Anatomical, behavioral, and cognitive teratogenicity associated with valproic acid: a systematic review.

IF 3.4 3区医学 Q2 CLINICAL NEUROLOGY

CNS Spectrums Pub Date : 2024-12-27 DOI:10.1017/S1092852924002311

Kyle Valentino, Kayla M Teopiz, Angela T H Kwan, Gia Han Le, Sabrina Wong, Joshua D Rosenblat, Rodrigo B Mansur, Heidi K Y Lo, Roger S McIntyre

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引用次数: 0

Abstract

Background: Recent guidance from UK health authorities strongly cautions against the use of valproic acid (VPA) in persons under 55 because of reevaluated risk of teratogenicity.

Objective: To summarize the extant literature documenting VPA-associated anatomical, behavioral, and cognitive teratogenicity.

Method: Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, Web of Science, and Google Scholar were searched in accordance with PRISMA guidelines. Collected data covered study design, participant characteristics, anatomical, behavioral, or cognitive effects, and folic acid outcomes.

Results: 122 studies were identified meeting inclusion comprised of studies evaluating anatomical (n = 67), behavioral (n = 28), and cognitive (n = 47) teratogenicity. Twenty studies were identified reporting on the risk mitigation effects of folic acid supplementation. Prenatal VPA exposure is associated with anatomical teratogenicity including major congenital malformations (odds ratio [OR] 2.47-9.30; p < 0.005). Behavioral teratogenicity including autism (OR 1.70-4.38), impaired motor development (OR 7.0), and ADHD (OR 1.39) are also significantly associated with VPA exposure. VPA was associated with intellectual disability and low IQ (hazard ratio [HR] 2.4-4.48, verbal intelligence: Spearman's ρ = -0.436, respectively). Teratogenic effects were dose-dependent across all domains and were significant when compared with controls and other antiepileptic drugs (eg, carbamazepine, lamotrigine, and levetiracetam). Folic acid supplementation does not significantly reduce the hazard associated with VPA.

Conclusions: VPA is significantly associated with anatomical, behavioral, and cognitive teratogenicity. Folic acid supplementation does not abrogate the risk of teratogenicity associated with VPA exposure. Available evidence supports recommendations to reduce VPA exposure in women of reproductive age.

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来源期刊

CNS Spectrums 医学-精神病学

CiteScore

6.20

自引率

6.10%

发文量

239

审稿时长

>12 weeks

期刊介绍： CNS Spectrums covers all aspects of the clinical neurosciences, neurotherapeutics, and neuropsychopharmacology, particularly those pertinent to the clinician and clinical investigator. The journal features focused, in-depth reviews, perspectives, and original research articles. New therapeutics of all types in psychiatry, mental health, and neurology are emphasized, especially first in man studies, proof of concept studies, and translational basic neuroscience studies. Subject coverage spans the full spectrum of neuropsychiatry, focusing on those crossing traditional boundaries between neurology and psychiatry.