Validity of Estimating the Maximal Oxygen Consumption by Consumer Wearables: A Systematic Review with Meta-analysis and Expert Statement of the INTERLIVE Network.

BACKGROUND: Technological advances have recently made possible the estimation of maximal oxygen consumption (VO2max) by consumer wearables. However, the validity of such estimations has not been systematically summarized using meta-analytic methods and there are no standards guiding the validation protocols. OBJECTIVE: The aim was to (1) quantitatively summarize previous studies investigating the validity of the VO2max estimated by consumer wearables and (2) provide best-practice recommendations for future validation studies. METHODS: First, we conducted a systematic review and meta-analysis of studies validating the estimation of VO2max by wearables. Second, based on the state of knowledge (derived from the systematic review) combined with the expert discussion between the members of the Towards Intelligent Health and Well-Being Network of Physical Activity Assessment (INTERLIVE) consortium, we provided a set of best-practice recommendations for validation protocols. RESULTS: Fourteen validation studies were included in the systematic review and meta-analysis. Meta-analysis results revealed that wearables using resting condition information in their algorithms significantly overestimated VO2max (bias 2.17 ml·kg-1·min-1; limits of agreement - 13.07 to 17.41 ml·kg-1·min-1), while devices using exercise-based information in their algorithms showed a lower systematic and random error (bias - 0.09 ml·kg-1·min-1; limits of agreement - 9.92 to 9.74 ml·kg-1·min-1). The INTERLIVE consortium proposed six key domains to be considered for validating wearable devices estimating VO2max, concerning the following: the target population, reference standard, index measure, testing conditions, data processing, and statistical analysis. CONCLUSIONS: Our meta-analysis suggests that the estimations of VO2max by wearables that use exercise-based algorithms provide higher accuracy than those based on resting conditions. The exercise-based estimation seems to be optimal for measuring VO2max at the population level, yet the estimation error at the individual level is large, and, therefore, for sport/clinical purposes these methods still need improvement. The INTERLIVE network hereby provides best-practice recommendations to be used in future protocols to move towards a more accurate, transparent and comparable validation of VO2max derived from wearables. PROSPERO ID: CRD42021246192.

Accelerometer-derived physical activity and sedentary behaviors in individuals with newly diagnosed type 2 diabetes: A cross-sectional study from the Danish nationwide DD2 cohort.

Introduction: Habitual physical activity behaviors of individuals with new-onset type 2 diabetes are largely unknown. We aimed to investigate accelerometer-derived physical activity behaviors in individuals with newly diagnosed type 2 diabetes. We also examined sociodemographic and health-related correlates of a high-risk physical activity profile. Methods: This cross-sectional study used data from 768 participants enrolled in an intervention study nested within the Danish Centre for Strategic Research in Type 2 diabetes (DD2) cohort. Physical activity was assessed by 24-h dual monitor accelerometry. Prevalence ratios of having a high-risk physical activity profile were estimated using Poisson regression adjusted for age and sex. Results: Study participants spent on average 9.7 (25th and 75th percentiles, 8.3; 11.1) hours/day sitting, walked for 1.1 (0.8; 1.6) hours/day and accumulated 4,000 (2,521; 5,864) steps/day. Still, 62% met the recommendations for physical activity. Characteristics associated with a high-risk physical activity profile (observed in 24.5% of participants) included older age, higher body mass index (BMI), unemployment, retirement, comorbidities, and current smoking. Hence, participants aged 60-69, 70-79 and 80+ years had prevalence ratios of 2.12 (95% CI 1.31; 3.42), 1.99 (1.18; 3.34) and 3.09 (1.42; 6.75) for a high-risk activity profile, respectively, versus participants <50 years. BMI values of 30-39 and 40+ were associated with 1.83 (1.06; 3.15) and 3.38 (1.88; 6.05) higher prevalence ratios compared to normal-weight. Unemployment or retirement was associated with 1.62 (1.09; 2.41) and 2.15 (1.37; 3.39) times higher prevalence ratios, compared to individuals in the working force. Having a Charlson Comorbidity Index score of 1-2 or 3+ was associated with 1.36 (1.03-1.79) and 1.90 (1.27-1.84) higher prevalence ratios, while current smoking was associated with a prevalence ratio of 1.72 (1.25; 2.35) compared to never smokers. Conclusion: This study shows that 62% of individuals with newly diagnosed type 2 diabetes met the recommendations for physical activity. Still, the majority of participants were also highly sedentary and accumulated very few daily steps, emphasizing the need for focusing on both increasing physical activity and reducing sedentary behaviors in the prevention of diabetes-related complications. Individuals with a high-risk physical activity profile were characterized by more obesity, socioeconomic inequalities, advanced age and comorbidities.Trial registration number: NCT02015130.

Association of Cycling With All-Cause and Cardiovascular Disease Mortality Among Persons With Diabetes: The European Prospective Investigation Into Cancer and Nutrition (EPIC) Study.

Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes. Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality. Design, Setting, and Participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020. Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination. Main Outcomes and Measures: The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors. Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of follow-up, a total of 975 deaths from all causes were recorded. Compared with people who reported no cycling at both examinations, the multivariable-adjusted hazard ratios for all-cause mortality were 0.90 (95% CI, 0.71-1.14) in those who cycled and then stopped, 0.65 (95% CI, 0.46-0.92) in initial noncyclists who started cycling, and 0.65 (95% CI, 0.53-0.80) for people who reported cycling at both examinations. Similar results were observed for CVD mortality. Conclusion and Relevance: In this cohort study, cycling was associated with lower all-cause and CVD mortality risk among people with diabetes independent of practicing other types of physical activity. Participants who took up cycling between the baseline and second examination had a considerably lower risk of both all-cause and CVD mortality compared with consistent noncyclists.

Resemblance in accelerometer-assessed physical activity in families with children: the Lolland-Falster Health Study.

BACKGROUND: Evidence of intra-family resemblance in physical activity (PA) is lacking. The association between parent and child PA appears weak, the influence of age and gender on this association is uncertain, and no studies have investigated the degree of resemblance in family members' PA behaviours such as walking, sitting/lying, and biking. Thus, the aims of the study were to examine the degree of resemblance in PA within families, specifically between parents and children, and to explore the size of resemblance across age of children, gender of parents and children, and intensity and type of PA. METHOD: The study is a cross-sectional analysis of a subsample (902 parents and 935 children nested within 605 families) of the Danish population study Lolland-Falster Health Study. PA was measured using a dual-accelerometer system (Axivity AX3) with subsequent processing of time spent in light PA (LPA), moderate-to-vigorous PA (MVPA), and vigorous PA and classification of PA behaviour types. Families with at least one son/daughter aged 0-22 years and one parent providing minimum 4 days of valid accelerometer data were included in the analysis. A linear mixed model regression analysis was used to determine the intraclass correlation coefficient (ICC) of clustering among family members for PA intensities and PA behaviours, adjusted for sex, age, parental education, and the interaction between sex and age. RESULTS: In the analysis of within-family variation in PA, the ICCs across PA intensities and PA behaviours ranged from 0.06 to 0.34. We found stronger clustering in family members' PA for LPA and behaviours requiring low energy expenditure (LPA: ICC 0.22 (95% confidence interval (CI) 0.17; 0.28), sitting/lying: ICC 0.34 (95% CI 0.28; 0.40)), and walking: ICC 0.24 (95% CI 0.19; 0.30) than for higher intensities (e.g. MVPA: ICC 0.07 (95% CI 0.03; 0.14)). The ICC for biking was 0.23 (95% CI 0.18; 0.29). Analyses on parent-child dyads gave similar results. No interaction effects for gender and age (except for biking) were found. CONCLUSION: Parents and children's time spent in PA behaviours requiring low energy expenditure had moderate resemblance within families, whereas engagement in PA with higher intensities showed small or close-to-zero resemblance.

Association between parent and child physical activity: a systematic review.

BACKGROUND: Childhood represents an important life stage for establishment of physical activity (PA) habits. Parents are assumed to play an important role in influencing children's PA. Earlier reviews have mainly focused on parental modelling, encouragement, and support for PA, rather than the actual PA levels of parents. Therefore, the purpose of this review was to systematically summarize the evidence on the relationship between parent and child PA. METHODS: Papers were identified using electronic databases and manual searches of reference lists. Papers reporting on associations between objectively measured child PA and at least one measure of parental PA were included. The quality of the papers was assessed using a modified version of the ROBINS-I tool. For interpretation of the results across studies, we produced albatross plots for all studies combined and by age-groups, sex of the parents, sex of the child, methodology of assessment of parental PA, and type of PA. RESULTS: Thirty-nine papers were included with sample size of parent-child dyads ranging from 15 to 1267 (mean = 319 dyads, median = 227 dyads). The majority of studies were published from 2008 to 2018 and used accelerometry to assess PA. Most of the studies were classified as having moderate, serious, or critical risk of bias. The albatross plot for all studies combined showed that the clear majority of studies observed a positive relationship between parent and child PA. The plot suggested an average magnitude of correlation across studies to be around 0.13, and the overall impression was that this was fairly similar across child age-groups and gender of parent-child dyads. Studies using objective assessment of parental PA showed stronger relationship between parent and child PA compared with studies using self-report (average magnitude of correlation around 0.16 vs 0.04 respectively). No clear evidence was found for the strength of relationship being dependent on type of PA measure of parent and child (total PA, moderate-to-vigorous PA, steps), however, the relationship for light PA appeared weaker. CONCLUSION: This systematic review showed that the clear majority of studies observed a weak positive relationship between parent and child PA regardless of age of the child, the gender of the parent-child dyad, and type of PA. TRIAL REGISTRATION: Registration in PROSPERO: CRD42019093462.

Variations in accelerometry measured physical activity and sedentary time across Europe - harmonized analyses of 47,497 children and adolescents.

BACKGROUND: Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe. METHODS: Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2-18 years) from 18 different European countries. RESULTS: Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age. CONCLUSIONS: Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.

Association of high amounts of physical activity with mortality risk: a systematic review and meta-analysis.

OBJECTIVES: To systematically review and analyse studies of high amounts of physical activity and mortality risk in the general population. ELIGIBILITY CRITERIA: Inclusion criteria related to follow-up (minimum 2 years), outcome (mortality from all causes, cancer, cardiovascular disease (CVD) or coronary heart disease), exposure (eg, a category of >1000 metabolic equivalent of task (MET) min/week), study design (prospective cohort, nested case control or case-cohort) and reports of cases and person years of exposure categories. INFORMATION SOURCES: Systematic searches were conducted in Embase and Pubmed from database inception to 2 March 2019. RISK OF BIAS: The quality of the studies was assessed with the Newcastle-Ottawa scale. INCLUDED STUDIES: From 31 368 studies identified, 48 were included. Two authors independently extracted outcome estimates and assessed study quality. SYNTHESIS OF RESULTS: We estimated hazard ratios (HRs) using random effect restricted cubic spline dose-response meta-analyses. Compared with the recommended level of physical activity (750 MET min/week), mortality risk was lower at physical activity levels exceeding the recommendations, at least until 5000 MET min/week for all cause mortality (HR=0.86, 95% CI 0.78 to 0.94) and for CVD mortality (HR=0.73, 95% CI 0.56 to 0.95). STRENGTHS AND LIMITATIONS OF EVIDENCE: The strengths of this study include the detailed dose-response analyses, inclusion of 48 studies and examination of sources of heterogeneity. The limitations include the observational nature of the included studies and the inaccurate estimations of amount of physical activity. INTERPRETATION: Compared with the recommended level, mortality risk was lower at physical activity levels well above the recommended target range. Further, there was no threshold beyond which lifespan was compromised. REGISTRATION: PROSPERO CRD42017055727.

Correction to: A closer look at the relationship among accelerometer-based physical activity metrics: ICAD pooled data.

Following publication of the original article [1], the author reported that the name of the collaborator group was missing from the author group.

A closer look at the relationship among accelerometer-based physical activity metrics: ICAD pooled data.

BACKGROUND: Accelerometers are widely used to assess child physical activity (PA) levels. Using the accelerometer data, several PA metrics can be estimated. Knowledge about the relationships between these different metrics can improve our understanding of children's PA behavioral patterns. It also has significant implications for comparing PA metrics across studies and fitting a statistical model to examine their health effects. The aim of this study was to examine the relationships among the metrics derived from accelerometers in children. METHODS: Accelerometer data from 24,316 children aged 5 to 18 years were extracted from the International Children's Accelerometer Database (ICAD) 2.0. Correlation coefficients between wear time, sedentary behavior (SB), light-intensity PA (LPA), moderate-intensity PA (MPA), vigorous-intensity PA (VPA), moderate- and vigorous-intensity PA (MVPA), and total activity counts (TAC) were calculated. RESULTS: TAC was approximately 22X103 counts higher (p < 0.01) with longer wear time (13 to 18 h/day) as compared to shorter wear time (8 to < 13 h/day), while MVPA was similar across the wear time categories. MVPA was very highly correlated with TAC (r = .91; 99% CI = .91 to .91). Wear time-adjusted correlation between SB and LPA was also very high (r = -.96; 99% CI = -.96, - 95). VPA was moderately correlated with MPA (r = .58; 99% CI = .57, .59). CONCLUSIONS: TAC is mostly explained by MVPA, while it could be more dependent on wear time, compared to MVPA. MVPA appears to be comparable across different wear durations and studies when wear time is ≥8 h/day. Due to the moderate to high correlation between some PA metrics, potential collinearity should be addressed when including multiple PA metrics together in statistical modeling.

Symptoms of depression in young adulthood is associated with unfavorable clinical- and behavioral cardiovascular disease risk factors.

Depression in young adults is a growing concern to public health. This study aims to investigate if depression status in young adults is related to clinical and behavioral cardiovascular disease (CVD) risk factors. Cross-sectional data from a population-based sample of young Danish adults participating in the European Youth Heart Study 2009-2010 were used to examine this (n = 644, mean age 24.3 years 47% male). Measures of cardiorespiratory fitness (CRF), body composition, blood pressure, fasting levels of high and low density lipids (HDL, LDL), insulin, and glucose were obtained. Symptoms of depression were obtained using the Major Depression Inventory scale. Information on sleep disorders; drinking and smoking habits were obtained by questionnaires. Associations of depression with CVD risk factors were examined using logistic and linear regression adjusted for age and sex. Prevalence of mild-moderate-severe depression was 8.7% (5.6% males, 11.5% females). Significant sex differences were found in the association between several CVD risk factors and depression status. Women with depression had higher odds of overweight (OR = 2.2, 95%CI: 1.01-4.0), abdominal adiposity (OR = 2.5, 95%CI: 1.2-4.8), low CRF (OR = 2.5, 95%CI: 1.2-5.5), insulin resistance (OR = 2.3, 95%CI: 1.1-4.6), low HDL (OR = 2.0, 95%CI: 1.01-4.1) and high LDL (OR = 2.2, 95%CI: 1.04-4.5) compared to women without depression. Men with depression had significantly increased odds of having high blood pressure and being smokers compared to men without depression (OR: 3.1, 95%CI: 1.1-8.8 and OR: 3.0, 95%CI: 1.1-8.4, respectively). Depression symptoms in young adulthood were related to unfavorable clinical- and behavioral CVD risk factors, particularly in women.

Associations between Recreational and Commuter Cycling, Changes in Cycling, and Type 2 Diabetes Risk: A Cohort Study of Danish Men and Women.

BACKGROUND: Cycling is a recreational activity and mode of commuting with substantial potential to improve public health in many countries around the world. The aim of this study was to examine prospective associations between recreational and commuter cycling, changes in cycling habits, and risk of type 2 diabetes (T2D) in Danish adults from the Diet, Cancer and Health cohort study. METHODS AND FINDINGS: At baseline from 1993 to 1997, 24,623 men and 27,890 women from Denmark, 50-65 y of age and free of T2D and other chronic diseases, underwent a number of assessments, including completing a lifestyle questionnaire also addressing cycling habits. Approximately 5 y later, at a second examination, participants completed a new, updated lifestyle questionnaire. Cox regression was used to estimate hazard ratios (HRs) of incident T2D registered in the Danish National Diabetes Registry, according to recreational and commuter cycling and changes in cycling habits, with adjustment for a priori known T2D risk factors. During 743,245.4 person-years of follow-up (mean follow-up 14.2 y), 6,779 incident cases of T2D were documented. Multivariable adjusted HRs (95% confidence interval [CI]) were 1, 0.87 (0.82, 0.93), 0.83 (0.77, 0.89), 0.80 (0.74, 0.86) and 0.80 (0.74, 0.87) (p for trend = <0.001) for 0, 1-60, 61-150, 151-300, and >300 min/wk of total cycling (recreational and commuter cycling), respectively. In analysis of seasonal cycling, multivariable adjusted HRs (95% CI) were 1, 0.88 (0.83, 0.94), and 0.80 (0.76, 0.85) for non-cyclists, seasonal cyclists (those cycling only in summer or winter), and those cycling during both summer and winter, respectively. How changes in total cycling from baseline to the second examination affected risk was also investigated, and multivariable adjusted HRs (95% CI) were 1, 0.88 (0.78, 1.01), 0.80 (0.69, 0.91), and 0.71 (0.65, 0.77) for non-cyclists and for those who ceased, initiated, or continued cycling between baseline and the second examination, respectively. Lastly, in the analysis of commuter cycling, multivariable HRs (95% CI) were 1, 0.72 (0.60, 0.87), 0.83 (0.69, 1.00), and 0.70 (0.57, 0.85) (p for trend = <0.001) for cycling 0, 1-60, 61-150, and >150 min/wk to work, respectively. The main limitation of the current study is the use of self-reported physical activity. CONCLUSIONS: Commuter and recreational cycling was consistently associated with lower risk of T2D in Danish adults. Our results also provide evidence that late-in-life initiation of or continued engagement in cycling lowers risk of T2D.

Muscle-strengthening and conditioning activities and risk of type 2 diabetes: a prospective study in two cohorts of US women.

BACKGROUND: It is well established that aerobic physical activity can lower the risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are beneficial for the prevention of T2D is unclear. This study examined the association of muscle-strengthening activities with the risk of T2D in women. METHODS AND FINDINGS: We prospectively followed up 99,316 middle-aged and older women for 8 years from the Nurses' Health Study ([NHS] aged 53-81 years, 2000-2008) and Nurses' Health Study II ([NHSII] aged 36-55 years, 2001-2009), who were free of diabetes, cancer, and cardiovascular diseases at baseline. Participants reported weekly time spent on resistance exercise, lower intensity muscular conditioning exercises (yoga, stretching, toning), and aerobic moderate and vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression with adjustment for major determinants for T2D was carried out to examine the influence of these types of activities on T2D risk. During 705,869 person years of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted models including aerobic MVPA, the pooled relative risk (RR) for T2D for women performing 1-29, 30-59, 60-150, and >150 min/week of total muscle-strengthening and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women reporting no muscle-strengthening and conditioning activities (p<0.001 for trend). Furthermore, resistance exercise and lower intensity muscular conditioning exercises were each independently associated with lower risk of T2D in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening activities had substantial risk reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29-0.38]). Limitations to the study include that muscle-strengthening and conditioning activity and other types of physical activity were assessed by a self-administered questionnaire and that the study population consisted of registered nurses with mostly European ancestry. CONCLUSIONS: Our study suggests that engagement in muscle-strengthening and conditioning activities (resistance exercise, yoga, stretching, toning) is associated with a lower risk of T2D. Engagement in both aerobic MVPA and muscle-strengthening type activity is associated with a substantial reduction in the risk of T2D in middle-aged and older women.

Association of genetic Loci with glucose levels in childhood and adolescence: a meta-analysis of over 6,000 children.

OBJECTIVE: To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS: A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9-16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS: Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced ß-cell function, as indicated by homeostasis model assessment of ß-cell function. Analysis using a weighted risk score showed an increase [ß (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021-0.031) for each unit increase in the score. CONCLUSIONS: Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.

Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals.

BACKGROUND: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. OBJECTIVE: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. DESIGN: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623); and 3) all published data (n(max) = 14,837). RESULTS: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (ß ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (ß ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing. CONCLUSIONS: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.