title: Effects of ibuprofen, diclofenac, naproxen, and piroxicam on the course of pregnancy and pregnancy outcome: a prospective cohort study.
abstract: OBJECTIVE
  To investigate the individual effects of ibuprofen, diclofenac, naproxen, and piroxicam on pregnancy outcome.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Norwegian population.
  
  
  METHODS
  A total of 90 417 women and singleton child pairs.
  
  
  METHODS
  The Norwegian Mother and Child Cohort Study and Medical Birth Registry of Norway data sets were used.
  
  
  METHODS
  Infant survival, congenital malformations, structural heart defects, neonatal complications, haemorrhage during pregnancy and postpartum, asthma at age of 18 months.
  
  
  RESULTS
  One or more of the four nonsteroidal anti-inflammatory drugs (NSAIDs) were used by 6511 pregnant women (7.2%). No effect on rates of infant survival, congenital malformation, or structural heart defects was found. The use of ibuprofen in the second trimester was significantly associated with low birthweight (adjusted OR 1.7, 95% CI 1.3-2.3), and ibuprofen use in the second and third trimesters was significantly associated with asthma in 18-month-old children (adjusted OR 1.5, 95% CI 1.2-1.9; adjusted OR 1.5, 95% CI 1.1-2.1). The use of diclofenac in the second trimester was significantly associated with low birthweight (adjusted OR 3.1, 95% CI 1.1-9.0), whereas diclofenac use in the third trimester was significantly associated with maternal vaginal bleeding (adjusted OR 1.8, 95% CI 1.1-3.0). No associations with other neonatal complications were found.
  
  
  CONCLUSIONS
  The lack of associations with congenital malformations is reassuring. The significant association between diclofenac and ibuprofen use late in pregnancy, and maternal bleeding and asthma in the child, respectively, is consistent with their pharmacological effects. The increased risk of low birthweight may partly have been caused by underlying inflammatory conditions, and was reassuringly similar to the expected baseline risk of low birthweight.
authors.affiliation: Division of Pharmacy, School of Pharmacy, University of Oslo, Oslo, Norway. katerina.nezvalova-henriksen@farmasi.uio.no
authors.forename: K
authors.initials: K
authors.lastname: Nezvalová-Henriksen
authors.forename: O
authors.initials: O
authors.lastname: Spigset
authors.forename: H
authors.initials: H
authors.lastname: Nordeng
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015331:Cohort Studies; D004008:Diclofenac / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D009288:Naproxen / Q000009:adverse effects*; D009664:Norway / Q000453:epidemiology; D010894:Piroxicam / Q000009:adverse effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced*; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011446:Prospective Studies; D012306:Risk; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; D004008:Diclofenac; D009288:Naproxen; D007052:Ibuprofen