Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study
Prenatal antibiotic exposure induces changes in infants' gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD. This was a p...
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| Veröffentlicht in: | PloS one 2019-08, Vol.14 (8), p.e0221921-e0221921 |
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| creator | Hamad, Amani F Alessi-Severini, Silvia Mahmud, Salaheddin M Brownell, Marni Kuo, I Fan |
| description | Prenatal antibiotic exposure induces changes in infants' gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD.
This was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort.
Of all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings' cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant.
Prenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant. |
| doi_str_mv | 10.1371/journal.pone.0221921 |
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This was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort.
Of all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings' cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant.
Prenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0221921</identifier><identifier>PMID: 31465485</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Analysis ; Anti-Bacterial Agents - adverse effects ; Antibiotics ; Autism ; Autism Spectrum Disorder - epidemiology ; Autism Spectrum Disorder - etiology ; Biology and Life Sciences ; Children ; Cohort analysis ; Complications and side effects ; Diagnosis ; Disorders ; Exposure ; Female ; Hazards ; Health care policy ; Health sciences ; Hospitals ; Humans ; Immunology ; Infants ; Infections ; Intestinal microflora ; Male ; Maternal Exposure - adverse effects ; Medicine ; Medicine and Health Sciences ; Microbiota ; Microbiota (Symbiotic organisms) ; Microorganisms ; Middle Aged ; Outcome and process assessment (Medical care) ; Patient outcomes ; Pediatrics ; People and Places ; Personal health ; Pervasive developmental disorders ; Pharmacy ; Population ; Population studies ; Population Surveillance ; Population-based studies ; Pregnancy ; Pregnant women ; Prenatal drug exposure ; Prenatal experience ; Prenatal Exposure Delayed Effects ; Primary care ; Proportional Hazards Models ; Public health ; Research and Analysis Methods ; Risk ; Risk Assessment ; Risk Factors ; Sensitivity and Specificity ; Siblings ; Social Sciences ; Statistical analysis ; Studies ; Young Adult</subject><ispartof>PloS one, 2019-08, Vol.14 (8), p.e0221921-e0221921</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Hamad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Hamad et al 2019 Hamad et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-97c0f1ce31b6e17dfc3a0dcc5b406f611d9b79d927a585589f17e67bd13110c63</citedby><cites>FETCH-LOGICAL-c758t-97c0f1ce31b6e17dfc3a0dcc5b406f611d9b79d927a585589f17e67bd13110c63</cites><orcidid>0000-0002-2660-2777</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715235/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715235/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31465485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rosenfeld, Cheryl S.</contributor><creatorcontrib>Hamad, Amani F</creatorcontrib><creatorcontrib>Alessi-Severini, Silvia</creatorcontrib><creatorcontrib>Mahmud, Salaheddin M</creatorcontrib><creatorcontrib>Brownell, Marni</creatorcontrib><creatorcontrib>Kuo, I Fan</creatorcontrib><title>Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Prenatal antibiotic exposure induces changes in infants' gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD.
This was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort.
Of all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings' cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant.
Prenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant.</description><subject>Adult</subject><subject>Analysis</subject><subject>Anti-Bacterial Agents - adverse effects</subject><subject>Antibiotics</subject><subject>Autism</subject><subject>Autism Spectrum Disorder - epidemiology</subject><subject>Autism Spectrum Disorder - etiology</subject><subject>Biology and Life Sciences</subject><subject>Children</subject><subject>Cohort analysis</subject><subject>Complications and side effects</subject><subject>Diagnosis</subject><subject>Disorders</subject><subject>Exposure</subject><subject>Female</subject><subject>Hazards</subject><subject>Health care policy</subject><subject>Health sciences</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunology</subject><subject>Infants</subject><subject>Infections</subject><subject>Intestinal microflora</subject><subject>Male</subject><subject>Maternal Exposure - adverse effects</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Microbiota</subject><subject>Microbiota (Symbiotic organisms)</subject><subject>Microorganisms</subject><subject>Middle Aged</subject><subject>Outcome and process assessment (Medical care)</subject><subject>Patient outcomes</subject><subject>Pediatrics</subject><subject>People and Places</subject><subject>Personal health</subject><subject>Pervasive developmental disorders</subject><subject>Pharmacy</subject><subject>Population</subject><subject>Population studies</subject><subject>Population Surveillance</subject><subject>Population-based studies</subject><subject>Pregnancy</subject><subject>Pregnant women</subject><subject>Prenatal drug exposure</subject><subject>Prenatal experience</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Primary care</subject><subject>Proportional Hazards Models</subject><subject>Public health</subject><subject>Research and Analysis Methods</subject><subject>Risk</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Sensitivity and Specificity</subject><subject>Siblings</subject><subject>Social Sciences</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Young 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One</addtitle><date>2019-08-29</date><risdate>2019</risdate><volume>14</volume><issue>8</issue><spage>e0221921</spage><epage>e0221921</epage><pages>e0221921-e0221921</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Prenatal antibiotic exposure induces changes in infants' gut microbiota composition and is suggested as a possible contributor in the development of autism spectrum disorders (ASD). In this study, we examined the association between prenatal antibiotic exposure and the risk of ASD.
This was a population-based cohort study utilizing the Manitoba Population Research Data Repository. The cohort included 214 834 children born in Manitoba, Canada between April 1, 1998 and March 31, 2016. Exposure was defined as having filled one or more antibiotic prescription during pregnancy. The outcome was autism spectrum disorder diagnosis. Multivariable Cox proportional hazards regression was used to estimate the risk of developing ASD in the overall cohort and in a sibling cohort.
Of all subjects, 80 750 (37.6%) were exposed to antibiotics prenatally. During follow-up, 2965 children received an ASD diagnosis. Compared to children who were not exposed to antibiotics prenatally, those who were exposed had a higher risk of ASD: (adjusted HR 1.10 [95% CI 1.01, 1.19]). The association was observed in those exposed to antibiotics in the second or third trimester (HR 1.11 [95% CI 1.01, 1.23] and 1.17 [95% CI 1.06, 1.30], respectively). In the siblings' cohort, ASD risk estimate remained unchanged (adjusted HR 1.08 [95% CI 0.90, 1.30], although it was not statistically significant.
Prenatal antibiotic exposure is associated with a small increase in the risk of ASD. Given the potential of residual confounding beyond what it was controlled through our study design and because of possible confounding by indication, such a small risk increase in the population is not expected to be clinically significant.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31465485</pmid><doi>10.1371/journal.pone.0221921</doi><tpages>e0221921</tpages><orcidid>https://orcid.org/0000-0002-2660-2777</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_2282685248 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Analysis Anti-Bacterial Agents - adverse effects Antibiotics Autism Autism Spectrum Disorder - epidemiology Autism Spectrum Disorder - etiology Biology and Life Sciences Children Cohort analysis Complications and side effects Diagnosis Disorders Exposure Female Hazards Health care policy Health sciences Hospitals Humans Immunology Infants Infections Intestinal microflora Male Maternal Exposure - adverse effects Medicine Medicine and Health Sciences Microbiota Microbiota (Symbiotic organisms) Microorganisms Middle Aged Outcome and process assessment (Medical care) Patient outcomes Pediatrics People and Places Personal health Pervasive developmental disorders Pharmacy Population Population studies Population Surveillance Population-based studies Pregnancy Pregnant women Prenatal drug exposure Prenatal experience Prenatal Exposure Delayed Effects Primary care Proportional Hazards Models Public health Research and Analysis Methods Risk Risk Assessment Risk Factors Sensitivity and Specificity Siblings Social Sciences Statistical analysis Studies Young Adult |
| title | Prenatal antibiotics exposure and the risk of autism spectrum disorders: A population-based cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T00%3A45%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prenatal%20antibiotics%20exposure%20and%20the%20risk%20of%20autism%20spectrum%20disorders:%20A%20population-based%20cohort%20study&rft.jtitle=PloS%20one&rft.au=Hamad,%20Amani%20F&rft.date=2019-08-29&rft.volume=14&rft.issue=8&rft.spage=e0221921&rft.epage=e0221921&rft.pages=e0221921-e0221921&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0221921&rft_dat=%3Cgale_plos_%3EA597815898%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2282685248&rft_id=info:pmid/31465485&rft_galeid=A597815898&rft_doaj_id=oai_doaj_org_article_4e0c5b8868ec4bcda3b5ba1411f59089&rfr_iscdi=true |