title: Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study.
abstract: BACKGROUND
  Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery.
  
  
  METHODS
  A Danish nationwide cohort study including all singletons born during 1997-2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes.
  
  
  RESULTS
  Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation.
  
  
  CONCLUSIONS
  Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section.
authors: Department of Gynecology and Obstetrics, Nordsjællands Hospital, University of Copenhagen, Hillerød, Denmark.
authors: Tine D
authors: http://orcid.org/0000-0001-5585-2153
authors: TD
authors: Clausen
authors: Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen OE, Denmark.
authors: Thomas
authors: T
authors: Bergholt
authors: Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen K, Denmark.|Laboratory MAP5, University Paris Descartes and CNRS, Sorbonne Paris Cité, Paris, France.
authors: Olivier
authors: O
authors: Bouaziz
authors: Department of Clinical Microbiology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors: Magnus
authors: M
authors: Arpi
authors: Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen K, Denmark.
authors: Frank
authors: F
authors: Eriksson
authors: Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors: Steen
authors: S
authors: Rasmussen
authors: Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen K, Denmark.
authors: Niels
authors: N
authors: Keiding
authors: Department of Gynecology and Obstetrics, Nordsjællands Hospital, University of Copenhagen, Hillerød, Denmark.
authors: Ellen C
authors: EC
authors: Løkkegaard
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002585:Cesarean Section / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D036861:Delivery, Obstetric / Q000009:adverse effects; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D016016:Proportional Hazards Models; D012042:Registries
chemical_list: D000900:Anti-Bacterial Agents