title: Disease-modifying anti-rheumatic drug use in pregnant women with rheumatic diseases: a systematic review of the risk of congenital malformations.
abstract: OBJECTIVE
  Despite the high incidence of rheumatic diseases during the reproductive years, little is known about the impact of disease-modifying anti-rheumatic drug (DMARD) use during pregnancy. Our objective was to systematically review and appraise evidence in women with rheumatic disease on the use of traditional and biologic DMARDs during pregnancy and the risk of congenital malformation outcomes.
  
  
  METHODS
  We conducted a systematic search of MEDLINE, EMBASE, and INTERNATIONAL PHARMACEUTICAL ABSTRACTS databases. Inclusion criteria were: 1) study sample including women with rheumatic disease; 2) use of traditional and/or biologic DMARDs during pregnancy; and 3) congenital malformation outcome(s) reported. We extracted information on study design, data source, number of exposed pregnancies, type of DMARD, number of live births, and number of congenital malformations.
  
  
  RESULTS
  Altogether, we included 79 studies; the majority were based on designs that did not involve a comparison group, including 26 case reports, 17 case series, 20 cross-sectional studies, and 4 surveys. Studies that had a comparator group included 1 case control, 10 cohort studies, and 1 controlled trial. Hydroxychloroquine and azathioprine represent the most studied traditional DMARD exposures and, among biologics, most of the reports were on infliximab and etanercept.
  
  
  CONCLUSIONS
  This is the first systematic review on the use of both traditional and biologic DMARDs during pregnancy among women with rheumatic diseases and congenital malformation outcomes, with a focus on study design and quality. Findings confirm the limited number of studies, as well as the need to improve study designs.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada.
authors.forename: Corisande
authors.initials: C
authors.lastname: Baldwin
authors.affiliation: Division of Rheumatology, Department of Medicine, University of British Columbia Faculty of Medicine; Arthritis Research Centre of Canada, Richmond; and Dept.of Experimental Medicine, University of British Columbia Faculty of Medicine, Vancouver, Canada.
authors.forename: Antonio
authors.initials: A
authors.lastname: Avina-Zubieta
authors.affiliation: Arthritis Research Centre of Canada, Richmond, Canada.
authors.forename: Sharan K
authors.initials: SK
authors.lastname: Rai
authors.affiliation: Arthritis Research Centre of Canada, Richmond, Canada.
authors.forename: Erin
authors.initials: E
authors.lastname: Carruthers
authors.affiliation: Arthritis Research Centre of Canada, Richmond; and University of British Columbia Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada. mary.devera@ubc.ca.
authors.forename: Mary A
authors.initials: MA
authors.lastname: De Vera
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D012216:Rheumatic Diseases / Q000188:drug therapy*; D012306:Risk
chemical_list: D018501:Antirheumatic Agents