Prenatal Diagnosis of Β Thalassemia: Experience With 133 Cases and the Effect of Fetal Blood Sampling on Child Development *

Abstract

Prenatal diagnosis was attempted in 133 pregnancies at risk for beta thalassemia (132 cases) or sickle-cell beta 0 thalassemia (1 case). Of these, 76 couples requested diagnosis because they already had children affected with homozygote beta thalassemia (72 cases) or beta+ thalassemia (4 cases). The others were probably at risk for beta 0 thalassemia since this is by far the predominant thalassemia type in Sardinia. Sufficient fetal blood for analysis was obtained by placental aspiration at 18--24 weeks gestation in 130 cases. Ten fetal losses occurred. The pregnancies were followed and no relevant complications were seen. Of the newborns delivered, 45 were followed from birth with particular attention to congenital malformation, neurological, growth, and maturity assessement. No major adverse effect of placentocentesis on child growth and development was observed. Placental samples were analyzed by globin chain synthesis analysis on carboxylmethylcellulose columns. When the placental samples contained more than 20% maternal red cells, fetal red cell enrichment was carried out by anti-i (53 cases) or anti-AB (2 cases) differential agglutination or NH4Cl-NH4HCO3 differential lysis of maternal cells (17 cases). Of the 130 cases, 32 fetuses had no beta-chain radioactivity and one had a beta/gamma ratio of 0.005. These were presumed to be homozygous and all but one were electively aborted. Absence of beta-chain radioactivity was confirmed in 10 abortuses with suitable cord blood samples. A total of 91 infants have been born and are nonhomozygous. Genotype assessment at 6 months after birth in 33 infants showed that there was only a slight overlap between the ranges of normal (0.095 +/- 0.016) and heterozygous (0.05 +/- 0.01) fetal beta/gamma globin chain synthesis ratios.

Haematological and obstetric aspects of antenatal diagnosis of beta-thalassaemia: experience with 200 cases.

“…Moreover, there was a decline in the failure rate from 3 % in the first series of 100 cases to 2% in the second 100 cases examined, through the obstetrician gaining experience and the introduction of 0rskov lysis, which allowed successful analysis even with relatively low fetal red blood cell percentages (less than 5 %). As we have already reported,16 17 The fetal loss rate was 6-5%, slightly higher in anterior than in posterior placentas (fig 1). Interestingly, as was seen in the failure rate, the fetal loss rate had a continuous decline from 10 % seen in the first 100 consecutive cases to 3% in the last 100 examined.…”

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

“…The placental samples were monitored for the presence and percentage of fetal red blood cells with the Coulter C-1000 Channelyzer (Coulter Electronics, Hileah, Florida) (Kan et al, 197.5, 1977). Fetal red cell enrichment was performed at the outset with anti-i serum (Kan et al, 1977;Cao et al, 1980) and, thereafter, by NH4C1-NH4HC03 differential lysis of maternal cells (Cao et al, 1982;Furbetta et al, 1980). Lysate, globin preparation and CM-52 column radiochromatography were carried out as previously described (Kan et al, 1975(Kan et al, , 1977.…”

Recent advances in haematology

“…3-chain synthesis is occurring, and it is possible with a small fetal blood sample to determine by isotopic methods whether normal amounts of 3-chain and HbA are being produced, and also if HbS rather than HbA is being synthesized (Editorial, 1977). Early attempts to obtain fetal blood by placental needling or aspiration through a fetoscope were associated with considerable risk to the fetus and there were also some misdiagnoses; however, sampling techniques and diagnostic accuracy have greatly improved and it is now possible to diagnose P-thalassaemia major with over 95 % accuracy, with a fetal wastage of 5-10% (Kan et al, 1980;Cao et al, 1980;Alter, 1980). With antenatal diagnosis it may be possible to eradicate the disease in restricted populations and greatly to reduce its overall incidence.…”