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ObjectiveResearch 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?SettingWestern Europe and Australia.ParticipantsWe 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 measuresThe 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.ResultsTwo patterns in children’s birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, pConclusionThe immigrant health advantage is not universally transferred to children in the form of higher birth weight in all host countries. Further research should investigate whether this cross-national variation is due to differences in immigrant communities, social and healthcare contexts across host countries.

Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7–17) months were used to estimate Horvath’s DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: −0.79 to 2.34 for low/medium education; 0.96, 95% CI: −1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath’s method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.

Background Early exposure to unhealthy lifestyles and environmental risk factors is known to affect health throughout the life-course. There is also evidence that the exposure patterns are influenced by the socioeconomic position (SEP). Methods We use the data of the Turin participants of the Italian NINFEA birth cohort (n∼2500) to study how family SEP drives the early life exposome. SEP at birth is measured through the EHII (Equivalized Household Income Indicator), while the exposome includes urban environment, diet and lifestyle exposures measured during infancy. We use standard regression models to evaluate the effect of EHII on each exposome variable accounting for multiple comparison and potential confounders (Drivers-Exposome Wide Association Study – DExWAS) and the hierarchical clustering on the principal components approach to identify groups with similar exposure pattern. Results The DExWAS show that low EHII is associated with lower consumption of fruit and vegetables, lower levels of NO2, building and facilities densities, traffic, walkability and connectivity index, higher land-use diversity index, and higher exposure to pets. The hierarchical cluster analysis identifies three groups, with subjects belonging to the cluster characterized by higher level of urban environment risk factors and a healthier diet having a higher mean EHII. Conclusions These SEP-early life exposome analyses will be replicated in several European birth cohorts participating in the H2020 ATHLETE and LifeCycle projects. Key messages In the Italian city of Turin children from low SEP family are exposed to higher levels of environmental risk factors and unhealthy lifestyles during infancy.

health literacy may contribute to the strategies to control the Coronavirus disease 2019 (COVID-19), as individuals need to acquire promptly new health information, understand the reasons behind recommendations, and adapt their behaviour accordingly.to investigate sociodemographic and disease-related factors that can influence self-perceived knowledge (poor/medium vs high) about COVID-19 in women of the Italian NINFEA birth cohort.cross-sectional study.a web-based anonymous survey on COVID-19 was sent in April 2020 to women participating in the NINFEA cohort. A total of 3,129 women were included in the study.using multiple weighted logistic regression models, self-perceived knowledge level was analysed in relation with the following variables: age, education level, family size, cumulative incidence of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) cases until 7 April 2020 by province, presence of COVID-19-like symptoms, SARS-CoV-2 testing, and COVID-19 diagnosis.the prevalence of self-perceived poor/medium knowledge was 57%. In multivariable logistic regression analyses, the odds ratio (OR) of self-perceived poor/medium COVID-19 knowledge level was increased for low/medium compared with high education level (OR 1.57; 95%CI 1.34-1.84), and decreased for SARS-CoV-2 testing (OR 0.25; 95%CI 0.16-0.39) and COVID-19 diagnosis (OR 0.20; 95%CI 0.07-0.60). There was no evidence of association between the other analysed variables and self-perceived knowledge level.the findings of this study suggest that low educational level is a determinant of low self-perceived knowledge on COVID-19 in middle-aged women.

Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to investigate whether cord blood birthweight-associated CpG sites identified by the PACE Consortium replicate in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 141 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7-17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in replication and exploratory EWAS analyses.Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was replicated in infant saliva. In saliva EWAS analyses, birthweight as continuous variable was associated with DNA methylation variation in 44 CpG sites, while being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation variation in 44 CpGs (all false discovery rate p-valuesMACROD1 and RPTOR).Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

Background A number of cases positive for SARS-CoV-2 escape surveillance systems, especially in the first epidemic waves and/or when the number of cases becomes too large to allow complete diagnostic coverage. Methods During the first SARS-CoV-2 epidemic wave hitting Italy in the spring 2020, mothers participating in an Italian NINFEA birth cohort were invited to complete an online questionnaire on COVID-19-like symptoms in the household. We estimated the population prevalence of COVID-19-like symptoms in children and adults, assessed their geographical correlation with the cumulative number of COVID-19 cases by province, analysed their clustering within families, and estimated their sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for COVID-19 diagnosis in individuals tested for SARS-CoV-2.Results Information was collected on 3184 households, 6133 adults, and 5751 children. In the period March-April 2020, 55.4% of the NINFEA families had at least one member with at least one COVID-19-like symptom. There was a strong geographical correlation between the population cumulative incidence of COVID-19 and the prevalence of muscle pain, fatigue, low-grade fever, and breathing difficulties in adults (Spearman’s rho ≥0.70). Having at least one family member with a COVID-19 diagnosis, compared with none tested for SARS-CoV-2, was associated with an increased prevalence ratio (PR) of almost all COVID-19-like symptoms in adults, and only of low-grade fever (37-37.5°C; PR 5.27; 95% confidence intervals: 2.37 to 11.74) and anosmia/dysgeusia in children. Among adults with COVID-19 diagnosis, fatigue, muscle pain, and fever had a sensitivity ≥70%. In individuals tested for SARS-CoV-2, with a 16.6% prevalence of COVID-19, breathing difficulties and nausea/vomiting had the highest PPVs, with point estimates close to 60%, and with NPVs close to 90%.Conclusions The geographical prevalence of COVID-19-like symptoms in adults may inform on local disease clusters, while certain symptoms in family members of confirmed COVID-19 cases could help identify the intra-familial spread of the virus and its further propagation in the community. Low-grade fever is frequent in children with at least one household member with COVID-19 and possibly indicates child infection.

Background Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children. Methods PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited. Results Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure. Conclusions Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.