GGD Amsterdam

Standard survival data measure the time span from some time origin until the occurrence of one type of event. If several types of events occur, a model describing progression to each of these competing risks is needed. Multi-state models generalize competing risks models by also describing transitions to intermediate events. Methods to analyze such models have been developed over the last two decades. Fortunately, most of the analyzes can be performed within the standard statistical packages, but may require some extra effort with respect to data preparation and programming. This tutorial aims to review statistical methods for the analysis of competing risks and multi-state models. Although some conceptual issues are covered, the emphasis is on practical issues like data preparation, estimation of the effect of covariates, and estimation of cumulative incidence functions and state and transition probabilities. Examples of analysis with standard software are shown.

Adaptive features of innate immunity, recently described as "trained immunity," have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. The enhanced function of circulating monocytes persisted for at least 3 mo after vaccination and was accompanied by increased expression of activation markers such as CD11b and Toll-like receptor 4. These training effects were induced through the NOD2 receptor and mediated by increased histone 3 lysine 4 trimethylation. In experimental studies, BCG vaccination induced T- and B-lymphocyte-independent protection of severe combined immunodeficiency SCID mice from disseminated candidiasis (100% survival in BCG-vaccinated mice vs. 30% in control mice). In conclusion, BCG induces trained immunity and nonspecific protection from infections through epigenetic reprogramming of innate immune cells.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. OBJECTIVES: to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. METHODS: a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. RECOMMENDATIONS: all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. CONCLUSIONS: the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.

Molecular typing based on 12 loci containing variable numbers of tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in combination with spoligotyping as the basis for large-scale, high-throughput genotyping of Mycobacterium tuberculosis. However, even the combination of these two methods is still less discriminatory than IS6110 fingerprinting. Here, we define an optimized set of MIRU-VNTR loci with a significantly higher discriminatory power. The resolution and the stability/robustness of 29 loci were analyzed, using a total of 824 tubercle bacillus isolates, including representatives of the main lineages identified worldwide so far. Five loci were excluded for lack of robustness and/or stability in serial isolates or isolates from epidemiologically linked patients. The use of the 24 remaining loci increased the number of types by 40%--and by 23% in combination with spoligotyping--among isolates from cosmopolitan origins, compared to those obtained with the original set of 12 loci. Consequently, the clustering rate was decreased by fourfold--by threefold in combination with spoligotyping--under the same conditions. A discriminatory subset of 15 loci with the highest evolutionary rates was then defined that concentrated 96% of the total resolution obtained with the full 24-locus set. Its predictive value for evaluating M. tuberculosis transmission was found to be equal to that of IS6110 restriction fragment length polymorphism typing, as shown in a companion population-based study. This 15-locus system is therefore proposed as the new standard for routine epidemiological discrimination of M. tuberculosis isolates and the 24-locus system as a high-resolution tool for phylogenetic studies.

We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and [Formula: see text] credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5-[Formula: see text] requires at least three detectors of sensitivity within a factor of [Formula: see text] of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

BACKGROUND: Depression and cardiovascular diseases are both common among elderly. Depression is suspected to be an independent risk factor for the onset of coronary heart disease, yet it is not clear to what extent and if depression also is associated with the onset of other diseases of the circulatory system. AIMS: To estimate the risk of depression as an independent risk factor for various cardiovascular diseases (CVD) and explore the effects of heterogeneity and methodological quality. METHOD: Meta-analyses and meta-regression analyses of longitudinal cohort and case-control studies reporting depression at baseline and CVD outcomes at follow-up. DATA SOURCES: MEDLINE (1966-2005) and PSYCHINFO (1966-2005). RESULTS: Of the 28 studies that met the inclusion criteria, 11 were assesed as high quality studies. Although depressed mood increased the risk for a wide range of CVDs, heterogeneity was substantial in most cases. Only the overall combined risk of depression for the onset of myocardial infarctions (n=8, OR=1.60, 95%CI 1.34-1.92) was homogenous. Clinically diagnosed major depressive disorder was identified as the most important risk factor for developing CVD. CONCLUSIONS: Depression seems to be an independent risk factor for the onset of a wide range of CVDs, although this evidence is related to a high level of heterogeneity.

In human immunodeficiency virus (HIV) infection, functional defects and deletion of antigen-reactive T cells are more frequent than can be explained by direct viral infection. On culturing, both CD4+ and CD8+ T cells from asymptomatic HIV-infected individuals died as a result of programmed cell death (apoptosis). Apoptosis was enhanced by activation with CD3 antibodies. Programmed cell death, associated with impaired T cell reactivity, may thus be responsible for the deletion of reactive T cells that contributes to HIV-induced immunodeficiency.

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

The human brain has evolved for group living [1Dunbar I.R. The social brain hypothesis.in: Cacioppo J.T. Foundations in Social Neuroscience. MIT Press, 2002: 69-88Google Scholar]. Yet we know so little about how it supports dynamic group interactions that the study of real-world social exchanges has been dubbed the “dark matter of social neuroscience” [2Schilbach L. Timmermans B. Reddy V. Costall A. Bente G. Schlicht T. Vogeley K. Toward a second-person neuroscience.Behav. Brain Sci. 2013; 36: 393-414Crossref PubMed Scopus (890) Google Scholar]. Recently, various studies have begun to approach this question by comparing brain responses of multiple individuals during a variety of (semi-naturalistic) tasks [3Babiloni F. Astolfi L. Social neuroscience and hyperscanning techniques: past, present and future.Neurosci. Biobehav. Rev. 2014; 44: 76-93Crossref PubMed Scopus (289) Google Scholar, 4Dmochowski J.P. Bezdek M.A. Abelson B.P. Johnson J.S. Schumacher E.H. Parra L.C. Audience preferences are predicted by temporal reliability of neural processing.Nat. Commun. 2014; 5: 4567Crossref PubMed Scopus (164) Google Scholar, 5Dumas G. Nadel J. Soussignan R. Martinerie J. Garnero L. Inter-brain synchronization during social interaction.PLoS ONE. 2010; 5: e12166Crossref PubMed Scopus (495) Google Scholar, 6Hasson U. Ghazanfar A.A. Galantucci B. Garrod S. Keysers C. Brain-to-brain coupling: a mechanism for creating and sharing a social world.Trends Cogn. Sci. 2012; 16: 114-121Abstract Full Text Full Text PDF PubMed Scopus (545) Google Scholar, 7Hari R. Himberg T. Nummenmaa L. Hämäläinen M. Parkkonen L. Synchrony of brains and bodies during implicit interpersonal interaction.Trends Cogn. Sci. 2013; 17: 105-106Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 8Jiang J. Chen C. Dai B. Shi G. Ding G. Liu L. Lu C. Leader emergence through interpersonal neural synchronization.Proc. Natl. Acad. Sci. USA. 2015; 112: 4274-4279Crossref PubMed Scopus (168) Google Scholar, 9Pfeiffer U.J. Timmermans B. Vogeley K. Frith C.D. Schilbach L. Towards a neuroscience of social interaction.Front. Hum. Neurosci. 2013; 7: 22Crossref PubMed Scopus (30) Google Scholar, 10Stephens G.J. Silbert L.J. Hasson U. Speaker-listener neural coupling underlies successful communication.Proc. Natl. Acad. Sci. USA. 2010; 107: 14425-14430Crossref PubMed Scopus (546) Google Scholar, 11Babiloni C. Buffo P. Vecchio F. Marzano N. Del Percio C. Spada D. Rossi S. Bruni I. Rossini P.M. Perani D. Brains “in concert”: frontal oscillatory alpha rhythms and empathy in professional musicians.Neuroimage. 2012; 60: 105-116Crossref PubMed Scopus (84) Google Scholar, 12Duan L. Dai R.N. Xiao X. Sun P.P. Li Z. Zhu C.Z. Cluster imaging of multi-brain networks (CIMBN): a general framework for hyperscanning and modeling a group of interacting brains.Front. Neurosci. 2015; 9: 267Crossref PubMed Scopus (28) Google Scholar, 13Hasson U. Nir Y. Levy I. Fuhrmann G. Malach R. Intersubject synchronization of cortical activity during natural vision.Science. 2004; 303: 1634-1640Crossref PubMed Scopus (1063) Google Scholar, 14Nummenmaa L. Glerean E. Viinikainen M. Jääskeläinen I.P. Hari R. Sams M. Emotions promote social interaction by synchronizing brain activity across individuals.Proc. Natl. Acad. Sci. USA. 2012; 109: 9599-9604Crossref PubMed Scopus (287) Google Scholar, 15Dikker S. Silbert L.J. Hasson U. Zevin J.D. On the same wavelength: predictable language enhances speaker-listener brain-to-brain synchrony in posterior superior temporal gyrus.J. Neurosci. 2014; 34: 6267-6272Crossref PubMed Scopus (71) Google Scholar]. These experiments reveal how stimulus properties [13Hasson U. Nir Y. Levy I. Fuhrmann G. Malach R. Intersubject synchronization of cortical activity during natural vision.Science. 2004; 303: 1634-1640Crossref PubMed Scopus (1063) Google Scholar], individual differences [14Nummenmaa L. Glerean E. Viinikainen M. Jääskeläinen I.P. Hari R. Sams M. Emotions promote social interaction by synchronizing brain activity across individuals.Proc. Natl. Acad. Sci. USA. 2012; 109: 9599-9604Crossref PubMed Scopus (287) Google Scholar], and contextual factors [15Dikker S. Silbert L.J. Hasson U. Zevin J.D. On the same wavelength: predictable language enhances speaker-listener brain-to-brain synchrony in posterior superior temporal gyrus.J. Neurosci. 2014; 34: 6267-6272Crossref PubMed Scopus (71) Google Scholar] may underpin similarities and differences in neural activity across people. However, most studies to date suffer from various limitations: they often lack direct face-to-face interaction between participants, are typically limited to dyads, do not investigate social dynamics across time, and, crucially, they rarely study social behavior under naturalistic circumstances. Here we extend such experimentation drastically, beyond dyads and beyond laboratory walls, to identify neural markers of group engagement during dynamic real-world group interactions. We used portable electroencephalogram (EEG) to simultaneously record brain activity from a class of 12 high school students over the course of a semester (11 classes) during regular classroom activities (Figures 1A–1C; Supplemental Experimental Procedures, section S1). A novel analysis technique to assess group-based neural coherence demonstrates that the extent to which brain activity is synchronized across students predicts both student class engagement and social dynamics. This suggests that brain-to-brain synchrony is a possible neural marker for dynamic social interactions, likely driven by shared attention mechanisms. This study validates a promising new method to investigate the neuroscience of group interactions in ecologically natural settings.

A general description of the mathematical and numerical formulations used in modern numerical reactive transport codes relevant for subsurface environmental simulations is presented. The formulations are followed by short descriptions of commonly used and available subsurface simulators that consider continuum representations of flow, transport, and reactions in porous media. These formulations are applicable to most of the subsurface environmental benchmark problems included in this special issue. The list of codes described briefly here includes PHREEQC, HPx, PHT3D, OpenGeoSys (OGS), HYTEC, ORCHESTRA, TOUGHREACT, eSTOMP, HYDROGEOCHEM, CrunchFlow, MIN3P, and PFLOTRAN. The descriptions include a high-level list of capabilities for each of the codes, along with a selective list of applications that highlight their capabilities and historical development.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals may be at increased risk of age-associated noncommunicable comorbidities (AANCCs). METHODS: Cross-sectional analyses of AANCC prevalence (including cardiovascular, metabolic, pulmonary, renal, bone, and malignant disease) and risk factors in a prospective cohort study of HIV type 1-infected individuals and HIV-uninfected controls, who were aged ≥45 years and comparable regarding most lifestyle and demographic factors. RESULTS: HIV-infected participants (n = 540) had a significantly higher mean number of AANCCs than controls (n = 524) (1.3 [SD, 1.14] vs 1.0 [SD, 0.95]; P < .001), with significantly more HIV-infected participants having ≥1 AANCC (69.4% vs 61.8%; P = .009). Hypertension, myocardial infarction, peripheral arterial disease, and impaired renal function were significantly more prevalent among HIV-infected participants. Risk of AANCC by ordinal logistic regression was independently associated with age, smoking, positive family history for cardiovascular/metabolic disease, and higher waist-to-hip ratio, but also with HIV infection (odds ratio, 1.58 [95% confidence interval, 1.23-2.03]; P < .001). In those with HIV, longer exposure to CD4 counts <200 cells/µL, and, to a lesser extent, higher levels of high-sensitivity C-reactive protein and soluble CD14, and longer prior use of high-dose ritonavir (≥400 mg/24 hours) were each also associated with a higher risk of AANCCs. CONCLUSIONS: All AANCCs were numerically more prevalent, with peripheral arterial, cardiovascular disease, and impaired renal function significantly so, among HIV-infected participants compared with HIV-uninfected controls. Besides recognized cardiovascular risk factors, HIV infection and longer time spent with severe immunodeficiency increased the risk of a higher composite AANCC burden. There was a less pronounced contribution from residual inflammation, immune activation, and prior high-dose ritonavir use.

BACKGROUND: Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters. METHODS: We identified relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and Medion databases (all records to April 2006) and by checking bibliographies of identified studies and consulting with experts. Four of us independently selected studies, extracted data and assessed study validity. We performed a bivariable meta-analysis of sensitivity and specificity and calculated likelihood ratios. RESULTS: We identified 74 studies of pre-eclampsia (total 79,547 patients) and 61 studies of intrauterine growth restriction (total 41 131 patients). Uterine artery Doppler ultrasonography provided a more accurate prediction when performed in the second trimester than in the first-trimester. Most Doppler indices had poor predictive characteristics, but this varied with patient risk and outcome severity. An increased pulsatility index with notching was the best predictor of pre-eclampsia (positive likelihood ratio 21.0 among high-risk patients and 7.5 among low-risk patients). It was also the best predictor of overall (positive likelihood ratio 9.1) and severe (positive likelihood ratio 14.6) intrauterine growth restriction among low-risk patients. INTERPRETATION: Abnormal uterine artery waveforms are a better predictor of pre-eclampsia than of intrauterine growth restriction. A pulsatility index, alone or combined with notching, is the most predictive Doppler index. These indices should be used in clinical practice. Future research should also concentrate on combining uterine artery Doppler ultrasonography with other tests.

BACKGROUND: To support the clinical distinction between systolic heart failure (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial structure and function were compared in LV endomyocardial biopsy samples of patients with systolic and diastolic heart failure. METHODS AND RESULTS: Patients hospitalized for worsening heart failure were classified as having SHF (n=22; LV ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had coronary artery disease or biopsy evidence of infiltrative or inflammatory myocardial disease. More DHF patients had a history of arterial hypertension and were obese. Biopsy samples were analyzed with histomorphometry and electron microscopy. Single cardiomyocytes were isolated from the samples, stretched to a sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated with calcium-containing solutions to measure total force. Cardiomyocyte diameter was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/-2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable. After administration of protein kinase A to the cardiomyocytes, the drop in Fpassive was larger (P<0.01) in DHF than in SHF. CONCLUSIONS: LV myocardial structure and function differ in SHF and DHF because of distinct cardiomyocyte abnormalities. These findings support the clinical separation of heart failure patients into SHF and DHF phenotypes.

The factor structure of the Dutch translation of the Autism-Spectrum Quotient (AQ; a continuous, quantitative measure of autistic traits) was evaluated with confirmatory factor analyses in a large general population and student sample. The criterion validity of the AQ was examined in three matched patient groups (autism spectrum conditions (ASC), social anxiety disorder, and obsessive-compulsive disorder). A two factor model, consisting of a "Social interaction" factor and "Attention to detail" factor could be identified. The internal consistency and test-retest reliability of the AQ were satisfactory. High total AQ and factor scores were specific to ASC patients. Men scored higher than women and science students higher than non-science students. The Dutch translation of the AQ is a reliable instrument to assess autism spectrum conditions.

OBJECTIVES. A number of studies have shown that victimization from bullying behavior is associated with substantial adverse effects on physical and psychological health, but it is unclear which comes first, the victimization or the health-related symptoms. In our present study, we investigated whether victimization precedes psychosomatic and psychosocial symptoms or whether these symptoms precede victimization. DESIGN. Six-month cohort study with baseline measurements taken in the fall of 1999 and follow-up measurements in the spring of 2000. SETTING. Eighteen elementary schools in the Netherlands. PARTICIPANTS. The study included 1118 children aged 9 to 11 years, who participated by filling out a questionnaire on both occasions of data collection. OUTCOME MEASURES. A self-administered questionnaire measured victimization from bullying, as well as a wide variety of psychosocial and psychosomatic symptoms, including depression, anxiety, bedwetting, headaches, sleeping problems, abdominal pain, poor appetite, and feelings of tension or tiredness. RESULTS. Victims of bullying had significantly higher chances of developing new psychosomatic and psychosocial problems compared with children who were not bullied. In contrast, some psychosocial, but not physical, health symptoms preceded bullying victimization. Children with depressive symptoms had a significantly higher chance of being newly victimized, as did children with anxiety. CONCLUSIONS. Many psychosomatic and psychosocial health problems follow an episode of bullying victimization. These findings stress the importance for doctors and health practitioners to establish whether bullying plays a contributing role in the etiology of such symptoms. Furthermore, our results indicate that children with depressive symptoms and anxiety are at increased risk of being victimized. Because victimization could have an adverse effect on children's attempts to cope with depression or anxiety, it is important to consider teaching these children skills that could make them less vulnerable to bullying behavior.

BACKGROUND: The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. METHODOLOGY AND PRINCIPAL FINDINGS: To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. CONCLUSIONS: Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Until quite recently, there has been a widespread belief in the popular media and scientific literature that the prevalence of childhood obesity is rapidly increasing. However, high quality evidence has emerged from several countries suggesting that the rise in the prevalence has slowed appreciably, or even plateaued. This review brings together such data from nine countries (Australia, China, England, France, Netherlands, New Zealand, Sweden, Switzerland and USA), with data from 467,294 children aged 2-19 years. The mean unweighted rate of change in prevalence of overweight and obesity was +0.00 (0.49)% per year across all age ×sex groups and all countries between 1995 and 2008. For overweight alone, the figure was +0.01 (0.56)%, and for obesity alone -0.01 (0.24)%. Rates of change differed by sex, age, socioeconomic status and ethnicity. While the prevalence of overweight and obesity appears to be stabilizing at different levels in different countries, it remains high, and a significant public health issue. Possible reasons for the apparent flattening are hypothesised.

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

The present volume could not have been produced without a two-year grant from the Research Pool of the University of Nijmegen and without the excellent services of Hans Verhuist, who took over my teaching duties during the period