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<p>We examined whether specific congenital malformations (CM) detected at birth are associated with increased likelihood of autism spectrum disorder (ASD), by a case-control study nested within a 12-year birth cohort derived from the Israel National Birth Registry. The cohort included all registered ASD cases (n = 2099) and 1:1 age- and sex- matched controls. Overall, CM were more prevalent in the ASD group as compared with controls [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.29–2.38]. This association remained robust after adjusting for birth weight, parental age, parental ethnicity, and maternal immigration [adjusted OR (aOR) 1.61, 95% CI 1.14–2.29]. The most prevalent CM types among the ASD group were circulatory system (2.1 vs. 1.2% among controls) and urogenital organs (1.8 vs. 0.8%). The association between ASD and genital CM was limited to males and persisted in the adjusted models (aOR 2.24, 95% CI 1.16–4.34). In the stratified by sex analysis, a strong association between all non-genitourinary CM and ASD was found in females (aOR 3.47, 95% CI 1.13–10.65). In conclusion, CM, most notably genitourinary in males exclusively, and others (mostly circulatory) in females, are more prevalent in newborns later diagnosed with ASD, as compared with age- and sex-matched controls. These sex-specific CM might represent useful pre- and postnatal markers of ASD, and their presence in newborns at-risk of ASD might indicate earlier and more frequent neurodevelopmental assessments. Our findings might also guide future research of plausible genetic, epigenetic, and prenatal underpinnings of ASD.</p>

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The association between autism spectrum disorder and congenital malformations: a population-based nested case-control study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月15日

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  • Rony Cleper,
  • Ori Kapra,
  • Nadav Goldental,
  • Raz Gross

摘要

We examined whether specific congenital malformations (CM) detected at birth are associated with increased likelihood of autism spectrum disorder (ASD), by a case-control study nested within a 12-year birth cohort derived from the Israel National Birth Registry. The cohort included all registered ASD cases (n = 2099) and 1:1 age- and sex- matched controls. Overall, CM were more prevalent in the ASD group as compared with controls [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.29–2.38]. This association remained robust after adjusting for birth weight, parental age, parental ethnicity, and maternal immigration [adjusted OR (aOR) 1.61, 95% CI 1.14–2.29]. The most prevalent CM types among the ASD group were circulatory system (2.1 vs. 1.2% among controls) and urogenital organs (1.8 vs. 0.8%). The association between ASD and genital CM was limited to males and persisted in the adjusted models (aOR 2.24, 95% CI 1.16–4.34). In the stratified by sex analysis, a strong association between all non-genitourinary CM and ASD was found in females (aOR 3.47, 95% CI 1.13–10.65). In conclusion, CM, most notably genitourinary in males exclusively, and others (mostly circulatory) in females, are more prevalent in newborns later diagnosed with ASD, as compared with age- and sex-matched controls. These sex-specific CM might represent useful pre- and postnatal markers of ASD, and their presence in newborns at-risk of ASD might indicate earlier and more frequent neurodevelopmental assessments. Our findings might also guide future research of plausible genetic, epigenetic, and prenatal underpinnings of ASD.