Antiepileptic medication, together with valproic acid, lamotrigine, and gabapentin, are used for the remedy of temper and anxiousness signs throughout completely different psychiatric issues. We’ve knowledge to point that prenatal publicity to some AEDs, particularly valproic acid, not solely will increase danger for main malformations however is related to an elevated danger for hostile neurodevelopmental outcomes. A systematic evaluate revealed in Neurology examines research assessing neurodevelopmental outcomes in kids prenatally uncovered to valproic acid and different AEDs. On this evaluation, knowledge from a complete of 43 research have been included.
Valproic Acid (Depakote)
Prenatal publicity to valproic acid was related to a 2- to 4-fold elevated danger of autism spectrum dysfunction (ASD), a 2- to 5-fold elevated danger of mental incapacity (ID), a 1.5-fold elevated danger of ADHD, a 2- to 4-fold larger danger of prognosis of emotional and behavioral issues, and poor adaptive functioning in comparison with offspring uncovered to different AEDs and unexposed controls.
The danger of hostile neurodevelopmental outcomes seems to be dose-dependent, with worse outcomes seen at doses of 900 mg per day or better; nevertheless, some research have reported worse neurodevelopmental outcomes with imply every day doses as little as 600 to 750 mg.
Carbamazepine (Tegretol)
Throughout three cohort research, carbamazepine-exposed offspring had the next prevalence (12%–14%) of behavioral regulation issues in contrast with unexposed kids, characterised by aggression and hyperactivity. Findings of mental incapacity have been inconsistent.
Topiramate (Topamax)
Much less info is out there relating to neurodevelopmental outcomes in kids with prenatal publicity to topiramate. Of the ten research that included on this evaluate, 5 contained samples of lower than 10 topiramate-exposed offspring.
That stated, there’s a rising physique of proof indicating that prenatal publicity to topiramate could also be related to worse neurodevelopmental outcomes. A population-based research together with 247 topiramate-exposed kids discovered a 2-fold elevated danger of ASD diagnoses and a 3.5-fold elevated danger of ID amongst topiramate-exposed offspring in contrast with unexposed offspring, notably in kids uncovered to doses above 100 mg every day.
One other latest population-based research of 290 topiramate-exposed offspring discovered a 2.38-fold elevated danger of ADHD in contrast with unexposed offspring.
Lamotrigine (Lamictal)
In comparison with unexposed offspring, lamotrigine-exposed offspring show comparable neurodevelopmental functioning. Potential cohort and population-based research have discovered no elevated danger of ASD diagnoses throughout samples together with over 15,000 exposures.
Not one of the 13 included research discovered proof of a dose-response relationship between lamotrigine and hostile neurodevelopmental outcomes.
Different Antiepileptic Medication
Proof for the remaining AEDs, together with gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is missing.
Scientific Implications
The present systematic evaluate confirms earlier research indicating worse neurodevelopmental outcomes associated to prenatal publicity to valproic acid, together with a 2- to 4-fold elevated danger of ASD, a 2- to 5-fold elevated danger of mental incapacity (ID), and a 2- to 4-fold larger danger of emotional and behavioral issues. This discovering, paired with the excessive danger of main malformations related to valproic acid, signifies that valproic acid must be prevented in girls throughout being pregnant. And since half of all pregnancies are unplanned, these findings help the avoidance of valproic acid in all girls of reproductive age.
There’s presently insufficient info on long-term neurodevelopmental outcomes in kids uncovered to different AEDs, corresponding to gabapentin and pregabalin. There’s, nevertheless, a rising literature to point that publicity to topiramate could also be related to worse neurodevelopmental outcomes, with one research exhibiting a 2-fold elevated danger of ASD and and a 3.5-fold elevated danger of mental incapacity. These research point out that topiramate could carry comparable long-term dangers to valproic acid. As well as, it’s regarding that hostile outcomes have been noticed at a comparatively low dose of topiramate (100 mg).
This systematic evaluate helps the reproductive security of lamotrigine, indicating no improve in danger of hostile neurodevelopmental outcomes in kids uncovered to this AED throughout being pregnant.
Ruta Nonacs, MD PhD
References
Honybun E, Cockle E, Malpas CB, O’Brien TJ, Vajda FJ, Perucca P, Rayner G. Neurodevelopmental and Useful Outcomes Following In Utero Publicity to Antiseizure Treatment: A Systematic Evaluate. Neurology. 2024 Apr 23;102(8):e209175.
