title: Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy.
abstract: BACKGROUND
  Both gastrointestinal microbiota composition and cesarean section have been linked to atopic manifestations. However, results are inconsistent, and the hypothesized intermediate role of the microbiota in the association between birth mode and atopic manifestations has not been studied yet.
  
  
  OBJECTIVE
  We sought to investigate the relationship between microbiota composition, mode and place of delivery, and atopic manifestations.
  
  
  METHODS
  The Child, Parent and Health: Lifestyle and Genetic Constitution Birth Cohort Study included data on birth characteristics, lifestyle factors, and atopic manifestations collected through repeated questionnaires from birth until age 7 years. Fecal samples were collected at age 1 month (n = 1176) to determine microbiota composition, and blood samples were collected at ages 1 (n = 921), 2 (n = 822), and 6 to 7 (n = 384) years to determine specific IgE levels.
  
  
  RESULTS
  Colonization by Clostridium difficile at age 1 month was associated with wheeze and eczema throughout the first 6 to 7 years of life and with asthma at age 6 to 7 years. Vaginal home delivery compared with vaginal hospital delivery was associated with a decreased risk of eczema, sensitization to food allergens, and asthma. After stratification for parental history of atopy, the decreased risk of sensitization to food allergens (adjusted odds ratio, 0.52; 95% CI, 0.35-0.77) and asthma (adjusted odds ratio, 0.47; 95% CI, 0.29-0.77) among vaginally home-born infants was only found for children with atopic parents. Mediation analysis showed that the effects of mode and place of delivery on atopic outcomes were mediated by C difficile colonization.
  
  
  CONCLUSIONS
  Mode and place of delivery affect the gastrointestinal microbiota composition, which subsequently influences the risk of atopic manifestations.
authors.affiliation: Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Frederika A
authors.initials: FA
authors.lastname: van Nimwegen
authors.forename: John
authors.initials: J
authors.lastname: Penders
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Stobberingh
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: Marjan
authors.initials: M
authors.lastname: Kerkhof
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Reijmerink
authors.forename: Edward
authors.initials: E
authors.lastname: Dompeling
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Monique
authors.initials: M
authors.lastname: Mommers
authors.forename: Carel
authors.initials: C
authors.lastname: Thijs
mesh_terms: D001249:Asthma / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000150:complications* / Q000453:epidemiology; D015331:Cohort Studies; D036861:Delivery, Obstetric / Q000009:adverse effects*; D005243:Feces / Q000382:microbiology; D005260:Female; D006761:Hospitals; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000382:microbiology*; D007223:Infant; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000382:microbiology*; D011247:Pregnancy; D011795:Surveys and Questionnaires