Type of epilepsy medication during pregnancy affected children differently

 A study shows that different types of epilepsy medication, when taken during pregnancy, affect children differently than the other types of medication.

Women with epilepsy usually need to take medications to treat the condition even while they are pregnant. But how do those medications affect their developing babies?

A recent study found that one epilepsy medication appeared to affect children's development less than another when the children were preschoolers.

The two medications studied were levetiracetam (brand name Keppra) and valproate sodium (brand name Depacon, Depakene or Depakote).

Children whose mothers took levetiracetam during pregnancy scored similarly to children not exposed to medications in the womb.

Children whose mothers took valproate sodium scored lower with motor skills and language skills.

This study, led by R. Shallcross, PhD, of the Department of Clinical Psychology at the University of Liverpool in the United Kingdom, looked at the development of children whose mothers took epilepsy medications while pregnant.

The researchers compared the children of 97 women who took either levetiracetam or valproate sodium while pregnant to the children of 131 women without epilepsy, who took no prescription medications during pregnancy.

The children were aged 3 to 4.5, and their cognitive skills and language development were tested with established scales.

After taking into account other characteristics that differed among the children and/or their mothers, the 53 children whose mothers took levetiracetam did not score any differently than children not exposed to medications during pregnancy.

Differences were seen, however, among the children whose mothers took valproate sodium during pregnancy.

The 44 children exposed to valproate sodium in the womb scored an average 15.8 points lower on gross motor skills than children exposed to levetiracetam in the womb.

The scale used is calculated similarly to an IQ scale, with 100 representing the average for children.

Children of mothers who took valproate sodium also scored an average 6.4 points lower on language comprehension and 9.5 points lower on expressive language skills, compared to children of mothers who took levetiracetam during pregnancy.

The researchers therefore concluded that children whose mothers used levetiracetam to treat their epilepsy during pregnancy fared better in motor skills and language development than children whose mothers used valproate sodium.

However, the researchers cautioned that their findings do not mean that valproate sodium should never be used during pregnancy.

Because this medication is used to treat seizures, which can also be dangerous for an unborn baby, some women may still need to take it while pregnant.

This study was published January 8 in the journal Neurology.

The research was funded by UCB Pharma Ltd., the Epilepsy Research Foundtion, GlaxoSmithKline, Sanofi Aventis, Janssen-Cilag, Novartis, Pfizer, Eisai and Epilepsy Research UK.

Five authors have received travel funds or advisory board honorariums from various pharmaceutical companies, including Sanofi Aventis and UCB Pharma Ltd.

Three of these authors have also given expert testimony in legal cases related to fetal anticonvulsant syndrome or the safety of anticonvulsants during pregnancy.

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Moms with epilepsy should breastfeed their infants

A study shows that breastfeeding mothers with epilepsy should continue to breastfeed their children regardless of taking antiepileptic drugs while breastfeeding. JR

The study aims to determine whether signs of impaired development appear already during the first months of life in children exposed prenatally to antiepileptic drugs, and to explore potential adverse effects of antiepileptic drug exposure through breastfeeding. Prenatal exposure to antiepileptic drugs was associated with impaired fine motor skills already at age 6 months, especially when the child was exposed to multiple drugs. There were no harmful effects of breastfeeding. Women with epilepsy should be encouraged to breastfeed their children irrespective of antiepileptic drug treatment.

Methods

• Mothers at 13 to 17 weeks of pregnancy were recruited in the population-based, prospective Norwegian Mother and Child Cohort Study from 1999 to 2009.
• The mothers reported on their child’s motor and social skills, language, and behavior using items from standardized screening tools at 6 months (n=78744), 18 months (n=61351), and 36 months (n=44147) of age.
• The mothers also provided detailed information on breastfeeding during the first year.
• The risk of adverse development in children according to maternal or paternal epilepsy was estimated as the odds ratio with corresponding 95% confidence interval, adjusted for maternal age, parity, education, smoking, breastfeeding, depression/anxiety, folate supplementation, and congenital malformation in the child.

Results

• At age 6 months, infants of mothers using antiepileptic drugs (n=223) had a higher risk of impaired fine motor skills compared with the reference group (11.5% vs 4.8%, respectively; odds ratio=2.1; 95% CI, 1.3-3.2).
• Use of multiple antiepileptic drugs compared with the reference group was associated with adverse outcome for both fine motor skills (25.0% vs 4.8%, respectively; odds ratio=4.3; 95% CI, 2.0-9.1) and social skills (22.5% vs 10.2%, respectively; odds ratio=2.6; 95% CI, 1.2-5.5).
• Continuous breastfeeding in children of women using antiepileptic drugs was associated with less impaired development at ages 6 and 18 months compared with those with no breastfeeding or breastfeeding for less than 6 months.
• At 36 months, prenatal antiepileptic drug exposure was associated with adverse development regardless of breastfeeding status during the first year.
• Children of women with epilepsy who did not use antiepileptic drugs and children of fathers with epilepsy had normal development at 6 months.

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Management of epilepsy in women of child bearing age - World Health Organization

Question -  In women with epilepsy, should antiepileptic therapy be prescribed as monotherapy or polytherapy to decrease the risk of fetal malformations?

11. Does the use of folic acid preconceptually decrease the risk of foetal malformations in women with epilepsy?

11. Do phenytoin, phenobarbital, valproic acid or carbamazepine enter breast milk in quantities which are clinically significant to the baby?

Management of epilepsy in women of child bearing age

Management of epilepsyPopulation:

• women with epilepsy who may become pregnant
• women with epilepsy on antiepileptic drug treatment wishing to breast feed
• Interventions:
• use of antiepileptic drugs as monotherapy or polytherapy during pregnancy
• use of phenobarbital, phenytoin, valproate or carbamazepine during pregnancy
• use of folic acid preconceptually and during early pregnancy
• breast feeding while taking phenobarbital, phenytoin, valproate or carbamazepine
• Comparison:
• pregnant women with epilepsy taking no antiepileptic drugs
• pregnant women without epilepsy
• Outcomes:
• congenital malformations in the infant
• clinically important amounts of antiepileptic drugs secreted in breast milk.

Recommendation(s)

Women with epilepsy should have seizures controlled as well as possible with the minimum dose of antiepileptic drug taken in monotherapy, wherever possible. Antiepileptic drug polytherapy should be avoided. Valproic acid should be avoided if possible.
Strength of recommendation: STRONG

Folic acid should routinely be taken by women with epilepsy of child bearing age who are on antiepileptic drugs.
Strength of recommendation: STRONG

Standard breast feeding recommendations remain appropriate for women with epilepsy on the antiepileptic drugs included in this review (phenobarbital, phenytoin, carbamazepine and valproic acid).
Strength of recommendation: STRONG