{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:02:36Z","timestamp":1790766156372,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pregnancy"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The consequences of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein dysfunction or absence begin during fetal development, with pancreatic, intestinal, hepatobiliary, and reproductive manifestations evident at birth. The advent of CFTR modulator therapies (CFTR modulator)\u2014most notably elexacaftor\/tezacaftor\/ivacaftor (ETI), approved for children and adults with CF who carry responsive variants, and the recently approved vanzacaftor\/tezacaftor\/deutivacaftor (VTD), currently indicated for older pediatric and adult populations\u2014has transformed long\u2010term health outcomes and substantially increased the number of pregnancies among individuals with CF. As maternal use of CFTR modulator during pregnancy has become more common, early observational studies and case series suggest potential fetal benefit for fetuses affected by CF, particularly with respect to inspissated meconium obstructing the terminal ileum, potentially reducing the need for postnatal surgical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To synthesize current evidence regarding maternal, fetal, and neonatal outcomes following prenatal CFTR modulator exposure; describe the rationale and early experience with intentional prenatal therapy for affected fetuses; and outline practical counseling and monitoring strategies. Evidence was drawn from clinical pregnancy cohorts, pharmacokinetic studies, case series treating fetal meconium ileus, mechanistic fetal and animal models, and expert consensus documents, including the PRenatal MOdulator Treatment to PrEvent CF ComplicaTions (PROTECT) Workshop summary. Both maternal\u2010 and fetal\u2010indication uses of CFTR modulator were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Continuation of ETI during pregnancy has been associated with stabilization of maternal pulmonary function and nutritional status and has not been linked to an increased risk of congenital anomalies, preterm delivery, or miscarriage in available observational cohorts. Both ETI and VTD cross the placenta and achieve fetal drug exposure at concentrations expected to be pharmacologically active. Case series in fetuses with CF describe improvement or resolution of prenatal bowel abnormalities indicative of evolving meconium ileus, with suggestive evidence of preservation of exocrine pancreatic function and the male reproductive tract in limited cases. Cataracts have rarely been reported, are typically small and not visually significant, and have not been consistently observed across cohorts. Prenatal exposure may result in falsely negative newborn screening results. However, the optimal timing and duration of prenatal modulator initiation for fetal benefit, fetal pharmacokinetics and pharmacodynamics, and long\u2010term neurodevelopmental outcomes remain uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Prenatal CFTR modulator therapy shows promise as the first fetal therapy for CF. While continuation for maternal CF is supported by available evidence (although not label\u2010approved), fetal\u2010indication use remains investigational. Robust counseling, interdisciplinary coordination, and structured monitoring are essential, alongside ongoing research to define therapeutic windows, safety, and long\u2010term outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pmf2.70317","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:06:38Z","timestamp":1784189198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal CFTR modulator therapy for fetal cystic fibrosis: Emerging evidence, clinical considerations, and future directions"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-1231","authenticated-orcid":false,"given":"Hiba J.","family":"Mustafa","sequence":"first","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine The Fetal Center at Indiana University and Riley Children's Health  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair J.","family":"Blumenfeld","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology Division of Maternal\u2010Fetal Medicine and Obstetrics School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramen H.","family":"Chmait","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Division of Maternal\u2010Fetal Medicine Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Taylor\u2010Cousar","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics National Jewish Health University of Colorado Anschutz Medical Campus  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1588-4852","authenticated-orcid":false,"given":"Jordana E.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital Colorado University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey L.","family":"Martiniano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital Colorado University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7247-7016","authenticated-orcid":false,"given":"Angela","family":"Metcalf","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital Colorado University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Sagel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital Colorado University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith T.","family":"Zemanick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital Colorado University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza A.","family":"Shamshirsaz","sequence":"additional","affiliation":[{"name":"Comprehensive Fetal Care Center at Dell Children's Dell Children's Medical Center  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E.","family":"Szentpetery","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4290-8044","authenticated-orcid":false,"given":"Aaron T.","family":"Trimble","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Allergy, and Critical Care Medicine Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8969-6232","authenticated-orcid":false,"given":"Elizabeth B.","family":"Burgener","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Pediatric Pulmonology &amp; Sleep Medicine Children's Hospital Los Angeles Keck School of Medicine at University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Luna\u2010Paredes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Unidad Multidisciplinar Fibrosis Qu\u00edstica Hospital Universitario 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5537-9482","authenticated-orcid":false,"given":"Isabelle","family":"Sermet\u2010Gaudelus","sequence":"additional","affiliation":[{"name":"Hospital Necker\u2010Enfants Malades, CF Center, Inserm U1151 Universite Paris Cite  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6465-8846","authenticated-orcid":false,"given":"Michael V.","family":"Zaretsky","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Colorado Fetal Care Center University of Colorado School of Medicine  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908639"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32597-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1807120"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000005732"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2024.09.019"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.03.002"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.07.015"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2024.11.011"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2022.04.005"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.03.009"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)64278-2"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32542-3"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.8120"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2023.02.002"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01609-4"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2024.09.011"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.03.006"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2020.02.018"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.03.018"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.12.004"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2022.10.004"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1274303"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000530261"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.7326\/L23-0112"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2024.06.003"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.01.012"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2025.07.013"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2024.2426677"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2011.04.031"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2026.02.001"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2024.09.007"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2024.11.014"},{"key":"e_1_2_12_34_1","volume-title":"Label: TRIKAFTA\u00ae (elexacaftor, tezacaftor, and ivacaftor) tablets [Internet]","author":"Administration. 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