CF treatment in pregnant women may also help their babies, per study
'Potential fetal benefit' seen in cases, but approach remains experimental
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Women with cystic fibrosis (CF) who continue on CFTR modulator therapy during pregnancy show stable health and no increase in birth complications, according to a new review.
At the same time, published case reports and small studies have found that intentionally treating a baby with CF before birth using these drugs — taken by the mother during pregnancy — has shown early signs of benefits for the fetus. This has included easing bowel blockages and improving pancreatic function for babies still in the womb.
Despite these positive early findings, the researchers stressed that this approach remains experimental, with unanswered questions about its long-term safety and the best timing of treatment for an affected fetus.
“Maternal continuation to treat maternal CF appears safe and beneficial, and early evidence indicates potential fetal benefit in selected circumstances,” the authors wrote, stressing, however, that “knowledge gaps remain, and therapy for fetal indications is investigational.”
Still, “prenatal CFTR modulator therapy shows promise as the first fetal therapy for CF,” the team wrote.
In all cases, the scientists noted, “robust counseling, interdisciplinary coordination, and structured monitoring are essential, alongside ongoing research to define therapeutic windows, safety, and long-term outcomes.”
The review study, “Prenatal CFTR modulator therapy for fetal cystic fibrosis: Emerging evidence, clinical considerations, and future directions,” was led by U.S. researchers and published in the journal Pregnancy.
Because CF is an inherited genetic disorder, the buildup of thick mucus in the lungs, pancreas, intestines, and other organs that marks the condition can begin during fetal development. Changes to the pancreas — an organ in the upper abdomen that plays a key role in digestion — can appear as early as the second trimester, or the middle part of pregnancy. There’s also evidence of thickened meconium, which is the earliest stool.
CFTR modulators, such as Trikafta and Alyftrek, are treatments designed to address the underlying cause of CF. Studies confirm these therapies can improve lung and digestive function and extend survival in people with CF.
As a result of such treatment advances, more CF patients are becoming pregnant, and many choose to continue taking their modulator throughout pregnancy.
Large study looked at impact of Trikafta on babies
In this review, the researchers examined the impact of these medications on the mother and fetus, either because the mother has CF and has chosen to continue treatment or the fetus has CF. The authors gathered data from pregnancy studies, drug measurements, case reports of treated fetuses, animal research, and a workshop of CF experts.
For mothers with CF who continue their modulator during pregnancy, the current evidence is reassuring, according to the researchers: Lung function and nutritional status tend to stay stable or improve for pregnant women. Additionally, there has been no increase in major birth defects, premature births, or miscarriages beyond what would normally be expected, the data show.
One large study found that babies born to mothers on Trikafta were less likely to be small for their gestational age, or how far along in the pregnancy the mothers were at the infants’ birth. Further, more than three-quarters of pregnancies reached full term.
No stillbirths or newborn deaths have been reported in the largest case series collected to date, the researchers also noted. Side effects in mothers are usually mild, such as a rash, headache, abdominal pain, or diarrhea, data show. In one study, severe liver injury occurred in less than 1% of cases.
Because these CF medications cross the placenta, the fetus is directly exposed. As such, some doctors may start a pregnant CF carrier or a mother with CF on modulator therapy specifically because an ultrasound has shown signs of meconium ileus, a blockage in the fetus’ intestine caused by thickened meconium.
Several case reports and small case series describe this blockage reducing or resolving after modulator therapy was started. One case saw worsening bowel dilation after Trikafta was started, which is why some protocols now recommend an MRI of the fetal bowel in more severe cases. Starting the medication earlier in pregnancy appears to be more effective than starting later, data show.
Prenatal CF treatment shows potential to prevent damage
Beyond the bowel, there are early, limited signs that prenatal exposure might help preserve other organs affected by CF, according to the review. Some fetuses exposed to Trikafta from conception have shown preserved pancreatic function despite being predicted to have pancreatic insufficiency.
In terms of the male reproductive tract, nearly all CF males are born without the vas deferens, the tube that carries sperm, due to damage that occurs before birth. One case report described two infants whose vas deferens appeared to be preserved after their mother took Trikafta throughout pregnancy. Still, the researchers noted the window for preventing this damage may occur earlier in pregnancy, in the first or early second trimester.
The medications also pass into breast milk, but at levels lower than what’s found in the mother’s blood — and too low for such CF treatment to be effective on its own. Yet, some case reports describe infants with CF maintaining good pancreatic function through breastfeeding alone when their mother was on Trikafta. Because of the uncertainty, some CF centers support continued breastfeeding with maternal modulator use while others do not, and this varies internationally, the researchers found.
Small cataracts, a clouding of the eye’s lens that’s not large enough to affect vision, have occasionally been reported in babies exposed to Trikafta before birth. Even so, this hasn’t been seen consistently across all groups studied, and has not been reproduced in CF animal models, the data showed.
Prenatal exposure can also lower a marker called immunoreactive trypsinogen, which is used in newborn screening, and this has led to false-negative CF screening results in some exposed infants, the researchers noted. Because of this, babies known to have been exposed before birth are advised to undergo additional diagnostic tests regardless of the newborn screening results.
Prenatal [CF treatment] is an emerging frontier in molecular fetal medicine. … CF specialists must provide nuanced counseling, structured monitoring, and interdisciplinary care while supporting ongoing research to define therapeutic windows, long-term safety, and standardized protocols.
The authors note that using CFTR modulators to treat a fetus diagnosed with CF is still investigational, meaning it isn’t approved and there are no long-term safety data in humans, including on brain development. The team recommended that this kind of treatment occur at specialized centers. In an additional consideration, insurance coverage for treating a carrier mother isn’t guaranteed and can be a barrier to access, the team noted.
As to future directions, the authors called for registries that track fetal imaging, cord blood drug levels, and long-term outcomes to better define when this prebirth treatment helps and how it should be used safely over time.
“Prenatal CFTR modulator therapy is an emerging frontier in molecular fetal medicine,” the researchers concluded. “CF specialists must provide nuanced counseling, structured monitoring, and interdisciplinary care while supporting ongoing research to define therapeutic windows, long-term safety, and standardized protocols.”
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