Patterns of perinatal polyunsaturated fatty acid status and associated dietary or candidate-genetic factors.

Perinatal exposure to omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can be characterized through biomarkers in maternal or cord blood or breast milk. Objectives were to describe perinatal PUFA status combining multiple biofluids and to investigate how it was influenced by dietary intake during pregnancy and maternal FADS and ELOVL gene polymorphisms. This study involved 1,901 mother-child pairs from the EDEN cohort, with PUFA levels measured in maternal and cord erythrocytes, and colostrum. Maternal dietary PUFA intake during the last trimester was derived from a food frequency questionnaire. Twelve single-nucleotide polymorphisms in FADS and ELOVL genes were genotyped from maternal DNA. Principal component analysis incorporating PUFA levels from the three biofluids identified patterns of perinatal PUFA status. Spearman's correlations explored associations between patterns and PUFA dietary intake, and linear regression models examined pattern associations with FADS or ELOVL haplotypes. Five patterns were retained: "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs"; "Omega-6 LC-PUFAs"; "Colostrum LC-PUFAs"; "Omega-6 precursor (LA) and DGLA"; "Omega-6 precursor and colostrum ALA". Maternal omega-3 LC-PUFA intakes were correlated with "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" (r(DHA) = 0.33) and "Omega-6 LC-PUFAs" (r(DHA) = -0.19) patterns. Strong associations were found between FADS haplotypes and PUFA patterns except for "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs". Lack of genetic association with the "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" pattern, highly correlated with maternal omega-3 LC-PUFA intake, emphasizes the importance of adequate omega-3 LC-PUFA intake during pregnancy and lactation. This study offers a more comprehensive assessment of perinatal PUFA status and its determinants.

Association between gut microbiota at 3.5 years of age and body mass index at 5 years: results from two French nationwide birth cohorts.

BACKGROUND/OBJECTIVES: The relationship between gut microbiota and changes in body mass index (BMI) or pediatric overweight in early life remains unclear, and information regarding the preterm population is scarce. This study aimed to investigate how the gut microbiota at 3.5 years of age is associated with (1) later BMI at 5 years, and (2) BMI z-score variations between 2 and 5 years in children from two French nationwide birth cohorts. SUBJECTS/METHODS: Bacterial 16S rRNA gene sequencing was performed to profile the gut microbiota at 3.5 years of age in preterm children (n = 143, EPIPAGE 2 cohort) and late preterm/full-term children (n = 369, ELFE cohort). The predicted abundances of metabolic functions were computed using PICRUSt2. Anthropometric measurements were collected at 2 and 5 years of age during medical examinations or retrieved from children's health records. Statistical analyses included multivariable linear and logistic regressions, random forest variable selection, and MiRKAT. RESULTS: The Firmicutes to Bacteroidetes (F/B) ratio at 3.5 years was positively associated with the BMI z-score at 5 years. Several genera were positively ([Eubacterium] hallii group, Fusicatenibacter, and [Eubacterium] ventriosum group) or negatively (Eggerthella, Colidextribacter, and Ruminococcaceae CAG-352) associated with the BMI z-scores at 5 years. Some genera were also associated with variations in the BMI z-scores between 2 and 5 years of age. Predicted metabolic functions, including steroid hormone biosynthesis, biotin metabolism, glycosaminoglycan degradation, and amino sugar and nucleotide sugar metabolism, were associated with lower BMI z-scores at 5 years. The unsaturated fatty acids biosynthesis pathway was associated with higher BMI z-scores. CONCLUSIONS: These findings indicate that the gut microbiota at 3.5 years is associated with later BMI during childhood, independent of preterm or term birth, suggesting that changes in the gut microbiota that may predispose to adult obesity begin in early childhood.

Long-term health in individuals born preterm or with low birth weight: A cohort study.

BACKGROUND: To measure the association of prematurity and non-preterm low birth weight (LBW) with several long-term health outcomes. METHODS: We selected adult participants from the Constances cohort. Associations between preterm birth (<37 weeks versus ≥37 weeks) and outcomes were measured using modified Poisson regression with adjustment for participant age and parental history. We used the same modeling methods to measure the association between LBW (i.e.,

Associations of screen use with cognitive development in early childhood: the ELFE birth cohort.

BACKGROUND: The associations of screen use with children's cognition are not well evidenced and recent, large, longitudinal studies are needed. We aimed to assess the associations between screen use and cognitive development in the French nationwide birth cohort. METHODS: Time and context of screen use were reported by parents at ages 2, 3.5 and 5.5. Vocabulary, non-verbal reasoning and general cognitive development were assessed with the MacArthur-Bates Communicative Development Inventory (MB) at age 2, the Picture Similarities subtest from the British Ability Scales (PS) at age 3.5 and the Child Development Inventory (CDI) at ages 3.5 and 5.5. Outcome variables were age-adjusted and standardized (mean = 100, SD = 15). Multiple imputations were performed among children (N = 13,763) with ≥1 screen use information and ≥1 cognitive measures. Cross-sectional and longitudinal associations between screen use and cognitive development were assessed by linear regression models adjusted for sociodemographic and birth factors related to the family and children, and children's lifestyle factors competing with screen use. Baseline cognitive scores were further considered in longitudinal analysis. RESULTS: TV-on during family meals at age 2, not screen time, was associated with lower MB scores at age 2 (ß [95% CI] = -1.67 [-2.21, -1.13]) and CDI scores at age 3.5 (-0.82 [-1.31, -0.33]). In cross-sectional analysis, screen time was negatively associated with CDI scores at ages 3.5 (-0.67 [-0.94, -0.40]) and 5.5 (-0.47 [-0.77, -0.16]), and, in contrast, was positively associated with PS scores (0.39 [0.07, 0.71]) at age 3.5. Screen time at age 3.5 years was not associated with CDI scores at age 5.5 years. CONCLUSIONS: Our study found weak associations of screen use with cognition after controlling for sociodemographic and children's birth factors and lifestyle confounders, and suggests that the context of screen use matters, not solely screen time, in children's cognitive development.

Prenatal dietary exposure to mixtures of chemicals is associated with allergy or respiratory diseases in children in the ELFE nationwide cohort.

INTRODUCTION: Prenatal exposure to environmental chemicals may be associated with allergies later in life. We aimed to examine the association between prenatal dietary exposure to mixtures of chemicals and allergic or respiratory diseases up to age 5.5 y. METHODS: We included 11,638 mother-child pairs from the French "Étude Longitudinale Française depuis l'Enfance" (ELFE) cohort. Maternal dietary exposure during pregnancy to eight mixtures of chemicals was previously assessed. Allergic and respiratory diseases (eczema, food allergy, wheezing and asthma) were reported by parents between birth and age 5.5 years. Associations were evaluated with adjusted logistic regressions. Results are expressed as odds ratio (OR[95%CI]) for a variation of one SD increase in mixture pattern. RESULTS: Maternal dietary exposure to a mixture composed mainly of trace elements, furans and polycyclic aromatic hydrocarbons (PAHs) was positively associated with the risk of eczema (1.10 [1.05; 1.15]), this association was consistent across sensitivity analyses. Dietary exposure to one mixture of pesticides was positively associated with the risk of food allergy (1.10 [1.02; 1.18]), whereas the exposure to another mixture of pesticides was positively but slightly related to the risk of wheezing (1.05 [1.01; 1.08]). This last association was not found in all sensitivity analyses. Dietary exposure to a mixture composed by perfluoroalkyl acids, PAHs and trace elements was negatively associated with the risk of asthma (0.89 [0.80; 0.99]), this association was consistent across sensitivity analyses, except the complete-case analysis. CONCLUSION: Whereas few individual chemicals were related to the risk of allergic and respiratory diseases, some consistent associations were found between prenatal dietary exposure to some mixtures of chemicals and the risk of allergic or respiratory diseases. The positive association between trace elements, furans and PAHs and the risk of eczema, and that between pesticides mixtures and food allergy need to be confirmed in other studies. Conversely, the negative association between perfluoroalkyl acids, PAHs and trace elements and the risk of asthma need to be further explored.

Sleep duration in preschool age and later behavioral and cognitive outcomes: an individual participant data meta-analysis in five European cohorts.

Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children's Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: - 1.27, 95% CI [- 2.22, - 0.32] / - 2.39, 95% CI [- 3.04, - 1.75]). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: - 0.28, 95% CI [- 0.83, 0.27] / - 0.42, 95% CI [- 0.99, 0.15]). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children's later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication.

Characteristics of infant formula consumed in the first months of life and allergy in the EDEN mother-child cohort.

The evidence regarding the association between infant formula (IF) composition and the prevention of allergy and respiratory diseases remains sparse and inconclusive. This study aimed to evaluate whether some IF characteristics were associated with the risk of allergy or respiratory diseases in childhood. Among 1243 formula-fed children from the EDEN mother-child cohort, IF characteristics concerning long-chain polyunsaturated fatty acids (LCPUFAs) enrichment, prebiotic/probiotic enrichment, and hydrolysis of proteins were identified from the ingredients list. Eczema, wheezing, food allergy, asthma, and allergic rhinitis up to age 8 years were prospectively collected and summarized into four allergic and respiratory multimorbidity clusters. Associations between 4-month IF characteristics and risk of allergy or respiratory diseases were tested using logistic regressions adjusted on main confounders. The consumption of LCPUFA-enriched formula was not linked to allergic and respiratory multimorbidity clusters, but to a lower risk of any allergy, eczema, and wheezing. Probiotic-enriched formula consumption was associated with a lower risk of belonging to the 'Allergy without asthma' cluster (odds ratio [OR] [95% confidence interval, CI] = 0.63 [0.40-0.99]), and consumption of a formula enriched in Bifidobacterium lactis was associated with a lower risk of any allergy (OR [95% CI] = 0.59 [0.41-0.85]). Partially hydrolysed formula (pHF) consumption was associated with a higher risk of belonging to the 'Allergy without asthma' cluster (OR [95% CI] = 2.73 [1.65-4.51]). This study confirms the positive association between pHF consumption and the risk of allergy found in previous observational studies and suggests that consumption of LCPUFA-enriched or probiotic-enriched formula was associated with a lower risk of allergy.

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.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Correction: 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.

[This corrects the article DOI: 10.1371/journal.pmed.1004036.].

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Parental feeding practices as potential moderating or mediating factors in the associations between children's early and later growth.

BACKGROUND: Given inconsistent results in the literature, our objective was to examine the role of early parental feeding practices in children's growth. METHODS: Analyses were based on 1245 children from the EDEN mother-child cohort. Parental feeding practices were assessed at the 2-year follow-up by using the Comprehensive Feeding Practices Questionnaire. International Obesity Task Force BMI z-scores were derived from weight and height assessed at 2, 4, 6, and 8 years. Associations between parental feeding practices and child BMI z-scores at 4, 6 and 8 years were assessed by multivariable linear regressions, notably adjusted for 2-year BMI z-score. Analyses were stratified by child sex when relevant. Moreover, interaction and mediation analyses were respectively performed to assess whether parental feeding practices could moderate or mediate the associations between early and later growth. RESULTS: For a given BMI z-score at 2 years, parental restriction for weight at 2 years was positively associated with child BMI z-scores from 4 to 8 years (at 8 years: ß [95% CI] = 0.09 [0.01; 0.16]). Among boys only, high use of food as a reward was positively associated with later BMI z-scores (at 8 years: ß [95% CI] = 0.15 [0.03; 0.27]). Parental feeding practices were not moderating factors in the associations between early and later growth. Parental restriction for weight was a mediating factor in the associations between 2-year BMI z-score and BMI z-scores up to 8 years (mediation: 2.69% [0.27%; 5.11%] of the total effect at 8 years). CONCLUSIONS: Restriction for weight reasons, often used by parents in response to the child's high appetite in infancy, appears to lie on the pathway between early and later BMI, but not restriction for health, suggesting that parental way of restricting the child's food intake matters.

Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community-based cohort.

BACKGROUND AND AIMS: The association between birth weight (BW) and metabolic outcomes has been described since the 1980s but NAFLD has been rarely studied. This study aimed to investigate the association between BW and NAFLD occurrence in adult subjects. APPROACH AND RESULTS: The study population consisted of participants from the French nationwide Constances cohort from 2012 to 2019. Participants with a history of chronic viral hepatitis or excessive alcohol consumption were excluded. Noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The relationship between BW and NAFLD was analyzed with a sex-stratified logistic regression model adjusted for sociodemographic parameters, lifestyle, and birth term, whereas liver fibrosis was analyzed with a sex-stratified linear regression model. In total, 55,034 individuals with reliable BW were included (43% men, mean age: 38 years). NAFLD (FLI ≥ 60) was present in 5530 individuals (10%). Multivariate logistic regression showed a significant U-shaped relationship between BW and NAFLD, with no significant interaction with sex. A significant and slightly decreasing association was found between BW and Forns Index (ß = -0.05; p = 0.04). Premature birth (OR, 1.23; 95% CI, 1.03-1.48 for birth between 33 and 37 weeks versus ≥ 37 weeks) was associated with NAFLD, with a significant direct effect of premature birth, and without an indirect effect of low BW in mediation analysis. Forns Index was not significantly higher in participants with preterm birth compared to full-term birth. CONCLUSIONS: This large prospective adult-based cohort confirms the relationship between BW and NAFLD occurrence.

Hydrolysed proteins in infant formula and child neurodevelopment up to the age of 3·5 years: the nationwide Étude Longitudinale Française depuis l'Enfance (ELFE) birth cohort.

While breast-feeding is the recommended feeding mode in infancy, rates are low in some Western societies, and infants are widely fed formula. France, in particular, shows high rates of infant formula use, including formulas with protein hydrolysates. The degree of protein hydrolysis has previously been associated with neurodevelopmental outcomes. The present study examines the associations between the protein's hydrolysis degree in infant formula and child neurodevelopment up to 3·5 years of age in the French nationwide Étude Longitudinale Française depuis l'Enfance (ELFE study). Parents reported on brand and name of the formula used at 2 months, and protein hydrolysis degree was derived from the ingredient list. Analyses were based on 6979 infants (92·2, 6·8 and 1 % consuming non-hydrolysed, partially and extensively hydrolysed formulas, respectively). Neurodevelopment was assessed at age 1 and 3·5 years with the Child Development Inventory (CDI), at age 2 years with the MacArthur-Bates Communicative Development Inventories and at age 3·5 years with the Picture Similarities sub-scale (British Ability Scales). Associations between protein hydrolysis degree and child neurodevelopment were assessed using linear and logistic regression for overall scores and poor CDI sub-domain scores (<25th centile), respectively. Among formula-fed infants, protein hydrolysis degree in infant formula was not associated with overall neurodevelopmental scores up to 3·5 years. Some associations were found with the motor skills CDI sub-domain, but they were not consistent at 1 and 3·5 years as well as across sensitivity analyses. The use of hydrolysed formula appears safe in terms of overall neurodevelopment, and research should further investigate specific neurodevelopmental domains.

Prospective associations of lifestyle patterns in early childhood with socio-emotional and behavioural development and BMI: An outcome-wide analysis of the EDEN mother-child cohort.

BACKGROUND: Children's energy balance-related behaviours (EBRB), comprising diet, screen time, physical activity, and sleep, combine into "lifestyle patterns", which may exert a synergistic effect on health. To date, studies investigating this synergy have primarily focused on obesity risk, without addressing other facets of health. OBJECTIVES: To examine the prospective associations of preschoolers' lifestyle patterns with socio-emotional, behavioural, and body mass index (BMI) outcomes at 8 years. METHODS: Participants were 876 children from the EDEN mother-child cohort. Three lifestyle patterns (unhealthy, healthy, and mixed) were previously identified at age 5, separately in boys and girls. At age 8, height and weight measures generated BMI z-scores while social-emotional and behavioural development was assessed by parents using the Strengths and Difficulties Questionnaire (SDQ). Drawing from the outcome-wide approach, sex- and outcome-specific adjusted linear regressions were fitted. RESULTS: Boys' adherence to a healthy lifestyle pattern (combining a nutrient-dense diet and limited screen time) at 5 years was positively associated with prosocial behaviours (ß = 0.14; 95% confidence interval [CI] 0.01, 0.26) and inversely related to hyperactivity-inattention symptoms (ß = -0.12; 95% CI -0.23, -0.01) at 8 years. Girls' mixed lifestyle pattern (sugar or artificially sweetened beverages, high screen, physical activity and low sleep times) was associated with prosocial behaviours (ß = 0.12; 95% CI 0.01, 0.23). There was no evidence of associations between lifestyle patterns and BMI z-scores. CONCLUSIONS: Findings suggest synergistic benefits of engaging in a combination of optimal EBRBs, especially in boys, and support intervention efforts at preschool age to enhance some dimensions of their later socio-emotional and behavioural development.

Measures of Early-life Behavior and Later Psychopathology in the LifeCycle Project - EU Child Cohort Network: A Cohort Description.

BACKGROUND: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. METHODS: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. RESULTS: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. CONCLUSION: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Determinants of incomplete vaccination in children at age two in France: results from the nationwide ELFE birth cohort.

Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries, but its determinants are poorly understood. Their identification is necessary to design target actions that can improve vaccination uptake. Our aim was to assess the determinants of incomplete vaccination in two-year-old children in France. Among the 18,329 children included in the 2011 ELFE French nationwide population-based birth cohort, we selected those for whom vaccination status was available at age two years. Incomplete vaccination was defined as ≥ 1 missing dose of recommended vaccines. Potential determinants of incomplete vaccination were identified by using logistic regression, taking into account attrition and missing data. Of the 5,740 (31.3%) children analyzed, 46.5% (95% confidence interval [CI] 44.7-48.0) were incompletely vaccinated. Factors independently associated with incomplete vaccination were having older siblings (adjusted odds ratio 1.18, 95% CI [1.03-1.34] and 1.28 [1.06-1.54] for one and ≥ 2 siblings, respectively, vs. 0), residing in an isolated area (1.92 [1.36-2.75] vs. an urban area), parents not following health recommendations or using alternative medicines (1.81 [1.41-2.34] and 1.23 [1.04-1.46], respectively, vs. parents confident in institutions and following heath recommendations), not being visited by a maternal and child protection service nurse during the child's first two months (1.19 [1.03-1.38] vs. ≥ 1 visit), and being followed by a general practitioner (2.87 [2.52-3.26] vs. a pediatrician). CONCLUSIONS: Incomplete vaccination was highly prevalent in the studied pediatric population and was associated with several socio-demographic, parental, and healthcare service characteristics. These findings may help in designing targeted corrective actions. WHAT IS KNOWN: • Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries. • The partial understanding of the determinants of incomplete vaccination precludes the design of effective targeted corrective actions. WHAT IS NEW: • High prevalence of incomplete vaccination at age two years in France. • Incomplete vaccination was independently associated with several socio-demographic, parental, and healthcare service characteristics.

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Maternal pre-pregnancy BMI and offspring hyperactivity-inattention trajectories from 3 to 8 years in the EDEN birth cohort study.

Evidence suggests obesity during pregnancy is associated with offspring attention-deficit hyperactivity disorder. However, studies have been limited to evaluating the association at a single age with inadequate data on important maternal lifestyle confounders and unmeasured familial confounding. The objective of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 3, 5 and 8 years. Data came from the EDEN mother-child cohort. Maternal pre-pregnancy BMI status (kg/m2) was calculated using pre-pregnancy weight and height (self-reported by mothers or measured by midwives). HIS were assessed by parental-report on the Strengths and Difficulties Questionnaire at 3, 5 and 8 years of age and used to derive developmental trajectories of HIS (n = 1428). Multivariate models were adjusted for confounders including socioeconomic status, maternal lifestyle behaviours (exercise, diet, smoking, alcohol), childcare and a stimulating home environment. Paternal BMI was used as a negative control. Compared to a normal pre-pregnancy BMI, pre-pregnancy maternal obesity was positively associated with increased odds of a high HIS trajectory between 3 and 8 years old in both unadjusted and adjusted logistic regression (adjusted odds ratio [aOR] 1.87 [95% CI 1.12, 3.12]). Pre-pregnancy overweight was not significantly associated after adjustment for confounders (aOR 1.32 [0.87, 2.01]). Maternal pre-pregnancy obesity, but not overweight, was associated with increased likelihood of a high HIS trajectory in children from 3 to 8 years old. This association persisted despite controlling for many important maternal lifestyle factors and paternal BMI. Further research is warranted to identify possible mediators involved.

Longitudinal impact of psychosocial status on children's mental health in the context of COVID-19 pandemic restrictions.

Emerging research suggests that the prevalence of child and adolescent mental health problems has increased considerably during the COVID-19 crisis. However, there have been few longitudinal studies on children's mental health issues according to their social determinants in this context, especially in Europe. Our aim was to investigate the association between family socioeconomic status (SES) and children' mental health during the period of school closure due to COVID-19. Longitudinal data came from 4575 children aged 8-9 years old in 2020 and participating in the ELFE population-based birth cohort that focuses on children's health, development and socialization. Parents completed the Strengths and Difficulties Questionnaire (SDQ) when children were (a) 5 years of age and (b) 9 years of age, which corresponded to the period of school closure due to the COVID-19 pandemic in France. We retrieved data from the ELFE cohort collected on children from birth to age 5 years (birth, 1 year, 2 years, 3,5 years and 5 years). Socioeconomic status (SES) was measured based on information obtained when the child was 5 years old. Data were analyzed using multinomial logistic regression models. Children's elevated levels of symptoms of Attention-deficit/Hyperactivity disorder (ADHD) during the period of school closure were significantly associated with prior low family SES (aOR 1.26, 95% CI 1.08-1.48). Children's elevated symptoms of hyperactivity/inattention and of emotional symptoms were associated with decline in income during the COVID crisis (respectively, aOR 1.38, 95% CI 1.16-1.63 and aOR 1.23, 95% CI 1.01-1.51). Moreover, when testing interactions, a low prior SES was significantly associated with a higher risk of emotional symptoms aOR 1.54 (1.07-2.21), only for children whose families experienced a decline in income, while gender, parental separation and prior mental health difficulties were not associated. This study underlines the impact of the financial crisis related to the COVID-19 epidemic on children's mental health. Both pre-existing family SES before lockdown and more proximal financial difficulties during the COVID crisis were negatively associated with children's psychological difficulties during the period of school closure. The pandemic appears to exacerbate mental health problems in deprived children whose families suffer from financial difficulties.

Infant feeding practices associated with adiposity peak and rebound in the EDEN mother-child cohort.

BACKGROUND/OBJECTIVE: High magnitude of adiposity peak and early adiposity rebound are early risk markers of later obesity. Infant diet represents one of the main modifiable determinants of early growth. This study aimed to investigate the association between infant feeding practices and age and magnitude of adiposity peak and rebound. SUBJECTS/METHODS: Analyses were based on data from the French EDEN mother-child cohort. Data on breastfeeding and complementary feeding were collected at birth and 4, 8, and 12 months. From clinical examinations and measurements collected in the child's health booklet up to 12 years, individual growth curves were modeled, and ages and magnitudes of adiposity peak and rebound were estimated. Associations between infant feeding practices and growth were investigated by multivariable linear regression in children after testing a child-sex interaction. RESULTS: In the studied population (n = 1225), adiposity peak occurred at a mean of 9.9 ± 2 months and adiposity rebound at 5.5 ± 1.4 years. Associations between infant feeding practices and adiposity peak or rebound were moderated by child sex. For girls, each additional month of breastfeeding was related to a 2-day increase in the age at adiposity peak (p < 0.001), and an 18-day increase in the age at adiposity peak (p = 0.004). Whereas for boys, each additional month for the age at complementary food introduction was associated with a 29-day increase in the age at adiposity rebound (p = 0.02). For boys, long breastfeeding duration was only related to reduced body mass index at adiposity peak. CONCLUSIONS: Child sex has a moderating effect on the association between infant feeding practices and adiposity peak or rebound. The well-known association between breastfeeding duration and early growth seems stronger in girls than boys. The association found for complementary feeding in boys may give new insights into preventing obesity.