{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:52:53Z","timestamp":1790214773315,"version":"4.1.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indiana Clinical and Translational Sciences Institute","award":["UL1TR002529"],"award-info":[{"award-number":["UL1TR002529"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR002529"],"award-info":[{"award-number":["UL1TR002529"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Most people with cystic fibrosis (CF) are diagnosed following abnormal newborn screening (NBS), which begins with measurement of immunoreactive trypsinogen (IRT) values. A case report found low concentrations of IRT in an infant with CF exposed to the CF transmembrane conductance regulator (CFTR) modulator, elexacaftor\u2013tezacaftor\u2013ivacaftor (ETI), in utero. However, IRT values in infants born to mothers taking ETI have not been systematically assessed. We hypothesized that ETI-exposed infants have lower IRT values than newborns with CF, CFTR-related metabolic syndrome\/CF screen positive, inconclusive diagnosis (CRMS\/CFSPID), or CF carriers. IRT values were collected from infants born in Indiana between 1 January 2020, and 2 June 2022, with \u22651 CFTR mutation. IRT values were compared to infants born to mothers with CF taking ETI followed at our institution. Compared to infants identified with CF (n = 51), CRMS\/CFSPID (n = 21), and CF carriers (n = 489), ETI-exposed infants (n = 19) had lower IRT values (p &lt; 0.001). Infants with normal NBS results for CF had similar median (interquartile range) IRT values, 22.5 (16.8, 30.6) ng\/mL, as ETI-exposed infants, 18.9 (15.2, 26.5). IRT values from ETI-exposed infants were lower than for infants with abnormal NBS for CF. We recommend that NBS programs consider performing CFTR variant analysis for all ETI-exposed infants.<\/jats:p>","DOI":"10.3390\/ijns9010010","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T02:07:44Z","timestamp":1676945264000},"page":"10","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Immunoreactive Trypsinogen in Infants Born to Women with Cystic Fibrosis Taking Elexacaftor\u2013Tezacaftor\u2013Ivacaftor"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3521-3124","authenticated-orcid":false,"given":"Payal","family":"Patel","sequence":"first","affiliation":[{"name":"Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Yeley","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Wesson","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara G.","family":"Lesko","sequence":"additional","affiliation":[{"name":"Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Slaven","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Chmiel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raksha","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6265-6249","authenticated-orcid":false,"given":"Don B.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0140-6736(20)32542-3","article-title":"Cystic fibrosis","volume":"397","author":"Shteinberg","year":"2021","journal-title":"Lancet"},{"key":"ref_2","first-page":"281","article-title":"CFTR modulators: Transformative therapies for cystic fibrosis","volume":"27","author":"Dwight","year":"2021","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1164\/rccm.202101-0090LE","article-title":"Elexacaftor\/Tezacaftor\/Ivacaftor Improved Clinical Outcomes in a Patient with N1303K-CFTR Based on In Vitro Experimental Evidence","volume":"204","author":"Huang","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","article-title":"Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: A double-blind, randomised, phase 3 trial","volume":"394","author":"Heijerman","year":"2019","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jcf.2021.12.004","article-title":"Drug exposure to infants born to mothers taking Elexacaftor, Tezacaftor, and Ivacaftor","volume":"21","author":"Collins","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"eaau7531","DOI":"10.1126\/scitranslmed.aau7531","article-title":"In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis","volume":"11","author":"Sun","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/S0140-6736(79)90825-0","article-title":"Dried-blood spot screening for cystic fibrosis in the newborn","volume":"1","author":"Crossley","year":"1979","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/MCP.0b013e3282f01120","article-title":"Pregnancy in cystic fibrosis","volume":"13","author":"Tonelli","year":"2007","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.jcf.2021.03.006","article-title":"Maternal and fetal outcomes following elexacaftor-tezacaftor-ivacaftor use during pregnancy and lactation","volume":"20","author":"Jain","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jain, R., and Taylor-Cousar, J.L. (2021). Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era. J. Pers. Med., 11.","DOI":"10.3390\/jpm11050418"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.jcf.2021.03.018","article-title":"Normal pancreatic function and false-negative CF newborn screen in a child born to a mother taking CFTR modulator therapy during pregnancy","volume":"20","author":"Fortner","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1080\/01621459.1955.10501294","article-title":"A multiple comparison procedure for comparing several treatments with a control","volume":"50","author":"Dunnett","year":"1955","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.jcf.2022.04.005","article-title":"A case report of CFTR modulator administration via carrier mother to treat meconium ileus in a F508del homozygous fetus","volume":"21","author":"Szentpetery","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/ajmg.a.30470","article-title":"Cystic fibrosis carriers have higher neonatal immunoreactive trypsinogen values than non-carriers","volume":"135","author":"Castellani","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1002\/ppul.21509","article-title":"Factors accounting for a missed diagnosis of cystic fibrosis after newborn screening","volume":"46","author":"Rock","year":"2011","journal-title":"Pediatr. Pulmonol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kharrazi, M., Sacramento, C., Comeau, A.M., Hale, J.E., Caggana, M., Kay, D.M., Lee, R., Reilly, B., Thompson, J.D., and Nasr, S.Z. (2022). Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors. Int. J. Neonatal Screen., 8.","DOI":"10.3390\/ijns8040058"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jcf.2016.04.008","article-title":"Toward quality improvement in cystic fibrosis newborn screening: Progress and continuing challenges","volume":"15","author":"Farrell","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00431-015-2616-3","article-title":"Screening for cystic fibrosis in New York State: Considerations for algorithm improvements","volume":"175","author":"Kay","year":"2016","journal-title":"Eur. J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/ppul.26209","article-title":"Detection of disease-causing CFTR variants in state newborn screening programs","volume":"58","author":"McGarry","year":"2022","journal-title":"Pediatr. Pulmonol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ymgme.2021.08.008","article-title":"Challenging the dogma of the healthy heterozygote: Implications for newborn screening policies and practices","volume":"134","author":"Farrell","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.jpeds.2005.08.004","article-title":"Newborn screening for cystic fibrosis in Wisconsin: Nine-year experience with routine trypsinogen\/DNA testing","volume":"147","author":"Rock","year":"2005","journal-title":"J Pediatr"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1542\/peds.107.1.1","article-title":"Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Wisconsin Cystic Fibrosis Neonatal Screening Study Group","volume":"107","author":"Farrell","year":"2001","journal-title":"Pediatrics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jmoldx.2015.07.005","article-title":"The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing","volume":"18","author":"Schrijver","year":"2016","journal-title":"J. Mol. Diagn."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Farrell, M.H., Mooney, K.E., Laxova, A., and Farrell, P.M. (2022). Parental Preferences about Policy Options Regarding Disclosure of Incidental Genetic Findings in Newborn Screening: Using Videos and the Internet to Educate and Obtain Input. Int. J. Neonatal Screen., 8.","DOI":"10.3390\/ijns8040054"}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/9\/1\/10\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:50Z","timestamp":1760121470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/9\/1\/10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijns9010010"],"URL":"https:\/\/doi.org\/10.3390\/ijns9010010","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]}}}