Liane Correia-Costa

Decreased renal function in overweight and obese prepubertal children

Background:Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl).Methods:Cross-sectional study of 313 children aged 8–9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference.Results:Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from −4.3 to −1.1 ml/min/1.73 m2 per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values.Conclusion:Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity.

Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children.

Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children.

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.

Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.

Maternal Smoking: A Life Course Blood Pressure Determinant?

Introduction Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children. Methods We evaluated 4295 of Generation XXI children, recruited at birth in 2005-2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and childrens BP measured. Linear regression models were fitted to estimate the association between maternal smoking and childrens BP. Results Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and childs body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (β = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (β = 0.08, 95% CI 0.03 to 0.13 before conception; β = 0.07, 95%CI 0.02 to 0.12; β = 0.04, 95%CI -0.02 to 0.10; and β = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and β = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels. Conclusion Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged. Implications Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking-before pregnancy, during pregnancy, and 4 years after delivery-was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.

Determinants of carotid-femoral pulse wave velocity in prepubertal children

BACKGROUND Pulse wave velocity (PWV) is a noninvasive technique to evaluate arterial stiffness, a dynamic property of the vessels, reflecting their structure and function. Childhood obesity is associated with several cardiovascular comorbidities and to the progression of atherosclerosis. We aimed to compare carotid-femoral PWV between normal weight and overweight/obese prepubertal children and to quantify its association with other cardiovascular risk factors. METHODS Cross-sectional study of 315 children aged 8-9years. Anthropometrics, 24-h ambulatory blood pressure (BP) and carotid-femoral PWV were measured. Classification of obesity was according to World Health Organization (WHO) body mass index (BMI)-for-age reference values. RESULTS Compared to normal weight children, overweight and obese children presented significantly higher levels of PWV (4.95 (P25-P75: 4.61-5.23), 5.00 (4.71-5.33), 5.10 (4.82-5.50) m/s, respectively; ptrend<0.001). Significant positive correlations were found between PWV and total cholesterol, LDL cholesterol, triglycerides, fasting insulin and insulin resistance levels (HOMA-IR) and with high-sensitivity C-reactive protein (hs-CRP). In a multivariate linear regression model adjusted for sex, age, height and 24-h systolic blood pressure z-score, the independent determinants of PWV were BMI, HOMA-IR and the absence of dipping. CONCLUSIONS The association between PWV and the loss of dipping and insulin resistance levels, independently of the BMI, reinforces the contribution of these comorbidities to vascular injury in early life.

Sex-Specific Mediating Role of Insulin Resistance and Inflammation in the Effect of Adiposity on Blood Pressure of Prepubertal Children.

Objective To evaluate the association between obesity indices and blood pressure (BP) at 4 years of age, in each sex, and to quantify to which extent this association is mediated by inflammation and insulin resistance (IR). Materials and Methods We studied 1250 4-year-old children selected from the population-based birth cohort Generation XXI. Associations between body mass index (BMI) z-score and waist-to-height ratio (WHtR), office BP, inflammation (high sensitivity C-reactive protein) and IR (HOMA-IR index) were assessed. Path Analysis, a modified multivariate regression approach, was applied to test causal models and quantify direct and indirect effects of predictors of systolic (SBP) and diastolic BP (DBP). Results SBP and DBP increased significantly with BMI and WHtR in both sexes. There was a strong direct association (explaining 74.1-93.2% of the total association) of both measures of adiposity with SBP, in both sexes. This association was additionally indirectly mediated by IR, particularly regarding WHtR (20.5% in girls and 9.4% in boys). Mediation by inflammation did not reach statistical significance in either sex. Regarding DBP, the direct effect of adiposity was strong (>95% for BMI and WHtR in boys) and the mediation by IR was much smaller in boys than in girls. Discussion The direct association between adiposity and BP in healthy 4-year-old children is strong and IR plays an important mediating role. The strength of effects of IR and inflammation suggests sex differences in the complex interplay between BP, adiposity and inflammation.

Perfusion index in preterm newborns during the first week of life and association with neonatal morbimortality: a prospective observational study

Introduction: Perfusion index (PI) is a noninvasive method of peripheral perfusion measurement. Previous publications suggest that PI might be an useful and accurate predictor of morbidity and mortality risk in preterm newborns. This study aims: 1) to assess the PI values of preterm newborns ( 2 (n = 10, 16.7%). Median PI values were found to be significantly lower in newborns with an adverse outcome (0.90 vs. 0.70 at 24 hours; 0.87 vs. 0.72 at 48 hours; 0.91 vs. 0.79 at 72 hours; and 0.90 vs. 0.80 at 168 hours) and/or death in neonatal period (0.87 vs. 0.55 at 1 hour; 0.80 vs. 0.70 at 24 hours; 0.81 vs. 0.55 at 48 hours; 0.88 vs. 0.74 at 72 hours; and 0.89 vs. 0.49 at 168 hours). Conclusions: PI values differed according to gestational age and to the presence of comorbidities, confirming that it might represent a valuable tool in the early identification of adverse outcomes in the neonatal period.

Accelerated growth during childhood is associated with increased arterial stiffness in prepubertal children

a EPIUnit—Institute of Public Health, University of Porto, Porto, Portugal b Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal c Department of Pediatrics, Faculty of Medicine of University of Porto, Portugal d Division of Pediatric Cardiology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal e Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine of University of Porto, Portugal f Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal g Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany

Childhood Obesity and Impact on the Kidney

Obesity is known to be associated with a myriad of cardiovascular and metabolic comorbidities. In children, several longitudinal studies have shown that obesity consequences start early in life and accompany the obese child into adulthood, implying a higher risk of adverse cardiovascular events. More recently, data related to the possible role of obesity in the risk of kidney disease in adults, independently of diabetes, has started to become more available. In children, the evidence is scarcer, but it has also been acknowledged that obesity acts as a risk factor for disease progression when kidney impairment already exists, thereby increasing the risk of death among children with end-stage renal disease (ESRD). Besides this, there is also evidence that otherwise healthy overweight and obese children have a significant increase in the risk of all-cause ESRD later in life. The potential mechanisms underlying this association need to be further discussed in order to allow the setting in motion of preventive strategies to halt chronic kidney disease development and progression.

Cystic Fibrosis and Beckwith-Wiedemann Syndrome: A Case Report

Cystic fibrosis (CF) is a hereditary disease of exocrine gland function that involves multiple systems but chiefly results in chronic respiratory infections, the major cause of death, pancreatic enzyme deficiency and severe malnutrition, mostly in untreated patients. The association between CF and other inherited diseases or congenital anomalies is rare. We describe for the first time the association of CF and Beckwith-Wiedemann syndrome (BWS). BWS is a genetic disorder commonly characterized by overgrowth. The most common features of BWS include macrosomia, macroglossia, abdominal wall defects, an increased risk for childhood tumors, kidney abnormalities, hypoglycemia in the newborn period and unusual ear creases or pits.