Antiepileptic drug use among women from the Taiwanese Registry of Epilepsy and Pregnancy: Obstetric complications and fetal malformation outcomes

<div><p>To investigate antiepileptic drugs (AEDs) prescription and pregnancy outcomes in pregnancies with epilepsy in Taiwan between 2004 and 2015. We retrospectively reviewed data from the Taiwanese Registry of Epilepsy and Pregnancy (TREP). The TREP registry is a voluntary prospective cohort registry, which tracks pregnant women with epilepsy and AED prescription throughout pregnancy, delivery, and early childhood development. All TREP pregnancies (n = 318) that had completed questionnaires up until delivery or had had an unsuccessful pregnancy were analyzed. Over 94.7% of women had been prescribed AEDs during pregnancy, with 69.0% and 25.7% having received monotherapy, or polytherapy, respectively. Among live births, 12 (3.9%) reported malformation. Cesarean section rate was reported higher than usual (54.5%). In 2004, 73.3% of AEDs prescribed were 1^st generation, with 1^st generation prescription rates falling to only 8.3% of total prescribed in 2015. AED polytherapy also fell during the study period (40.0% to 20.0%). Cesarean sections were found to be higher for women over 35 years, who had generalized epilepsy, or had experienced an obstetric complication during pregnancy term. Binary logistic regression revealed that Cesarean section was associated with maternal complications (OR = 5.11, CI 95% = 1.11–23.51, p = 0.036), while malformations were associated with obstetric complication (OR = 20.46, CI 95% = 4.80–87.21, p<0.001). Both AED risk types were not associated with complications or malformations. Our sample provides a unique insight into the women with epilepsy with AED use during pregnancy. Cesarean section rate was observed to be higher than usual, but malformation rates remained low. Results indicate a decrease in both 1^st generation AEDs and proportion of patients receiving polytherapy over the study period. Obstetric complications were associated with Cesarean section. Fetal malformations were significantly associated with obstetric complications. AED risk factors were not significantly associated with either complications or malformations.</p></div

AED prescription by year (2004–2015) and AED generation (1st vs. 2nd) (Total AEDs prescribed: n = 411).

<p>AED prescription by year (2004–2015) and AED generation (1st vs. 2nd) (Total AEDs prescribed: n = 411).</p

Associated factors with malformation rate among WWE pregnancies, n = 318.

<p>Associated factors with malformation rate among WWE pregnancies, n = 318.</p

AED monotherapy, polytherapy, and no prescription rates among TREP WWE pregnancies (n = 318).

<p>AED monotherapy, polytherapy, and no prescription rates among TREP WWE pregnancies (n = 318).</p

Associated factors with maternal complications of WWE^a pregnancies, n = 318.

<p>Associated factors with maternal complications of WWE<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189497#t003fn003" target="_blank">^a</a> pregnancies, n = 318.</p

WWE related factors by delivery group (N = 307; aborted: n = 11 excluded).

<p>WWE related factors by delivery group (N = 307; aborted: n = 11 excluded).</p

Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings

<div><p>The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.</p></div

Clinical characteristic of TLE patients.

<p>R, right; L, left; T, temporal lobe; CPS, complex partial seizure</p><p>SPS, simple partial seizure; SGTCS, secondary generalized tonic-clonic seizure</p><p>MTS, mesial temporal sclerosis; VM, vascular malformation</p><p>Encephalom, encephalomalacia; F, frontal; AEDs, anti-epileptic drugs</p><p>Clinical characteristic of TLE patients.</p

Bar plots for the laterality effect on functional connectivity.

<p>(a) The difference in the delta functional connectivity in the left and right MT regions between controls, and left and right TLE patients is shown. (b) There were significant differences in the theta functional connectivity in the left and right ACC regions between controls, and left and right TLE patients. Each error bar represents the <i>standard error of the mean</i> (<i>SEM</i>). * p < 0.05; ** p < 0.01; *** p < 0.001.</p

Difference of functional connectivity between control subjects and TLE patients.

<p>The p-value maps on the sagittal, coronal and axial MR images show the significant differences in mean functional connectivity within the DMN between control subjects and TLE patients in the delta, theta, alpha, beta and gamma bands. Cortical areas encircled by dashed circles indicate cortical areas with significant changes. The maps are color coded with significant values (p < 0.05) denoted in white. The number above the image indicates the slice number.</p