Prenatal CFTR Modulator Therapy for Fetal CF: A Promising but Still Investigational Frontier

Hiba J Mustafa, Yair J Blumenfeld, Ramen H Chmait, et al.

Summary: This review article brings together current evidence on what happens when pregnant people with CF take CFTR modulator medicines — particularly ETI and a newer combination called vanzacaftor/tezacaftor/deutivacaftor (VTD) — during pregnancy. Studies show that these medicines cross the placenta and reach the developing baby at levels that may be biologically active. Early reports suggest that continuing these medicines during pregnancy can help stabilize the mother's lung health and nutrition. There are also case reports of bowel problems in the unborn baby — a CF complication called meconium ileus — appearing to improve after the mother started or continued modulator therapy. The review also raises concerns, including the risk of falsely reassuring newborn screening results in babies exposed to these medicines before birth, and open questions about the long-term effects on the baby's development.

Why it matters: CF can begin causing damage before birth — conditions like meconium ileus, pancreatic problems, and certain reproductive complications are already present at delivery. The possibility of treating the disease before birth, using medicines that cross the placenta, is a genuinely new frontier. The question of whether to continue these medicines during pregnancy is also immediately practical: because ETI has dramatically improved health and life expectancy, many more people with CF are now becoming pregnant, and their doctors need guidance. There is also an urgent, practical concern: babies exposed to modulators in the womb may test falsely negative on standard newborn CF screening, meaning the disease could be missed unless screening protocols are updated.

What to keep in mind: The evidence reviewed here comes from case reports, small observational studies, animal research, and expert opinion — not from clinical trials designed to test this question directly. Trials in pregnant people are very difficult to conduct for ethical and practical reasons, but the absence of controlled evidence means great caution is warranted. Women who chose to continue their medicines during pregnancy may have been healthier to begin with, making it hard to draw conclusions about outcomes. Eye problems (cataracts) have been observed in some animal studies and require ongoing careful monitoring in humans. The authors appropriately describe treating the unborn baby as an investigational use of these medicines, not a standard recommendation. Long-term follow-up of children born to mothers on these medicines, including careful assessment of brain development, will be essential. The newborn screening problem deserves immediate clinical attention, regardless of broader questions about fetal treatment.

Relevance: Cystic Fibrosis

Source: https://pubmed.ncbi.nlm.nih.gov/42819752/

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