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 journalArticlepeer-review

5 Scopus citations

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 languageEnglish
Pages (from-to)4076-4084
Number of pages9
JournalPsychological Medicine
Volume52
Issue number16
DOIs
StatePublished - 26 Dec 2022
Externally publishedYes

Bibliographical note

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

Keywords

  • Autism
  • diagnosis-wide
  • maternal health
  • prenatal effects

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