The Plasma Concentrations Changes Of Lamotrigine And The Related Factors During Pregnancy In Women With Epilepsy:A Systematic Review

Objective:To evaluate changes in lamotrigine(LTG)plasma concentrations before,during,and after pregnancy,To investigate the physiological mechanisms behind the pronounced decline of LTG serum concentrations during pregnancy via a systematic review.Methods:Pubmed,Cochrane Library,Embase,CNKI,VIP,CBM and Wanfang Data were collected for Cohort study and case control study in which lamotrigine was used in pregnant woman for epilepsy.In order to increase the recall ratio,We also find out theses papers' references.Literature screening,data extraction were performed according to the method recommended by Cochrane Collaboration by two experts independently.We extracted the published years,authors,LTG dose,LTG blood concentration,2-N-GLUC/LTG ratio,blood volume,estrogen and other indicators from those Literature.Two researchers assessment article quality by STROBE V4 Checklist Cross-Sectional.Results:We studied initially 4410 articles,but 7 follow-up studies and 5 retrospective descriptive studies,were included finally.In 12 studies,Two studies described LTG blood concentration changes in maternal serum during pregnancy.Two studies described the ratio of LTG in amniotic fluid,umbilical cord blood and maternal blood in 6 hours after delivery.Six studies described the change of LTG clearance in different pregnancy cycles.Two studies described the change of LTG and its metabolite 2-N-GLUC ratio in maternal serum and urine during pregnancy.LTG blood concentration decreased with the increase of the gestational cycle,reaching the lowest level in the third trimester,and reaching the pre-pregnancy level after delivery.In the early stage of pregnancy,the renal LTG clearance rate and the clearance dose began to increase,reaching the highest in the late pregnancy,the 2-N-GLUC dose and the ratio of 2-N-GLUC to LTG increased with the increase of gestational cycle.Part of the LTG can reach amniotic fluid and the umbilical cord through the placenta,and some of it can be left in cord blood.Conclusion:Pregnancy is a complex state where changes in maternal physiology have evolved to favor the development and growth of the placenta and the fetus.The special physiological changes in pregnancy will lead to the decrease of the concentration of LTG blood,which makes the mother increase the dose of LTG during the pregnancy to maintain the stability of the blood drug concentration.