Perspectives in Biology and Medicine

PRENATAL SCREENING FOR NEURAL TUBE DEFECTS: A CHOICE FOR ALL LEE N. MUECKE* Introduction Although the association between elevated maternal serum alphafetoprotein and neural tube defects was first recognized in 1972 and is now well established [1], population-based screening programs have yet to gain broad acceptance in this country. Various obstacles appear to be responsible for thwarting the successful implementation of screening, including anxiety among screening participants [2], false positive results [2], cost-effectiveness [3—5], and fear of coerced termination of pregnancy [6]. On the basis of prevalence and required burden of care, neural tube defects qualify as a significant public health problem. They occur commonly , with a collective incidence for anencephaly and spina bifida of 1-2 per 1,000 live births [7]. AU these infants will die in the neonatal period if afflicted with anencephaly, as will one-third of those with open spina bifida. The majority (65%), however, survive [8] with permanent physical and/or mental disability and require varying degrees of lifetime chronic care. Screening of maternal serum alpha-fetoprotein levels is now based on well-developed technology. Alpha-fetoprotein, a glycoprotein synthesized by the fetus, crosses the placenta and appears in maternal serum and is optimally measured at 16-18 weeks gestation. Correct interpretation of the screening result requires accurate knowledge of the mother's gestational age and is determined from normative data [8]. Elevated The author gratefully acknowledges the helpful comments of Drs. Frank Greenberg, Guy Parcel, and Denise Simons-Morton. Work done at Center for Health Promotion Research and Development, University of Texas School of Public Health, 1200 Herman Pressler, Houston, Texas 77030. *Present address: Examination Team Physician, NHANES III, 1650 Research Boulevard , Rockville, Maryland 20850.© 1992 by The University of Chicago. All rights reserved. 003 1 -5982/93/360 1-0796$0 1 .00 Perspectives in Biology and Medicine, 36, 1 ¦ Autumn 1992 87 values are determined by setting cut-off points that provide optimal sensitivity and specificity, and usually range from 2.5 to 4 "multiples of the mean" in the baseline reference population [9]. Sensitivity of the tests for open neural tube defects (with a cut-off at three standard deviations ) ranges from 96 to 100 percent, while specificity is greater than 99 percent [9]. The number of false positives and false negatives is determined by the exact cut-off point chosen [8]. Women who screen positive routinely receive a repeat screening, and if truly elevated, are referred for serial diagnostic procedures including ultrasound, amniocentesis , and serum acetylcholinesterase determination [9]. The detection capability of screening maternal serum alphafetoprotein levels has steadily expanded. In addition to neural tube defects , a variety of birth conditions can now be detected. High values can detect numerous genetic defects including omphalocele, Turner's syndrome with cystic hygroma, teratoma, or may simply indicate a multiple pregnancy [7, 9]. In addition to screening for high values, low values of maternal serum alpha-fetoprotein are now identified as a risk factor for Down syndrome (Trisomy 21) [7]. Thus, in light of the increased utility and refined technology of maternal serum alpha-fetoprotein screening, the public's health would be greatly benefitted if barriers to implementation can be successfully overcome. Background Steinbrook [6] notes that in the late 1970s an enthusiastic American public embraced the notion of large screening programs for neural tube defects. Momentum was lost, however, due to the perceived threat of unnecessary abortions and concerns over possible misinterpretations of test results. Specific concerns associated with testing became evident following the nation's first statewide effort, in California, to implement screening for neural tube defects. Implemented in April 1986, California has eighteen statewide "prenatal diagnostic centers" [6, 10] that provide follow-up evaluation of women with positive results. This program has been criticized by physicians on the basis of patient anxiety [2], difficulty in laboratory standardization [2], and variable access to screening due to differing policies of reimbursement. For example, statefunded medical insurance in California covers the $40 screening fee while some private insurers do not [3]. Fortunately, concerns about laboratory inaccuracies have been largely allayed over the last decade by technical advances [9], and adequate quality control can now be achieved with proper regulation...