{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:40:31Z","timestamp":1777434031835,"version":"3.51.4"},"reference-count":0,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2003,5,1]],"date-time":"2003-05-01T00:00:00Z","timestamp":1051747200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Clin Biochem"],"published-print":{"date-parts":[[2003,5,1]]},"abstract":"<jats:p>Background: In a previous study we examined the changes in the median multiple of the median (MoM) with gestation of free beta human chorionic gonadotrophin (F\u03b2-hCG), total human chorionic gonadotrophin (ThCG), \u03b1-fetoprotein (AFP) and pregnancy-associated plasma protein A (PAPP-A) in a large series of Down's syndrome pregnancies. Results showed that there was a significant temporal variation of the MoM for each marker. In this paper, we assess the impact of this temporal shift on the estimation of patient-specific risks and the detection rates (DRs) for Down's syndrome pregnancies.<\/jats:p>\n                  <jats:p>\n                    Methods: Individual patient-specific risks, DRs and false positive rates were estimated using statistical modelling techniques and computer simulations. The data for these simulations were the regressed mean log\n                    <jats:sub>10<\/jats:sub>\n                    analyte MoMs, marker standard deviations (as log\n                    <jats:sub>10<\/jats:sub>\n                    MoM) and correlation coefficients derived from the analysis of over 1000 cases of Down's syndrome and 150 000 unaffected pregnancies between 6 and 20 weeks of gestation reported in our previous study. Two models were compared: the classical constant median separation model, which assumes no variation in median shift with gestation (model 1), and a variable median separation model (model 2), which takes account of the changes in median shift with gestation as described in our previous study.\n                  <\/jats:p>\n                  <jats:p>Results: When individual patient-specific risks calculated for various MoM values using model 1 were compared with those derived from model 2, considerable differences in risk estimates were observed for all marker combinations, particularly in the first trimester. Using a 1 in 250 cut-off risk, DRs at each gestation in the second trimester for the AFP+F\u03b2-hCG combination were maximized at 14-17 weeks of gestation and were virtually identical at 63-65% for model 1 and model 2. A similar trend was observed for the AFP+ThCG combination, with an optimum gestational range of 15-18 weeks and DRs of 66-68%. In the first trimester, using a 1 in 250 cut-off risk, DRs were more variable with gestation for the prime marker combination of F\u03b2-hCG+PAPP-A, varying from 73% at 8 weeks to 65% at 13 weeks with model 1 and from 75% to 66% with model 2.<\/jats:p>\n                  <jats:p>Conclusion: Risk algorithms should take into account temporal variation in marker MoMs in order to produce accurate patient-specific risks. This also helps to maximize DRs, particularly when samples are taken outwith the optimal gestational range.<\/jats:p>","DOI":"10.1258\/000456303321610501","type":"journal-article","created":{"date-parts":[[2003,5,21]],"date-time":"2003-05-21T20:17:02Z","timestamp":1053548222000},"page":"219-231","source":"Crossref","is-referenced-by-count":43,"title":["The effect of temporal variation in biochemical markers of trisomy 21                across the first and second trimesters of pregnancy on the estimation of individual                patient-specific risks and detection rates for Down's syndrome"],"prefix":"10.1177","volume":"40","author":[{"given":"K","family":"Spencer","sequence":"first","affiliation":[{"name":"Endocrine Unit, Clinical Biochemistry Department, Harold Wood\r                  Hospital, Romford RM3 0BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JA","family":"Crossley","sequence":"additional","affiliation":[{"name":"Duncan Guthrie Institute of Medical Genetics, Glasgow G3 8SJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DA","family":"Aitken","sequence":"additional","affiliation":[{"name":"Duncan Guthrie Institute of Medical Genetics Glasgow G3 8SJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ABJ","family":"Nix","sequence":"additional","affiliation":[{"name":"Department of Medical Computing and Statistics, University of Wales\r                  College of Medicine, Cardiff, CF14 4XN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FDJ","family":"Dunstan","sequence":"additional","affiliation":[{"name":"Department of Medical Computing and Statistics, University of Wales\r                  College of Medicine, Cardiff, CF14 4XN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medical Computing and Statistics, University of Wales\r                  College of Medicine, Cardiff, CF14 4XN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2003,5,1]]},"container-title":["Annals of Clinical Biochemistry: International Journal of Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1258\/000456303321610501","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1258\/000456303321610501","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:52:37Z","timestamp":1777377157000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1258\/000456303321610501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,5,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,5,1]]}},"alternative-id":["10.1258\/000456303321610501"],"URL":"https:\/\/doi.org\/10.1258\/000456303321610501","relation":{},"ISSN":["0004-5632","1758-1001"],"issn-type":[{"value":"0004-5632","type":"print"},{"value":"1758-1001","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,5,1]]}}}