Medicamentos anticonvulsivos y desarrollo infantil

What We Know About ASMs & Risk of Major Congenital Malformations and Adverse Neurodevelopmental Outcomes

Los estudios que examinan los efectos de los medicamentos anticonvulsivos (ASM, por sus siglas en inglés) en niños expuestos durante el embarazo se han centrado principalmente en dos resultados clave:

• Malformaciones fetales 
• Resultados adversos del desarrollo neurológico

La mayoría de las investigaciones han encontrado que los riesgos asociados con la exposición a las ASM son relativamente bajos en comparación con la exposición a otras sustancias como la talidomida o la exposición fetal al alcohol.

However, some ASMs carry a higher risk than others. Clinicians need to consider these variations and weigh the potential risks and benefits of different ASMs when treating pregnant patients with epilepsy.

Limited or no data on major congenital malformations or neurodevelopment

Visit the American Academy of Neurology's Practice Guidelines for additional information.

Los temas que se tratan en esta página incluyen:

• ASMs y resultados del neurodesarrollo
• MAS y malformaciones congénitas mayores
• Impacto de las MAPE en el crecimiento fetal
• ASM Polytherapy
• ASM Generic vs Brand Names

Resultados del desarrollo neurológico para los niños nacidos de padres que toman ASM

Several studies have followed children exposed to ASMs during pregnancy and assessed neurodevelopmental outcomes. These studies also found that: 

• Data on valproic acid suggests highly elevated risk:
  • Valproic acid exposure has the highest risk of exposed children having lower global IQ and verbal IQ when compared to other ASMs
  • Valproic acid associated with increased risk of autistic spectrum disorder when compared to other ASMs
• La exposición a lamotrigina parece conllevar un riesgo relativamente bajo de resultados adversos en el desarrollo neurológico. 
• El levetiracetam también conlleva un riesgo bajo, según datos más limitados. 
• Los datos sobre la carbamazepina son contradictorios, pero en general sugieren un riesgo bajo.
• The data on topiramate are more mixed and suggest no clear effect on neurodevelopmental outcomes.
• Los datos sobre el ácido valproico sugieren un riesgo muy elevado.

Valproic acid exposure during pregnancy was found to be associated with adverse neurodevelopmental outcomes (cognitive and behavioral)  in children when compared to children born to mothers without epilepsy and children born to mothers taking other anti-seizure medications. Specifically, children exposed to valproic acid during pregnancy may exhibit lower global IQ, lower verbal abilities, and have an increased risk of autism and autism spectrum disorder. Moreover, these neurodevelopmental effects continue into the school-age years.

Se dispone de datos limitados sobre los otros medicamentos anticonvulsivos, y se necesita más investigación para comprender sus efectos en el desarrollo neurológico de los niños nacidos de pacientes que toman estos medicamentos durante el embarazo.

MAS y malformaciones congénitas mayores

Las malformaciones congénitas mayores (MCM) son anomalías fetales que afectan la salud y la función diarias o requieren cirugía. En la población general, los embarazos conllevan un riesgo de fondo del 2-3% para las MCM. Algunos ejemplos son:

• Espina bífida
• Defectos cardíacos
• Labio leporino/paladar hendido
• Defectos urogenitales

Los registros de embarazos han proporcionado información valiosa sobre el riesgo de MCM asociados con ASM mediante el seguimiento de las pacientes desde sus primeras etapas de embarazo. Entre todas las MAPE:

• Lamotrigine (3.1%), levetiracetam (3.5%), and oxcarbazepine (3.1%) have the lowest prevalence of malformations based on data from these pregnancy registries and meta analysis. Prevalence of MCMs were within the range for children who were not exposed to any ASM during pregnancy (2.4-2.9%).
• Valproic acid has the highest prevalence of malformations (9.7%) and neural tube defects (1.4%).
• Phenobarbital has the highest prevalence of child having a heart defect (4.4%)
• Phenobarbital (2.2%) and topiramate (1.2%) exposure results in increased prevalence of oral clefts 
• Valproic acid has the highest prevalence of urogenital (1.2%) and renal (1.4%) malformations. Research suggests that carbamazepine is generally low-risk.

Visit the American Academy of Neurology's Practice Guidelines for additional information.

Importantly, the risk of MCMs appears to correlate with the valproic acid dose and level of the medication. For example, a patient taking valproic acid at the dose of:

• 700 - 1500 mg/día tiene un riesgo del 10,4% de MCM
• >1500 mg/día tiene un riesgo del 24,2% de MCM.

Es esencial reconocer que incluso las dosis bajas de ácido valproico presentan algún riesgo, junto con riesgos potenciales de efectos en el desarrollo neurológico, como se puede ver en la tabla anterior. Los médicos deben ser conscientes de estos riesgos variables al tratar a personas embarazadas con epilepsia para optimizar la salud de la paciente y su bebé. 

Impacto de las MAPE en el crecimiento fetal

Ciertas ASM pueden afectar el crecimiento fetal de manera diferente. 

• Topiramate exposure during pregnancy has been linked to a risk of infants being born small for their gestational age (SGA).
• La exposición fetal al topiramato también se asocia con los bebés que nacen con bajo peso al nacer, lo que conlleva mayores riesgos para la salud a largo plazo.

Fetal growth monitoring can help identify any potential problems early on and is recommended for pregnant patients with epilepsy, especially those on these medications. Visit the pregnancy management page to see when this monitoring is recommended during pregnancy. 

ASM Polytherapy 

There is no definitive increased risk of polytherapy compared to monotherapy in pregnancy. There is, however, limited study. In some patients, combining safer medications can be a good strategy. For example, a baby exposed to the combination of levetiracetam and lamotrigine in pregnancy is at lower risk for malformations and adverse neurodevelopmental outcomes than a baby exposed to valproic acid.

ASM Generic vs Brand Names

Guíe a sus pacientes

There are ASMs with a low risk of fetal malformations or adverse neurodevelopmental outcomes. These ASMs also present little risk to babies if women take them while breastfeeding. It is important to be very clear with patients about the existing research, what it shows, and what we don’t yet know.

Patients considering pregnancy should be advised of the potential risks of certain ASMs on child development. However, patients should be reassured that there are options with little or no elevated risk to the fetus. Emphasize that they should not stop taking medication due to fear or perceived risk, as abrupt discontinuation can be harmful. Instead, a collaborative approach should be taken to assess the benefits and risks of ASMs for both the patient and the developing fetus. Ensure your patients with epilepsy are aware that a healthy pregnancy is achievable with some preparatory planning.

Reviewed by: EPMC Expert Panel, March 2025