Reference ranges for the size of the fetal cardiac outflow tracts from 13 to 36 weeks gestation: a single-center study of over 7000 cases

BACKGROUND: Assessment of the outflow tract views is an integral part of routine fetal cardiac scanning. For some congenital heart defects, notably coarctation of the aorta, pulmonary valve stenosis, and aortic valve stenosis, the size of vessels is important both for diagnosis and prognosis. Existing reference ranges of fetal outflow tracts are derived from a small number of cases. METHODS AND RESULTS: The study population comprised 7945 fetuses at 13 to 36 weeks’ gestation with no detectable abnormalities from pregnancies resulting in normal live births. Prospective measurements were taken of (1) the aortic and pulmonary valves in diastole at the largest diameter with the valve closed, (2) the distal transverse aortic arch on the 3 vessel and trachea view beyond the trachea at the distal point at its widest systolic diameter, and (3) the arterial duct on the 3 vessel and trachea view at its widest systolic diameter. Regression analysis, with polynomial terms to assess for linear and nonlinear contributors, was used to establish the relationship between each measurement and gestational age. The measurement for each cardiac diameter was expressed as a z score (difference between observed and expected value divided by the fitted SD corrected for gestational age) and percentile. Analysis included calculation of gestation-specific SDs. Regression equations are provided for the cardiac outflow tracts and for the distal transverse aortic arch:arterial duct ratio. CONCLUSIONS: The study established reference ranges for fetal outflow tract measurements at 13 to 36 weeks’ gestation that are useful in clinical practice

Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring

BACKGROUND: Maternal obesity increases the risk for pregnancy complications and adverse neonatal outcome and it has also been associated with long lasting adverse effects in the offspring, including increased body fat mass, insulin resistance and increased risk for premature cardiovascular disease. Lifestyle interventions in pregnancy have produced none or modest effects in reducing adverse pregnancy outcomes in obese mothers. Metformin use in Obese Pregnant women trial was associated with reduced adverse pregnancy outcomes and had no effect on birthweight. However, the long-term implications of metformin on the health of offspring remain unknown. OBJECTIVE: The purpose of this study was to assess whether prenatal exposure to metformin can improve the cardiovascular profile and body composition in the offspring of obese mothers. STUDY DESIGN: In 151 children from the Metformin use in Obese-Pregnant women trial we measured body composition, peripheral blood pressure and arterial pulse wave velocity. Central hemodynamics (central blood pressure and augmentation index) were estimated using the Vicorder device. Left ventricular cardiac function and structure were assessed by echocardiography. RESULTS: Children were 3.9±1.0 years of age and 77 were exposed to metformin prenatally. There was no significant difference in peripheral blood pressure, arterial stiffness and body composition apart from gluteal and tricep circumferences which were lower in the metformin group (p<0.05). The metformin, compared to the placebo group, had lower central hemodynamics (mean adjusted decrease - 0.707mmHg for aortic systolic blood pressure, -1.65mmHg for aortic pulse pressure and -2.68% for augmentation index, p<0.05 for all) and lower left ventricular diastolic function (adjusted difference in left atrial area -0.525cm2, in isovolumic relaxation time -0.324msec and in pulmonary venous systolic wave 2.97cm/s, p<0.05 for all). There were no significant differences in metabolic profile between the groups. CONCLUSION: Children of obese mothers who were prenatally exposed to metformin, compared to those exposed to placebo, have lower central hemodynamic and cardiac diastolic indices. These results suggest that administration of metformin in obese pregnant women may potentially have a beneficial cardiovascular effect for their offspring

Response to 'Does smoking or alcohol cause early vascular damage in teenage years?'

This commentary refers to ‘Early vascular damage from smoking and alcohol in teenage years: the ALSPAC study’, by M. Charakida et al., 345–353

Intimal and medial arterial changes defined by ultra-high-frequency ultrasound: Response to changing risk factors in children with chronic kidney disease

BACKGROUND: Patients with chronic kidney disease (CKD) are exposed to both traditional 'Framingham' and uremia related cardiovascular risk factors that drive atherosclerotic and arteriosclerotic disease, but these cannot be differentiated using conventional ultrasound. We used ultra-high-frequency ultrasound (UHFUS) to differentiate medial thickness (MT) from intimal thickness (IT) in CKD patients, identify their determinants and monitor their progression. METHODS: Fifty-four children and adolescents with CKD and 12 healthy controls underwent UHFUS measurements using 55-70MHz transducers in common carotid and dorsal pedal arteries. Annual follow-up imaging was performed in 31 patients. RESULTS: CKD patients had higher carotid MT and dorsal pedal IT and MT compared to controls. The carotid MT in CKD correlated with serum phosphate (p<0.001, r = 0.42), PTH (p = 0.03, r = 0.36) and mean arterial pressure (p = 0.03, r = 0.34). Following multivariable analysis, being on dialysis, serum phosphate levels and mean arterial pressure remained the only independent predictors of carotid MT (R2 64%). Transplanted children had lower carotid and dorsal pedal MT compared to CKD and dialysis patients (p = 0.02 and p = 0.01 respectively). At 1-year follow-up, transplanted children had a decrease in carotid MT (p = 0.01), but an increase in dorsal pedal IT (p = 0.04) that independently correlated with annualized change in BMI. CONCLUSIONS: Using UHFUS, we have shown that CKD is associated with exclusively medial arterial changes that attenuate when the uremic milieu is ameliorated after transplantation. In contrast, after transplantation intimal disease develops as hypertension and obesity become prevalent, representing rapid vascular remodeling in response to a changing cardiovascular risk factor profile

Determinants of intima-media thickness in the young: the ALSPAC Study

Objectives: This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n &gt; 4,000) longitudinal cohort of healthy young people age 9 to 21 years. Background: Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. Methods: Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences. Results: Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p &lt; 0.001), whereas fat mass was negatively associated with cIMT (difference: −0.0032; 95% CI: 0.004 to −0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor−associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor. Conclusions: Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures might be more appropriate for the identification of arterial disease before adulthood

Screening for familial hypercholesterolaemia in childhood:Avon Longitudinal Study of Parents and Children (ALSPAC)

Background and aims: Familial hypercholesterolaemia (FH) is an autosomal-dominant disease with frequency of 1/500 to 1/250 that leads to premature coronary heart disease. New approaches to identify FH mutation-carriers early are needed to prevent premature cardiac deaths. In a cross-sectional study of the Avon Longitudinal Study of Parents and Children (ALSPAC), we evaluated the biochemical thresholds for FH screening in childhood, and modelled a two-stage biochemical and sequencing screening strategy for FH detection. Methods: From 5083 ALSPAC children with cholesterol measurement at age nine years, FH genetic diagnosis was performed in 1512 individuals, using whole-genome or targeted sequencing of known FH-causing genes. Detection rate (DR) and false-positive rate (FPR) for proposed screening thresholds (total-cholesterol &gt; 1.53, or LDL-C &gt; 1.84 multiples of the median (MoM)) were assessed. Results: Six of 1512 sequenced individuals had an FH-causing mutation of whom five had LDL-C &gt; 1.84 MoM, giving a verification-bias corrected DR of 62.5% (95% CI: 25–92), with a FPR of 0.2% (95% CI: 0.1–0.4). The DR for the TC cut-point of 1.53 MoM was 25% (95% CI: 3.2–65.1) with a FPR of 0.4% (95% CI: 0.2–0.6). We estimated 13 of an expected 20 FH mutation carriers (and 13 of the 20 parental carriers) could be detected for every 10,000 children screened, with false-positives reliably excluded by addition of a next generation sequencing step in biochemical screen-positive samples. Conclusions: Proposed cholesterol thresholds for childhood FH screening were less accurate than previously estimated. A sequential strategy of biochemical screening followed by targeted sequencing of FH genes in screen-positive children may help mitigate the higher than previously estimated FPR and reduce wasted screening of unaffected parents

Patterns of adiposity, vascular phenotypes and cognitive function in the 1946 British Birth Cohort.

BACKGROUND: The relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations. METHODS: The study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes. RESULTS: Longer exposure to elevated WC was related to lower memory performance (p < 0.001 for both) and longer choice reaction time (p = 0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P < 0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations. CONCLUSIONS: Longer exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships