EDITORIALS 23. Mosley WH (ed.): Nutrition and Human Reproduction. New York: Plenum Press, 1978. 24. Mata UJ: The Children of Santa Maria Cauqde: A Prospective Field Study of Health and Growth. Cambridge, MA: MIT Press, 1978. 25. Berggren WL: Administration and evaluation of rural health services: I. a tetanus control program in Haiti. Am J Trop Med
and Hygiene 23:936-949, 1974. 26. Morley D: Paediatric Priorities in the Developing World. London: Butterworths, 1973. 27. Cassel JC: Community diagnosis, pp. 345-362 In Omran, AR (ed.) Community Medicine in Developing Countries. New York: Springer, 1974.
Alpha-Fetoprotein and the Prenatal Detection of Neural Tube Defects Delay in the utilization of a new diagnostic tool may on occasion be considerable. The alpha-fetoprotein (AFP) assay is a current good example. First recognized in 1972 in Edinburgh' as an important tool for the early detection of open neural tube defects (NTDS), many have subsequently confirmed the utility of AFP as both a diagnostic and screening test.2-7 Despite the introduction of AFP into the United Kingdom seven years ago, the Food and Drug Administration in the United States has yet to license the necessary reagents for sale and distribution. Now with the licensing process nearing completion, the FDA has been besieged by concerned public interest groups (such as the Spina Bifida Association of America and the Women's Defense Fund), demanding that even more control be required. There are sound reasons for their concern about how the AFP test may be used, abused, and monitored. The use of amniotic fluid AFP assays is in the diagnostic test category and, hence, as for any other such test, various control mechanisms are already in place. In our laboratories, experience with over 14,000 pregnancies has allowed for the detection of 110 open NTDS (with none missed) and a false positive rate of well below 0.1 per cent. There have thus far also been only four closed, and hence undiagnosable, lesions. The diagnostic role of this AFP assay in amniotic fluid seems straightforward and unchallenged in experienced laboratories. Problems beset the use of AFP as a screening tool. We have previously noted the essential criteria for a national screening strategy for all pregnancies.8 Quality control, monitoring and surveillance of laboratories, voluntarism, equal access, and the provision of expert ancillary services for genetic counseling and ultrasound are all crucial. Concerned citizen groups are worried inter alia about: * informed consent (virtually impossible to achieve in a large screening program, and impractical to boot); * the lack of an established nationwide laboratory quality control scheme (often unavailable for many other important diagnostic tests); * the ability of laboratories and physicians to interpret assay results; * the efficiency of urgent communication processes between laboratory, physician and patient under tight time constraints; * the opportunities to examine a second blood sample; * the degree of nationwide expertise with ultrasound; * the nature of genetic counseling (directive or non-directive);2 and 552
* the frequency with which a normal fetus will be aborted because of the screening process (rare when the assay is performed in experienced centers). While Layde, et al, have addressed the cost-benefit aspects in this issue of the Journal,9 it would seem injudicious at present, in the face of the real concerns expressed, to launch a nationwide AFP screening program. Intensive statewide pilot demonstration projects should reveal in a relatively short time the appropriateness and efficacy of screening in the U.S. Meanwhile, it is clear that a simple, unrestricted licensing of reagents for the AFP assay may precipitate an unfortunate sequence of events in some areas-leading ultimately to missed diagnoses as well as the avoidable termination of some normal pregnancies. Through the exercise of its statutory power, the FDA should be able not only to license products, but also to restrict their usage by specification. Moreover, another agency, such as the Center for Disease Control, could be called upon to exercise their authority for monitoring surveillance and proficiency testing. The responsibility presently rests squarely with the FDA to move expeditiously as well as to prevent a valuable diagnostic and screening tool from being abused and falling into disrepute. All prospective parents, and especially those who have had children with neural tube defects, should have the opportunity to benefit from advances in medical technology without fear of spurious or unreliable test results.
AUBREY MILUNSKY, MBBCH, MRCP, DCH. Address reprint requests to Dr. Aubrey Milunsky, Director, Genetics Division, Eunice Kennedy Shriver Center, 200 Trapelo Road, Waltham, MA 02154. Dr. Milunsky is also affiliated with the Department of Pediatrics, Harvard Medical School, and the Massachusetts General Hospital.
REFERENCES
1. Brock DJH and Sutcliffe RG: Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet 2:197, 1972. 2. Milunsky A (ed.): The Prevention of Genetic Disease and Mental Retardation. W.B. Saunders Company, Philadelphia, 1975. 3. Brock DJH: Biochemical and cytological methods in the diagnosis of neural tube defects. In Progress in Medical Genetics, Vol. II. Edited by AC Steinberg, AG Bearn, AG Motulsky, et al. W.B. Saunders Co., Philadelphia, 1977. AJPH June, 1979, Vol. 69, No. 6
EDITORIALS 4. U.K. collaborative study on alpha-fetoprotein in relation to neural-tube defects, maternal serum alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet 1:1324, 1977. 5. Ferguson-Smith MA, Rawlinson HA, May HM, et al: Avoidance of anencephalic and spina bifida births by maternal serum-alphafetoprotein screening. Lancet 1:1330, 1978. 6. Crandall BF and Brazier MA (eds.): Prevention of Neural Tube Defects: The Role of Alpha-Fetoprotein. Academic Press, New
York, 1978. 7. Milunsky A (ed.): Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment. Plenum Press, New York (in press 1979). 8. Milunsky A and Alpert E: Maternal serum AFP screening (editorial). New Eng J Med 298:738, 1978. 9. Layde PM, Von Allmen SD and Oakley GP, Jr.,: Maternal serum alpha-fetoprotein screening: a cost-benefit analysis. Am J Public Health 69:566-573, 1979.
ERRATUM The table below is a corrected version of Table 4 in the article "A Comparison of Mail, Telephone, and Home Interview Strategies for Household Health Surveys," by Jack Siemiatycki, PhD. The article appeared in the March 1979 issue of the Journal, pp. 238-245. TABLE 4-Per Cent Underreporting of Doctor Visits Recorded In QHIB Files, by Strategy Strategy Mail* Question
Seen doctor in past 2 weeks? Seen doctor 2-4 weeks ago? Seen doctor in past year?
(1974)
23.2 (267) 37.1 (283)
11.9 (1206)
Tele, phone* (1974)
Home" (1971-72)
30.1 (256) 43.7 (238) 13.2 (1201)
23.8 (?3) NP 16.1 (408)
*Includes all follow-up media "Adjusted to the linguistic and social class distributions of 1974 respondents ***Denominator is number of persons for whom OHIB records indicate at least one visit at the time interval NP Question not posed in 1971-72
AJPH June, 1979, Vol. 69, No. 6
553
and Hygiene 23:936-949, 1974. 26. Morley D: Paediatric Priorities in the Developing World. London: Butterworths, 1973. 27. Cassel JC: Community diagnosis, pp. 345-362 In Omran, AR (ed.) Community Medicine in Developing Countries. New York: Springer, 1974.
Alpha-Fetoprotein and the Prenatal Detection of Neural Tube Defects Delay in the utilization of a new diagnostic tool may on occasion be considerable. The alpha-fetoprotein (AFP) assay is a current good example. First recognized in 1972 in Edinburgh' as an important tool for the early detection of open neural tube defects (NTDS), many have subsequently confirmed the utility of AFP as both a diagnostic and screening test.2-7 Despite the introduction of AFP into the United Kingdom seven years ago, the Food and Drug Administration in the United States has yet to license the necessary reagents for sale and distribution. Now with the licensing process nearing completion, the FDA has been besieged by concerned public interest groups (such as the Spina Bifida Association of America and the Women's Defense Fund), demanding that even more control be required. There are sound reasons for their concern about how the AFP test may be used, abused, and monitored. The use of amniotic fluid AFP assays is in the diagnostic test category and, hence, as for any other such test, various control mechanisms are already in place. In our laboratories, experience with over 14,000 pregnancies has allowed for the detection of 110 open NTDS (with none missed) and a false positive rate of well below 0.1 per cent. There have thus far also been only four closed, and hence undiagnosable, lesions. The diagnostic role of this AFP assay in amniotic fluid seems straightforward and unchallenged in experienced laboratories. Problems beset the use of AFP as a screening tool. We have previously noted the essential criteria for a national screening strategy for all pregnancies.8 Quality control, monitoring and surveillance of laboratories, voluntarism, equal access, and the provision of expert ancillary services for genetic counseling and ultrasound are all crucial. Concerned citizen groups are worried inter alia about: * informed consent (virtually impossible to achieve in a large screening program, and impractical to boot); * the lack of an established nationwide laboratory quality control scheme (often unavailable for many other important diagnostic tests); * the ability of laboratories and physicians to interpret assay results; * the efficiency of urgent communication processes between laboratory, physician and patient under tight time constraints; * the opportunities to examine a second blood sample; * the degree of nationwide expertise with ultrasound; * the nature of genetic counseling (directive or non-directive);2 and 552
* the frequency with which a normal fetus will be aborted because of the screening process (rare when the assay is performed in experienced centers). While Layde, et al, have addressed the cost-benefit aspects in this issue of the Journal,9 it would seem injudicious at present, in the face of the real concerns expressed, to launch a nationwide AFP screening program. Intensive statewide pilot demonstration projects should reveal in a relatively short time the appropriateness and efficacy of screening in the U.S. Meanwhile, it is clear that a simple, unrestricted licensing of reagents for the AFP assay may precipitate an unfortunate sequence of events in some areas-leading ultimately to missed diagnoses as well as the avoidable termination of some normal pregnancies. Through the exercise of its statutory power, the FDA should be able not only to license products, but also to restrict their usage by specification. Moreover, another agency, such as the Center for Disease Control, could be called upon to exercise their authority for monitoring surveillance and proficiency testing. The responsibility presently rests squarely with the FDA to move expeditiously as well as to prevent a valuable diagnostic and screening tool from being abused and falling into disrepute. All prospective parents, and especially those who have had children with neural tube defects, should have the opportunity to benefit from advances in medical technology without fear of spurious or unreliable test results.
AUBREY MILUNSKY, MBBCH, MRCP, DCH. Address reprint requests to Dr. Aubrey Milunsky, Director, Genetics Division, Eunice Kennedy Shriver Center, 200 Trapelo Road, Waltham, MA 02154. Dr. Milunsky is also affiliated with the Department of Pediatrics, Harvard Medical School, and the Massachusetts General Hospital.
REFERENCES
1. Brock DJH and Sutcliffe RG: Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet 2:197, 1972. 2. Milunsky A (ed.): The Prevention of Genetic Disease and Mental Retardation. W.B. Saunders Company, Philadelphia, 1975. 3. Brock DJH: Biochemical and cytological methods in the diagnosis of neural tube defects. In Progress in Medical Genetics, Vol. II. Edited by AC Steinberg, AG Bearn, AG Motulsky, et al. W.B. Saunders Co., Philadelphia, 1977. AJPH June, 1979, Vol. 69, No. 6
EDITORIALS 4. U.K. collaborative study on alpha-fetoprotein in relation to neural-tube defects, maternal serum alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet 1:1324, 1977. 5. Ferguson-Smith MA, Rawlinson HA, May HM, et al: Avoidance of anencephalic and spina bifida births by maternal serum-alphafetoprotein screening. Lancet 1:1330, 1978. 6. Crandall BF and Brazier MA (eds.): Prevention of Neural Tube Defects: The Role of Alpha-Fetoprotein. Academic Press, New
York, 1978. 7. Milunsky A (ed.): Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment. Plenum Press, New York (in press 1979). 8. Milunsky A and Alpert E: Maternal serum AFP screening (editorial). New Eng J Med 298:738, 1978. 9. Layde PM, Von Allmen SD and Oakley GP, Jr.,: Maternal serum alpha-fetoprotein screening: a cost-benefit analysis. Am J Public Health 69:566-573, 1979.
ERRATUM The table below is a corrected version of Table 4 in the article "A Comparison of Mail, Telephone, and Home Interview Strategies for Household Health Surveys," by Jack Siemiatycki, PhD. The article appeared in the March 1979 issue of the Journal, pp. 238-245. TABLE 4-Per Cent Underreporting of Doctor Visits Recorded In QHIB Files, by Strategy Strategy Mail* Question
Seen doctor in past 2 weeks? Seen doctor 2-4 weeks ago? Seen doctor in past year?
(1974)
23.2 (267) 37.1 (283)
11.9 (1206)
Tele, phone* (1974)
Home" (1971-72)
30.1 (256) 43.7 (238) 13.2 (1201)
23.8 (?3) NP 16.1 (408)
*Includes all follow-up media "Adjusted to the linguistic and social class distributions of 1974 respondents ***Denominator is number of persons for whom OHIB records indicate at least one visit at the time interval NP Question not posed in 1971-72
AJPH June, 1979, Vol. 69, No. 6
553
