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International audience; Background: COVID-19 triggered an unprecedented crisis affecting society at every level. Research in pediatric and congenital cardiology is currently in full development and may have been disrupted. The aim of the study was to determine the impact of COVID-19 on pediatric and congenital cardiology clinical research and to analyze decision-making and adaptation processes, from a panel of ongoing academic and industry-sponsored research at the time of the pandemic.Methods: This observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care pediatric and congenital cardiology centers. Investigators and clinical research assistants from each participating research center completed an online survey questionnaire, and each principal investigator underwent a 1-h web-based videoconference interview.Results: A total of 34 study questionnaires were collected, reporting that 18 studies were totally suspended. Upon the investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to that in non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study.Conclusion: The impact of the COVID-19 pandemic on clinical research in pediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies.

International audience; Background: : The aim of this retrospective study is to explore the prognostic value of different contrast enhancement imaging patterns in childhood Guillain–Barré syndrome by comparing the clinical, laboratory, and therapeutic outcomes.Methods: : We included a total of 37 patients who were diagnosed and followed up by a pediatric neurology team at Montpellier University Hospital between 2000 and 2016. All images were reinterpreted by the first author and a senior pediatric neuroradiology staff member in two different sessions; in the case of disagreement, the expert's reading was considered.Results: : The study group comprised 22 (59.5%) boys and 15 (40.5%) girls. The age ranged from 1.5 year to 14.8 years. Muscle weakness was present in 33 (89.2%) patients. Cranial nerves involvement was observed in 22 (59.5%) patients, while 29 (78.4%) patients had albuminocytological dissociation. In 27 (73%) patients, contrast enhancement or thickening of the lumbosacral nerve roots was found. Simultaneous spinal nerve root and cranial nerve enhancement was noted in five (17.2%) patients, while isolated cranial nerve enhancement was identified in three (10.3%) patients. Clinical and radiological cranial nerve involvement was found in seven (18.9%) patients, while isolated clinical cranial nerves involvement occurred in 13 (35.1%) patients. No significant correlation between different magnetic resonance imaging (MRI) enhancement patterns and short-term or long-term outcomes was found in our cohort.Conclusion: : Contrast-enhanced brain and spinal MRI is a sensitive and recommended supportive test for diagnosing acute inflammatory polyradiculopathy in children. Its predictive value for clinical, and therapeutic outcomes in the short or long term has not yet been proved

International audience; Aim The aim of this paper was to review the role that donor human milk plays in caring for very low birth weight (VLBW) infants. Methods This review focussed on academic papers and background information published in English and French up to 8 August 2021. Results Donor human milk provides a useful bridge to successful breastfeeding in hospitalised neonates and does not have a negative impact on the use of mother's own milk and breastfeeding rates at discharge. It helps to prevent key complications of prematurity, particularly necrotising enterocolitis up to 36 weeks of postmenstrual age, which is more common in infants fed formulas based on cows' milk. When it is carefully fortified, it supports the postnatal growth of the majority of very preterm infants. Well-organised, accessible human milk banks are required to cover the needs of hospitalised infants, and donor human milk must be prioritised for patients who derive the greatest health benefit from it. These include very preterm infants and those born at term, or near term, with surgical digestive malformations or congenital heart disease. Conclusion Safe, high-quality donor human milk, which is distributed by well-organised human milk banks, is essential for the most vulnerable hospitalised neonates.

Key MessageAlthough obesity measures have been consistently associated with a lower FEV1/FVC ratio in adolescents, no previous study has assessed the underlying mechanisms of this association This population-based study assessed whether insulin resistance and CRP levels at 15 years partially mediate the association between fat mass and FEV1/FVC using a causal mediation analysis approach. The findings suggest that insulin resistance at 15 years may mediate over 20% of this association, but no evidence of a mediating role of CRP was found. Further, longitudinal studies that evaluate other biomarkers of systemic inflammation and examine other potential mechanisms are needed to better understand the pathways linking obesity and respiratory health in adolescence. This is key for public health interventions and targeting clinical interventions.AbstractBackgroundWe previously reported an association of high fat mass levels from age 9 to 15 years with lower forced expiratory flow in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years. Here, we aimed to assess whether insulin resistance and C-reactive protein (CRP) at 15 years partially mediate this association.MethodsWe included 2263 children from the UK Avon Longitudinal Study of Parents and Children population-based cohort (ALSPAC). Four fat mass index (FMI) trajectories (“low,” “medium-low,” “medium-high,” “high”) from 9 to 15 years were previously identified using Group-Based Trajectory Modeling. Data on CRP, glucose, insulin, and post-bronchodilator FEV1/FVC were available at 15 years. We defined insulin resistance by the homeostasis model assessment-estimated insulin resistance index (HOMA-IR). We used adjusted linear regression models and a causal mediation analysis to assess the mediating role of HOMA-IR and CRP.ResultsCompared to children in the “low” FMI trajectory, children in the “medium-high” and “high” FMI trajectories had lower FEV1/FVC at 15 years. The percentage of the total effect explained by HOMA-IR was 19.8% [−114.1 to 170.0] and 20.4% [1.6 to 69.0] for the “medium-high” and “high” trajectories, respectively. In contrast, there was little evidence for a mediating role of CRP.ConclusionThe association between mid-childhood fat mass and FEV1/FVC ratio at 15 years may be partially mediated by insulin resistance.

International audience; Objective: To compare the efficacy of, and complications from, the 2 main treatments for achalasia: endoscopic dilatation and surgical cardiomyotomy (Heller's myotomy).Study design: We retrospectively collected data on children treated for achalasia over an 11-year period from 8 tertiary pediatric centers. A line of treatment was defined as performing either Heller's myotomy or 1-3 sessions of endoscopy dilatation over 3 months. Treatment success was a priori defined as clinical improvement and no need for new treatment.Results: Ninety-seven children (median age, 12 years; 57% boys) were included. The median time to diagnosis was 10.5 months, and the median follow-up period was 27 months. Thirty-seven children were treated by Heller's myotomy and 60 by endoscopy dilatation as the first-line treatment. After adjustment for potentially confounding factors, Heller's myotomy was significantly more successful than endoscopy dilatation (hazard ratio, 3.93 [1.74; 8.88]; P = .001), with a median survival without failure of 49 and 7 months, respectively, and with no significant difference in the occurrence of complications (35.2% for Heller's myotomy, 29.7% for endoscopy dilatation, P = .56). Hydrostatic dilatation was as successful as pneumatic dilatation (hazard ratio, 1.35 [0.56; 3.23]; P = .50).Conclusions: Heller's myotomy is more successful than endoscopy dilatation, with no significant difference in the occurrence of serious complications. This raises the potential role of peroral endoscopic myotomy as an alternative treatment to Heller's myotomy.

International audience; Background: Respiratory viruses can be responsible for severe apneas and bradycardias in newborn infants. The link between systemic inflammation with viral sepsis and cardiorespiratory alterations remains poorly understood. We aimed to characterize these alterations by setting up a full-term newborn lamb model of systemic inflammation using polyinosinic:polycytidylic acid (Poly I:C). Methods: Two 6-h polysomnographic recordings were carried out in eight lambs on two consecutive days, first after an IV saline injection, then after an IV injection of 300 mu g/kg Poly I:C. Results Poly I:C injection decreased locomotor activity and increased NREM sleep. It also led to a biphasic increase in rectal temperature and heart rate. The latter was associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Lastly, brainstem inflammation was found in the areas of the cardiorespiratory control centers 6 h after Poly I:C injection. Conclusions: The alterations in heart-rate variability induced by Poly I:C injection may be, at least partly, of central origin. Meanwhile, the absence of alterations in respiratory-rate variability is intriguing and noteworthy. Although further studies are obviously needed, this might be a way to differentiate bacterial from viral sepsis in the neonatal period. Impact Provides unique observations on the cardiorespiratory consequences of injecting Poly I:C in a full-term newborn lamb to mimic a systemic inflammation secondary to a viral sepsis. Poly I:C injection led to a biphasic increase in rectal temperature and heart rate associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Brainstem inflammation was found in the areas of the cardiorespiratory control centers.

International audience; Introduction: Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome.Methods: We performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018.Results: A total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m2 (4.9-62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (-4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m2 (60.3-152.7) and

National audience

Background: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections. A comprehensive list of grant funding is available on the ALSPAC website (www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). BAMSE: BAMSE was funded by the Swedish Research Council, the Swedish Heart Lung Foundation, ALF Region Stockholm and SFO Epidemiology Karolinska Institutet. E. Mélen is supported by a European Research Council grant (TRIBAL, 757919). BiB (Born in Bradford): BiB is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, practitioners and researchers who have made BiB happen. The BiB study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044). Core support for BiB is also provided by the Wellcome Trust (WT101597MA). BILD: This study was funded by the Swiss National Science Foundation (320030_163311). CoNER: Funds were obtained from the special programme (Programmi speciali – Art.12 bis, comma 6 D.lgs.229/99 Sanitaria e della Vigilanza sugli Enti) funded by the Italian Ministry of Health. Approval for the study was obtained from the Ethics Committee of the S. Orsola-Malpighi Teaching Hospital in April 2004 (52/2004/U/Tess). COPSAC 2000 and COPSAC 2010: All funding received by COPSAC is listed on www.copsac.com. The Lundbeck Foundation (R16-A1694), Ministry of Health (903516), Danish Council for Strategic Research (0603-00280B) and Capital Region Research Foundation have provided core support to the COPSAC research centre. We express our deepest gratitude to the children and families of the COPSAC 2000 and COPSAC 2010 cohort studies for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. DNBC (Danish National Birth Cohort): The authors would like to thank the participants, the first Principal Investigator of DNBC, Jørn Olsen, the scientific managerial team and DNBC secretariat for being, establishing, developing and consolidating the DNBC. The DNBC was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, Pharmacy Foundation, Egmont Foundation, March of Dimes Birth Defects Foundation, Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and Lundbeck Foundation. Follow-up of mothers and children has been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), Lundbeck Foundation (195/04, R100-A9193), Innovation Fund Denmark 0603-00294B (09-067124), Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012) and Danish Council for Independent Research (DFF-4183-00594, DFF-4183-00152). A. Pinot de Moira is funded by a Lundbeck Foundation grant (R264-2017-3099). EDEN: We thank the EDEN mother–child cohort study group (I. Annesi-Maesano, J.Y. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A. Germa, V. Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G. Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer and O. Thiebaugeorges). We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 programme), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, MeDALL projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l'Education Nationale complementary health insurance (MGEN), French national agency for food security, and French speaking association for the study of diabetes and metabolism (ALFEDIAM). The funding source had no involvement in the conception of the present study. FLEHS: This study was conducted within the framework of the Flemish Centre of Expertise on Environment and Health, funded by the Dept of the Environment of the Flemish Government, Flemish Agency of Care and Health, and Flemish Dept of Economy, Science and Innovation. GASPII: The GASPII cohort was funded by the Italian Ministry of Health (2001), the research leading to these results has received funding from the European Community's Seventh Framework Program under grant agreement 261357 (MeDALL). Generation R: This study was funded by Erasmus MC Rotterdam, Erasmus University Rotterdam and the Netherlands Organisation for Health Research and Development. V.W.V. Jaddoe received a grant from the European Research Council (ERC-2014-CoG-648916). L. Duijts received funding from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 (696295; 2017), the Netherlands Organisation for Health Research and Development (ZonMw; 529051014; 2017), Science Foundation Ireland (SFI/16/ERA-HDHL/3360), and European Union (ALPHABET project). The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206, 2016; EUCAN-Connect 824989; ATHLETE, 874583). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data or writing of this report. Generation XXI: Generation XXI was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education, and by the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020), Administração Regional de Saúde Norte (Regional Dept of Ministry of Health) and Fundação Calouste Gulbenkian. A.C. Santos is founded by FCT Investigator contracts IF/01060/2015. GINI: The GINIplus study was mainly supported for the first 3 years by the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum München (former GSF) (observational arm). The 4- and 6-year follow-up examinations of the GINIplus study were covered from the respective budgets of the five study centres (Helmholtz Zentrum München (former GSF), Research Institute at Marien-Hospital, Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf). HUMIS: We thank all mothers for participating in the HUMIS study. HUMIS was funded by a grant from the Norwegian Research Council (226402). The HUMIS study was approved by the Norwegian Data Inspectorate (2002/1398) and by the Regional Ethics Committee for Medical Research in Norway (S-02122), and the specific use in the current study was approved by the Ethics Committee as well (2010/1259/REK sør-øst). INMA: Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI09/00090, FIS-PI18/01142 including FEDER funds), CIBERESP, Dept of Health of the Basque Government (2013111089) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia and Beasain). Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2, PI061756; PS0901958, PI14/00677 including FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigación en Enfemerdades Neurodegeneratives de La Caixa, and EC contract QLK4-CT-200-00263. Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 including FEDER funds), Generalitat de Catalunya-CIRIT 1999SGR 00241 and Fundació La marató de TV3 (090430). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. M. Casas holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and cofunded by the European Social Fund “Investing in your future”. Valencia: This study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, UGP-15-249), and Alicia Koplowitz Foundation 2017. Isle of Wight: This study was funded by grants from the National Institutes of Health USA (R01HL082925), Asthma UK (364), Isle of Wight NHS Trust and the British Medical Association. KOALA: The collection of data relevant for this study was funded by grants from the Netherlands Organisation for Health Research and Development (ZonMw; 2100.0090) and the Netherlands Asthma Foundation (3.2.03.48, 3.2.07.022). The researchers are independent from the funders. The funders had no role in the study design, data analysis, interpretation of data or writing of this report. We thank the children and parents for their participation in the KOALA study. LRC (Leicestershire Respiratory Cohorts): This study was funded by grants from the Swiss National Science Foundation (SNF: 320030-182628, 320030-162820, 3233-069348, 3200-069349) and Asthma UK 07/048. Lifeways Cross-Generation Cohort Study: This study was funded by the Health Research Board, Ireland, and the Irish Dept of Health and Children's Health Promotion Policy Unit. LISA: The LISA study was mainly supported by grants from the Federal Ministry for Education, Science, Research and Technology and in addition from Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Bad Honnef for the first 2 years. The 4-, 6-, 10- and 15-year follow-up examinations of the LISA study were covered from the respective budgets of the involved partners (Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf) and in addition by a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the LISA study was supported by the Commission of the European Communities, the Seventh Framework Program: MeDALL project. This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (949906). LucKi: LucKi is supported by Child and Youth Health Care Zuyderland, Public Health Service South Limburg and Maastricht University. We thank all parents and children for their participation in LucKi. LUKAS: This study was funded by research grants from the Academy of Finland (139021, 287675, 296814, 296817, 308254); Juho Vainio Foundation; EVO/VTR funding; Päivikki and Sakari Sohlberg Foundation; Farmers’ Social Insurance Institution (Mela); Finnish Cultural Foundation; Foundation for Pediatric Research; European Union QLK4-CT-2001-00250; and Finnish Institute for Health and Welfare, Finland. MAS-90: This study was funded by grants from the German Federal Ministry of Education and Research (MBMF; 07015633m 07ALE27, 01EE9405/5, 01EE9406) and the German Research Foundation (DFG; KE1462/2-1). Millennium Cohort Study: This study was funded by the Economic and Social Research Council and a consortium of UK government funders. We are grateful to the participating families and the Centre for Longitudinal Studies (CLS), UCL Institute of Education, for the use of these data and to the UK Data Service for making them available. However, neither CLS nor the UK Data Service bear any responsibility for the analysis or interpretation of these data. This work was supported by the Welcome Trust (187389/B/08/Z). MoBa: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this ongoing cohort study. This research was supported by the Research Council of Norway through its Centres of Excellence funding scheme (262700). NINFEA: The authors are grateful to all the participants of the NINFEA cohort. The NINFEA study was partially funded by the Compagnia San Paolo Foundation. This research was partially funded by the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). PELAGIE: We are grateful to the families who participated and continue to participate in the study. The cohort is supported by INSERM and received funding from the French National Research Agency, Fondation de France, French Agency for Food, Environmental and Occupational Health & Safety, National Institute for Public Health Surveillance (InVS), French Ministry of Labour, and French Ministry of Ecology. PIAMA: This study was funded by the Netherlands Organisation of Health Research and Development, Netherlands Organisation for Scientific Research, Netherlands Asthma Fund, Netherlands Ministry of Spatial Planning, Housing and the Environment, and Netherlands Ministry of Health, Welfare and Sport. REPRO_PL: This study was funded by the National Science Center Poland (DEC-2014/15/B/N27/00998). Rhea: This study was funded by the European Union Social Fund and the Hellenic Ministry of Health (“Program of prevention and early diagnosis of obesity and neurodevelopment disorders in preschool age children in the prefecture of Heraklion, Crete, Greece”; MIS 349580, NSRF 2007–2013). Additional funding from the National Institute of Environmental Health Sciences (NIEHS) supported L. Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, R21ES028903, P30ES007048). STEPS: This study was funded by the University of Turku, Abo Akademi University, Turku University Hospital, Academy of Finland (123571, 140251, 277535) and Foundation for Pediatric Research Finland. SWS: This study was funded by the Medical Research Council, British Heart Foundation, Arthritis Research UK, Food Standards Agency, NIHR Southampton Biomedical Research Centre and the European Union's Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition (289346), and the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). WHISTLER: The WHISTLER birth cohort was supported with a grant from the Netherlands Organisation for Health Research and Development (2001-1-1322) and by an unrestricted grant from GlaxoSmithKline Netherlands. GlaxoSmithKline had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the report for publication. WHISTLER-Cardio was supported with an unrestricted strategic grant from the University Medical Center Utrecht (UMCU).