title: Diclofenac/misoprostol during early pregnancy and the risk of miscarriage: a Danish nationwide cohort study.
abstract: Misoprostol can be used in the prevention of gastric ulcer in treatment with diclofenac and is used in rheumatic diseases. Since misoprostol causes contractions of the uterus, it can also be used to induce abortions when administrated vaginally. The aim of the study was to investigate if early pregnancy exposure to oral diclofenac/misoprostol was associated with miscarriage.
  
  
  
  We conducted a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2011. All births were identified using the Medical Birth Registry, and all records of induced abortion and miscarriage were from the National Hospital Register. Data on drug use were from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women exposed to diclofenac/misoprostol in early pregnancy.
  
  
  
  We identified 1,338,824 pregnancies (970,491 births, 142,147 miscarriages, 226,145 induced abortions). One hundred sixty-six were exposed to diclofenac/misoprostol in the early pregnancy of which 28.3 % (47) ended up in a miscarriage compared to 10.6 % among unexposed. The adjusted hazard ratio of having a miscarriage after exposure to diclofenac/misoprostol in the first trimester was 3.6 (CI 95 % 2.6-4.9).
  
  
  
  We found an increased risk of miscarriage after exposure to diclofenac/misoprostol during the early pregnancy. Women in the fertile age should not be treated with the combination of diclofenac/misoprostol if other options were available.
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark. jta@rh.dk.|Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark. jta@rh.dk.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Andersen
authors.affiliation: Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mastrogiannis
authors.affiliation: Mental Health Centre Copenhagen, Copenhagen, Denmark.
authors.forename: Nadia L
authors.initials: NL
authors.lastname: Andersen
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Petersen
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Broedbaek
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark.
authors.forename: Vanja
authors.initials: V
authors.lastname: Cejvanovic
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark.
authors.forename: Torben K
authors.initials: TK
authors.lastname: Nielsen
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark.
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Poulsen
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark.
authors.forename: Espen
authors.initials: E
authors.lastname: Jimenez-Solem
mesh_terms: D000028:Abortion, Induced / Q000706:statistics & numerical data; D000022:Abortion, Spontaneous / Q000453:epidemiology* / Q000209:etiology; D000328:Adult; D015331:Cohort Studies; D003718:Denmark; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D016595:Misoprostol; D004008:Diclofenac
keywords: Arthrotec; Drug during pregnancy; Maternal fetal medicine; Miscarriage; Misoprostol; Rhematology; Spontaneous abortion