title: Pregnancy among cystic fibrosis women in the era of CFTR modulators.
abstract: BACKGROUND
  Little is known about how new therapies that partially correct the basic cystic fibrosis (CF) defect (ivacaftor and lumacaftor) might alter hormonal contraceptive effectiveness, impact pregnancy outcomes, or affect pregnancy timing. Examination of pregnancy rates among CF women during periods of CFTR modulator therapy initiation will provide foundation for further research in this area.
  
  
  METHODS
  The Cystic Fibrosis Foundation Patient Registry was used to examine pregnancy rates and outcomes by genotype class before, during, and after the introduction of CFTR modulator therapies between 2005 and 2014.
  
  
  RESULTS
  Among women with CF, ages 15-44years, there was a slight downward trend in annual pregnancy rates from 2005 to 2014 (2% reduction per year, p=0.041). Among women with G551D, pregnancy rates during phase 3 ivacaftor trial years was 14.4/1000 women-years compared to 34.0/1000 prior to the trial period (relative risk [RR]=0.65; 95% CI=0.43-0.96; p=0.011) and 38.4/1000 after drug approval in June 2012 (RR=1.52 post-approval compared to trial period; 95% CI=1.26, 1.83; p<0.001). Pregnancy outcomes did not significantly change between 2005 and 2014 for any genotype class.
  
  
  CONCLUSIONS
  Evidence of significantly increased numbers of pregnancies among women taking approved CFTR modulators is important because of the unknown risk to pregnancy and fetal outcomes. Increases may be temporary following pregnancy prevention during controlled clinical trials, or from altered perceptions about maternal survival with new approved treatments. As more women with CF become eligible to receive modulators, the CF community must study their effect on contraceptive efficacy and safety during pregnancy. With increased health and survival due to modulation, family planning topics will become more common in CF.
authors.affiliation: University of Washington School of Medicine, Department of Pediatrics, Division of Pulmonology, 4800 Sand Point Way NE, Seattle, WA 98105, USA; Seattle Children's Research Institute, Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, PO Box 5371, Seattle, WA 98145, USA. Electronic address: Sonya.Heltshe@Seattlechildrens.org.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: University of Washington School of Medicine, Department of Family Medicine, 4311 11th Ave. NE, Seattle, WA 98105, USA; University of Washington School of Medicine, Department of Obstetrics and Gynecology, 4311 11th Ave. NE, Seattle, WA 98105, USA. Electronic address: godfreye@uw.edu.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Godfrey
authors.affiliation: University of Washington School of Medicine, Department of Family Medicine, 4311 11th Ave. NE, Seattle, WA 98105, USA; University of Washington School of Medicine, Department of Obstetrics and Gynecology, 4311 11th Ave. NE, Seattle, WA 98105, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Josephy
authors.affiliation: University of Washington School of Medicine, Division of Pulmonary and Critical Care Medicine, 1959 N.E. Pacific, Campus Box 356522, Seattle, WA 98195-6522, USA. Electronic address: Moira@uw.edu.
authors.forename: Moira L
authors.initials: ML
authors.lastname: Aitken
authors.affiliation: National Jewish Health Departments of Medicine and Pediatrics, Division of Pulmonary, Critical Care, and Sleep Medicine, 1400 Jackson St. Denver, CO 80206, USA. Electronic address: Taylor-CousarJ@NJHealth.org.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Taylor-Cousar
mesh_terms: D000293:Adolescent; D000328:Adult; D000627:Aminophenols / Q000627:therapeutic use*; D000631:Aminopyridines / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000627:therapeutic use*; D065101:Chloride Channel Agonists / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D018566:Pregnancy, High-Risk; D015363:Quinolones / Q000627:therapeutic use*; D020379:Risk Adjustment / Q000379:methods / Q000458:organization & administration; D014481:United States / Q000453:epidemiology
chemical_list: D000627:Aminophenols; D000631:Aminopyridines; D052117:Benzodioxoles; D065101:Chloride Channel Agonists; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; C569105:lumacaftor
keywords: G551D; Ivacaftor; Lumacaftor; Pregnancy