Gestational Exposure to Valproate and Autism Spectrum Disorder or Attention‐Deficit/Hyperactivity Disorder in Offspring: Systematic Review and Meta‐Analysis.
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| Title: | Gestational Exposure to Valproate and Autism Spectrum Disorder or Attention‐Deficit/Hyperactivity Disorder in Offspring: Systematic Review and Meta‐Analysis. |
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| Authors: | Andrade, Chittaranjan (AUTHOR), Varadharajan, Natarajan (AUTHOR), Bascarane, Sharmi (AUTHOR), Kale, Akshayee (AUTHOR), Gnanadhas, Jilisha (AUTHOR), Menon, Vikas (AUTHOR) |
| Source: | Acta Psychiatrica Scandinavica. Jun2025, Vol. 151 Issue 6, p668-679. 12p. |
| Subjects: | Autism spectrum disorders, Attention-deficit hyperactivity disorder, Valproic acid, Pregnancy outcomes, Prenatal exposure, Risk assessment |
| Abstract: | Introduction: Gestational exposure to valproate has been associated with a wide range of adverse pregnancy outcomes, including major congenital malformations in offspring. However, to date, no meta‐analysis has comprehensively examined the risk of autism spectrum disorder (ASD) and attention‐deficit/hyperactivity disorder (ADHD) in children gestationally exposed to valproate. Methods: We searched MEDLINE, Embase, and Scopus from inception until 15 May 2024 for relevant English‐language articles. Primary outcomes of interest were the risk of ASD and ADHD, two independent primary outcomes, in children exposed to valproate anytime during pregnancy relative to unexposed children. Secondary outcomes were trimester‐wise analyses of risk. We used a random effects model to pool the overall and trimester‐wise hazard ratios (HRs) and obtained 95% confidence intervals (CIs), separately for the risks of ASD and ADHD. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. Results: Eight cohort studies (pooled N = 6,033,300) met our search criteria. Anytime gestational exposure to valproate was associated with a large increase in the risk of ASD (adjusted HR [aHR], 3.10; 95% confidence interval [CI], 2.24–4.28; N = 1,841,198) and a modest increase in the risk of ADHD (aHR, 1.62; 95% CI, 1.30–2.01; N = 24,295). The findings in sensitivity analyses for both outcomes were generally consistent with those of the main analyses. Notably, anytime gestational exposure to high‐dose valproate (> 1.0 to 1.1 g/day) was associated with a substantially elevated risk of ASD (aHR, 6.32; 95% CI, 3.12–12.80, N = 1,719,825). Likewise, in monotherapy (aHR, 4.21; 95% CI, 2.97–5.95; N = 1,745,253) and discordant sibling pair (aHR, 6.42; 95% CI, 2.02–20.42; N = 1133) analyses, the risk of ASD was substantially elevated. Conclusion: Gestational exposure to valproate was associated with an increased risk of ASD and ADHD; the risks for ASD were greater at doses ≥ 1000 mg/day. These findings add to the literature that strongly discourages the use of valproate by women of childbearing age, especially during pregnancy. [ABSTRACT FROM AUTHOR] |
| Copyright of Acta Psychiatrica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 184868522 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Gestational Exposure to Valproate and Autism Spectrum Disorder or Attention‐Deficit/Hyperactivity Disorder in Offspring: Systematic Review and Meta‐Analysis. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Andrade%2C+Chittaranjan%22">Andrade, Chittaranjan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Varadharajan%2C+Natarajan%22">Varadharajan, Natarajan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bascarane%2C+Sharmi%22">Bascarane, Sharmi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kale%2C+Akshayee%22">Kale, Akshayee</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gnanadhas%2C+Jilisha%22">Gnanadhas, Jilisha</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Menon%2C+Vikas%22">Menon, Vikas</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Acta+Psychiatrica+Scandinavica%22">Acta Psychiatrica Scandinavica</searchLink>. Jun2025, Vol. 151 Issue 6, p668-679. 12p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Autism+spectrum+disorders%22">Autism spectrum disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Attention-deficit+hyperactivity+disorder%22">Attention-deficit hyperactivity disorder</searchLink><br /><searchLink fieldCode="DE" term="%22Valproic+acid%22">Valproic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Pregnancy+outcomes%22">Pregnancy outcomes</searchLink><br /><searchLink fieldCode="DE" term="%22Prenatal+exposure%22">Prenatal exposure</searchLink><br /><searchLink fieldCode="DE" term="%22Risk+assessment%22">Risk assessment</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Introduction: Gestational exposure to valproate has been associated with a wide range of adverse pregnancy outcomes, including major congenital malformations in offspring. However, to date, no meta‐analysis has comprehensively examined the risk of autism spectrum disorder (ASD) and attention‐deficit/hyperactivity disorder (ADHD) in children gestationally exposed to valproate. Methods: We searched MEDLINE, Embase, and Scopus from inception until 15 May 2024 for relevant English‐language articles. Primary outcomes of interest were the risk of ASD and ADHD, two independent primary outcomes, in children exposed to valproate anytime during pregnancy relative to unexposed children. Secondary outcomes were trimester‐wise analyses of risk. We used a random effects model to pool the overall and trimester‐wise hazard ratios (HRs) and obtained 95% confidence intervals (CIs), separately for the risks of ASD and ADHD. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. Results: Eight cohort studies (pooled N = 6,033,300) met our search criteria. Anytime gestational exposure to valproate was associated with a large increase in the risk of ASD (adjusted HR [aHR], 3.10; 95% confidence interval [CI], 2.24–4.28; N = 1,841,198) and a modest increase in the risk of ADHD (aHR, 1.62; 95% CI, 1.30–2.01; N = 24,295). The findings in sensitivity analyses for both outcomes were generally consistent with those of the main analyses. Notably, anytime gestational exposure to high‐dose valproate (> 1.0 to 1.1 g/day) was associated with a substantially elevated risk of ASD (aHR, 6.32; 95% CI, 3.12–12.80, N = 1,719,825). Likewise, in monotherapy (aHR, 4.21; 95% CI, 2.97–5.95; N = 1,745,253) and discordant sibling pair (aHR, 6.42; 95% CI, 2.02–20.42; N = 1133) analyses, the risk of ASD was substantially elevated. Conclusion: Gestational exposure to valproate was associated with an increased risk of ASD and ADHD; the risks for ASD were greater at doses ≥ 1000 mg/day. These findings add to the literature that strongly discourages the use of valproate by women of childbearing age, especially during pregnancy. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Acta Psychiatrica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=184868522 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1111/acps.13797 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 668 Subjects: – SubjectFull: Autism spectrum disorders Type: general – SubjectFull: Attention-deficit hyperactivity disorder Type: general – SubjectFull: Valproic acid Type: general – SubjectFull: Pregnancy outcomes Type: general – SubjectFull: Prenatal exposure Type: general – SubjectFull: Risk assessment Type: general Titles: – TitleFull: Gestational Exposure to Valproate and Autism Spectrum Disorder or Attention‐Deficit/Hyperactivity Disorder in Offspring: Systematic Review and Meta‐Analysis. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Andrade, Chittaranjan – PersonEntity: Name: NameFull: Varadharajan, Natarajan – PersonEntity: Name: NameFull: Bascarane, Sharmi – PersonEntity: Name: NameFull: Kale, Akshayee – PersonEntity: Name: NameFull: Gnanadhas, Jilisha – PersonEntity: Name: NameFull: Menon, Vikas IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 0001690X Numbering: – Type: volume Value: 151 – Type: issue Value: 6 Titles: – TitleFull: Acta Psychiatrica Scandinavica Type: main |
| ResultId | 1 |
