{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:36:55Z","timestamp":1782740215439,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Cystic Fibrosis Foundation","award":["CFF LAI17A0"],"award-info":[{"award-number":["CFF LAI17A0"]}]},{"name":"U.S. Cystic Fibrosis Foundation","award":["CFF PAUL18Q10"],"award-info":[{"award-number":["CFF PAUL18Q10"]}]},{"name":"U.S. Cystic Fibrosis Foundation","award":["CFF PAUL25Q10"],"award-info":[{"award-number":["CFF PAUL25Q10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Because a delayed diagnosis of cystic fibrosis (CF) is detrimental and may be fatal, screening at birth has become routine in the Western world and has proven beneficial for many reasons, in addition to enabling prompt specialized care. Newborn screening (NBS) programs have elucidated the true incidence of CF in a variety of populations and enabled rapid genotype identification through the analysis of the cystic fibrosis transmembrane regulator (CFTR) gene. NBS studies also have revealed regional and population differences in CFTR variants and refuted the dogma that CF is a \u201cwhite person\u2019s disease\u201d. But some regions have not yet implemented CF NBS, particularly in Asia where the disease prevalence has been uncertain. While the needs of a few low-and-middle-income countries are being addressed sequentially, one of the regions of greatest current interest is the Indian subcontinent because of recent data suggesting a higher incidence than that previously assumed, and clinical observations indicating tragic outcomes due to delayed diagnoses or failure to diagnose the disorder in young children. Thus, we conclude that the opportunities for research combined with service in the Indian subcontinent are urgent and potentially very impactful. Consequently, India is the last and best frontier for CF NBS, as we argue herein.<\/jats:p>","DOI":"10.3390\/ijns11020027","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T20:05:56Z","timestamp":1744920356000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["India: The Last and Best Frontier for Cystic Fibrosis Newborn Screening with Perspectives on Special Challenges"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0036-7016","authenticated-orcid":false,"given":"Philip M.","family":"Farrell","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0963-1784","authenticated-orcid":false,"given":"Grace R.","family":"Paul","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Sleep Medicine, Nationwide Children\u2019s Hospital, 700 Children\u2019s Drive, Columbus, OH 43025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha D.","family":"Varkki","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Christian Medical College, IDA Scudder Road, Vellore 632004, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0065-3101(24)00075-6","article-title":"Newborn screening: Principles and practice","volume":"43","author":"Allen","year":"1996","journal-title":"Adv. Pediatr."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0022-3476(84)80128-6","article-title":"Nutritional deficits exist before 2 months of age in some infants with cystic fibrosis identified by screening test","volume":"105","author":"Reardon","year":"1984","journal-title":"J. Pediatr."},{"key":"ref_4","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_5","first-page":"1","article-title":"Newborn Screening for Cystic Fibrosis: Evaluation of Benefits and Risks and Recommendations for State Newborn Screening Programs","volume":"Volume 53","author":"Grosse","year":"2004","journal-title":"MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.jpeds.2005.08.016","article-title":"Newborn Screening for Cystic Fibrosis: An Opportunity to Improve Care and Outcomes","volume":"147","author":"Campbell","year":"2005","journal-title":"J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1056\/NEJM199710023371403","article-title":"Nutritional benefits of neonatal screening for cystic fibrosis. Wisconsin Cystic Fibrosis Neonatal Screening Study Group","volume":"337","author":"Farrell","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1001\/jamapediatrics.2022.2674","article-title":"Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes","volume":"176","author":"Rosenfeld","year":"2022","journal-title":"JAMA Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1002\/ppul.25658","article-title":"Outcomes of infants born during the first 9 years of CF newborn screening in the United States: A retrospective Cystic Fibrosis Foundation Patient Registry cohort study","volume":"56","author":"Martiniano","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cystic Fibrosis Foundation, Ad Hoc Committee Task Force on Neonatal Screening (1983). Neonatal screening for cystic fibrosis: Position paper. Pediatrics, 72, 741\u2013745.","DOI":"10.1542\/peds.72.5.741"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1126\/science.2570460","article-title":"Identification of the cystic fibrosis gene: Genetic analysis","volume":"245","author":"Kerem","year":"1989","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18825","DOI":"10.1073\/pnas.0904709106","article-title":"Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770","volume":"106","author":"Hadida","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","article-title":"A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation","volume":"365","author":"Ramsey","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Scotet, V., Gutierrez, H., and Farrell, P.M. (2020). Newborn Screening for CF across the Globe\u2014Where Is It Worthwhile?. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6010018"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1542\/peds.32.3.338","article-title":"A Simple Phenylalanine Method for Detecting Phenylketonuria in Large Populations of Newborn Infants","volume":"32","author":"Guthrie","year":"1963","journal-title":"Pediatrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ajhg.2013.07.006","article-title":"Genetic evidence for recent population mixture in India","volume":"93","author":"Moorjani","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","first-page":"22522","article-title":"Linkages between consanguinity, pregnancy outcomes and offspring mortality in twenty-first century India","volume":"14","author":"Kalam","year":"2024","journal-title":"Nat. Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100434","DOI":"10.1016\/j.lansea.2024.100434","article-title":"CFTR mutations and phenotypic correlations in people with cystic fibrosis: A retrospective study from a single centre in south India","volume":"27","author":"Varkki","year":"2024","journal-title":"Lancet Reg. Health Southeast Asia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1007\/s13312-022-2608-0","article-title":"Is Cystic Fibrosis Contributing Significantly to Infant Mortality Rate in India?","volume":"59","author":"Varkki","year":"2022","journal-title":"Indian Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e001459","DOI":"10.1136\/bmjph-2024-001459","article-title":"Implementing and validating newborn screening for inborn errors of metabolism in South India: A 2-year observational study at a tertiary care hospital","volume":"2","author":"Chikkalingaiah","year":"2024","journal-title":"BMJ Public Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"348","DOI":"10.4103\/ijem.ijem_220_21","article-title":"Optimizing Cord Blood Thyroid Stimulating Hormone Cutoff for Screening of Congenital Hypothyroidism-Experience from Screening 164,000 Newborns in a Tertiary Hospital in India","volume":"25","author":"Paul","year":"2021","journal-title":"Indian. J. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.4103\/ijem.IJEM_640_17","article-title":"Congenital Hypothyroidism Screening in Term Neonates using Umbilical Cord Blood TSH Values","volume":"22","author":"Bhatia","year":"2018","journal-title":"Indian. J. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/01.med.0000433063.78799.c2","article-title":"Hypothyroidism in the newborn period","volume":"20","author":"Wassner","year":"2013","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tippabathani, J., Seenappa, V., Murugan, A., Phani, N.M., Hampe, M.H., Appaswamy, G., and Sadashiv Gambhir, P. (2023). Neonatal Screening for Congenital Adrenal Hyperplasia in Indian Newborns with Reflex Genetic Analysis of 21-Hydroxylase Deficiency. Int. J. Neonatal Screen., 9.","DOI":"10.3390\/ijns9010009"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s12020-024-03747-x","article-title":"High carrier frequency of CYP21A2 gene mutations in Southern India\u2014Underscoring the need for genetic testing in Congenital Adrenal Hyperplasia","volume":"85","author":"Ravichandran","year":"2024","journal-title":"Endocrine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117881","DOI":"10.1016\/j.cca.2024.117881","article-title":"Improving newborn screening in India: Disease gaps and quality control","volume":"557","author":"Panchbudhe","year":"2024","journal-title":"Clin. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4103\/0019-557X.157537","article-title":"Newborn screening for G6PD deficiency: A 2-year data from North India","volume":"59","author":"Goyal","year":"2015","journal-title":"Indian J. Public Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.25259\/NMJI_110_20","article-title":"Healthcare innovation in India: Addressing challenges, understanding progress and offering opportunities","volume":"35","author":"Raj","year":"2022","journal-title":"Natl. Med. J. India"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114968","DOI":"10.1016\/j.socscimed.2022.114968","article-title":"Digital health for all: The turn to digitized healthcare in India","volume":"319","author":"Mishra","year":"2023","journal-title":"Soc. Sci. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/ng.2745","article-title":"Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene","volume":"45","author":"Sosnay","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1007\/s12098-020-03342-8","article-title":"Cystic Fibrosis Presenting as Pseudo-Bartter Syndrome: An Important Diagnosis that is Missed!","volume":"87","author":"Mantoo","year":"2020","journal-title":"Indian J. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e257348","DOI":"10.1136\/bcr-2023-257348","article-title":"Pseudo-Bartter syndrome as the initial presentation of cystic fibrosis in children: An important diagnosis not to be missed","volume":"17","author":"Lopes","year":"2024","journal-title":"BMJ Case Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Therrell, B.L., Padilla, C.D., Abadingo, M.E., Adhikari, S.P., Aung, T., Aye, T.T., Dey, S.K., Faizi, M., Ganbaatar, E., and Giang, T.T. (2024). Consolidated Newborn Bloodspot Screening Efforts in Developing Countries in the Asia Pacific-2024. Int. J. Neonatal Screen., 11.","DOI":"10.3390\/ijns11010002"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1136\/archdischild-2021-323549","article-title":"Immunoreactive trypsinogen in healthy newborns and infants with cystic fibrosis","volume":"108","author":"Fingerhut","year":"2023","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2012.02.013","article-title":"Immunoreactive Trypsinogen (IRT) as a Biomarker for Cystic Fibrosis: Challenges in Newborn Dried Blood Spot Screening","volume":"106","author":"Therrell","year":"2012","journal-title":"Mol. Genet. Metab."}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/11\/2\/27\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:16:27Z","timestamp":1760030187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/11\/2\/27"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":36,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijns11020027"],"URL":"https:\/\/doi.org\/10.3390\/ijns11020027","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]}}}