SARS-CoV-2 Antibody Kinetics in Unvaccinated Hospitalized Children With COVID-19.

BACKGROUND: Antibody levels decline a few months post-acute COVID-19, but humoral memory persists in adults. Age and disease severity may affect antibody responses. This study aims to evaluate the presence and durability of antibody responses in children with COVID-19. METHODS: A prospective, single-center study, involving unvaccinated children 0-16 years of age who were hospitalized with COVID-19 between October 2020 and December 2021, was conducted. Serological testing for anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and neutralizing antibodies was performed at diagnosis and at 1-, 3-, 6- and 12-months post-infection. RESULTS: A total of 65 immunocompetent children were enrolled [mean age (±SD): 6.7 (±6.4) years; males: 56.9%]. At 3 months, 40/44 (91%) children were seropositive; seropositivity persisted in 22/26 (85%) children at 6 months and in 10/12 (83%) children at 12 months. There was no evidence that age was modifying the prediction of variance of SARS-CoV-2 IgG levels. In contrast, SARS-CoV-2 IgG levels varied with time and disease severity. The association with time was non-linear, so that with increasing time there was a significant reduction in SARS-CoV-2 IgG levels [coef, 0.044 (95% confidence interval {CI}: 0.061-0.028), P < 0.001]. For each increment of time, the higher disease severity group was associated with 0.9 lower SARS-CoV-2 IgG levels. Everyone varied from the average effect of time with an SD of 0.01, suggesting that individuals may have different trajectories across time. CONCLUSION: Disease severity, but not age, influences antibody titers among children hospitalized with COVID-19. SARS-CoV-2 infection induces durable seroconversion in these children with detectable IgG levels at 1 year after infection.

Multisystem inflammatory syndrome in children (MIS-C): A nationwide collaborative study in the Greek population.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition that may occur following SARS-CoV-2 infection. This retrospective, descriptive study of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) in 12 tertiary care centers from 3/11/2020 to 12/31/2021. Demographics, clinical and laboratory characteristics, treatment and outcomes are described. Among 145 patients (95 males, median age 8.2 years) included, 123 met the WHO criteria for MIS-C, while 112 (77%) had serological evidence of SARS-CoV-2 infection. Fever was present in 99%, gastrointestinal symptoms in 77%, mucocutaneous involvement in 68% and respiratory symptoms in 28%. Fifty-five patients (38%) developed myocarditis, 29 (20%) pericarditis and 19 (13%) coronary aneurysms. Among the above cases 11/55 (20%), 1/29 (3.4%) and 5/19 (26.3%), respectively, cardiac complications had not fully resolved at discharge. Underlying comorbidities were reported in 18%. Median CRP value was 155 mg/l, ferritin 535 ng/ml, PCT 1.6 ng/ml and WBC 14.2 × 109/mm3. Most patients had elevated troponin (41.3%) and/or NT-pro-BNP (49.6%). Intravenous immunoglobulin plus corticosteroids were used in 117/145 (80.6%), monotherapy with IVIG alone in 13/145 (8.9%) and with corticosteroids alone in 2/145 (1.3%). Anti-IL1 treatment was added in 15 patients (10.3%). Thirty-three patients (23%) were admitted to the PICU, 14% developed shock and 1 required ECMO. Mortality rate was 0.68%. The incidence of MIS-C was estimated at 0.69/1000 SARS-CoV-2 infections. Patients who presented with shock had higher levels of NT-pro-BNP compared to those who did not (p < 0.001). Acute kidney injury and/or myocarditis were associated with higher risk of developing shock. CONCLUSION: MIS-C is a novel, infrequent but serious disease entity. Cardiac manifestations included myocarditis and pericarditis, which resolved in most patients before discharge. Timely initiation of immunomodulatory therapy was shown to be effective. NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. Further research is required to elucidate the pathogenesis, risk factors and optimal management, and long-term outcomes of this clinical entity. WHAT IS KNOWN: • MIS-C is an infrequent but serious disease entity. • Patients with MIS-C present with multi-organ dysfunction, primarily involving the gastrointestinal and cardiovascular systems. WHAT IS NEW: • NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. • Acute kidney injury and/or myocarditis were associated with higher risk of developing shock.

Pregnancy-An Ideal Period to Identify Women at Risk for Chronic Hypertension.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in women. Pregnancy is an ideal period to implement cardiovascular prevention strategies as women seek medical help. We aimed to develop a predictive model to identify women at increased risk for chronic hypertension (CH) based on information collected in the index pregnancy. METHODS: Cohort of 26 511 women seen in 2 consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure at 11 to 13 weeks' gestation, and the development of preeclampsia or gestational hypertension (GH) in the index pregnancy. Logistic regression models were fitted for the prediction of the development of future CH by the 20th week of the subsequent pregnancy. The performance of screening and risk calibration of the model were assessed. RESULTS: In this study 1560 (5.9%) women developed preeclampsia or GH (index pregnancy), and 215 (0.8%) developed future CH, with a median of 3.0 years later. Predictors of development of future CH were maternal age, weight, and blood pressure; Black and South Asian ethnicity; family history of preeclampsia; parity; and development of preeclampsia or GH. Preeclampsia or GH detected 52.1% (45.2%-58.9%) of future CH. At a screen-positive rate of 10%, a model including maternal characteristics, early pregnancy blood pressure, and development of preeclampsia or GH detected 73.5% (67.1-79.3) of future CH. CONCLUSIONS: Early pregnancy maternal characteristics, blood pressure, and development of preeclampsia or GH identify three-fourths of women at risk for future CH. Our results offer an important preventative strategy for identifying women at increased risk of future CH, which is applicable worldwide.

Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Maternal and Offspring Cardiovascular Function following Pregnancy with Hypertensive Disorder.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) have been associated with increased cardiovascular risk for the mother and her offspring. However, it remains unknown whether cardiovascular changes are present in the postpartum period. METHODS: This was a cross-sectional study of women with singleton pregnancies. We recruited 33 women (20 following preeclampsia and 13 following gestational hypertension) and an equal number of women with uncomplicated pregnancy. Conventional and more advanced echocardiographic modalities such as speckle tracking were used to assess maternal and offspring cardiac function at 3-9 months postpartum. RESULTS: In women with HDP compared to those without, there was higher mean arterial pressure (mean 92.3 (SD 7.3) vs. 86.8 (8.3) mmHg, p = 0.007), left-ventricular mass indexed for body-surface area (64.5 (10.5) vs. 56.8 (10.03), p < 0.003), and E/e' (3.6 (0.8) vs. 3.1 (0.9), p = 0.022). There were no significant differences between groups in maternal left-ventricular systolic-functional indices and in offspring cardiac function between groups. CONCLUSIONS: At 3-9 months postpartum, mothers with HDP had higher blood pressure, higher left-ventricular mass, and reduced left-ventricular diastolic function. However, in their offspring, cardiac function was preserved. These findings suggest that mothers who experienced an HDP would benefit from cardio-obstetric follow-up in the postpartum period.

Fetal Cardiac Function at Midgestation and Subsequent Development of Preeclampsia.

OBJECTIVE: To assess differences in cardiac morphology and function at midgestation in fetuses from pregnancies that subsequently developed preeclampsia (PE) or gestational hypertension (GH). METHODS: This was a prospective study in 5,801 women with singleton pregnancies attending for a routine ultrasound examination at midgestation, including 179 (3.1%) who subsequently developed PE and 149 (2.6%) who developed GH. Conventional and more advanced echocardiographic modalities, such as speckle-tracking, were used to assess fetal cardiac function in the right and left ventricle. The morphology of the fetal heart was assessed by calculating the right and left sphericity index. RESULTS: In fetuses from the PE group (vs the no PE or GH group) there was a significantly higher left ventricular global longitudinal strain and lower left ventricular ejection fraction that could not be accounted for by fetal size. All other indices of fetal cardiac morphology and function were comparable between groups. There was no significant correlation between fetal cardiac indices and uterine artery pulsatility index multiple of the median or placental growth factor multiple of the median. CONCLUSION: At midgestation, fetuses of mothers at risk of developing PE, but not those at risk of GH, have mild reduction in left ventricular myocardial function. Although absolute differences were minimal and most likely not clinically relevant, these may suggest an early programming effect on left ventricular contractility in fetuses of mothers who develop PE.

Fetal Cardiac Function at Midgestation in Women Who Subsequently Develop Gestational Diabetes.

Importance: Fetuses in women with gestational diabetes (GD) compared with those without GD show evidence of subclinical cardiac functional and morphological changes. However, it is uncertain whether glycemia or the adverse maternal underlying risk factor profile is the main driver for fetal cardiac remodeling. Objective: To assess cardiac morphology and function at midgestation in fetuses of mothers prior to development of GD and compare them with those of unaffected controls. Design, Setting, and Participants: During this prospective nonintervention screening study at 19 to 23 weeks' gestation, fetal cardiac morphology and function were assessed in all participants. Pregnancy complications were obtained from the medical records of the women. Fetal cardiac morphology and function were assessed in all participants at Harris Birthright Research Institute at King's College Hospital, London, United Kingdom. Participants included pregnant women with singleton pregnancy who attended their routine fetal ultrasound examination at midgestation and agreed to participate in the Advanced Cardiovascular Imaging Study in pregnancy. Main Outcome and Measures: Comparison of fetal cardiac morphology and function between mothers who subsequently developed GD and those who did not develop GD. Methods: This was a prospective nonintervention screening study of 5620 women with singleton pregnancies at 19 to 23 weeks' gestation. Conventional and more advanced echocardiographic modalities, such as speckle tracking, were used to assess fetal cardiac function in the right and left ventricle. The morphology of the fetal heart was assessed by calculating the right and left sphericity index. Results: The 5620 included patients had a mean age of 33.6 years. In 470 cases, the women were diagnosed with GD after the midgestation echocardiographic assessment (8.4%). Women with GD, compared with the non-GD group, were older, had higher BMI, higher prevalence of family history of diabetes, non-White ethnicity, chronic hypertension, and GD in a previous pregnancy. In fetuses of the GD group compared with the non-GD group, there was mild increase in interventricular millimeter thickness (0.04; 95% CI, 0.03-0.06 mm) and left atrial area (0.04; 95% CI, 0.04-0.05), whereas left and right functional indices were comparable between groups with the exception of left ventricular ejection fraction, which was marginally improved in the GD group (0.02; 95% CI, 0.03-0.03). Conclusions and Relevance: This study demonstrates that prior to development of GD, there was mild alteration in fetal cardiac morphology without affecting cardiac function. This suggests that the adverse maternal risk factor profile and not only the glycemia might contribute to cardiac remodeling noted in fetuses of women with GD.

Glycoprotein Acetyls: A Novel Inflammatory Biomarker of Early Cardiovascular Risk in the Young.

Background Low-grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high-sensitivity CRP (C-reactive protein). Methods and Results A total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4±0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1±5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross-sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9-to-10-year follow-up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within-subject correlation over 9-to-10-year follow-up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle-related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow-mediated dilation=-1.2 [-1.8, -0.7]% per z-score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], ≈1.1 per z-score increase for both cohorts) and metabolic syndrome (RR, ≈1.2-1.3 per z-score increase for both cohorts) in 9-to-10-year follow-up. Conclusions Low-grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10-year follow-up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.

Maternal Cardiac Function at Midgestation and Development of Preeclampsia.

BACKGROUND: Preeclampsia (PE) is an independent risk factor for adverse maternal cardiovascular outcomes. The role of maternal cardiac function in the pathophysiology of PE remains unclear. OBJECTIVES: This study sought to describe differences in cardiac function at midgestation between women who develop PE and those with uncomplicated pregnancy and to establish whether routine cardiac assessment at midgestation can improve performance of screening for PE achieved by established biomarkers. METHODS: Mean arterial pressure was measured, medical history was obtained, and left ventricular (LV) systolic and diastolic functions were assessed using standard echocardiography and speckle tracking imaging. Uterine artery pulsatility index and serum placental growth factor and soluble fms-like tyrosine kinase-1 were measured. RESULTS: In 4,795 pregnancies, 126 (2.6%) developed PE. Following multivariable analysis, peripheral vascular resistance was significantly higher and LV global longitudinal systolic strain, ejection fraction, cardiac output, and left atrial area were mildly lower in women who developed PE compared to those who did not. There was a weak association between maternal cardiovascular indices and biomarkers of placental perfusion and function. Cardiac indices did not improve the performance of screening for PE on top of maternal risk factors, mean arterial pressure, and biomarkers of placental perfusion and function. CONCLUSION: Women who develop PE have an increase in peripheral vascular resistance and a mild reduction in LV functional cardiac indices long before PE development. However, cardiac indices do not improve the performance of screening for PE; thus, their routine clinical use is not advocated.

Outcome and Impact of Associated Left-Sided Cardiac Lesions in Coarctation of the Aorta Diagnosed During Fetal Life.

Significant effort has been put into the optimization of the antenatal diagnosis of coarctation of the aorta (CoA). However, although left-sided cardiac lesions are known to cluster, the necessity to intervene postnatally for other left-sided cardiac lesions has not been reported in a cohort of fetuses with suspected CoA. We report a study of all 89 fetuses with antenatally suspected and postnatally confirmed diagnosis of CoA who underwent CoA repair as the primary procedure at a single tertiary congenital heart disease center over 10 years (January 1, 2010, to December 31, 2019). Almost 1 in 5 patients (18%) had to undergo surgery and/or transcatheter intervention on additional left-sided cardiac lesions (14%) and/or reintervention on the aortic arch (12%) during follow-up to median age of 2.85 years. Freedom from intervention at 5 years was 78% (95% confidence interval [CI] 67 to 88%) if reintervention on CoA was excluded, and 72% (95% CI 60 to 82%) if this was included. Five-year survival was 95% (95% CI 90 to 100%). Furthermore, 20% of affected infants had genetic (10%) and/or extracardiac (16%) abnormalities. Our study highlights the need for comprehensive antenatal counseling, including the prognosis of primary repair of CoA and the potential development of additional left-sided cardiac lesions, which may be difficult to diagnose prenatally even in expert hands or impossible to diagnose because of the physiology of the fetal circulation.

Dilated ascending aorta in the fetus.

INTRODUCTION: Prenatal recognition of dilated aortic root is extremely rare and there are significant challenges in counselling these patients. The primary aim of this case series is to describe the prevalence, associations and outcome of dilated ascending aorta diagnosed during fetal life. METHODS: This is a retrospective cohort study from two tertiary fetal cardiology centres. Dilated ascending aorta was defined as gestation-specific standard deviation > 1.96 at some point during gestation. RESULTS: Sixteen infants were live born and underwent postnatal echocardiography. Prenatally suspected bicuspid aortic valve (BAV) (n = 6) was confirmed in 5 cases (83%) postnatally. Thirteen children have been followed up for a period of minimum one year. No connective tissue disease was found. CONCLUSIONS: Prenatal dilated ascending aorta is a rare finding (0.06%). It is associated with BAV in 37% of cases and extracardiac abnormalities in 15.7%. Nuchal translucency measurement was >3.5 in 13% of cases. Connective tissue disease was not diagnosed postnatally. This is the largest prenatal cohort with dilated ascending aorta and postnatal outcomes to date. We showed a postnatal persistence of ascending aortic dilatation in 43% of babies. In the absence of extra-cardiac abnormalities, medium term outcome appears good but postnatal surveillance of aortic dilation is required.

Analysis of 3-Dimensional Arch Anatomy, Vascular Flow, and Postnatal Outcome in Cases of Suspected Coarctation of the Aorta Using Fetal Cardiac Magnetic Resonance Imaging.

BACKGROUND: Identifying fetuses at risk of severe neonatal coarctation of the aorta (CoA) can be lifesaving but is notoriously challenging in clinical practice with a high rate of false positives. Novel fetal 3-dimensional and phase-contrast magnetic resonance imaging (MRI) offers an unprecedented means of assessing the human fetal cardiovascular system before birth. We performed detailed MRI assessment of fetal vascular morphology and flows in a cohort of fetuses with suspected CoA, correlated with the need for postnatal intervention. METHODS: Women carrying a fetus with suspected CoA on echocardiography were referred for MRI assessment between 26 and 36 weeks of gestation, including high-resolution motion-corrected 3-dimensional volumes of the fetal heart and phase-contrast flow sequences gated with metric optimized gating. The relationship between aortic geometry and vascular flows was then analyzed and compared with postnatal outcome. RESULTS: Seventy-two patients (51 with suspected fetal CoA and 21 healthy controls) underwent fetal MRI with motion-corrected 3-dimensional vascular reconstructions. Vascular flow measurements from phase-contrast sequences were available in 53 patients. In the CoA group, 25 of 51 (49%) required surgical repair of coarctation after birth; the remaining 26 of 51 (51%) were discharged without neonatal intervention. Reduced blood flow in the fetal ascending aorta and at the aortic isthmus was associated with increasing angulation (P=0.005) and proximal displacement (P=0.006) of the isthmus and was seen in both true positive and false positive cases. A multivariate logistic regression model including aortic flow and isthmal displacement explained 78% of the variation in outcome and correctly predicted the need for intervention in 93% of cases. CONCLUSIONS: Reduced blood flow though the left heart is associated with important configurational changes at the aortic isthmus in fetal life, predisposing to CoA when the arterial duct closes after birth. Novel fetal MRI techniques may have a role in both understanding and accurately predicting severe neonatal CoA.

Reference Ranges for Pulsed-Wave Doppler of the Fetal Cardiac Inflow and Outflow Tracts from 13 to 36 Weeks' Gestation.

BACKGROUND: Doppler assessment of ventricular filling and outflow tract velocities is an integral part of fetal echocardiography, to assess diastolic function, systolic function, and outflow tract obstruction. There is a paucity of prospective data from a large sample of normal fetuses in the published literature. The authors report reference ranges for pulsed-wave Doppler flow of the mitral valve, tricuspid valve, aortic valve, and pulmonary valve, as well as heart rate, in a large number of fetuses prospectively examined at a single tertiary fetal cardiology center. METHODS: The study population comprised 7,885 fetuses at 13 to 36 weeks' gestation with no detectable abnormalities from pregnancies resulting in normal live births. Prospective pulsed-wave Doppler blood flow measurements were taken of the mitral, tricuspid, aortic, and pulmonary valves. The fetal heart rate was recorded at the time of each assessment. Regression analysis, with polynomial terms to assess for linear and nonlinear contributors, was used to establish the relationship between each measurement and gestational age. RESULTS: The measurement for each cardiac Doppler measurement was expressed as a Z score (difference between observed and expected values 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 inflow and outflow tracts. CONCLUSIONS: This study establishes reference ranges for fetal cardiac Doppler measurements and heart rate between 13 to 36 weeks' gestation that may be useful in clinical practice.

Childhood vascular phenotypes have differing associations with prenatal and postnatal growth.

OBJECTIVE: In children aged 8--9 years, we examined the associations of linear and abdominal circumference growth during critical stages of prenatal and postnatal development with six vascular measurements commonly used as early markers of atherosclerosis and later cardiovascular disease (CVD) risk. METHODS: In 724 children from the UK Southampton Women's Survey mother--offspring cohort, offspring length/height and abdominal circumference measurements were collected at 10 ages between 11 weeks' gestation and age 8--9 years. Using residual growth modelling and linear regression, we examined the independent associations between growth and detailed vascular measures made at 8--9 years. RESULTS: Postnatal linear and abdominal circumference growth were associated with higher childhood SBP and carotid--femoral pulse wave velocity, whereas prenatal growth was not. For example, 1SD faster abdominal circumference gain between ages 3 and 6 years was associated with 2.27 [95% confidence interval (CI): 1.56--2.98] mmHg higher SBP. In contrast, faster abdominal circumference gain before 19 weeks' gestation was associated with greater carotid intima--media thickness [0.009 mm (0.004--0.015) per 1SD larger 19-week abdominal circumference), whereas later growth was not. We found no strong associations between prenatal or postnatal growth and DBP or measures of endothelial function. CONCLUSION: Higher postnatal linear growth and adiposity gain are related to higher SBP and carotid--femoral pulse wave velocity in childhood. In contrast, faster growth in early gestation is associated with greater childhood carotid intima--media thickness, perhaps resulting from subtle changes in vascular structure that reflect physiological adaptations rather than subclinical atherosclerosis.

A Bayesian meta-analysis on early tobacco exposure and vascular health: From childhood to early adulthood.

BACKGROUND: Smoking has been consistently associated with increased cardiovascular risk in adults. Although exposure to tobacco products often starts in early life, evidence for the possible adverse effects on the cardiovascular system of the young is scarce. We sought to derive pooled estimates of smoking effects on indices of early vascular damage in children and adolescents. DESIGN AND METHODS: We performed a systematic review and meta-analysis of clinical studies involving young individuals up to 21 years old that provided data on smoking exposure (active or passive) and flow-mediated dilatation, carotid to femoral pulse wave velocity and maximum carotid intima-media thickness. We employed three distinct methodologies of random-effects data synthesis, including the Sidik-Jonkman estimator, the Hartung and Knapp correction and a Bayesian method with a well-informed prior on the level of between-study variance. RESULTS: In 12 studies and 5279 individuals in total, smoking exposure was related to deterioration in all three outcomes (mean adjusted flow-mediated dilatation decrease: -0.77%, 95% confidence interval -1.38--0.15, mean adjusted pulse wave velocity increase: 0.1 m/s, 95% confidence interval 0.02-0.17 and mean adjusted carotid intima-media thickness increase: 0.35 mm, 95% confidence interval 0.16-0.55, for the Sidik-Jonkman estimator). No difference was established between active and passive smoking on associations with arterial damage. CONCLUSIONS: Exposure to tobacco products is associated with subclinical vascular damage early in life, even from childhood. Public health initiatives should target these very young age groups to prevent early smoking exposure and associated arterial damage and its sequelae.

Prenatal incidence of isolated right aortic arch and double aortic arch.

OBJECTIVE: To define the incidence of variants of aortic arch sidedness in fetuses undergoing routine first trimester ultrasound examination. METHODS: The data for this study were derived from prospective routine ultrasound examination at 11+0 to 13+6 weeks' gestation in singleton pregnancies examined in a local population between January 2014 and March 2018. We examined the incidence of isolated right aortic arch (RAA) and double aortic arch (DAA) in the local, screened population and compared the groups with and without these abnormalities. RESULTS: The study population of 33,202 pregnancies included 18 (5.4 per 10,000) cases with isolated RAA and 5 (1.5 per 10,000) with DAA. In the group with isolated RAA or DAA, compared to those without, the median maternal age was higher and the incidence of conceptions from in vitro fertilization (IVF) was eight-fold higher. The prevalence of 22q11microdeletion was 5% in patients with RAA from this local population. CONCLUSIONS: The incidence of isolated RAA and DAA in a local population undergoing routine first-trimester ultrasound examination is 2-3-fold higher than that reported in postnatal studies and the risk for these abnormalities is substantially increased in fetuses conceived by IVF.

Estimating central blood pressure from aortic flow: development and assessment of algorithms.

Central blood pressure (cBP) is a highly prognostic cardiovascular (CV) risk factor whose accurate, invasive assessment is costly and carries risks to patients. We developed and assessed novel algorithms for estimating cBP from noninvasive aortic hemodynamic data and a peripheral blood pressure measurement. These algorithms were created using three blood flow models: the two- and three-element Windkessel (0-D) models and a one-dimensional (1-D) model of the thoracic aorta. We tested new and existing methods for estimating CV parameters (left ventricular ejection time, outflow BP, arterial resistance and compliance, pulse wave velocity, and characteristic impedance) required for the cBP algorithms, using virtual (simulated) subjects (n = 19,646) for which reference CV parameters were known exactly. We then tested the cBP algorithms using virtual subjects (n = 4,064), for which reference cBP were available free of measurement error, and clinical datasets containing invasive (n = 10) and noninvasive (n = 171) reference cBP waves across a wide range of CV conditions. The 1-D algorithm outperformed the 0-D algorithms when the aortic vascular geometry was available, achieving central systolic blood pressure (cSBP) errors ≤ 2.1 ± 9.7 mmHg and root-mean-square errors (RMSEs) ≤ 6.4 ± 2.8 mmHg against invasive reference cBP waves (n = 10). When the aortic geometry was unavailable, the three-element 0-D algorithm achieved cSBP errors ≤ 6.0 ± 4.7 mmHg and RMSEs ≤ 5.9 ± 2.4 mmHg against noninvasive reference cBP waves (n = 171), outperforming the two-element 0-D algorithm. All CV parameters were estimated with mean percentage errors ≤ 8.2%, except for the aortic characteristic impedance (≤13.4%), which affected the three-element 0-D algorithm's performance. The freely available algorithms developed in this work enable fast and accurate calculation of the cBP wave and CV parameters in datasets containing noninvasive ultrasound or magnetic resonance imaging data.NEW & NOTEWORTHY First, our proposed methods for CV parameter estimation and a comprehensive set of methods from the literature were tested using in silico and clinical datasets. Second, optimized algorithms for estimating cBP from aortic flow were developed and tested for a wide range of cBP morphologies, including catheter cBP data. Third, a dataset of simulated cBP waves was created using a three-element Windkessel model. Fourth, the Windkessel model dataset and optimized algorithms are freely available.

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 > 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 < 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 may be more appropriate for the identification of arterial disease before adulthood.