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Maternal health around pregnancy and autism risk: a diagnosis-wide, population-based study

Published online by Cambridge University Press:  26 March 2021

Arad Kodesh ,
Stephen Z. Levine ,
Vahe Khachadourian ,
Rayees Rahman ,
Avner Schlessinger ,
Paul F. O'Reilly ,
Jakob Grove ,
Diana Schendel ,
Joseph D. Buxbaum  and
Lisa Croen
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Arad Kodesh
Affiliation:
Department of Community Mental Health, University of Haifa, Haifa, Israel Meuhedet Health Services, Tel Aviv, Israel
Stephen Z. Levine
Affiliation:
Department of Community Mental Health, University of Haifa, Haifa, Israel
Vahe Khachadourian
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Rayees Rahman
Affiliation:
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Avner Schlessinger
Affiliation:
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Paul F. O'Reilly
Affiliation:
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Jakob Grove
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark Department of Biomedicine – Human Genetics, Aarhus University, Aarhus, Denmark Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
Diana Schendel
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark Section for Epidemiology, National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
Joseph D. Buxbaum
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Lisa Croen
Affiliation:
Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
Abraham Reichenberg
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Sven Sandin
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Magdalena Janecka*
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, New York, USA Department of Biomedicine – Human Genetics, Aarhus University, Aarhus, Denmark Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
*
Author for correspondence: Magdalena Janecka, E-mail: [email protected]
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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.

Keywords

Autismdiagnosis-widematernal healthprenatal effects
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 16 , December 2022 , pp. 4076 - 4084
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Acosta, O., Ramirez, V., Powell, L., Jansson, T., Lager, S., Gaccioli, F., … Jansson, T. (2015). Increased glucose and placental GLUT-1 in large infants of obese nondiabetic mothers. American Journal of Obstetrics and Gynecology, 212(2), 227e1–227e7.CrossRefGoogle ScholarPubMed
Atladóttir, H. Ó., Pedersen, M. G., Thorsen, P., Mortensen, P. B., Deleuran, B., Eaton, W. W., & Parner, E. T. (2009). Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics, 124(2), 687–694.CrossRefGoogle ScholarPubMed
Atladóttir, H. Ó., Thorsen, P., Østergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., & Parner, E. T. (2010). Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders, 40(12), 1423–1430. https://doi.org/10.1007/s10803-010-1006-y.CrossRefGoogle ScholarPubMed
Bai, D., Hon, B., Yip, K., Windham, G. C., Sourander, A., Francis, R., … Sandin, S. (2019). Association of genetic and environmental factors with autism in a 5-country cohort. JAMA Psychiatry, 76(10), 1035–1043. https://doi.org/10.1001/jamapsychiatry.2019.1411.CrossRefGoogle Scholar
Baio, J., Wiggins, L., Christensen, D., Maenner, M., Daniels, J., Warren, Z., … Dowling, N. (2018). Prevalence of autism spectrum disorder among children aged 8 years – autism and developmental disabilities monitoring network, 11 sites, United States, 2014. MMWR Surveillance Summaries, 67(6), 1–23.CrossRefGoogle Scholar
Barlow, W. (1994). Robust variance estimation for the case-cohort design. Biometrics, 50(4), 1064–1072.CrossRefGoogle ScholarPubMed
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society, 157(1), 289–300.Google Scholar
Castanha, P. M. S., Braga, C., Cordeiro, M. T., Souza, A. I. Jr, C. D., S., Martelli, C. M. T., … Marques, E. T. A. (2016). Placental transfer of dengue virus (DENV) – specific antibodies and kinetics of DENV infection – enhancing activity in Brazilian infants. The Journal of Infectious Diseases, 214, 265–272. https://doi.org/10.1093/infdis/jiw143.CrossRefGoogle ScholarPubMed
Chan, S. Y., Vasilopoulou, E., & Kilby, M. D. (2009). The role of the placenta in thyroid hormone delivery to the fetus. Nature Endocrinology, 5, 45–54.Google Scholar
Croen, L., Grether, J., Yoshida, C., Odouli, R., & Van de Water, J. (2005). Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders. Archives of Pediatrics & Adolescent Medicine, 159, 151–157.CrossRefGoogle ScholarPubMed
Dancis, J., Jansen, V., & Levitz, M. (1980). Placental transfer of steroids : Effect of binding to serum albumin and to placenta. American Physiological Society, 7, 208–213.Google Scholar
Davidovitch, M., Hemo, B., Manning-Courtney, P., & Fombonne, E. (2013). Prevalence and incidence of autism spectrum disorder in an Israeli population. Journal of Autism and Developmental Disorders, 43(4), 785–793. https://doi.org/10.1007/s10803-012-1611-z.CrossRefGoogle Scholar
Delobel-Ayoub, M., Saemundsen, E., Ego, A., Moilanen, I., Ebeling, H., Rafnsson, V., … Schendel, D. (2020). Prevalence of autism spectrum disorder in 7–9-year-old children in Denmark, Finland, France and Iceland: A population-based registries approach within the ASDEU project. Journal of Autism and Developmental Disorders, 50, 949–959.CrossRefGoogle ScholarPubMed
Demographic Characteristics of the Population in Localities and Statistical Areas. (1995) Jerusalem: State of Israel, Central Bureau of Statistics.Google Scholar
Gardener, H., Spiegelman, D., & Buka, S. L. (2009). Prenatal risk factors for autism: Comprehensive meta-analysis. The British Journal of Psychiatry : The Journal of Mental Science, 195(1), 7–14. https://doi.org/10.1192/bjp.bp.108.051672.CrossRefGoogle ScholarPubMed
Grambsch, P., & Therneau, T. (1994). Proportional hazard tests and diagnostics based on weight residuals. Biometrika, 81(3), 515–526.CrossRefGoogle Scholar
Greenland, S., Mansournia, M. A., & Altman, D. G. (2016). Sparse data bias: A problem hiding in plain sight. BMJ (Online), 353, 1–6. https://doi.org/10.1136/bmj.i1981.Google Scholar
ICD10Data. (2021). Convert ICD-9-CM codes to ICD-10-CM/PCS, or convert ICD-10-CM/PCS codes to ICD-9-CM.Google Scholar
Janecka, M., Hansen, S. N., Modabbernia, A., Browne, H. A., Buxbaum, J. D., Schendel, D. E., … Grice, D. E. (2019). Parental age and differential estimates of risk for neuropsychiatric disorders: Findings from the Danish birth cohort. Journal of American Academy of Child Psychiatry. https://doi.org/https://doi.org/10.1016/j.jaac.2018.09.447.CrossRefGoogle ScholarPubMed
Janecka, M., Kodesh, A., Levine, S. Z., Lusskin, S. I., Viktorin, A., Rahman, R., … Reichenberg, A. (2018). Association of autism spectrum disorder with prenatal exposure to medication affecting neurotransmitter systems. JAMA Psychiatry, 10029(12), 1217–1224. https://doi.org/10.1001/jamapsychiatry.2018.2728.CrossRefGoogle Scholar
Kohler, P., & Farr, R. (1966). Placental IgG transport. Nature, 210(5040), 1070–1071.CrossRefGoogle ScholarPubMed
Levine, S. Z., Kodesh, A., Viktorin, A., Smith, L., Uher, R., Reichenberg, A., & Sandin, S. (2018). Association of maternal use of folic acid and multivitamin supplements in the periods before and during pregnancy with the risk of autism spectrum disorder in offspring. JAMA Psychiatry, 75(2), 176–184. https://doi.org/10.1001/jamapsychiatry.2017.4050.CrossRefGoogle ScholarPubMed
Ludbrook, J., & Dudley, H. (1998). Why permutation tests are superior to t and F tests in biomedical research. American Statistician, 52(2), 127–132. https://doi.org/10.1080/00031305.1998.10480551.Google Scholar
Mahadevan, U., Wolf, D. C., Dubinsky, M., Cortot, A., Lee, S., Siegel, C. A., … Abreu, M. (2013). Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clinical Gastroenterology and Hepatology, 11(3), 286–292.CrossRefGoogle ScholarPubMed
Mannion, A., & Leader, G. (2013). Comorbidity in autism spectrum disorder: A literature review. Research in Autism Spectrum Disorders, 7(12), 1595–1616. https://doi.org/10.1016/j.rasd.2013.09.006.CrossRefGoogle Scholar
Palmeira, P., Quinello, C., Ana, L., Zago, A., & Carneiro-sampaio, M. (2012). IgG placental transfer in healthy and pathological pregnancies. Clinical and Developmental Immunology, 2012, 1–13. https://doi.org/10.1155/2012/985646.CrossRefGoogle ScholarPubMed
Peduzzi, P., Concato, J., Kemper, E., Halford, T. R., & Feinstein, A. R. (1996). A simulation study of the number of events per variable recommended in multivariable regression analyses. Journal of Clinical Epidemiology, 49(12), 1373–1379. https://doi.org/10.1016/0197-2456(93)90084-q.CrossRefGoogle Scholar
Rahman, R., Kodesh, A., Levine, S. Z., Sandin, S., Reichenberg, A., & Schlessinger, A. (2020). Identification of newborns at risk for autism using electronic medical records and machine learning. European Psychiatry, 63(1), e22. https://doi.org/10.1192/j.eurpsy.2020.17.CrossRefGoogle ScholarPubMed
Rai, D., Lee, B. K., Dalman, C., Golding, J., Lewis, G., & Magnusson, C. (2013). Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: Population based case-control study. BMJ (Clinical Research Ed.), 346(April), f2059. https://doi.org/10.1136/bmj.f2059.Google ScholarPubMed
Razaz, N., Tomson, T., Wikström, A. K., & Cnattingius, S. (2017). Association between pregnancy and perinatal outcomes among women with epilepsy. JAMA Neurology, 74(8), 983–991. https://doi.org/10.1001/jamaneurol.2017.1310.CrossRefGoogle ScholarPubMed
R Core Team. (2014). R: A language and environment for statistical computing. R Foundation for Statistical Computing. http://www.r-project.org/.Google Scholar
Rutter, M. (2005). Incidence of autism spectrum disorders: Changes over time and their meaning. Acta Paediatrica, International Journal of Paediatrics, 94(1), 2–15. https://doi.org/10.1080/08035250410023124.CrossRefGoogle ScholarPubMed
Sandin, S., Hultman, C. M., Kolevzon, A., Gross, R., MacCabe, J. H., & Reichenberg, A. (2012). Advancing maternal age is associated with increasing risk for autism: A review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 51(5), 477–486.e1. https://doi.org/10.1016/j.jaac.2012.02.018.CrossRefGoogle ScholarPubMed
Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Larsson, H., Hultman, C. M., & Reichenberg, A. (2014). The familial risk of autism. JAMA : The Journal of the American Medical Association, 311(17), 1770–1777. https://doi.org/10.1001/jama.2014.4144.CrossRefGoogle ScholarPubMed
Therneau, T. M., & Li, H. (1999). Computing the Cox model for case cohort designs. Lifetime Data Analysis, 5(2), 99–112. https://doi.org/10.1023/A:1009691327335.CrossRefGoogle ScholarPubMed
Viktorin, A., Uher, R., Reichenberg, A., Levine, S. Z., & Sandin, S. (2017). Autism risk following antidepressant medication during pregnancy. Psychological Medicine, 47(16), 2787–2796. https://doi.org/10.1017/S0033291717001301.CrossRefGoogle ScholarPubMed
Walker, N., Filis, P., Shaughnessy, P. J. O., Bellingham, M., & Fowler, P. A. (2019). Nutrient transporter expression in both the placenta and fetal liver are affected by maternal smoking. Placenta, 78(September 2018), 10–17. https://doi.org/10.1016/j.placenta.2019.02.010.CrossRefGoogle ScholarPubMed
Wiggins, L. D., Baio, J., & Rice, C. (2006). Examination of the time between first evaluation and first autism spectrum diagnosis in a population-based sample. Journal of Developmental and Behavioral Pediatrics, 27(2), 79–87. https://doi.org/10.1097/00004703-200604002-00005.CrossRefGoogle Scholar
Xiang, A. H., Wang, X., Martinez, M. P., Walthall, J. C., Curry, E. S., Page, K., … Getahun, D. (2019). Association of maternal diabetes with autism in offspring. JAMA, 91101(14), 1425–1434. https://doi.org/10.1001/jama.2015.2707.Google Scholar
Zhang, Z. (2016). Multiple imputation with multivariate imputation by chained equation (MICE) package. Annals of Translational Medicine, 4(2), 30.Google ScholarPubMed
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