Early life factors and childhood obesity development

L’obesitat infantil és un dels majors problemes de Salut Pública i comença en edat primerenca. Per tant, identificar factor de risc podria ajudar en la prevenció del desenvolupament d’obesitat infantil. L’objectiu principal d’aquesta tesi va ser investigar les associacions prospectives entre factors de risc potencialment modificables de l’embaràs i la infància, i el desenvolupament d’obesitat infantil. Vam utilitzar dades de dues cohorts de naixement del projecte INMA (Espanya) i del Projecte Viva (Estats Units). Vam explorar les associacions entre varis factors de risc pre i postnatals i l’obesitat infantil general i abdominal, el risc metabòlic i les trajectòries de creixement infantil. Vam trobar que els factors de risc presents en l’edat primerenca i modificables juguen un paper important en el desenvolupament d’obesitat. Les combinacions de factors de risc modificables que prediuen més obesitat infantil difereixen segons la població. Tot i que, el guany ràpid de pes durant la infància és un factor de risc comú pel desenvolupament d’obesitat infantil, tal general com abdominal . Els nostres resultats suggereixen que prendre una Dieta Mediterrània durant l’embaràs podria tenir un efecte positiu en la mida del neonat, el patró de creixement i l’obesitat infantil abdominal. Tanmateix, aquest patró alimentari no deu estar associat amb l’obesitat general o el risc cardiometabòlic.La obesidad infantil es uno de los mayores problemas en Salud Pública y empieza en edad temprana. Por lo tanto, identificar factores de riesgo podría ayudar en la prevención del desarrollo de obesidad infantil. El objetivo principal de esta tesis fue investigar la asociación prospectiva entre factores de riesgo durante el embarazo y la primera infancia, y el desarrollo de obesidad infantil. Usamos datos de dos cohortes de nacimiento del Proyecto INMA (España) y del Proyecto Viva (Estados Unidos). Exploramos las asociaciones entre varios factores de riesgo pre y postnatales y la obesidad infantil general y abdominal, el riesgo cardiometabólico y las trayectorias infantiles de crecimiento. Encontramos que factores de riesgo modificables en etapas tempranas juegan un papel importante en el desarrollo de obesidad. Las combinaciones de factores de riesgo modificables que predicen mayor obesidad difieren entre poblaciones. Sin embargo, la rápida ganancia de peso en la infancia es un factor de riesgo común de obesidad infantil, tanto general como abdominal. Nuestros resultados sugieren que la Dieta Mediterránea durante el embarazo podría tener un efecto protector en el tamaño del recién nacido, en el patrón de crecimiento y en la obesidad abdominal en la infancia. Sin embargo, este patrón alimentario podría no estar asociado con la obesidad infantil general y el riesgo cardiometabólico.Childhood obesity is one of the main public health problems and starts in early life. Thus identifying risk factors could help to prevent childhood obesity development. The main objective of this thesis was to investigate the prospective association between potentially modifiable factors in pregnancy and infancy, and offspring childhood obesity development. We used data from two birth cohorts studies INMA project (Spain) and Project Viva (USA). We explored the associations between several pre and postnatal risk factors and childhood general and abdominal obesity, cardiometabolic risk and child longitudinal growth trajectories. We found that modifiable early-life risk factors play an important role in obesity development. The combinations of modifiable risk factors that predict higher obesity differed across populations. However, rapid infant weight gain is a common risk factor of general and abdominal obesity in childhood. Our findings suggest that the Mediterranean diet during pregnancy may have a protective effect on birth size, growth pattern and childhood abdominal adiposity in early childhood. However, this dietary pattern may not be associated with childhood general obesity and cardiometabolic risk

Prenatal Omega-6:Omega-3 Ratio and Attention Deficit and Hyperactivity Disorder Symptoms

Objective: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. Study design: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. Results: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. Conclusions: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring

High adherence to a mediterranean diet at age 4 reduces overweight, obesity and abdominal obesity incidence in children at the age of 8

Background/objectives A higher adherence to a Mediterranean diet has been shown to be protective against obesity in adults, but the evidence is still inconclusive in children at early ages. Our objective was to explore the association between adherence to Mediterranean Diet at the age of 4 and the prevalence of overweight, obesity, and abdominal obesity at 4 years of age, and incidence at the age of 8. Subjects/methods We analyzed data from children of the INMA cohort study who attended follow-up visits at age 4 and 8 years (n = 1801 and n = 1527, respectively). Diet was assessed at the age of 4 using a validated food frequency questionnaire. The adherence to MD was evaluated by the relative Mediterranean diet (rMED) score, and categorized as low (0–6), medium (7–10), and high (11–16). Overweight and obesity were defined according to the age-sex specific BMI cutoffs proposed by the International Obesity Task Force, and abdominal obesity as waist circumference >90th percentile. We used Poisson regression models to estimate prevalence ratios at 4 years of age, and Cox regression analysis to estimate hazard ratios (HR) from 4–8 years of age. Results In cross-sectional analyses at the age of 4 no association was observed between adherence to MD and overweight, obesity, or abdominal obesity. In longitudinal analyses, a high adherence to MD at age 4 was associated with lower incidence of overweight (HR = 0.38; 95% CI: 0.21–0.67; p = 0.001), obesity (HR = 0.16; 95% CI: 0.05–0.53; p = 0.002), and abdominal obesity (HR = 0.30; 95% CI: 0.12–0.73; p = 0.008) at the age of 8. Conclusion This study shows that a high adherence to MD at the age of 4 is associated with a lower risk of developing overweight, obesity, and abdominal obesity at age 8. If these results are confirmed by other studies, MD may be recommended to reduce the incidence of obesity at early ages

Maternal Mediterranean diet in pregnancy and newborn DNA methylation:a meta-analysis in the PACE Consortium

Data de publicació electrònica: 02-03-2022Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. DNA methylation may be an underlying biological mechanism. We evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation.We meta-analysed epigenome-wide association studies (EWAS) of maternal adherence to the Mediterranean diet during pregnancy and offspring cord blood DNA methylation in 2802 mother-child pairs from five cohorts. We calculated the relative Mediterranean diet (rMED) score with range 0-18 and an adjusted rMED excluding alcohol (rMEDp, range 0-16). DNA methylation was measured using Illumina 450K arrays. We used robust linear regression modelling adjusted for child sex, maternal education, age, smoking, body mass index, energy intake, batch, and cell types. We performed several functional analyses and examined the persistence of differential DNA methylation into childhood (4.5-7.8 y).rMEDp was associated with cord blood DNA methylation at cg23757341 (0.064% increase in DNA methylation per 1-point increase in the rMEDp score, SE = 0.011, P = 2.41 × 10-8). This cytosine-phosphate-guanine (CpG) site maps to WNT5B, associated with adipogenesis and glycaemic phenotypes. We did not identify associations with childhood gene expression, nor did we find enriched biological pathways. The association did not persist into childhood.In this meta-analysis, maternal adherence to the Mediterranean diet (excluding alcohol) during pregnancy was associated with cord blood DNA methylation level at cg23757341. Potential mediation of DNA methylation in associations with offspring health requires further study.This work was supported by the Foundation for the National Institutes of Health [R01 HD034568, UH3 OD023286, R01 NR013945, R01 HL111108]; Joint Programming Initiative A healthy diet for a healthy life [529051023, MR/S036520/1, 529051022, MR/S036520/1, MR/S036520/1]; National Institute of Environmental Health Sciences [R00ES025817]; National institute of diabetes and digestive and kidney diseases [R01DK076648]; National Institutes of Health Office of the Director [UH3OD023248]; Horizon 2020 research and innovation [874739, 733206, 848158, 824989]; Medical Research Council [MR/S009310/1]

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

Early life factors and childhood obesity development

L’obesitat infantil és un dels majors problemes de Salut Pública i comença en edat primerenca. Per tant, identificar factor de risc podria ajudar en la prevenció del desenvolupament d’obesitat infantil. L’objectiu principal d’aquesta tesi va ser investigar les associacions prospectives entre factors de risc potencialment modificables de l’embaràs i la infància, i el desenvolupament d’obesitat infantil. Vam utilitzar dades de dues cohorts de naixement del projecte INMA (Espanya) i del Projecte Viva (Estats Units). Vam explorar les associacions entre varis factors de risc pre i postnatals i l’obesitat infantil general i abdominal, el risc metabòlic i les trajectòries de creixement infantil. Vam trobar que els factors de risc presents en l’edat primerenca i modificables juguen un paper important en el desenvolupament d’obesitat. Les combinacions de factors de risc modificables que prediuen més obesitat infantil difereixen segons la població. Tot i que, el guany ràpid de pes durant la infància és un factor de risc comú pel desenvolupament d’obesitat infantil, tal general com abdominal . Els nostres resultats suggereixen que prendre una Dieta Mediterrània durant l’embaràs podria tenir un efecte positiu en la mida del neonat, el patró de creixement i l’obesitat infantil abdominal. Tanmateix, aquest patró alimentari no deu estar associat amb l’obesitat general o el risc cardiometabòlic.La obesidad infantil es uno de los mayores problemas en Salud Pública y empieza en edad temprana. Por lo tanto, identificar factores de riesgo podría ayudar en la prevención del desarrollo de obesidad infantil. El objetivo principal de esta tesis fue investigar la asociación prospectiva entre factores de riesgo durante el embarazo y la primera infancia, y el desarrollo de obesidad infantil. Usamos datos de dos cohortes de nacimiento del Proyecto INMA (España) y del Proyecto Viva (Estados Unidos). Exploramos las asociaciones entre varios factores de riesgo pre y postnatales y la obesidad infantil general y abdominal, el riesgo cardiometabólico y las trayectorias infantiles de crecimiento. Encontramos que factores de riesgo modificables en etapas tempranas juegan un papel importante en el desarrollo de obesidad. Las combinaciones de factores de riesgo modificables que predicen mayor obesidad difieren entre poblaciones. Sin embargo, la rápida ganancia de peso en la infancia es un factor de riesgo común de obesidad infantil, tanto general como abdominal. Nuestros resultados sugieren que la Dieta Mediterránea durante el embarazo podría tener un efecto protector en el tamaño del recién nacido, en el patrón de crecimiento y en la obesidad abdominal en la infancia. Sin embargo, este patrón alimentario podría no estar asociado con la obesidad infantil general y el riesgo cardiometabólico.Childhood obesity is one of the main public health problems and starts in early life. Thus identifying risk factors could help to prevent childhood obesity development. The main objective of this thesis was to investigate the prospective association between potentially modifiable factors in pregnancy and infancy, and offspring childhood obesity development. We used data from two birth cohorts studies INMA project (Spain) and Project Viva (USA). We explored the associations between several pre and postnatal risk factors and childhood general and abdominal obesity, cardiometabolic risk and child longitudinal growth trajectories. We found that modifiable early-life risk factors play an important role in obesity development. The combinations of modifiable risk factors that predict higher obesity differed across populations. However, rapid infant weight gain is a common risk factor of general and abdominal obesity in childhood. Our findings suggest that the Mediterranean diet during pregnancy may have a protective effect on birth size, growth pattern and childhood abdominal adiposity in early childhood. However, this dietary pattern may not be associated with childhood general obesity and cardiometabolic risk

Gestational age at birth and body size from infancy through adolescence: an individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies

Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother–child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child’s birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: −0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.This collaborative project received funding from the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle, Grand Recipient VWVJ; Grant Agreement No. 824989 EUCAN-Connect, Grand Recipient AMNA). Please, see S1 Appendix for list of cohort-specific funding/support. DAL is supported by the UK Medical Research Council (MC_UU_00011/6) and British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). RCW is supported by UKRI Innovation Fellowship with Health Data Research UK [MR/S003959/1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The EU Child Cohort Network's core data: establishing a set of findable, accessible, interoperable and re-usable (FAIR) variables

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.The LifeCycle project received funding from the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle). All study specific acknowledgements and funding are presented in the supplementary material. This manuscript reflects only the author’s view and the Commission is not responsible for any use that may be made of the information it contains

Consumption of ultra-processed foods and drinks and colorectal, breast, and prostate cancer

Aims: To study whether the consumption of ultra-processed foods and drinks is associated with breast, colorectal, and prostate cancers. Methods: Multicentric population-based case-control study (MCC-Spain) conducted in 12 Spanish provinces. Participants were men and women between 20 and 85 years of age with diagnoses of colorectal (n = 1852), breast (n = 1486), or prostate cancer (n = 953), and population-based controls (n = 3543) frequency-matched by age, sex, and region. Dietary intake was collected using a validated food frequency questionnaire. Foods and drinks were categorized according to their degree of processing based on the NOVA classification. Unconditional multivariable logistic regression was used to evaluate the association between ultra-processed food and drink consumption and colorectal, breast, and prostate cancer. Results: In multiple adjusted models, consumption of ultra-processed foods and drinks was associated with a higher risk of colorectal cancer (OR for a 10% increase in consumption: 1.11; 95% CI 1.04-1.18). The corresponding odds for breast (OR 1.03; 95% CI 0.96-1.11) and prostate cancer (OR 1.02; 95% CI 0.93-1.12) were indicative of no association. Conclusions: Results of this large population-based case-control study suggest an association between the consumption of ultra-processed foods and drinks and colorectal cancer. Food policy and public health should include a focus on food processing when formulating dietary guidelines

A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4-10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (PFDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies