Anna Sara Oberg1, Brian M D'Onofrio2, Martin E Rickert2, Sonia Hernandez-Diaz3, Jeffrey L Ecker4, Catarina Almqvist5, Henrik Larsson6, Paul Lichtenstein6, Brian T Bateman7. 1. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 2. Department of Psychological and Brain Sciences, Indiana University, Bloomington. 3. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 4. Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston. 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden5Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 7. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts7Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Abstract
IMPORTANCE: Induction of labor is a frequently performed obstetrical intervention. It would thus be of great concern if reported associations between labor induction and offspring risk of autism spectrum disorders (ASD) reflected causal influence. OBJECTIVE: To assess the associations of labor induction with ASD, comparing differentially exposed relatives (siblings and cousins discordant for induction). DESIGN, SETTING, AND PARTICIPANTS: Follow-up of all live births in Sweden between 1992 and 2005, defined in the Medical Birth Register. The register was linked to population registers of familial relations, inpatient and outpatient visits, and education records. Diagnoses of ASD were from 2001 through 2013, and data were analyzed in the 2015-2016 year. EXPOSURES: Induction of labor. MAIN OUTCOMES AND MEASURES: Autism spectrum disorders identified by diagnoses from inpatient and outpatient records between 2001 and 2013. Hazard ratios (HRs) quantified the association between labor induction and offspring ASD. In addition to considering a wide range of measured confounders, comparison of exposure-discordant births to the same woman allowed additional control for all unmeasured factors shared by siblings. RESULTS: The full cohort included 1 362 950 births, of which 22 077 offspring (1.6%) were diagnosed with ASD by ages 8 years through 21 years. In conventional models of the full cohort, associations between labor induction and offspring ASD were attenuated but remained statistically significant after adjustment for measured potential confounders (HR, 1.19; 95% CI, 1.13-1.24). When comparison was made within siblings whose births were discordant with respect to induction, thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD (HR, 0.99; 95% CI, 0.88-1.10). CONCLUSIONS AND RELEVANCE: In this nationwide sample of live births we observed no association between induction of labor and offspring ASD within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor.
IMPORTANCE: Induction of labor is a frequently performed obstetrical intervention. It would thus be of great concern if reported associations between labor induction and offspring risk of autism spectrum disorders (ASD) reflected causal influence. OBJECTIVE: To assess the associations of labor induction with ASD, comparing differentially exposed relatives (siblings and cousins discordant for induction). DESIGN, SETTING, AND PARTICIPANTS: Follow-up of all live births in Sweden between 1992 and 2005, defined in the Medical Birth Register. The register was linked to population registers of familial relations, inpatient and outpatient visits, and education records. Diagnoses of ASD were from 2001 through 2013, and data were analyzed in the 2015-2016 year. EXPOSURES: Induction of labor. MAIN OUTCOMES AND MEASURES: Autism spectrum disorders identified by diagnoses from inpatient and outpatient records between 2001 and 2013. Hazard ratios (HRs) quantified the association between labor induction and offspring ASD. In addition to considering a wide range of measured confounders, comparison of exposure-discordant births to the same woman allowed additional control for all unmeasured factors shared by siblings. RESULTS: The full cohort included 1 362 950 births, of which 22 077 offspring (1.6%) were diagnosed with ASD by ages 8 years through 21 years. In conventional models of the full cohort, associations between labor induction and offspring ASD were attenuated but remained statistically significant after adjustment for measured potential confounders (HR, 1.19; 95% CI, 1.13-1.24). When comparison was made within siblings whose births were discordant with respect to induction, thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD (HR, 0.99; 95% CI, 0.88-1.10). CONCLUSIONS AND RELEVANCE: In this nationwide sample of live births we observed no association between induction of labor and offspring ASD within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor.
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