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Maternal smoking during pregnancy contributes to poor birth outcomes. Here the authors perform a meta-analysis of the associations between maternal smoking during pregnancy and placental DNA methylation and identify links between these and poor birth outcomes, which may better inform the mechanisms through which smoking impacts placental function and fetal growth.

Abstract Evidence linking maternal diet during pregnancy to allergic or respiratory diseases in children remains sparse, and outcomes were mainly studied separately. We aim to investigate these associations by considering clusters of allergic and respiratory multimorbidity among 9679 mother–child pairs from the Elfe birth cohort. Maternal diet quality was evaluated using a food-based score (Diet Quality score), a nutrient-based score (PANDiet score) and food group intakes. Adjusted multinomial logistic regressions on allergic and respiratory multimorbidity clusters up to 5.5 years were performed. Child allergic and respiratory diseases were described through five clusters: “asymptomatic” (43%, reference), “early wheeze without asthma” (34%), “asthma only” (7%), “allergies without asthma” (7%), “multi-allergic” (9%). A higher PANDiet score and an increased legume consumption were associated with a reduced risk of belonging to the “early wheeze without asthma” cluster. A U-shaped relationship was observed between maternal fish consumption and the “allergies without asthma” cluster. To conclude, adequate nutrient intake during pregnancy was weakly associated with a lower risk of “early wheeze without asthma” in children. No association was found with food groups, considered jointly or separately, except for legumes and fish, suggesting that maternal adherence to nutritional guidelines might be beneficial for allergic and respiratory diseases prevention.

Background: Urban environments are characterized by many factors that may influence children’s energy balance-related behaviors (EBRBs), but there is limited research on the impact of prospective exposure to multiple urban factors in preschoolers. We evaluated prospective associations between various urban exposures and EBRBs in preschoolers across Europe, with EBRBs considered both individually and combined into lifestyle patterns. Methods: We used data from 4,073 preschoolers (aged 3–4 years) participating in three European cohorts from the EU Child Cohort Network: BiB (United Kingdom), EDEN (France), and INMA (Spain). Eighteen built and food environment, green spaces, road traffic and ambient air pollution exposures were characterized at residential addresses. Various EBRBs were considered as the outcomes including screen time, sleep duration and diet (fruit, vegetables, discretionary sweet foods, sweet beverages) individually and combined into unhealthy lifestyle patterns, using principal components analysis. Associations between urban exposures and outcomes were estimated using a single-exposure analysis and the deletion-substitution-addition algorithm was used to construct multi-exposure models. Results: In multi-exposure models, greater walkability and smaller distance to the nearest road were associated with higher scores on the unhealthy lifestyle patterns. Likewise, greater walkability was associated with higher screen time and more frequent discretionary sweet food consumption. A smaller distance to the nearest road was also associated with lower sleep duration and more frequent sweet beverages consumption. On the other hand, higher levels of street connectivity showed an inverse association with the unhealthy lifestyle patterns. In the same vein, greater street connectivity was associated with decreased screen time. Conclusion: This comprehensive examination of multiple urban exposures indicates that residing in walkable environments and in close proximity to roads in densely-populated areas may not be advantageous for children EBRBs, while residing in neighborhoods with higher street connectivity appears to supposedly be beneficial.

Background: Bisphenol A (BPA; or 4,4′-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. Objective: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18–73 years (n = 4,226) and its determinants. Methods: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. Results: Total BPA was quantified in 85–100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA’s BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. Conclusion: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Abstract The effect of screen viewing on children’s cognitive development has been of concern among parents and researchers. This study investigated the association between children screen time, as reported by parents, and drawing ability, and the confounding effects of socioeconomic characteristics (such as parental education, household income, migration status) and children’s competing activities (such as drawing practice, extracurricular activity, outdoor time, sleep time, time playing with parents). Participants included 7577 children aged 3.5 years (50% girls) who underwent the Draw-a-person test (McCarthy score [range = 0–12 points]) in the French nationwide Elfe birth cohort, initiated in 2011. Sex-stratified zero-inflated Poisson regression models were used. Increased screen time was associated with a higher likelihood to obtain a null score in boys (OR 1.15, 95% CI 1.07–1.23) and girls (1.13 [1.03–1.24]) and a lower score in girls only (β = − 0.02, 95% CI − 0.04; − 0.01). After adjusting for SES, associations were no longer observed, indicating that the association between screen time and drawing abilities was confounded by socioeconomic characteristics.

Abstract 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.

Summary: Background: Early childcare attendance may be related to children's internalizing and externalizing symptoms throughout childhood and young adolescence, however evidence from Europe is limited. We aimed to assess this association across multiple population-based birth cohorts of children recruited in different European countries. Methods: Data come from six parent-offspring prospective birth cohort studies across five European countries within the EU Child Cohort Network. A total of 87,208 parent-child dyads were included in the study. To test associations between childcare attendance (centre-based or informal) anytime between ages 0 and 4 years and children's internalizing and externalizing symptoms in middle childhood and young adolescence (measured at: 5–6 years, 7–9 years, and 10–13 years) a two-stage individual participant data meta-analysis was implemented. Linear regression models were performed in each cohort separately; combined random-effects meta-analysis was then used to obtain overall association estimates. In secondary analyses, we tested interactions between childcare attendance and mother's post-partum depression, low education status, and the child's sex. Findings: Compared to children who were exclusively cared for by their parents prior to school entry, those who attended centre-based childcare had lower levels of internalizing symptoms in all age groups [5–6 years: β: −1.78 (95% CI: −3.39, −0.16); 7–9 years: β: −0.55 (95% CI: −0.88, −0.73); 10–13 years: β: −0.76 (95% CI: −1.15, −0.37)]. Children who attended informal childcare appeared to have elevated levels of internalizing symptoms between 7–9 and 10–13 years, respectively [β: 1.65 (95% CI: 1.25, 2.06); β: 1.25 (95% CI: 0.96, 1.54)]. Informal childcare attendance was also associated with increased levels of children's externalizing symptoms between 7–9 and 10–13 years, respectively [β: 2.84 (95% CI: 1.41, 4.26); β: 2.19 (95% CI: 0.54, 3.84)]. Interpretation: Early centre-based childcare is associated with decreased levels of children's internalizing symptoms compared to exclusive parental care. For informal childcare, opposite associations were observed. Overall, our results suggest that centre-based childcare attendance may be associated with slight positive impacts on children's emotional development and should be encouraged by public policies. In addition, children from socioeconomically disadvantaged families require special attention, as they may not sufficiently benefit from universal early childhood education and care (ECEC). Funding: This research was funded by the ERC Consolidator grant RESEDA (Horizon Europe, 101001420).

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.

Abstract An inverse social gradient in early childhood overweight has been consistently described in high-income countries; however, less is known about the role of migration status. We studied the social patterning of overweight in preschool children according to the mother’s socio-economic and migration background. For 9250 children of the French ELFE birth cohort with body mass index collected at age 3.5 years, we used nested logistic regression to investigate the association of overweight status in children with maternal educational level, occupation, household income and migration status. Overall, 8.3% (95%CI [7.7–9.0]) of children were classified as overweight. The odds of overweight was increased for children from immigrant mothers (OR 2.22 [95% CI 1.75–2.78]) and descendants of immigrant mothers (OR 1.35 [1.04–2.78]) versus non-immigrant mothers. The highest odds of overweight was also observed in children whose mothers had low education, were unemployed or students, or were from households in the lowest income quintile. Our findings confirm that socio-economic disadvantage and migration status are risk factors for childhood overweight. However, the social patterning of overweight did not apply uniformly to all variables. These new and comprehensive insights should inform future public health interventions aimed at tackling social inequalities in childhood overweight.

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.

IntroductionChildren have been significantly less affected by COVID-19 than adults and presented with milder and less symptomatic forms of the disease. However, there has been suggestion that children older than 10 years and adolescents exhibits features closer to that of young adults. Most studies combine children in different age-groups and lack sufficient numbers to explore in detail age specificities. We report data on a population-based sample of 2,555 children at the pivotal age of 9 years.MethodsIn April 2020, the participants in two French nationwide cohorts of children, Elfe and Epipage2, were invited to take part into an online survey about Covid related symptoms and family life during the lockdown. A second questionnaire was sent on May 5. This questionnaire also proposed to the child included in the cohort and to one of his/her parents to take part into a capillary blood collection for Covid serology. Families who agreed to the serological survey were sent kits for dried blood spots self-sampling (DBS) with instructions. Samples were processed with a commercial Elisa test (Euroimmun®, Lübeck, Germany) to detect anti-SARS-CoV-2 antibodies (IgG) directed against the S1 domain of the spike protein of the virus.ResultsChildren's acceptance rate for the serological survey was around 60%. 2,555 serological results were analyzed. The weighted prevalence of a positive Elisa Spike serology was 2.8% in 9 yr-old children (95% CI: 1.7%–4.0%). Positive serology was found in 8.6% (7.4%–9.7%) of parents who provided blood. There was a significant association (p < 0.001) between serology of the child and parent from the same household with an odds ratio of 13.8 (7.9–24.2).DiscussionWe have shown that 9-yr old children had a lower susceptibility to SARS-Cov2 infection than adults with the initial Chinese strain, similar to younger children and estimated that around 3% of them have developed antibodies against SARS-Cov2 in France after the first wave of the Covid-19 epidemics.

Introduction: Maternal exposure to food chemicals may increase the risk of allergy and respiratory disorders in offspring. We aimed to assess the association of prenatal dietary exposure to single chemicals and chemical mixtures with allergy or respiratory events reported before age 8 y in children. Methods: We included 1428 mother–child pairs enrolled in the EDEN mother–child cohort. Maternal dietary exposure to 209 chemicals and eight associated mixtures was investigated. Allergic and respiratory diseases (wheezing, asthma, allergic rhinitis, eczema and food allergy) were reported by parents between birth and age 8 y. Associations with the studied outcomes were evaluated with three approaches based on adjusted logistic regression, estimating odds ratios (ORs) and 95 % confidence intervals (CIs). First, food chemicals were considered individually, with correction for multiple testing. Second, chemicals selected by elastic net regression were considered simultaneously in a multiple exposure model. Third, predefined mixtures were introduced in the same adjusted logistic regression. Results are expressed as odds ratio (OR[95 % CI]). Results: Prenatal single exposure to 74 food chemicals was associated with higher risk of allergic rhinitis. Prenatal single exposure to 11 chemicals was associated with higher risk of wheezing. In the multi-exposure approach, risk of wheezing was associated with the pesticides diazinon and triadimenol, and polycyclic aromatic hydrocarbon 5-methylchrysene. Phytoestrogen resveratrol was negatively associated with lower risk of both wheezing and allergic rhinitis, and mycotoxin monoacetoxyscirpenol was negatively associated with risk of eczema. Finally, a chemical mixture composed mainly of trace elements, furans and polycyclic aromatic hydrocarbons, was associated with higher risk of allergic rhinitis (1.33 [1.02;1.73]). Conclusion: Prenatal dietary exposure to chemicals was associated with risk of allergic rhinitis or wheezing up to age 8 y. A few chemicals were associated with other allergic and respiratory diseases. Larger prospective studies are needed to confirm these findings.

Abstract Several risk factors of children’s mental health issues have been identified during the pandemic of COronaVIrus Disease first appeared in 2019 (COVID-19). This study aims to fill the knowledge gap regarding the association between parents’ and children’s mental health issues during the COVID-19 school closure in France. We conducted a cross-sectional analysis of data collected in the SAPRIS-ELFE study during the COVID-19 pandemic in France. Using multinomial logistic regressions, we estimated associations between parents’ and children’s mental health issues. Symptoms of anxiety were assessed by the General Anxiety Disorder-7 (GAD-7) and depression by the Patient Health Questionnaire-9 (PHQ-9) for the parents. Hyperactivity/inattention and emotional symptoms in children were assessed by the Strengths and Difficulties Questionnaire (SDQ). The sample included 3496 children aged 8 to 9 years, of whom 50.0% were girls. During the school closure, 7.1% of responding parents had moderate to severe levels of anxiety and 6.7% had moderate to severe levels of depression. A total of 11.8% of the children had an abnormal hyperactivity/inattention score and 6.6% had an abnormal emotional symptoms score. In multivariate regression models, parental moderate to severe level of anxiety and moderate to severe level of depression were associated with abnormal hyperactivity-inattention score (adjusted Odds Ratio (aOR) 3.31; 95% Confidence Interval (CI) 2.33–4.70 and aOR 4.65; 95% CI 3.27–6.59, respectively) and abnormal emotional symptoms score in children (aOR 3.58; 95% CI 2.33–5.49 and aOR 3.78; 95 CI 2.47–5.78 respectively). Children whose parents have symptoms of anxiety and/or depression have an increased likelihood of symptoms of hyperactivity/inattention and emotional symptoms during school closures in France due to COVID-19. Our findings suggest that public health initiatives should target parents and children to limit the impact of such crises on their mental health issues.

Abstract The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m2). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.

Abstract Background Excessive screen time in infancy and childhood has been associated with consequences on children’s development and health. International guidelines call for no screen time before age 2 years, whereas in France, the most prominent guidelines recommend no screen before age 3 years. However, data are lacking on parental adherence to the no-screen guideline for toddlers and factors of adherence in France. Using data from the French nationwide Elfe birth cohort, we estimated adherence to the no-screen guideline at age 2 years and examined related factors, including sociodemographic characteristics, parental leisure activities and screen time. Methods In 2011, 18,329 newborns and their parents were enrolled in 349 randomly selected maternity units across mainland France. At age 2 years, screen exposure of 13,117 toddlers was reported by parents in phone interviews. Data on sociodemographic characteristics, parental leisure activities and screen time were collected from both parents. Three patterns of parental leisure activities were derived by principal component analysis: literate (e.g.,reading), screen-based, and physical/artistic activities. Multivariable logistic regression models were used to examine the associations of sociodemographic characteristics, parental leisure activities and parental screen time with adherence to the no-screen guideline for toddlers. Results Overall, 1809/13,117 (13.5%) families adhered to the no-screen guideline for toddlers. Adherence was reduced with maternal age

The preconception period represents an important window for foetal and epigenetic programming. Some micronutrients (B vitamins, choline, betaine, methionine) implicated in one-carbon metabolism (OCM) are essential for major epigenetic processes that take place in early pregnancy. However, few studies have evaluated the implication of the micronutrients in placental DNA methylation. We investigated whether intake of OCM nutrients in the year before pregnancy was associated with placental DNA methylation in the EDEN mother–child cohort. Maternal dietary intake was assessed with a food-frequency questionnaire. Three dietary patterns, ‘varied and balanced diet,’ ‘vegetarian tendency,’ and ‘bread and starchy food,’ were used to characterize maternal OCM dietary intake. The Illumina Infinium HumanMethylation450 BeadChip was used to measure placental DNA methylation of 573 women included in the analyses. We evaluated the association of dietary patterns with global DNA methylation. Then, we conducted an agnostic epigenome-wide association study (EWAS) and investigated differentially methylated regions (DMRs) associated with each dietary pattern. We found no significant association between the three dietary patterns and global DNA methylation or individual CpG sites. DMR analyses highlighted associations between the ‘varied and balanced’ or ‘vegetarian tendency’ pattern and DMRs located at genes previously implicated in functions essential for embryonic development, such as neurodevelopment. The ‘bread and starchy food’ pattern was associated with regions related to genes whose functions involve various metabolic and cell synthesis-related processes. In mainly well-nourished French women without major deficiencies, OCM intake before pregnancy was not associated with major variation in DNA methylation.

IntroductionHigh prevalence of overweight and obesity already observed in preschool children suggests the involvement of early-life risk factors. Preconception period and pregnancy are crucial windows for the implementation of child obesity prevention interventions with parental lifestyle factors as relevant targets. So far, most studies have evaluated their role separately, with only a few having investigated their potential synergistic effect on childhood obesity. Our objective was to investigate parental lifestyle patterns in the preconception and pregnancy periods and their association with the risk of child overweight after 5 years.Materials and methodsWe harmonized and interpreted results from four European mother-offspring cohorts participating in the EndObesity Consortium [EDEN, France; Elfe, France; Lifeways, Ireland; and Generation R, Netherlands] with data available for 1,900, 18,000, 1,100, and 9,500 families, respectively. Lifestyle factors were collected using questionnaires and included parental smoking, body mass index (BMI), gestational weight gain, diet, physical activity, and sedentary behavior. We applied principal component analyses to identify parental lifestyle patterns in preconception and pregnancy. Their association with risk of overweight (including obesity; OW-OB) and BMI z-scores between 5 and 12 years were assessed using cohort-specific multivariable logistic and linear and regression models (adjusted for potential confounders including parental age, education level, employment status, geographic origin, parity, and household income).ResultsAmong the various lifestyle patterns derived in all cohorts, the two explaining the most variance were characterized by (1) “high parental smoking, low maternal diet quality (and high maternal sedentary behavior in some cohorts)” and, (2) “high parental BMI and low gestational weight gain.” Patterns characterized by high parental BMI, smoking, low diet quality or high sedentary lifestyle before or during pregnancy were associated with higher risk of OW-OB in children, and BMI z-score at any age, with consistent strengths of associations in the main cohorts, except for lifeways.ConclusionThis project provides insight into how combined parental lifestyle factors in the preconception and pregnancy periods are associated with the future risk of child obesity. These findings are valuable to inform family-based and multi-behavioural child obesity prevention strategies in early life.

ObjectivesThe study aims to describe the output of routine health screening performed in French nursery schools by the maternal and child health services among children aged 3–4 years and to quantify the level of early socioeconomic health disparities.MethodsIn 30 participating départements, data on screening for vision and hearing impairments, overweight and thinness, dental health, language, psychomotor development, and immunizations were collected for children born on specific dates in 2011 and enrolled in nursery school in 2014–2016. Information was collected on the children, their socioeconomic characteristics and on the school attended. Odds of abnormal screening results were compared for each socioeconomic factor by logistic regressions adjusted for age, sex, prematurity and bilingualism.ResultsAmong the 9,939 children screened, prevalence of disorders was 12.3% for vision, 10.9% for hearing, 10.4% for overweight, 7.3% for untreated caries, 14.2% for language and 6.6% for psychomotricity. Newly detected visual disorders were more frequent in disadvantaged areas. Children with unemployed parents were three time more likely to have untreated caries and twice as likely to present language or psychomotor impairments; 52% were referred to a health professional following screening compared to 39% of children with employed parents. Except for children in disadvantaged areas, vaccine coverage was lower among disadvantaged groups.ConclusionThe prevalences of impairments, which are higher among disadvantaged children, highlight the potential preventive impact of systematic screening under the comprehensive maternal and child healthcare program. These results are important to quantify early socioeconomic inequalities in a Western country known for its generous social welfare system. A more holistic approach to child health is needed with a coherent system involving families and aligning primary care, local child health professionals, general practitioners, and specialists. Further results are needed to evaluate its impact on later child development and health.

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

Objective Research on adults has identified an immigrant health advantage, known as the ‘immigrant health paradox’, by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives?Setting Western Europe and Australia.Participants We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants’ children: Etude Longitudinale Française depuis l’Enfance—France (N=12 494), the Raine Study—Australia (N=2283), Born in Bradford—UK (N=4132), Amsterdam Born Children and their Development study—Netherlands (N=4030) and the Generation R study—Netherlands (N=4877). We include male and female babies born to immigrant and native parents.Primary and secondary outcome measures The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0–1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad.Results Two patterns in children’s birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p

BackgroundPreterm 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 findingsWe 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.ConclusionsThis 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.

Abstract Background Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods Ten behavioural variables related to child’s diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5–6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. Results Three broadly similar lifestyle patterns were identified in both cohorts: “discretionary consumption and high screen time”, “fruit, vegetables, and low screen time” and “high outdoor playtime and walking”. The latter two patterns showed small differences between cohorts and sexes. The “discretionary consumption and high screen time” pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. Conclusions Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.

Prematurity is a risk factor for dysbiosis of the gut microbiota due to particular birth conditions and frequent prolonged hospitalization of neonates. Although gut microbiota colonization after birth and its establishment during the hospitalization period have been studied in preterm infants, data on gut microbiota following discharge, particularly during early childhood, are scarce. The present study investigated the relationship between gut microbiota at 1 month after birth (hospitalization period) and 3.5 years of age in 159 preterm children belonging to the French EPIFLORE prospective observational cohort study. Analysis using bacterial 16S rRNA gene sequencing showed that the gut microbiota of preterm neonates at 1 month was highly variable and characterized by six distinct enterotypes. In contrast, the gut microbiota of the same children at 3.5 years of age showed less variability, with only two discrete enterotypes. An absence of association between enterotypes at 1 month and 3.5 years of age was observed. While the alpha diversity of gut microbiota significantly increased between 1 month and 3.5 years of age, for both alpha and beta diversities, there was no correlation between the 1-month and 3.5-years time points. Comparison at 3.5 years between children born either preterm (n = 159) or full-term (n = 200) showed no differences in terms of enterotypes, but preterm children harbored a lower Shannon diversity index and a different overall composition of microbiota than full-term children. This study suggests that the characteristics of the early gut microbiota of preterm children are not predictive of the microbial community composition at 3.5 years of age. However, the impact of gestational age is still noticeable on the gut microbiota up to 3.5 years of age.

Early life gut microbiota-influencing factors may play an important role in programming individuals long-term health and substantial efforts have been devoted into studying the development of the gut microbiota in relation to early life events. This study aimed to examine in a single study, the persistence of associations between 20 factors occurring in the early life and the gut microbiota at 3.5 years of 798 children from two French nationwide birth cohorts, EPIPAGE 2 (very preterm children) and ELFE (late preterm and full-term children). Gut microbiota profiling was assessed using 16S rRNA gene sequencing-based method. Upon thorough adjustment of confounding factors, we demonstrated that gestational age was one of the factors most associated with gut microbiota differences with a noticeable imprint of prematurity at 3.5 years of age. Children born by cesarean section harbored lower richness and diversity and a different overall gut microbiota composition independently of preterm status. Children who had ever received human milk were associated with a Prevotella-driven enterotype (P_type) compared to those who had never received human milk. Living with a sibling was associated with higher diversity. Children with siblings and those attending daycare centers were associated with a P_type enterotype. Maternal factors including the country of birth and preconception maternal body mass index were associated with some microbiota characteristics: children born to overweight or obese mothers showed increased gut microbiota richness. This study reveals that multiple exposures operating from early life imprint the gut microbiota at 3.5 years that is a pivotal age when the gut microbiota acquires many of its adult characteristics.

Objective: The risk factors for postnatal depressive symptoms (PNDS) are numerous, but little is known about the protective factors or the interactions between different exposures. The present study explored the pathways between maternal, infant and parenthood vulnerabilities or risk/protective factors and PNDS at 2 months postpartum (PP) in a large sample of women from the general population. Methods: We used data from the French ELFE cohort, a nationally representative cohort of children followed-up from birth. The available information about vulnerabilities or risk/protective factors for PNDS was collected during the maternity ward stay (mother or medical records) and at 2 months PP (mother by phone). PNDS were evaluated with the Edinburgh Postnatal Depression Scale (EPDS) at 2 months. A measurement model was built based on the psychosocial model for PNDS of Milgrom and colleagues using exploratory factor analysis. The Structural Equation Model was used to investigate the pathways between vulnerability, risk/protective factors and PNDS at 2 months PP. Results: In the study sample (n = 11,583), a lack of a partner’s perceived antenatal emotional support, consultation with a mental health specialist before pregnancy, family financial difficulties, prenatal psychological distress and a difficult pregnancy experience were directly associated with the severity of maternal PNDS at 2 months PP, as well as lack of perceived postnatal support. Family financial difficulties and consultation with a mental health specialist before pregnancy were also indirectly associated with the intensity of PNDS through a lack of perceived antenatal emotional support, a difficult pregnancy experience, prenatal psychological distress and a lack of perceived postnatal support. Regarding infant and parenthood characteristics, infant self-regulation difficulties, maternal difficulty in understanding infant crying and infant hospitalisation were directly associated with PNDS severity at 2 months PP, while maternal difficulty in understanding an infant’s cries was also indirectly associated with infant self-regulation difficulties. Conclusions: Perinatal professional support should begin antenatally and target the couple’s prenatal functioning, with particular attention to women presenting a history of psychiatric disorders, especially those of low socioeconomic status. After delivery, addressing infant and parenthood characteristics is also recommended.

Background: Maternal smoking during pregnancy has adverse health effects on the offspring, including lower birth weight and increased risk for obesity. These outcomes are also influenced by common genetic polymorphisms. We aimed to investigate the combined effect of maternal smoking during pregnancy and genetic predisposition on birth weight and body mass index (BMI)-related traits in 1,086 children of the Human Early Life Exposome (HELIX) project.Methods: Maternal smoking during pregnancy was self-reported. Phenotypic traits were assessed at birth or at the age of 8 years. Ten polygenic risk scores (PRSs) per trait were calculated using the PRSice v2 program. For birth weight, we estimated two sets of PRSs based on two different base GWAS summary statistics: PRS-EGG, which includes HELIX children, and PRS-PanUK, which is completely independent. The best PRS per trait (highest R2) was selected for downstream analyses, and it was treated in continuous or categorized into three groups. Multivariate linear regression models were applied to evaluate the association of the explanatory variables with the traits of interest. The combined effect was evaluated by including an interaction term in the regression models and then running models stratified by the PRS group.Results: BMI-related traits were correlated among them but not with birth weight. A similar pattern was observed for their PRSs. On average, the PRSs explained ∼4% of the phenotypic variation, with higher PRS values related to higher trait values (p-value 0.237).Conclusion: Sustained maternal smoking and the PRSs were independently associated with birth weight and childhood BMI-related traits. There was low evidence of GxE interactions.

Sleep is essential for optimal child development and health during the life course. However, sleep disturbances are common in early childhood and increase the risk of cognitive, metabolic and inflammatory disorders throughout life. Sleep and immunity are mutually linked, and cytokines secreted by immune cells could mediate this interaction. The sleep modulation of cytokines has been studied mostly in adults and adolescents; few studies have focused on school-aged children and none on preschoolers. We hypothesized that night sleep duration affects cytokine levels in preschoolers. In a sample of 687 children from the EDEN French birth cohort, we studied the associations between night sleep duration trajectories from age to 2–5 years old and serum concentrations of four cytokines (Tumor necrosis factor α [TNF-α], Interleukin 6 [IL-6], IL-10, Interferon γ [IFN)-γ] at age 5, adjusting for relevant covariates. As compared with the reference trajectory (≈11h30/night sleep, 37.4% of children), a shorter sleep duration trajectory (

BackgroundEarly childhood may represent an opportune time to commence primordial prevention of cardiovascular disease (CVD, i.e., prevention of risk factors onset), but epidemiological evidence is scarce. We aimed to examine the distribution and parental and early life determinants of ideal cardiovascular health (CVH) in children up to 5 years and to compare the level of cognitive development between children with and without ideal CVH at age 5 years.MethodsUsing data from the Etude sur les déterminants pré et post natals précoces du Développement psychomoteur et de la santé de l'Enfant (EDEN) study, a French population-based mother–child cohort study, CVH was examined in children at 5 years of age based on the American Heart Association CVH metrics (ideal body mass index, physical activity, diet, blood pressure, cholesterol and glucose levels, and passive smoking, considered in sensitivity analysis only). Children were categorized as having ideal (five to six ideal metrics) or non-ideal CVH (

Abstract Aim To explore communication experiences between family caregivers of adults with intellectual and developmental disabilities (I/DD) and healthcare personnel during hospitalization. Design A qualitative descriptive study approach with interviews of family caregivers was used. Method Face‐to‐face, semi‐structured interviews were conducted from June–September 2015 with ten family caregivers of adults with I/DD. Participants were recruited through an advocacy organization in the north‐eastern United States. Data were analysed by content analysis. The Standards for Reporting Qualitative Research was the chosen checklist. Results The four overarching themes: “Need for Advocacy”; “Need for Better Communication”; “Sense of Abandonment”; and “Lack of Confidence” along with 12 subthemes were identified. Overall, participants reported miscommunications leading to instances of mistrust in hospital staff's competence to deliver quality patient care.

Abstract Background Although exposure to cigarette smoking during pregnancy has been associated with alterations of DNA methylation in the cord blood or placental cells, whether such exposure before pregnancy could induce epigenetic alterations in the placenta of former smokers has never been investigated. Methods Our approach combined the analysis of placenta epigenomic (ENCODE) data with newly generated DNA methylation data obtained from 568 pregnant women, the largest cohort to date, either actively smoking during their pregnancy or formerly exposed to tobacco smoking. Results This strategy resulted in several major findings. First, among the 203 differentially methylated regions (DMRs) identified by the epigenome-wide association study, 152 showed “reversible” alterations of DNA methylation, only present in the placenta of current smokers, whereas 26 were also found altered in former smokers, whose placenta had not been exposed directly to cigarette smoking. Although the absolute methylation changes were smaller than those observed in other contexts, such as in some congenital diseases, the observed alterations were consistent within each DMR. This observation was further supported by a demethylation of LINE-1 sequences in the placentas of both current (beta-coefficient (β) (95% confidence interval (CI)), − 0.004 (− 0.008; 0.001)) and former smokers (β (95% CI), − 0.006 (− 0.011; − 0.001)) compared to nonsmokers. Second, the 203 DMRs were enriched in epigenetic marks corresponding to enhancer regions, including monomethylation of lysine 4 and acetylation of lysine 27 of histone H3 (respectively H3K4me1 and H3K27ac). Third, smoking-associated DMRs were also found near and/or overlapping 10 imprinted genes containing regions (corresponding to 16 genes), notably including the NNAT, SGCE/PEG10, and H19/MIR675 loci. Conclusions Our results pointing towards genomic regions containing the imprinted genes as well as enhancers as preferential targets suggest mechanisms by which tobacco could directly impact the fetus and future child. The persistence of significant DNA methylation changes in the placenta of former smokers supports the hypothesis of an “epigenetic memory” of exposure to cigarette smoking before pregnancy. This observation not only is conceptually revolutionary, but these results also bring crucial information in terms of public health concerning potential long-term detrimental effects of smoking in women.

Background: Leptin is potentially involved in the correction of early postnatal growth of infants having deviated from their genetic trajectory in utero. Aim: To analyse the potential mediating role of cord blood leptin level in the association between neonatal anthropometry and early postnatal growth in the mother–child EDEN cohort. Subjects and methods: We included term newborns with information on leptin, birth weight and length, and weight and length SD-score changes over the first 2 months. The Baron and Kenny method was used to quantify the mediation contribution of leptin in the association between neonatal anthropometry and postnatal growth, considering several confounders. Analyses were stratified to consider sexual dimorphism. Results: A 1 SD higher birth weight was associated with a lower 2-months weight variation of 0.27 (0.18; 0.36) SD and a 0.16 (0.06; 0.26) SD, in boys and girls, respectively. Leptin explained 20% and 25% of these associations, respectively. Leptin did not mediate the association between birth length and birth-to-2 months length variation. Conclusion: Our results suggest that cord blood leptin may not be involved in the negative association between birth length and postnatal length growth but may play a modest mediating role in early postnatal catch-up or catch-down in weight.

To talk about domestic cults seems more appropriate than to talk about private cults, since most of the non-public religious acts take place around the domestic hearth, under the pater familias’ direction. However, the term domestic cults is too restrictive in so far as the citizen can participate in non-public worship acts outside his home. Indeed, let us not forget that individuals were always inserted in a set of social relations. Therefore, private cults include domestic cults as well as association cults, neighborhood cults such as the Lares compitales cult transformed by Augustus in Lares Augusti as part of the “imperial cult”. Throughout our period, private cults do not seem to change : what essentially changes is the expansion of the family pantheon to new deities and the introduction of the “imperial cult” at the level of domus and compitum.

We investigated the associations between maternal diet quality and allergic and respiratory diseases in children. Analyses were based on 1316 mother–child pairs from the EDEN mother–child cohort. Maternal diet quality during pregnancy was assessed through a food-based score (the Diet Quality), a nutrient-based score (the PANDiet), and the adherence to guidelines for main food groups. Clusters of allergic and respiratory multimorbidity clusters up to 8 years were identified using Latent Class Analysis. Associations were assessed by adjusted multinomial logistic regressions. Four clusters were identified for children: “asymptomatic” (67%, reference group), “asthma only” (14%), “allergies without asthma” (12%), “multi-allergic” (7%). These clusters were not associated with mother diet quality assessed by both scores. Children from mothers consuming legumes once a month or less were at higher risk of belonging to the “multi-allergic” cluster (odds ratio (OR) (95% confidence interval (95%CI)) = 1.60 (1.01;2.54)). No association was found with other food groups or other clusters. In our study, allergic and respiratory multimorbidity in children was described with four distinct clusters. Our results suggest an interest in legumes consumption in the prevention of allergic diseases but need to be confirmed in larger cohorts and randomized control trials.

Background: In France, updated data on food allergies (FAs) are lacking, despite the need for efficient FA management and prevention. This study aimed to evaluate the prevalence of FAs in children in France, describe the most common allergens and determine the prevalence of atopic diseases in children with FAs. Methods: The ELFE study comprises a French nationwide birth cohort, including 18,329 children born in 2011. FAs were assessed by parental reports of food avoidance based on medical advice related to FAs, provided at 2 months and 2, 3.5 and 5.5 years of age. Data regarding FAs were available for 16,400 children. Data were weighted to account for selection and attrition bias. Results: From birth to 5.5 years of age, FAs were reported for 5.94% (95% CI: 5.54–6.34) children. Milk was the most common allergen, followed by egg, peanut, exotic fruits, tree nuts, gluten and fish. Among children with FAs, 20.5% had an allergy to at least two different groups of allergens; 71% reported eczema at least once before 5.5 years of age; 24.4% reported incidence of asthma; and 42.3% reported incidence of allergic rhinitis or conjunctivitis. Conclusion: In France, the prevalence of FAs in children up to 5.5 years of age is approximately 6%. It was demonstrated that 1 in 5 children with allergies had multiple FAs.

Abstract Background Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. Methods We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. Results We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4–17.4) for underweight women, 14.5 kg (11.5–17.7) for normal weight women, 13.9 kg (10.1–17.9) for overweight women, and 11.2 kg (7.0–15.7), 8.7 kg (4.3–13.4) and 6.3 kg (1.9–11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. Conclusions Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

Summary: Background: Both national and WHO growth charts have been found to be poorly calibrated with the physical growth of children in many countries. We aimed to generate new national growth charts for French children in the context of huge datasets of physical growth measurements routinely collected by office-based health practitioners. Methods: We recruited 32 randomly sampled primary care paediatricians and ten volunteer general practitioners from across the French metropolitan territory who used the same electronic medical records software, from which we extracted all physical growth data for the paediatric patients, with anonymisation. We included measurements from all children born from Jan 1, 1990, and aged 1 month to 18 years by Feb 8, 2018, with birthweight greater than 2500 g, to which an automated process of data cleaning developed to detect and delete measurement or transcription errors was applied. Growth charts for weight and height were derived by using generalised additive models for location, scale, and shape with the Box-Cox power exponential distribution. We compared the new charts to WHO growth charts and existing French national growth charts, and validated our charts using growth data from recent national cross-sectional surveys. Findings: After data cleaning, we included 1 458 468 height and 1 690 340 weight measurements from 238 102 children. When compared with the existing French national and WHO growth charts, all height SD and weight percentile curves for the new growth charts were distinctly above those for the existing French national growth charts, as early as age 1 month, with an average difference of −0·75 SD for height and −0·50 SD for weight for both sexes. Comparison with national cross-sectional surveys showed satisfactory calibration, with generally good fit for children aged 5–6 years and 10–11 years in height and weight and small differences at age 14–15 years. Interpretation: We successfully produced calibrated paediatric growth charts by using a novel big-data approach applied to data routinely collected in clinical practice that could be used in many fields other than anthropometry. Funding: The French Ministry of Health; Laboratoires Guigoz—General Pediatrics section of the French Society of Pediatrics—Pediatric Epidemiological Research Group; and the French Association for Ambulatory Pediatrics.

Abstract Background In Haiti, the number of women dying in pregnancy, during childbirth and the weeks after giving birth remains unacceptably high. The objective of this research was to explore determinants of maternal mortality in rural Haiti through Community-Based Action Research (CBAR), guided by the delays that lead to maternal death. This paper focuses on socioecological determinants of maternal mortality from the perspectives of women of near-miss maternal experiences and community members, and their solutions to reduce maternal mortality in their community. Methods The study draws on five semi-structured Individual Interviews with women survivors of near-misses, and on four Focus Group Discussions with Community Leaders and with Traditional Birth Attendants. Data collection took place in July 2013. A Community Research Team within a resource-limited rural community in Haiti undertook the research. The methods and analysis process were guided by participatory research and CBAR. Results Participants identified three delays that lead to maternal death but also described a fourth delay with respect to community responsibility for maternal mortality. They included women being carried from the community to a healthcare facility as a special example of the fourth delay. Women survivors of near-miss maternal experiences and community leaders suggested solutions to reduce maternal death that centered on prevention and community infrastructure. Most of the strategies for action were related to the fourth delay and include: community mobilization by way of the formation of Neighbourhood Maternal Health/Well-being Committees, and community support through the provision/sharing of food for undernourished women, offering monetary support and establishment of a communication relay/transport system in times of crisis. Conclusions Finding sustainable ways to reduce maternal mortality requires a community-based/centred and community-driven comprehensive approach to maternal health/well-being. This includes engagement of community members that is dependent upon community knowledge, political will, mobilization, accountability and empowerment. An engaged/empowered community is one that is well placed to find ways that work in their community to reduce the fourth delay and in turn, maternal death. Potentially, community ownership of challenges and solutions can lead to more sustainable improvements in maternal health/well-being in Haiti.

Peroxisome proliferator-activated receptor γ (PPARγ) is essential for placental development, whose SNPs have shown increased susceptibility to pregnancy-related diseases, such as preeclampsia. Our aim was to investigate the association between preeclampsia and three PPARγ SNPs (Pro12Ala, C1431T, and C681G), which together with nine clinical factors were used to build a pragmatic model for preeclampsia prediction. Data were collected from 1648 women from the EDEN cohort, of which 35 women had preeclamptic pregnancies, and the remaining 1613 women had normal pregnancies. Univariate analysis comparing preeclamptic patients to the control resulted in the SNP C1431T being the only factor significantly associated with preeclampsia (p < 0.05), with a confidence interval of 95% and odds ratio ranging from 4.90 to 8.75. On the other hand, three methods of multivariate feature selection highlighted seven features that could be potential predictors of preeclampsia: maternal C1431T and C681G variants, obesity, body mass index, number of pregnancies, primiparity, cigarette use, and education. These seven features were further used as input into eight different machine-learning algorithms to create predictive models, whose performances were evaluated based on metrics of accuracy and the area under the receiver operating characteristic curve (AUC). The boost tree-based model performed the best, with respective accuracy and AUC values of 0.971 ± 0.002 and 0.991 ± 0.001 in the training set and 0.951 and 0.701 in the testing set. A flowchart based on the boost tree model was constructed to depict the procedure for preeclampsia prediction. This final decision tree showed that the C1431T variant of PPARγ is significantly associated with susceptibility to preeclampsia. We believe that this final decision tree could be applied in the clinical prediction of preeclampsia in the very early stages of pregnancy.

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