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OBJECTIVE: To test whether parental rules regarding the amount of digital media use is associated with the sleep of Dutch adolescents, and whether this is indirectly due to lower digital media use. DESIGN: Cross-sectional study METHOD: Adolescents and their parents of the Amsterdam Born Children and their Development (ABCD) study completed questionnaires in 2019 at the age of 15-16 years (n=1369; 56% girls). Parents and adolescents reported whether there are rules regarding the amount of digital media use. The adolescents also reported their daily amount of digital media use, sleep duration, bedtime and sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). We tested the association between rules and sleep duration, bedtime and sleep quality in adolescents using multivariate regression analysis. Using mediation analysis we tested whether rules were also indirectly associated with sleep outcome measures through the amount of digital media use. RESULTS: Setting rules regarding digital media use was related to sleep duration; 6.8 minutes (95%CI:0.1;13.5) longer with inconsistently experienced rules and 18.5 minutes (95%CI:9.2;27.8) longer with consistently existing rules. Setting rules was also related to bedtime; 10 minutes (95%CI: -17;-4) earlier with inconsistently experienced rules and 29 minutes (95%CI:-38;-2) earlier with consistently existing rules. Setting rules was not directly associated with sleep quality. Indirectly, rules were associated with longer sleep duration, earlier bedtime and better sleep quality due to lower digital media use per day. CONCLUSION: Parental rules regarding the amount of digital media use is associated with better sleep of adolescents. This is partly explained by lower digital media use.

IMPORTANCE People conceived using assisted reproductive technology (ART) make up anincreasing proportion of the world’s population.OBJECTIVE To investigate the association of ART conception with offspring growth and adiposityfrom infancy to early adulthood in a large multicohort study.DESIGN, SETTING, AND PARTICIPANTS This cohort study used a prespecified coordinated analysisacross 26 European, Asia-Pacific, and North American population-based cohort studies that includedpeople born between 1984 and 2018, with mean ages at assessment of growth and adiposityoutcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 andFebruary 2022.EXPOSURES Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, andembryo transfer) vs natural conception (NC; without any medically assisted reproduction).MAIN OUTCOMES AND MEASURES The main outcomes were length / height, weight, and bodymass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohortwas analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, andethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13age groups.RESULTS Up to 158 066 offspring (4329 conceived by ART) were included in each age-group metaanalysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who wereNC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence,with differences largest at the youngest ages and attenuating with older child age. For example,adjusted mean differences in offspring weight were −0.27 (95% CI, −0.39 to −0.16) SD units at ageyounger than 3 months, −0.16 (95% CI, −0.22 to −0.09) SD units at age 17 to 23 months, −0.07 (95%CI, −0.10 to −0.04) SD units at age 6 to 9 years, and −0.02 (95% CI, −0.15 to 0.12) SD units at age 14to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryotransfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was −0.14[95% CI, −0.20 to −0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, −0.15 to 0.15SD units for frozen embryo transfer vs NC). More marked differences were seen for body fatmeasurements, and there was imprecise evidence that offspring conceived by ART developedgreater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17years: 0.23 [95% CI, −0.04 to 0.50] SD units).CONCLUSIONS AND RELEVANCE These findings suggest that people conceiving or conceived byART can be reassured that differences in early growth and adiposity are small and no longer evidentby late adolescence

Study objectives Early life determinants of sleep problems are mostly unknown. The first 1000 days of life (ie, the time between conception and a child's second birthday) is a period where the foundations for optimum health, growth and neurodevelopment are established. The aim of this explorative study is to identify potential early life determinants of sleep problems at age 7–8 years. Methods Data from the Amsterdam Born Children and their Development cohort study (n = 2746) were analyzed. Sleep problems at age 7–8 years were reported by the caregiver in the ‘Child Sleep Habits Questionnaire’. A higher total score indicates more sleep problems. After multiple imputation (n = 20), we studied multivariable associations between all potential determinants and sleep problems using regression analysis. Results A higher pre-pregnancy body mass index (BMI) was associated with more sleep problems at age 7–8 years [β 0.12 (95% CI 0.05, 0.18)]. Children of mothers with symptoms of anxiety during pregnancy [β 0.06 (95% CI 0.03, 0.09)] and infancy period [β 0.04 (95% CI 0.00, 0.07)] had more sleep problems. Children of mothers drinking ≥1 glass of alcohol a day around 14 weeks of gestation had a 2 points higher sleep problem score [β 2.55 (95% CI 0.21, 4.89)] and children of mothers smoking ≥1 cigarette per day in that period had a one point higher score [β 1.07 (95% CI 0.10, 2.03)]. Infants with relative weight loss (delta BMI-SD) had a higher sleep problem score during childhood [β −0.32 (95%CI -0.60, −0.04)]. Conclusions We identified several potential determinants during pregnancy and infancy associated with childhood sleeping problems. We encourage further research into these and other potential determinants to replicate results and to identify underlying mechanisms.

Importance Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity’s effect on drug safety, pharmacokinetics, and dosing in obese children is unknown. Objective To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children. Evidence Review We searched the MEDLINE, Cochrane, and EMBASE databases (January 1, 1970-December 31, 2012) and included studies if they contained data on drug clearance, volume of distribution, or drug concentration in obese children (aged ≤18 years). We compared exposure and weight-normalized volume of distribution and clearance between obese and nonobese children. We explored the association between drug physicochemical properties and clearance and volume of distribution. Findings Twenty studies met the inclusion criteria and contained pharmacokinetic data for 21 drugs. The median number of obese children studied per drug was 10 (range, 1-112) and ages ranged from newborn to 29 years (1 study described pharmacokinetics in children and adults together). Dosing schema varied and were either a fixed dose (6 [29%]) or based on body weight (10 [48%]) and body surface area (4 [19%]). Clinically significant pharmacokinetic alterations were observed in obese children for 65% (11 of 17) of the studied drugs. Pharmacokinetic alterations resulted in substantial differences in exposure between obese and nonobese children for 38% (5 of 13) of the drugs. We found no association between drug lipophilicity or Biopharmaceutical Drug Disposition Classification System class and changes in volume of distribution or clearance due to obesity. Conclusions and Relevance Consensus is lacking on the most appropriate weight-based dosing strategy for obese children. Prospective pharmacokinetic trials in obese children are needed to ensure therapeutic efficacy and enhance drug safety.

The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood. This work was partially supported by the Southern California Environmental Health Sciences Center (grant # P30ES007048) funded by the National Institute of Environmental Health Sciences [PI Gilliland]. Dr. Contreras was supported by a grant from the NIH T32ES013678. MEDALL and CHICOS Projects: The research leading to these results has received funding from the European Community’s Seventh Framework Program(Health–F2-grantagreements No. 261357 and 241604). Per cohort ABCD: Data of the Amsterdam Born Children and their Development cohort study used in this research was in part supported by funds from the Netherlands Organisation for Health Research and Development (ZonMw 40–00812-98–11010). The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. BAMSE: We acknowledge all funding sources: The Swedish Research Council, The Swedish Heart and Lung Foundation, The Swedish Research Council for Working Life and Social Welfare, the Swedish Asthma and Allergy Association Research Foundation, The Swedish Research Council Formas, Stockholm County Council, and the European Commission’s Seventh Framework 29 Program Me DALL under grant agreement No.261357. We thank all the children and their parents for participating in the BAMSE cohort and the nurses and other staff members working in the BAMSE project. EDEN: We acknowledge all the funding sources for the EDEN study: Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris–Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS),French National Institute for Health Education (INPES), the European Union FP7programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN),French national agency for food security, French speaking association for the study ofdiabetes and metabolism (ALFEDIAM).We acknowledge the commitment of the EDEN mother-child cohort study group: I.Annesi-Maesano, JY. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, , A. Forhan, X. Fritel, A. Germa, V.Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G.Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M.Schweitzer, O. Thiebaugeorges.The Generation R Study:The Generation R study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfareand Sport and the Ministry of Youth and Families. The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE project, grant agreement no 733206; 2016), the European Research Council (ERC-2014-CoG-648916) and from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERAHDHL), Horizon 2020 (grant agreement no 696295; 2017), ZonMW The Netherlands (no529051014; 2017), Science Foundation Ireland (no SFI/16/ERA-HDHL/3360), and the European Union (ALPHABET project).The researchers are independent from the funders. The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. INMA: Data used for this research was provided by the INMA-Environment and Childhood Project (www.proyectoinma.org). This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), Spanish Ministry of Health (FIS-PIO41436, PI06/0867, PI081151, and FIS-FEDER 03/1615, 04/1112,04/1931, 05/1079, 05/1052, 06/1213, 07/0314 and 09/02647), Generalitat de Catalunya-CIRIT 1999SGR00241, the Conselleria de Sanitat Generalitat Valenciana, Department of Health of the Basque Government (2005111093 and 2009111069), the ProvincialGovernment of Gipuzkoa (DFG06/004 and DFG08/001).KOALA: The collection of the data from the KOALA Birth Cohort Study used in this analysis was financially supported by Friesland Foods (now Friesland Campina),Netherlands Asthma Foundation (grant numbers 3.2.07.022 and 3.2.03.48), Netherlands Heart Foundation (grant number 2014 T037, the Netherlands Organization for Health Research and Development (Zon Mw Prevention Program number 1.210-00-090), Triodos Foundation, Phoenix Foundation, Raphaël Foundation, Iona Foundation, Foundation forthe Advancement of Heilpedagogie, all in the Netherlands. MAS:The MAS birth cohort was funded by grants from the German Federal Ministry ofEducation and Research (BMBF; reference numbers 07015633, 07 ALE 27, 01EE9405/5,01EE9406) and the German Research Foundation (DFG; reference number KE 1462/2-1).PIAMA: The PIAMA study has been funded by The Netherlands Organisation for Health Research and Development; The Netherlands Organisation for Scientific Research; The Netherlands Asthma fund; The Netherlands Ministry of Spatial Planning Housing, and the Environment; and The Netherlands Ministry of Health, Welfare and Sport. RHEA: The Rhea project was financially supported by European projects (EU FP6-003-Food-3-NewGeneris -Contract No16320, EU FP6 STREP Hiwate -Contract No36224,EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers Contract No226756, EU FP7-HEALTH-2009-single stage CHICOS Contract No241604, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU-FP7,Proposal No 264357 MeDALL, EU- FP7-HEALTH-2012 Proposal No 308333 HELIX),and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece:2011-2014; “Rhea Plus”: Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-2015).ROBBIC: Data of the Rome cohort was in part supported byfunds from the Italian Ministry of Health (Programma speciale ex art. 12, comma 2, lettera b) del D. Lgs. 502/92,2001, 2003). We thank all the fields workers and the families for their contribution to thestudy. SWS: We thank the members of the Southampton Women's Survey Study group and the many participants in the SWS for their contribution to the study. The Southampton Women’s Survey is supported by grants from the Medical Research Council, British Heart Foundation, Food Standards Agency, British Lung Foundation, Arthritis Research UK, NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and the European Union's Seventh Framework Programme (FP7/2007-2013), project Early Nutrition under grant agreement n°289346.