Eleven studies met the inclusion criteria, but only the seven studies (n=1,102 participants) that used IQ testing as a measure of cognitive development were included in the meta-analysis. Five of the seven studies used the Wechsler IQ scale and two studies used Bayley or McCarthy scale. Overall numbers of children included in the meta-analysis were: 67 exposed to valproic acid; 151 to carbamazepine; and 21 to phenytoin. Controls were 494 children born to mothers with epilepsy (n=58) or mothers with epilepsy but not exposed to antiepileptic drugs and healthy mothers without epilepsy (n=436).
Weighted mean scores of verbal IQ (VIQ), performance IQ (PIQ) and full-scale IQ (FSIQ) were significantly lower in the children exposed to valproic acid: VIQ (mean 83.9, 95% CI 64.2 to 103.6); PIQ (mean 93.7, 95% CI 72.6 to 114.7) and FSIQ (mean 88.3, 95% CI 69.6 to 106.9) compared with children whose mothers had epilepsy but were not exposed: VIQ (mean 97.5, 95% CI 73.3 to 121.7); PIQ (mean 98.6, 95% CI 70.4 to 126.8); and FSIQ (mean 98.7, 95% CI 73.1 to 124.3) or whose mothers did not have epilepsy and were not exposed: VIQ (99.7, 95% CI 87.8 to 111.6); PIQ (mean 100.5, 95% CI 86.1 to 114.8); and FSIQ (mean 99.6, 95% CI 88.1 to 111.2). Intelligent quotient was significantly lower in valproate exposed compared with controls in a subgroup analysis.
For carbamazepine, mean VIQ and FSIQ scores on the Wechsler scale for exposed children were not statistically significantly different from the unexposed children. However, mean PIQ was significantly lower than all-group control (p<0.002). Compared with children whose mothers had epilepsy but were not exposed, mean VIQ, PIQ and FSIQ were not statistically significantly different from children who were exposed to carbamazepine. Using the Bayley/McCarthy scale, the mean FSIQ of children exposed to carbamazepine versus children of mothers without epilepsy and who were not exposed were similar (98 versus 102 points).