title: Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children.
abstract: BACKGROUND
  Children born preterm or with a small size for gestational age are at increased risk for childhood asthma.
  
  
  OBJECTIVE
  We sought to assess the hypothesis that these associations are explained by reduced airway patency.
  
  
  METHODS
  We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma.
  
  
  RESULTS
  Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma.
  
  
  CONCLUSIONS
  Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Herman T
authors.initials: HT
authors.lastname: den Dekker
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Agnes M M
authors.initials: AMM
authors.lastname: Sonnenschein-van der Voort
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Johan C
authors.initials: JC
authors.lastname: de Jongste
authors.affiliation: EPAR, UMR-S 707 INSERM Paris, France; EPAR, UMR-S 707, Université Pierre et Marie Curie Paris, France.
authors.forename: Isabella
authors.initials: I
authors.lastname: Anessi-Maesano
authors.affiliation: David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, United Kingdom; Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: S Hasan
authors.initials: SH
authors.lastname: Arshad
authors.affiliation: Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Barros
authors.affiliation: Division of Child Health, Department of Infection, Immunity & Inflammation, University of Leicester and Institute for Lung Health, Leicester, United Kingdom.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Beardsmore
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
authors.affiliation: Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal.
authors.forename: Sofia Correia
authors.initials: SC
authors.lastname: Phar
authors.affiliation: Public Health Nutrition Research Group, University of Aberdeen, Aberdeen, United Kingdom; Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Leone
authors.initials: L
authors.lastname: Craig
authors.affiliation: Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Devereux
authors.affiliation: Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C Kors
authors.initials: CK
authors.lastname: van der Ent
authors.affiliation: Faculty of Nursing and Chiropody, Valencia, Spain; FISABIO, Valencia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Esplugues
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Fantini
authors.affiliation: Helmholtz Zentrum München, Institute of Epidemiology I, Neuherberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Flexeder
authors.affiliation: University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Frey
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Forastiere
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gehring
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gori
authors.affiliation: Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anne C
authors.initials: AC
authors.lastname: van der Gugten
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: A John
authors.initials: AJ
authors.lastname: Henderson
authors.affiliation: CESP Inserm, UMRS 1018, Team 10, Villejuif, France; Université Paris-Sud, UMRS 1018 Team 10, Villejuif, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Heude
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Public Health Division of Gipuzkoa, San Sebastian, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ibarluzea
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Inskip
authors.affiliation: Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany; Institute for Clinical Epidemiology and Biometry, University of Würzburg, Wurzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Keil
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; National School of Public Health, Athens, Greece; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Eskil
authors.initials: E
authors.lastname: Kreiner-Møller
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Kuehni
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charité University Medical Centre, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lau
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and Sach's Children Hospital, Stockholm, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: Mélen
authors.affiliation: Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Mommers
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Morales
authors.affiliation: Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Penders
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Katy C
authors.initials: KC
authors.lastname: Pike
authors.affiliation: Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Porta
authors.affiliation: Department of Pediatrics, Division of Neonatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Irwin K
authors.initials: IK
authors.lastname: Reiss
authors.affiliation: David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, United Kingdom; Faculty of Medicine, University of Southampton, Southampton, United Kingdom; NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Roberts
authors.affiliation: University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland; Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and Sach's Children Hospital, Stockholm, Switzerland.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Schultz
authors.affiliation: Helmholtz Zentrum München, Institute of Epidemiology I, Neuherberg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
authors.affiliation: IB-SALUT, Area de Salut de Menorca, Balearic Islands, Spain.
authors.forename: Matias
authors.initials: M
authors.lastname: Torrent
authors.affiliation: Department of Social Medicine, School of Medicine, University of Crete, Crete, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Vassilaki
authors.affiliation: Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Alet H
authors.initials: AH
authors.lastname: Wijga
authors.affiliation: Nuestra Señora de la Antigua Hospital, OSAKIDETZA Basque Health Service, San Sebastian, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Zabaleta
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VWV
authors.lastname: Jaddoe
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Pediatrics, Division of Neonatology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: l.duijts@erasmusmc.nl.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Duijts
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology; D002648:Child; D002657:Child Development / Q000502:physiology*; D002675:Child, Preschool; D005541:Forced Expiratory Volume; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development* / Q000502:physiology; D007235:Infant, Premature, Diseases / Q000209:etiology* / Q000503:physiopathology; D007236:Infant, Small for Gestational Age / Q000254:growth & development* / Q000502:physiology; D008168:Lung / Q000503:physiopathology*; D015233:Models, Statistical; D012307:Risk Factors; D014797:Vital Capacity; D015430:Weight Gain / Q000502:physiology
keywords: Preterm birth; asthma; children; infant growth; low birth weight; lung function; meta-analysis