Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6years

Cohen et al, Epilepsy Behav. 2013 Nov

The Neu­rode­vel­op­men­tal Effects of Antiepilep­tic Drugs (NEAD) study is a prospec­tive obser­va­tion­al mul­ti­cen­ter study in the USA and UK, which enrolled preg­nant women with epilep­sy on antiepilep­tic drug (AED) monother­a­py from 1999 to 2004. The study aimed to deter­mine if dif­fer­en­tial long-term neu­rode­vel­op­men­tal effects exist across four com­mon­ly used AEDs (car­ba­mazepine, lam­ot­rig­ine, pheny­toin, and val­proate). In this report, we exam­ine fetal AED expo­sure effects on adap­tive and emotional/behavioral func­tion­ing at 6years of age in 195 chil­dren (includ­ing three sets of twins) whose par­ent (in most cas­es, the moth­er) com­plet­ed at least one of the rat­ing scales. Adjust­ed mean scores for the four AED groups were in the low aver­age to aver­age range for par­ent rat­ings of adap­tive func­tion­ing on the Adap­tive Behav­ior Assess­ment Sys­tem-Sec­ond Edi­tion (ABAS-II) and for par­ent and teacher rat­ings of emotional/behavioral func­tion­ing on the Behav­ior Assess­ment Sys­tem for Chil­dren (BASC). How­ev­er, chil­dren whose moth­ers took val­proate dur­ing preg­nan­cy had sig­nif­i­cant­ly low­er Gen­er­al Adap­tive Com­pos­ite scores than the lam­ot­rig­ine and pheny­toin groups. Fur­ther, a sig­nif­i­cant dose-relat­ed per­for­mance decline in parental rat­ings of adap­tive func­tion­ing was seen for both val­proate and pheny­toin. Chil­dren whose moth­ers took val­proate were also rat­ed by their par­ents as exhibit­ing sig­nif­i­cant­ly more atyp­i­cal behav­iors and inat­ten­tion than those in the lam­ot­rig­ine and pheny­toin groups. Based upon BASC par­ent and teacher rat­ings of atten­tion span and hyper­ac­tiv­i­ty, chil­dren of moth­ers who took val­proate dur­ing their preg­nan­cy were at a sig­nif­i­cant­ly greater risk for a diag­no­sis of ADHD. The increased like­li­hood of dif­fi­cul­ty with adap­tive func­tion­ing and ADHD with fetal val­proate expo­sure should be com­mu­ni­cat­ed to women with epilep­sy who require antiepilep­tic med­ica­tion. Final­ly, addi­tion­al research is need­ed to con­firm these find­ings in larg­er prospec­tive study sam­ples, exam­ine poten­tial risks asso­ci­at­ed with oth­er AEDs, bet­ter define the risks to the neonate that are asso­ci­at­ed with AEDs for treat­ment of seizures, and under­stand the under­ly­ing mech­a­nisms of adverse AED effects on the imma­ture brain.