Pregnancy outcomes in CF before and after introduction of CFTR gene modulator therapy

Pregnancy has historically been uncommon in women with cystic fibrosis (CF) due to poor survival, female subfertility and impact on lung function. The advent of cystic fibrosis transmembrane conductance regulator modulators (CFTRM) has transformed the management of CF by improving lung function, nutritional status and reducing pulmonary exacerbations. Despite more women with CF becoming pregnant, there are few studies assessing pregnancy outcomes before and after the introduction of CFTRM. To study this further, we looked at all live births to women with CF attending our large adult CF Centre between August 2010 and March 2023, comparing those on a CFTRM at conception with the remainder. We looked at demographics, pregnancy complications, length of gestation, birth-weight and neonatal complications. There were 41 pregnancies in 36 women, 23 taking CFTRM therapy at conception. Two women in the non-CFTRM group have since died, 1 from a CF-related cause. The mean age at conception (28 vs 30) and BMI (24.5 vs 24.3) were similar between the two groups (CFTRM and remainder respectively). In the CFTRM group there were more high risk (FEV1 <60% predicted) pregnancies (30% vs 5%) and fewer women required IVF (9% vs 39%). Interestingly, more pregnancies were delivered by elective C-section in the CFTRM group (43% vs 17%). Pregnancy outcomes were similar between the two groups and were generally favourable in both. The pregnancy rate has increased since the widespread introduction of CFTRM in September 2020 – there were 21 live births between Aug. 2010 and Aug. 2020, and 19 since Sept. 2020 (2.5 births/year vs 5.8 births/year). The increased birth rate and high risk pregnancies may reflect growing confidence.