title: Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta-analysis.
abstract: OBJECTIVE
  The objective of this meta-analysis was to determine whether gestational use of hydroxychloroquine (HCQ) for autoimmune disorders leads to an increase in the risk for adverse pregnancy outcomes.
  
  
  METHODS
  MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched from inception to November 21 2014. Studies which reported the outcomes of pregnant women after exposure to HCQ during pregnancy and including a control (unexposed) group were included. Two independent reviewers carried out the review and the quality assessment using the Methodological Index for Non-Randomized Studies (MINORS). A random effects method was used to calculate the odds ratios (OR) for the outcomes.
  
  
  RESULTS
  The meta-analysis reported no significant increases in rates of major congenital (OR 1.13, 95% confidence interval (CI) 0.59, 2.17), craniofacial (OR 0.62, 95% CI 0.13, 3.03), cardiovascular (OR 1.06, 95% CI 0.29, 3.86), genitourinary (OR 1.38, 95% CI 0.42, 4.53), nervous system malformations (OR 1.81, 95% CI 0.31, 10.52), stillbirth (OR 0.69, 95% CI 0.35, 1.34), low birth weight (OR 0.69, 95% CI 0.21, 2.27) or prematurity (OR 1.75, 95% CI 0.95, 3.24). The rate of spontaneous abortions, however, was found to be significantly increased in HCQ exposed pregnancies (OR 1.85, 95% CI 1.10, 3.13). No significant heterogeneity was detected among the studies for the evaluated outcomes except prematurity.
  
  
  CONCLUSIONS
  Prenatal exposure to HCQ for autoimmune diseases does not appear to increase the risk of adverse pregnancy outcomes except spontaneous abortion rate, which may be associated with the underlying disease activity (bias by indication) and needs further investigation.
authors.affiliation: Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey.|The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, 555 University Ave, Toronto, ON, M5G 1X8.|Izmir Katip Celebi Ataturk Egitim ve Arastirma Hastanesi, Klinik Farmakoloji ve Toksikoloji Birimi, 35360, Karabaglar, Izmir, Turkey.
authors.forename: Yusuf Cem
authors.initials: YC
authors.lastname: Kaplan
authors.affiliation: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, 555 University Ave, Toronto, ON, M5G 1X8.
authors.forename: Jak
authors.initials: J
authors.lastname: Ozsarfati
authors.affiliation: Hospital Library & Archives, Hospital for Sick Children and University of Toronto, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
authors.forename: Cheri
authors.initials: C
authors.lastname: Nickel
authors.affiliation: The Motherisk Program, Division of Clinical Pharmacology and Toxicology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, 555 University Ave, Toronto, ON, M5G 1X8.|Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced / Q000453:epidemiology*; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects* / Q000627:therapeutic use; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D064887:Observational Studies as Topic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome / Q000453:epidemiology*; D047928:Premature Birth / Q000139:chemically induced / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine
keywords: autoimmune diseases; congenital abnormalities; hydroxychloroquine; pregnancy; systemic lupus erythematosus