GENEWATCH
 
THE COMPLICATED COST-BENEFIT CALCULUS OF NEWBORN SCREENING
By Vani Kilakkathi
 

In their first days of life, 98 percent of the 4.3 million babies born annually in the United States undergo a form of genetic screening.1 Doctors in all fifty states and the District of Columbia collect blood samples from these infants and send the specimens to laboratories to be tested for a variety of metabolic conditions. Unlike many medical tests, the information from newborn screening tests are obtained and maintained by the state.

To date, studies have not offered an explanation accounting for this difference, but perhaps one can look to the history of newborn screening for an answer. Modern newborn screening programs can trace their roots back to the 1960s. In 1961, Robert Guthrie developed a simple test to screen for phenylketonuria (PKU), a metabolic condition, which, if left untreated, can lead to mental retardation.2 A few years later, disability activists successfully persuaded states to mandate newborn screening for this condition.3 Because these tests were originally conducted by the states, it is possible that modern newborn screening occurs at the state level purely through happenstance.

Since the 1960s, screening for newborn conditions has expanded greatly. To respond to the variance among the states regarding the number and list of conditions tested, in 2005 the American College of Medical Genetics (ACMG) proposed a “uniform screening panel”4—in other words, a standard list of metabolic conditions that newborns should or could be screened for. The ACMG assessed the screening potential of eighty-four conditions and ultimately grouped them into three categories: “core panel” conditions, “secondary panel” conditions, and conditions deemed to be “inappropriate for screening.”5 From this category construction, it appears that conditions on the core panel and the secondary panel are appropriate screening targets, since they are set apart from the group of conditions that the ACMG determined was “inappropriate for screening.” As further support for this idea, in its report, the ACMG stated: “The expert group recommends that State newborn screening programs: 1. Mandate screening for all core panel conditions defined by this report; [and] 2. Mandate reporting of all secondary target conditions defined by this report and of any abnormal results that may be associated with clinically significant conditions.”6

When asked about this report, ACMG Executive Director Michael S. Watson responded that “we never recommend screening for secondary conditions.”7 This is technically true; the report does recommend “reporting,” rather than “screening,” of secondary conditions. However, this semantic distinction is not particularly meaningful if one considers how the secondary conditions are identified. The ACMG core panel consists of twenty-nine conditions that should be primary screening targets, and the secondary panel consists of twenty-five conditions that, while not initial screening targets, may still be diagnosed and disclosed to patients if they are identified while screening for a core panel condition.8 Watson provided the following analogy: The secondary panel conditions “are secondary to the targets of screening as is a tumor found in a chest x-ray that is done to evaluate the victim of a car accident.”9 Just as the cancer would be reported to the accident victim, so too would a secondary condition that appeared during the screening for a core panel condition. However, it is important to note that both the cancer and the secondary condition would still be diagnosed as a result of some form of screening, despite the fact that they were not the initial targets of the X-ray or metabolic assay. Thus, if the ACMG mandates reporting of secondary conditions, they necessarily mandate some form of screening as well to identify these conditions.

This distinction between screening and reporting may indeed have been too nuanced, because after the ACMG published its report, jurisdictions increasingly began screening for conditions listed on the ACMG secondary panel as well as those on the core panel.10 Although the expansion of screening seems like a relatively benign or even beneficial development, there are a few reasons why such expansion should give pause. For one, the ACMG report departs from the traditional Wilson and Jungner criteria for screening, which emphasize the importance of treatment: "Of all the criteria that a screening test should fulfill, the ability to treat the condition adequately, when discovered, is perhaps the most important."11 Instead, the ACMG effectively loosened the screening requirements, as the report states that secondary panel conditions may "lack . . . proven efficacious treatment," or may have natural histories that are "not sufficiently well understood."12 This move by the ACMG may have propelled some states to go beyond screening for the core and secondary panel conditions and begin including other conditions, like Krabbe.13 Krabbe illustrates the dangers of adopting looser screening requirements: Of the twenty-four children who were screened for and “found to have genetic markers associated with the disease” in the state of New York, “only four . . . have developed Krabbe symptoms, whereas the other 20 continue to appear healthy.”14

This is not to say that newborn screening should be abandoned, or that these screening programs do not have benefits. It has been estimated that “[e]very year, between 4,000 and 5,000 infants are correctly identified as having serious genetic disorders, including some that would result in disability or death if they weren’t flagged so treatment could begin.”15 But even this number cannot capture the value of screening to the individual parents whose children have been able to lead normal, healthy lives because of early identification.

While this social value should not be diminished, it is possible that the benefits of screening have been somewhat overstated. One reason why the benefits of screening may be exaggerated is that the rarity of the conditions is often underemphasized. George Annas noted that “[a]t the observed rate [of screening], it would take 500 years before one case [of PKU] was missed because of parental refusal.” He also predicted that the same would be true of other conditions subsequently added to the newborn screening panels.16 Another reason why the benefits of screening are overstated is that many initial positives are actually false positives. One professor of pediatrics estimated that only about “one in fifty of every ‘positive’ newborn screening test detects actual disease” and stated that the average rate of false positives “can vary widely” between the conditions tested. As an additional complication, state-to-state differences in skill and resource availability may lead to situations where “parents in one state might find that false positive rates are as low as 0.01 percent of all newborn tests, while parents a few states over may find as many as 1.52 percent of those tests are false alarms.”17

An additional reason why the value of newborn screening may be exaggerated is that the public health benefits of screening may not live up to their promise. In its 2005 report, the ACMG stated that newborn screening offers the opportunity to “better [understand] disease history and characteristics” and provides hope for “earlier medical interventions” to be developed in the future.18 However, according to officials administering the screening programs in New York, Massachusetts, and North Carolina, newborn screening is mostly used to ensure that existing tests meet quality control standards, and, in certain cases, used to formulate new screening tests.19 While these are certainly beneficial applications of newborn screening, they seem to fall short of the stated promises of elucidating disease characteristics and generating earlier interventions. When asked about other applications of newborn screening, none of these public health officials could offer examples of research projects that had yielded results aligned with the promises stated in the ACMG paper; a survey of the available medical literature also failed to turn up any studies reflecting the benefits promised by the ACMG.20 Thus, it appears that the cost-benefit calculus of newborn screening is more complicated than one might expect.

When analyzing newborn screening programs, it is important to critically consider all of the potential benefits, as well as any associated disadvantages. The current systems for screening appear to have evolved organically, instead of developing through critical, strategic planning. As a result, the disadvantages of the current screening system may be overlooked or dismissed. For this reason, it is important to stimulate a national discussion about newborn screening that involves multiple perspectives, so that the full complexity of the issue is represented and considered. 

Vani Kilakkathi is a Fellow of the Council for Responsible Genetics and a second year student at Harvard Law School.

This article is based on the CRG report “Newborn Screening in America: Problems and Policies,” also by the author. For the full report, click here or visit www.councilforresponsiblegenetics.org.

 

ENDNOTES

 

1. Janis L. Gonzales, Genetic Testing and Newborn Screening, ETHICS FOR THE PEDIATRICIAN, Nov. 2011, at 490, 490.

2. Lainie Friedman Ross, Mandatory versus Voluntary Consent for Newborn Screening?, KENNEDY INST. ETHICS J., Dec. 2010, at 299-301.

3. Id. at 302-303.

4. Id. at 310.

5. AMERICAN COLLEGE OF MEDICAL GENETICS, NEWBORN SCREENING: TOWARD A UNIFORM SCREENING PANEL AND SYSTEM 13S-14S (2005), available at http://www.acmg.net/ resources/policies/NBS/NBS_Main_Report_00.pdf.

6. Id. at 43S (emphasis added).

7. Email from Michael S. Watson, Executive Director, Am. Coll. of Med. Genetics, to Jeremy Gruber, President, Council for Responsible Genetics (Oct. 4, 2012, 14:19 EST) (on file with author) (emphasis added).

8. See AMERICAN COLLEGE OF MEDICAL GENETICS, supra note 5.

9. Email from Michael S. Watson, supra note 7.

10. VANI KILAKKATHI, NEWBORN SCREENING IN AMERICA: PROBLEMS AND POLICIES app. A (2012), available at http://www.councilforresponsiblegenetics.org/pageDocuments/ WNMAKEPP1P.pdf.

11. J. M. G. WILSON & G. JUNGNER, PRINCIPLES AND PRACTICE OF SCREENING FOR DISEASE 27 (1968).

12. AMERICAN COLLEGE OF MEDICAL GENETICS, supra note 5, at 38S.

13. KILAKKATHI, supra note 10.

14. Ariel Bleicher, Perils of Newborn Screening, SCIENTIFIC AMERICAN, http://www.scientificamerican.com/article.cfm?id=perils-of-newborn-screening&page=2 (last visited Nov. 7, 2012).

15. JoNel Aleccia, Babies' blood tests can end in false-positive screening scares, TODAY HEALTH, http://today.msnbc.msn.com/id/42829175/ns/today-today_health/t/babies-blood-tests-can-end-false-positive-screening-scares/#.T_HoCr9Yv2g (last visited Nov. 8, 2012).

16. Ross, supra note 2, at 305.

17. Aleccia, supra note 15.

18. AMERICAN COLLEGE OF MEDICAL GENETICS, supra note 5, at 17S.

19. E.g., Telephone Interview with Newborn Screening Official, Massachusetts State Newborn Screening Program (July 26, 2012); Telephone Interview with Newborn Screening Official, New York State Newborn Screening Program (July 12, 2012); Telephone Interview with Newborn Screening Official, North Carolina State Newborn Screening Program (July 26, 2012). All sources asked to have their names withheld.

20. KILAKKATHI, supra note 10, at 11.

 
 
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