{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T18:11:50Z","timestamp":1759687910473,"version":"build-2065373602"},"reference-count":36,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1982,4]]},"abstract":"<jats:p>The results of 200 antenatal diagnoses in pregnancies at risk for homozygous beta-thalassaemia, carried out on fetal blood samples obtained by placental aspiration in the second trimester, are described. Globin chain synthesis in the fetuses was measured by means of 3H-leucine incorporation and separation of the chains on carboxy-methyl-cellulose columns. Fetal red cell enrichment was performed by NH4Cl-NH4HCO3 differential lysis of maternal cells or anti-i differential agglutination. Sufficient fetal blood for analysis was obtained in 97.5% of the cases. The overall fetal loss rate was 6.5%, but it declined from 10% in the first consecutive 100 cases to 3% in the last 100 cases. Fetal loss was the result of early or late intrauterine death or spontaneous abortion. Forty-two homozygous fetuses had no beta-chain synthesis and one had a very low beta\/gamma ratio (0.005). Of the pregnancies, 37 were terminated at parental request and four aborted spontaneously. Absence of beta-chain radioactivity was confirmed in 12 abortuses with suitable cord blood samples for analysis. Two pregnancies with homozygous fetuses were not terminated, as one member of each couple was a devout Catholic. As expected, both infants developed Cooley's anaemia. Follow-up of the 146 infants, diagnosed in utero as non-homozygotes, showed cerebral palsy in one and a small cutaneous needle injury in three. None of these developed homozygous beta-thalassaemia. Even beta-thalassaemia trait with a beta\/gamma ratio of 0.046 +\/- 0.012 can be distinguished from normal, showing a beta\/gamma ratio of 0.086 +\/- 0.019 with a high degree of certainty.<\/jats:p>","DOI":"10.1136\/jmg.19.2.81","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T14:52:06Z","timestamp":1226328726000},"page":"81-87","source":"Crossref","is-referenced-by-count":11,"title":["Haematological and obstetric aspects of antenatal diagnosis of beta-thalassaemia: experience with 200 cases."],"prefix":"10.1136","volume":"19","author":[{"given":"A","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Furbetta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Angius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Ximenes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Rosatelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Tuveri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M T","family":"Scalas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A M","family":"Falchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Angioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Caminiti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1982,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1056\/NEJM197405092901908","article-title":"In utero diagnosis of hemoglobinopathies: technic for obtaining fetal blood","volume":"290","author":"Hobbins, J.C.; Mahoney, M.J.","year":"1974","unstructured":"Hobbins JC, Mahoney MJ. In utero diagnosis of hemoglobinopathies: technic for obtaining fetal blood. N Engl J Med 1974;290:1065-7.","journal-title":"N Engl J Med"},{"key":"ref_2","first-page":"79","article-title":"Fetal blood sampling in utero","volume":"i:","author":"Kan, Y.W.; Valenti, C.; Carnazza, V.; Guidotti, R.; Rieder, R.F.","year":"1974","unstructured":"Kan YW, Valenti C, Carnazza V, Guidotti R, Rieder RF. Fetal blood sampling in utero. Lancet 1974;i:79-80.","journal-title":"Lancet"},{"key":"ref_3","first-page":"780","volume":"30","author":"Fetoscopy, Benzie R.J.","year":"1975","unstructured":"Benzie RJ. Fetoscopy. Mod Med 1975;30:780-3.","journal-title":"Mod Med"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1136\/bmj.2.6139.728","article-title":"Sampling of pure fetal blood by fetoscopy in second trimester of pregnancy","volume":"ii:","author":"Rodeck, C.M.; Campbell, S.","year":"1978","unstructured":"Rodeck CM, Campbell S. Sampling of pure fetal blood by fetoscopy in second trimester of pregnancy. Br Med J 1978;ii:728.","journal-title":"Br Med J"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1471-0528.1980.tb04499.x","article-title":"Obstetric aspects of mid-trimester fetal blood sampling by needling or fetoscopy","volume":"87","author":"Fairweather, D.V.I.; Ward, R.M.T.; Modell, B.","year":"1980","unstructured":"Fairweather DVI, Ward RMT, Modell B. Obstetric aspects of mid-trimester fetal blood sampling by needling or fetoscopy. 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J Med Genet 1979;16:366-8.","journal-title":"J Med Genet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1136\/jcp.25.8.738","article-title":"Reliable routine estimation of small amount of foetal haemoglogin by alkali denaturation","volume":"25","author":"Penibrey, M.E.; McWade, P.; Weatherall, D.J.","year":"1972","unstructured":"Penibrey ME, McWade P, Weatherall DJ. Reliable routine estimation of small amount of foetal haemoglogin by alkali denaturation. J Clin Pathol 1972;25:738-40.","journal-title":"J Clin Pathol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1365-2141.1978.tb01050.x","article-title":"Beta thalassaemia trait: imprecision of diagnosis at birth","volume":"38","author":"Alter, B.P.","year":"1978","unstructured":"Alter BP. Beta thalassaemia trait: imprecision of diagnosis at birth. Br J Haematol 1978;38:323-7.","journal-title":"Br J Haematol"},{"key":"ref_30","first-page":"217","article-title":"Diagnosis of the PO-thalassemia trait at birth","volume-title":"Hemoglobin","volume":"3","author":"Furbetta, M.; Angius, A.; Tuveri, T.","year":"1981","unstructured":"Furbetta M, Angius A, Tuveri T, et al. Diagnosis of the PO-thalassemia trait at birth. Hemoglobin 1981;3:217-29."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1471-0528.1980.tb04577.x","article-title":"Fetoscopy guided by real time ultrasound for pure fetal blood samples, fetal skin samples and examination of the fetus in utero","volume":"87","author":"Rodeck, C.H.","year":"1980","unstructured":"' Rodeck CH. Fetoscopy guided by real time ultrasound for pure fetal blood samples, fetal skin samples and examination of the fetus in utero. Br J Obstet Gynaecol 1980;87:449-51.","journal-title":"Br J Obstet Gynaecol"},{"key":"ref_32","article-title":"Haematological aspects of antenatal diagnosis for thalassaemia in Britain","author":"Matsakis, M.; Berdukas, V.A.; Angostiniotis, M.","unstructured":"Matsakis M, Berdukas VA, Angostiniotis M, et al. Haematological aspects of antenatal diagnosis for thalassaemia in Britain. Br J Haematol (in press).","journal-title":"Br J Haematol"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1651-2227.1975.tb03820.x","article-title":"The changing panorama of cerebral palsy in Sweden 1954-1970","volume":"64","author":"Hagberg, B.; Hagberg, G.; Olow, I.","year":"1975","unstructured":"Hagberg B, Hagberg G, Olow I. The changing panorama of cerebral palsy in Sweden 1954-1970. 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Application to prenatal diagnosis of fO-thalassemia in Sardinia. N Engl J Med 1980; 185-8.","journal-title":"N Engl J Med"},{"key":"ref_36","first-page":"144","article-title":"Model for antenatal diagnosis of r-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphism","author":"Little, P.F.R.; Annison, G.; Darling, S.; Williamson, R.; Cambe, L.; Modell, B.","year":"1980","unstructured":"Little PFR, Annison G, Darling S, Williamson R, Cambe L, Modell B. Model for antenatal diagnosis of r-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphism. 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