Fetal anticonvulsant syndrome

How common is fetal anticonvulsant syndrome?

For women with epilepsy who are not taking medicines called antiepileptic drugs (AEDs), the chance of the baby having a major problem (such as fetal anticonvulsant syndrome (FACS)) is similar to the risk of women who do not have epilepsy. One study showed that approximately 3 babies out of 100 born to these women, would have a malformation.

For women who are taking AEDs, the risk of their baby having a major problem (congenital malformation) depends on the type, number and dose of the medication.

The risk for any one drug is about 6 out of 100 (that is double the background level of risk). The risk increases with the number of drugs. This means that babies of women taking two or more AEDs have between 10-14 out of 100 risk of being born with a problem. For those taking the combination of valproate, carbamazepine and phenytoin, the risk can be as high as 50 out of 100.

There is also evidence that taking a larger dose of antiepileptic medication carries a greater risk for the baby. Babies of mothers taking more than 1 g per day of valproate have more than twice the risk of congenital malformations, compared with those exposed to 600 mg or less.

The risk of the baby having a major malformation depends on the type, number and dose of the antiepilepsy medication.

The commonly known antiepileptic drugs (AEDs) which are associated with FACS are:

• Valproato de sodio

• Carbamazepina

• Phenytoin

• Primidona

• Fenobarbital

There is little difference in the level of risk between these medications except for sodium valproate, which is thought to have the largest risk.

Lamotrigine and levetiracetam are reported to be associated with FACS but fewer women take these medications. This means there are fewer reported cases anyway.

Amongst the AEDs listed above, lower-dose treatment with just one medication - lamotrigine or carbamazepine - has the least risk of major congenital malformation in the baby.

There is not enough evidence to accurately work out the risk of major congenital malformation for other AEDs taken on their own, such as:

• Eslicarbazepine

• Gabapentina

• Lacosamide

• Oxcarbazepine

• Perampanel

• Pregabalina

• Topiramato

• Zonisamide

• Tiagabine

• Vigabatrin

Benzodiazepine medicines such as clobazam y clonazepam, which are normally used as extra therapies, are not thought to harm the baby.

FACS includes structural abnormalities as well as developmental, behavioural and learning difficulties. Children with FACS can have a mixture of mild to more serious symptoms.

This can happen during the first few weeks of pregnancy when organs are developing. This is because the medications can cross the placenta.

There can also be developmental delay as well as speech and language problems, autistic spectrum disorders and poor motor control.

The most common major congenital malformations associated with antiepileptic drugs (AEDs) are:

• Neural tube defects including spina bifida: particularly with sodium valproate and carbamazepine.

• Congenital heart disorders: particularly with phenytoin, phenobarbital and sodium valproate.

• Orofacial clefts such as cleft lip and palate: particularly with phenytoin, carbamazepine and phenobarbital.

• Urogenital defects such as hypospadias.

• Skeletal abnormalities.

Minor malformations associated with AEDs include:

• Unusual facial features such as v-shaped eyebrows, low-set ears, broad nasal bridge, irregular teeth.

• Wide spacing between the eyes, known as hypertelorism.

• Poor growth of nails and digits.

• Poor development of the middle of the face.

Antiepilepsy medicines (especially sodium valproate) may have a negative effect on the long-term brain development of your baby.

There are very few cases involving levetiracetam use but initial findings (based on small numbers of women and babies) have been reassuring.

Little is known about other new AEDs or combinations of treatments; however, this does not always mean that your baby will be safe. When you discuss this with your consultant, they will say that the evidence on long-term outcomes for babies is based on small numbers of children.

FACS may first be suspected during the ultrasound scan in pregnancy in women who have taken epilepsy medicines.

A number of structural abnormalities can be seen during ultrasound in pregnancy. These include spina bifida, cardiac defects or facial defects. There are many different ways to deal with these problems. The correct approach for the family can be decided after in-depth counselling.

However, some characteristic facial abnormalities can often be subtle and likely to be noticed only after birth. As with any other infant with a facial abnormality, other possible diagnoses include genetic or chromosomal causes. These can be diagnosed (or ruled out) by special blood tests.

The management of FACS will depend on the type of birth defect. Each birth defect is managed individually and usually will require a multidisciplinary approach with involvement of different types of specialists.

Children born with developmental delay require supportive treatment under the guidance of a developmental paediatrician. This might include a physiotherapist and a speech and language therapist. Children with special educational needs benefit from additional educational support.

Pregnant women with epilepsy should have access to regular, planned antenatal care with a designated epilepsy care team. Women with epilepsy taking antiepileptic drugs (AEDs) who become unexpectedly pregnant, should be able to discuss therapy with an epilepsy specialist on an urgent basis.

As a pregnant women with epilepsy, you should be provided with information about the UK Epilepsy and Pregnancy Register and invited to register.

As a pregnant woman with epilepsy, you should be offered a detailed ultrasound in line with the NHS Fetal Anomaly Screening Programme standards. Early pregnancy can be an opportunity to look for structural abnormalities. The fetal anomaly scan at 18-20 weeks of gestation can identify major heart (cardiac) problems as well as brain and spinal cord (neural tube) problems.

Studies looking at the effect of folic acid supplements in pregnancy on major congenital malformation have shown mixed results. Two studies showed an association between low folate levels (or no supplements) and major congenital malformation. A further two studies did not show any benefit with folic acid in reducing major congenital malformation. This could be due to different mechanisms causing FACS.

Taking folic acid 5 mg per day from when you decide to start trying to become pregnant may be helpful in reducing the risk of AED-related learning difficulties. Long-term follow-up of children whose mothers were taking lamotrigine, carbamazepine, phenytoin or sodium valproate in pregnancy showed that (compared with unexposed children) the average IQs were higher when the mothers had taken folic acid.

Women with epilepsy are often worried about the effect of epilepsy and its treatment on motherhood. This includes fear of potential harm to the baby or not being able to fulfil the role of being a mother as they would want. If you have these worries, you are not alone.

Women with epilepsy can also feel that there is a lack of understanding among healthcare professionals about epilepsy and the specific issues related to pregnancy. Your healthcare professionals should acknowledge your concerns and be aware that this may effect how you take your medicines. A survey of women with epilepsy showed that 87 out of 100 women would like to be counselled about the risk of epilepsy and antiepileptic drugs (AEDs) to their unborn child. It also showed that 50 out of 100 women would like to be more involved in the discussions about treatment. Be sure you are happy with the conversations you have about your pregnancy and your epilepsy treatment.

As a woman with epilepsy you should be provided with verbal and written information on:

• Prenatal screening and its implications.

• The risks of stopping your epilepsy medications.

• The effects of seizures and medications on the baby and on the pregnancy.

• Breast-feeding and contraception.

It may also be sensible to introduce a few safety precautions to significantly reduce the risk of accidents and minimise worry. See separate leaflets called Living with Epilepsy y Epilepsy - Contraception/Pregnancy Issues para más detalles.