Association between unplanned pregnancies and maternal exacerbations in cystic fibrosis

Introduction: Following availability of the highly effective cystic fibrosis (CF) transmembrane conductance regulator modulator, elexacaftor/tezacaftor/ivacaftor, there was a near doubling of pregnancies reported in the United States (US) in people with CF. We sought to determine health impacts of planned (PP) versus unplanned pregnancies (UP).

Methods: We collected retrospective pregnancy data from January 2010-December 2020 from 11 US CF centers. After adjusting for potential confounding effects, we conducted multivariable, multilevel longitudinal regression analysis using mixed effect modeling to assess whether changes in percent predicted forced expiratory volume in one second (ppFEV₁), body mass index (BMI), and pulmonary exacerbations (PEx) 1-year-pre- to 1-year-post-pregnancy were associated with pregnancy planning.

Results: Our analysis included 163 people with 226 pregnancies; the cohort had a mean age at conception of 29.6 years, mean pre-pregnancy ppFEV₁ of 75.4 and BMI of 22.5 kg/m². PpFEV₁ declined in both PP (adjusted decline of -2.5 (95% CI: -3.8, -1.2)) and UP (adjusted decline of -3.0 (95% CI: -4.6, -1.4)) groups, they did not differ from each other (p = 0.625). We observed a difference in change in the annual number of PEx pre- to post-pregnancy (PP: 0.8 (0.7, 1.1); UP: 1.3 (1.0, 1.7); interaction effect p = 0.029). In a subset of people with available infant data, infants resulting from UP had more preterm births, lower APGAR scores, and more intensive care unit stays.

Conclusions: Following UP, there is an increased trajectory for PEx and potentially for infant complications compared to PP. Clinicians should consider increased surveillance in the setting of UP.