Pediatric Annals

FROM THE NICHD 

Predictors of Hereditary Disease or Congenital Defects

Abstract

On March 5-7, 1979, on the NIH campus in Bethesda, Md., the NICHD brought together three task forces made up of scientists, practicing physicians, lawyers, ethicists, and representatives of the public to evaluate and reach some agreement about the safety, efficacy, and proper uses at present of new technologies of antenatal diagnosis. One task force considered predictors of hereditary disease or congenital defects. Their discussion of midtrimester amniocentesis was reported in Pediatric Annals, June, 1979. Other predictors - ultrasound, fetoscopy, and measurement of alpha-fetoprotein (AFP) in amniotic fluid and maternal serum - are covered in this article.*

Ultrasound. Although pulse echo ultrasonography, better known as ultrasound, has applications in many areas of clinical practice, the discussion at the conference was confined to its use in antenatal diagnosis. The technology employs inaudible sound waves that are beamed through the mother's abdomen and reflected off the fetus. A transducer then translates these reflected waves (or echoes) into a series of impulses that make up a visual image of the fetus and placenta on a screen. The technique is noninvasive, greatly reduces the need for x-rays or radioisotope scanning, causes little or no discomfort, and generally takes only a few minutes. The most extensive examination may take only a half hour.

The task force strongly recommended that ultrasound be employed before midtrimester amniocentesis to choose the site for amniocentesis, to establish gestational age (by measurement of fetal head size), to determine if the fetus is alive, to detect possible multiple pregnancy, and to disclose uterine abnormalities. Ultrasound was also recommended as a follow-up procedure after elevated AFP has been found in maternal serum or amniotic fluid, to provide visual evidence of major structural defects in the brain or spinal cord (neural tube defects, such as spina bifida and anencephaly). In addition, members of the task force considered the procedure essential to determine the position of the fetus and the placenta before fetoscopy or placental aspiration. Ultrasound has also been employed by itself to detect certain fetal structural abnormalities. The task force had reservations about this application and concluded that most such uses of ultrasound are still in the area of clinical research, to be pursued only in specialized research centers. More clinical research was recommended.

It was the consensus of the conference that ultrasound is valuable as an adjunct procedure and contributes to the safety of amniocentesis. The majority of studies of ultrasound have shown no harmful effects to the fetus or the mother. However, the participants cautioned that negative results indicate relative harmlessness rather than absolute safety and that careful prospective studies need to be done on the outcome of pregnancies in which the procedure is used.

Fetoscopy and placental aspiration. The major application of these technologies has been to the diagnosis of hemoglobinopathies and other blood and chemical disorders. Guided by ultrasound, the fetoscope provides direct, but limited, visualization of the fetus, and a minute sample of fetal blood can be aspirated from the placental vessels and analyzed. The accuracy of diagnosis is approximately 98 per cent, but the risk to the fetus is significantly greater than in the case of amniocentesis. The task force judged these technologies to be experimental and not yet ready for general use. Further research was recommended to include assessment of immediate and long-term risks to the fetus and mother.

These techniques have great potential for the antenatal treatment of disease as well as diagnosis. Fetoscopy may one day play a major role as a means of introducing medicine, cell transplants, and genetic material into fetal tissues. Further research toward these ends was encouraged.

Alpha fetoprotein…

On March 5-7, 1979, on the NIH campus in Bethesda, Md., the NICHD brought together three task forces made up of scientists, practicing physicians, lawyers, ethicists, and representatives of the public to evaluate and reach some agreement about the safety, efficacy, and proper uses at present of new technologies of antenatal diagnosis. One task force considered predictors of hereditary disease or congenital defects. Their discussion of midtrimester amniocentesis was reported in Pediatric Annals, June, 1979. Other predictors - ultrasound, fetoscopy, and measurement of alpha-fetoprotein (AFP) in amniotic fluid and maternal serum - are covered in this article.*

Ultrasound. Although pulse echo ultrasonography, better known as ultrasound, has applications in many areas of clinical practice, the discussion at the conference was confined to its use in antenatal diagnosis. The technology employs inaudible sound waves that are beamed through the mother's abdomen and reflected off the fetus. A transducer then translates these reflected waves (or echoes) into a series of impulses that make up a visual image of the fetus and placenta on a screen. The technique is noninvasive, greatly reduces the need for x-rays or radioisotope scanning, causes little or no discomfort, and generally takes only a few minutes. The most extensive examination may take only a half hour.

The task force strongly recommended that ultrasound be employed before midtrimester amniocentesis to choose the site for amniocentesis, to establish gestational age (by measurement of fetal head size), to determine if the fetus is alive, to detect possible multiple pregnancy, and to disclose uterine abnormalities. Ultrasound was also recommended as a follow-up procedure after elevated AFP has been found in maternal serum or amniotic fluid, to provide visual evidence of major structural defects in the brain or spinal cord (neural tube defects, such as spina bifida and anencephaly). In addition, members of the task force considered the procedure essential to determine the position of the fetus and the placenta before fetoscopy or placental aspiration. Ultrasound has also been employed by itself to detect certain fetal structural abnormalities. The task force had reservations about this application and concluded that most such uses of ultrasound are still in the area of clinical research, to be pursued only in specialized research centers. More clinical research was recommended.

It was the consensus of the conference that ultrasound is valuable as an adjunct procedure and contributes to the safety of amniocentesis. The majority of studies of ultrasound have shown no harmful effects to the fetus or the mother. However, the participants cautioned that negative results indicate relative harmlessness rather than absolute safety and that careful prospective studies need to be done on the outcome of pregnancies in which the procedure is used.

Fetoscopy and placental aspiration. The major application of these technologies has been to the diagnosis of hemoglobinopathies and other blood and chemical disorders. Guided by ultrasound, the fetoscope provides direct, but limited, visualization of the fetus, and a minute sample of fetal blood can be aspirated from the placental vessels and analyzed. The accuracy of diagnosis is approximately 98 per cent, but the risk to the fetus is significantly greater than in the case of amniocentesis. The task force judged these technologies to be experimental and not yet ready for general use. Further research was recommended to include assessment of immediate and long-term risks to the fetus and mother.

These techniques have great potential for the antenatal treatment of disease as well as diagnosis. Fetoscopy may one day play a major role as a means of introducing medicine, cell transplants, and genetic material into fetal tissues. Further research toward these ends was encouraged.

Alpha fetoprotein in amniotic fluid and maternal serum. High levels of AFP in amniotic fluid may indicate that the fetus has a neural tube defect, and measurement of AFP in amniotic fluid is now an accepted practice in pregnancies known to be at special risk for these disorders. The task force approved both the continuation and the expansion of this use and also advised that AFP should be routinely measured whenever amniocentesis is performed.

At present there are too few laboratories in the United States with the capacity of analyzing AFP in amniotic fluid. The task force members recommended that more laboratories be encouraged but cautioned that the expansion should be carefully monitored. They expressed concern about the current wide variation in standards for the assay as well as in the interpretation of results and the need for improved specificity and sensitivity of the test. Quality-control studies need to be conducted on test accuracy, the problems of false positives and negatives, and the methodology employed.

The measurement of AFP levels in maternal serum between the 1 4th and 20th week of pregnancy can also detect neural tube defects. A number of pilot programs in this country have begun to screen large numbers of pregnant women to locate those with elevated serum AFP levels. Those women identified by serum screening are then studied with more definitive diagnostic techniques - ultrasonography and determination of AFP concentration in amniotic fluid. Mass screening has also been done in England, where the incidence of neural tube defects is known to be high. The task force agreed that the pilot projects in the United States should be followed carefully. Data must be obtained on the efficacy of serum-AFP screening and the incidence of neural tube defects in this country to see if mass screening is warranted. Pending outcome of these pilot studies, the Conference members considered mass screening premature for general use.

The consensus of the conference, for all the predictors of hereditary disease and congenital defects - amniocentesis, ultrasound, fetoscopy, and AFP measurement - was that research should continue to assess safety, to refine technology, and to monitor use and outcome. The conference participants stressed the importance of genetic counseling so that the pregnant woman or couple who must make the decision to undergo any of the procedures should be well and fully informed.

Copies of the final report of the task force may be obtained by writing to the Office of Research Reporting. NICHD, Building 31, Room 2A-34, National Institutes of Health. Bethesda. Md. 20205.

10.3928/0090-4481-19791201-09

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