Relation Between Infant Microbiota and Autism?: Results from a National Cohort Sibling Design Study
| Autor: | Tine D. Clausen, Lars Vedel Kessing, Steen Rasmussen, Anja Pinborg, Thomas Bergholt, Paul Bryde Axelsson, Niels Keiding, Anne Helby Petersen, Ida Hageman, Ellen Løkkegaard |
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| Rok vydání: | 2018 |
| Předmět: |
Research design
Male Pediatrics medicine.medical_specialty Adolescent Epidemiology Denmark 01 natural sciences Cohort Studies 010104 statistics & probability 03 medical and health sciences 0302 clinical medicine Pregnancy medicine Humans 030212 general & internal medicine Prospective Studies 0101 mathematics Autistic Disorder Prospective cohort study Child Proportional Hazards Models Proportional hazards model business.industry Cesarean Section Microbiota Siblings Hazard ratio Infant Newborn Infant medicine.disease Confidence interval Anti-Bacterial Agents Research Design Child Preschool Prenatal Exposure Delayed Effects Autism Population study Female business Cohort study |
| Zdroj: | Epidemiology (Cambridge, Mass.). 30(1) |
| ISSN: | 1531-5487 |
| Popis: | Background Hypotheses concerning adverse effects of changes in microbiota have received much recent attention, but unobserved confounding makes them difficult to test. We investigated whether surrogate markers for potential adverse microbiota change in infancy affected autism risk, addressing unobserved confounding using a sibling study design. Methods This is a population-based, prospective cohort study including all singleton live births in Denmark from 1997 to 2010. The exposure variables were cesarean delivery and antibiotic use in the first 2 years of life. The outcome was a subsequent autism diagnosis. We used the between- and within-sibling model and compared it with sibling-stratified Cox models and simpler standard Cox models that ignored sibship. Results Of our study population including 671,606 children, who were followed for up to 15 years (7,341,133 person-years), 72% received antibiotics, 17.5% were delivered by cesarean, and 1.2% (8,267) developed autism. The standard Cox models predicted that both cesarean (compared with vaginal) delivery and antibiotics increased the risk of autism. In the sibling-stratified Cox model, only broader spectrum antibiotics were associated with increased risk of autism: hazard ratio (HR) = 1.16 (95% confidence interval = 1.01, 1.36). The between-within model estimated no exposure effects: intrapartum cesarean HR = 1.06 (0.89, 1.26); prelabor cesarean HR = 0.97 (0.83, 1.15); exclusively penicillin HR = 1.05 (0.93, 1.18); and broader spectrum antibiotics HR = 1.05 (0.95, 1.16). Conclusions The between-within model rendered more precise estimates than sibling-stratified Cox models, and we believe that it also provided more valid estimates. Results from these preferred models do not support a causal relation between antibiotic treatment during infancy, cesarean delivery, and autism. See video abstract at, http://links.lww.com/EDE/B432. |
| Databáze: | OpenAIRE |
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