Abstract

• What are the main data available in mid-2019 that compare the long-term effects of the most widely used antieleptics on children exposed to these drugs in utero?
  
  
• Two systematic reviews with meta-analysis and four studies published since 2017, including a large French cohort study, provide information about the long-term risk of disorders of neurological and behavioural development in children exposed in utero to monotherapy with various antiepileptic drugs. The comparator groups were children born to women with the same disease but who received either no treatment, or placebo or other antiepileptics; or children born to women without epilepsy.
   
• With lamotrigine, an approximately 1.6-fold increased risk of early developmental disorders was demonstrated in about 3000 children included in the French cohort study who had been exposed to this antiepileptic in utero and followed up until the age of 5 years. A meta-analysis of data from almost 300 pregnancies showed an approximately 9-fold increased risk of autism and dyspraxia with lamotrigine; other studies in fewer patients yielded conflicting results.
   
• Very limited data are available on pregabalin, carbamazepine, topiramate, gabapentin and levetiracetam. Pregabalin may increase the risk of intellectual disability, mental disorders and behavioural disorders. A 2-fold increased risk of disorders of early mental development was observed with carbamazepine.
   
• Limited data on topiramate in 2014 showed a long-term impact on motor development and cognitive and visual function, sometimes with maladaptive behaviour. The 2018 French study also showed a risk of learning disabilities in the 500 children exposed in utero to topiramate.
   
• With gabapentin, there are concerns over a potential risk of early mental, behavioural and developmental disorders.
   
• Data are available on too few pregnancies exposed to levetiracetam to determine its long-term consequences.
   
• In summary, as of mid-2019, no antiepileptic drugs are risk-free for the unborn child. Lamotrigine is the antiepileptic on which the most data are available. Lamotrigine appears to be associated with a lower risk of learning disabilities than the other antiepileptics. The long-term effects of pregabalin, carbamazepine, topiramate, levetiracetam and gabapentin remain highly uncertain. Valproic acid and its derivatives are teratogenic and provoke serious disorders of neuropsychological and psychomotor development.

©Prescrire 1 January 2020

"Antiepileptics and pregnancy: potential long-term effects in children" Prescrire Int 2020; 29 (211): 13-20. (Pdf, subscribers only).

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