Search

Advances in prenatal diagnostic techniques allow for earlier, more rapid, and more effective detection of congenital disorders. The indications, diagnostic accuracy, and risks for invasive diagnostic techniques including amniocentesis, chorionic villus sampling, and fetal blood sampling are reviewed. Recent advances in non-invasive detection methods, such as fetal ultrasound and the isolation of fetal cells in the maternal circulation are discussed. Additionally, the intrauterine diagnosis of congenital infections and chromosomal and Mendelian disorders, as well as hematologic disorders are summarized.

With the improvement of imaging techniques as well as the trend toward routine antenatal ultrasound scanning, the intrauterine diagnosis of fetal ovarian cysts is encountered more frequently. The authors described the laparoscopic approach to the management of ovarian cysts. This approach is tolerated well by infants, and it may overcome the controversy between conservative and early surgical management by facilitating the subtle transition from diagnostic to therapeutic means, with salvation of the ovary whenever possible.

The value of improved intrauterine diagnostic capability is unquestioned; however, as with all new technologic advancements, the problems created by this new diagnostic tool need review. This article examines some of the more critical of these difficulties.

Amniocentesis for intrauterine diagnosis of genetic disease is a safe and highly accurate procedure. This is most fortunate since the timing of the procedure (14 to 16 weeks) and the length of time necessary to cultivate the cells and perform the analysis (3 to 5 weeks) makes it almost mandatory, and almost unique in medicine, that patient management be based on a single non-repeated laboratory procedure. It should be recommended to all patients for whom there is a specific indication for antenatal genetic studies.

Although major advances have been made in -the epidemiology of birth defect surveillance, in intrauterine diagnosis and treatment, and In clarifying the role of environ-mental factors, we are uncertain about the causes of the majority of birth defects. Miseducation of the public and some professional groups has led to an overemphasis on the importance of drugs and chemicals as causes of birth defects and has resulted in major health and social problems. Many problems remain in preventing or reducing the Incidence of human malformations, which may be solved by the combined efforts of clinical surveillance programs and advances in the fields of genetics, developmental biology, and biochemistry.

A very rare case of a sustained fetal ventricular arrythmia in the form of bigeminy, trigeminy, and quadrigeminy during labor is described. The rhythm disturbance failed to respond to sedatives and narcotics but was successfully reverted to sinus rhythm following the administration of intravenous propranolol to the mother. The significance and possible mechanism of the arrhythmia is discussed.

This article presents an overview of the use of fetal blood and DNA for prenatal testing. The molecular organization of the human hemoglobin genes, the structure of human hemoglobins, and the molecular defects of hemoglobinopathies are also discussed.

The hazards of amniocentesis for intrauterine diagnosis have yet to be established. We are particularly concerned by the high incidence (7.5 per cent) of postamniocentesis abortions and amniotic fluid leaks in our series. A larger experience is certainly needed before these concerns can be disregarded. Until then, it is important that indications for this procedure be strictly adhered to.

Assay procedures are currently available for the detection of patients and carriers for all nine lipid storage diseases. In six of these conditions reliable determinations may be carried out with commercially available artificial substrates. In the remaining three diseases the use of radioactively labeled lipids is required for enzyme assays. Detection of heterozygotes for Niemann-Pick disease is reported for the first time. A potentially useful artificial substrate is proposed for the detection of patients with Niemann-Pick disease. Automated serum enzyme assays may be useful for large scale screening of heterozygous carriers of lipid storage diseases, and in combination with intrauterine diagnosis could lead to the preventive control of such disorders.

Similar concerns have been noted previously for a different disease and distinct enzyme deficiency. In 1973 Vidgoff and associates 1~ reported a family which included a woman with a marked deficiency of hexosominidase A in all tissues studied. She actually represents the carrier state for Tay-Sachs disease, though her hexosominidase A level taken alone would have suggested that she was an affected homozygote. There are thus at least two heritable disorders for which there is overlap between the carrier and the affected person in terms of enzyme activity. Based on these findings, and considering the greater availability and less strict indications for prenatal diagnostic amniocentesis, it is suggested that great care be exercised in the diagnosis of these diseases, particularly in the interpretation of data for intrauterine diagnosis. The data and conclusions discussed here were presented in preliminary form to the Society for Pediatric Research, Denver, April 18, 1975.11