Predicting the earliest deviation in weight gain in the course towards manifest overweight in offspring exposed to obesity in pregnancy: a longitudinal cohort study.

BACKGROUND: Obesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify "high-risk" offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system. METHODS: This study uses data from the prospective mother-child cohort study Programming of Enhanced Adiposity Risk in CHildhood-Early Screening (PEACHES) comprising 1671 mothers with pre-conception obesity and without (controls) and their offspring. Exposures were pre- and postnatal risks documented in patient-held maternal and child health records. The main outcome was a "higher-than-normal BMI growth pattern" preceding overweight, defined as BMI z-score >1 SD (i.e., World Health Organization [WHO] cut-off "at risk of overweight") at least twice during consecutive offspring growth periods between age 6 months and 5 years. The independent cohort PErinatal Prevention of Obesity (PEPO) comprising 11,730 mother-child pairs recruited close to school entry (around age 6 years) was available for data validation. Cluster analysis and sequential prediction modelling were performed. RESULTS: Data of 1557 PEACHES mother-child pairs and the validation cohort were analyzed comprising more than 50,000 offspring BMI measurements. More than 1-in-5 offspring exposed to obesity in pregnancy belonged to an upper BMI z-score cluster as a distinct pattern of BMI development (above the cut-off of 1 SD) from the first months of life onwards resulting in preschool overweight/obesity (age 5 years: odds ratio [OR] 16.13; 95% confidence interval [CI] 9.98-26.05). Contributing early-life factors including excessive weight gain (OR 2.08; 95% CI 1.25-3.45) and smoking (OR 1.94; 95% CI 1.27-2.95) in pregnancy were instrumental in predicting a "higher-than-normal BMI growth pattern" at age 3 months and re-evaluating the risk at ages 1 year and 2 years (area under the receiver operating characteristic [AUROC] 0.69-0.79, sensitivity 70.7-76.0%, specificity 64.7-78.1%). External validation of prediction models demonstrated adequate predictive performances. CONCLUSIONS: We devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in "high-risk" infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care.

Late-pregnancy dysglycemia in obese pregnancies after negative testing for gestational diabetes and risk of future childhood overweight: An interim analysis from a longitudinal mother-child cohort study.

BACKGROUND: Maternal pre-conception obesity is a strong risk factor for childhood overweight. However, prenatal mechanisms and their effects in susceptible gestational periods that contribute to this risk are not well understood. We aimed to assess the impact of late-pregnancy dysglycemia in obese pregnancies with negative testing for gestational diabetes mellitus (GDM) on long-term mother-child outcomes. METHODS AND FINDINGS: The prospective cohort study Programming of Enhanced Adiposity Risk in Childhood-Early Screening (PEACHES) (n = 1,671) enrolled obese and normal weight mothers from August 2010 to December 2015 with trimester-specific data on glucose metabolism including GDM status at the end of the second trimester and maternal glycated hemoglobin (HbA1c) at delivery as a marker for late-pregnancy dysglycemia (HbA1c ≥ 5.7% [39 mmol/mol]). We assessed offspring short- and long-term outcomes up to 4 years, and maternal glucose metabolism 3.5 years postpartum. Multivariable linear and log-binomial regression with effects presented as mean increments (Δ) or relative risks (RRs) with 95% confidence intervals (CIs) were used to examine the association between late-pregnancy dysglycemia and outcomes. Linear mixed-effects models were used to study the longitudinal development of offspring body mass index (BMI) z-scores. The contribution of late-pregnancy dysglycemia to the association between maternal pre-conception obesity and offspring BMI was estimated using mediation analysis. In all, 898 mother-child pairs were included in this unplanned interim analysis. Among obese mothers with negative testing for GDM (n = 448), those with late-pregnancy dysglycemia (n = 135, 30.1%) had higher proportions of excessive total gestational weight gain (GWG), excessive third-trimester GWG, and offspring with large-for-gestational-age birth weight than those without. Besides higher birth weight (Δ 192 g, 95% CI 100-284) and cord-blood C-peptide concentration (Δ 0.10 ng/ml, 95% CI 0.02-0.17), offspring of these women had greater weight gain during early childhood (Δ BMI z-score per year 0.18, 95% CI 0.06-0.30, n = 262) and higher BMI z-score at 4 years (Δ 0.58, 95% CI 0.18-0.99, n = 43) than offspring of the obese, GDM-negative mothers with normal HbA1c values at delivery. Late-pregnancy dysglycemia in GDM-negative mothers accounted for about one-quarter of the association of maternal obesity with offspring BMI at age 4 years (n = 151). In contrast, childhood BMI z-scores were not affected by a diagnosis of GDM in obese pregnancies (GDM-positive: 0.58, 95% CI 0.36-0.79, versus GDM-negative: 0.62, 95% CI 0.44-0.79). One mechanism triggering late-pregnancy dysglycemia in obese, GDM-negative mothers was related to excessive third-trimester weight gain (RR 1.72, 95% CI 1.12-2.65). Furthermore, in the maternal population, we found a 4-fold (RR 4.01, 95% CI 1.97-8.17) increased risk of future prediabetes or diabetes if obese, GDM-negative women had a high versus normal HbA1c at delivery (absolute risk: 43.2% versus 10.5%). There is a potential for misclassification bias as the predominantly used GDM test procedure changed over the enrollment period. Further studies are required to validate the findings and elucidate the possible third-trimester factors contributing to future mother-child health status. CONCLUSIONS: Findings from this interim analysis suggest that offspring of obese mothers treated because of a diagnosis of GDM appeared to have a better BMI outcome in childhood than those of obese mothers who-following negative GDM testing-remained untreated in the last trimester and developed dysglycemia. Late-pregnancy dysglycemia related to uncontrolled weight gain may contribute to the development of child overweight and maternal diabetes. Our data suggest that negative GDM testing in obese pregnancies is not an "all-clear signal" and should not lead to reduced attention and risk awareness of physicians and obese women. Effective strategies are needed to maintain third-trimester glycemic and weight gain control among otherwise healthy obese pregnant women.

Reduced arterial stiffness in very fit boys and girls.

Low cardiorespiratory fitness is associated with higher cardiovascular risk, whereas high levels of cardiorespiratory fitness protect the cardiovascular system. Carotid intima-media thickness and arterial distensibility are well-established parameters to identify subclinical cardiovascular disease. Therefore, this study investigated the influence of cardiorespiratory fitness and muscular strength on carotid intima-media thickness and arterial distensibility in 697 children and adolescents (376 girls), aged 7-17 years. Cardiorespiratory fitness and strength were measured with the test battery FITNESSGRAM; carotid intima-media thickness, arterial compliance, elastic modulus, stiffness index ß, and pulse wave velocity ß were assessed by B- and M-mode ultrasound at the common carotid artery. In bivariate correlation, cardiorespiratory fitness was significantly associated with all cardiovascular parameters and was an independent predictor in multivariate regression analysis. No significant associations were obtained for muscular strength. In a one-way variance analysis, very fit boys and girls (58 boys and 74 girls>80th percentile for cardiorespiratory fitness) had significantly decreased stiffness parameters (expressed in standard deviation scores) compared with low fit subjects (71 boys and 77 girls<20th percentile for cardiorespiratory fitness): elastic modulus -0.16±1.02 versus 0.19±1.17, p=0.009; stiffness index ß -0.15±1.08 versus 0.16±1.1, p=0.03; and pulse wave velocity ß -0.19±1.02 versus 0.19±1.14, p=0.005. Cardiorespiratory fitness was associated with healthier arteries in children and adolescents. Comparison of very fit with unfit subjects revealed better distensibility parameters in very fit boys and girls.

Obese Nondiabetic Pregnancies and High Maternal Glycated Hemoglobin at Delivery as an Indicator of Offspring and Maternal Postpartum Risks: The Prospective PEACHES Mother-Child Cohort.

BACKGROUND: We investigated whether obese pregnant women negative for gestational diabetes (GDM) still experience dysglycemia, as indicated by high glycated hemoglobin (Hb A1c) at delivery, and whether this impacts offspring and long-term maternal outcomes. METHODS: Data of 462 mother-child pairs of our prospective Programming of Enhanced Adiposity Risk in Childhood - Early Screening (PEACHES) cohort study were analyzed. Of 885 obese and normal-weight pregnancies prospectively enrolled after GDM testing according to the International Association of Diabetes and Pregnancy Study Groups criteria, 462 GDM-negative mothers and their offspring were investigated. We assessed associations of maternal Hb A1c at delivery with large-for-gestational-age (LGA) birth weights, cord-blood C-peptide, and biomarkers of glucose metabolism and inflammation in obese mothers followed for 2.9 years (median) postpartum (n = 42). RESULTS: Cumulative distribution analysis in GDM-negative normal-weight women (n = 155) revealed that 12% had Hb A1c ≥5.7% at delivery (high Hb A1c). Among obese GDM-negative women (n = 307), 31.9% (95% CI, 26.7%-37.4%) equaled or exceeded this cutoff. In obese GDM-negative women with Hb A1c ≥5.7% (n = 98) vs <5.7% (n = 209) at delivery, newborns were more likely to be born LGA [adjusted odds ratio 3.56 (95% CI, 1.64-8.02)], and mean cordblood serum C-peptide was increased by 0.09 ng/mL (95% CI, 0.01-0.17 ng/mL). In the mothers at follow-up, mean postpartum Hb A1c, fasting glucose, high-sensitivity C-reactive protein, and fibrinogen concentrations were higher by 0.3% (95% CI, 0.1%-0.5%), 6.0 mg/dL (95% CI, 2.4-9.5 mg/dL), 6.8 mg/L (95% CI, 1.4-12.3 mg/L), and 74.9 mg/dL (95% CI, 13.6-136.2 mg/dL), respectively. CONCLUSIONS: Increased Hb A1c in obese GDM-negative women at delivery indicates gestational dysglycemia, potentially conferring offspring and long-term maternal health risks. These findings should raise awareness as to careful monitoring of obese pregnancies. Measurement of Hb A1c at delivery could help select women who may need closer postpartum health checks.

An unusual form of supracardiac total anomalous pulmonary venous return via a right-sided vertical vein in a heterotaxy syndrome case.

Heterotaxy syndromes comprise a great variety of possible cardiac defects. Anomalies of the pulmonary venous system are well recognized in heterotaxy syndromes but constitute a frequently underdiagnosed subgroup. The case report describes a girl with a rare form of supracardiac total anomalous pulmonary venous return via a right-sided vertical vein to the right innominate vein in heterotaxy syndrome with dextrocardia, unbalanced atrioventricular septal defect with severe left ventricular hypoplasia, and transposition of the great arteries with pulmonary stenosis. Careful evaluation and imaging before surgical repair is crucial for such complex cardiac anomalies.

Pediatric heart transplantation in infants and small children under 3 years of age: Single center experience - "Early and long-term results".

OBJECTIVES: We analyzed the early and long-term survival after ABO-compatible heart transplantation in children under 3 years of age from 1991 to 2021 at our center. This retrospective and descriptive study aimed to identify serious adverse events associated with mortality after pediatric heart transplantation. PATIENTS AND METHODS: 46 patients with congenital heart failure (37%) in end-stage heart failure have undergone a pediatric heart transplantation. Primary outcome of interest was survival at follow-up time. RESULTS: Median (IQR) follow-up time (y), age (y), body-weight (kg) and BMI (kg/cm2) were 13.2 (5.7-19.5), 0.9 (0.2-2.0), 6.8 (4.3-10.0) and 14.2 (12.3-15.7). Twenty-four (52%) patients were male. 15 patients (33%) had a single ventricle physiology. At 30- days survival rate was 94 ± 4%. Survival rate at 1, 5, 10 and 15 years post HTx was 87 ± 5%, 84 ± 6%, 79 ± 6% and 63 ± 8%. One child underwent re-transplantation after 4 years, and another one after 11 years - in both cases due to graft failure. Higher early mortality in patients under 3 months of age and in patients with single ventricle physiology. Transplant free survival at 15 years was in children with cardiomyopathy better (71 ± 10%) than in those with congenital heart disease (50 ± 13%). One or more previous heart surgeries prior to HTx (n = 21) were associated to more mortality. CONCLUSION: Pediatric heart transplantation has acceptable long-term results and is still the best therapeutic option in children with end-stage cardiac failure. Underlying anomalies and single ventricle physiology, age below 3 months had a significant impact on survival.

The effect of cardiovascular risk factors on the longitudinal evolution of the carotid intima medial thickness in children with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus is a generally accepted atherogenic risk factor. The aim of this prospective longitudinal study was to evaluate changes in carotid intima media thickness (cIMT) in children and adolescents with type 1 diabetes mellitus (T1DM) using standardized methods. METHODS: We re-evaluated cIMT in 70 (38 f) of initial 150 (80 f) patients with T1DM after 4 years. At re-evaluation, mean (±SD) age was 16.45±2.59 y, mean diabetes duration was 9.2±3.24 y and patients had a mean HbA1c of 8.14±1.06%. RESULTS: Mean cIMT z-scores increased significantly during 4 years (0.58±0.75, p<0.001) as well as BMI-z-score (0.41±0.81, p<0.01), systolic blood pressure (0.77±1.15, p<0.01) and HbA1c (0.90±1.07, <0.001). In a linear regression model systolic blood pressure z-score at first measurement (0.02, CI: 0.01, 0.04) was a significant predictor for the mean effect on cIMT z-score. In a logistic regression model significant risk factors for an increase in IMT of ≥1.5 z-scores were BMI z-scores (OR: 3.02, CI:1.11, 10.14), diabetes duration (OR:1.32, CI:1.04, 1.77) and systolic blood pressure (OR: 1.14, CI: 1.04, 1.27) at first measurement each. CONCLUSIONS: Longitudinal cIMT measurements revealed progression in subclinical atherosclerosis during a four year period in diabetic children and adolescents. Systolic blood pressure and BMI were related to cIMT increment. Control of these risk factors by lifestyle and medical intervention may prevent progression of cIMT in diabetic children.

Hypertension after heart and heart/lung transplantation in childhood--study on the evolution of short-term blood pressure regulation.

Arterial hypertension complicates the follow-up of heart- and heart/lung-transplanted children. We investigated the evolution of BRS as short-time BP regulation mechanism and BP after heart and heart/lung transplantation. Twenty patients (15 males; mean age 15.1 ± 4.3 yr) were studied twice at intervals of 2.96 ± 0.87 yr. BRS was calculated using non-invasive beat-to-beat BP measurement system. HRV was calculated (LF, sympathetic influence; HF, parasympathetic influence). BRS increased in 10 patients (3.67 ± 1.43 ms/mmHg vs. 7.59 ± 3.40 mmHg, p = 0.005) (group 1). Six of 10 patients received antihypertensive medication. BRS decreased or remained unchanged in 10 patients (8.93 ± 7.9 ms/mmHg vs. 5.32 ± 6.6 ms/mmHg, p = 0.008) (group 2) with 9/10 patients necessitating antihypertensive medication. Group 1 showed LF/HF increase (LF/HF 1.03 ± 0.9 vs. 4.36 ± 2.32, p = 0.03); group 2 showed LF/HF decrease (LF/HF 3.7 ± 2.1 vs. 1.84 ± 1.1, p = 0.023). Evolution of BRS after heart and heart/lung transplantation in childhood seems to influence the necessity of antihypertensive medication. With time, increasing short-time BP regulation involving sympathetic reinnervation may improve BP.

Impaired cellular immune response to diphtheria and tetanus vaccines in children after thoracic transplantation.

Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p < 0.001), with more patients having protective antibody levels against diphtheria (p < 0.02) and tetanus (p < 0.001). There was no increased proliferation in non-stimulated or stimulated cultures after vaccination. The number of T-lymphocytes activated by the vaccination antigens was similar pre- and post-vaccination, whereas HLA-DR-expression on stimulated and non-stimulated CD4(+) T-cells increased significantly. Increase in antibodies was negatively correlated with tacrolimus dose, and impaired cellular immunity was associated with higher tacrolimus dose and steroid use. Adverse events were similar to the general population; serious adverse events and rejection did not occur. Vaccination with inactivated vaccines can be performed safely in immunosuppressed children after thoracic transplantation and induces protective antibody levels in the majority of patients. Impaired induction of specific cellular immunity is correlated with intensity of immunosuppression and may explain reduced sustainability of antibodies.

Preclinical evaluation of a new self-expanding device for closure of muscular ventricular septal defects in a pig model.

OBJECTIVES: Aim of our study was the preclinical evaluation of a new self expanding device for interventional closure of muscular ventricular septal defects (mVSDs) in an acute pig model. BACKGROUND: Devices currently in use for closure of mVSDs still have their limitations. The deployment of the disks is dependent from the expansion of the stent, which can be associated with problems for sufficient closure of the mVSDs. This was the reason for developing a modified device with only one disk MATERIALS AND METHODS: The device was constructed in a single wire technique with a unique configured retention disk. mVSDs were created in six pigs with a specially designed punch instrument, and subsequently closed with our new device during the same session using a jugular or femoral vein approach. Potential residual shunting volumes were estimated by echocardiography and hemodynamic measurements. After closure, animals were sacrificed, and hearts were harvested for macropathologic evaluation. In two animals, MRI was performed for additional noninvasive evaluation. RESULTS: Devices were successfully implanted in all animals with good alignment of the disk to the left ventricular septum, even if the stent was oversized. Echocardiography, hemodynamics, angiography and macropathology revealed complete closure of all mVSDs. MRI and echocardiography showed a good visibility of the device. CONCLUSIONS: Our preclinical study shows successful closure of iatrogenic created mVSDs without residual shunting. The device is characterized by a more controlled deployment, an independent deployment of disk and waist, and a good alignment of the left ventricular disk to the muscular septum.

Subclinical atherosclerosis in diabetic children: results of a longitudinal study.

CONTEXT: Cardiovascular disease caused by atherosclerosis is a major cause of morbidity and mortality in adult diabetic patients. In children, we detected signs of subclinical atherosclerosis in a large patient cohort. This study reports the results of a longitudinal observation in this patient group. PATIENTS AND METHODS: Of the 37/150 diabetic children in whom an increased intima-media thickness (IMT) of the carotid artery had been found, 27 (mean age 14.6 +/- 2.6 yrs) could be reevaluated 2 yrs after the initial study. Of the 27, 5 patients were on medication with angiotensin-converting enzyme (ACE) inhibitors, and all patients underwent detailed counselling of their lifestyle, sports activity, and nutritional habits. RESULTS: Mean IMT increased significantly (0.49 +/- 0.02 mm vs. 0.51 +/- 0.026 mm, p < 0.05) However, there was no significant change compared to normal values (mean IMT z-score 2.4 +/- 0.3 vs. 2.6 +/- 0.5). Of the 27, 13 patients (48%) showed a progression of the IMT whereas in 14/27 patients the IMT values remained stable. In these subgroups, patients with IMT progression showed a higher hemoglobin A1c (HbA1c) (7.5 +/- 0.8 vs. 7.1 +/- 0.7, p < 0.05) and a slightly higher systolic blood pressure (120 +/- 14.4 vs. 113.9 +/- 12.1, p = 0.08). CONCLUSIONS: In a well-selected group of diabetic children, mean IMT progression during a 2-yr period did not exceed the physiological increase. Children with a higher HbA1c and a higher systolic blood pressure showed a progression of the IMT. Control of atherogenic risk factors in diabetic children may help to avoid subclinical atherosclerosis progression.

Lack of serologic immunity against vaccine-preventable diseases in children after thoracic transplantation.

We investigated whether children after heart- (HTx) or heart-lung transplantation (HLTx) show protective antibody levels against recommended vaccinations, whether vaccination schedules are completed and which factors influence serologic immunity. We performed a cross sectional ELISA - quantification of specific antibodies in 46 patients after pediatric thoracic Tx. Findings were correlated to vaccination history, age at Tx, clinical course and immunosuppressive regimen. We found protective antibody levels against diphtheria in 74% of patients, against tetanus in 22%, against Haemophilus influenzae type b in 30% and against Streptococcus pneumoniae in 59%. Antibody concentrations against live attenuated vaccines were significantly lower in children transplanted in the first 2 years of life. Antibodies were absent for measles in 55% of late - and 81% of early transplanted children, for mumps in 66%/94%, for rubella in 30%/56% and for Varicella in 34%/63%. We found significant correlation of low antibody concentrations and age at Tx. Patients without protective antibody concentrations had significantly longer use of steroids. Vaccination schedules were incomplete or delayed in the majority of patients associated with more days in hospital pre-Tx. Our study shows that closer adherence to pretransplantation vaccination schedules and also post-transplantation monitoring of antibody levels are required in transplant patients.

Modification of a hybrid technique for closure of muscular ventricular septal defects in a pig model.

OBJECTIVE: Closure of muscular ventricular septal defects (mVSDs) beyond the moderator band is still a challenge for both surgeons and interventional cardiologists. We evaluated a new technique in a pig model for hybrid patch closure of mVSDs via 2 stab wound incisions in the left ventricle (LV) without cardiopulmonary bypass. METHODS: Ten pigs underwent left anterolateral thoracotomy to expose the LV. mVSDs were created via a stab wound incision of the lateral wall of the LV under epicardial echocardiographic control. The patch system was forwarded through a second puncture of the LV apex and positioned in front of the mVSD. The stapler for fixation of the patch was introduced through the same incision as used for VSD creation. Finally, the patch was attached to the septum with nitinol anchors under epicardial echocardiographic and fluoroscopic guidance. Finally, detailed echocardiographic evaluation was done. All hearts were explanted, and macroscopic evaluation was done, either immediately after patch implantation (n = 4) or after 90 days (n = 6). RESULTS: mVSD creation was successful in all pigs. Closure of mVSDs was successful in 8 of 10 pigs, as confirmed by echocardiography, hemodynamic measurements, and macroscopic examination. One patch embolized through the mVSD into the pulmonary artery because of insecure fixation, and 1 animal died during the procedure because of ventricular fibrillation. The final echocardiographic evaluation revealed good LV function and no damage to the valves. CONCLUSIONS: Closure of mVSDs can be successfully performed in a hybrid technique on the beating heart with 2 stab wound incisions; however, further modifications need to be developed before clinical application.

Paediatric heart transplantation - the impact of a ventricular assist device on operative outcomes.

BACKGROUND: The use of a ventricular assist device (VAD) is a life-saving option for patients with heart failure refractory to conventional therapy. AIM: To assess the effect of VAD on outcomes of heart transplantation in children. METHODS: Between October 1988 and June 2009, a consecutive series of 95 children (mean age 8.6 + or - 6.7 years, range 5 days-17.9 years) underwent heart transplantation: patients in group 1 (n = 11) received VAD as a bridge to cardiac transplantation (left ventricular VAD in 4, biventricular VAD in 7), and patients in group 2 (n = 84) underwent heart transplantation without previous cardiac support using VAD. The indication for heart transplantation was cardiomyopathy/myocarditis in 66 (69.5%) of children and congenital heart disease in 29 (30.5%) patients. RESULTS: Congenital heart disease was diagnosed more often in group 2 than in group 1 (p = 0.047). The two groups did not differ significantly with respect to age, weight and parameters of preoperative liver and kidney function (except for aspartate aminotransferase activity, p = 0.020). The mean waiting time for transplantation was 64.2 + or - 87.4 days (range 1-443 days) and did not differ between the groups. The mean follow-up was 6.8 + or - 5.4 years (range 1 day-17.6 years). Mortality during long-term follow-up was 9.1% (n = 1) in group 1 and 20.2% (n=17) in group 2 (p = 0.632). We found no significant differences in postoperative ventilatory support time (p = 0.773), duration of hospital stay (p = 0.853), and incidence of acute rejection episodes (p = 0.575). CONCLUSIONS: The use of VAD as a bridge to heart transplantation in children with severe heart failure had no negative effect on treatment outcomes.

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG.

BACKGROUND: Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. MATERIALS AND METHODS: Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. RESULTS: None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, p<0.05, respectively). We conclude that exercise testing and 24-h ECG recording provide valuable information about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

Off-pump extraanatomic bypass from the ascending to the descending aorta for re-operation of interrupted aortic arch in an adolescent.

The appearance of re-stenosis after repair of an interrupted aortic arch may be a surgical challenge due to adhesions. Here, we describe an approach using off-pump coronary artery bypass grafting techniques to reach the descending aorta through a median sternotomy in a patient with aortic arch stenosis after conduit repair. The 17-year-old patient with diagnoses of interrupted aortic arch and ventricular septal defect presented after two previous operations (one left lateral thoracotomy and one median sternotomy) with a stenosed vascular graft between ascending and descending aorta. Surgery was done via re-sternotomy without cardio-pulmonary bypass. An extraanatomic graft was used to connect ascending and descending aorta. When performing the distal anastomosis, the heart was exposed using a standard suction device. This case demonstrates that the use of modern techniques may facilitate surgical approaches dramatically. In our opinion the above-described technique is the first choice for all patients requiring arch repair following multiple previous operations, performed via sternotomy and thoracotomy.

Subclinical atherosclerosis after heart and heart-lung transplantation in childhood.

Children after heart transplantation are considered as at-risk patients for extracardiac atherosclerotic complications. Noninvasive ultrasound measurement of the common carotid artery (IMT) provides valid information about the endothelial structure of the vascular system. Twenty-two patients (17 male, mean age 12.4 +/- 4.5 yr) after heart and (5.7 +/- 4.5 yr) heart-lung transplantation were enrolled. The mean IMT was measured and compared with a control group (18 children, 10 male, mean age 11.8 +/- 1.8 yr) and to normative data. Transplanted children had a higher IMT than controls (0.453 +/- 0.003 vs. 0.424 +/- 0.002 mm, p < 0.001). IMT-SDS was increased as well (1.6 +/- 0.1 vs. 0.8 +/- 0, p < 0.001). Transplanted children had a higher LDL/HDL-ratio (2.2 +/- 0.2 vs. 1.2 +/- 0.1, p < 0.001). Time after transplantation, age at the time of transplantation, or medical therapy did not influence the findings. We found evidence for subclinical atherosclerosis in children after heart and heart-lung transplantation. Even if single atherosclerotic risk factors could not be identified, transplanted children seem to be at risk for atherosclerosis. Our findings support the recently published statement of the AHA-Expert panel: after heart transplantation atherosclerotic complications may occur with increased incidence. We propose the IMT-measurement in these patients as an easy method to assess the vascular status and to guide preventive measures.

Age of onset of type 1 diabetes in children and carotid intima medial thickness.

CONTEXT: Cardiovascular disease due to atherosclerosis is a major cause of morbidity and mortality in adult diabetic patients. In children, signs of subclinical atherosclerosis such as increased intima-media thickness (IMT) of the common carotid arteries have been detected in several studies. However, concerns may arise about the different analyzing methods used because measurements in patients and controls differ significantly. PATIENTS AND METHODS: We studied 208 children [150 patients with diabetes mellitus type 1, mean age (+/-sd) 13.9 +/- 2.8 yr, 66 males, mean glycosylated hemoglobin (+/-sd) 7.8 +/- 1.4%, and 58 healthy controls, mean age (+/-sd) 14.1 +/- 3.1 yr, 32 males] and used normal IMT values published recently for comparison of the results. RESULTS: Of 150 patients, 37 had an increased IMT [mean IMT (+/-sd) 1.6 +/- 0.6], whereas healthy controls had nearly normal IMT values [mean IMT (+/-sd) 0.3 +/- 0.1; P < 0.001]. Age at onset of diabetes, mean daily insulin dosage, systolic blood pressure, and total cholesterol level were significantly related to IMT in a multilinear regression model. A total of 25 diabetic patients were hypertensive and had a significantly increased IMT (mean IMT 0.475 +/- 0.03 mm) compared to the remaining patients (mean IMT 0.459 +/- 0.02 mm; P < 0.05). CONCLUSIONS: The IMT measurement detected subclinical atherosclerosis in a large cohort of diabetic children. Systolic blood pressure, total cholesterol level, insulin dosage, and age at onset of the disease were significantly related to the IMT. Longitudinal measurements may help to identify patients at special risk for atherosclerotic changes and cardiovascular disease.

Subclinical atherosclerosis, but normal autonomic function after Kawasaki disease.

OBJECTIVE: To compare the carotid artery intima-media-thickness (IMT) of children with Kawasaki disease with normative data for Western children. STUDY DESIGN: Forty-eight children (20 patients after Kawasaki disease, mean age 12.1 +/- 4.7 years; 28 age- and sex-matched healthy controls, mean age 12.0 +/- 3.1 years) were studied. RESULTS: Mean (IMT differed significantly (0.449 +/- 0.02 vs 0.424 +/- 0.01, P < .001) as well as IMT standard deviation score (1.2 +/- 0.6 vs 0.3 +/- 0.1, P < .001). Patients with coronary arterial involvement (n = 15) showed a further increase of the IMT (0.459 +/- 0.01 vs 0.436 +/- 0.01, P < .05). There was no difference regarding short-term blood pressure regulation. CONCLUSIONS: In this small patient group, signs of subclinical atherosclerosis after Kawasaki disease have been detected. These preliminary data indicate that these patients may be at risk for cardiovascular disease even in the absence of permanent alterations of the coronary arteries.

Hypertension in heart and heart-lung transplanted children: does impaired baroreceptor function play a role?

BACKGROUND: Baroreceptor control of beat-to-beat blood pressure in heart and heart-lung-transplanted children is impaired. Time-related trends of baroreceptor function recovery are studied and a possible correlation of baroreflex impairment and systolic hypertension may give evidence for supplemental medical treatment of hypertension. METHODS: Seventeen patients (six female) 6.1 +/- 3.7 years (range 0.8-13.0 years) after heart (n = 14) and heart-lung (n = 3) transplantation (TX) were studied. Twelve healthy children and 10 children after liver and bone marrow TX taking cyclosporine A (CyA) served as control groups 1 and 2, respectively. Baroreceptor sensitivity (BRS) was calculated from noninvasive systolic beat-to-beat blood pressure (sBP) measurement during a resting phase and a tilt-table test. RESULTS: BRS was significantly impaired in the study group at rest and during tilting; mean sBP was slightly elevated. Significant difference between patients on CyA and healthy controls was not observed. Discrete recovery of BRS occurred after 4 years postTX with decreased sBP (n = 12 pts, BRS 6.78 +/- 7.44 msec/mmHg, sBP 116.2 +/- 12.4 mmHg) when compared to a postTX time course of less than 4 years (n = 5 pts, BRS 4.02 +/- 4.21 msec/mmHg, sBP 122.0 +/- 6.7 mmHg, P = NS). CONCLUSION: BRS is disturbed after TX in children; four years postTX, a minimal recovery of BRS and a discrete reduction of sBP seem to occur. Those patients with a persistent low BRS and elevated sBP may profit from pharmacological influence in sympathovagal imbalance.