. Physical growth measures were converted to z scores using World Health Organization growth charts. Venous blood was collected for assessment of anemia. Our findings indicated that young children in institutions were developmentally compromised, with duration of institutional care correlated with the severity of delay. Negative predictors of developmental status included: Poor emotional-behavioral regulation, degree of stunting and age at assessment. A particularly large percentage of children were found to be anemic. Additionally, low birth weight was found to be a significant negative predictor of development. Our findings indicate that institutional care has a detrimental impact on the development and emotional regulation of young children. Time in institutional care is a negative predictor for cognitive status for children placed at birth. Moreover stunting was found to be a useful indicator of the degree of impact of early adversity on cognitive development. Particular attention is needed for special-needs children such as those with low birth weight, since their development was found to be more sensitive to early adversity than that of normal birth weight children.

Transoral incisionless fundoplication for treatment of gastroesophageal reflux disease in clinical practice.

BACKGROUND: Transoral incisionless fundoplication is a recently introduced endoluminal technique for the treatment of gastroesophageal reflux disease (GERD). The objective of this study was to determine outcomes in chronic GERD patients who were referred for surgical management. METHODS: A cohort of 38 patients underwent transoral incisionless fundoplication (TIF) in a tertiary care setting. Pre- and post-procedure assessment included GERD-related quality of life questionnaires, proton pump inhibitor (PPI) usage, 24-h pH measurements, upper gastrointestinal endoscopy, esophageal manometry, and registration of adverse events. Duration of follow-up was 36 months. RESULTS: Gastroesophageal valves were constructed of 4 cm (range, 4-6) in length and 220° (range, 180-240) in circumference. One serious adverse event occurred, consisting of intraluminal bleeding at a fastener site. Hiatal hernia was completely reduced in 56 % and esophagitis was cured in 47 % of patients. Postprocedure esophageal acid exposure did not significantly improve (p > 0.05). At 36 (range, 29-41) months follow-up 14 patients (36 %) had undergone revisional laparoscopic fundoplication. Quality of life scores of the remaining cohort showed significant improvement (p < 0.0001) and daily use of antisecretory medication was discontinued by 74 %. CONCLUSIONS: Endoluminal fundoplication improved quality of life and reduced the need for PPIs in only a subgroup of patients at 3 years follow-up. The amount of patients requiring additional medication and revisional surgery was high.