Search

Objectives: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study., Design: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined., Setting: Children aged 0-18 years from 26 European birth cohorts., Participants: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood., Main Outcome Measure: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity) at age 6-18 years., Results: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results., Conclusions: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Investigate the cross-sectional association between the psychosocial status of mothers and fathers and the BMI z-scores of their 10 to 12-year-old children. Explore whether this association is mediated by children's diet, physical activity, screen time and sleep. Analyze the moderating effect of the educational levels of both the mother and father on the association., Design: In a cross-sectional study design, children's height and weight were measured following a standardized protocol. Parents completed the validated Depression Anxiety and Stress questionnaire, while diet quality, sports participation, time spent in bed and screen time were assessed through child-report using previously validated questions., Participants: The data for this study were obtained from the Amsterdam Born Children and their Development study, involving children aged 10 to 12 years and both of their parents (N = 1315)., Results: The majority, 80%, of the parents were highly educated and born in the Netherlands, and 68% of the children had a healthy BMI. Maternal or paternal psychosocial status was not significantly associated with children's BMI z-score (maternal β -0.0037; 95% CI: -0.008 to 0.0007, paternal β 0.0028; 95% CI: -0.007 to 0.002). Screen time mediated the association between paternal psychosocial status and children's BMI z-score (β = 0.010, 95% CI: 0.002; 0.020). Children's diet, physical activity, and sleep did not mediate the association between paternal psychosocial status and children's BMI z-score. Parental educational level was not a moderator., Conclusions: This research is unique in including four energy balance behaviors and including both mothers and fathers' psychosocial status. Children withfathers experiencing poorer psychosocial status engaged in more screen time which partly explained their higher BMI z-score., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Overman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The majority of expectant mothers report sleep alterations during pregnancy and almost 40% report poor sleep quality. There is growing evidence that sleep quality (SQ) during pregnancy influences maternal health. This review focuses on how SQ during pregnancy relates to maternal health-related quality of life (HRQoL). The review also aims to identify whether this relation varies between pregnancy trimesters, and for different subdomains of HRQoL., Methods: A systematic review was performed according to PRISMA guidelines and registered on Prospero in August 2021 with ID no: CRD42021264707. Pubmed, Psychinfo, Embase, Cochrane, and trial registries were searched up to June 2021. Studies with any design that investigated the relation between SQ and quality of life/HRQoL in pregnant women, published in English, and peer-reviewed, were included. Two independent reviewers screened titles, abstracts, and full texts, and extracted data from the included papers. The quality of the studies was evaluated using the Newcastle-Ottawa Scale., Results: Three hundred and thirteen papers were identified in the initial search, of which 10 met the inclusion criteria. Data included 7330 participants from six different countries. The studies had longitudinal ( n  = 1) or cross-sectional designs ( n  = 9). In nine studies SQ was reported subjectively by self-report questionnaires. Actigraphic data was available from two studies. HRQoL was assessed by validated questionnaires in all studies. Due to high levels of clinical and methodological heterogeneity in included studies, a narrative synthesis was employed. Nine studies found that poor sleep quality was related to a lower overall HRQoL during pregnancy. Effect sizes were low to medium. This relation was reported most during the third trimester. Especially sleep disturbances and subjective low SQ seemed to be related consistently to lower HRQoL. Furthermore, an indication was found that SQ might have a relation with the mental and physical domain of HRQoL. The social and environmental domain may also be associated with overall SQ., Conclusion: Despite the scarcity of studies available, this systematic review found evidence that low SQ is related to low HRQoL during pregnancy. An indication was found that the relationship between SQ and HRQoL during the second trimester might be less prominent.

Background: Problematic sleep in infants can have a high impact on families. We examined parental discontent with infant sleep in the first six months of life and parent-perceived problematic sleep during the second year of life., Methods: We used Sarphati Cohort data of 1471 children. During periodic youth health care visits in the first six months of life, professionals registered parental discontent with infant sleep. In the second year of life, parents filled out the Brief Infant Sleep Questionnaire (BISQ), from which we defined parent-perceived problematic sleep and BISQ-defined problematic sleep. We examined the association of parental discontent with infant sleep during the first six months with both BISQ-derived outcomes up to age two, using multivariable logistic regression analysis., Results: 26% of parents were discontented with infant sleep during the first six months of life. During the second year of life, 27% of the parents perceived their child's sleep as problematic, and 9% of the infants had BISQ-defined problematic sleep. Early parental discontent with infant sleep was associated with parent-perceived problematic sleep [adjusted OR 2.50 (95% CI 1.91-3.28)], and BISQ-defined problematic sleep [adjusted OR 1.88 (1.11-3.17)]., Conclusions: Early registered parental discontent with infant sleep was a predictor of parent-perceived problematic sleep in early toddlerhood. Registering parental discontent during infancy might enable professionals to identify a group of infants at risk for later problematic sleep. We recommend screening and parental support for sleep difficulties in an early stage.

Aims: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age., Methods and Results: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant., Conclusion: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease., Competing Interests: Conflict of interest: D.A.L. reported grants from national and international government and charity funders, Roche Diagnostics, and Medtronic Ltd for work unrelated to this publication. S.M.N. reported grants from Roche Diagnostics, Access Fertility, Modern Fertility, Ferring Pharmaceuticals, TFP, and Merck for work unrelated to this publication. The other authors report no conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Research on adults has identified an immigrant health advantage, known as the 'immigrant health paradox', by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives?, Setting: Western Europe and Australia., Participants: We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants' children: Etude Longitudinale Française depuis l'Enfance-France (N=12 494), the Raine Study-Australia (N=2283), Born in Bradford-UK (N=4132), Amsterdam Born Children and their Development study-Netherlands (N=4030) and the Generation R study-Netherlands (N=4877). We include male and female babies born to immigrant and native parents., Primary and Secondary Outcome Measures: The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0-1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad., Results: Two patterns in children's birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p<0.10) and Australia (+40 g, p<0.10) and lower birth weight among children of immigrants in the UK (-82 g, p<0.05) and the Netherlands (-80 g and -73 g, p<0.001) compared with natives' children. Smoking during pregnancy emerged as a mechanism explaining some of the birth weight gaps between children of immigrants and natives., Conclusion: The immigrant health advantage is not universally transferred to children in the form of higher birth weight in all host countries. Further research should investigate whether this cross-national variation is due to differences in immigrant communities, social and healthcare contexts across host countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Aim: Excessive infant crying increases parents' concerns regarding their infant's health and the burden of parenting. We aimed to gain insight into the healthcare support needs of parents with excessively crying infants., Methods: An exploratory qualitative study was conducted in the Netherlands. We performed semi-structured interviews with parents of 12 infants between June and December 2020, followed by inductive and deductive thematic analysis., Results: Parents described what their needs were with regard to the assessment of infant crying and support by professionals. Long-lasting crying made parents feel that there must be a somatic cause. If they could soothe their infant, they gained more confidence that their infant was healthy. We identified four interrelated themes: (i) confidence in the professional; (ii) seeking a somatic cause for the crying; (iii) seeking acknowledgment; and (iv) exhaustion of parents and feelings of failure., Conclusion: Parental support needs were best fulfilled by professionals who took them seriously, demonstrated medical expertise, and offered a practical plan. Perinatal parental education on normal infant behaviour and infant soothing techniques might improve parental self-efficacy at an early stage and prevent medicalization of excessive crying., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 an increasing proportion of the world's population., Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study., Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022., Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction)., Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups., Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, 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 age younger 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 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer 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 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units)., Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Study Objectives: The objective of this study was to evaluate the association between gestational sleep deprivation and childhood adiposity and cardiometabolic profile., Methods: Data were used from two population-based birth cohorts (Rhea study and Amsterdam Born Children and their Development study). A total of 3,608 pregnant women and their children were followed up until the age of 11 years. Gestational sleep deprivation was defined as 6 or fewer hours of sleep per day, reported by questionnaire. The primary outcomes included repeated measures of body mass index (BMI), waist circumference, body fat, serum lipids, systolic and diastolic blood pressure (DBP) levels in childhood. We performed a pooled analysis with adjusted linear mixed effect and Cox proportional hazards models. We tested for mediation by birthweight, gestational age, and gestational diabetes., Results: Gestational sleep deprivation was associated with higher BMI (beta; 95% CI: 0.7; 0.4, 1.0 kg/m2) and waist circumference (beta; 95% CI: 0.9; 0.1, 1.6 cm) in childhood, and increased risk for overweight or obesity (HR; 95% CI: 1.4; 1.1, 2.0). Gestational sleep deprivation was also associated with higher offspring DBP (beta; 95% CI: 1.6; 0.5, 2.7 mmHg). The observed associations were modified by sex (all p-values for interaction < 0.05); and were more pronounced in girls. Gestational diabetes and shorter gestational age partly mediated the seen associations., Conclusions: This is the first study showing that gestational sleep deprivation may increase offspring's adiposity and blood pressure, while exploring possible mechanisms. Attention to glucose metabolism and preterm birth might be extra warranted in mothers with gestational sleep deprivation., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Prevention of childhood overweight should start as early as possible preferably in "the first 1000 days of life." Sleep is one of the modifiable health behaviors during this age period, besides dietary intake and physical activity. The aim of this systematic review is to summarize the existing literature regarding the association between sleep during infancy (age ≤24 months) and body composition measures during childhood (age ≤12 years). Methods: We registered the protocol of this systematic review (PROSPERO registration no. CRD42018087088) and conducted the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We searched for articles published until July 31, 2019 reporting on longitudinal associations with a minimal follow-up of 6 months. Methodological Quality was assessed and a narrative synthesis was performed. Results: We included 19 studies. Sleep was reported as sleep duration ( n  = 18) or sleep problems ( n  = 2). Sleep was assessed at least once before the age of 12 months in 14 out of the 19 studies. Methodological quality was rated as strong for five studies, moderate for five studies, and weak for nine studies. Conclusion: This narrative synthesis found inconsistent evidence that longer infant sleep duration during the first 2 years of life is associated with a healthier body composition during childhood.

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., Competing Interests: Conflict of interest: L. Duijts reports grants from European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (the ALPHABET project (number 696295; 2017) and ZonMW The Netherlands (number 529051014; 2017)) and grants from the European Union's Horizon 2020 programme (the LIFECYCLE project, grant agreement number 733206; 2016), during the conduct of the study. Conflict of interest: B. Gerhard reports grants from the EU FP7, during the conduct of the study. Conflict of interest: H. Inskip reports grants (salary) from the UK Medical Research Council, grants from the British Heart Foundation, the UK Food Standards Agency, the British Lung Foundation, Arthritis Research UK, the NIHR Southampton Biomedical Research Centre and the European Union's Seventh Framework Programme (FP7/2007-2013, project EarlyNutrition under grant agreement number 289346), during the conduct of the study; and members of H. Inskip's team have received funding from Nestec, Abbott Nutrition and Danone Nutricia for various projects to which she is linked, but she has received no direct funding herself. Conflict of interest: S. Lau reports grants and personal fees (honoraria) from Symbiopharm and Allergopharma, personal fees (honoraria) and non-financial support (advisory board work) from DBV, personal fees from ALK, and non-financial support (advisory board work) from Boehringer and Merck, outside the submitted work. Conflict of interest: D. Maier reports grants from the European Commission (FP7 MeDALL, 261357), during the conduct of the study., (Copyright ©ERS 2018.)

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.

Background: A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7-8 years of life in a large Amsterdam born birth cohort., Methods: For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes "ever being diagnosed with asthma" and "wheezing in the past 12 months" on questionnaires. We measured offspring height and weight at age 5-6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma., Results: At the age of 7-8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49-3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28-3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma., Conclusions: Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child's own BMI.

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.