Preterm Birth, Kidney Function and Cardiovascular Disease in Children and Adolescents.

Over recent decades, there has been a global increase in preterm birth rate, which constitutes about 11% of total births worldwide. The present review aims to summarize the current knowledge on the long-term consequences of prematurity on renal and cardiovascular development and function. Recent literature supports that prematurity, intrauterine growth restriction or low birth weight (LBW) may have an adverse impact on the development of multiple organ systems, predisposing to chronic diseases in childhood and adulthood, such as arterial hypertension and chronic kidney disease. According to human autopsy and epidemiological studies, children born preterm have a lower nephron number, decreased kidney size and, in some cases, affected renal function. The origin of hypertension in children and adults born preterm seems to be multifactorial as a result of alterations in renal, cardiac and vascular development and function. The majority of the studies report increased systolic and diastolic blood pressure (BP) in individuals born preterm compared to full term. The early prevention and detection of chronic non-communicable diseases, which start from childhood and track until adulthood in children with a history of prematurity or LBW, are important.

Arterial stiffness and nocturnal hypertension in preterm children and adolescents.

BACKGROUND AND OBJECTIVES: Preterm birth has been associated with increased risk for developing hypertension and other chronic diseases during childhood and adulthood. The aim of the current prospective case-control study was to investigate the associations of preterm birth with ambulatory blood pressure (BP) levels and arterial stiffness during childhood and adolescence. METHODS: The study population included 52 children and adolescents born preterm and 26 healthy children born full term with similar age. The participants underwent ambulatory BP monitoring (ABPM) and assessment of carotid-femoral pulse wave velocity (PWV). RESULTS: Preterm children presented higher night SBP z score values compared to controls, but did not differ in other ABPM parameters, office peripheral and central SBPs. Nocturnal hypertension was found in 78% (7/9) of ex-preterm children with ambulatory BP hypertension. Preterm birth was an independent predictor of PWV z score adjusted for heart rate. Estimated marginal means for PWV z score adjusted for age, sex, presence of kidney disease at birth, office BPs, night BPs, central SBP, and BMI z scores were significantly higher in preterm individuals compared to controls (0.703, 95% confidence interval [CI] 0.431-0.975 versus -0.19, 95% CI -0.574-0.536, respectively, P  = 0.027). Preterm children who were overweight presented the highest values of night SBP and PWV z score. CONCLUSION: Preterm birth is associated with higher nocturnal BP and increased arterial stiffness in childhood and adolescence. Increased awareness for detection of hypertension and prevention of obesity in childhood could prevent future adverse cardiovascular outcomes in preterm individuals.

Subcutaneous Fat Necrosis and Hypercalcemia with Nephrocalcinosis in Infancy: Case Report and Review of the Literature.

Subcutaneous fat necrosis is an uncommon benign panniculitis affecting more commonly full-term newborns. It has been associated with birth asphyxia and meconium aspiration, as well as therapeutic hypothermia. Although the prognosis is generally favorable, complications such as hypercalcemia, thrombocytopenia, hypoglycemia and hypertriglyceridemia may complicate its course. The most serious complication is hypercalcemia that may reach life threatening levels and can be associated with nephrocalcinosis. We thereby describe a case of subcutaneous fat necrosis after therapeutic hypothermia, which presented with late-onset refractory severe hypercalcemia and persistent nephrocalcinosis during the follow up of the patient. Due to the risk of the development of chronic kidney disease, we highlight the importance of careful monitoring of hypercalcemia and review the literature of subcutaneous fat necrosis related to nephrocalcinosis.

Uric Acid Associates With Executive Function in Children and Adolescents With Hypertension.

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Estimated Arterial Stiffness and Prediction of Vascular Aging: The Rising of a New Era.

Arterial stiffness has been associated with cardiovascular events and correlated with cardiovascular risk factors. In the new guidelines of the European Society of Hypertension, the evaluation of arterial stiffness, and specifically carotid-femoral pulse wave velocity (c-f PWV), was taken into account for the detailed screening of the hypertensive population. Despite the importance of arterial stiffness as a target organ damage, the measurement is time-consuming, not practical, needs expensive equipment and experienced staff. For all these reasons, c-f PWV is not recommended for the everyday clinical practice and its current use is restricted for research purposes. The importance of arterial properties in clinical practice and cardiovascular prevention is well known. Hence, the estimation of arterial stiffness and vascular health based on parameters that affect arterial stiffness, but without the use of a machine, is a new promising field. Furthermore, the relationship between age-related MRI abnormalities as well as ultrafast ultrasound with vascular effect gives a new promise for future vascular aging assessment.

Arterial stiffness in children and adolescents with masked and sustained hypertension.

This study recruited 85 healthy children and adolescents, aged 6-18 years, from a school-based blood pressure (BP) screening study and performed office BP measurements, 24-h ambulatory blood pressure monitoring (24-h ABPM) and 24-h pulse wave analysis. Prevalence of BP phenotypes was assessed, factors that may predict hypertension (HTN) in ABPM were examined and the effect of BP phenotypes, as well as school, office, and ambulatory BP parameters on pulse wave velocity (PWV), was investigated. Forty-five (54.9%) of the children were normotensives, 8 (9.7%) were white coat hypertensives (WCH), 19 (23.2%) had masked hypertension (MH), and 10 (12.2%) had sustained HTN. Estimated adjusted marginal means for 24-h PWV were 4.79 m/s (95% CI 4.65-4.94) for sustained hypertensives, 4.72 m/s (95% CI 4.62-4.82) for MH, 4.38 m/s (95% CI 4.23-4.54) for WCH, and 4.33 m/s (95% CI 4.26-4.40) for normotensives (sustained hypertensives versus normotensives and WCH, p < 0.001, MH versus normotensives and WCH, p < 0.005). Neither body mass index (BMI) z-score nor school systolic BP (SBP) z-score could predict HTN by ABPM. Office SBP z-score was associated with 1.74 times increased odds ratio to have HTN in ABPM. Sustained HTN and MH were independent predictors of 24-h PWV after adjustment for age, sex, and BMI z-score. In conclusion, arterial stiffness in children and adolescents was assessed by 24-h PWV associates with mean ambulatory BP. Both school and office BP measurements could not predict HTN in ABPM or increasing PWV. HTN in ABPM was independently associated with the risk of higher PWV compared with normotensive and WCH phenotype.

Central SBP and executive function in children and adolescents with primary and secondary hypertension.

OBJECTIVES: The aims of the study were to assess executive function performance in children and adolescents with primary and secondary hypertension, and to investigate for associations with central SBP and ambulatory blood pressure. METHODS: Forty-six pediatric patients with secondary hypertension because of kidney diseases and 46 patients with primary hypertension underwent ambulatory blood pressure monitoring, pulse wave analysis, and assessment of executive function using Behavior Rating Inventory of Executive Function. Results for comparisons are presented as mean (SD). Analysis of covariance was performed to examine the effect of blood pressure parameters and hypertension cause. RESULTS: Patients with secondary hypertension had higher T scores in parent and self-reported Metacognition Indices compared with those with primary hypertension (51.2 ±â€Š8.9 vs. 47.6 ±â€Š7.5, P = 0.05 and 49.6 ±â€Š9.1 vs. 42.1 ±â€Š7.9, P = 0.001, respectively), but did not differ in Behavior Regulation Index T scores, as well as in mean arterial pressure z-score. Patients with secondary hypertension had higher central SBP z-scores (P = 0.05). Adjustment for central SBP attenuated differences in parent Metacognition Index between groups. Central SBP z-score associated with parent Metacognition (B = 0.95, 95% CI 0.02-1.87), Behavior Regulation (B = 1.14, 95% CI 0.07-2.21), and self-reported Metacognition Indices T scores (B = 1.48, 95% CI 0.39-2.56), independent of mean arterial pressure z-score, age, sex, socioeconomic status, hypertension cause, and antihypertensive treatment. CONCLUSION: Central SBP associates with executive function performance in youth with hypertension and could have complementary role to ambulatory blood pressure for identifying children at risk for adverse cognitive outcomes.

Ambulatory hemodynamic patterns, obesity, and pulse wave velocity in children and adolescents.

BACKGROUND: In recent years, pulse wave velocity (PWV) has emerged as a surrogate marker of cardiovascular disease in children with cardiovascular risk factors. The aims of the present study were to identify determinants of PWV in children according to their weight status and to investigate the role of peripheral blood pressure and central hemodynamic parameters in the association between PWV and obesity. METHODS: We included in the study healthy children and adolescents randomly selected from a school-based blood pressure screening study. All participants underwent ambulatory blood pressure monitoring and 24-h pulse wave analysis. RESULTS: Overweight and obese children had higher 24-h PWV, 24-h peripheral and central systolic blood pressure (SBP), and cardiac output than normal weight ones. Children with both overweight and hypertension presented the highest 24-h PWV values (p < 0.001). Peripheral and central SBP, body mass index (BMI), and hemodynamic parameters, including stroke volume, cardiac output, total peripheral resistance, and cardiac index, were all associated with 24-h PWV. However, in stepwise regression analysis, 24-h peripheral and central SBP and cardiac index, but not BMI, were independent predictors of 24-h PWV. There were statistically significant differences in 24-h blood pressure and hemodynamic parameters among those on the lower and highest 24-h PWV quartile, but there were no significant differences in BMI among 24-h PWV quartile groups. CONCLUSIONS: Arterial stiffness is higher in overweight and obese children in the co-presence of hypertension. Peripheral and central SBP are the main determinants of 24-h PWV independent of weight status. Graphical abstract.

Impact of ambulatory SBP and overweight on executive function performance in children and adolescents.

BACKGROUND AND AIM: Neurocognitive impairment has recently emerged as a hypertensive target organ damage in children and adolescents. In the present study, we aimed to examine the effect of hypertension and overweight on executive function performance in youth. METHODS: The study population included 116 consecutive children and adolescents referred to our outpatient hypertension clinic who underwent ambulatory blood pressure monitoring (ABPM) and assessment of executive function by Behavior Rating Inventory of Executive Function (BRIEF). RESULTS: Children and adolescents with hypertension presented higher T scores in shift sub-scale of Behavior Regulation Index (BRI) compared with normotensives. Participants with hypertension in the ABPM also presented higher T scores in subscales of metacognition (metacognition index). Night-time SBP correlated with BRI (r = 0.21, P < 0.05) and metacognition index (r = 0.19, P < 0.05) composite scales. BMI z score also correlated with BRI (r = 0.28, P < 0.005) and metacognition index (r = 0.22, P < 0.05) scales. The associations of night-time SBP with monitor and plan/organize subscales of metacognition index remained significant after adjustment for BMI z score and socioeconomical status. However, the associations of BMI z score with monitor scale was found to be mediated by night-time SBP. In ROC curve analysis, only night-time SBP could predict impaired performance in monitor and plan/organize scales (AUC 0.68 and 0.70, respectively). CONCLUSION: Night-time SBP may predict a poor performance in domains of executive function in youth. Although overweight/obese status was negatively associated with executive performance, mediation analysis showed that not obesity per se, but BP exerted negative impact on executive performance.

The challenge of simplifying blood pressure screening in children and adolescents.

Simplified methods of blood pressure screening could facilitate the clinical routine of the primary care physicians and may increase adherence to pediatric hypertension guidelines. Blood-pressure-to-height ratios are appealing for the simplicity of data needed to evaluate a child's blood pressure status, including only office blood pressure values and height. In several epidemiological studies around the world blood-pressure-to-height ratios showed good predictive power in identifying children with high blood pressure in terms of area under the curve and sensitivity compared to the gold standard National High Blood Pressure Education Program blood pressure tables, but low positive predictive values meaning a high rate of false-positive cases and possibly increased subsequent work load for primary physicians. Finally, blood-pressure-to height ratios seem to be dependent to age, sex, and weight status. In conclusion, blood-pressure-to-height ratios need to be further improved and validated in different pediatric populations before routine clinical use.

Secondary Hypertension in Children and Adolescents: Novel Insights.

Hypertension is a significant risk factor for cardiovascular morbidity and mortality, not only in adults, but in youths also, as it is associated with long-term negative health effects. The predominant type of hypertension in children is the secondary hypertension, with the chronic kidney disease being the most common cause, however, nowadays, there is a rising incidence of primary hypertension due to the rising incidence of obesity in children. Although office blood pressure has guided patient management for many years, ambulatory blood pressure monitoring provides useful information, facilitates the diagnosis and management of hypertension in children and adolescents, by monitoring treatment and evaluation for secondary causes or specific phenotypes of hypertension. In the field of secondary hypertension, there are numerous studies, which have reported a strong association between different determinants of 24-hour blood pressure profile and the underlying cause. In addition, in children with secondary hypertension, ambulatory blood pressure monitoring parameters offer the unique advantage to identify pediatric low- and high-risk children for target organ damage. Novel insights in the pathogenesis of hypertension, including the role of perinatal factors or new cardiovascular biomarkers, such as fibroblast growth factor 23, need to be further evaluated in the near future.

Neurological complications in childhood nephrotic syndrome: A systematic review.

BACKGROUND AND OBJECTIVE: Nephrotic syndrome (NS) in childhood can be accompanied by serious neurological complications increasing the morbidity of disease. The study aimed to assess the spectrum of neurological complications in children with in terms of clinical presentation, contributory risk factors, and outcome. METHODS: In this systematic review, we searched for articles in PubMed, providing individual patient-level data for any neurological complication in children and adolescents with primary NS, between January 1, 1990 and April 30, 2018. FINDINGS: The search yielded 63 articles, involving 103 patients. Events occurred more frequently during nephrotic state relapses; 71.6% of cerebral thromboembolic (TE) events and 81.2% of posterior reversible encephalopathy (PRES) cases. Median duration of disease before a cerebral TE event was 3 months (IQR 0-27), and 18 months (IQR 1-37.5) for PRES. Among cases with TE, 73.1% presented with cerebral sinovenous thrombosis (CSVT), and 16.9% parenchymal lesions. 70% of patients had a risk factor for neurological complication including NS-associated thrombophilia, hypertension, and treatment with immunosuppressive agents. Outcome was favorable in 93.8% of the patients with PRES. In patients with cerebral TE outcome was favorable in 95.8% of the cases with CSVT only, and in 64.7% of the cases with parenchymal lesions. CONCLUSIONS: Neurological complications may occur in children with primary NS and risk factors during nephrotic state relapses. The outcome for PRES has been reported favorable. Outcome in cerebral TE events may differ by the presence of venous or artery infarct. Recognition of additional protrombotic state risk factors may help to lower the incidence of neurological complications.

Sleep disorders and executive function in children and adolescents with chronic kidney disease.

OBJECTIVE: The impact of sleep-related disorders in children and adolescents with chronic kidney disease on executive function performance has been scarcely studied. The aims of the present study were to assess the prevalence of sleep-related disorders in chronic kidney disease pediatric patients, and to examine possible correlations with measures of executive function. METHODS: We performed a case-control study including 51 children with chronic kidney disease stages 2-5, aged 5-18 years, and 51 healthy controls. The parents of both patients and controls completed the Pediatric Seep Questionnaire (PSQ), and the Behavior Rating Inventory of Executive Function (BRIEF) questionnaire. RESULTS: Children with chronic kidney disease presented lower executive performance with higher scores in scales of executive function, and an increased risk of presenting a sleep-related disorder (odds ratio (OR) = 7.58, 95% confidence interval (CI) 2.36-24.31, p < 0.005) compared to controls. In the patient group, age of chronic kidney disease onset correlated with Behavior Regulation Index T-score (r = 0.32, p < 0.05). In multivariate analysis, differences between patients and controls for Metacognition Index T-scores did not persist after adjustment for sleep-related breathing disorder and insomnia scores, while differences in Behavior Regulation Index T-scores remained significant (54.15 vs 49.14, p < 0.02). Moreover, mediational analyses showed that sleep-related disorders mediated the effect of chronic kidney disease on metacognition, but not on behavioral regulation. CONCLUSION: Sleep-related disorders may in part explain the lower executive function performance during everyday life in chronic kidney disease pediatric patients. However, additional disease-related factors may influence executive function, especially in the domains of behavior regulation.

Comparison of the SphygmoCor XCEL device with applanation tonometry for pulse wave velocity and central blood pressure assessment in youth.

BACKGROUND: Vascular phenotype by assessing carotid-femoral pulse wave velocity (cf-PWV) and central SBP (cSP) in the young could be used as an intermediate cardiovascular outcome measure. Tonometry is considered the gold-standard technique, but its use is challenging in clinical practice, especially when used in children. The purpose of this study was to validate cf-PWV and cSP assessment with novel oscillometric device (SphygmoCor XCEL) in children and adolescents. METHODS: cf-PWV and cSP were measured in 72 children and adolescents aged 6-20 years. Measurements were performed by applanation tonometry and by the SphygmoCor XCEL device at the same visit under standardized conditions. Regression analysis and Bland-Altman plots were used for comparison of the tonometer-based with oscillometric-based method. RESULTS: Mean cf-PWV measured by applanation tonometry was 4.85 ±â€Š0.81 m/s and measured by SpygmoCor XCEL was 4.75 ±â€Š0.81 m/s. The mean difference between the two devices was 0.09 ±â€Š0.47 m/s (P = NS). cSP measured by SpygmoCor XCEL was strongly correlated with cSP measured by applanation tonometry (R = 0.87, P < 0.001). Mean cSP measured by applanation tonometry was 103.23 ±â€Š9.43 mmHg and measured by SpygmoCor XCEL was 103.54 ±â€Š8.87 mmHg. The mean cSP difference between the two devices was -0.30 ±â€Š3.34 mmHg (P = NS), and fulfilled the AAMI criterion 1. The estimated intersubject variability was 2.17 mmHg. CONCLUSION: The new oscillometric SphygmoCor XCEL device provides equivalent results for cf-PWV and cSP values to those obtained by tonometry in children and adolescents. Thus, the SphygmoCor XCEL device could be appropriate for assessing cf-PWV and cSP in the pediatric population.

Treatment of Hypertension Induced Target Organ Damage in Children and Adolescents.

High blood pressure in children and adolescents may have an adverse impact on the heart, the vessels, the kidney, and the central nervous system causing early functional or structural changes. The most prevalent subclinical hypertensive target organ damage in children and adolescents is left ventricular hypertrophy, and echocardiographic assessment of left ventricular mass is suggested in all hypertensive children. There is evolving evidence that antihypertensive treatment in children and adolescents could lead to regression of target organ damage, emphasizing also the importance of adequate blood pressure control. Assessment of subclinical organ damage could guide clinical decisions from diagnosis with regard to intensity non-pharmacological treatment, time to wait for initiation of pharmacological treatment, and choice of drug. Longitudinal studies are needed to relate the effectiveness of antihypertensive treatment and blood pressure targets in childhood with future cardiovascular or renal events. This review summarizes evidence on the associations of hypertension with target organ damage in children and adolescents and the role of antihypertensive therapy on the regression of target organ damage in the pediatric age group.