Pregnancy among cystic fibrosis women in the era of CFTR modulators

J Cyst Fibros. 2017 Nov;16(6):687-694. doi: 10.1016/j.jcf.2017.01.008. Epub 2017 Feb 10.


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.

Conclusion: 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.

Keywords: G551D; Ivacaftor; Lumacaftor; Pregnancy.

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols / therapeutic use*
  • Aminopyridines / therapeutic use*
  • Benzodioxoles / therapeutic use*
  • Chloride Channel Agonists / therapeutic use
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / epidemiology
  • Cystic Fibrosis* / genetics
  • Female
  • Humans
  • Pregnancy
  • Pregnancy Complications* / diagnosis
  • Pregnancy Complications* / drug therapy
  • Pregnancy Complications* / epidemiology
  • Pregnancy Complications* / genetics
  • Pregnancy Outcome
  • Pregnancy Rate
  • Pregnancy, High-Risk
  • Quinolones / therapeutic use*
  • Risk Adjustment / methods
  • Risk Adjustment / organization & administration
  • United States / epidemiology


  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Chloride Channel Agonists
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor
  • lumacaftor