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Background Mitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4L10550A>G heteroplasmy has been associated with BMI in adults. Therefore, we hypothesized that in utero PM2.5 exposure is associated with cord blood MT-ND4L10550A>G heteroplasmy and early life growth. In addition, the role of cord blood MT-ND4L10550A>G heteroplasmy in overweight during early childhood is investigated. Methods This study included 386 mother-newborn pairs. Outdoor PM2.5 concentrations were determined at the maternal residential address. Cord blood MT-ND4L10550A>G heteroplasmy was determined using Droplet Digital PCR. Associations were explored using logistic regression models and distributed lag linear models. Mediation analysis was performed to quantify the effects of prenatal PM2.5 exposure on childhood overweight mediated by cord blood MT-ND4L10550A>G heteroplasmy. Results Prenatal PM2.5 exposure was positively associated with childhood overweight during the whole pregnancy (OR = 2.33; 95% CI: 1.20 to 4.51; p = 0.01), which was mainly driven by the second trimester. In addition, prenatal PM2.5 exposure was associated with cord blood MT-ND4L10550A>G heteroplasmy from gestational week 9 – 13. The largest effect was observed in week 10, where a 5 µg/m3 increment in PM2.5 was linked with cord blood MT-ND4L10550A>G heteroplasmy (OR = 0.93; 95% CI: 0.87 to 0.99). Cord blood MT-ND4L10550A>G heteroplasmy was also linked with childhood overweight (OR = 3.04; 95% CI: 1.15 to 7.50; p = 0.02). The effect of prenatal PM2.5 exposure on childhood overweight was mainly direct (total effect OR = 1.18; 95% CI: 0.99 to 1.36; natural direct effect OR = 1.20; 95% CI: 1.01 to 1.36)) and was not mediated by cord blood MT-ND4L10550A>G heteroplasmy. Conclusions Cord blood MT-ND4L10550A>G heteroplasmy was linked with childhood overweight. In addition, in utero exposure to PM2.5 during the first trimester of pregnancy was associated with cord blood MT-ND4L10550A>G heteroplasmy in newborns. Our analysis did not reveal any mediation of cord blood MT-ND4L10550A>G heteroplasmy in the association between PM2.5 exposure and childhood overweight.

Telomere length (TL) and telomere shortening are biological indicators of aging, and epigenetic associates have been found for TL in adults. However, the role of epigenetic signatures in setting newborn TL and early life telomere dynamics is unknown. In the present study, based on 247 participating newborns from the ENVIRONAGE birth cohort, whole-genome DNA methylation, profiled on the Illumina MethylationEPIC BeadChip microarray, and TL were measured in cord blood. In a follow-up visit at a mean age of 4.58 years, leukocyte TL was evaluated. We combined an epigenome-wide association study and a statistical learning method with re-sampling to select CpGs and their two-way interactions to model baseline (cord blood) TL and early-life telomere attrition rate, where distinct epigenetic signatures were identified for the two outcomes. In addition, a stronger epigenetic regulation was suggested in setting newborn TL than that of telomere dynamics in early life: 47 CpGs and 7 between-CpG interactions explained 76% of the variance in baseline TLs, while 72% of the total variance in telomere attrition rate was explained by 31 CpGs and 5 interactions. Functional enrichment analysis based on the selected CpGs in the two models revealed GLUT4 translocation and immune cell signaling pathways, respectively. These CpGs and interactions, as well as the cellular pathways, are potential novel targets of further investigation of telomere biology and aging. Funding The ENVIRONAGE birth cohort is supported by grants from the European Research Council (Grant No. ERC-2012-StG310898), the Flemish Scientific Fund (FWO, Grant No. G073315N) and Kom Op Tegen Kanker DSM (FWO grant 12X9620N) is postdoctoral fellows of the Flanders Research Foundation. SL is the beneficiary of a post-doctoral fellowship (12L5216N) provided by The Research Foundation-Flanders (FWO) and the Flemish Institute of Technological Research (VITO). Acknowledgments We acknowledge the cohort participants, midwives, the staff of the maternity ward and the clinical laboratory of East-Limburg Hospital in Genk.

Background. The Covid-19 pandemic has deeply impacted the oncology community. The European Society for Medical Oncology (ESMO) suggests strengthening telemedicine services, reducing clinic visits and switching to subcutaneous or oral, rather than intravenous, therapies whenever possible. Methods. This study was conducted at the Oncology Complex Operating Unit by collecting data on all patients who accessed in 2019-2020. The aim was to understand how Covid-19 affected hospital admissions. Statistical tests and Logistic Regression were implemented. Results. The statistical analysis carried out showed that between 2019 and 2020 there was less use of emergency admission and voluntary discharge, while highlighting the increase in the "Protected with integrated home care"discharge mode. Conclusion. The results show how the European guidelines have improved the health process, from admission with the reduction of emergencies to discharge.

Mitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4LThis study included 386 mother-newborn pairs. Outdoor PMPrenatal PMCord blood MT-ND4L

Healthcare-associated infections (HAIs) are a common complication among hospitalized patients and an important cause of mortality and morbidity in Neonatal Intensive Care Unit (NICU). New technologies have significantly improved the neonatal survival rate, while causing an increase in the spread of infections. Contracting HAIs means an increase in hospital days, specific drug therapy and greater care that translate into increased costs. Understanding the main risk factors in neonates can help prevent their spread. In this study conducted at the NICU of the "Federico II"University Hospital of Naples in 2019, statistical analysis and logistic regression were used to analyze the association between blood-stream HAIs (BSIs) and the available risk factors. The analysis showed that birthweight and central line catheterization days are significant predictors of suffering from BSIs.

Introduction Metabolomics may identify biological pathways predisposing children to the risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts. Methods Untargeted liquid chromatography-mass spectrometry metabolomic profiles were measured in cord blood from 399 newborns from four European cohorts (ENVIRONAGE, Rhea, INMA and Piccolipiu). Rapid growth in the first year of life and overweight in childhood was defined with reference to WHO growth charts. Metabolome-wide association scans for rapid growth and overweight on over 4500 metabolic features were performed using multiple adjusted logistic mixed-effect models and controlling the false discovery rate (FDR) at 5%. In addition, we performed a look-up analysis of 43 pre-annotated metabolites, previously associated with birthweight or rapid growth. Results In the Metabolome-Wide Association Study analysis, we identified three and eight metabolites associated with rapid growth and overweight, respectively, after FDR correction. Higher levels of cholestenone, a cholesterol derivative produced by microbial catabolism, were predictive of rapid growth (p = 1.6 x 10(-3)). Lower levels of the branched-chain amino acid (BCAA) valine (p = 8.6 x 10(-6)) were predictive of overweight in childhood. The area under the receiver operator curve for multivariate prediction models including these metabolites and traditional risk factors was 0.77 for rapid growth and 0.82 for overweight, compared with 0.69 and 0.69, respectively, for models using traditional risk factors alone. Among the 43 pre-annotated metabolites, seven and five metabolites were nominally associated (P < 0.05) with rapid growth and overweight, respectively. The BCAA leucine, remained associated (1.6 x 10(-3)) with overweight after FDR correction. Conclusion The metabolites identified here may assist in the identification of children at risk of developing obesity and improve understanding of mechanisms involved in postnatal growth. Cholestenone and BCAAs are suggestive of a role of the gut microbiome and nutrient signalling respectively in child growth trajectories. This research was supported by European Commission Horizon 2020 Grant to the ‘STOP Project’ (Grant ref. 774548). This study was funded by the European Union Social Fund and the Hellenic Ministry of Health (“Programme of prevention and early diagnosis of obesity and neurodevelopment disorders in preschool-age children in the prefecture of Heraklion, Crete, Greece’ MIS number 349580, NSRF 2007-2013). Additional funding from the National Institute of Environmental Health Sciences (NIEHS) supported Dr. Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, R21ES028903 and P30ES007048). The ENVIRONAGE birth-cohort is supported by the EU Program ‘Ideas’ (ERC-2012-StG-310898) and the FWO (G082317N), a PhD fellowship of the Bijzonder Onderzoeksfonds (BOF) at Hasselt University supported MD Alfano. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities, ‘Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208 and ‘Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya’ (2017SGR595). O.R. was supported by a UKRI Future Leaders Fellowship (MR/S03532X/1).

Background The IGF2 (insulin-like growth factor 2) and H19 gene cluster plays an important role during pregnancy as it promotes both foetal and placental growth. We investigated the association between cord blood DNA methylation status of the IGF2/H19 gene cluster and maternal fine particulate matter exposure during fetal life. To the best of our knowledge, this is the first study investigating the association between prenatal PM2.5 exposure and newborn DNA methylation of the IGF2/H19. Methods Cord blood DNA methylation status of IGF2/H19 cluster was measured in 189 mother-newborn pairs from the ENVIRONAGE birth cohort (Flanders, Belgium). We assessed the sex-specific association between residential PM2.5 exposure during pregnancy and the methylation level of CpG loci mapping to the IGF2/H19 cluster, and identified prenatal vulnerability by investigating susceptible time windows of exposure. We also addressed the biological functionality of DNA methylation level in the gene cluster. Results Prenatal PM2.5 exposure was found to have genetic region-specific significant association with IGF2 and H19 during specific gestational weeks. The association was found to be sex-specific in both gene regions. Functionality of the DNA methylation was annotated by the association to fetal growth and cellular pathways. Conclusions The results of our study provided evidence that prenatal PM2.5 exposure is associated with DNA methylation in newborns’ IGF2/H19. The consequences within the context of fetal development of future phenotyping should be addressed.

to evaluate the implementation of an integrated care model for thyroid disease on thyroid surgery at the University Hospital "Federico II" of Naples (Campania Region, Southern Italy).quasi-experimental design employing an interrupted time series analysis.all subjects who were admitted to the University Hospital "Federico II" for thyroid surgery between January 2008 and December 2018. The integrated care model for thyroid disease was implemented starting from January 2016.rate of partial thyroidectomies over all thyroidectomies; rate of diagnosed thyroid cancers over all diagnosed thyroid tumours; length of stay (LOS). Differences pre- and post-interventions were assessed employing Poisson (for count outcomes) and linear (for continuous outcomes) regression models. Models were adjusted for age, gender, tumour diagnosis (none, benign, malignant), Charlson index, and discharge month.data on 4,233 thyroidectomies were included. There was no difference between pre- and post-intervention trends for the rate of partial thyroidectomies over all thyroidectomies (pre-intervention: IRR 1.00; 95%CI 0.99;1.00 - post-intervention: IRR 1.00; 95%CI 0.98;1.02) and for the rate of diagnosed thyroid cancers over all thyroid tumours (pre-intervention IRR 0.99; 95%CI 0.99;1.00 - post-intervention IRR 1.00; 95%CI 0.99;1.01). On the contrary, the LOS reduced from 4.5 (±4.3) days in 2008 to 3.2 (±3.2) days in 2018. The multivariate analysis confirmed this reduction, estimated to be 1.1 days on average in the pre-intervention eight-year period (pre-intervention coefficient -0.01; 95%CI -0.02;-0.01), followed by an even greater reduction in the post-intervention three-year period which was estimated to be 1.1 day (post-intervention: coefficient -0.03; 95%CI -0.05;-0.01).the implementation of an integrated care model for thyroid disease contributed to reduce the LOS for thyroidectomies, improving the efficiency in the management of thyroid disease. However, this intervention had no impact in reducing the rate of total thyroidectomies.

BackgroundAccumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.Methods and findingsIn the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated epigenome-wide association studies (EWAS) of paternal prenatal Body Mass Index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982). We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In sex-stratified analyses, we found just four CpGs where there was robust evidence of association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.ConclusionOur findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring blood DNA methylation, even at imprinted regions.Author SummaryPrevious small, mostly candidate gene studies have shown associations between paternal pre-pregnancy BMI and offspring blood DNA methylation. However, in our large meta-analysis of co-ordinated EWAS results from a total of 19 datasets across two timepoints, we found little evidence to support these findings, even at imprinted regions. This does not rule out the possibility of a paternal epigenetic effect in different tissues, at regions not covered by the 450k array, via different mechanisms, or in populations with greater extremes of paternal BMI. More research is warranted to help understand the size and nature of contributions of paternal adiposity to offspring epigenetics and health outcomes.

Background: Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited. Methods: To investigate the systems biology of birthweight, we integrated methylome, transcriptome, metabolome and a set of inflammatory proteins measured in cord blood samples from four birth-cohorts (n=489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all the other variables from different groups of omic data via bipartite Pearson correlations. Findings: Results substantiated previously identified biomarkers related to birthweight in cord blood, mostly involved in the regulation of the immune system, and identified new multiple omic features. Three metabolic features [PC(34:2), plasmalogen PC(36:4)/PC(O-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22), were identified as key signals related to birthweight. Due to importance of the epigenetic signals in cholesterol biosynthesis, we further studied the association of cholesterol levels in cord blood with birthweight in the ENVIRONAGE cohort (n=1,096), finding that the increase of birthweight an was associated with increment of high-density lipoprotein cholesterol. Interpretation: Our data suggested that cholesterol metabolism in cord blood is involved in the birthweight mechanism and that integration of different omic layers is a useful approach to generate new hypotheses about biological mechanisms. Funding Statement: This work is supported by the Bijzonder Onderzoeksfonds (BOF) Hasselt University through a PhD fellowship [to RA], the “EXPOsOMICS” grant [grant number 308610-FP7 European Commission to PV], and the “STOP” grant [grant number 774548-European Commission H2020 to PV]. The ENVIRONAGE birth-cohort is supported by the EU Program “Ideas” (ERC-2012-StG 310898) and the FWO (G082317N). Piccolipiu cohort has been approved and initially funded by the CCM grant 2010 and by the Italian Ministry of Health. Declaration of Interests: The authors declare that they have no conflict of interests. Ethics Approval Statement: Piccolipiu cohort has been approved and initially funded by the CCM grant 2010 and by the Italian Ministry of Health.

In Italy, to show the willingness to donate one's organs, there is the principle of the explicit consensus (or disagreement) (Law n. 91 of the 01.04.1999, Art. 23; Decree of the Italian Health Ministry of the 08.04.2000). According to data of the Italian Association for the donation of organs, tissues and cells (AIDO), in 2017 in Campania Region (Southern Italy) an average of 12.5 people x1,000,000 donated their organs vs. a national average of 23.7. This negative discrepancy between national and regional data highlights that it is imperative to promote awareness-raising measures to address to the population of Campania Region in order to improve the following of a practice which is still object of preconceptions and scarce knowledge. This paper describes a pilot project started in 2017 by the "Sportello amico trapianti" (friendly access to transplantation) to promote the donation of organs within the university-hospital "Federico II" (Naples, Campania Region). The first phase of this project was based on the nudge theory, that is the "little push" to direct decisional processes of groups and individuals. This phase took place during the "Atelier della salute" (a health workshop), organized by the Medicine and Surgery school of the university-hospital "Federico II": here, a questionnaire was administered to 60 people. The questionnaire consisted in 12 questions, answered by volunteers, which aim was to test the general knowledge about organ donation and transplantation. Analysing the answers, a panel of 7 experts (2 epidemiologists, 1 social worker, 2 experts in public and institutional communication, 1 biologist expert in donation of haematopoietic progenitor cell, 1 transplant surgeon), responsible for the coordination and monitoring of the activities, identified the critical elements to bring attention to in order to raise awareness in the population. The second phase consisted in a literary workshop which aim was to identify nudge cases. The text used was Never let me go by Kazuo Ishiguro, a novel focused on organ donation in a dystopic context where the protagonists are clones created to facilitate the donation of organs. Six students participated in this workshop: all six considered the dystopic scenario as a potential nudge to humanize the approach to organ donation and transplant. In conclusion, we believe that the nudge methodology may be used in order to improve awareness and adherence to donation of organs.

recently, healthcare network models have been proposed to improve general awareness of rare diseases for patients and specific knowledge about diagnosis, treatment, and management for healthcare services. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare haematological disease that still has no framing in an official network.to describe the use of network models in diagnosis, treatment, and management of PNH patients both in Italy and abroad and its impact on patients and healthcare service. DISEGN: literature search was performed using the keywords "Hemoglobinuria", "Network", "PHN", and "Screening" in both MedLine and EMBASE. Search was restricted to the articles published in the last 5 years and written in English, French or Italian language.from the total 251 articles of the initial search, only 21 were finally included in our review. None of the included study explicitly described a network model. In general, we were able to identify two different kind of networks implicitly described in the studies: laboratory networks for diagnostic harmonization or screening of the population at risk of PNH (10/21 studies) and PNH registry as network of clinical information to be use for better understanding of the natural history of the disease and to assess therapeutic effectiveness (11/21 studies).few network approaches in PNH diagnosis, treatment, and management are described in literature. Despite the scarce application of the networks, our review highlights the positive impact that networks have in both patients and healthcare services.

Background Legionellosis’ treatment failures have been recently reported showing the possibility of resistance development to traditional therapy, especially in healthcare related disease cases. Environmental impact of antibiotic residues, especially in hospital waters, may act on the resistome of Legionella resulting in developing resistance mechanisms. Objectives In this study we investigate the antibiotic susceptibility of environmental Legionella pneumophila (Lpn) strains isolated from hospital water systems in Campania, a region located in Southwest Italy. Methods 5321 hospital water samples were investigated for the presence of Lpn. Among positive samples, antibiotic susceptibility was tested for a random subset of 125 Lpn strains (25 Lpn isolates from each of the following serogroups: 1, 3, 5, 6, 8). Susceptibility testing was performed, using the E-test on buffered charcoal yeast extract agar supplemented with α-ketoglutarate, for 10 antimicrobial drugs: azithromycin, cefotaxime, clarithromycin, doxycycline, erythromycin, rifampicin, tigecycline, ciprofloxacin, levofloxacin and moxifloxacin. Non parametric tests were used to determine and assess the significant differences in susceptibility to the different antimicrobics between the serogroups. Results Among the isolated strains, none showed resistance to the antibiotics tested. Rifampicin was the most active antibiotic against overall Legionella strains, followed by levofloxacin. Between the macrolides the clarithromycin was overall the most active drug, instead the azithromycin was the less active. Analyzing the different serogroups a significant difference was found between serogroup 1 and non-1 serogroup isolates for doxycycline and tigecycline. Conclusions Antibiotic susceptibility of environmental isolates of Legionella spp. might be useful for the early detection of resistance to antibiotics that directly impacts on mortality and length of hospital stay.

Background: The epidemiological decrease of Helicobacter pylori (Hp) infection has been recently associated to the increase of several extra-intestinal allergic disorders. Objective: We investigated the role of specific Hp IgG production in the development of IgE or not IgE mediated food allergy (FA) in children affected by atopic dermatitis (AD). Methods: From January 2010 to July 2013, 290 South Italian children, aged between 26 and 142 months, were consecutively referred to the Pediatric Clinic of the Pediatric Department at Second University of Naples and were diagnosed as affected by AD. The patients were classified in two groups on the basis of diagnosis of food allergy (88 FA affected and 202 not FA affected) and further divided on the basis of the diagnosis of atopy (63 IgE mediated and 23 not IgE mediated). Hp serum IgG was detected using an enzyme linked immunosorbent assay (ELISA) kit (Wampole Helicobactor pylori IgG ELISA II, Wampole Laboratories, Cranbury, NJ) and Hp stool antigens using enzyme immunoassay (Premier Platinum HpSa plus, Cincinnati OH). Results: We found a statistically significant higher prevalence of Hp serology positivity in not FA vs. FA AD-affected children (p ¼0.032) and a significant inverse association between FA and Hp immunization (1/OR 0.32 95% CI 0.11–0.95). Further, we identified an absolute prevalence Hp serology positivity in not-IgE-mediated rather than in IgE-mediated FA AD-affected patients (p ¼0.0006). Conclusion: We hypothesize that specific Hp IgG production could protect against the development of both FA and atopy in AD-affected children.

Exposure to chemicals released during urban waste disposal and treatment is increasingly regarded as a potential occupational health issue. Indeed, several toxic metals emitted by an incinerator, including As, Be, Cd, Cr, Pb, Mn, Hg, Ni and V, have potentially toxic properties and their exposure, therefore, may be of concern for the health of the workers involved. The levels of exposure should therefore be carefully measured. Environmental monitoring, however, may be unable, alone, to assess true exposure, due to its intrinsic limitations mainly concerning its inability to assess oral and dermal absorption. In these cases biological monitoring may represent a fundamental supplementary tool for the definition of the workers' true occupational exposure and for the prevention of the related health effects. There is, therefore, an increasing interest in developing and using, in these workers, sensitive and specific biomarkers for health risk assessment, particularly at low or even very low levels of exposure. Despite the large number of original and review articles present in the literature on the biomonitoring of workers exposed to metals, the data on subjects employed in waste treatment activities are scattered and results are sometimes inconsistent. This is the first systematic review, performed according to PRISMA methodology, of the major studies investigating the levels of different toxic metals measured in the main biological matrices (blood, urine, hair) of incinerator workers. The results show that the levels of metals measured in incinerators' workers are generally low, with some notable exceptions for Cd and Pb. These results, though, can be affected by several confounders related either to non-occupational exposure, including diet, area of residence and others, and/or by a number of methodological limitations, as we found in the reported studies. Future work should focus on an integrated approach, using ideally both biological and environmental monitoring. A particular emphasis should be given to the measurement of the different granulometric fractions of the dust containing metals, i.e. inhalable, thoracic, respirable and ultrafine fractions. Moreover, an accurate description of the work tasks and the characteristics and levels of non-occupational exposure should always be provided.

Introduction Birthweight is a known risk factor for diseases in adult life however; the biomolecular mechanisms leading to disease processes remain poorly understood. DNA modifications, transcripts, proteins and metabolites have the potential to imprint biological responses during early life and drive adult risk profiles to chronic conditions. The aim of this study is to enhance the understanding of the complex pathways related to birthweight through integration of multiple OMIC techniques. Methods This study combines methylation (n = 468,408 CpGs), transcriptomics (n = 29,164 transcripts), inflammatory proteins (n = 16) and metabolomics (n = 4712 metabolic features) profiles from cord blood of participants in the EXPOsOMICS birth cohort consortium including ENVIRONAGE (n = 200), INMA (n = 85), Rhea (n = 99) and Piccolipiu (n = 99). We computed Pearson correlation coefficients between pairs of OMICs. Specifically, using a metabolites and methylation driven approaches, we respectively correlated metabolic (n = 68) and epigenetic (n = 8696) signatures of birthweight identified in previous EXPOsOMICS birth cohort study with the other omics platforms. The OMIC platforms have been denoised using technical variables, pairs were considered significant after Bonferroni correction for multiple testing. Significant correlations were visualized in a globe plot with the Circos visualization toolkit version 0.69–6. Transcripts that were significantly correlated to metabolites and to CpGs sites were studied in an overrepresentation analysis (ORA) using DAVID software ( https://www.david.ncifcrf.gov ). Results In the metabolites driven approach, of 33,835,984 correlations between metabolomics and the other levels, 20,097 (0.06%) were significant, mainly inverse (94%) and with a mean absolute correlation coefficient of 0.30 (range = 0.19–0.57). Over the 68 metabolites under study, 13 were significantly correlated with inflammatory proteins, 9 with the transcriptome and 20 with the methylome for a total of 28 unique metabolites. A globe plot of significant correlations showed that all the 9 metabolites were positively correlated with the transcriptome and had an inverse correlation with methylome. Few overlaps (n = 5) were detected in metabolites correlated with both methylome and proteins; the correlations in both pairs went in the same direction (mainly positive). ORA of the 38 genes associated to the significant 41 transcripts resulted in 8 significant pathways, including immune response (such as NK mediated cell cytotoxicity), signaling (MAPK signaling pathway) and also diseases-related (diabetes mellitus and thyroid autoimmunity) pathways. In the methylation driven approach, 0.02% (n = 66,719) of a total 293,606,396 correlations were identified as significant with correlation coefficients having absolute mean of 0.42 (range 0.23–0.69), and mostly negative (67%). Over the 8,663 CpG sites under study, 57 were significantly correlated with proteins, 1,467 with the transcriptome and 2174with the methylome. The globe plot of the significant correlations showed that 13 CpGs appeared in both transcripts and proteins correlation sets, 27 CpGs were common to metabolites and proteins correlation sets, and 791 CpGs were common to metabolites and transcripts correlation sets. Significant correlations in the metabolites and methylation driven approaches shared 34 transcripts, 14 metabolites, 529 CpG sites and 3 proteins. ORA among the 333 genes associated to the 391 unique transcripts significantly correlated to the methylome identified 61 pathways including 4 over the 9 pathways detected in the metabolites driven analysis (including NK mediated cell cytotoxicity and antigen processing and presentation), and also hormone (progesterone-mediated oocyte maturation) and nitrogen metabolism pathways. Conclusion This study provides initial insights into the molecular mechanisms related to birthweight and the biological pathways potentially leading to adverse health effects.