Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

European expert recommendations on clinical investigation and evaluation of high-risk medical devices for children.

Several high-risk medical devices for children have become unavailable in the European Union (EU), since requirements and costs for device certification increased markedly due to the EU Medical Device Regulation. The EU-funded CORE-MD project held a workshop in January 2023 with experts from various child health specialties, representatives of European paediatric associations, a regulatory authority and the European Commission Directorate General Health and Food Safety. A virtual follow-up meeting took place in March 2023. We developed recommendations for investigation of high-risk medical devices for children building on participants' expertise and results of a scoping review of clinical trials on high-risk medical devices in children. Approaches for evaluating and certifying high-risk medical devices for market introduction are proposed.

Effects of infant feeding with goat milk formula or cow milk formula on atopic dermatitis: protocol of the randomised controlled Goat Infant Formula Feeding and Eczema (GIraFFE) trial.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin condition significantly affecting quality of life. A small randomised trial showed an approximately one-third lower incidence of AD in goat milk formula-fed compared with cow milk formula-fed infants. However, due to limited statistical power, AD incidence difference was not found to be significant. This study aims to explore a potential risk reduction of AD by feeding a formula based on whole goat milk (as a source of protein and fat) compared with a formula based on cow milk proteins and vegetable oils. METHODS AND ANALYSIS: This two-arm (1:1 allocation), parallel, randomised, double-blind, controlled nutritional trial shall enrol up to 2296 healthy term-born infants until 3 months of age, if parents choose to start formula feeding. Ten study centres in Spain and Poland are participating. Randomised infants receive investigational infant and follow-on formulas either based on whole goat milk or on cow milk until the age of 12 months. The goat milk formula has a whey:casein ratio of 20:80 and about 50% of the lipids are milk fat from whole goat milk, whereas the cow milk formula, used as control, has a whey:casein ratio of 60:40 and 100% of the lipids are from vegetable oils. The energy and nutrient levels in both goat and cow milk formulas are the same. The primary endpoint is the cumulative incidence of AD until the age of 12 months diagnosed by study personnel based on the UK Working Party Diagnostic Criteria. The secondary endpoints include reported AD diagnosis, measures of AD, blood and stool markers, child growth, sleep, nutrition and quality of life. Participating children are followed until the age of 5 years. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethical committees of all participating institutions. TRIAL REGISTRATION NUMBER: NCT04599946.

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.

Eating Frequency in European Children from 1 to 96 Months of Age: Results of the Childhood Obesity Project Study.

We aimed to investigate the eating frequency (EF) in children over age, and examined the influence of country, sex, feeding mode and weight status on EF. We used the dietary data of the Childhood Obesity Project, which comprised European children from five countries. Dietary data of 3-days weighed and estimated records were available monthly from 1 to 9 and at 12-, 24-, 36-, 48-, 60-, 72- and 96-months old. Generalized additive mixed effects models were used to estimate EF trajectories with EF as outcome and applying age splines. Additionally, the models were further adjusted for country, feeding mode, sex or weight status. Data from 1244 children were analysed. EF was highest at 1 month with on average 7.3 ± 1.9 feeds per day, and fell to 5.1 ± 1.1 eating occasions at the age 96 months. Night feeding was similarly often than day feeding at 1 month but declined thereafter. Significant differences in EF were observed between countries (p < 0.05), with the highest EF in Poland, and between infant feeding modes, with a higher EF in breastfed than non-breastfed infants (p < 0.05). Sex and body weight were not associated with EF. Despite the importance of EF towards total energy intake, no association with weight status was found.

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.

Different protein intake in the first year and its effects on adiposity rebound and obesity throughout childhood: 11 years follow-up of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Infant feeding affects child growth and later obesity risk. We examined whether protein supply in infancy affects the adiposity rebound, body mass index (BMI) and overweight and obesity up to 11 years of age. METHODS: We enrolled healthy term infants from five European countries in a double blind randomized trial, with anticipated 16 examinations within 11 years follow-up. Formula-fed infants (n = 1090) were randomized to isoenergetic formula with higher or lower protein content within the range stipulated by EU legislation in 2001. A breastfed reference group (n = 588) was included. Adiposity rebound and BMI trajectories were estimated by generalized additive mixed models in 917 children, with 712 participating in the 11 year follow-up. RESULTS: BMI trajectories were elevated in the higher compared to the lower protein group, with significantly different BMI at adiposity rebound (0.24 kg/m2, 0.01-0.47, p = 0.040), and an increased risk for overweight at 11 years (adjusted Odds Ratio 1.70; 1.06-2.73; p = 0.027) but no significant difference for obesity (adjusted Odds Ratio 1.47; 0.66-3.27). The two formula groups did not differ in the timing of adiposity rebound, but all children with obesity at 11 years had an early adiposity rebound before four years. CONCLUSIONS: Compared to conventional high protein formula, feeding lower protein formula in infancy lowers BMI trajectories up to 11 years and achieves similar BMI values at adiposity rebound as observed in breastfed infants.

Time of Dietary Energy and Nutrient Intake and Body Mass Index in Children: Compositional Data Analysis from the Childhood Obesity Project (CHOP) Trial.

Meal timing is suggested to influence the obesity risk in children. Our aim was to analyse the effect of energy and nutrient distributions at eating occasions (EO), including breakfast, lunch, supper, and snacks, on the BMI z-score (zBMI) during childhood in 729 healthy children. BMI and three-day dietary protocols were obtained at 3, 4, 5, 6, and 8 years of age, and dietary data were analysed as the percentage of the mean total energy intake (TEI; %E). Intakes at EOs were transformed via an isometric log-ratio transformation and added as exposure variables to linear mixed-effects models. Stratified analyses by country and recategorization of EOs by adding intake from snacks to respective meals for further analyses were performed. The exclusion of subjects with less than three observations and the exclusion of subjects who skipped one EO or consumed 5% energy or less at one EO were examined in sensitivity analyses. Around 23% of the children were overweight at a given time point. Overweight and normal-weight children showed different distributions of dietary intakes over the day; overweight children consumed higher intakes at lunch and lower intakes of snacks. However, no significant effects of timing of EOs on zBMI were found in regression analyses.

Effect of maternal smoking during pregnancy on child blood pressure in a European cohort.

Hypertension is a public health issue that can have its origin in the early phases of development. Maternal smoking during pregnancy (MSDP) could play a role in offspring's cardio-metabolic programming. To assess the relationship between MSDP and later blood pressure (BP) in children we conducted a secondary analysis of a randomized dietary intervention trial (EU-Childhood Obesity Project). Healthy term infants with normal birth weight were recruited during the first 8 weeks of life in 5 European countries and followed until 11 years of age. Data on MSDP was collected at recruitment. BP and anthropometry were assessed at 11 years of age. Children were classified according to AAP guidelines as normal BP: BP < 90th percentile; high BP: ≥ 90th percentile with the subset of children having BP > 95th percentile categorized as hypertensive. Out of 572 children, 20% were exposed to MSDP. At 11 years, 26.8% had BP over the 90th centile. MSDP beyond 12 weeks of gestation was associated with higher systolic BP percentile (adjusted B 6.935; 95% CI 0.454, 13.429; p = 0.036) and over twofold increase likelihood of hypertension (OR 2.195; 95% CI 1.089, 4.423; p = 0.028) in children at 11 years. MSDP was significantly associated with later BP in children.

Assessing Neonatal Pain with NIPS and COMFORT-B: Evaluation of NICU's Staff Competences.

Background: Pain is considered "the 5th vital sign" that should be regularly assessed in the neonatal intensive care setting. Although over 40 pain assessment tools have been developed for neonates, their implementation in everyday practice is challenging. Epidemiological studies demonstrate that pain is still underassessed and undertreated in European NICUs. Purpose: To evaluate the interrater and intrarater reliability of the NIPS and COMFORT-B scales among the tertiary NICU's staff members 4 years after their implementation in local pain guidelines with no prior dedicated training. Methods: Physicians and nurses were invited to evaluate 5 video recordings of infants hospitalized in the intensive care settings, using the NIPS and COMFORT-B scales. The assessment took part twice at a 3-month interval. Interrater reliability was calculated for both scales using Kendall's W coefficient of concordance and Krippendorff's alpha coefficient. Cohen's kappa was used to assess intrarater reliability. Results: 17 physicians and 19 nurses took part in the study. Interrater agreement for the COMFORT-B scale was above 0.8 for Kendall's W coefficient (p < .01) and above 0.667 for Krippendorff's alpha coefficient. Kendall's W coefficient for the NIPS scores ranged between 0.7 and 0.8 (p < .01). Krippendorff's alpha was above 0.667. Intrarater agreement for both the COMFORT-B and NIPS scales was 0.693 and 0.724, respectively. Conclusions: Overall, the agreement between our staff members was moderately good for both scales. This is not enough to avoid inadequate pain assessment. More training is needed to improve NICU's staff competences in using pain scales.

Usefulness of the waist-to-height ratio for predicting cardiometabolic risk in children and its suggested boundary values.

BACKGROUND & AIMS: Only limited information is available on the usefulness of the waist-to-height ratio (WHtR) as an abdominal obesity marker in children. Our aim was to compare the ability of a WHtR >90th percentile, a WHtR ≥0.50, a WHtR ≥0.55 and a BMI z-score ≥2 SD to predict cardiometabolic risk in children followed-up at different ages. METHODS: We evaluated data from 660 children at 5, 8 and 11 years of age who participated in the Childhood Obesity Project trial in 5 European countries. We classified children with or without cardiometabolic (CMet) risk (yes vs. no) according to the presence of ≥2 parameters (blood pressure, HOMA-IR, triglyceride levels and high-density lipoprotein (HDL) cholesterol levels) ≥90th percentile. RESULTS: The odds ratio for CMet risk in children at all followed-up ages was statistically significant for all measures. The OR for the WHtR≥0.55 cut-off was 29.1 (5.6, 151.7) at 5 years of age, 11.8 (4.1, 33.8) at 8 year of age and 3.6 (1.7, 7.7) at 11 years of age, compared to the WHtR<0.55 cut-off. The WHtR≥0.55 cut-off showed a higher OR at younger ages than the BMI z-score ≥2SD, WHtR ≥90th percentile and WHtR≥0.50 cut-offs and a higher positive predictive value (82% at 5 years of age compared to 55%, 36% and 41%, respectively). CONCLUSION: A WHtR≥0.55 is a suitable cut-off for screening children at high cardiometabolic risk in the general young European population.

Sleep duration and problem behaviour in 8-year-old children in the Childhood Obesity Project.

There is growing evidence that insufficient sleep has negative effects on the mental health of children. The aim of this study is to examine the associations between device-measured sleep duration and internalizing and externalizing problems in 8-year-old children. The study is a secondary analysis of data from the Childhood Obesity Project conducted in five European countries. Nocturnal sleep duration was measured with the SenseWear™ Armband 2. Parents rated their child's internalizing and externalizing problems on the Child Behaviour Checklist. Behaviour scores were dichotomized at the 90th percentile based on sex- and country-specific z-scores. Logistic regression models were applied to test the associations between sleep duration and behaviour. Data were available for 406 8-year-old children. The average sleep duration was 9.25 h per night (SD: 0.67) with 1464 nights measured in total. The sleep duration recommendation of the American Academy of Sleep Medicine for school-aged children (9-12 h) was met by 66.7% of children. One hour of additional sleep per night significantly reduced the risk of having internalizing problems (adjusted OR = 0.51; 95% CI 0.29-0.91). Children who adhered to the sleep duration recommendation had a lower risk for internalizing problems (adjusted OR = 0.45; 95% CI 0.21-0.99). Sleep duration and externalizing problems showed no significant association. Longer sleep duration was associated with a reduced risk of having internalizing problems but not externalizing problems. Results highlight that it is important to ensure adequate sleep duration throughout primary-school years for the optimal emotional health of children. Trial registration number: NCT00338689. Registered: June 19, 2006.

Dietary patterns acquired in early life are associated with cardiometabolic markers at school age.

BACKGROUND & AIMS: it has previously been described that dietary patterns established early in life tracked to late childhood. The aim of the present work was to analyse the association of dietary patterns that tracked from 2 to 8y with cardiometabolic markers at 8y of age. METHODS: The 3 identified patterns at 2y (that previous analyses showed to track to age 8y) were: "CoreDP", loaded for vegetables, fruits, fish, olive oil, etc.; "F&SDP", loaded by poor-quality fats and sugars; and "ProteinDP", mainly loaded by animal protein sources. Cardiometabolic markers at 8y were systolic blood pressure (SBP), insulin resistance (HOMA-IR), and triglycerides, and BMI z-score. To examine whether the association of diet with the outcomes was the result of a direct effect of diet at either two or 8y, or synergy between them, we used structural equation models. RESULTS: the associations between the patterns and the health outcomes were: CoreDP was inversely associated with SBP and HOMA-IR; ProteinDP was directly associated with HOMA-IR and SBP; and adherence to F&SDP was directly associated with triglycerides and SBP. The associations between the patterns and the health outcomes were independent of BMI and were the result of a direct effect of diet at 2y, an indirect effect of diet at 2y through diet at 8y or a combination between both pathways. CONCLUSION: dietary patterns acquired in early life, persisting to later childhood, were associated with cardiometabolic markers at school age independently of BMI.

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 .

Fibre Intake Is Associated with Cardiovascular Health in European Children.

BACKGROUND: We aimed at analysing the association between dietary fibre intake during childhood and cardiovascular health markers. METHODS: We used observational longitudinal analysis and recorded diet using 3-day diaries at the ages of 3, 4, 5, 6, and 8 years in children from the EU Childhood Obesity Project Trial. At the age of 8, waist circumference, systolic and diastolic blood pressure (SBP and DBP) and biochemical analyses (lipoproteins, triglycerides and homeostasis model for insulin resistance (HOMA-IR)) were evaluated. Those parameters were combined into a cardiometabolic risk score through the sum of their internal z-scores. RESULTS: Four-hundred children (51.8% girls) attended to the 8-year visit with a 3-day diary. Adjusted linear regression models showed that children who repeatedly stayed in the lowest tertile of fibre intake during childhood had higher HOMA-IR (p = 0.004), higher cardiometabolic risk score (p = 0.02) and a nonsignificant trend toward a higher SBP at 8 years. The higher the dietary intake of soluble fibre (from fruits and vegetables) at 8 years, the lower the HOMA-IR and the cardiometabolic risk score (p = 0.002; p = 0.004). SBP was directly associated with fibre from potatoes and inversely with fibre from nuts and pulses. CONCLUSION: A diet rich in dietary fibre from fruits, vegetables, pulses and nuts from early childhood was associated to a healthier cardiovascular profile, regardless of children's weight.

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

BACKGROUND: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. METHODS: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. RESULTS: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7). CONCLUSIONS: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

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.

Complete closure of the ductus arteriosus in the foetus with transposition of the great arteries.

Prenatal restriction of the ductus arteriosus can manifest as persistent pulmonary hypertension in the newborn, especially dangerous with the transposition of the great arteries. Its aetiology has long been related to maternal intake of non-steroidal anti-inflammatory drugs; however, some other substances, including polyphenols, may have similar properties. We describe a case of complete prenatal closure of the ductus arteriosus in the foetus with transposition of the great arteries. The newborn presented with pulmonary hypertension unresponsive to pharmacotherapy and died of multi-organ failure.

Effects of screen time and playing outside on anthropometric measures in preschool aged children.

OBJECTIVE: In view of the current obesity epidemic, studies focusing on the interplay of playing outside (PO), screen time (ST) and anthropometric measures in preschool age are necessary to guide evidence-based public health planning. We therefore investigated the relationship between average time spent PO and ST from the ages 3 to 6 years and anthropometric measures at 6 years of age. METHODS: PO and ST of 526 children of the European Childhood Obesity Project (CHOP) were annually assessed by questionnaire from 3 until 6 years of age. Body weight, waist circumference and height were measured at 3 and 6 years of age to calculate Body-Mass-Index z-Scores (zBMI) and waist-to-height ratio (WTH). Linear, logistic and quantile regressions were used to test whether average time spent PO and ST in the 4 year period had an effect on anthropometric measures at age 6 years. RESULTS: Longer daily ST was associated with a higher zBMI (P = 0.002) and WTH (P = 0.001) at 6 years of age. No significant associations were found for time spent PO. Each additional hour of average ST during the 4 year period resulted in a 66% higher risk of having a zBMI score over 1 (P < 0.001) and almost twice the risk (94% higher risk) of having an zBMI score over 2 (P < 0.001) at 6 years. CONCLUSIONS: Excessive ST during preschool age is a risk factor for increased zBMI at 6 years, regardless of time spent PO. Reducing high levels of ST during preschool age, for e.g. at least 1h per week, could help preventing childhood obesity.