Arad Kodesh1,2, Stephen Z Levine1, Vahe Khachadourian3,4, Rayees Rahman5, Avner Schlessinger5, Paul F O'Reilly6, Jakob Grove7,8,9,10, Diana Schendel7,11, Joseph D Buxbaum3,4,12,13, Lisa Croen14, Abraham Reichenberg3,4,12,15, Sven Sandin3,4,16, Magdalena Janecka3,4,9,12,13. 1. Department of Community Mental Health, University of Haifa, Haifa, Israel. 2. Meuhedet Health Services, Tel Aviv, Israel. 3. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 4. Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 5. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 6. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 7. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. 8. iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark. 9. Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. 10. Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. 11. Section for Epidemiology, National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark. 12. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 13. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 14. Division of Research, Kaiser Permanente Northern California, Oakland, California, USA. 15. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 16. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND: Many studies have reported an increased risk of autism spectrum disorder (ASD) associated with some maternal diagnoses in pregnancy. However, such associations have not been studied systematically, accounting for comorbidity between maternal disorders. Therefore our aim was to comprehensively test the associations between maternal diagnoses around pregnancy and ASD risk in offspring. METHODS: This exploratory case-cohort study included children born in Israel from 1997 to 2008, and followed up until 2015. We used information on all ICD-9 codes received by their mothers during pregnancy and the preceding year. ASD risk associated with each of those conditions was calculated using Cox proportional hazards regression, adjusted for the confounders (birth year, maternal age, socioeconomic status and number of ICD-9 diagnoses during the exposure period). RESULTS: The analytic sample consisted of 80 187 individuals (1132 cases, 79 055 controls), with 822 unique ICD-9 codes recorded in their mothers. After extensive quality control, 22 maternal diagnoses were nominally significantly associated with offspring ASD, with 16 of those surviving subsequent filtering steps (permutation testing, multiple testing correction, multiple regression). Among those, we recorded an increased risk of ASD associated with metabolic [e.g. hypertension; HR = 2.74 (1.92-3.90), p = 2.43 × 10-8], genitourinary [e.g. non-inflammatory disorders of cervix; HR = 1.88 (1.38-2.57), p = 7.06 × 10-5] and psychiatric [depressive disorder; HR = 2.11 (1.32-3.35), p = 1.70 × 10-3] diagnoses. Meanwhile, mothers of children with ASD were less likely to attend prenatal care appointment [HR = 0.62 (0.54-0.71), p = 1.80 × 10-11]. CONCLUSIONS: Sixteen maternal diagnoses were associated with ASD in the offspring, after rigorous filtering of potential false-positive associations. Replication in other cohorts and further research to understand the mechanisms underlying the observed associations with ASD are warranted.
BACKGROUND: Many studies have reported an increased risk of autism spectrum disorder (ASD) associated with some maternal diagnoses in pregnancy. However, such associations have not been studied systematically, accounting for comorbidity between maternal disorders. Therefore our aim was to comprehensively test the associations between maternal diagnoses around pregnancy and ASD risk in offspring. METHODS: This exploratory case-cohort study included children born in Israel from 1997 to 2008, and followed up until 2015. We used information on all ICD-9 codes received by their mothers during pregnancy and the preceding year. ASD risk associated with each of those conditions was calculated using Cox proportional hazards regression, adjusted for the confounders (birth year, maternal age, socioeconomic status and number of ICD-9 diagnoses during the exposure period). RESULTS: The analytic sample consisted of 80 187 individuals (1132 cases, 79 055 controls), with 822 unique ICD-9 codes recorded in their mothers. After extensive quality control, 22 maternal diagnoses were nominally significantly associated with offspring ASD, with 16 of those surviving subsequent filtering steps (permutation testing, multiple testing correction, multiple regression). Among those, we recorded an increased risk of ASD associated with metabolic [e.g. hypertension; HR = 2.74 (1.92-3.90), p = 2.43 × 10-8], genitourinary [e.g. non-inflammatory disorders of cervix; HR = 1.88 (1.38-2.57), p = 7.06 × 10-5] and psychiatric [depressive disorder; HR = 2.11 (1.32-3.35), p = 1.70 × 10-3] diagnoses. Meanwhile, mothers of children with ASD were less likely to attend prenatal care appointment [HR = 0.62 (0.54-0.71), p = 1.80 × 10-11]. CONCLUSIONS: Sixteen maternal diagnoses were associated with ASD in the offspring, after rigorous filtering of potential false-positive associations. Replication in other cohorts and further research to understand the mechanisms underlying the observed associations with ASD are warranted.
Authors: Magdalena Janecka; Stefan N Hansen; Amirhossein Modabbernia; Heidi A Browne; Joseph D Buxbaum; Diana E Schendel; Abraham Reichenberg; Erik T Parner; Dorothy E Grice Journal: J Am Acad Child Adolesc Psychiatry Date: 2019-02-27 Impact factor: 8.829
Authors: M Delobel-Ayoub; E Saemundsen; M Gissler; A Ego; I Moilanen; H Ebeling; V Rafnsson; D Klapouszczak; E Thorsteinsson; K M Arnaldsdóttir; B Roge; C Arnaud; D Schendel Journal: J Autism Dev Disord Date: 2020-03
Authors: Hjördís O Atladóttir; Marianne G Pedersen; Poul Thorsen; Preben Bo Mortensen; Bent Deleuran; William W Eaton; Erik T Parner Journal: Pediatrics Date: 2009-07-05 Impact factor: 7.124