Isabella Hornick , 2025-04-14 12:06:00
April 14, 2025
4 min read
Key takeaways:
- Lung function in pregnant women with cystic fibrosis not using CFTR modulators went down after pregnancy.
- There was no negative change in lung function in those using highly effective modulator therapy.
Percent-predicted FEV1 measured before pregnancy did not fall 1 year after in women with highly effective cystic fibrosis transmembrane conductance regulator modulator exposure during pregnancy, according to data published in CHEST.
Raksha Jain
“[These findings] help clinicians be more supportive of a female with CF becoming pregnant,” Raksha Jain, MD, MSc, ATSF, professor of medicine and director of the adult cystic fibrosis and bronchiectasis program at University of Texas Southwestern Medical Center, told Healio.
Data were derived from Jain R, et al. CHEST. 2024;doi:10.1016/j.chest.2024.09.019.
In a National Jewish Health press release, Jennifer Taylor-Cousar, MD, co-director of the Adult CF Program at the facility, explained that modulators yield better pregnancy outcomes for women, with babies born to women who used modulators being “generally healthy.”
“There used to be 200 or fewer pregnancies for people with CF per year in the U.S. because women with CF died before childbearing age or couldn’t sustain the pregnancy due to their disease,” Taylor-Cousar said in the release.
In a multicenter, retrospective study, Jain, Taylor-Cousar and colleagues analyzed 307 pregnancies of 235 patients with CF (mean age at conception, 28.52 years; 93.61% white; 94.04% non-Hispanic) occurring between 2010 and 2021 to uncover if having vs. not having CFTR modulator exposure impacts percent-predicted FEV1 (ppFEV1), BMI, pulmonary exacerbations and the prevalence of Pseudomonas aeruginosa at three different times: before to during pregnancy, during to after pregnancy and before to after pregnancy.
The group with CFTR modulator exposure was made up of 114 pregnancies, of which 77 received a highly effective modulator therapy (HEMT).
Notably, 74.23% predicted was the mean FEV1 before pregnancy in the total population, according to the study.
In the pregnancies without CFTR modulator exposure, researchers reported that ppFEV1 measured before pregnancy went down during pregnancy (adjusted mean change, –2.36; 95% CI, –3.56 to –1.16), whereas this measure went up in the pregnancies with HEMT exposure (2.6; 95% CI, 0.23-4.97).
Unlike pregnancies with HEMT exposure, pregnancies with exposure to a different CFTR modulator had a lower ppFEV1 during vs. before pregnancy (adjusted mean change, –2.57; 95% CI, –5.62 to 0.47).
The study noted that the adjusted change accounted for several confounders: “age at conception, race and ethnicity, planned pregnancy, baseline BMI and CF-related diabetes and CF-related liver disease before pregnancy, mucolytic and inhaled anti-[P. aeruginosa] antibiotic use, and conception year.”
Similarly, researchers found that ppFEV1 measured before pregnancy in those without CFTR modulator exposure decreased after pregnancy (adjusted mean change, –2.56; 95% CI, –3.62 to –1.49), whereas the change in ppFEV1 between these two times was positive in those with HEMT exposure (1.1; 95% CI, –1.13 to 3.34).
Again, pregnancies with exposure to a different CFTR modulator had a lower ppFEV1 after vs. before pregnancy (adjusted mean change, –1.99; 95% CI, –4.85 to 0.86), according to the study.
When comparing ppFEV1 measures from during vs. 1 year after pregnancy, researchers noted no significant change in each of the groups.
Switching to pulmonary exacerbations, pregnancies exposed to HEMT had a significant reduction in this outcome based on the measures taken before and after pregnancy (adjusted rate ratio = 0.54; 95% CI, 0.33-0.89), according to the study.
Researchers reported the BMI before pregnancy went up during pregnancy regardless of CFTR modulator exposure; however, the change was only significant in pregnancies with no exposure (adjusted mean difference, 2.73; 95% CI, 1.33-4.13).
All three groups showed a decrease in BMI from during to after pregnancy, with the only significant change observed again in pregnancies with no exposure (adjusted mean difference, –2.68; 95% CI, –4.06 to –1.29).
Compared with BMI recorded before pregnancy, BMI after pregnancy did not significantly change in any group.
Additionally, pregnancies with HEMT exposure had a lower prevalence of P. aeruginosa during vs. before pregnancy and after vs. before pregnancy, but researchers said there is a potential confounder to consider when interpreting the results for this outcome.
“Given that [P. aeruginosa] data in sputum could be confounded by ability to collect sputum in people on HEMT, we limit drawing definite conclusions from this information,” Jain, Taylor-Cousar and colleagues wrote.
In terms of outcomes related to delivery and the infant, several did not significantly differ between the pregnancies with no modulator exposure, the pregnancies with HEMT exposure and the pregnancies with other CFTR modulator exposure. These included spontaneous abortions, cesarean section deliveries, preterm birth, low birth weight infants, low 1-minute Apgar scores and low 5-minute Apgar scores. However, the study noted missing data when assessing infant outcomes, which “precluded firm conclusions.”
“When people are considering pregnancy, it is important for clinicians to have more information on the risks and benefits of CFTR modulator use to guide discussions about the implications both of pregnancy itself and of treatments used during pregnancy,” Jain, Taylor-Cousar and colleagues wrote.
“As more [females with] CF reach and surpass their reproductive years, prospective studies and long-term maternal and fetal outcome data are needed to support the best approach to care,” researchers wrote.
Jain told Healio a prospective study with herself and Taylor-Cousar as co-primary investigators is in progress.
“There is an ongoing prospective observational study of pregnancy being sponsored by the CF Foundation called the MAYFLOWERS (Maternal and Fetal Outcomes in the Era of Modulators) study,” Jain said.
For more information:
Raksha Jain, MD, MSc, ATSF, can be reached at raksha.jain@utsouthwestern.edu.
Reference:
Perspective
This carefully designed study is a major milestone in understanding the health of women with CF before, during and after pregnancy. Comparing outcomes of women who took no CFTR modulator therapy, the highly effective modulator elexacaftor/tezacaftor/ivacaftor (ETI) and other modulators (those approved for use prior to the 2019 FDA approval of ETI) is important to allow pregnant people with CF and their health care providers to understand the risks and benefits of continuing this medication regime during pregnancy. Pregnant people are regularly excluded from clinical trials of new medicines, so observational research is critically important. The data clearly show better outcomes for women with CF who took ETI during pregnancy compared with those who took other modulators or no modulators. It’s also reassuring that delivery and infant outcomes were equal among the groups, although longer term outcomes were not evaluated since this study was conducted using medical records of the people with CF.
Susanna A. McColley, MD
Disclosures: McColley reports receiving compensation for being a speaker for and for serving as an advisor for Vertex Pharmaceuticals Inc.
Sources/Disclosures
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Disclosures:
Jain reports receiving funding from the CFF and serving on the Vertex Innovation Awards review committee. Taylor-Cousar reports receiving Cystic Fibrosis Foundation institutional research funding for work related to the manuscript. Please see the study for all other authors’ relevant financial disclosures.