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What is the association of gestational weight gain (across a range of prepregnancy weights) with maternal and infant outcomes?
In this meta-analysis of individual participant data from 25 pooled cohort studies and 196 670 participants, prepregnancy weight and the magnitude of gestational weight gain were associated with risk for any adverse outcome (defined as ≥1 of the following: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth); however, the magnitude of gestational weight gain was weakly associated with the adverse outcomes assessed.
These findings may inform prenatal counseling regarding optimal weight gain during pregnancy; however, the magnitude of gestational weight gain was weakly associated with the outcomes assessed.
Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges.
To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories.
Design, Setting, and Participants
Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015.
Gestational weight gain.
Main Outcomes and Measures
The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth.
Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79).
Conclusions and Relevance
In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.
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Accepted for Publication: March 29, 2019.
Corresponding Author: Romy Gaillard, MD, PhD, Generation R Study Group (Room Na-2908), Erasmus MC, University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands (firstname.lastname@example.org).
LifeCycle Project-Maternal Obesity and Childhood Outcomes Authors: The following investigators take authorship responsibility for the study results: Ellis Voerman, MSc; Susana Santos, PhD; Hazel Inskip, MSc, PhD; Pilar Amiano, PharmD, MSc; Henrique Barros, MD, PhD; Marie-Aline Charles, MD, MPH; Leda Chatzi, MD, PhD; George P. Chrousos, MD, ScD; Eva Corpeleijn, PhD; Sarah Crozier, PhD; Myriam Doyon, MSc; Merete Eggesbø, MD, PhD; Maria Pia Fantini, MD; Sara Farchi, MSc; Francesco Forastiere, MD, PhD; Vagelis Georgiu, MSc; Davide Gori, MD, PhD; Wojciech Hanke, PhD; Irva Hertz-Picciotto, PhD; Barbara Heude, PhD; Marie-France Hivert, MD; Daniel Hryhorczuk, MD, MPH; Carmen Iñiguez, PhD; Anne M. Karvonen, PhD; Leanne K. Küpers, PhD; Hanna Lagström, PhD; Debbie A. Lawlor, PhD; Irina Lehmann, PhD; Per Magnus, MD, PhD; Renata Majewska, MSc; Johanna Mäkelä, PhD; Yannis Manios, PhD, MMedSc; Monique Mommers, PhD; Camilla S. Morgen, MSc, PhD; George Moschonis, PhD; Ellen A. Nohr, PhD; Anne-Marie Nybo Andersen, MD, PhD; Emily Oken, MD, MPH; Agnieszka Pac, MSc, PhD; Eleni Papadopoulou, PhD; Juha Pekkanen, MD, PhD; Costanza Pizzi, PhD; Kinga Polanska, PhD; Daniela Porta, MSc; Lorenzo Richiardi, MD, PhD; Sheryl L. Rifas-Shiman, MPH; Nel Roeleveld, PhD, MSc; Luca Ronfani, MD, PhD; Ana C. Santos, PhD; Marie Standl, PhD; Hein Stigum, PhD; Camilla Stoltenberg, MD, PhD; Elisabeth Thiering, PhD; Carel Thijs, MD, PhD; Maties Torrent, MD, PhD; Tomas Trnovec, MD, PhD; Marleen M. H. J. van Gelder, PhD; Lenie van Rossem, PhD; Andrea von Berg, MD; Martine Vrijheid, PhD; Alet Wijga, PhD; Oleksandr Zvinchuk, MS; Thorkild I. A. Sørensen, MD, Dr Med Sci; Keith Godfrey, BM, PhD; Vincent W. V. Jaddoe, MD, PhD; Romy Gaillard, MD, PhD.
Affiliations of LifeCycle Project-Maternal Obesity and Childhood Outcomes Authors: Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (Voerman, S. Santos, Jaddoe, Gaillard); Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (Voerman, S. Santos, Jaddoe, Gaillard); MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, England (Inskip, Crozier, Godfrey); NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England (Inskip, Godfrey); Public Health Division of Gipuzkoa, San Sebastián, Spain (Amiano); BioDonostia Research Institute, San Sebastián, Spain (Amiano); CIBER Epidemiología y Salud Pública, Madrid, Spain (Amiano, Iñiguez, Vrijheid); EPI Unit-Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal (Barros, A. C. Santos); Department of Public Health and Forensic Sciences and Medical Education, Unit of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal (Barros, A. C. Santos); INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center, ORCHAD Team, Villejuif, France (Charles, Heude); Paris Descartes University, Villejuif, France (Charles, Heude); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles (Chatzi); Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece (Chatzi, Georgiu); Department of Genetics and Cell Biology, Maastricht University, Maastricht, the Netherlands (Chatzi); First Department of Pediatrics, National and Kapodistrian University of Athens, Medical School, Aghia Sophia Children’s Hospital, Athens, Greece (Chrousos); University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands (Corpeleijn, Küpers); Centre de Recherche du Centre Hospitalier de l’Universite de Sherbrooke, Sherbrooke, Quebec, Canada (Doyon, Hivert); Department of Exposure and Environmental Epidemiology, Norwegian Institute of Public Health, Oslo, Norway (Eggesbø); Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy (Fantini, Gori); Department of Epidemiology, Lazio Regional Health Service, Rome, Italy (Farchi, Forastiere, Porta); Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland (Hanke, Polanska); Department of Public Health Sciences, School of Medicine, University of California, Davis (Hertz-Picciotto); Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, Massachusetts (Hivert, Oken, Rifas-Shiman); Diabetes Unit, Massachusetts General Hospital, Boston (Hivert); Center for Global Health, College of Medicine, University of Illinois, Chicago (Hryhorczuk); Department of Statistics and Computational Research, Universitat de València, València, Spain (Iñiguez); Department of Health Security, National Institute for Health and Welfare, Kuopio, Finland (Karvonen, Pekkanen); Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands (Küpers); MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England (Küpers, Lawlor); Population Health Science, Bristol Medical School, University of Bristol, Bristol, England (Küpers, Lawlor); Department of Public Health, University of Turku, Turku, Finland (Lagström); Department of Environmental Immunology/Core Facility Studies, Helmholtz Centre for Environmental Research–UFZ, Leipzig, Germany (Lehmann); Division of Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway (Magnus); Department of Epidemiology, Jagiellonian University Medical College, Krakow, Poland (Majewska, Pac); Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland (Mäkelä); Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece (Manios); Department of Epidemiology, Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands (Mommers, Thijs); National Institute of Public Health, University of Southern Denmark, Copenhagen (Morgen); Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark (Morgen, Nybo Andersen, Sørensen); Department of Dietetics, Nutrition, and Sport, La Trobe University, Melbourne, Australia (Moschonis); Research Unit for Gynaecology and Obstetrics, Institute for Clinical Research, University of Southern Denmark, Odense (Nohr); Department of Environmental Exposures and Epidemiology, Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway (Papadopoulou); Department of Public Health, University of Helsinki, Helsinki, Finland (Pekkanen); Department of Medical Sciences, University of Turin, Turin, Italy (Pizzi, Richiardi); Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (Roeleveld, van Gelder); Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy (Ronfani); Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany (Standl, Thiering); Department of Noncommunicable Diseases, Norwegian Institute of Public Health, Oslo, Norway (Stigum); Norwegian Institute of Public Health, Oslo, Norway (Stoltenberg); Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway (Stoltenberg); Dr von Hauner Children’s Hospital, Ludwig-Maximilians-University Munich, Munich, Germany (Thiering); Ib-Salut, Area de Salut de Menorca, Palma, Spain (Torrent); Department of Environmental Medicine, Slovak Medical University, Bratislava, Slovakia (Trnovec); Radboud Reshape Innovation Center, Radboud University Medical Center, Nijmegen, the Netherlands (van Gelder); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (van Rossem); Research Institute, Department of Pediatrics, Marien-Hospital Wesel, Wesel, Germany (von Berg); ISGlobal, Institute for Global Health, Barcelona, Spain (Vrijheid); Universitat Pompeu Fabra, Barcelona, Spain (Vrijheid); National Institute for Public Health and the Environment, Bilthoven, the Netherlands (Wijga); Department of Medical and Social Problems of Family Health, Institute of Pediatrics, Obstetrics and Gynecology, Kyiv, Ukraine (Zvinchuk); Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (Sørensen); Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (Jaddoe).
Author Contributions: Ms Voerman and Dr Gaillard had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Jaddoe and Gaillard contributed equally to this work.
Concept and design: Voerman, S. Santos, Barros, Doyon, Hivert, Hryhorczuk, Lawlor, Mäkelä, Manios, Moschonis, Thijs, Godfrey, Jaddoe, Gaillard.
Acquisition, analysis, or interpretation of data: Voerman, S. Santos, Inskip, Amiano, Barros, Charles, Chatzi, Chrousos, Corpeleijn, Crozier, Eggesbø, Fantini, Farchi, Forastiere, Georgiu, Gori, Hanke, Hertz-Picciotto, Heude, Hryhorczuk, Iñiguez, Karvonen, Küpers, Lagström, Lawlor, Lehmann, Magnus, Majewska, Manios, Mommers, Morgen, Moschonis, Nohr, Nybo Andersen, Oken, Pac, Papadopoulou, Pekkanen, Pizzi, Polanska, Porta, Richiardi, Rifas-Shiman, Roeleveld, Ronfani, A. Santos, Standl, Stigum, Stoltenberg, Thiering, Thijs, Torrent, Trnovec, van Gelder, van Rossem, Vrijheid, Wijga, Zvinchuk, Sørensen, Godfrey, Jaddoe, Gaillard.
Drafting of the manuscript: Voerman, S. Santos, Jaddoe, Gaillard.
Critical revision of the manuscript for important intellectual content: Inskip, Amiano, Barros, Charles, Chatzi, Chrousos, Corpeleijn, Crozier, Doyon, Eggesbø, Fantini, Farchi, Forastiere, Georgiu, Gori, Hanke, Hertz-Picciotto, Heude, Hivert, Hryhorczuk, Iñiguez, Karvonen, Küpers, Lagström, Lawlor, Lehmann, Magnus, Majewska, Mäkelä, Manios, Mommers, Morgen, Moschonis, Nohr, Nybo Andersen, Oken, Pac, Papadopoulou, Pekkanen, Pizzi, Polanska, Porta, Richiardi, Rifas-Shiman, Roeleveld, Ronfani, A. Santos, Standl, Stigum, Stoltenberg, Thiering, Thijs, Torrent, Trnovec, van Gelder, van Rossem, Vrijheid, Wijga, Zvinchuk, Sørensen, Godfrey, Jaddoe.
Statistical analysis: Voerman, Inskip, Georgiu, Hryhorczuk, Stigum, Gaillard.
Obtained funding: Inskip, Barros, Corpeleijn, Hanke, Hertz-Picciotto, Karvonen, Lawlor, Nybo Andersen, Oken, Pekkanen, Polanska, A. Santos, Thijs, Torrent, Godfrey, Jaddoe.
Administrative, technical, or material support: Barros, Corpeleijn, Doyon, Fantini, Farchi, Iñiguez, Karvonen, Küpers, Lagström, Lehmann, Magnus, Mäkelä, Manios, Morgen, Moschonis, Nohr, Nybo Andersen, Oken, Papadopoulou, Pekkanen, Pizzi, Rifas-Shiman, Stoltenberg, Thijs, Torrent, van Gelder, van Rossem, Wijga, Zvinchuk, Jaddoe.
Supervision: Amiano, Barros, Charles, Chatzi, Forastiere, Hivert, Manios, Moschonis, Roeleveld, Torrent, Vrijheid, Jaddoe, Gaillard.
Conflict of Interest Disclosures: Dr Godfrey reported receiving speakers fees from companies selling nutritional products; and being part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Dr Lawlor reported receiving support from Roche Diagnostics and Medtronic for biomarker research. No other disclosures were reported.
Funding/Support:Avon Longitudinal Study of Parents and Children (ALSPAC): Funded by grant 102215/2/13/2 from the UK Medical Research Council and Wellcome, core support from the University of Bristol, grant R01 DK10324 from the US National Institutes of Health, grant agreement 669545 from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013), award MC_UU_12013/5 from the UK Medical Research Council, and Dr Lawlor is a National Institute for Health Research senior investigator (NF-SI-0611-10196). Cohort of Newborns in Emilia Romagna (CoNER): No funding reported. Danish National Birth Cohort (DNBC): The Danish Epidemiology Science Centre initiated and created the DNBC and this center was established by the Danish National Research Foundation via a major grant. Additional support was obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation. The 7-year follow-up study was supported by award 195/04 from the Lundbeck Foundation and award SSVF 0646 from the Danish Medical Research Council. Étude des Déterminants pré et postnatals du développement et de la santé de l’ENfant (EDEN): Supported by the French foundation for medical research, the French national agency for research, the French national institute for research in public health (IRESP: TGIR cohorte santé 2008 program), the French ministry of health, the French ministry of research, the INSERM bone and joint diseases national research and human nutrition national research programs, Paris-Sud University, Nestlé, the French national institute for population health surveillance, the French national institute for health education, the European Union FP7 programs (2007-2013; HELIX, ESCAPE, ENRIECO, and Medall projects), the French diabetes national research program through a collaboration with the French association of diabetic patients, the French agency for environmental health safety (now ANSES), the Mutuelle Générale de l’Education Nationale (a complementary health insurance), the French national agency for food security, and the French-speaking association for the study of diabetes and metabolism. Family and Children of Ukraine (FCOU): Supported by the Fogarty International Center at the US National Institutes of Health, the US National Institute of Environmental Health Sciences, the US Centers for Disease Control and Prevention, the US Environmental Protection Agency, and the National Academy of Medical Sciences of Ukraine. Genetica e Ambiente: Studio Prospettico dell’Infanzia in Italia (GASPII): Supported by the Italian ministry of health. Groningen Expert Center for Kids with Obesity (GECKO Drenthe): Supported by an unrestricted grant from Hutchison Whampoa Ltd and funding from the University of Groningen, Well Baby Clinic Foundation Icare, Noordlease, the Paediatric Association of the Netherlands, and Youth Health Care Drenthe. Genetics of Glucose regulation in Gestation and Growth (Gen3G): Supported by operating grant 20697 from the Fonds de recherche du Québec en santé, operating grant MOP 115071 from the Canadian Institute of Health Reseach, a grant from Diabète Québec, and operating grant OG-3-08-2622-JA from the Canadian Diabetes Association. Generation R: The general design of the study received financial support from Erasmus MC, University Medical Center Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development, the Netherlands Organisation for Scientific Research and the Ministry of Health, Welfare, and Sport, and the Ministry of Youth and Families. The research leading to these results received funding from the European Union Horizon 2020 Research and Innovation Programme under grant 733206 (LifeCycle Project). Dr Jaddoe received grant ERC-2014-CoG-648916 from the European Research Council. Dr Gaillard received grant 2017T013 from the Dutch Heart Foundation, grant 2017.81.002 from the Dutch Diabetes Foundation, and grant 543003109 from the Netherlands Organisation for Health Research and Development. Generation XXI: Funded by Programa Operacional de Saúde–Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health), by POCI-01-0145-FEDER-016837 through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (Portuguese Ministry of Science, Technology, and Higher Education) under the project PathMOB, by FCT PTDC/DTP-EPI/3306/2014 (Risco cardiometabólico na infância: desde o início da vida ao fim da infância), by POCI-01-0145-FEDER-006862 and UID/DTP/04750/2013 (Unidade de Investigação em Epidemiologia-Instituto de Saúde Pública da Universidade do Porto), and FCT investigator contract IF/01060/2015 awarded to Dr A. C. Santos. Growth, Exercise and Nutrition Epidemiological Study In preSchoolers (GENESIS): Supported by a research grant from Friesland Hellas. German Infant Nutritional Intervention plus environmental and genetic influences (GINIplus): Supported for the first 3 years by the Federal Ministry for Education, Science, Research, and Technology (intervention group) and Helmholtz Zentrum Munich (observation group). The 4-, 6-, 10-, and 15-year follow-up examinations were covered from the respective budgets of the 5 study centers (Helmholtz Zentrum Munich, Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich, IUF-Leibniz Research-Institute for Environmental Medicine at the University of Düsseldorf) and by funding from the European Commission 7th Framework Programme (MeDALL project), Mead Johnson, and Nestlé and grant FKZ 20462296 from the Federal Ministry for Environment (awarded to IUF Düsseldorf). Norwegian Human Milk Study (HUMIS): Funded by award FP7/2007-2013 from the European Commission 7th Framework Programme, grant 289346 from European Union EarlyNutrition project, and by funds for project 213148 from the Norwegian Research Council’s MILPAAHEL programme. INfancia y Medio Ambiente (INMA)-Sabadell: Funded by grant Red INMA G03/176 from the Instituto de Salud Carlos III in Spain and grant 1999SGR 00241 from the Generalitat de Catalunya-CIRIT. INMA-Valencia: Funded by grants FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1 from the European Commission, grants G03/176, FIS-FEDER PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, Miguel Servet FEDER CP11/00178, CP15/00025, and CPII16/00051 from the Instituto de Salud Carlos III in Spain, and grants UGP 15-230, UGP-15-244, and UGP-15-249 from the Generalitat Valenciana, Foundation for the Promotion of Health and Biomedical Research of Valencia Region. INMA-Gipuzkoa: Funded by grants FISFIS PI06/0867, FIS-PS09/0009 0867, and Red INMA G03/176 from the Instituto de Salud Carlos III in Spain, grants 2005111093 and 2009111069 from the Departamento de Salud del Gobierno Vasco, and grants DFG06/004 and FG08/001 from the Provincial Government of Guipúzcoa. INMA-Menorca: This study was funded by grant Red INMA G03/176 from the Instituto de Salud Carlos III in Spain. Child, parents and health: lifestyle and genetic constitution (KOALA): Data collection from pregnancy up to the age of 1 year was supported by grants from Royal Friesland Foods, the Triodos Foundation, the Phoenix Foundation, the Raphaël Foundation, the Iona Foundation, the Foundation for the Advancement of Heilpedagogie, the Netherlands Organisation for Health Research and Development (2100.0090), the Netherlands Asthma Foundation (3.2.03.48 and 3.2.07.022), and the Netherlands Heart Foundation (2008B112). Krakow Cohort: Funded by grants R01ES010165 and R01ES015282 from the US National Institute of Environmental Health Sciences and by funding from the Lundin Foundation, the John and Wendy Neu Family Foundation, the Gladys and Roland Harriman Foundation, and the Anonymous Foundation. Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus the influence of traffic emissions and genetics (LISAplus): Mainly supported by grants for the first 2 years from the Federal Ministry for Education, Science, Research, and Technology, the Helmholtz Zentrum Munich, the Helmholtz Centre for Environmental Research-UFZ, the Research Institute at Marien-Hospital Wesel, and a pediatric practice in Bad Honnef. The 4-, 6-, 10-, and 15-year follow-up examinations were funded by the respective budgets of the involved partners (the Helmholtz Zentrum Munich, the Helmholtz Centre for Environmental Research-UFZ, the Research Institute at Marien-Hospital Wesel, a pediatric practice in Bad Honnef, and the IUF–Leibniz-Research Institute for Environmental Medicine at the University of Düsseldorf), by grant FKZ 20462296 from the Federal Ministry for Environment (awarded to IUF Düsseldorf), and by support from the European Commission 7th Framework Programme (MeDALL project). LUKAS Cohort: Funded by EVO/VTR grants, grants 139021 and 287675 from the Academy of Finland, grant QLK4-CT-2001-00250 from the European Union, and funding from the Juho Vainio Foundation, the Foundation for Pediatric Research, the Päivikki and Sakari Sohlberg Foundation, the Finnish Cultural Foundation, and the National Institute for Health and Welfare in Finland. Norwegian Mother and Child Cohort Study (MoBa): Supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, contract N01-ES-75558 with the US National Institute of Environmental Health Sciences, and grants UO1 NS 047537-01 and UO1 NS 047537-06A1 from the US National Institute of Neurological Disorders and Stroke. Nascita e INFanzia: gli Effetti dell’Ambiente (NINFEA): Partially funded by the Compagnia San Paolo Foundation and by the Piedmont Region. Prevention and Incidence of Asthma and Mite Allergy (PIAMA): Supported by the Organization for Health Research and Development, the Organization for Scientific Research, the Asthma Fund, the Ministry of Spatial Planning, Housing, and the Environment, and the Ministry of Health, Welfare, and Sport (all organizations in the Netherlands). Piccolipiù Project: Financially supported by CCM grants during 2010 and 2014 from the Italian National Center for Disease Prevention and Control and funding (art 12 and 12 bis D.lgs 502/92) from the Italian Ministry of Health. PRegnancy and Infant DEvelopment (PRIDE Study): Supported by grants from the Netherlands Organization for Health Research and Development, the Radboud Institute for Health Sciences, and the Lung Foundation Netherlands. Project Viva: Funded by grants R01 HD034568 and UG3OD023286 from the US National Institutes of Health. Polish Mother and Child Cohort Study (REPRO_PL): Funded by grants DEC-2014/15/B/NZ7/00998 and FP7 HEALS 603946 from the National Science Centre in Poland and grant 3068/7.PR/2014/2 from the Polish Ministry of Science and Higher Education. Exposure of Preschool-Age Greek Children (RHEA): Financially supported by European Commission projects FP6-2003-Food-3-NewGeneris, FP6-STREP Hiwate, FP7-ENV.2007.1.2.2.2, FP7-2008-ENV-184.108.40.206 Envirogenomarkers, FP7-HEALTH-2009-single stage CHICOS, FP7-ENV.2008.1.2.1.6, FP7-HEALTH-2012, and 211250-Escape and proposals 226285 ENRIECO and 308333 HELIX and by the Greek Ministry of Health. Slovak PCB Study: Support was provided by grants R01 CA096525, R03 TW007152, P30 ES001247, P30 ES023513, and K12 ES019852 from the US National Institutes of Health. STEPS: This study was supported by the University of Turku, Abo Akademi University, the Turku University Hospital, the City of Turku, the Juho Vainio Foundation, and the Yrjö Jahnsson Foundation and by grants 121569 and 123571 from the Academy of Finland. Southampton Women’s Survey (SWS): Supported by funding from the Medical Research Council, the National Institute for Health Research Southampton Biomedical Research Centre, the University of Southampton, Dunhill Medical Trust, and the University Hospital Southampton National Health Service Foundation Trust, FP7/2007-2013 from the European Commission 7th Framework Programme, and grant 289346 from the European Union EarlyNutrition project.
Role of the Funder/Sponsor: Investigators from the US National Institute of Environmental Health Sciences were only involved in the design of the birth outcomes phase of the FCOU study. All of the other funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions:ALSPAC: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. DNBC: We thank all the families for participating. EDEN: We thank the mother-child cohort study group. FCOU: We acknowledge the individuals at the Louise Hamilton Kyiv Data Management Center (located within the School of Public Health, University of Illinois, Chicago) for their assistance in the data management. GASPII: We acknowledge the families involved. GECKO Drenthe: We are grateful for the participating families, the whole study team, and particularly the midwives, gynecologists, nurses, and general practioners for their help in the recruitment and measurement of participants. Gen3G: We acknowledge the support from clinical and research staff with blood sampling in the pregnancy clinic and for their help with recruitment along with the biomedical laboratory for performing the assays (all located at Centre Hospitalier Universitaire de Sherbrooke). Generation R: We gratefully acknowledge the contribution of the general practitioners, hospitals, midwives, and pharmacies in Rotterdam. Generation XXI: We gratefully acknowledge the families for their kindness, all the members of the research team for their enthusiasm and perseverance, and the participating hospitals and their staff for their help and support. GENESIS: We thank the research group for their contribution in the execution and completion of the study. GINIplus: We thank all the participating families and all the members of the study group for their excellent work. HUMIS: We thank the mothers who participated in the study and the Norwegian Research Council. INMA-Valencia: We particularly thank all the participants for their generous collaboration. INMA-Gipuzkoa: We thank the children and parents who participated. INMA-Menorca: We thank all the participants for their generous collaboration. KOALA: We thank the children and parents who participated. Krakow Cohort: We acknowledge the teams from Jagiellnonian University Medical College (W. Jedrychowski, MD, PhD, coinvestigator) and Columbia University (F. P. Perera, PhD, principal investigator). Drs Jedrychowski and Perera initiated the cohort and were awarded grants. LISAplus: We thank the participating families and the members of the study group for their excellent work. LUKAS: We thank all the participating families. MoBa: We are grateful to all the participating families in Norway who continue to take part in this ongoing study. NINFEA: We thank all the participating families. PÉLAGIE: We thank the gynecologists, obstetricians, ultrasonographers, midwives, pediatricians, and families who participated. PIAMA: We thank the participants for their ongoing collaboration. Piccolipiù: We acknowledge the working group and the families involved in the study. PRIDE Study: We thank the mothers and infants who continue to participate in this ongoing study as well as all the midwives, gynecologists, and general practitioners for their contributions to the data collection. Project Viva: We thank the mothers, children, and families for their ongoing participation. REPRO_PL: We particularly thank all the cohort participants for their collaboration. RHEA: We particularly thank all the cohort participants for their generous collaboration. Slovak PCB Study: We thank the study participants for their ongoing cooperation. STEPS: We are grateful to all the families who took part. SWS: We are grateful to the women of Southampton who gave their time to take part in the survey and to the research nurses and other staff who collected and processed the data.
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