To compare the antiepileptic drug (AED) treatment patterns, seizure control, and folic acid supplementation between planned and unplanned pregnancy in women with epilepsy (WWE) and to investigate the effects of planned pregnancy on fetal outcomes. Methods: A prospectively collected database including WWE with pregnancy from Feb 2010 to Dec 2018 was retrospectively analyzed. Planned pregnancy was defined as WWE being regularly supervised by epileptologists from the time of intended pregnancy until delivery. Clinical characteristics and fetal outcomes were compared between the planned and unplanned pregnancy groups. Logistic regression was used to identify modifiable factors associated with adverse fetal outcomes. Results: A total of 188 planned pregnancies and 289 unplanned pregnancies were enrolled in our study. Among planned pregnancies, 66.0 % took AED monotherapy, and 32.4 % received polytherapy. Among unplanned pregnancies, 58.1 % didn't take AEDs, 28.0 % took monotherapy, and 12.8 % received polytherapy. The planned pregnancies had less generalized tonic-clonic seizures (P = 0.002) and higher proportion of being seizure-free (41.0 % vs. 22.8 %; P < 0.001). All planned pregnancies took folic acid while 39.8 % of unplanned pregnancies never took it (P < 0.001). The planned pregnancies had less rates of induced abortions (2.7 % vs. 13.5 %; P < 0.001), preterm births (3.3 % vs. 20.4 %; P < 0.001), and major congenital malformations (1.6 % vs. 7.5 %; P = 0.016). Pregnancy planning was independently associated with adverse fetal outcomes (adjusted OR, 0.14; 95 % CI, 0.08−0.27; P < 0.001). Conclusion:Planned pregnancy in WWE contributes to more optimized AED pattern, better seizure control, more appropriate folic acid supplementation, and less adverse fetal outcomes.

Background: Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) and lamotrigine (LTG) would bring some abnormalities on liver function, ranging from mild malfunction of liver tests to serious hepatotoxicity. The former manifests temporary and reversible elevation of bilirubin and liver enzyme, which is usually dose-dependent and the abnormality can return to normal shortly after the drug was withdrawn. Levetiracetam (LEV), as a newly broad-spectrum AED with relatively fewer side-effects and fewer drug interactions, is increasingly used as adjunctive therapy to treat generalized epilepsy. Gilbert syndrome（GS）is characterized by mild, chronic, intermittent unconjugated hyperbilirubinemia without other hepatic diseases. Fasting, stress, along with some liver toxic drugs would make it clinically apparent. However, when GS co-exists with epilepsy, how to differentiate which one is responsible for the abnormality of bilirubin poses a challenge to us. We herein describes a patient with epilepsy complicated by mildly and intermittently elevated bilirubin, and after various examinations especially for whole-exome sequencing（WES）and liver biopsy, we made a definite diagnosis of GS. Case presentation: A 25-year-old male with epilepsy suffering from intermittently and mildly elevated bilirubin, and relevant imaging information led us consider the diagnosis of idiopathic generalized epilepsy (IGE). After administration of AEDs, the indirect bilirubin remained still slightly elevated even while taking LEV. Then he was referred to the department of gastroenterology in our hospital, the results of diagnostic tests, clinical manifestation, imaging studies, WES and liver biopsy all made contributions to our diagnosis of GS rather than the hepatic injury induced by AEDs. Conclusions: This report presents us with a case of an epilepsy patient complicated by repeatedly elevated bilirubin and finally was diagnosed with GS. By referring to literatures and genetic testing, though, no shared genetic and pathophysiological basis between epilepsy and GS was found, and enzymes responsible for the metabolism of AEDs took no part in the pathogenesis of GS. Our experiences will help clinicians to better differentiate the etiology of repeatedly elevated bilirubin of epilepsy patients during the process of treatment. Key words: Epilepsy, Gilbert syndrome, Valproic acid, Lamotrigine, Levetiracetam, hyperbilirubinemia.