Prenatal diagnosis of beta-thalassaemia and other haemoglobinopathies in India.

This paper reports prenatal diagnosis of 787 fetuses of beta-thalassaemia and other haemoglobinopathies in Indian high-risk communities. DNA based diagnosis was offered in the first, as well as the second trimester, in 489 pregnancies (with five twins) on fetal tissues such as chorionic villus (CV) and amniocytes using the amplification refractory mutation system (ARMS) and restriction fragment length polymorphism (RFLP) techniques. Two hundred and ninety-two women (with one twin), who either presented late in the second trimester or whose DNA diagnosis was not informative, were offered prenatal diagnosis using globin chain synthesis (GCS) on fetal blood cells. Maternal contamination of fetal DNA was ruled out by variable number tandem repeat (VNTR) analysis using sites in four different genes (Apo-B, D1S-80, Ig-JH and Ha-ras), while contamination of fetal blood was checked by a particle size distribution channelyzer. Using both techniques we were able to offer complete diagnosis in 99.8% cases. Out of 494 fetuses tested by DNA analysis, 135 were found to be normal, 201 were carriers, whereas 146 were affected. Out of 293 fetuses analysed by GCS, 215 were unaffected and 71 were affected. In this study, both fetuses were tested in twin pregnancies, of which three required selective termination of one fetus. Because of social, religious taboos and family influences, genetic counselling was found to be an important guideline for couples selecting options for prenatal diagnosis. Our experience suggests that because of late presentation by many couples to the diagnostic centres, in developing countries like India, both the techniques of DNA analysis and GCS should be made available at major referral centres for maximum benefit to couples.

Rapid mid-trimester prenatal diagnosis of beta-thalassaemia and other haemoglobinopathies using a non-radioactive anion exchange HPLC technique--an Indian experience.

Anion exchange high performance liquid chromatography (AX-HPLC) has been widely used for separating and quantifying various haemoglobin fractions especially in the haemoglobinopathies. We have evaluated the reliability of this technique to measure low concentrations of adult haemoglobin (HbA) in fetal blood to enable differentiation between affected and unaffected fetuses at risk for beta-thalassaemia (85) and other haemoglobinopathies such as delta beta/beta-thalassaemia (1), E-beta-thalassaemia (2), S-beta-thalassaemia (1), and sickle cell anaemia (1). The HbA values obtained ranged between 0 and 9.51 per cent. The HbA for 27 affected fetuses was 0 per cent, while two showed a HbA value of 0.5 per cent. The mean HbA for 61 unaffected fetuses was 4.8 +/- 2.08 per cent. Thirty cord blood samples (cord abortus in cases of affected fetuses and cord full term in cases of unaffected fetuses) were analysed to reconfirm the diagnosis. Ten babies between 8 and 18 months of age could be followed up for confirmation. AX-HPLC was found to be a simple and rapid procedure with high sensitivity and there was a good correlation between the HbA values obtained by AX-HPLC and the diagnosis by carboxymethyl cellulose (CMC) chromatography.

Plasma noradrenaline and adrenaline levels in normal pregnancy and in pregnancy-induced hypertension.

Plasma concentrations of noradrenaline and adrenaline were measured serially during normal pregnancy in 52 women who remained normotensive and in nine who developed pregnancy-induced hypertension but were otherwise normal. There was a significant fall in both noradrenaline (P less than 0.005) and adrenaline (P less than 0.05) levels during normal pregnancy. Throughout pregnancy the mean levels of both catecholamines were lower in the patients who developed pregnancy-induced hypertension than in the normotensive patients. There was no evidence of increased sympathetic nervous system activity in the women who developed pregnancy-induced hypertension.