Tricco Andrea C, Cogo Elise, Angeliki Veroniki A, Soobiah Charlene, Hutton Brian, Hemmelgarn Brenda R, Moher David, Finkelstein Yaron, Straus Sharon E
Li Ka Shing Knowledge Institute, St, Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario M5B 1 T8, Canada.
Syst Rev. 2014 Jun 25;3:68. doi: 10.1186/2046-4053-3-68.
Epilepsy affects about 1% of the general population. Anti-epileptic drugs (AEDs) prevent or terminate seizures in individuals with epilepsy. Pregnant women with epilepsy may continue taking AEDs. Many of these agents cross the placenta and increase the risk of major congenital malformations, early cognitive and developmental delays, and infant mortality. We aim to evaluate the comparative safety of AEDs approved for chronic use in Canada when administered to pregnant and breastfeeding women and the effects on their infants and children through a systematic review and network meta-analysis.
Studies examining the effects of AEDs administered to pregnant and breastfeeding women regardless of indication (e.g., epilepsy, migraine, pain, psychiatric disorders) on their infants and children will be included. We will include randomized clinical trials (RCTs), quasi-RCTs, non-RCTs, controlled before-after, interrupted time series, cohort, registry, and case-control studies. The main literature search will be executed in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We will seek unpublished literature through searches of trial protocol registries and conference abstracts. The literature search results screening, data abstraction, and risk of bias appraisal will be performed by two individuals, independently. Conflicts will be resolved through discussion. The risk of bias of experimental and quasi-experimental studies will be appraised using the Cochrane Effective Practice and Organization of Care Risk-of-Bias tool, methodological quality of observational studies will be appraised using the Newcastle-Ottawa Scale, and quality of reporting of safety outcomes will be conducted using the McMaster Quality Assessment Scale of Harms (McHarm) tool. If feasible and appropriate, we will conduct random effects meta-analysis. Network meta-analysis will be considered for outcomes that fulfill network meta-analysis assumptions.The primary outcome is major congenital malformations (overall and by specific types), while secondary outcomes include fetal loss/miscarriage, minor congenital malformations (overall and by specific types), cognitive development, psychomotor development, small for gestational age, preterm delivery, and neonatal seizures.
Our systematic review will address safety concerns regarding the use of AEDs during pregnancy and breastfeeding. Our results will be useful to healthcare providers, policy-makers, and women of childbearing age who are taking anti-epileptic medications.
PROSPERO CRD42014008925.
癫痫影响着约1%的普通人群。抗癫痫药物（AEDs）可预防或终止癫痫患者的发作。患有癫痫的孕妇可能会继续服用AEDs。这些药物中的许多会穿过胎盘，增加重大先天性畸形、早期认知和发育迟缓以及婴儿死亡率的风险。我们旨在通过系统评价和网状荟萃分析，评估加拿大批准长期使用的AEDs在孕妇和哺乳期妇女中使用时的相对安全性，以及对其婴儿和儿童的影响。
将纳入研究AEDs（无论其适应证如何，如癫痫、偏头痛、疼痛、精神疾病）在孕妇和哺乳期妇女中使用对其婴儿和儿童影响的研究。我们将纳入随机临床试验（RCTs）、准RCTs、非RCTs、前后对照研究、中断时间序列研究、队列研究、登记研究和病例对照研究。主要文献检索将在MEDLINE、EMBASE和Cochrane对照试验中央注册库中进行。我们将通过检索试验方案注册库和会议摘要来查找未发表的文献。文献检索结果筛选、数据提取和偏倚风险评估将由两人独立进行。如有分歧将通过讨论解决。实验性和准实验性研究的偏倚风险将使用Cochrane有效实践和护理组织偏倚风险工具进行评估，观察性研究的方法学质量将使用纽卡斯尔-渥太华量表进行评估，安全结果报告质量将使用麦克马斯特伤害质量评估量表（McHarm）工具进行评估。如果可行且合适，我们将进行随机效应荟萃分析。对于符合网状荟萃分析假设的结果将考虑进行网状荟萃分析。主要结局是重大先天性畸形（总体及按特定类型），次要结局包括胎儿丢失/流产、轻微先天性畸形（总体及按特定类型）、认知发育、精神运动发育、小于胎龄、早产和新生儿惊厥。
我们的系统评价将解决孕期和哺乳期使用AEDs的安全性问题。我们的结果将对医疗保健提供者、政策制定者以及正在服用抗癫痫药物的育龄妇女有用。
PROSPERO CRD42014008925。
