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A bioethicist discusses the history of newborn screenings and the serious reasons behind the need for informed consent.
Imagine you are leaving your local hospital or clinic, having just completed a routine visit for a nonserious problem. As you approach the main exit you are tackled and held down by 4 strong men in white coats. One of them grabs your arm, and another sticks your finger with a lancet and guides a few drops onto a small paper card. He applies a small Band-Aid and then they let you go.
“What the hell was that all about!?” you sputter.
“Well,” says the apparent leader, “We think there’s a 1:10,000 chance you have a really bad disease that could cause your brain to rot, and if you do have it, and if you go on this pretty unpleasant diet for the next 5 years, you will probably be OK.”
What’s wrong with this picture? Let me count the ways. First, it seems to be a simple case of battery, with witnesses, and you should be able to get a substantial settlement from the hospital that employs these guys, assuming they have enough sense not to go to trial.
Second, there are laws in every state that generally require healthcare providers to ask you if you would be interested in getting medical care. There are exceptions, but not for situations like this. The laws are based, among other things, on the foundational ethical principle of liberty: the notion that a competent adult should be free to live his or her life the way he wants, unless he or she is causing harm to someone else.1 Because you’ve never heard of the disease they’re talking about, you might have a lot of questions. That is, before deciding whether you wanted to have this test and before consenting to have the test, you would need to be informed of some basic facts.
You might want to know, for example, whether or not this test is accurate, particularly whether there are false positives that could the scare the bejeezus out of you and lead you to start on this nasty diet for no good reason. Also, you might want to know what the evidence is that the diet really worked, or worse, whether it might be harmful.
“Time out!” you might say at this point. Why is the absurd story appearing in a respected medical publication? Everyone knows these principles. Adults don’t get assaulted like this in trusted healthcare facilities.
Precisely, but children do-the persons least able to defend themselves, run away, or hire lawyers. Not big children so much, but the smallest most vulnerable ones-newborn infants.
Theoretically, the same rules are supposed to apply. Children are not supposed to be attacked like this without consent, and because they are incapable of providing meaningful consent (although they are pretty good at expressing their dissent!) someone has to do it for them, presumably their parents. That’s what the laws and innumerable professional guidelines say.2,3
However, since the early 1960s, virtually all children have been restrained, stuck, tested, and referred for treatment with very little involvement by their parents until after a test result comes back positive, when the parent is presented with a Hobson-like choice: "Treat or die!” or suffer profound brain damage or some other serious disability.
The usual rationale for this is that some rare but horrible preventable disease will befall the child; parents and doctors can’t be trusted to test for or treat these diseases; hence, the usual requirements for consent need to be suspended to protect children from harm.
Of course, the same argument could be made about adults-that they, and their doctors, commonly fail to get needed tests or treatments and suffer great harm as a result-but no one has suggested that assaulting them, without their consent, is justified to protect them from harm. Let’s skip that pesky inconsistency and get back to the infants.
The claim that it’s OK to invade a child’s body, without the parent’s consent, falls apart if the invasion involves a test of uncertain or unknown validity, and treatment of uncertain benefit and risks. Suspending the basic principle of consent, one would think, is a really big deal, and the invader should be really sure that the alleged harms and benefits are based on good science, not just a hunch that the test and treatment plan are good ideas. In fact, there is a federal law that prohibits newborn screening for research purposes without explicit consent.4
Unfortunately, newborn screening without consent got off to a bad start when the first disease targeted by this approach-phenylketonuria (PKU)-was mandated by state statutes in the 1960s. The idea was promulgated by a passionate group of well-meaning advocates, including Robert Guthrie, who developed the ingenious screening test, and President John Kennedy, whose family was devoted to improving the well-being of people with retardation because of their experience with the President’s sister, Rosemary.
However, passion is not a substitute for science, and the PKU mandatory screening program went from idea to implementation without reliable information about the characteristics of the screening test or the safety and efficacy of the diet. The test, it turned out years later, had a false-positive rate of around 20:1, so that many children labeled as having PKU were, in fact, destined to be normal.5 It also slowly came to light that phenylalanine restriction could be more harmful than phenylalanine excess, so that excessive restriction could cause not only severe brain damage, but also death attributed to protein malnutrition.
No one knows how often this happened because the screening program was not thought of as a research project, so there was not a systematic study of its benefits and risks. The American Academy of Pediatrics (AAP) thought it was a serious enough problem that it recommended shutting down the program, after most states had passed laws requiring screening, until experts could figure out the problems with the test and the diet. This was eventually accomplished, but it was a big enough problem that a congressional investigation was held, which recommended that the National Academy of Sciences (NAS) convene an expert committee to look into the problem and make recommendations in anticipation of other proposals for newborn screening.
One of the key recommendations of the NAS committee was that informed consent should be an essential prerequisite for newborn screening. That recommendation has been endorsed by innumerable committees and organizations, most recently the AAP and the American College of Medical Genetics (ACMG),2,3 but is honored more in the breach.
Some might say that the PKU story was long ago and far away, and we have learned our lessons. Would that it were so. In the 2000s, spurred by the development of tandem mass spectroscopy, it became easy to screen for dozens of abnormalities on the same drop of blood obtained for PKU screening. An expert committee of the ACMG, using criteria that were widely criticized,6 recommended a dramatic expansion of newborn screening, without the benefit of scientific studies of the tests or requirements for meaningful consent.7
One outcome of these recommendations was the labeling of dozens of children with 2-methylbutyryl-CoA dehydrogenase deficiency (MBADD), previously thought to be so rare that only 5 cases had ever been identified. Parents of the “affected” children identified in the new screening program were told their children would die, or suffer profound damage, if they were not maintained on a strict diet. Because virtually all of the affected children were from Hmong parents, with limited understanding of what the doctors were saying and little confidence in Western ideas of health and disease, compliance with the recommendations was close to zero, but years later the children seemed to be developing normally.8 It gradually came to light that the children did not have the dreaded disease MBADD, but a different mutation that led to an abnormal test and no apparent risk for serious disease. Unlike the PKU program that had a 20:1 false-positive rate, the children caught up in the MBADD program had 100% false-positive results and no true positives-possibly the worst test in medical history, but supported and recommended by experts.
Newborn screening and treatment with unproven remedies is not confined to state-mandated screening. In the 1970s, thousands of premature infants were screened for acidosis, for a decade or more, in virtually every neonatal intensive care unit in North America, and treated with concentrated bicarbonate solutions, often resulting in severe intracranial bleeding with no evidence of improved outcomes.9,10 A larger number of otherwise healthy newborns were screened for hyperbilirubinemia, and for decades treated with exchange transfusions using blood with unknown levels of hepatitis virus, with no evidence that the magic threshold of 20 mg/dL had any association with neurologic damage in this population.11 An even larger number of premature infants were screened for low oxygen levels for more than a century and treated with indiscriminate amounts of oxygen, causing blindness and lung damage, until studies showed that oxygen, like all drugs, had a dose-response curve, some doses being too high, some too low.12
Newborn screening has had many successes. Hundreds of thousands of children have been able to enjoy long healthy lives, free of disability, because of tests and treatments that turned out to have good benefit/risk profiles. However, there is still no “tollgate” for new ideas in newborn screening, no equivalent entity such as the US Food and Drug Administration with the authority to require that new ideas be tested before being unleashed on the population with no requirement for meaningful scientific studies or informed consent. Some committees have done better than others in using rigorous methods to sort out good from bad ideas.13
Taking consent seriously doesn’t necessarily mean reading an incomprehensible long document. For some tests an “opt-out” process might be appropriate, although you need to know some basic facts before deciding whether to opt out.
Imagine that the guy who was tackled and tested was told, “We think you might have a disease that affects 1:10,000 persons, but we’re not really sure, and we don’t really know whether the diet will help you or hurt you.” Faced with those facts, at least a few persons, given the choice, might pass on the test, whether for themselves or for their apparently healthy children.
1. Mill JS. On Liberty. 2nd ed. London: John W. Parker & Son; 1859.
2. Ross LF, Saal HM, David KL, Anderson RR; American Academy of Pediatrics; American College of Medical Genetics and Genomics. Technical report: Ethical and policy Issues in genetic testing and screening of children. Genet Med. 2013;15(3):234-245.
3. Committee on Bioethics; Committee on Genetics; American College of Medical Genetics; Genomics Social, Ethical, and Legal Issues Committee. Policy statement: Ethical and policy issues in genetic testing and screening of children. Pediatrics. 2013;131(3):620-622.
4. March of Dimes. Fact sheet: Research involving newborn blood spots. http://www.marchofdimes.org/materials/March-of-Dimes-NewbornBloodSpots-Paul_Amendment-Fact-Sheet-March-19-2015.pdf. Published March 19, 2015. Accessed September 16, 2016.
5. Paul DB, Brosco JP. The PKU Paradox: A Short History of a Genetic Disease. Baltimore, Maryland: Johns Hopkins University Press; 2013.
6. Botkin JR, Clayton EW, Fost NC, et al. Newborn screening technology: proceed with caution. Pediatrics. 2006;117(5):1793-1799.
7. Watson MS, Lloyd-Puryear MA, Mann MY, Rinaldo P, Howell RR, eds. Main report: Neonatal screening panel and system. Genet Med. 2006;8(5 suppl):12S-252S. Available at: https://www.acmg.net/resources/policies/NBS/NBS_Main_Report_00.pdf. Accessed September 16, 2016.
8. van Calcar SC, Gleason LA, Lindh H, et al. 2-methylbutyryl-CoA dehydrogenase deficiency in Hmong infants identified by expanded newborn screen. WMJ. 2007;106(1):12-15.
9. Simmons MA, Adcock EW 3rd, Bard H, Battaglia FC. Hypernatremia and intracranial hemorrhage in neonates. N Engl J Med. 1974;291(1):6-10.
10. Aschner JL, Poland RL. Sodium bicarbonate: basically useless therapy. Pediatrics. 2008;122(4):831-835.
11. Newman TB, Liljestrand P, Jeremy RJ, et al; Jaundice and Infant Feeding Study Team. Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more. N Engl J Med. 2006;354(18):1889-1900.
12. Silverman WA. A cautionary tale about supplemental oxygen: the albatross of neonatal medicine. Pediatrics. 2004;113(2):394-396.
13. Perrin JM, Knapp AA, Browning MF, et al. An evidence development process for newborn screening. Genet Med. 2010;12(3):131-134.
Dr Fost is Professor Emeritus, Departments of Pediatrics and Medical History and Bioethics, University of Wisconsin School of Medicine and Public Health, Madison, and the author of “Informed consent should be a required element for newborn screening, even for disorders with high benefit-risk ratios” (J Law Med Ethics. 2016;42:241-255), from which this article is derived. He discloses that he served as a nonvoting member of the National Academy of Sciences expert committee for newborn screening as referenced in this article.