Effect of Protein Intake Early in Life on Kidney Volume and Blood Pressure at 11 Years of Age.

High protein intake has been associated with kidney hypertrophy, which is usually reversible; however, when it occurs early in life, it could lead to cell programming with a long-lasting effect. This study aimed to assess whether higher protein ingestion early in life has a persistent effect on kidney volume at 11 years of age, as well as its influence on blood pressure. This is a secondary analysis of a randomized control trial that compared the growth of infants fed with a higher-protein formula versus those fed with a lower-protein formula, with a control group of breastfed infants. Renal ultrasound and anthropometric measurements were assessed at 6 months and 11 years of age. At 11 years, urinary protein, albumin and creatinine, and blood pressure were measured in 232 children. Feeding with a higher-protein formula was associated with a larger kidney volume (ß = 8.71, 95%CI 0.09-17.33, p = 0.048) and higher systolic blood pressure (ß = 3.43, 95%CI 0.78-6.08, p = 0.011) at 11 years of age. Microalbuminuria was detected in 7% of the patients, with no differences among groups (p = 0.56). The effect of increased protein ingestion early in life may condition kidney volume and blood pressure in later childhood.

Distribution of energy and macronutrient intakes across eating occasions in European children from 3 to 8 years of age: The EU Childhood Obesity Project Study.

PURPOSE: We aimed to characterize the distribution of energy and macronutrient intakes across eating occasions (EO) in European children from preschool to school age. METHODS: Data from 3-day weighed food records were collected from children at ages 3, 4, 5, 6 and 8 years from Belgium, Germany, Italy, Poland and Spain. Food intakes were assigned to EO based on country-specific daytimes for breakfast, lunch, supper and snacks (morning, afternoon). The average energy and nutrient intakes were expressed as percentage of total energy intake (%E). Nutrients were additionally expressed as percentage per EO (%EEO). Foods were assigned to food groups; variation in intake was calculated via coefficient of variation (CV). We analyzed age trends in diurnal intake using mixed-effects beta regression. RESULTS: The 740 healthy children included in the analysis consumed the largest proportion of daily energy at lunch (31%E ± 8, M ± SD) and supper (26%E ± 8), followed by breakfast (19%E ± 7) and snacks [afternoon (16%E ± 8); morning (8%E ± 7)], with the most variable intake at morning snack (CV = 0.9). The nutrient composition at lunch and supper was highest for fat (36 ± 9%ELunch; 39 ± 11%ESupper) and protein (18 ± 5%ELunch; 18 ± 6%ESupper) and at breakfast and snacks for carbohydrates (54 ± 12%EBreakfast; 62 ± 12%ESnacks). High-sugar content foods were consumed in relatively large proportions at breakfast and snacks. Food intakes varied significantly with age, with lower snack intakes at later ages (p < 0.001). CONCLUSION: Possibly unhealthy EOs with high-fat intakes and high-sugar-content foods were observed. Changes in nutrient composition of EOs may be beneficial for health. TRIAL REGISTRY: ClinicalTrials.gov: NCT00338689; 19/June/2006.

Single Nucleotide Polymorphisms of Interleukins and Toll-like Receptors and Neuroimaging Results in Newborns with Congenital HCMV Infection.

Congenital cytomegalovirus infection (cCMV) is the most common intrauterine infection with central nervous system (CNS) involvement. There is limited data on the associations between Single Nucleotide Polymorphisms (SNPs) in genes involving the first-line defense mechanism and the risk of CNS damage during cCMV. We investigated the associations between neuroimaging findings and SNPs in genes encoding the following cytokines and cytokine receptors in 92 infants with cCMV: interleukins (IL1B rs16944, IL12B rs3212227, IL28B rs12979860), C-C motif chemokine ligand 2 (CCL2 rs1024611), dendritic cell-specific intercellular adhesion grabbing non-integrin (DC-SIGN rs735240), Toll-like receptors (TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140). The SNP of IL1B rs16944 (G/A) was associated with a reduced risk of ventriculomegaly on MRI (OR = 0.46, 95% CI, 0.22-0.95; p = 0.03) and cUS (OR = 0.38, 95% CI, 0.0-0.93; p = 0.034). Infants carrying heterozygous (T/C) genotype at IL28B rs12979860 had an increased risk of cystic lesions on cUS (OR = 3.31, 95% CI, 1.37-8.01; p = 0.0064) and MRI (OR = 4.97, 95% CI, 1.84-13.43; p = 0.001), and an increased risk of ventriculomegaly on MRI (OR = 2.46, 95% CI, 1.03-5.90; p = 0.04). No other associations between genotyped SNPs and neuroimaging results were found. This is the first study demonstrating new associations between SNPs of IL1B and IL28B and abnormal neuroimaging in infants with cCMV.

The Limitations of Cytomegalovirus DNA Detection in Cerebrospinal Fluid of Newborn Infants With Congenital CMV Infection: A Tertiary Care Neonatal Center Experience.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection of the central nervous system (CNS) can cause ventriculomegaly, gliosis, calcifications and cortical defects. Detection of CMV DNA in cerebrospinal fluid by PCR (CSF-CMV-PCR) is a marker of CNS involvement. OBJECTIVE: To evaluate a diagnostic value of the positive CSF-CMV-PCR in cCMV. METHODS: Analysis of clinical, laboratory, neuroimaging and single-nucleotide polymorphisms (SNPs) data according to the results of CSF-CMV-PCR were performed in infants with cCMV. RESULTS: A total of 168 infants were included; 145 (86.3%) had negative and 23 (13.7%) had positive CSF-CMV-PCR results. Associations between the positive CSF-CMV-PCR results and prematurity (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 1.30-8.07), microcephaly (OR = 5.67; 95% CI: 2.08-15.41), seizures (OR = 4.15; 95% CI: 1.10-15.67), sensorineural hearing loss (OR = 6.6; 95% CI: 2.49-17.46), splenomegaly (OR = 8.13; 95% CI: 3.12-21.16), hepatitis (OR = 10.51; 95% CI: 3.31-33.35), petechiae (OR = 10.21; 95% CI: 3.78-27.57) and heterozygous T/C genotype at TLR4rs4986791 (OR = 7.88; 95% CI: 1.55-40.12) were observed. When using a multivariate logistic regression analysis, only the presence of severe sensorineural hearing loss (OR = 7.18; 95% CI: 1.75-29.34, P = 0.006), cystic lesions on MRI (OR 5.29; 95% CI: 1.31-21.36, P = 0.02), and calcifications on MRI (OR = 7.19; 95% CI: 1.67-30.97, P = 0.008) remained as the significant independent predictors of the positive CSF-CMV-PCR results. CONCLUSIONS: The detection of CMV DNA in CSF is associated with a higher rate of CNS damage including abnormal MRI neuroimaging and severe hearing loss. Therefore, detection of CMV DNA in CSF may be considered as a marker of severe CNS injury in cCMV infection. However, the very low prevalence of the positive CSF-CMV-PCR results, even in infants with proven CNS involvement, may imply its limited role in clinical practice.

Influence of total sugar intake on metabolic blood markers at 8 years of age in the Childhood Obesity Project.

PURPOSE: We aimed to characterize the association of dietary sugar intake with blood lipids and glucose-related markers in childhood. METHODS: Data from the multicentric European Childhood Obesity Project Trial were used. Three-day weighed dietary records were obtained at 8 years of age along with serum concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), glucose, and insulin. Total sugar intake comprised all mono- and disaccharides; different sugar sources were defined. Linear regression models were applied to investigate the cross-sectional association of total sugar intake with blood lipids and glucose-related markers with adjustment for total energy intake using the residual method. RESULTS: Data were available for 325 children. Children consumed on average 332 kcal (SD 110) and 21% (SD 6) of energy from total sugar. In an energy-adjusted model, an increase of 100 kcal from total sugar per day was significantly associated with a z score HDL-C decrease (- 0.14; 95% CI - 0.01, - 0.27; p value = 0.031). Concerning different food groups of total sugar intake, 100 kcal total sugar from sweetened beverages was negatively associated with z score HDL-C (- 1.67; 95% CI - 0.42, - 2.91; p value = 0.009), while total sugar from milk products was positively related to z score HDL-C (1.38, 95% CI 0.03, 2.72; p value = 0.045). None of the other blood lipids or glucose-related markers showed a significant relationship with total sugar intake. CONCLUSION: Increasing dietary total sugar intake in children, especially from sweetened beverages, was associated with unfavorable effects on HDL-C, which might increase the long-term risk for dyslipidemia and cardiovascular disease. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: https://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1 .

Antiviral treatment in congenital HCMV infection: The six-year experience of a single neonatal center in Poland.

BACKGROUND: Antiviral treatment is recommended for symptomatic newborns with congenital cytomegalovirus infection (cCMV). OBJECTIVES: To compare 2 treatment methods in neonates with cCMV - ganciclovir-based therapy (intravenous ganciclovir (GCV) or sequential GCV + valganciclovir (VGCV) therapy) with oral VGCV-based therapy - in Polish neonates. MATERIAL AND METHODS: A total of 98 symptomatic infants with cCMV (positive HCMV DNA in urine ≤21st day of life) hospitalized in the neonatal intensive care unit (NICU) between 2012 and 2017 were enrolled. Clinical characteristics, the viral load in blood and urine, hematological and biochemical tests, neuroimaging results, and the length of hospitalization were compared between the study groups at baseline and at the 2nd hospitalization. RESULTS: In 2012, GCV was used in 57% of the cases, sequential therapy in 33% and VGCV in 10%. In 2017, VGCV monotherapy was used in 83% of the infants treated. Valganciclovir treatment allowed the length of hospitalization to be shortened over 2.5 times during the six-year observation period. Infants treated intravenously had lower birth weights and head circumferences, and more frequently presented splenomegaly, petechiae, thrombocytopenia, and hepatitis. The baseline viral load in the blood and urine were similar in both groups, but at follow-up visits 4-6 weeks later, a viral load about 70 times lower was observed in the blood of the VGCV-based group (1029 viral copies/mL compared to 72,188 viral copies/mL in the GCV-based group; p = 0.04). The prevalence of neutropenia was similar in both groups at the follow-up visits. CONCLUSIONS: Valganciclovir became the first line of antiviral therapy in cCMV in the study population. Compared to GCV-based therapy, VGCV monotherapy allowed shorter hospital stays and reduced the viral load in blood due to continuing treatment at home. Valganciclovir monotherapy did not provoke more side effects such as neutropenia. Intravenous GCV is still suitable for patients with severe disseminated disease, born prematurely, with low birth weights, or not tolerating enteral feeding. In those infants, the sequential therapy seems to be optimal.

Impact of infant protein supply and other early life factors on plasma metabolome at 5.5 and 8 years of age: a randomized trial.

OBJECTIVES: A high dairy protein intake in infancy, maternal pre-pregnancy BMI, and delivery mode are documented early programming factors that modulate the later risk of obesity and other health outcomes, but the mechanisms of action are not understood. METHODS: The Childhood Obesity Project is a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants. Participating infants were either breastfed (BF) or randomized to receive higher (HP) or lower protein (LP) content formula in the first year of life. At the ages 5.5 years (n = 276) and 8 years (n = 232), we determined plasma metabolites by liquid chromatography tandem-mass-spectrometry of which 226 and 185 passed quality control at 5.5 years and 8 years, respectively. We assessed the effects of infant feeding, maternal pre-pregnancy BMI, smoking in pregnancy, delivery mode, parity, birth weight and length, and weight gain (0-24 months) on the metabolome at 5.5 and 8 years. RESULTS: At 5.5 years, plasma alpha-ketoglutarate and the acylcarnitine/BCAA ratios tended to be higher in the HP than in the LP group, but no metabolite reached statistical significance (Pbonferroni>0.09). There were no group differences at 8 years. Quantification of the impact of early programming factors revealed that the intervention group explained 0.6% of metabolome variance at both time points. Except for country of residence that explained 16% and 12% at 5.5 years and 8 years, respectively, none of the other factors explained considerably more variance than expected by chance. CONCLUSIONS: Plasma metabolome was largely unaffected by feeding choice and other early programming factors and we could not prove the existence of a long term programming effect of the plasma metabolome.

Commercial complementary food use amongst European infants and children: results from the EU Childhood Obesity Project.

PURPOSE: The objective of this secondary analysis is to describe the types of commercial complementary foods (CCF) consumed by infants and young children enrolled in the European Childhood Obesity Project (CHOP), to describe the contribution of CCF to dietary energy intakes and to determine factors associated with CCF use over the first 2 years of life. METHODS: The CHOP trial is a multicenter intervention trial in Germany, Belgium, Italy, Poland and Spain that tested the effect of varying levels of protein in infant formula on the risk for childhood obesity. Infants were recruited from October 2002 to June 2004. Dietary data on CCF use for this secondary analysis were taken from weighted, 3-day dietary records from 1088 infants at 9 time points over the first 2 years of life. RESULTS: Reported energy intakes from CCF during infancy (4-9 months) was significantly higher (p ≤ 0.002) amongst formula-fed children compared to breastfed children. Sweetened CCF intakes were significantly higher (p ≤ 0.009) amongst formula-fed infants. Female infants were fed significantly less CCF and infant age was strongly associated with daily CCF intakes, peaking at 9 months of age. Infants from families with middle- and high-level of education were fed significantly less quantities of CCF compared to infants with parents with lower education. Sweetened CCF were very common in Spain, Italy and Poland, with over 95% of infants and children fed CCF at 9 and 12 months of age consuming at least one sweetened CCF. At 24 months of age, 68% of the CHOP cohort were still fed CCF. CONCLUSIONS: CCF comprised a substantial part of the diets of this cohort of European infants and young children. The proportion of infants being fed sweetened CCF is concerning. More studies on the quality of commercial complementary foods in Europe are warranted, including market surveys on the saturation of the Western European market with sweetened CCF products.

Associations of sugar intake with anthropometrics in children from ages 2 until 8 years in the EU Childhood Obesity Project.

PURPOSE: We determined the association of total sugar intake with body weight and fat mass in children on an energy-equivalent basis and potential changes in the association from 2 to 8 years of age. METHODS: Data were available from the Childhood Obesity Project Trial initiated in 2002. Sugar intake was measured by 3-day weighed food protocols at 2, 3, 4, 5, 6, and 8 years of age. Body mass index (BMI) and fat mass index (FMI) were available at the same time points. To investigate the association of sugar intake with anthropometrics over time, linear mixed models were applied. Odds ratios for having a high BMI or FMI (above one standard deviation) were estimated by logistic random-effects models. To control for total energy intake, the residual method was chosen and models were additionally adjusted for total energy intake. RESULTS: Data were available for 809 children with in total 2846 observations. In an isocaloric model, an increase of 100 kcal from sugar per day was significantly associated with lower zBMI (- 0.033; 95% CI -0.061, - 0.005) and zFMI (- 0.050; 95% CI - 0.089, - 0.011). In addition, a 100 kcal higher sugar intake was related to lower odds of having a high zBMI (OR 0.743; 95% CI 0.611, 0.903). CONCLUSION: This study provides no indication that increased total sugar intake positively affects BMI on an energy-equivalent basis. Whether the negative association of sugar is due to physiological effects or points more to macronutrient preferences or a reporting bias (lower sugar intake) in children with higher BMI can be debated. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: http://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1 .

Lipomas of the central nervous system in the newborns - a report of eight cases.

BACKGROUND: Central nervous system lipomas are rare tumours. In most of the cases they are located in corpus callosum of the brain. The ultrasonographic image of lipomas tends to be quite characteristic. Final diagnosis is however done on a basis of brain resonance. The purpose of this work is to present proceeding in case of central nervous system lipomas with particular attention to diagnostic imaging. This work is based on own research. CASE REPORT: There are eight patients with central nervous system lipomas described in this work. The ultrasonographic imaging performed upon patients' birth revealed features of agenesis of corpus callosum with presence of hyperechoic structure in the area of median line within corpus callosum. This image correlated with Nuclear Magnetic Resonance examination results. Our research confirms that patients with central nervous system lipomas represent rare diagnostic and therapeutic cases. Due to characteristic results of ultrasonographic imaging of the brain, recognition of agenesis of corpus callosum would not cause difficulties. However the presence of hyperechoic structure without vascular flow which may suggest lipomas of corpus callosum would require final verification of the diagnosis and wider assessment of brain with NMR examination. We did not recognize any relation between corpus callosum pathology and neuroinfection of cytomegalovirus etiology. In all of the eight research cases there were malformations diagnostics conducted. There were genetic irregularities in case of two of the neonates only. Until today, all of the patients remain under neurological care. Their psychomotor development is regularly controlled. CONCLUSIONS: Taking into consideration that numerous malformations occur altogether with brain lipomas, it is recommended to conduct appropriate diagnostics, to inform parents on an essence of diagnosis and on necessity of observing child's psychomotor development. Obviously, it is crucial to secure a patient with paediatric and neurological care.