Prenatal diagnosis of thalassemia major by fetal blood analysis: Experience with 1000 cases

Abstract

In this report we have summarized our experience with the prenatal diagnosis of beta-thalassemia in 1000 pregnancies followed at least until 12 months after birth. In the majority of these cases, the thalassemia lesion was the nonsense mutation at the codon corresponding to amino acid 39, which produces the hematological phenotype of beta o-thalassemia. Fetal blood sampling was carried out by placental aspiration, by which a sufficient amount of fetal blood for analysis was obtained in the majority of cases (99 per cent). The fetal mortality associated with fetal blood sampling was 6.3 per cent. Those placental samples contaminated by maternal cells were successfully purified by Orskov lysis. Fetal blood was analysed by globin chain synthesis on CM-52 columns, which gave reliable results. Two misdiagnoses (0.2 per cent) have been made of which one was due to a non-globin protein co-migrating with the beta-chains while the other resulted from a misclassification of the type of thalassemia segregating in the family.

Fetal blood sampling in twin pregnancies

“…The procedure‐related fetal loss varies in different studies from < 1% to about 7%, although most recent series agree on a fetal loss rate of about 1–2%9–18. In a series of 1981 FBS procedures from our department the procedure‐related loss was 2.5%19.…”

Changes in the Approach for Invasive Prenatal Diagnosis in 35,127 Cases at a Single Center from 1977 to 2004

“…Regarding molecular biology techniques for ␤ -thalassemia analysis, from 1977 to 1982 the method of diagnosis was chain globin synthesis on fetal blood [11] , while since 1982 the majority of diagnoses have been made by DNA analysis. Analysis was accomplished initially on enzymatic restricted genomic DNA using allelespecifi c oligonucleotide radioactive probes [12] .…”

“…In our center, invasive prenatal diagnosis started in 1977 with diagnosis for ␤ -thalassemia using fetal blood obtained by placentacentesis at 20 weeks of gestation [1,11] . In 1982, amniocentesis by a 22 G (gauge) spinal needle under continuous ultrasound monitoring at 16 weeks was introduced for diagnosis of ␤ -thalassemia [12] , with sampling of 30-40 ml of amniotic fl uid.…”

Chorionic villus sampling and acceptance rate of prenatal diagnosis

“…Prenatal diagnosis of a-thalassemia can nowadays be carried out either by fetal blood analysis (Loukopoulos, 1984, Alter, 1985and Cao et al, 1986a) or amniocyte or chorionic villus DNA analysis (Weatherall et al, 1985;Cao el al., 1986b).…”