Systematic review of epilepsy in pregnancy: neurodevelopmental and malformation outcomes in the child

Article type
Authors
Bromley R1, Pulman J2, Adab N3, Greenhalgh J4, McKay A5, Tudur-Smith C5, Marson A6, Dickson R4
1Division of Clinical Psychology, University of Manchester, UK
2Cochrane Epilepsy Group, University of Liverpool, UK
3Department of Neuroscience, University Hospitals of Coventry and Warwickshire, UK
4Liverpool Reviews and Implementation Group, University of Liverpool, UK
5Department of Biostatistics, University of Liverpool, UK
6Department of Molecular and Clinical Pharmacology, University of Liverpool, UK
Abstract
Background: Adverse events due to antiepileptic drug (AED) exposure during pregnancy have been well recognised however the level of risk remains unclear. Decisions weighing up the risk of seizures occurring to the mother and harm to the child are important and require best level evidence to support them.

Objectives: To assess the association between prenatal exposure to AED treatments and child outcome including neurodevelopmental functioning and the presence of congenital malformations. Two systematic reviews will be undertaken, one investigating the neurodevelopmental outcomes in the child, one examining major and minor congenital malformations.

Search Methods: We intend to include prospective cohort controlled studies, registry studies and randomised controlled trials (RCTs). We plan to search the Epilepsy Specialised Register, CENTRAL,MEDLINE, EMBASE, Pharmline, Reprotox, conference proceedings, journal supplements and reference lists.

Results: For the neurodevelopmental review, a total of 10 939 reports were available for eligibility checks. Over 550 reports from databases and 46 reports identified from conference proceedings were initially identified as relevant. Further results to follow.

Risk of Bias Assessment: Risk of bias in non-randomised study designs will be assessed using the extended Cochrane risk of bias tool developed by the Non-randomised Studies Methods Group. The tool examines selection bias, performance bias, attrition bias, detection bias and reporting bias with the addition of the influence of confounding variables. A five-point scale ranging from low in bias to high risk of bias according to the risk on the outcome will be employed for several domains. The tool was trialled, amended and made specific to the review content.

Practical Difficulties: Challenges faced include decisions regarding the inclusion of a diverse range of outcomes, eligible study designs, managing data extraction with large number of reviewers and incorporating non-randomised data into risk of bias assessments.