Reference 5

Level I Good quality evidence Systematic review of RCTs with
consistent findings
High quality individual RCT
Level II Limited quality patient
orientated evidence
Systematic review of lower quality
studies or studies with inconsistent
findings
Low quality clinical trial
Cohort studies
Case-control studies
Level III Other Consensus guidelines, extrapolations
from bench research, usual practice,
opinion, disease-oriented evidence
(intermediate or physiologic outcomes
only), or case series

[5] Valproic acid – caution in pregnancy: European Medicines Agency - Pharmacovigilance Risk Assessment Committee. Assessment report EMA/198940/2018 - valproate exposure in pregnancy, 8 February 2018. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Valproate_2017_31/Position_provided_by_CMDh/WC500250221.pdf

Valproic acid – caution in pregnancy: Meador K, Reynolds MW, Crean S, Fahrbach K, Probst C. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008 Sep;81(1):1-13. https://www.ncbi.nlm.nih.gov/pubmed/18565732