{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:24:04Z","timestamp":1790238244676,"version":"4.1.0"},"reference-count":32,"publisher":"BMJ","issue":"6942","license":[{"start":{"date-parts":[[1994,6,4]],"date-time":"1994-06-04T00:00:00Z","timestamp":770688000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.bmj.com\/company\/legal-information\/terms-conditions\/legal-information\/tdm-licencepolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ"],"published-print":{"date-parts":[[1994,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Objective<\/jats:bold>\n                    : To assess the performance and impact of a two tier neonatal screening programme for cystic fibrosis based on an initial estimation of immunoreactive trypsinogen followed by direct gene analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    &gt;\n                    <jats:bold>Design<\/jats:bold>\n                    : Four year prospective study of two tier screening strategy. First tier: immunoreactive trypsinogen measured in dried blood spot samples from neonates aged 3-5 days. Second tier: direct gene analysis of cystic fibrosis mutations (\u03b4F508, \u03b4I506, G551D, G542X, and R553X) in samples with immunoreactive trypsinogen concentrations in highest 1% and in all neonates with meconium ileus20or family history of cystic fibrosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Setting<\/jats:bold>\n                    : South Australian Neonatal Screening Programme, Adelaide.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Subjects<\/jats:bold>\n                    : All 88 752 neonates born in South Australia between December 1989 and December 1993.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Interventions<\/jats:bold>\n                    : Neonates with two identifiable mutations were referred directly for clinical assessment and confirmatory sweat test; infants with only one identifiable mutation were recalled for sweat test at age 3-4 weeks. Parents of neonates identified as carriers of cystic fibrosis mutation were counselled and offered genetic testing. Main outcome measures - Identification of20all children with cystic fibrosis in the screened population.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : Of 1004 (1.13%) neonates with immunoreactive trypsinogen &gt;=99th centile, 912 (90.8%) had no identifiable mutation. 23 neonates were homozygotes or compound heterozygotes; 69 carried one identifiable mutation, of whom six had positive sweat tests. Median age at clinical assessment for the 29 neonates with cystic fibrosis was 3 weeks; six had meconium ileus and two had affected siblings. 63 neonates were identified as carriers of a cystic fibrosis mutation. Extra laboratory costs for measuring immunoreactive trypsinogen and direct gene analysis were $A1.50 per neonate screened.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : This strategy results in early and accurate diagnosis of cystic fibrosis and performs better than screening strategies based on immunoreactive trypsinogen measurement alone.\n                  <\/jats:p>","DOI":"10.1136\/bmj.308.6942.1469","type":"journal-article","created":{"date-parts":[[2011,10,27]],"date-time":"2011-10-27T19:22:47Z","timestamp":1319743367000},"page":"1469-1472","source":"Crossref","is-referenced-by-count":63,"title":["Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis: four years' experience"],"prefix":"10.1136","volume":"308","author":[{"given":"E","family":"Ranieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B D","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R L","family":"Gerace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R G","family":"Ryall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C P","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P V","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W F","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E F","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1994,6,4]]},"reference":[{"key":"2025122310365260000_308.6942.1469.1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0065-3101(24)00279-2","article-title":"Newborn screening for cystic fibrosis. 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