Aim: To assess the relative risks of antiepileptic drug (AED) polytherapy and monotherapy in relation to foetal malformation during human pregnancy.
Methods: Statistical analysis of data from the Australian Pregnancy Register and from the literature
Results: In the Australian Register,791 of 1073 AED exposed pregnancies received AED monotherapy (73.7%), and 282 AED polytherapy (26.3%). In the monotherapy group there were 44 pregnancies with foetal malformations detected by the neonatal period (5.18%) and 62 (7.84%) reported at 1 year post-natally: in the polytherapy group the corresponding figures were 11 (3.90%) and 15 (5.32%).For pregnancies involving polytherapy as compared with monotherapy, the Relative Risk (RR) value for associated foetal malformations was 0.75 (95% CI = 0.38, 1.44) as determined neonatally, and 0.68 (95% CI = 0.39, 1.17) as determined after the post-natal year.In 4 of the 14 publications from the literature the individual RR value calculated from published data was statistically significantly higher for the polytherapy group,in none statistically significantly lower, and in only 3 below 1.0. The Australian RR value was appreciably lower than the published ones. The risk was statistically significantly less overall, and also less for a given valproate dose, when valproate was co-administered with other AEDs, in particular lamotrigine.
Conclusions: It may be unwise to generalise regarding foetal hazards of AED polytherapy versus monotherapy without assessment of the role of valproate. At the same dose, valproate in polytherapy, particularly if lamotrigine is involved, may be significantly less hazardous for foetal development than valproate monotherapy.