Antenatal paediatrics by amniocentesis.

The finding that amniotic fluid contains living cells which may be cultured (Fuchs, 1966; Steele and Breg, 1966; Nadler, 1968) offers important and interesting prospects for antenatal paediatrics. There is, however, much yet to be learnt both about the safety of the operative procedure and about the techniques of culturing the cells. The only extensive experience of amniocentesis hitherto has been in relation to Rh-isoimmunization, and here the procedure is carried out later in pregnancy. The operation is best carried out suprapubically at the 12th to 14th post-conceptional week, with the withdrawal of 5 to 10 ml. amniotic fluid (Nadler, 1968). The risk of infection is small, the risk to the mother is small, the risk to the fetus is not yet reliably established. An approach through the anterior fornix may be made two or three weeks earlier, buit probably carries a higher risk of infection and of inducing abortion. The alternative procedure of chorion biopsy (Hahnemann and Mohr, 1969) also makes cells available two or three weeks earlier in pregnancy, but appears less reliable and less safe. The first application has been in genetic counselling: for the diagnosis of chromosome anomalies in pregnancies where the mother is already known to have a high risk of producing an abnormal child. An example is where a mother has a D/G translocation with perhaps a 1 in 5 chance of producing a liveborn child with Down's syndrome, and both parents are asking for a termination (Jacobson and Barter, 1967; Nadler, 1968). In this case the procedure is being used essentially to avoid the unnecessary termination of a normal pregnancy. In these circumstances the small risk of inducing an abortion by the procedure is acceptable, as is the small risk of damaging the fetus. The procedure has also been used when parents with similar risks have wished deliberately to plan a pregnancy on the understanding that if the fetus is found to be abnormal they will be offered a termination. Amniocentesis at the 14th week followed by 3 weeks of cell culture makes possible termination before the 18th week. A similar and more widespread potential use of amniocentesis in genetic counselling is where there is a high risk of an inborn error of metabolism. The list of metabolic errors detectable in amniotic cells is growing fast, and includes, for example, the autosomal recessive conditions, galactosaemia, cystathioninuria and homocystinuria, and the Xlinked conditions, the Lesch-Nyhan hyperuricaemia syndrome and G6PD deficiency. In these instances culture of the cells is unnecessary, and the enzyme deficiency, it is claimed, may be demonstrated directly on the cells in the amniotic fluid (Nadler and Gerbie, 1969). Amniocentesis has already been used where the mother was a known carrier of the gene for the Lesch-Nyhan syndrome (Fujimoto et al., 1968). In other instances, for example in Hurler's syndrome, some weeks of culture are at present necessary before the accumulation of mucopolysaccharides is demonstrable, and here the homozygote cannot be distinguished reliably from the heterozygote (Danes and Beam, 1966). There is, however, a good chance that the metabolic errors that are demonstrable in fibroblast culture-and this includes most of them, with phenylketonuria a notable exception-will also be demonstrable in amniotic cell culture. A biochemical test for the fetus with cystic fibrosis would be especially valuable and the demonstration of metachromasia in both fibroblast and lymphocyte culture (Danes and Beam, 1969) from such patients suggests that such a test may not be too far away, though the metachromasia itself is too non-specific to be useful. The prevention of conditions such as cystic fibrosis is likely to come from the detection before they marry of the 5% of the population in Britain who are heterozygotes, combined with the offer of pregnancy testing for homozygous fetuses when two heterozygotes do marry each other. Looking to future advances, a test for women heterozygous for the gene for X-linked muscular dystrophy combined with a test for the male fetuses who are hemizygous for the gene would be of great value, and permit a reduction of the frequency of affected boys to those affected by a fresh mutation-perhaps to about a third of the present frequency. There is even a prospect that amniocentesis may play a