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Aim In 2004, a model identifying children at risk of academic or behavioural limitations after bacterial meningitis ( BM) was presented. Risk factors were male gender, low birthweight, lower educational level of the father, Streptococcus pneumoniae, lower cerebrospinal fluid ( CSF) leucocyte count, delay between admission and start of antibiotics, dexamethasone <2 days, seizures and prolonged fever. The aim of this study was to validate that prediction model in an independent cohort. Methods Academic or behavioural limitations were determined in 93 Dutch school-age BM survivors. Risk factors for limitations were obtained from medical files. Validation was performed by applying the model in the cohort, then assessing discrimination and goodness of fit. Multiple imputation techniques were used to deal with missing values. Results Although fit of the model appeared good when it came to similarity of expected and observed cases (p-value of the Hosmer-Lemeshow test 0.24-0.57), discrimination was poor. Area under the curve ( AUC) of the receiver operated characteristics ( ROC) curve of the model was 0.83 (95% CI: 0.77-0.89) in the development cohort and 0.53 (95% CI: 0.41-0.65) in the validation cohort. Conclusion External validation of the model was unsuccessful. It is not suitable for implementation in practice. [ABSTRACT FROM AUTHOR]

Introduction: Sleep is crucial for physical and psychological health, and disturbances are closely linked to psychiatric disorders, making their management essential for improving treatment outcomes and preventing relapse. Although sleep disturbances are implicated in psychopathology of eating disorders, its role in anorexia nervosa (AN) remains unclear. This review aimed to characterise sleep in AN., Methods: A systematic search was conducted in four scientific databases, including papers from inception to 25 May 2024. A machine learning algorithm (ASReview) was utilised to screen titles and abstracts for eligibility. Sleep quantity, architecture, and quality were investigated. Meta-analyses were conducted to investigate the difference between patients with AN and healthy controls (HC) in total sleep time (TST), wake after sleep onset (WASO), sleep onset latency (SOL), sleep efficiency, Sleep Stage 1, 2, slow wave sleep, rapid eye movement (REM) sleep and REM latency. Certainty of evidence was assessed using the GRADE approach., Results: Out of 67 potentially eligible papers, 31 were included in this review, with 15 in the meta-analyses. Statistically significant average mean differences were found for TST (-32.1 min [95% CI: -50.9, -13.4]), WASO (19.0 min [95% CI: -2.4, 40.3]), and sleep efficiency (-4.4% [95% CI: -7.9, -0.9]). Additionally, Sleep stage 1 was significantly increased (2.4% [95%-CI: 0.05, 4.7]), while REM sleep was reduced (-2.1% [95%-CI: -4.2, -0.02]). Subgroup analysis showed that TST and WASO did not improve significantly after weight restoration., Conclusion: Sleep in patients with AN is impaired, with lower TST and sleep efficiency, higher WASO, more time in stage 1 sleep, and less in REM. Weight restoration alone may not improve sleep. While more research is needed, substantial accompanying sleep disturbances in AN justifies addressing these in current treatment practice, also because of the chronic character of AN and importance of sleep for long term (mental) health., (© 2024 The Author(s). European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Polysomnography, the gold-standard for measuring sleep, is costly, intrusive and usually limited to 1 night. Actigraphy offers a more affordable, less intrusive method over multiple nights. However, little research validates ActiGraph accelerometers against polysomnography, especially in children. This study evaluated the validity of different algorithms and compared wrist versus ankle accelerometer placements for estimating sleep in children aged 1-12 years. Twenty-nine children undergoing overnight type 1 polysomnography wore ActiGraph accelerometers. Six algorithms were evaluated against polysomnography using Pearson correlations, intraclass correlation, paired t-tests and Bland-Altman plots. Agreement was classified as poor (intraclass correlation coefficient < 0.4), fair (0.4 < intraclass correlation coefficient < 0.6), good (0.6 < intraclass correlation coefficient < 0.75) or excellent (intraclass correlation coefficient > 0.75). Total sleep time was the primary outcome. For wrist-worn devices, the Sadeh (Actilife) and Cole-Kripke (Actilife and GGIR) algorithms showed excellent agreement with polysomnography (intraclass correlation coefficient = 0.80-0.85), while vanHees showed good agreement (intraclass correlation coefficient = 0.67) and Galland showed fair agreement (intraclass correlation coefficient = 0.46). The Cole-Kripke algorithm did not significantly differ from polysomnography total sleep time, whereas others underestimated total sleep time. For ankle-worn devices, Sadeh (Actilife), Cole-Kripke (Actilife) and vanHees algorithms demonstrated excellent agreement (intraclass correlation coefficient = 0.75-0.82). No significant differences were found between wrist and ankle placements for certain algorithms. The findings support accelerometry as a valid tool for sleep assessment in children, recommending that algorithm selection be tailored to specific study requirements., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Sleep is essential for the cognitive, emotional, and physical development of children. Common sleep problems occur in 20-30% of children and are often resolved by improved sleep hygiene. Sleep disorders are more severe conditions, e.g., insomnia, obstructive sleep apnea, and circadian rhythm disturbances. If left untreated, these can have significant long-term consequences, including impaired cognitive function, increased risk of psychiatric conditions like anxiety and depression, and higher risk of obesity and cardiovascular diseases. To prevent these complications, timely recognition and management is essential. In this paper, we address the medical perspectives of common sleep disturbances in children, focusing on their diagnosis and treatment. Sleep hygiene education, behavioral interventions, and ambient adaptations are first-line interventions for managing all sleep disturbances in children. In cases where behavioral approaches are insufficient, other (non-)pharmacological options are discussed, with a focus on their efficacy and safety in children. Conclusions: Finally, potential long-term consequences and directions for future research are discussed that may improve sleep-related health and well-being., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fatigue is a commonly reported clinical symptom, yet research on fatigue in children with severe asthma is missing. We aimed to explore the extent of fatigue in severe pediatric asthma and identify associated factors., Method: This study was conducted within the Pediatric Asthma Non-Invasive Diagnostic Approaches (PANDA), an observational cohort of 6- to 17-year-old Dutch children with severe asthma. The Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL™-MFS) was used to measure self-reported fatigue. Fatigue levels were compared with a general pediatric Dutch population using linear regression, and quantifying the prevalence of "fatigued" (-2 < Standard deviations [SD] ≤ -1) and "severely fatigued" (SD ≤ -2) children. Secondly, we performed linear regression analyses to explore whether fatigue levels were independently associated with asthma attacks, comorbidities, medication, pulmonary function, symptom control, and asthma-related quality of life (QoL)., Results: Severe pediatric asthma patients (n = 78, mean age 11.8 ± 3.1 years) reported significantly more fatigue than Dutch peers (n = 328, mean age 11.8 ± 3.2 years) mean difference in z-score: -0.68; 95%CI -0.96, -0.40. In the severe asthma group, 28.2% scored as "fatigued" and 15.4% as "severely fatigued," compared with 14.0% and 3.4% in the general population. In pediatric asthma patients, asthma-related QoL (β = 0.77, p < .01, ΔR 2  = .43), symptom control (β = 0.56, p < .01, ΔR 2  = .24) and a dysfunctional breathing pattern (β = -0.36, p < .01, ΔR 2  = .12) were most strongly associated with fatigue scores., Conclusion: Fatigue is a common symptom in children with severe asthma and is associated with multiple clinical factors and patient-reported outcomes. It should be considered as an important treatment target., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Although sleep is essential for (recovery of) health, it is adversely affected by hospitalization, due to disease discomfort, environmental noise, and care routines, causing reduced sleep and increased disturbances. This study evaluates factors affecting sleep quality and quantity in hospitalized children and compares inpatient sleep with sleep at home. Using an observational, prospective study design, we assessed sleep in hospitalized children aged 1-12 years, admitted to a tertiary center, and compared this with home 6-8 weeks after discharge. We measured total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency, awakenings, and subjective sleep quality, using actigraphy, sleep diaries, and PROMIS questionnaires. We explored an array of sleep-disturbing factors. Regression analyses identified key determinants affecting sleep patterns, while mixed linear models compared sleep in hospital to sleep at home. Out of 621 eligible patients, 467 were invited, and 272 (58%) consented to participate. Key determinants of sleep included pain, number of previous admissions, (underlying) chronic illness, and environment-, staff-, and disease-related factors. Parents reported lower perceived sleep quality in the hospital compared to at home, 97-min (SE 9) lower TST, 100-min (5) longer WASO, more difficulties with falling asleep, lower sleep satisfaction, and more awakenings. Actigraphy outcomes revealed shorter TST (20 min (6)), but better sleep efficiency and fewer awakenings in the hospital. Conclusion: Sleep in hospital was compromised in comparison to sleep at home, primarily due to disturbances related to treatment, environment, and staff. These findings underscore the necessity and potential of relative simple interventions to improve sleep quality and minimize sleep disturbances in hospitalized children., (© 2024. The Author(s).)

Polysomnography (PSG) is the reference standard of sleep measurement, but is burdensome for the participant and labor intensive. Affordable electroencephalography (EEG)-based wearables are easy to use and are gaining popularity, yet selecting the most suitable device is a challenge for clinicians and researchers. In this systematic review, we aim to provide a comprehensive overview of available EEG-based wearables to measure human sleep. For each wearable, an overview will be provided regarding validated population and reported measurement properties. A systematic search was conducted in the databases OVID MEDLINE, Embase.com and CINAHL. A machine learning algorithm (ASReview) was utilized to screen titles and abstracts for eligibility. In total, 60 papers were selected, covering 34 unique EEG-based wearables. Feasibility studies indicated good tolerance, high compliance, and success rates. The 42 included validation studies were conducted across diverse populations and showed consistently high accuracy in sleep staging detection. Therefore, the recent advancements in EEG-based wearables show great promise as alternative for PSG and for at-home sleep monitoring. Users should consider factors like user-friendliness, comfort, and costs, as these devices vary in features and pricing, impacting their suitability for individual needs., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sleep is essential for maintenance and restoration of health, yet studies exploring this in hospitalized children are scarce. In a qualitative study, we assessed the perceived quality of sleep, factors affecting sleep, and the role of health care professionals in the sleep environment for hospitalized children aged 1 to 12 years. Data were obtained from 11 semi-structured, audio-recorded, and verbatim-transcribed interviews with parents, and analyzed using a systematic thematic analysis. The interviews were coded based on iterative assessment of transcripts. Subsequently, categories and interpretative main themes were identified. Four themes emerged: (1) being informed, keeping informed; (2) coordination of care; (3) parents as main advocates for their child's sleep; and (4) environmental disturbers. Parents reported differences in their child's sleep quality during hospital compared with home. Sleep is substantially affected during hospitalization, prompting the need for interventions to improve the quality of sleep of children. Parents provided valuable suggestions for improvements., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Maternal obesity during pregnancy is associated with poorer cardiovascular health (CVH) in children. A strategy to improve CVH in children could be to address preconception maternal obesity by means of a lifestyle intervention. We determined if a preconception lifestyle intervention in women with obesity improved offspring's CVH, assessed by magnetic resonance imaging (MRI)., Methods: We invited children born to women who participated in a randomised controlled trial assessing the effect of a preconception lifestyle intervention in women with obesity. We assessed cardiac structure, function and geometric shape, pulse wave velocity and abdominal fat tissue by MRI., Results: We included 49 of 243 (20.2%) eligible children, 24 girls (49%) girls, mean age 7.1 (0.8) years. Left ventricular ejection fraction was higher in children in the intervention group as compared to children in the control group (63.0% SD 6.18 vs. 58.8% SD 5.77, p = 0.02). Shape analysis showed that intervention was associated with less regional thickening of the interventricular septum and less sphericity. There were no differences in the other outcomes of interest., Conclusion: A preconception lifestyle intervention in women with obesity led to a higher ejection fraction and an altered cardiac shape in their offspring, which might suggest a better CVH., Impact: A preconception lifestyle intervention in women with obesity results in a higher ejection fraction and an altered cardiac shape that may signify better cardiovascular health (CVH) in their children. This is the first experimental human evidence suggesting an effect of a preconception lifestyle intervention in women with obesity on MRI-derived indicators of CVH in their children. Improving maternal preconception health might prevent some of the detrimental consequences of maternal obesity on CVH in their children., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To determine factors affecting inpatient sleep and assess the range and effectiveness of non-pharmacological interventions aimed at improving the sleep of patients admitted to regular care wards., Methods: A systematic literature search was conducted in five scientific databases, including articles published from inception to June 23rd, 2023. Eligible studies evaluated sleep disturbing factors or the effect of non-pharmacological intervention(s). Meta-analyses on intervention studies were conducted using a random effects model. Certainty of evidence was assessed using the GRADE approach., Results: Out of 591 potentially eligible studies, 229 were included in this review. Sleep disturbers were identified in 153 studies, and 102 studies were eligible for meta-analysis. Common factors contributing to poor sleep included noise, light, care-related interruptions, pain, and anxiety. The meta-analyses revealed large pooled effects in favor of sleep for the use of eye masks and earplugs, headphones and white noise, aromatherapy, massage, muscle relaxation and breathing exercises, and advanced nursing strategies. However, the certainty of the evidence ranged from moderate to very low., Conclusion: Inpatient sleep is often disturbed by patient-related, care-related, and environmental factors. While there are promising non-pharmacological interventions, the overall quality of studies, heterogeneity in study populations, and differences in outcome measures present challenges for drawing definitive conclusions.

Background: Sleep is essential for recovery from illness. As a result, researchers have shown a growing interest in the sleep of hospitalized patients. Although many studies have been conducted over the past years, an up to date systematic review of the results is missing., Objective: The objective of this systematic review was to assess sleep quality and quantity of hospitalized patients and sleep disturbing factors., Methods: A systematic literature search was conducted within four scientific databases. The search focused on synonyms of 'sleep' and 'hospitalization'. Papers written in English or Dutch from inception to April 25th,2022 were included for hospitalized patients >1 year of age. Papers exclusively reporting about patients receiving palliative, obstetric or psychiatric care were excluded, as well as patients in rehabilitation and intensive care settings, and long-term hospitalized geriatric patients. This review was performed in accordance with the PRISMA guidelines., Results: Out of 542 full text studies assessed for eligibility, 203 were included, describing sleep quality and/or quantity of 17,964 patients. The median sample size of the studies was 51 patients (IQR 67, range 6-1472). An exploratory meta-analysis of the Total Sleep Time showed an average of 7.2 h (95%-CI 4.3, 10.2) in hospitalized children, 5.7 h (95%-CI 4.8, 6.7) in adults and 5.8 h (95%-CI 5.3, 6.4) in older patients (>60y). In addition, a meta-analysis of the Wake After Sleep Onset (WASO) showed a combined high average of 1.8 h (95%-CI 0.7, 2.9). Overall sleep quality was poor, also due to nocturnal awakenings. The most frequently cited external factors for poor sleep were noise and number of patients in the room. Among the variety of internal/disease-related factors, pain and anxiety were most frequently mentioned to be associated with poor sleep., Conclusion: Of all studies, 76% reported poor sleep quality and insufficient sleep duration in hospitalized patients. Children sleep on average 0.7-3.8 h less in the hospital than recommended. Hospitalized adults sleep 1.3-3.2 h less than recommended for healthy people. This underscores the need for interventions to improve sleep during hospitalization to support recovery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V.)

Background: Improving maternal lifestyle before conception may prevent the adverse effects of maternal obesity on their children's future cardiovascular disease (CVD) risk. In the current study, we examined whether a preconception lifestyle intervention in women with obesity could alter echocardiographic indices of cardiovascular health in their children., Methods: Six years after a randomized controlled trial comparing the effects of a 6-month preconception lifestyle intervention in women with obesity and infertility prior to fertility care to prompt fertility care, 315 of the 341 children conceived within 24 months after randomization were eligible for this study. The intervention was aimed at weight loss (≥5% or until BMI < 29 kg/m 2 ). Children underwent echocardiographic assessment of cardiac structure and function, conducted by a single pediatric cardiologist, blinded to group allocation. Results were adjusted for multiple variables including body surface area, age, and sex in linear regression analyses., Results: Sixty children (32 girls, 53%) were included, mean age 6.5 years (SD 1.09). Twenty-four children (40%) were born to mothers in the intervention group. Children of mothers from the intervention group had a lower end-diastolic interventricular septum thickness (-0.88 Z-score, 95%CI -1.18 to -0.58), a lower left ventricle mass index (-8.56 g/m 2 , 95%CI -13.09 to -4.03), and higher peak systolic and early diastolic annular velocity of the left ventricle (1.43 cm/s 95%CI 0.65 to 2.20 and 2.39 cm/s 95%CI 0.68 to 4.11, respectively) compared to children of mothers from the control group., Conclusions: Children of women with obesity, who underwent a preconception lifestyle intervention, had improved cardiac structure and function; a thinner interventricular septum, lower left ventricle mass, and improved systolic and diastolic tissue Doppler velocities. Despite its high attrition rates, our study provides the first experimental human evidence suggesting that preconception lifestyle interventions may present a method of reducing CVD risk in the next generation., Clinical Trial Registration: LIFEstyle study: Netherlands Trial Register: NTR1530 ( https://www.trialregister.nl/trial/1461 ). This follow-up study was approved by the medical ethics committee of the University Medical Centre Groningen (METC code: 2008/284)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Sleep is vital for recovery during hospital stay. Many sleep-promoting interventions have been investigated in the past. Nurses seem to overestimate their patients sleep and their perspective is needed for these interventions to be successfully implemented., Objectives: To assess the patient's and nurse's agreement on the patient's sleep and factors disturbing sleep., Methods: The instruments used included 1) five Richard-Campbell Sleep Questionnaire (RCSQ) items plus a rating of nighttime noise and 2) the Consensus Sleep Diary (CSD). The mean of the five RCSQ items comprised a total score, which reflects sleep quality. Once a week, unannounced, nurses and patients were asked to fill in questionnaires concerning last night's sleep. Neither nurses nor patients knew the others' ratings. Patient-nurse agreement was evaluated by using median differences and Bland-Altman plots. Reliability was evaluated by using intraclass correlation coefficients., Results: Fifty-five paired patient-nurse assessments have been completed. For all RCSQ subitems, nurses' scores were higher (indicating "better" sleep) than patients' scores, with a significantly higher rating for sleep depth (median [IQR], 70 [40] vs 50 [40], P = .012). The Bland-Altman plots for the RSCQ Total Score (r = 0.0593, P = .008) revealed a significant amount of variation (bias). The intra-class correlation coefficient (ICC) indicated poor reliability for all 7 measures (range -0.278 - 0.435). Nurses were relatively overestimating their own role in causing sleep disturbances and underestimating patient-related factors., Conclusions: Nurses tend to overestimate patients' sleep quality as well as their own role in causing sleep disturbances., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors. Published by Elsevier B.V.)

Maternal obesity is associated with adverse metabolic outcomes in her offspring, from the earliest stages of development leading to obesity and poorer cardiometabolic health in her offspring. We investigated whether an effective preconception lifestyle intervention in obese women affected cardiometabolic health of their offspring. We randomly allocated 577 infertile women with obesity to a 6-month lifestyle intervention, or to prompt infertility management. Of the 305 eligible children, despite intensive efforts, 17 in the intervention and 29 in the control group were available for follow-up at age 3-6 years. We compared the child's Body Mass Index (BMI) Z score, waist and hip circumference, body-fat percentage, blood pressure Z scores, pulse wave velocity and serum lipids, glucose and insulin concentrations. Between the intervention and control groups, the mean (±SD) offspring BMI Z score (0.69 (±1.17) vs. 0.62 (±1.04)) and systolic and diastolic blood pressure Z scores (0.45 (±0.65) vs. 0.54 (±0.57); 0.91 (±0.66) vs. 0.96 (±0.57)) were similar, although elevated compared to the norm population. We also did not detect any differences between the groups in the other outcomes. In this study, we could not detect effects of a preconception lifestyle intervention in obese infertile women on the cardiometabolic health of their offspring. Low follow-up rates, perhaps due to the children's age or the subject matter, combined with selection bias abating contrast in periconceptional weight between participating mothers, hampered the detection of potential effects. Future studies that account for these factors are needed to confirm whether a preconception lifestyle intervention may improve the cardiometabolic health of children of obese mothers.

Objectives: To conduct a scoping review to 1) describe findings and determinants of physical functioning in children during and/or after PICU stay, 2) identify which domains of physical functioning are measured, 3) and synthesize the clinical and research knowledge gaps., Data Sources: A systematic search was conducted in PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews guidelines., Study Selection: Two investigators independently screened and included studies against predetermined criteria., Data Extraction: One investigator extracted data with review by a second investigator. A narrative analyses approach was used., Data Synthesis: A total of 2,610 articles were identified, leaving 68 studies for inclusion. Post-PICU/hospital discharge scores show that PICU survivors report difficulties in physical functioning during and years after PICU stay. Although sustained improvements in the long-term have been reported, most of the reported levels were lower compared with the reference and baseline values. Decreased physical functioning was associated with longer hospital stay and presence of comorbidities. A diversity of instruments was used in which mobility and self-care were mostly addressed., Conclusions: The results show that children perceive moderate to severe difficulties in physical functioning during and years after PICU stay. Longitudinal assessments during and after PICU stay should be incorporated, especially for children with a higher risk for poor functional outcomes. There is need for consensus on the most suitable methods to assess physical functioning in children admitted to the PICU., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The mean of GFR-estimates based on serum creatinine (eGFR crea ) and cystatin C (eGFR cys ) has superior accuracy than each estimate alone. Recent studies have shown that agreement between eGFR crea and eGFR cys is an indicator for the accuracy of the mean of the two estimates. As long as the difference between the two (|ΔeGFR|) is below 40%, a high P 30 accuracy rate of more than 90% was documented in research settings using gold-standard GFR measurements. This was the case in approximately 80% of the measurements. The study was set out to explore | Δ eGFR| in a broader pediatric nephrological population and identify factors influencing the discrepancy between eGFR crea and eGFR cys . We retrospectively analyzed 1596 simultaneous cystatin C and creatinine measurements in 649 unique patients at the pediatric nephrology outpatient clinic of VU university medical center. The FASage equation was used to calculate eGFR crea , FAScys for eGFR cys . |ΔeGFR| was calculated as 100x(|eGFR crea -eGFR cys |)/(0.5x(eGFR crea +eGFR cys ). ΔeGFR below 40% was considered high agreement. Patient characteristics like age, diagnosis, glucocorticosteroid use, eGFR, BMI and sex were analyzed for their effect on ΔeGFR below or above 40% using non-parametric tests and a potential explanation for measurements with low agreement was sought. Eighty-seven percent of the population had a |ΔeGFR| lower than 40%. Measurements with |ΔeGFR| above 40% were significantly more frequent from patients with neural tube defects. In 102 out of 208 measurements with low agreement, a potential explanation was found. In a broad pediatric nephrological population, |ΔeGFR| is below 40% in the vast majority of measurements. In this group, the mean of eGFR crea and eGFR cys can be used as an accurate estimate of GFR.

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.

Objective: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring?, Study Design: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance., Results: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences., Conclusions: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Women's lifestyle has important implications for the development and health of their offspring. Yet little is known about the association between women's preconception dietary intake and physical activity with cardiovascular health of the offspring. We therefore examined this association in a group of Dutch women with overweight or obesity (BMI ≥ 29 kg/m 2 ) and infertility, who participated in a 6-month randomized preconception lifestyle intervention trial, and their offspring ( n = 46). Preconception dietary intake and physical activity were assessed during the 6-month intervention using a food frequency questionnaire and the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH), respectively. Offspring cardiovascular health (i.e., BMI, waist:height ratio, systolic and diastolic blood pressure, fat and fat free mass, and pulse wave velocity) was measured at age 3-6 years. Multivariable linear regression analyses were used to examine the associations between preconception lifestyle and offspring cardiovascular health. Higher preconception vegetable intake (per 10 g/day) was associated with lower offspring diastolic blood pressure (Z-score: -0.05 (-0.08; -0.01); p = 0.007) and higher preconception fruit intake (per 10 g/day) was associated with lower offspring pulse wave velocity (-0.05 m/s (-0.10; -0.01); p = 0.03). Against our expectations, higher preconception intake of sugary drinks was associated with a higher offspring fat free mass (0.54 kg (0.01; 1.07); p = 0.045). To conclude, preconception dietary intake is associated with offspring health.

Background: Postgraduate medical education (PGME) has become increasingly individualized, and entrustable professional activities (EPAs) have been adopted to operationalize this. At the same time, the process and content to determine residents' progress using high-stakes summative entrustment decisions by clinical competency committees (CCCs) is not yet well established., Objective: We evaluated the experiences with a structured process for assessment of EPAs to attain uniform summative entrustment decisions for a national sample of pediatric residents., Methods: An EPA-based national PGME program for pediatric residents was introduced in the Netherlands, including a process of uniform summative entrustment decisions, termed the Evaluation and Assessment of Residents by Supervisors (EARS) procedure. To evaluate the program, we assessed survey data and information from invitational conferences., Results: Beginning in January 2017, 125 pediatric residents in all 8 Dutch residency regions started training in the EARS program. The program enabled robust summative entrustment decisions. Preliminary data suggested that faculty, despite increased preparation time, appreciated the comprehensive appraisal of resident qualifications. The EPA-based program was well accepted by residents. Fifty-one percent (57 of 112) had at least 2 EARS procedures per year, and for 75% (84 of 112) the level of supervision was often or always adjusted to their level of training., Conclusions: A national EPA-based program provided a structured process for summative entrustment decisions by CCCs and enabled individualized stepwise progression of residents toward unsupervised practice. Broader application of these concepts may require adaptations to accommodate different health care systems and specialties., Competing Interests: The authors present this work on behalf of the TOP2020 group, also including J. van der Velden, Radboud University Nijmegen, D. Bosman, Amsterdam University Medical Center/Emma Children's Hospital, L. Rotte, Utrecht University Medical Center, L. Sonneveld, Erasmus Medical Center, Rotterdam, L. Tjaden, Amsterdam University Medical Center/Emma Children's Hospital, G. van Well, Maastricht University Medical Center. Conflict of interest: The authors declare they have no competing interests.

There is increasing evidence linking maternal diet and physical activity before and during pregnancy with offspring's cardiovascular health. Although many studies examined this association, the evidence has not been reviewed systematically. We therefore undertook a systematic review to synthesize evidence examining the association of maternal diet and physical activity before and during pregnancy with offspring's blood pressure and vascular health. We systematically searched the databases MEDLINE and EMBASE from inception to June 30, 2017. Eligibility screening, data extraction and quality assessment were performed by two independent reviewers. A total of 19 articles were included comprising three randomized controlled trials and 16 observational studies. Of the studies that examined the association of interest, 60% (three out of five studies) showed that high maternal carbohydrate intake was associated with higher offspring's blood pressure. Maternal protein intake during pregnancy was negatively associated with offspring carotid intima-media thickness in two out of two studies. No consistent findings for maternal fatty acid intake were found. There were too few studies to draw conclusions on energy intake, fibre intake, protein/carbohydrate ratio, specific foods, dietary patterns and maternal physical activity. Heterogeneity in exposure and outcome assessment hampered pooling. Also, owing to the observational nature of most studies, causality cannot be established. Harmonization of valid exposure and outcome measurements, and the development of core outcome sets are needed to enable more robust conclusions.

Background: The preconceptional period may be an optimal window of opportunity to improve lifestyle. We previously showed that a 6 month preconception lifestyle intervention among women with obesity and infertility was successful in decreasing the intake of high caloric snacks and beverages, increasing physical activity and in reducing weight in the short term. We now report the effects of the preconception lifestyle intervention on diet, physical activity and body mass index (BMI) at 5.5 years (range = 3.7-7.0 years) after the intervention., Methods: We followed women who participated in the LIFEstyle study, a multicentre RCT in which women with obesity and infertility were assigned to a six-month lifestyle intervention program or prompt infertility treatment (N = 577). Diet and physical activity 5.5 years later were assessed with an 173-item food frequency questionnaire (N = 175) and Actigraph triaxial accelerometers (N = 155), respectively. BMI was calculated from self-reported weight and previously measured height (N = 179). Dietary intake, physical activity, and BMI in the intervention and control group were compared using multivariate regression models. Additionally, dietary intake, physical activity and BMI of women allocated to the intervention arm with successful weight loss during the intervention (i.e. BMI < 29 kg/m 2 or ≥ 5% weight loss), unsuccessful weight loss and the control group were compared with ANCOVA., Results: Although BMI did not differ between the intervention and control group 5.5 years after the intervention (- 0.5 kg/m 2 [- 2.0;1.1]; P = 0.56), the intervention group did report a lower energy intake (- 216 kcal/day [- 417;-16]; P = 0.04). Women in the intervention arm who successfully lost weight during the intervention had a significantly lower BMI at follow-up compared to women in the intervention arm who did not lose weight successfully (- 3.4 kg/m 2 [- 6.3;-0.6]; P = 0.01), and they reported a significantly lower energy intake compared to the control group (- 301 kcal [- 589;-14]; P = 0.04). Macronutrient intake, diet quality, and physical activity did not differ between the intervention and control group, irrespective of successful weight loss during the intervention., Conclusions: In our study population, a preconception lifestyle intervention led to reduced energy intake 5.5 years later. Additionally, women allocated to the intervention group who were successful in losing weight during the intervention also had a lower BMI at follow-up. This shows the potential sustainable effect of a preconception lifestyle intervention., Trial Registration: This trial was registered on 16 November 2008 in the Dutch trial register; clinical trial registry number NTR1530 .

Background: Maternal overweight/obesity during pregnancy increases offspring's risks of obesity and cardiovascular disease (CVD). A possible pathway is by reduced physical fitness and physical activity (PA) levels in children of overweight/obese mother. We assessed whether maternal prepregnancy overweight/obesity independently determines cardiorespiratory fitness (CRF), muscular strength, moderate-to-vigorous physical activity (MVPA), and sedentary behavior (SB) in 8- to 9-year-old children. We also assessed whether child's fat mass (FM) mediates these associations., Methods: One hundred ninety-four children of Dutch ethnicity aged 8.6 (± 0.4) years were randomly selected from a prospective birth cohort, the Amsterdam Born Children and their Development (ABCD) study. CRF was assessed by the 20-m multistage shuttle run test (20-m MSRT), muscular strength by hand dynamometry, and MVPA and SB by accelerometry. The association of prepregnancy body mass index (BMI) ≥ 25 kg/m 2 with these outcome measures was assessed by multivariable linear regressions., Results: Mean (± standard deviation) attained 20-m MSRT stage was 5.3 (± 1.7). Compared with children from normal weight women, children of women with prepregnancy overweight/obesity attained a 0.80 (95% confidence interval: 0.15-1.50) lower stage, adjusted for child's sex and MVPA. This association was not mediated by birthweight or child's FM at age 5 years. Maternal prepregnancy overweight/obesity was not associated with child's muscular strength, MVPA, or SB., Conclusions: Maternal prepregnancy overweight/obesity was associated with reduced childhood CRF, but not with muscular strength, PA, or SB. Birthweight and FM at age 5 years did not mediate this association. Reduced CRF may partly explain the increased CVD risk in children of overweight/obese women.

The degree to which individuals change their lifestyle in response to interventions differs and this variation could affect cardiometabolic health. We examined if changes in dietary intake, physical activity and weight of obese infertile women during the first six months of the LIFEstyle trial were associated with cardiometabolic health 3⁻8 years later ( N = 50⁻78). Lifestyle was assessed using questionnaires and weight was measured at baseline, 3 and 6 months after randomization. BMI, blood pressure, body composition, pulse wave velocity, glycemic parameters and lipid profile were assessed 3⁻8 years after randomization. Decreases in savory and sweet snack intake were associated with lower HOMA-IR 3⁻8 years later, but these associations disappeared after adjustment for current lifestyle. No other associations between changes in lifestyle or body weight during the first six months after randomization with cardiovascular health 3⁻8 years later were observed. In conclusion, reductions in snack intake were associated with reduced insulin resistance 3⁻8 years later, but adjustment for current lifestyle reduced these associations. This indicates that changing lifestyle is an important first step, but maintaining this change is needed for improving cardiometabolic health in the long-term.

Background: Lifestyle changes are notoriously difficult. Since women who intend to become pregnant are more susceptible to lifestyle advice, interventions during this time window might be more effective than interventions during any other period in life. We here report the effects of the first large preconception lifestyle intervention RCT on diet and physical activity in obese infertile women., Methods: In total, 577 women were randomized between a six-month lifestyle intervention program (intervention group; N = 290) or prompt infertility treatment (control group; N = 287). Self-reported dietary behaviors and physical activity were assessed at baseline, three, six and twelve months after randomization. Mixed models were used to analyze differences between groups., Results: Compared to the control group, the intervention group reduced their intake of sugary drinks at three months (-0.5 glasses/day [95% C.I. = -0.9;-0.2]), of savory snacks at three (-2.4 handful/week [-3.4;-1.4]) and at six months (-1.4 handful/week [-2.6;-0.2]), and of sweet snacks at three (-2.2 portion/week [-3.3;-1.0]) and twelve months after randomization (-1.9 portion/week [-3.5;-0.4]). Also, the intervention group was more moderate to vigorous physically active at three months after randomization compared to the control group (169.0 minutes/week [6.0; 332.1])., Conclusion: Our study showed that obese infertile women who followed a six-month preconception lifestyle intervention program decreased their intake of high caloric snacks and beverages, and increased their physical activity. These changes in lifestyle may not only improve women's health but their offspring's health too., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: The department of Obstetrics and Gynaecology of the UMCG received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands, outside the submitted work (Prof. Dr. A. Hoek). Prof. Dr. B.W. Mol is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for ObsEva, Merck Merck KGaA and Guerbet. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare that they have no competing interests.

Background: Although cardiorespiratory fitness (CRF) in childhood and adolescence may be linked to future cardiovascular health, there is currently limited evidence for a longitudinal association., Objectives: To provide a systematic review on the prospective association between CRF in childhood and adolescence and cardiovascular disease (CVD) risk factors at least 2 years later., Methods: Using a systematic search of Medline, Embase, and SPORTDiscus, relevant articles were identified by the following criteria: generally healthy children and adolescents between 3 and 18 years of age with CRF assessed at baseline, and a follow-up period of ≥ 2 years. The outcome measures were CVD risk factors. We appraised quality of the included articles with STROBE and QUIPS checklists., Results: After screening 7524 titles and abstracts, we included 38 articles, assessing 44,169 children and adolescents followed up for a median of 6 years. Eleven articles were of high quality. There was considerable heterogeneity in methodology, measurement of CRF, and outcomes, which hampered meta-analysis. In approximately half of the included articles higher CRF in childhood and adolescence was associated with lower body mass index (BMI), waist circumference, body fatness and lower prevalence of metabolic syndrome in later life. No associations between CRF in childhood and adolescence and future waist-to-hip ratio, blood pressure, lipid profile, and glucose homeostasis were observed., Conclusion: Although about half of the included articles reported inverse associations between CRF in childhood and adolescence and future BMI, body fatness, and metabolic syndrome, evidence for other CVD risk factors was unconvincing. Many articles did not account for important confounding factors such as adiposity. Recommendations for future research include standardizing the measurement of CRF, i.e. by reporting VO 2max , using standardized outcome assessments, and performing individual patient data meta-analyses.

Objective: To comprehensively describe the natural history of vanishing white matter (VWM), aiming at improving counseling of patients/families and providing natural history data for future therapeutic trials., Methods: We performed a longitudinal multicenter study among 296 genetically confirmed VWM patients. Clinical information was obtained via disease-specific clinical questionnaire, Health Utilities Index and Guy's Neurological Disability Scale assessments, and chart review., Results: First disease signs occurred at a median age of 3 years (mode = 2 years, range = before birth to 54 years); 60% of patients were symptomatic before the age of 4 years. The nature of the first signs varied for different ages of onset. Overall, motor problems were the most common presenting sign, especially in children. Adolescent and adult onset patients were more likely to exhibit cognitive problems early after disease onset. One hundred two patients were deceased. Multivariate Cox regression analysis revealed a positive relation between age at onset and both preservation of ambulation and survival. Absence of stress-provoked episodes and absence of seizures predicted more favorable outcome. In patients with onset before 4 years, earlier onset was associated with more severe disability and higher mortality. For onset from 4 years on, disease course was generally milder, with a wide variation in severity. There were no significant differences for sex or for the 5 eIF2B gene groups. The results confirm the presence of a genotype-phenotype correlation., Interpretation: The VWM disease spectrum consists of a continuum with extremely wide variability. Age at onset is a strong predictor for disease course. Ann Neurol 2018;84:274-288., (© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Objective: Early life stress has been shown to influence the developing autonomic nervous system. Stressors in infancy may program the autonomic nervous system resting state set point, affecting cardiovascular function in later life. Excessive crying may be an indicator of increased stress arousal in infancy. We hypothesized that excessive infant crying is related to altered cardiac autonomic nervous system activity and increased blood pressure at age 5-6 years., Methods: In the Amsterdam Born Children and their Development study, excessive crying, maternal burden of infant care and maternal aggressive behavior in the 13th week after birth (range 11-16 weeks) were reported using questionnaires. Blood pressure, heart rate, heart rate variability and indicators of cardiac autonomic nervous system activity (sympathetic drive by pre-ejection period, parasympathetic drive by respiratory sinus arrhythmia) were measured at age 5-6 years during rest. Inclusion criteria were singleton birth, term-born, and no reported congenital or cardiovascular problems (N = 2153 included)., Results: Excessive crying (2.8%) was not associated with resting heart rate, heart rate variability, pre-ejection period, respiratory sinus arrhythmia nor with blood pressure at age 5-6 years., Conclusions: Excessive infant crying as an indicator of increased stress arousal does not seem to be related to resting activity of the autonomic nervous system or blood pressure at age 5-6. Potential associations may become visible under stressed conditions., Competing Interests: The authors have declared that no competing interests exist.

Although glomerular filtration rate (GFR) in children can be measured using a gold-standard technique following injection of an exogenous marker, this invasive and cumbersome technique is not widely available and GFR is commonly estimated using serum levels of endogenous markers. Creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin are well-established endogenous markers of kidney function. These markers differ in site of production and effects of diet and medication, as well as renal-tubular handling and extra-renal elimination. For each marker, different methods are available for measurement. Importantly, the measurements of creatinine and cystatin C have recently been standardized with the introduction of international reference standards. In order to allow estimation of GFR from serum marker concentrations, different equations for estimated GFR (eGFR) have been developed in children, using simple or more complex regression strategies with gold standard GFR measurements as a dependent variable. As a rule, estimation strategies relying on more than one marker - either by calculating the average of single parameter equations or by using more complex equations incorporating several parameters - outperform eGFR estimations using only a single marker. This in-depth review will discuss the physiology, measurement and clinical use of creatinine, urea, cystatin C, beta-trace protein, and beta-2 microglobulin in children. It will also address the generation of eGFR equations in children and provide an overview of currently available eGFR equations for the pediatric age group.

Introduction: Women, their Offspring and iMproving lifestyle for Better cardiovascular health of both (WOMB) project is the follow-up of the LIFEstyle study, a randomised controlled trial in obese infertile women, and investigates the effects of a preconception lifestyle intervention on later health of women (WOMB women) and their children (WOMB kids)., Methods and Analysis: Obese infertile women, aged between 18 and 39 years, were recruited in 23 Dutch fertility clinics between June 2009 and June 2012. The 284 women allocated to the intervention group received a 6-month structured lifestyle programme. The 280 women in the control group received infertility care as usual. 4 to 7 years after inclusion in the trial, all women (n=564) and children conceived during the trial (24 months after randomisation) (n=305 singletons and age 3-5 years) will be approached to participate in this follow-up study (starting in 2015). The main focus of outcome will be cardiovascular health, but the dataset comprises a wide range of physical and mental health measures, diet and physical activity measures, child growth and development measures, biological samples and genetic and epigenetic information. The follow-up assessment consists of three stages that take place between 2016 and 2018, and includes (online) questionnaires, accelerometry and physical and behavioural measurements in a mobile research vehicle. A subsample of 100 women and 100 children are planned for cardiac ultrasound measurements., Ethics and Dissemination: The protocol of this follow-up study is approved by the local medical ethics committee (University Medical Centre Groningen). Study findings of the WOMB project will be widely disseminated to the scientific community, healthcare professionals, policy makers, future parents and general public., Trial Registration Number: The original LIFEstyle study is registered at The Netherlands Trial Registry (number 1530)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)