Sodium valproate should be avoided in the treatment of pregnant women due to the possible developmental problems for a child.
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.
Most women with epilepsy should continue their medication during pregnancy as uncontrolled seizures also carries a maternal risk.
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