Open defects of the neural tube (anencephaly and meningomyelocele) are re­latively frequent congenital malformations of multifactorial origin. The recur­rence risk after one affected child is about 5% and after two affected child­ren it increases to + 10% (Bonaiti-Pellie & Smith, 1974). The malformation in the subsequent child may be either identical or of a different type. An affected parent has a 3 - 4% risk for an affected child (Carter, 1974). Prenatal detection of open neural tube defects is possible by analysis of the concentration of alpha-fetoprotein in the amniotic fluid (Brock & Sutcliffe, 1972; Allan et aL, 1973); closed defects, some of which may have milder clinical manifestations, cannot be detected with this method (Laurence et al., 1973) and the parents should be informed accordingly.

This recent development will be a quite common indication for prenatal moni­toring, and in most cases this will be for parents with an affected child. Elevated levels of amniotic fluid alpha-fetoprotein can in some cases also be detected in maternal serum (Brock et al., 1973). In a number of studies the value of this maternal indicator for fetal neural tube defects was explored (Harris et al., 1974; Seller et al., 1974; Wald et al., 1974). The possibili­ties for large-scale screening so far are not very promising.

Future developments in prenatal diagnosis

The actual techniques of prenatal diagnosis by amniocentesis and anal/sis of amniotic fluid and cultured amniotic fluid cells seem to be preferable over proposed other approaches to fetal specimens for diagnosis. Recently, the use of placental biopsies (Kullander & Sandahl, 1973; Ogita et al., 1974) was advocated as a source for material for prenatal cytogenetic diagnosis. Valenti (1973) proposed intrauterine blood sampling by puncture of fetal blood vessels with an endamnioscope, which could enable intrauterine detection of hemoglo­binopathies.

Preliminary results of techniques for fetal observation and biopsy through am-nioscopes (Scrimgeour, 1974; Wheeless, 1974; Levine et al., 1974; Laurence et al., 1974 ) warrant the conclusion, that as yet this procedure is too dangerous for clinical application.

Safe techniques for fetal observation and blood sampling might be a signifi­cant contribution to prenatal detection of some congenital malformations, fetal hemoglobinopathies and possibly in the future hemophilia, when analytical me­thods are available. Methods for the detection of hemoglobinopathies in small samples of blood have been described (Cividalli et al., 1974; Chang et al., 1974; Hobbins et al., 1974). Attempts are being made to detect HbS on indi­vidual erythrocytes occuring in the amnioting fluid (Boyer et al., 1974; Hea­dings et al., 1974). In contrast to earlier reports (Fortune & Fox, 1973), the activity of factor VIII is present in fetal blood in early pregnancy and if ap-propiate sampling techniques become available, prenatal diagnosis of hemophi­lia could become possible (Holmberg et al., 1974).

The extension of possibilities for prenatal diagnosis in the near future will be mainly dependent on the further clarification of biochemical defects in gene­tic diseases. The recent finding of adenosine deaminase deficiency in cultured amniotic fluid cells from a fetus, postnatally shown to be affected with severe combined immonodeficiency disease (Hirschhom et al., 1975) is an example of this rapidly expanding field.

Another important contribution would be the development of methods for the induction of the expression of genes normally not expressed in cultured cells.

The present state of prenatal diagnosis leaves much to be done. Although ma­ny papers appeared about this method, still too many people involved in me­dical care are unaware of its possibilities. Information about prenatal diagno­sis, as well as on principles of genetics, recurrence risks and on modern me­thods for the diagnosis of chromosomal disorders and inborn errors of metabo­lism, should be incorporated into (postgraduate) medical education. At this moment, genetic counseling is the most effective way for prevention of congenital diseases. For those parents at risk for a chromosomal aberration, one of some fifty metabolic diseases, a severe X-linked disease or a neural tube defect, prenatal monitoring may be of great help in the diffi­cult choice between the acceptance of a (high) risk for an affected child or the impossibility of having their own healthy children. The discrepancy be­tween the number of prenatal analyses made and the number of pregnancies that are at risk according to the present categories of indications shows that much improvement is possible in diagnosis and genetic counseling of conge­nital diseases.

The decisions by parents or patients at risk for affected offspring should not be influenced by fears for future generations. Several population geneticists (Mo-tulsky et al., 1971; Fraser, 1972; Fraser and Mayo, 1974) calculated that even extensive use of prenatal diagnosis and selective abortion only have a minor effect on the gene frequencies of autosomal recessive diseases. For X-linked recessive diseases there may be an increase of female heterozygotes but not of an extend to cause any concern.

Prenatal diagnosis may therefore be considered as a useful means to prevent the birth of affected children in individual families and in this way if offers the possibility for parents at risk to extend their families with unaffected children.