Prenatal Therapy for Cystic Fibrosis Shows Promise in Early Cases

Over the past 15 years, cystic fibrosis transmembrane conductance regulator (CFTR) modulators have dramatically improved the lives of individuals with cystic fibrosis (CF), enhancing lung function and overall quality of life. Now, experts at Children’s Hospital Los Angeles (CHLA) are at the forefront of exploring a modern frontier in CF treatment: prenatal therapy for babies diagnosed with the condition.

Addressing Complications Before Birth

The goal of this innovative approach is to reduce the risk of serious CF complications that can arise at birth, most notably bowel obstruction, which often necessitates surgery and prolonged hospitalization. “When babies are born with CF, their lungs are structurally normal, but bowel obstruction can cause major problems,” explains Elizabeth Burgener, MD, a pediatric pulmonologist at CHLA specializing in CF. “The question is whether these therapies can reduce that risk and allow more babies with CF to get a healthier start.”

Early Successes at CHLA

Dr. Burgener and the team at CHLA have successfully treated two pregnancies with CFTR modulators. In both cases, the mothers were carriers of the CF gene but did not have CF themselves. Prenatal ultrasound imaging had raised concerns about meconium ileus—a blockage in the infant’s intestine caused by thickened stool.

Each mother began CFTR modulator therapy around 26 to 27 weeks’ gestation. Following treatment, the ultrasound findings stabilized. Importantly, both babies were born without bowel obstruction and did not require admission to the neonatal intensive care unit.

One of the pregnancies was managed through CHLA’s Fetal-Maternal Center, where maternal-fetal medicine specialists collaborated with pediatric Pulmonology and Neonatology to provide comprehensive counseling, assess fetal imaging, and coordinate care before and after delivery. The second pregnancy was referred from a community maternal-fetal medicine practice.

“These are just two cases, but it is encouraging to see these outcomes,” says Philippe Friedlich, MD, MSEpi, MBA, Chief of Neonatology and Co-Director of the Fetal and Neonatal Institute at CHLA. “Meconium ileus can be life-threatening in some infants. Reducing that complication could have a huge impact on babies and families.”

Continued Therapy and Pancreatic Function

Typically, mothers continue CFTR modulator therapy while breastfeeding, allowing some medication to transfer to the infant. In these two cases, both babies transitioned to direct CFTR modulator therapy after birth and are currently doing well under Dr. Burgener’s close supervision.

Researchers are likewise investigating whether prenatal CFTR modulator therapy can help preserve pancreatic function. Approximately 80% to 90% of individuals with CF experience pancreatic insufficiency—damage to the pancreas that occurs before birth—requiring lifelong enzyme supplementation with meals.

“Meconium ileus almost always occurs in the setting of pancreatic insufficiency,” Dr. Burgener notes. “From other case reports, it appears prenatal therapy can potentially preserve pancreatic function, but there is likely a critical window when it needs to be started.” One of the babies treated prenatally was initially born with pancreatic insufficiency but later regained function after starting direct modulator therapy as an infant. The other baby was born with sufficient pancreatic function.

Uncertainties and Future Directions

While promising, prenatal apply of CFTR modulators is not without uncertainties. Potential risks include effects on liver function, which are closely monitored in both mother and infant, as well as the possibility of cataracts. There are also questions regarding neurodevelopmental outcomes following in-utero exposure.

“There are no prospective clinical trials evaluating CFTR modulators during pregnancy, and these drugs are not FDA approved for prenatal use,” Dr. Burgener emphasizes. “We counsel families very carefully about what we know and what we don’t know.”

Decision-making can be particularly complex when prenatal genetic testing identifies CFTR variants of uncertain significance—mutations that may or may not cause cystic fibrosis. In these situations, physicians must consider incomplete genetic information alongside fetal imaging and family preferences.

Access to this therapy can also be a challenge, as insurance coverage for off-label prenatal use is inconsistent.

Looking Ahead

Clinicians are expanding their thinking beyond gastrointestinal complications, exploring whether early intervention—and continued therapy after birth—could influence the overall course of CF. “We don’t know yet what the long-term impact of prenatal CFTR modulator exposure will be,” Dr. Burgener says. “But it’s compelling to consider whether this could ultimately change the trajectory of this disease for some children.”

Dr. Burgener and Dr. Friedlich stress the importance of early referral to specialized centers like CHLA, which can provide comprehensive care—including genetic counseling, fetal imaging, neonatal management, and long-term CF follow-up. “This is not a decision that should be made in isolation,” Dr. Friedlich says. “You need expertise in maternal-fetal medicine, neonatology, and pulmonology. At CHLA, we work together across all these areas to help each family make the best decision for their baby.”