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Evidence summaries

Treatment for Epilepsy in Pregnancy

Prenatal exposure to valproate may be associated with an increased risk of neurodevelopmental deficits, including poorer early development, lower IQ in school aged children and an increased risk of autistic spectrum disorders. In comparison to other treatments, valproate is probably associated with reduced IQ compared to carbamazepine, lamotrigine and phenytoin and there may also be a dose effect for valproate. Level of evidence: "C"

Sodium valproate should be avoided in the treatment of pregnant women due to the possible developmental problems for a child.

Summary

A Cochrane review [Abstract] 1 included 28 prospective cohort studies with a total of 5317 children. The developmental quotient (DQ) was lower in children exposed to carbamazepine (CBZ) (n = 50) than in children born to women without epilepsy (n = 79); MD of -5.58 (95% CI -10.83 to -0.34, p = 0.04). The DQ of children exposed to CBZ (n = 163) was also lower compared to children of women with untreated epilepsy (n = 58) (MD -7.22, 95% CI -12.76 to - 1.67, p = 0.01). The intelligence quotient (IQ) of older children exposed to CBZ (n = 150) was not lower than that of children born to women without epilepsy (n = 552) (MD -0.03, 95% CI -3.08 to 3.01, p = 0.98). Similarly, children exposed to CBZ (n = 163) had no poorer IQ in comparison to the children of women with untreated epilepsy (n = 87) (MD 1.84, 95% CI -2.13 to 5.80, p = 0.36). The DQ in children exposed to sodium valproate (VPA) (n = 123) was lower than the DQ in children of women with untreated epilepsy (n = 58) (MD -8.72, 95% -14.31 to -3.14, p = 0.002). The IQ of children exposed to VPA (n = 76) was lower than for children born to women without epilepsy (n = 552) (MD -8.94, 95% CI -11.96 to -5.92, p < 0.00001). Children exposed to VPA (n = 89) also had lower IQ than children born to women with untreated epilepsy (n = 87) (MD -8.17, 95% CI -12.80 to -3.55, p = 0.0005).In terms of drug comparisons, in younger children there was no significant difference in the DQ of children exposed to CBZ (n = 210) vs. VPA (n=160) (MD 4.16, 95% CI -0.21 to 8.54, p = 0.06). However, the IQ of children exposed to VPA (n = 112) was significantly lower than for those exposed to CBZ (n = 191) (MD 8.69, 95% CI 5.51 to 11.87, p < 0.00001). The IQ of children exposed to CBZ (n = 78) vs. lamotrigine (LTG) (n = 84) was not significantly different (MD -1.62, 95% CI -5.44 to 2.21, p = 0.41). There was no significant difference in the DQ of children exposed to CBZ (n = 172) vs. phenytoin (PHT) (n = 87) (MD 3.02, 95% CI -2.41 to 8.46, p = 0.28). The IQ of children exposed to CBZ (n = 75) were not different from the children exposed to PHT (n = 45) (MD -3.30, 95% CI -7.91 to 1.30, p = 0.16). IQ was significantly lower for children exposed to VPA (n = 74) vs. LTG (n = 84) (MD -10.80, 95% CI -14.42 to -7.17, p < 0.00001). DQ was higher in children exposed to PHT (n = 80) versus VPA (n = 108) (MD 7.04, 95% CI 0.44 to 13.65, p = 0.04). Similarly IQ was higher in children exposed to PHT (n = 45) vs. VPA (n = 61) (MD 9.25, 95% CI 4.78 to 13.72, p < 0.0001). A dose effect for VPA was reported in 6 studies, with higher doses (800 to 1000 mg daily or above) associated with a poorer cognitive outcome in the child. There was no convincing evidence of a dose effect for CBZ, PHT or LTG.

Clinical comments

Most women with epilepsy should continue their medication during pregnancy as uncontrolled seizures also carries a maternal risk.

Note

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References

Primary/Secondary Keywords