Awareness and knowledge of heterozygous familial hypercholesterolemia among Serbian pediatricians.

Objective: Published reports describing awareness and knowledge of familial hypercholesterolemia (FH) among pediatricians are few and differ considerably across countries. We aimed to assess awareness and knowledge of the FH among pediatricians in Serbia. Methods: A web-based cross-sectional study using a self-designed questionnaire was conducted during the annual congress of the Serbian Association of Preventive Pediatrics in 2020. Results: A total of 141 pediatricians completed the questionnaire (response rate 16.1%). Overall, 91% of participants have knowledge about genetic inheritance of FH, 84.3% were aware of long-term health risks of FH, 77% were familiar with normal cholesterol values in children and 71% knew the FH prevalence in the general population. On the other hand, only 36.8% declared that they were familiar with international guidelines for FH drug treatment and only 26.2% declared to have patients with FH. Conclusion: There is a substantial lack of practical clinical knowledge among Serbian pediatricians on managing children with FH. In addition, an extremely low questionnaire response rate (16.1%) suggests that most pediatricians are not aware of the clinical importance of FH in childhood.

Hypovitaminosis D in infants: Evidence that increased intake of vitamin D reduces the incidence of allergic and respiratory disorders.

AIM: The study assessed the relationship between vitamin D status in infants and the presence of allergic and/or respiratory disorders. MATERIALS AND METHODS: The study cohort comprised 81 hospitalized infants presenting at the Pediatric Clinic, University Clinical Center Kragujevac, Serbia, between January 2011 and June 2016. RESULTS: The age of the infants ranged from 29 days to 12 months. All infants received prophylactic doses of vitamin D3 of 400 IU/daily until the end of the first year of life regardless of whether they are fed with adapted infant formula (n = 20) or breast milk (n = 37) or concurrently both (n = 24), up to the 5th month of life. The mean level of plasma 25(OH)D was 29.65 ng/mL. Hypovitaminosis D (mean serum level of 25(OH)D < 30 ng/mL) was found in n = 38 infants of which 6 presented with severe vitamin D deficiency (level below 10 ng/mL), 13 presented with vitamin D deficiency (level between 10 and 20 ng/mL) and 19 had vitamin D insufficiency (levels between 20 and 30 ng/mL). The median vitamin D serum level in infants with allergic disease (n = 16) was 32.35 ng/mL and in infants with respiratory disease (n = 65) 28.99 ng/mL. CONCLUSION: Daily vitamin D3 supplementation with 400 IU in infants until the end of the first year of life is too low to provide optimal defense against respiratory and/or allergic conditions.

Prevalence of left ventricular hypertrophy in children and young people with primary hypertension: Meta-analysis and meta-regression.

Background: Left ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH). Methods: A meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity. Results: The search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m2.7 in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2-33.9), while heterogeneity was high (I 2 = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity (I 2 = 84%). Two studies involving patients identified through community screening (n = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08-0.39, p = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%). Conclusion: Left ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.

Disparities between determinants of impaired vascular structure and function in young people with primary hypertension: a systematic review.

OBJECTIVE: Early effects of primary hypertension on arterial structure and function in children and young people (CYP) and their determinants remain elusive. We aimed to review independent determinants of carotid intima-media thickness (cIMT), carotid wall cross-sectional area (WCSA) and carotid-femoral pulse wave velocity (cfPWV) in CYP with primary hypertension. METHODS: We performed a systematic review of studies reporting multivariable analysis of cfPWV, cIMT and WCSA in CYP (up to 25 years of age) with primary hypertension. Literature search was performed in PubMed database and 13, 12 and two articles including 3860 (age range 4-25 years, 50% male individuals), 2038 children (5-25 years, 55% male individuals) and 136 children (5-17 years, 85% male individuals) were selected for final analysis of cfPWV, cIMT and WCSA, respectively. RESULTS: Ninety and 86% of the studies reported higher cfPWV and cIMT in CYP with elevated blood pressure (BP) compared with normotensive controls. Different indices of BP were positively associated with cfPWV in 92% of studies, whereas BMI showed association in 31%. Carotid IMT associated with BP indices in 50% and with BMI in 25% of the studies. WCSA was studied longitudinally and its improvement associated with decrease in measures of central obesity. CONCLUSION: We found a disparity between the determinants of structural and functional impairment of arterial tree in CYP with primary hypertension. In contrast to cIMT and WCSA, increase of cfPWV is almost exclusively determined by BP.

Risk Assessment and Clinical Management of Children and Adolescents with Heterozygous Familial Hypercholesterolaemia. A Position Paper of the Associations of Preventive Pediatrics of Serbia, Mighty Medic and International Lipid Expert Panel.

Heterozygous familial hypercholesterolaemia (FH) is among the most common genetic metabolic lipid disorders characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and a significantly higher risk of developing premature atherosclerotic cardiovascular disease. The majority of the current pediatric guidelines for clinical management of children and adolescents with FH does not consider the impact of genetic variations as well as characteristics of vascular phenotype as assessed by recently developed non-invasive imaging techniques. We propose a combined integrated approach of cardiovascular (CV) risk assessment and clinical management of children with FH incorporating current risk assessment profile (LDL-C levels, traditional CV risk factors and familial history) with genetic and non-invasive vascular phenotyping. Based on the existing data on vascular phenotype status, this panel recommends that all children with FH and cIMT ≥0.5 mm should receive lipid lowering therapy irrespective of the presence of CV risk factors, family history and/or LDL-C levels Those children with FH and cIMT ≥0.4 mm should be carefully monitored to initiate lipid lowering management in the most suitable time. Likewise, all genetically confirmed children with FH and LDL-C levels ≥4.1 mmol/L (160 mg/dL), should be treated with lifestyle changes and LLT irrespective of the cIMT, presence of additional RF or family history of CHD.

Could the unfortunate outcome of pediatric acute myocarditis be predicted? Factors contributing to a poor outcome in myocarditis.

OBJECTIVE: Myocarditis has spontaneous resolution in 50% of patients. Our study aimed to define risk factors for developing dilated cardiomyopathy (DCM) and death in pediatric patients with acute myocarditis (AM). METHODS: The retrospective cohort study included all patients with treated AM. The Mother and Child Health Institute from January 2011 to March 2019. RESULTS: In the study, 62 patients were included, 40 boys and 22 girls (11.15±5.86 years) with AM. Twelve out of sixty-two children had acute fulminant myocarditis. Four patients died in the acute phase of AM, and 11 developed DCM. Follow up was 27.14±36.52 months. Patients with poor outcome (DCM development) were under the age of seven (odds ratio [OR] 10.1; p=0.003), more likely to be girls (OR 4.6; p=0.03), and had fulminant myocarditis (OR 27.0; <0.001). An ejection fraction (EF) <55% and fractional shortening (FS) <30% increased risk of DCM 13- and 5-fold, respectively, but patients with EF between 40 and 55% remain at highest risk of developing DCM. There was a 12-fold increased risk for DCM in patients with left ventricular end-diastolic diameter Z score >2+. The receiver operator curve showed that the lactate dehydrogenase (LDH) cut-off value for developing DCM was 1780 mmol/l (sensitivity 80%, specificity 100%). CONCLUSION: Acute fulminant myocarditis was an independent risk factor for DCM. Children with EF between 40 and 50% at admission were at highest risk of developing DCM. Lactate dehydrogenase value could be a significant prognostic value for the outcome of pediatric myocarditis.

Insulin resistance surrogates and left ventricular hypertrophy in normotensive obese children.

BACKGROUND: The relationship between different surrogates of insulin resistance and left ventricular geometry in obese children is still unclear. OBJECTIVE: We sought to explore the relationship between commonly used measures of insulin sensitivity/resistance (homeostatic model assessment index, serum uric acid, and triglycerides to high-density lipoprotein cholesterol ratio) and left ventricular geometry in normotensive obese children. METHODS: In this cross-sectional study, 32 normotensive obese children were examined. Transthoracic echocardiography was used to measure left ventricular mass index and relative wall thickness. Homeostasis model assessment index, serum uric acid level, and a ratio of triglycerides to high-density lipoprotein cholesterol were used as markers of the insulin resistance. Simple and partial correlation analyses (to control for the effects of body mass index) were conducted to explore relationship between studied variables and left ventricular mass index or relative wall thickness as outcome variables. RESULTS: We found positive correlations between homeostasis model assessment index and relative wall thickness (r = 0.47, p = 0.03) which remained significant after controlling for the effect of body mass index, z-score (r = 0.48, p = 0.03). The cutoff level of homeostasis model assessment index with the optimum sensitivity (Sn) and specificity (Sp) derived from the receiver operating characteristic (ROC) curves for predicting concentric remodelling was ≥5.51 with Sn = 83.33 and Sp = 68.75. CONCLUSION: There is a positive relationship between homeostasis model assessment index and relative wall thickness of obese normotensive children which may help to distinguish at risk obese normotensive children for the development of concentric left ventricular remodelling.

Lipid profile and left ventricular geometry pattern in obese children.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children. PATIENTS AND METHODS: In this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex. RESULTS: Our study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12-16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p < 0.01; effect = 34.90, SE = 6.84, p < 0.01; effect = 0.32, SE = 0.12, p < 0.01, respectively). On the other hand, in model with RWT as outcome variable, only BMI and insulin were significantly linked (BMI: effect = 13.07, SE = 5.02, p = 0.01 Insulin: effect = 2.80, SE = 0.97). CONCLUSION: Increased TG/HDL ratio in obese children is associated with the development of eccentric left ventricular hypertrophy while increased BMI and insulin were associated with concentric left ventricular hypertophy.

Homozygous familial hypercholesterolaemia in childhood - The first case report in Southeast Europe.

Homozygous familial hypercholesterolaemia (HoFH) is the rare, severe, but treatable disease characterised by exceedingly high levels of low-density lipoprotein cholesterol (LDL-C) and subsequent premature coronary heart disease. Of note, HoFH detection rate and patient access to healthcare and treatment modalities still differ considerably across EU countries. To our current knowledge, there are still no published reports describing HoFH in the paediatric population of Southeastern Europe. In this case report, a few important topics on obstacles in getting adequate health care service and management of HoFH children from Southeastern Europe are tackled.

Serum uric acid and left ventricular geometry pattern in obese children.

BACKGROUND: Relative importance of traditional and non-traditional components of metabolic syndrome (MetSy) as risk factors for subclinical target organ damage in obese children is still under investigation. Recent studies highlight the role of serum uric acid (SUA) as an emerging non-traditional independent risk factor which correlates with obesity, MetSy, type 2 diabetes, preclinical cardiac and extracardiac organ damage, as well as cardiovascular events. AIMS: To study the relationship between SUA and left ventricular geometry pattern in obese children with or without MetSy. PATIENTS AND METHODS: In this cross-sectional study, a total of 73 obese children, 64.4% male, and 35.6% female, with median age of 15 years (IQR = 12-16) were examined. Body mass index, glycaemia, standard lipid profile, fasting insulin level, HOMA index, serum uric acid level, 24-h average systolic blood pressure, left ventricular mass index (LVMI) and relative wall thickness (RWT) were evaluated in all children. RESULTS: LVMI in our study group was 46 g/m2.7 (IQR = 42-55) while the RWT was 37% (IQR = 31-41). Median SUA level was 341 µmol/L (IQR = 283-387). In the entire sample of children, SUA was independently associated with the RWT (coeff = 0.02, p < 0.01). In a sub-group of metabolically unhealthy children, we found no statistically significant association between SUA and LVMI nor between SUA and RWT (coeff. = 0.002, p = 0.92; coeff. = 0.01, p = 0.20, respectively). CONCLUSION: Serum uric acid is an important independent non-traditional risk factor for the development of concentric left ventricular geometry in obese children. These findings deserve further investigation to determine whether high SUA in obese children may be a therapeutic target.

Does Colchicine Substitute Corticosteroids in Treatment of Idiopathic and Viral Pediatric Pericarditis?

Background and Objectives: Recurrence of pericarditis (ROP) is an important complication of the acute pericarditis. The aim of this study was to analyse the influence of aetiology, clinical findings and treatment on the outcome of acute pericarditis. Methods: Data were retrospectively collected from medical records of patients treated from 2011 to 2019 at a tertiary referent heart paediatric center. Results: Our investigation included 56 children with idiopathic and viral pericarditis. Relapse was registered in 8/56 patients, 2/29 (7.41%) treated with nonsteroidal anti-inflammatory drugs (NSAID) and 6/27 (28.57%) treated with corticosteroids (CS) and NSAID. Independent risk factors for ROP were viral pericarditis (p = 0.01, OR 31.46), lack of myocardial affection (p = 0.03, OR 29.15), CS use (p = 0.02, OR 29.02) and ESR ≥ 50 mm/h (p = 0.03, OR 25.23). In 4/8 patients the first recurrence was treated with NSAID and colchicine, while treatment of 4/8 patients included CS. Children with ROP treated with CS had higher median number of recurrence (5, IQR: 2-15) than those treated with colchicine (0, IQR: 0-0.75). Conclusions: Independent risk factors for recurrence are CS treatment, viral aetiology, pericarditis only and ESR ≥ 50 mm/h. Acute pericarditis should be treated with NSAID. Colchicine and NSAID might be recommended in children with the first ROP.

Visceral Adiposity Index is not Superior over Anthropometric Parameters with regards to Inflammation in Healthy Adolescent Girls.

OBJECTIVE: Better than simple anthropometric parameters, the visceral adiposity index (VAI) has recently been proposed as a predictor of cardiometabolic risk in adults. However, there are conflicting results on the associations of these parameters in children and adolescents. Therefore, we aimed to estimate this potential relationship between VAI, anthropometric parameters (i.e., body mass index [BMI], waist circumference [WC], and waist-to-height ratio [WHtR], respectively), and inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) levels in a cohort of adolescent girls. METHODS: A total of 90 adolescent girls from 16 to 19 years old were included in cross-sectional study. Anthropometric and biochemical parameters (glucose, lipid parameters, and hsCRP) were measured. The VAI, derived from anthropometric and lipid parameters, calculated {[WC/36.58 + (1.89 × BMI)] × (triglycerides/0.81) × (1.52/HDL-cholesterol)} was calculated. RESULTS: A comparison of the receiver operating characteristic (ROC) curves showed that all the curves for the anthropometric parameters (e.g., BMI, WC, WHtR) had excellent discriminatory capability with regard to inflammation level status (low vs. high level) and significantly larger areas under the curve (AUC = 0.885, AUC = 0.863, AUC = 0.860, respectively; P < 0.001) than the ROC curve for VAI did (AUC = 0.686; P = 0.021). CONCLUSION: Visceral adiposity index is not superior over anthropometric parameters in relation to inflammation as measured by high sensitivity C-reactive protein in adolescent girls.

Cardiovascular Risk Assessed by Reynolds Risk Score in Relation to Waist Circumference in Apparently Healthy Middle-Aged Population in Montenegro.

Reynolds Risk Score (RRS) is regarded as a good screening tool for cardiovascular disease (CVD) risk. Since CVD is the leading cause of death in Montenegro, we aimed to assess the risk of CVD as assessed by RRS and to examine its association with cardiometabolic parameters in apparently healthy middle-aged population. In addition, we aimed to test whether obesity had an independent influence on RRS. A total of 132 participants (mean age 56.2±6.73 years, 69% females) were included. Body mass index (BMI), waist circumference (WC), blood pressure (BP) and biochemical parameters (fasting glucose, insulin, lipid parameters, creatinine and high sensitivity C-reactive protein) were determined. Insulin resistance (HOMA-IR) and glomerular filtration rate (eGFR) were calculated. Compared with females, a significantly higher number of males were in the high RRS subgroup (χ2=45.9, p<0.001). Furthermore, significantly higher fasting glucose (p=0.030), insulin, HOMA-IR, triglycerides (p<0.001 all), anthropometric parameters (e.g., BMI and WC; p=0.004 and p<0.001, respectively), and creatinine, but lower eGFR and HDL-c (p<0.001 both) were recorded in the high-risk subgroup compared with low and medium risk subgroups. In all participants, in addition to LDL-c, diastolic BP and creatinine, WC was independently positively associated with RRS (ß=0.194, p=0.006; ß=0.286, p=0.001; ß=0.267, p=0.001; and ß=0.305, p=0.019, respectively), and 40% of variation in RRS could be explained with this model. In conclusion, middle-aged population with higher WC should be screened for RRS in order to estimate CVD risk.

The Association Between Retinol-Binding Protein 4 and Cardiovascular Risk Score is Mediated by Waist Circumference in Overweight/Obese Adolescent Girls

Retinol-binding protein 4 (RBP4) is an emerging risk factor for atherosclerotic disease in adults. However, to our knowledge, there are no studies examining the relationship between RBP4 and cardiovascular risk in young population. Therefore, we aimed to estimate this potential relationship in overweight/obese adolescent girls. Seventy overweight/obese adolescent girls, mean age 17.6±1.20 years, were included. Anthropometric and biochemical parameters were measured. Cardiovascular risk score (CVRS) was calculated by adding points for each risk factor (e.g., sex, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, smoking, blood pressure and fasting glycemia). According to the risk status, we divided adolescent girls into low, medium and high risk groups (-2≤ CVRS ≤1, 2≤ CVRS ≤4 and CVRS ≥5, respectively). We found significantly higher RBP4 in the high risk group as compared with low risk group (p<0.001). However, multiple linear regression analysis showed waist circumference (beta=0.257, p=0.031) to be the only independent predictor of higher cardiovascular risk (adjusted R(2)=0.342, p<0.001). In conclusion, RBP4 may be associated with higher cardiovascular risk in overweight/obese adolescent girls, but this association is mediated by abdominal obesity.

Heart rate recovery time in metabolically healthy and metabolically unhealthy obese children.

BACKGROUND: Autonomic dysfunction is an emerging non-traditional cardiovascular risk factor that correlates with obesity, components of metabolic syndrome, as well as cardiorespiratory fitness. As a simple and validated index of autonomic balance, heart rate recovery (HRR) has been reported as a useful biomarker for predicting cardiovascular morbidity and mortality. OBJECTIVES: The aim of this study was to compare HRR in metabolically healthy vs. metabolically unhealthy obese children. METHODS: A total of 56 obese children of whom 31 had metabolic syndrome were examined. All the participants underwent the multistage submaximal cycle ergometer test and HRR was determined one minute after the test. RESULTS: The HRR was significantly lower (18.9 ± 3.7) in a group of metabolically unhealthy obese children compared to metabolically healthy obese children (24 ± 4.1) p < 0.001. Logistic regression analysis showed that reduction in HRR was also influenced by higher BMI. CONCLUSION: Our findings implicate the presence of the autonomic dysfunction as reflected by impaired heart rate recovery (HRR) in obese children with metabolic syndrome.

Reproducibility of 24-h heart rate variability in children.

BACKGROUND: Over the last decades, time domain heart rate (HR) variability analysis has been explored in different pediatric clinical settings to obtain information on the cardiac autonomic tone. However, the consistency over time of 24 h time domain HRV measurements in children is not well-known. METHODS: We investigated the reproducibility of 24 h HRV time-domain indices (1 day apart), from 39 healthy children (9.5 ± 5.3 years, 56.4% girls). The parameters analysed included: standard deviation of all the adjacent NN intervals, standard deviation of the averages of NN intervals (the intervals between normal R-peaks) in all 5-min segments, and square root of the mean of the sum of the squares of the differences between adjacent NN intervals, uncorrected and corrected for HR. Reproducibility between two 24-h ECG recordings was evaluated by intraclass correlation coefficients, standard error of measurement, coefficients of variation and Bland-Altman plots. RESULTS: For the analyzed time-domain indices, standard deviation of all the adjacent NN intervals corrected for HR showed best reproducibility with the highest intraclass correlation coefficient (0.987), the lowest coefficients of variation (5.5%) and the best level of agreement between two recordings as assessed by Bland-Altman plots. CONCLUSIONS: Our results indicate that the standard deviation of all the adjacent NN intervals corrected for the HR parameter obtained from 24-h ambulatory recordings in children is consistent and reproducible over time, thus allowing reliable identification of cardiac autonomic tone in this age group.

The Association of Prenatal Tocolysis and Breastfeeding Duration.

BACKGROUND: To date there are no clinical studies analyzing potential effects of tocolytics on breastfeeding duration in humans. OBJECTIVES: The purpose of this study was to evaluate the association between beta 2 agonists prescribed for tocolysis during pregnancy and breastfeeding duration. METHODS: We conducted a cross-sectional questionnaire study of 114 mothers and filled in the questionnaire developed to directly address the goals of the study. RESULTS: There was a statistically significant difference between breastfeeding duration of mothers who were on tocolytics during pregnancy versus those who were not prescribed tocolytics (9.5 ± 5.7 months versus 4.5 ± 2.1 months) p < 0.001. In addition, hypogalactia was statistically significantly more prevalent in mothers with positive history versus mothers with negative history of tocolytic usage p < 0.001. CONCLUSION: The results of our study indicate that tocolytic treatment in pregnancy is associated with shorter breastfeeding duration and hypogalactia.

Assessment of general movements and heart rate variability in prediction of neurodevelopmental outcome in preterm infants.

BACKGROUND: Adverse neurologic outcome in preterm infants could be associated with abnormal heart rate (HR) characteristics as well as with abnormal general movements (GMs) in the 1st month of life. AIMS: To demonstrate to what extent GMs assessment can predict neurological outcome in preterm infants in our clinical setting; and to assess the clinical usefulness of time-domain indices of heart rate variability (HRV) in improving predictive value of poor repertoire (PR) GMs in writhing period. STUDY DESIGN: Qualitative assessment of GMs at 1 and 3 months corrected age; 24h electrocardiography (ECG) recordings and analyzing HRV at 1 month corrected age. SUBJECTS: Seventy nine premature infants at risk of neurodevelopmental impairments were included prospectively. OUTCOME MEASURES: Neurodevelopmental outcome was assessed at the age of 2 years corrected. Children were classified as having normal neurodevelopmental status, minor neurologic dysfunction (MND), or cerebral palsy (CP). RESULTS: We found that GMs in writhing period (1 month corrected age) predicted CP at 2 years with sensitivity of 100%, and specificity of 72.1%. Our results demonstrated the excellent predictive value of cramped synchronized (CS) GMs, but not of PR pattern. Analyzing separately a group of infants with PR GMs we found significantly lower values of HRV parameters in infants who later developed CP or MND vs. infants with PR GMs who had normal outcome. CONCLUSIONS: The quality of GMs was predictive for neurodevelopmental outcome at 2 years. Prediction of PR GMs was significantly enhanced with analyzing HRV parameters.

Relationship between Cardiovascular Risk Score and Traditional and Nontraditional Cardiometabolic Parameters in Obese Adolescent Girls.

BACKGROUND: Since the cardiovascular (CV) risk score in the young population, children and adolescents, is underestimated, especially in developing countries such as Montenegro, where a strong interaction exists between the genetically conditioned CV risk and environmental factors, the purpose of this study was to estimate CV risk in apparently healthy adolescent girls. Moreover, we aimed to test some new, emerging CV risk factors and their interaction with the traditional ones, such as obesity. Precisely, we aimed to assess the impact of low bilirubin levels, as a routine biochemical parameter, as an additional risk factor for atherosclerotic disease in the adult phase. METHODS: Forty-five obese adolescent girls (mean age 17.8±1.22 years) and forty-five age- and sex-matched normal weight controls, all nonsmokers, were included. Anthropometric and biochemical parameters were measured. Cardiovascular Risk Score (CVRS) was calculated by adding the points for each risk factor (e.g. sex, HDL-c, non-HDL-c, blood pressure and fasting glycemia). RESULTS: A significant positive relationship between CVRS and ALT, hsCRP and TG/HDL-c, but an opposite relationship between CVRS and total bilirubin were found (P<0.001). Multiple linear regression analysis showed that higher waist circumference (WC) and LDL-c, but lower HDL-c were independent predictors of lower bilirubin values (adjusted R2=0.603, P<0.001). CONCLUSIONS: Obese adolescent girls are at an increased risk of cardiovascular disease late in life. In addition to the traditional risk factors, total bilirubin may have the potential to discriminate between low and higher risk for cardiovascular disturbances in healthy adolescent girls.