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ADVERSE EFFECTS

Antiepileptics and pregnancy: potential long-term effects in children


ABSTRACT

● In summary, as of mid-2019, no antiepileptic drugs are risk-free for the unborn child. Lamo- trigine is the antiepileptic on which the most data are available. Lamotrigine appears to be associat- ed with a lower risk of learning disabilities than the other antiepileptics. The long-term effects of pregabalin , carbamazepine , topiramate , leveti- racetam and gabapentin remain highly uncertain. Valproic acid and its derivatives are teratogenic and provoke serious disorders of neuropsycho­ logical and psychomotor development. Rev Prescrire 2019; 39 (430): 587-595 A ntiepileptic drugs are used in various forms of epilepsy; some are also used in the treat- ment of certain psychiatric disorders or pain syndromes. Many women who could become pregnant are exposed to these drugs. Yet most of the antiepileptic drugs taken by pregnant women expose the unborn child to the risk of malformations, fetotoxic effects and neonatal disorders (see the insets “Short-term effects of in utero exposure to antiepileptics” and “Valproic acid: the consequenc- es of in utero exposure”, Prescrire Int n° 211, pp. 16-19). Antiepileptics also have psychotropic prop- erties and could therefore interfere with the psy- chomotor and behavioural development of children exposed in utero. For example, valproic acid can delay psychomotor development and cause be- havioural disorders in the long term.These serious adverse effects must be weighed against the harm- ful consequences of untreated maternal epilepsy on the pregnancy and its outcome: preeclampsia, bleeding, fetal growth restriction, preterm birth, miscarriage, and maternal or fetal death. Prescrire reviewed the risk of malformations and long-term effects in children exposed in utero to valproic acid , carbamazepine , lamotrigine , phenytoin and topiramate in 2009, and has since reported on additional findings concerning these risks. What are the main data available in 2019 on the long-term consequences for children exposed in utero to these antiepileptic drugs? ▶ Excerpt from Rev Prescrire August 2019 Volume 39 N° 430 • Page 587-595 Full review (8 pages) available at english.prescrire.org for subscribers

● 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 antiepilep- tics; 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 includ- ed 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 approxi­ mately 9-fold increased risk of autism and dys­ praxia with lamotrigine ; other studies in fewer patients yielded conflicting results. ● Very limited data are available on pregabalin , carbamazepine, topiramate , gabapentin and leve- tiracetam . Pregabalin may increase the risk of intel- lectual disability, mental disorders and behavioural disorders. A 2-fold increased risk of disorders of early mental development was observed with car- bamazepine . ● Limited data on topiramate in 2014 showed a long-term impact on motor development and cog- nitive and visual function, sometimes with mal- adaptive behaviour. The 2018 French study also showed a risk of learning disabilities in the 500 chil- dren 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.

Prescrire Int • January 2020

P rescrire I nternational S pecial E dition 2020 • P age 11