Parenthood impacts short-term health outcomes in people with cystic fibrosis.

People with cystic fibrosis (CF) are living longer, healthier lives. A growing number are considering parenthood. There is a substantial knowledge gap regarding the health impacts of parenthood on people with CF. Using data from the United Kingdom CF registry from 2015 to 2019, we evaluated the impact of having a child on percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), and pulmonary exacerbations via multivariable longitudinal data analysis adjusting for age and sex in the year before a person with CF became a parent to the first year following parenthood. We examined whether changes from pre- to post-parenthood differed by sex or CF transmembrane conductance regulator (CFTR) modulator use. Among 296 people with CF who became parents, we found a significant decrease in ppFEV1, (adjusted mean difference -3.19, CI: -4.31, -2.07; p<0.01) and BMI (adjusted mean difference -0.28, CI: -0.51, -0.05; p<0.02) and a significant increase in pulmonary exacerbations (adjusted rate ratio 1.3, CI: 1.13, 1.49; p<0.01) in the year following the birth of a child compared to the year prior. Further analysis showed that CFTR modulator use mitigated parenthood impacts on ppFEV1, but not on BMI and pulmonary exacerbations. Females experienced significantly worse impacts on BMI from pre- to post-parenthood compared to males. Parenthood adversely impacts short-term health outcomes for people with CF and CFTR modulator use mitigates such effects. To better understand the impact of the widespread use of highly effective CFTR modulators, longer-term, prospective parenthood studies are needed.

Kazmerski TM ，Jain R ，Lee M ，Taylor-Cousar JL ... -  《-》

Association between unplanned pregnancies and maternal exacerbations in cystic fibrosis.

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). 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. 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. 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.

Peng G ，Taylor-Cousar JL ，Lee M ，Keller A ，West NE ，Kazmerski TM ，Goralski JL ，Aitken ML ，Roe AH ，Hadjiliadis D ，Uluer A ，Flume PA ，Mody S ，Bray LA ，Jain R ... -  《-》

Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy.

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States; little is known about pregnancy outcomes with modulator use. The aim of this retrospective study was to determine the impact of CFTR modulators on maternal outcomes. Does pregnancy differentially affect outcomes in female individuals with CF with and without CFTR modulator exposure? Data on pregnancies from 2010 to 2021 were collected from 11 US adult CF centers. Multivariable longitudinal regression analysis was performed to assess whether changes in percent predicted FEV1 (ppFEV1), BMI, pulmonary exacerbations (PEx), and Pseudomonas aeruginosa prevalence differed from prior to, during, and following pregnancy according to CFTR modulator use while adjusting for confounders. Infant outcomes are also described based on maternal modulator use. Among 307 pregnancies, mean age at conception was 28.5 years (range, 17-42 years), before pregnancy ppFEV1 was 74.2, and BMI was 22.3 kg/m2. A total of 114 pregnancies (37.1%) had CFTR modulator exposure during pregnancy (77 with highly effective modulator therapy [HEMT] and 37 with other modulators). The adjusted mean change in ppFEV1 from before pregnancy to during pregnancy was -2.36 (95% CI, -3.56 to -1.16) in the unexposed group and 2.60 (95% CI, 0.23 to 4.97) in the HEMT group, with no significant change from during pregnancy to 1 year after pregnancy. There was an overall decline in ppFEV1 from before pregnancy to after pregnancy in the no modulator group (-2.56; 95% CI, -3.62 to -1.49) that was not observed in the HEMT group (1.10; 95% CI, -1.13 to 3.34). PEx decreased from before pregnancy to after pregnancy in the HEMT group, and BMI increased from before pregnancy to during pregnancy in all groups but with no significant change after pregnancy. Missing infant outcomes data precluded firm conclusions. We observed superior pregnancy and after pregnancy pulmonary outcomes in individuals who used HEMT, including a preservation of ppFEV1, compared with those unexposed to HEMT.

Jain R ，Peng G ，Lee M ，Keller A ，Cosmich S ，Reddy S ，West NE ，Kazmerski TM ，Goralski JL ，Flume PA ，Roe AH ，Hadjiliadis D ，Uluer A ，Mody S ，Ladores S ，Taylor-Cousar JL ... -  《-》

Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis.

Patel S ，Sinha IP ，Dwan K ，Echevarria C ，Schechter M ，Southern KW ... -  《Cochrane Database of Systematic Reviews》

Assessing the health impacts of parenthood on people with cystic fibrosis: the HOPeCF prospective cohort protocol.

People with cystic fibrosis (CF) are living longer and healthier lives with a growing number considering and pursuing parenthood. The decision of whether to become a parent is complex for people with CF, and CF is a major factor in reproductive decision-making. Unfortunately, in people with CF who become parents, there are no prospective studies of disease trajectory, no data on the impact of parenthood on mental health, disease self-management, or quality of life, and no research regarding non-genetic parenthood. Health Outcomes of Parents with CF (HOPeCF) is a prospective, multicentre observational cohort study which will enrol 146 new parents with CF of children less than 5 years of age. The primary aim of this 60-month study is to assess the rate of lung function decline as impacted by mental health, parental stress and responsibility, and the use of CF transmembrane conductance regulator modulators. In addition, we will conduct dyadic interviews with a subset of study participants and their key supports (partner/family/friend) to inform future interventions. This longitudinal, observational multicentre study is a necessary and timely step in understanding parental health outcomes in CF and will provide data essential for care guidance to people with CF, their partners, and healthcare providers. The University of Pittsburgh Institutional Review Board approved this study (STUDY23080161). As people with a variety of paediatric-onset chronic diseases are living longer and considering parenthood, these results may have widespread applicability and will be distributed at international meetings and submitted to peer-reviewed journals.

Kazmerski TM ，Stransky OM ，Lee M ，Prangley KA ，Jain R ，Georgiopoulos AM ，Shaw DS ，Taylor-Cousar J ... -  《BMJ Open Respiratory Research》