Written by: Lauren Hardy
Edited by: Akshay Pokala, Shivani Patel, Howard Nicholson III
Illustrated by: Ariel Brown-Ogha
In the Summers of 2022 and 2023, I had the opportunity to work alongside pulmonologists Emily DiMango and Claire Keating and their dedicated Cystic Fibrosis (CF) research team at the Gunnar Esiason Adult Cystic Fibrosis and Lung Program within Columbia University Irving Medical Center. Pulmonologists primarily focus on the respiratory system, which includes the lungs and respiratory tracts [1]. They often specialize in respiratory diseases, such as asthma, pulmonary fibrosis, and Chronic Obstructive Pulmonary Disease (COPD) [1]. During this enriching experience, I was immersed in the world of pulmonology and CF, gaining a significant understanding of the challenges and potential solutions in the lives of individuals affected by this complex genetic condition.
The Gunnar Esiason Adult Cystic Fibrosis and Lung Program stands as a premier site for diagnostic care with a mission to offer comprehensive treatment of CF and related comorbidities in adults [2]. CF is a multifaceted genetic condition, mainly impacting the respiratory and digestive systems [3]. The hallmark of CF is the production of thick, sticky mucus, which, in turn, leads to severe respiratory issues, digestive problems, and an overall decline in health. It is a life-altering condition, but recent advancements have brought a glimmer of hope to those affected [3].
In 2020, the CF community celebrated a beacon of hope in the form of Trikafta which gained FDA approval and brought about remarkable improvements in the lives of CF patients. Trikafta is a medication that enhances the function of the CFTR protein, which is responsible for regulating salt and water movement in and out of cells [4]. This protein aids in thinning and clearing the thick mucus found in the organs of CF patients, ultimately improving lung function and overall health [4]. The arrival of Trikafta significantly improved the quality of life for CF patients, specifically in regards to respiratory status [5-7].
Unfortunately, CF poses unique reproductive challenges for those endeavoring to conceive and expectant mothers with the condition [8]. However, Trikafta has been a game-changer. While it offered newfound fertility opportunities to women with CF who had long battled infertility, the introduction of a new medication during such a critical period as pregnancy is still understudied [9]. Many women I worked with at the Gunnar Esiason Adult Cystic Fibrosis and Lung Program were eager to understand the potential impact of Trikafta on fertility, especially those who had struggled with infertility for years, and they were concerned about the medication's effects throughout the course of a pregnancy. Moreover, there were heightened worries about health and safety during pregnancy, given the uncertainties surrounding how Trikafta might affect both the mother and the developing fetus and long-term implications postpartum. These questions and concerns underscore the importance of conducting comprehensive research and monitoring of patients to ensure the well-being of both the mother and fetus when considering Trikafta use during pregnancy [10].
This is where the Mayflower Project comes into the spotlight. The Mayflower Project is an initiative that focuses on closely monitoring the health of pregnant women with CF who are taking Trikafta [11]. Many programs, including the Gunnar Esiason Adult Cystic Fibrosis and Lung Program, participate in the project. Its primary objective is to assess the well-being of both the pregnant woman and her unborn fetus. Since there is not much data on how the medication affects unborn fetuses, there are many unknowns. Understanding the effects of Trikafta on pregnant women is vital for several reasons. Firstly, the health and development of the unborn fetus are of overriding concern, and any potential risks or benefits need to be thoroughly evaluated to ensure the well-being of the fetus. Secondly, this knowledge is essential for providing informed medical advice to pregnant women with CF, helping them make the best choices for their health and their fetus' future. By shedding light on these unknowns, the Mayflower Project plays a crucial role in improving the quality of care and decision-making for pregnant women with CF and their unborn fetus [11].
One of the dilemmas faced by pregnant women with CF is whether to continue taking Trikafta during pregnancy or to discontinue it temporarily [12]. The decision is far from straightforward. Discontinuing the medication during pregnancy poses its own set of risks. It may weaken the mother's immune system, potentially making her more susceptible to infections, which can harm both her and the developing fetus [13]. Additionally, discontinuation may lead to a decline in lung function, potentially increasing the risk of miscarriage [11, 13].
The Mayflowers (participants in the Mayflower project) undergo a carefully structured process during their pregnancies [11]. Throughout three trimesters of their pregnancies, these women participate in a series of critical medical examinations. These evaluations involve monitoring their vitals and conducting blood tests to assess how the prescribed medications are working in conjunction with the growth of the fetus and the overall health of the mothers who have CF [11]. The process also entails collaboration with obstetricians and gynecologists (OB-GYNs) to ensure the best possible outcomes for both mother and fetus [2].
The Mayflower Project's long-term vision extends beyond the immediate pregnancy-related concerns of women with CF [2]. Instead, it aims to contribute to broader research efforts in managing CF and addressing infertility issues in affected women. It also aspires to make it easier for individuals with CF by potentially developing new, effective drugs akin to Trikafta, which has already revolutionized the treatment of the illness. The project also focuses on women who have successfully become pregnant despite having CF, which is a significant achievement in itself. The Mayflower Project is committed to the long-term plan of improving the quality of life and health outcomes for future generations of individuals with CF [2].
The Mayflower Project shines a spotlight on the often overlooked experiences of pregnant women living with CF. Their unique journey is a delicate balance between managing their health and ensuring the well-being of their fetus. Through careful monitoring, the project aims to provide insights that will help expectant mothers and their healthcare providers make informed decisions about the use of Trikafta during pregnancy. From my experience, during my time at Gunnar Esiason Adult Cystic Fibrosis and Lung Program, I find the Mayflower Project stands as a beacon of hope for pregnant women with CF. It represents a vital step towards understanding the impact of Trikafta on fetal development and the overall health of expectant mothers. As research continues, this initiative promises to provide the answers and guidance needed to navigate the complex intersection of CF, pregnancy, and cutting-edge treatments like Trikafta. Ultimately, it is about empowering women with CF to make the best decisions for themselves and their growing families.
References
[1] Kimble, B. (2019, May 14). Know your providers: What does a pulmonologist do?. American Lung Association. https://www.lung.org/blog/know-your-providers-pulmonologist#:~:text=A%20pulmonologist%20is%20a%20physician,want%20to%20solve%20the%20problem.
[2] DiMango, E., & Keating, C. (2023, September 11). Cystic fibrosis: Columbiadoctors - New York. ColumbiaDoctors. https://www.columbiadoctors.org/specialties/lung-breathing-disorders/our-services/cystic-fibrosis
3] Foundation, C. F. (2023). About Cystic Fibrosis. Cystic Fibrosis Foundation. https://www.cff.org/intro-cf/about-cystic-fibrosis
[4] Zaher, A., ElSaygh, J., Elsori, D., ElSaygh, H., Sanni, A., Elsaygh, H., & Sanni, A. (2021). A review of Trikafta: triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Cureus, 13(7).
[5] Zemanick, E. T., Taylor-Cousar, J. L., Davies, J., Gibson, R. L., Mall, M. A., McKone, E. F., ... & McColley, S. A. (2021). A phase 3 open-label study of elexacaftor/tezacaftor/ivacaftor in children 6 through 11 years of age with cystic fibrosis and at least one F508del allele. American journal of respiratory and critical care medicine, 203(12), 1522-1532.
[6] Middleton, P. G., Mall, M. A., Dřevínek, P., Lands, L. C., McKone, E. F., Polineni, D., ... & Jain, R. (2019). Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. New England Journal of Medicine, 381(19), 1809-1819.
[7] Pharmaceuticals, V. (2019). TRIKAFTA® is a breakthrough treatment for people with cystic fibrosis (CF) as young as 2 years old. Patient Information | TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor). https://www.trikafta.com/
[8] Shteinberg, M., Taylor-Cousar, J. L., Durieu, I., & Cohen-Cymberknoh, M. (2021). Fertility and pregnancy in cystic fibrosis. Chest, 160(6), 2051-2060.
[9] Taylor-Cousar, J. L. (2020). CFTR modulators: impact on fertility, pregnancy, and lactation in women with cystic fibrosis. Journal of Clinical Medicine, 9(9), 2706.
[10] Foundation, C. F. (2023). MAYFLOWERS: Study of pregnancy in women with cystic fibrosis (MAYFLOWERS-OB-20) | CFF Clinical Trials Tool. Cystic Fibrosis Foundation https://apps.cff.org/Trials/Finder/details/618/MAYFLOWERS-Study-of-pregnancy-in-women-with-cystic-fibrosis
[11] Jain, R., Magaret, A., Vu, P. T., VanDalfsen, J. M., Keller, A., Wilson, A., ... & Taylor-Cousar, J. L. (2022). Prospectively evaluating maternal and fetal outcomes in the era of CFTR modulators: the MAYFLOWERS observational clinical trial study design. BMJ Open Respiratory Research, 9(1), e001289.
[12] Burn, S. C., Looby, A. A., Johnson, K., Cross, S. N., & Jones, C. (2022). Trikafta in pregnancy: a clinical case series. American Journal of Obstetrics & Gynecology, 226(1), S393-S394.
[13] Qiu, F., Habgood, M., & Schneider-Futschik, E. K. (2020). The balance between the safety of mother, fetus, and newborn undergoing cystic fibrosis transmembrane conductance regulator treatments during pregnancy. ACS Pharmacology & Translational Science, 3(5), 835-843.