Complete Guide to Epilepsy and Pregnancy

Complete Guide to Epilepsy and Pregnancy

Epilepsy affects men slightly more than women. However, women with epilepsy have to deal with pregnancy and the effects this disease and its treatment have on it.

Pregnancy with epilepsy is associated with several dangers for mother and baby. Prominent among the risks are that seizures may increase, and the antiepileptic drugs may cause malformations in the baby.

The incidence of epilepsy in women of childbearing age is 4-7 per thousand. Around the world, thousands of women live with epilepsy and have to deal with these issues.

If you’re one of them, this article is for you. We’ll discuss the pregnancy-related problems unique to women with this disease, and what you should do about each one.

What We’ll Discuss

Effect on Birth Control

Several of the drugs used for pregnancy stimulate the liver to increase the metabolism of the hormones in birth control pills. Not all drugs used for epilepsy have this effect; carbamazepine, phenytoin, phenobarbital, lamotrigine, and primidone are the ones you should be careful about.

This causes the failure of birth control in a significant number of women taking antiepileptic drugs. You cannot depend on hormonal oral contraceptive pills, patches, or implants.

Alternative methods like condoms and intrauterine devices should be used for birth control. If hormonal birth control must be used, the estrogen component of any combination birth control pills should be at least 50 mcg.

Epilepsy and Infertility

Women with epilepsy (WWE) are more likely to have fertility issues. Their periods are often irregular, and up to a third of their cycles may be anovulatory — no ovum is released from the ovary.

Seizures also affect the hormones that run the reproductive system. Serum prolactin, luteinizing hormone (LH) and others fluctuate with seizures.

Polycystic ovary syndrome (PCOS) is more common in women with epilepsy; this condition by itself is associated with infertility.

Some of the reasons women with epilepsy have lower fertility may be social. These women marry late, when fertility is lower. Fear of disease worsening during pregnancy, side effects of the drugs on the unborn baby, and worry about their ability to care for the child may also be reasons for avoiding pregnancy.

Pregnancy Planning

Talk to your neurologist when planning a pregnancy.

If you’ve been seizure-free for a significant time, your doctor may stop the treatment.

If that’s not possible, treatment should be changed to a single drug. It should, of course, be one of the drugs that are safe for the unborn baby.

Reduce the dose of the drug(s) to the lowest level that gives seizure control.

Valproate is most commonly associated with fetal malformations, but sometimes has to be continued. Reducing the daily dose and dividing it into three or four doses (instead of the usual two) is recommended. High blood levels of valproate are more likely to cause malformations.

What About Folate/Folic Acid?

Antiepileptic drugs reduce blood folate levels. Low levels of folate in pregnancy are associated with congenital malformations, some of them life-threatening.

Folate is given to restore blood levels and protect the baby, but is not a magical shield. It cannot be depended upon to prevent congenital malformations in women taking antiepileptic drugs during pregnancy (Vajda).

However, folate is currently recommended for all women pre-conceptionally and during pregnancy, to reduce birth defects called neural tube defects. It is a safe drug; you should follow your folate prescription sincerely.

Effect of Pregnancy on Epilepsy

Pregnancy is a time of great changes in the body. Body weight and blood volume increase, diluting the drug(s) you are taking. Liver metabolism of antiepileptic drugs increases in pregnancy, further lowering their levels in the blood.

As long as your epilepsy is well-controlled before you conceive, you should be fine. The overwhelming majority of women go through pregnancy and delivery smoothly.

Doctors know that 17-33% of women have more seizures during pregnancy, and take steps to prevent them. Most likely, you will not have increased seizures during pregnancy, as long as:

  • Drug doses are appropriate.
  • You consume them regularly.
  • You get enough sleep.

What can you do? Dig out your old laboratory reports. The blood levels of your antiepileptic drugs that control the seizures are crucial at this time. Your neurologist will adjust your drugs’ dose to maintain the known effective levels and keep you seizure-free.

Effect of Epilepsy on Pregnancy

What about pregnancy itself? Is the ability to nourish a baby and carry it safely to term affected?

Very slightly. Spontaneous miscarriage, early (premature) labor, and reduced growth of the baby happen sometimes. Stillbirths are rare.

Induction of labor is more likely in women with epilepsy. This means a delay or failure of spontaneous labor. Operative deliveries (C-sections) are also more likely.

Most types of seizures do not harm a baby in the womb. However, seizures with loss of awareness and falls are dangerous.

Other conditions to be aware of are hypertension (raised blood pressure), antepartum hemorrhage (bleeding from the uterus before the baby’s birth), and post-partum hemorrhage (bleeding from the uterus after the baby’s birth). These occur more frequently in pregnancy with epilepsy.

Is Labor Safe?

Among women with epilepsy, 1-3% develop seizures during labor.

Normal delivery is safe enough, in a good hospital. Everyone there will know what to do; just make sure they know you have epilepsy and what drugs you are on.

Some precautions may be necessary. Your doctor may decide to give you some extra drugs to prevent seizures. Your baby will be given vitamin K at birth, and laboratory tests for bleeding disorders will be performed.

Having epilepsy does not make it compulsory for you to have an operative delivery.

Antiepileptic Drugs – Fetal Malformations

Epilepsy itself does not affect the fetus. Women who are not on drugs for epilepsy do not have more malformations than women without epilepsy.

Though the disease does not harm, antiepileptic drugs aren’t good for the little human inside you. That’s been known for over fifty years now. The placenta does a marvellous job of providing nutrition and oxygen to the growing baby; unfortunately, it allows antiepileptic drugs to pass through.

The commonly seen malformations are:

  • Hare lips and cleft palate.
  • Defects of the toes and fingers.
  • Spine and brain defects (neural tube defects).
  • Short nose.
  • Low-set ears.
  • Drooping eyelids (ptosis)
  • Poor growth in the womb

The fetal hydantoin syndrome was first described in 1973, based on a case series of only 12 patients who had received phenytoin during pregnancy. The babies had defects of the head, face, fingers, ears, and eyes. They also had developmental delay. Eleven of these women had received other drugs also.

Among women who receive phenytoin during pregnancy, some anomalies are seen in 10-30% of babies. Most are minor; the incidence of major anomalies is 4-7%.

Even a single antiepileptic drug increases the possibility of birth defects. Higher doses, and the use of more than one drug, further increase the risk.

The most dangerous drug is trimethadione. One study found significant anomalies or fetal death in 87% of cases. This drug is not used much now, and must never be used during pregnancy.

We’ve made progress in the last half-century, however. Newer drugs like lamotrigine, levetiracetam, gabapentin, lamotrigine, felbamate, topiramate, and oxcarbazepine are safer than older drugs like valproate, phenytoin, primidone, carbamazepine, and phenobarbitone.

However, seizure control is probably better with valproate. This fact makes it hard to give general recommendations; decisions must be individualized.

What should you do? Talk to your neurologist when planning a pregnancy. See Pregnancy Planning

Risk Factors for Malformations

A family history of abnormalities increases the risk.

The risk to a second child, if the first had a malformation, is very high (17-36%)

Testing for Malformations

Most malformations are minor, and have only cosmetic effects. Some, like cleft lip or palate, can be surgically corrected.

Neural tube defects affect the brain and spine, and lead to severe disabilities in the baby.

Your doctor will try to detect such defects early, by doing alpha-fetoprotein (AFP) levels at 14-16 weeks, and high-resolution ultrasound at 16-20 weeks. Sometimes, you may also be advised amniocentesis, which is a somewhat invasive procedure and carries a small but definite risk.

Bleeding Disorders in Baby

Several of the antiepileptic drugs are associated with bleeding disorders in the baby. The blood does not clot because of a deficiency of clotting factors.

This can show up as something minor. A heel prick for blood sampling continues to bleed, for example. However, serious bleeding also happens. Bleeding into the brain, for example, can be fatal.

Serious bleeding is rare, but precautions are always taken. Vitamin K is given to the baby at birth, and blood is tested for clotting. If there is a severe problem, blood or plasma may be needed.

Is Breastfeeding Safe?

Probably.

Most drugs are present in breast milk, but they’ve not been shown to be harmful to babies.

Of the antiepliptic drugs primidone, phenobarbitone, levetiracetam, lamotrigine, gabapentin, benzodiazepines, topiramate, and ethosuximide are present in breast milk in significant amounts.

If you were planning to breastfeed, taking drugs for seizure control should not stop you.

Long-Term Effects on Children

Intellectual disability and delayed development are major concerns in children born with exposure to antiepileptic drugs before birth. Valproate in pregnancy is associated with reduced IQ, verbal ability, non-verbal ability, and memory in the children. Carbamazepine, clonazepam, and oxcarbazepine also have these effects (Daugaard). Among the newer drugs, lamotrigine appears safe in this regard.

Children born to women taking antiepileptics have delays in language skills, too (Unnikrishnan). This may persist for several years.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are also more common in children whose mothers took valproate during pregnancy. Carbamazepine and lamotrigine appear to be safer (Wiggs).

Will Your Baby Develop Epilepsy?

Worries you, doesn’t it?

The chances are about four per cent. That’s higher than the general population’s risk, but not enough of a reason to avoid babies or to worry a lot.

Gestational epilepsy

This is a rare condition. Seizures occur for the first time during pregnancy, do not occur after it is over, only to appear again in a subsequent pregnancy.

A single seizure is usually not treated. However, if there are more than one, the seizures must be controlled with drugs.

All seizures are not epilepsy, and a neurologist will want to look for other causes like a tumor, venous thrombosis, or vascular malformation. Eclampsia, a dangerous condition associated with high blood pressure, is another consideration.

Computed tomography (CT scans) use x-rays, and the fetus needs to be kept safe from radiation by suitable lead shielding. Magnetic resonance imaging (MRI) is a safer choice.

Is Pregnancy Safe?

Women with epilepsy have a higher risk of death during pregnancy. The risk depends on seizure-control.

If your seizures are completely controlled by medication, then pregnancy is safe for you.

If your seizures are completely controlled by a safe drug at low doses, pregnancy is safe for baby also.

However, 30% of people with epilepsy continue having seizures even on medication. Seizures occurring during pregnancy are dangerous to the lives of both mother and baby.

Conclusion

In the end, it’s a balancing act. The need to control the seizures and prevent danger to you and baby, against the need to protect baby from the dangers of antiepileptic treatment.

Important point: uncontrolled seizures are a far greater risk to the fetus than a single antiepileptic drug at an optimized dose.

You need an expert team, careful preparation, and extreme care through pregnancy and at birthing. Contemporary medical care has it sorted; the incidence of seizures in pregnant women is not more than non-pregnant women with epilepsy (Pennell). With such care, 90% of women have an uneventful pregnancy and birth.

References

  1. Pennell et al. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy.
  2. Chang et al. Update to the Hong Kong Epilepsy Guideline: evidence-based recommendations for clinical management of women with epilepsy throughout the reproductive cycle.
  3. Wiggs et al. Antiseizure medication use during pregnancy and risk of ASD and ADHD in children.
  4. Vajda et al. Folic acid dose, valproate, and fetal malformations.