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

Arad Kodesh; Stephen Z. Levine; Vahe Khachadourian; Rayees Rahman; Avner Schlessinger; Paul F. O'Reilly; Jakob Grove; Diana Schendel; Joseph D. Buxbaum; Lisa Croen; Abraham Reichenberg; Sven Sandin; Magdalena Janecka

doi:10.1017/S0033291721001021

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

Arad Kodesh, Stephen Z. Levine, Vahe Khachadourian, Rayees Rahman, Avner Schlessinger, Paul F. O'Reilly, Jakob Grove, Diana Schendel, Joseph D. Buxbaum, Lisa Croen, Abraham Reichenberg, Sven Sandin, Magdalena Janecka

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	4076-4084
Number of pages	9
Journal	Psychological Medicine
Volume	52
Issue number	16
Early online date	26 Mar 2021
DOIs	https://doi.org/10.1017/S0033291721001021
State	Published - 26 Dec 2022

Bibliographical note

Funding Information:
This work was supported in part by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, and the National Institute of Neurological Disorders and Stroke (Dr Reichenberg, Dr Kodesh, Dr Levine [grant number HD 073978]); by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Dr Reichenberg, Dr Sandin, Dr Schendel, Dr Buxbaum [grant number HD098883]); by a grant from the National Institute of Mental Health (Dr Janecka, Dr Reichenberg, Dr Sandin, Dr Schendel, Dr Grove, Dr Croen [grant number MH124817]); and by T32 award from the National Institute of Mental Health to Dr Khachadourian [grant number MH122394]. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Publisher Copyright:
© The Author(s), 2021.

Keywords

Autism
diagnosis-wide
maternal health
prenatal effects

ASJC Scopus subject areas

Applied Psychology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1017/S0033291721001021

Cite this

Kodesh, A., Levine, S. Z., Khachadourian, V., Rahman, R., Schlessinger, A., O'Reilly, P. F., Grove, J., Schendel, D., Buxbaum, J. D., Croen, L., Reichenberg, A., Sandin, S., & Janecka, M. (2022). Maternal health around pregnancy and autism risk: A diagnosis-wide, population-based study. Psychological Medicine, 52(16), 4076-4084. https://doi.org/10.1017/S0033291721001021

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title = "Maternal health around pregnancy and autism risk: A diagnosis-wide, population-based study",

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 = "Autism, diagnosis-wide, maternal health, prenatal effects",

author = "Arad Kodesh and Levine, {Stephen Z.} and Vahe Khachadourian and Rayees Rahman and Avner Schlessinger and O'Reilly, {Paul F.} and Jakob Grove and Diana Schendel and Buxbaum, {Joseph D.} and Lisa Croen and Abraham Reichenberg and Sven Sandin and Magdalena Janecka",

note = "Funding Information: This work was supported in part by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, and the National Institute of Neurological Disorders and Stroke (Dr Reichenberg, Dr Kodesh, Dr Levine [grant number HD 073978]); by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Dr Reichenberg, Dr Sandin, Dr Schendel, Dr Buxbaum [grant number HD098883]); by a grant from the National Institute of Mental Health (Dr Janecka, Dr Reichenberg, Dr Sandin, Dr Schendel, Dr Grove, Dr Croen [grant number MH124817]); and by T32 award from the National Institute of Mental Health to Dr Khachadourian [grant number MH122394]. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} The Author(s), 2021.",

year = "2022",

month = dec,

day = "26",

doi = "10.1017/S0033291721001021",

language = "English",

volume = "52",

pages = "4076--4084",

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TY - JOUR

T1 - Maternal health around pregnancy and autism risk

T2 - A diagnosis-wide, population-based study

AU - Kodesh, Arad

AU - Levine, Stephen Z.

AU - Khachadourian, Vahe

AU - Rahman, Rayees

AU - Schlessinger, Avner

AU - O'Reilly, Paul F.

AU - Grove, Jakob

AU - Schendel, Diana

AU - Buxbaum, Joseph D.

AU - Croen, Lisa

AU - Reichenberg, Abraham

AU - Sandin, Sven

AU - Janecka, Magdalena

N1 - Funding Information: This work was supported in part by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, and the National Institute of Neurological Disorders and Stroke (Dr Reichenberg, Dr Kodesh, Dr Levine [grant number HD 073978]); by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Dr Reichenberg, Dr Sandin, Dr Schendel, Dr Buxbaum [grant number HD098883]); by a grant from the National Institute of Mental Health (Dr Janecka, Dr Reichenberg, Dr Sandin, Dr Schendel, Dr Grove, Dr Croen [grant number MH124817]); and by T32 award from the National Institute of Mental Health to Dr Khachadourian [grant number MH122394]. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © The Author(s), 2021.

PY - 2022/12/26

Y1 - 2022/12/26

N2 - 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.

AB - 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.

KW - Autism

KW - diagnosis-wide

KW - maternal health

KW - prenatal effects

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U2 - 10.1017/S0033291721001021

DO - 10.1017/S0033291721001021

M3 - Article

AN - SCOPUS:85103337864

SN - 0033-2917

VL - 52

SP - 4076

EP - 4084

JO - Psychological Medicine

JF - Psychological Medicine

IS - 16

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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