Correspondence
Prenatal Diagnosis
N Engl J Med 1993; 328:1710-1712June 10, 1993
- Article
To the Editor:
In their discussion of prenatal diagnosis and the role of the “triple test” in screening for Down's syndrome, D'Alton and DeCherney (Jan. 14 issue)1 stated that the triple test “can identify approximately 60 percent of cases of Down's syndrome, with a false positive rate of 6.6 percent,” a rate that is reduced to 3.8 percent if ultrasonography is used to confirm gestational age. However, they failed to comment that lower detection rates (48 percent, with a false positive rate of 5.7 percent -- 4.1 percent after ultrasonography) have been shown in other prospective studies of triple screening,2 that other workers have shown that unconjugated estriol is of no benefit whatsoever in screening for Down's syndrome,3,4 or that an assay of a new analyte (the free β subunit of human chorionic gonadotropin) has been shown to improve detection rates significantly when used in place of assays of total human chorionic gonadotropin4.
A further concern about their article is that unlike screening for neural-tube defects, in screening for Down's syndrome the rates of detection and false positive results are age-dependent because of the mathematics of risk derivation5. Thus, in 18-year-old women, the detection rate may be as low as 44 percent, with a false positive rate of 3.1 percent; whereas in 36-year-old women, the detection rate may be 78 percent, but the false positive rate will also be much higher at 19 percent. This is important because if screening is introduced only for women younger than 35 while amniocentesis is offered automatically to all older women, the apparent detection rate of a screening program will fall far short of the rate expected by the public. A further area of consideration is that of pre-screening counseling of women, when knowledge of the age-dependent effectiveness of the test may allow the counselor to provide women with realistic expectations of screening.
5 ReferencesT.M. Reynolds, M.B., Ch.B., B.Sc., M.R.C.Path.
M.D. Penney, M.D., B.Sc., M.R.C.Path.
Royal Gwent Hospital, Newport, Gwent NP9 2UB, United Kingdom1
D'Alton ME ,DeCherney AH . Prenatal diagnosis. N Engl J Med 1993;328:114-120
Full Text | Web of Science | Medline2
Wald NJ ,Kennard A ,Densem JW ,Cuckle HS ,Chard T ,Butler L . Antenatal maternal serum screening for Down's syndrome: results of a demonstration project. BMJ 1992;305:391-394
CrossRef | Web of Science | Medline3
Crossley J, Aitken D, Connor J. Second trimester unconjugated oestriol levels in maternal serum from chromosomally abnormal pregnancies using an optimized assay. Prenat Diagn (in press).
4
Spencer K ,Coombes EJ ,Mallard AS ,Ward AM . Free β human choriogonadotropin in Down's syndrome screening: a multicentre study of its role compared with other biochemical markers. Ann Clin Biochem 1992;29:506-518
Web of Science | Medline5
Reynolds T, Nix B, Dunstan F, Dawson A. Age-specific detection and false positive rates: an aid to counseling in Down syndrome risk screening. Obstet Gynecol (in press).
To the Editor:
The first paragraph of D'Alton and DeCherney's concise and cogent overview of prenatal diagnosis refers to the costs of congenital medical problems without mentioning the benefits afforded by caring for and raising children with these problems. Although perhaps an effective gambit for grant applications, this style of presentation in peer-reviewed journals intimates that the costs far outweigh all benefits. Yet, there is a broad spectrum of outcomes in children with congenital problems; their future, for better or worse, is wrapped in prognostic uncertainty. . . .
Discussions of handicapped infants that mention only costs invoke a one-sided cost-benefit analysis that, even if pursued only in brief opening remarks, is intellectually restrictive, biased, and inappropriate. Regardless of what one thinks about the difficult ethical dilemmas involved in prenatal testing (which have recently been discussed in the Journal1,2), the medical profession clearly needs to be vigilant and apply the same ideal of “nondirectiveness” that governs prenatal counseling to the way in which health care for medically disadvantaged children is discussed in the literature, presenting both sides. For none of us are perfect. We all have our “costs” and our “benefits.” The challenge for the profession in these coming decades of tightening finances will be to resist becoming cost-obsessed providers of technical offerings, striving instead to maintain an intelligent and broadly informed compassion in print and in practice.
2 ReferencesChris Feudtner, M.A.
University of Pennsylvania, Philadelphia, PA 191041
Thorp JM Jr ,Bowes WA Jr . Prolife perinatologist -- paradox or possibility? N Engl J Med 1992;326:1217-1219
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"Prolife" perinatologistN Engl J Med 1992;327:812-814
Full Text
To the Editor:
It was disappointing that D'Alton and DeCherney did not discuss the emotional consequences of test results that reveal a serious or lethal fetal anomaly. Prenatal diagnosis has an important role in the management of many pregnancies, and parents who receive news of normal results are reassured. But far too often the emotional and psychological ramifications for parents faced with abnormal results are overlooked.
The loss of an unborn baby is devastating1. Those who work with parents who decide to terminate a wanted pregnancy because of the discovery of a fetal anomaly know that this loss is complicated by the fact that the parents have actively decided to end the pregnancy2. This loss is further complicated by the isolation that often accompanies the decision to terminate a pregnancy3. Parents report that they are reluctant to share the circumstances of their loss for fear of retaliatory remarks. Consequently, at a time when the support of family and friends is most needed, parents grieve alone.
As professionals involved in the expanding and important field of prenatal diagnosis and reproductive genetics, we must include in articles on prenatal diagnosis a discussion of the psychological and emotional consequences for parents when testing reveals a fetal anomaly. To do any less ignores one of the most difficult and emotionally charged issues we face.
3 ReferencesMolly A. Minnick, M.S.W.
Burns Clinic Medical Center, Petoskey, MI 497701
Stack JM . Reproductive casualties: effects on families and professional caregivers. Semin Fam Med 1982;3:98-1042
Minnick MA, Delp KD, Ciotti MC. A time to decide, a time to heal. 3rd ed. Mullet Lake, Mich.: Pineapple Press, 1992.
3
Lyon WL. A mother's dilemma. Mullett Lake, Mich.: Pineapple Press, 1993.
To the Editor:
The article on prenatal diagnosis by D'Alton and DeCherney superbly covered the medical issues and mentioned one ethical issue: nondirective genetic counseling. In 1985 and 1986, a multinational study1 of 682 geneticists and physicians who perform prenatal diagnosis identified a cluster of social and ethical issues, and these issues can only have increased as the diagnostic alternatives have expanded (Table 1Table 1
Social and Ethical Issues in Prenatal Diagnosis.).Research on prenatal diagnosis has increased, but the increase in research on fetal therapy has been much smaller. Since the late 1970s in the United States, fetal research has been limited by federal bans and restrictive policies2. The new administration has begun to restore some research freedom to the federal sector of science. To review the large agenda in fetal and embryo research beyond that pertaining to the transplantation of fetal tissue, an ethics advisory board should be restored to advise the secretary of the Department of Health and Human Services.
The decisions to be made with respect to inadequate access to genetic services require guidance from society. Ought prenatal diagnosis and other genetic services be included in a package of basic primary health care for Americans? Oregon's Medicaid Demonstration Project included prenatal diagnosis in routine prenatal care, giving it high priority (Kirk EP: personal communication). In view of the human suffering caused by hereditary disease, health care reform should consider giving priority to genetic services offered on a voluntary basis3. With respect to the other issues listed in Table 1, centers providing prenatal diagnosis need internal guidelines to assist clinicians, counselors, and trainees with difficult ethical issues4.
4 ReferencesJohn C. Fletcher, Ph.D.
University of Virginia School of Medicine, Charlottesville, VA 22908Dorothy C. Wertz, Ph.D.
Shriver Center for Mental Retardation, Inc., Waltham, MA 022541
Wertz DC ,Fletcher JC ,Mulvihill JJ . Medical geneticists confront ethical dilemmas: cross-cultural comparisons among 18 nations. Am J Hum Genet 1990;46:1200-1213
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Fletcher JC . Controversies in research ethics affecting the future of human gene therapy. Hum Gene Ther 1990;1:307-324
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Powledge TM ,Fletcher J . Guidelines for the ethical, social and legal issues in prenatal diagnosis: a report from the Genetics Research Group of the Hastings Center, Institute of Society, Ethics and the Life Sciences. N Engl J Med 1979;300:168-172
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Fletcher JC, Wertz DC. Ethics and prenatal diagnosis: problems, positions, and proposed guidelines. In: Milunsky A, ed. Genetic disorders and the fetus: diagnosis, prevention, and treatment. 3rd ed. Baltimore: Johns Hopkins University Press, 1992:823-54.
Author/Editor Response
The authors reply:
To the Editor: We did not discuss the role of triple-test screening in Down's syndrome, but simply mentioned the results of a large, prospective study of such screening in the Journal1. We agree that serum alpha-fetoprotein and human chorionic gonadotropin concentrations are currently the two most effective markers for the detection of aneuploidy and that the single marker that yields the highest rate of detection for Down's syndrome is the level of human chorionic gonadotropin. The addition of a new analyte -- the free β subunit of human chorionic gonadotropin -- to screening is promising; however, additional data are needed before the relative value of tests involving human chorionic gonadotropin and the free β subunit of chorionic gonadotropin can be assessed. Two references cited by Reynolds and Penney in their letter are in press. We look forward to the opportunity to evaluate them.
Space limitations did not allow us to discuss fully the emotional consequences for parents of antenatal test results that reveal a fetal anomaly. We believe, however, that centers that offer prenatal diagnosis are cognizant of this issue and have genetic counseling and support groups in place to help families who need them.
We are disappointed that Feudtner interpreted an introductory sentence regarding the cost of neonatal intensive care and rehabilitation programs as invoking a “one-sided cost-benefit analysis.” Our review of the indications and techniques of current practice was not a socioeconomic policy statement.
Fetal therapy was not the focus of our report, but guidelines published in the Journal in 1982 address the ethics of fetal intervention2. As fetal diagnostic techniques and therapy advance, pregnant women and obstetricians will face an ever-increasing number of difficult decisions. In our judgment, the role of the obstetrician should be one of informed educator and counselor. Obstetricians should consult with other professionals in the discipline when appropriate -- for example, pediatricians, geneticists, pediatric surgeons, and psychologists. This improves the quality of the decision-making process and, in our experience, usually helps patients and their families reach a decision. When one is considering the option of abortion, the medical factors are only one component. Religious beliefs, cultural and ethnic backgrounds, and economic and family situations also affect a woman's decision. When clinicians, patients, and their families reach an impasse, consultation with an institutional ethics committee provides a useful forum for discussion and resolution.
Finally, we welcome and support the suggestions of Fletcher and Wertz that prenatal diagnosis and access to other genetic services be included as basic components of a health care package available to all Americans.
2 ReferencesMary E. D'Alton, M.D.
Alan H. DeCherney, M.D.
Tufts University-New England Medical Center, Boston, MA 021111
Haddow JE ,Palomaki GE ,Knight GJ , et al. Prenatal screening for Down's syndrome with use of maternal serum markers. N Engl J Med 1992;327:588-593
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Harrison MR ,Filly RA ,Golbus MS , et al. Fetal treatment 1982. N Engl J Med 1982;307:1651-1652
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