Comparative safety of anti-epileptic drugs among infants and children exposed in utero or during breastfeeding: Protocol for a systematic review and network meta-analysis

被引：10
作者：
Tricco A.C. [1 ]
Cogo E. [1 ]
Angeliki V.A. [1 ]
Soobiah C. [1 ,2 ]
Hutton B. [3 ]
Hemmelgarn B.R. [4 ]
Moher D. [3 ]
Finkelstein Y. [5 ,6 ,7 ]
Straus S.E. [1 ,8 ]
机构：
[1] Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, M5B 1 T8, ON
[2] Institute of Health Policy Management and Evaluation, University of Toronto, Health Sciences Building, 155 College Street, Suite 425, Toronto, M5T 3 M6, ON
[3] Centre for Practice-Changing Research, Ottawa Hospital Research Institute, The Ottawa Hospital - General Campus and University of Ottawa, 501 Smyth Road, Box 711, Ottawa, K1H 8 L6, On
[4] Departments of Medicine and Community Health Sciences, University of Calgary, TRW Building, 3rd Floor, 3280 Hospital Drive NW, Calgary, T2N 4Z6, AL
[5] The Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, ON
[6] Department of Pediatrics, University of Toronto, 172 St. George Street, Toronto, M5R 0A3, ON
[7] Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 4207, Toronto, M5S 1A8, ON
[8] Department of Geriatric Medicine, University of Toronto, 172 St. George Street, Toronto, M5R 0A3, ON
来源：
Systematic Reviews | / 3卷 / 1期
关键词：
Anti-epileptic drug; Breastfeeding; Comparative safety; Congenital malformation; Epilepsy; Fetus; Infant; Network meta-analysis; Pregnancy; Systematic review;
D O I：
10.1186/2046-4053-3-68
中图分类号：
学科分类号：
摘要：
Background: 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. Methods: 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. Discussion: 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. Systematic review registration: PROSPERO CRD42014008925. © 2014 Tricco et al.; licensee BioMed Central Ltd.
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