Overdiagnosis occurs when a true abnormality is discovered, but detection of that abnormality does not benefit the patient. It should be distinguished from misdiagnosis, in which the diagnosis is inaccurate, and it is not synonymous with overtreatment or overuse, in which excess medication or procedures are provided to patients for both correct and incorrect diagnoses. Overdiagnosis for adult conditions has gained a great deal of recognition over the last few years, led by realizations that certain screening initiatives, such as those for breast and prostate cancer, may be harming the very people they were designed to protect. In the fall of 2014, the second international Preventing Overdiagnosis Conference will be held, and the British Medical Journal will produce an overdiagnosis-themed journal issue. However, overdiagnosis in children has been less well described. This special article seeks to raise awareness of the possibility of overdiagnosis in pediatrics, suggesting that overdiagnosis may affect commonly diagnosed conditions such as attention-deficit/hyperactivity disorder, bacteremia, food allergy, hyperbilirubinemia, obstructive sleep apnea, and urinary tract infection. Through these and other examples, we discuss why overdiagnosis occurs and how it may be harming children. Additionally, we consider research and education strategies, with the goal to better elucidate pediatric overdiagnosis and mitigate its influence.
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November 2014
Special Article|
November 01 2014
Overdiagnosis: How Our Compulsion for Diagnosis May Be Harming Children
Eric R. Coon, MD;
aDivision of Inpatient Medicine, University of Utah School of Medicine, Primary Children’s Hospital, Salt Lake City, Utah;
Address correspondence to Eric R. Coon, MD, Department of Pediatrics, Division of Inpatient Medicine, University of Utah School of Medicine, Primary Children’s Hospital, 100 North Mario Capecchi Dr, Salt Lake City, UT 84113. E-mail: [email protected]
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Ricardo A. Quinonez, MD;
Ricardo A. Quinonez, MD
bBaylor College of Medicine, San Antonio Children’s Hospital, San Antonio, Texas;
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Virginia A. Moyer, MD;
Virginia A. Moyer, MD
cAmerican Board of Pediatrics, Maintenance of Certification and Quality, Chapel Hill, North Carolina; and
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Alan R. Schroeder, MD
Alan R. Schroeder, MD
dDepartment of Pediatrics, Santa Clara Valley Medical Center, San Jose, California
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Address correspondence to Eric R. Coon, MD, Department of Pediatrics, Division of Inpatient Medicine, University of Utah School of Medicine, Primary Children’s Hospital, 100 North Mario Capecchi Dr, Salt Lake City, UT 84113. E-mail: [email protected]
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
Pediatrics (2014) 134 (5): 1013–1023.
Article history
Accepted:
August 20 2014
Citation
Eric R. Coon, Ricardo A. Quinonez, Virginia A. Moyer, Alan R. Schroeder; Overdiagnosis: How Our Compulsion for Diagnosis May Be Harming Children. Pediatrics November 2014; 134 (5): 1013–1023. 10.1542/peds.2014-1778
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Re:Under-treatment, not over-diagnosis, of MCAD Deficiency poses a greater harm to children.
It is common for the same diagnosis to be beneficial to some patients but be overdiagnosed in others. The context of testing is often the critical factor in moderating the balance between benefit and harm. For example, testing asymptomatic individuals (screening) for certain deadly cancers (breast, prostate, neuroblastoma), does not benefit patients and exposes them to unnecessary harm. However, diagnosing symptomatic individuals with the same cancers can improve morbidity and mortality.
Similarly, we hypothesize that some children diagnosed with MCADD by newborn screening may be overdiagnosed, despite the fact that other diagnosed children can be spared severe neurologic morbidity or death. For example, a Danish study comparing MCADD diagnoses before and after implementation of newborn screening found that four times more MCADD diagnoses were made with screening.1 Because the first child with MCADD and the first MCADD enzyme assay were discovered in Denmark, awareness for this disease is particularly high there. For this reason, the authors of that study do not believe that the lower number of diagnoses prior to screening was due to missed diagnoses of clinically relevant disease. Because it is unlikely that the true incidence of MCADD increased fourfold during this time period, overdiagnosis is the most likely explanation for this finding.
Genetic testing is particularly susceptible to overdiagnosis because defective genes often do not translate into clinically important manifestations (reduced penetrance). The c.985A>G mutation is the most common genotype detected among symptomatic MCADD children diagnosed in the absence of screening. However, there are individuals homozygous for this mutation who are asymptomatic into adulthood2 and the authors of the Danish study speculate that as many as 50% of children with the c.985A>G mutation may be asymptomatic long term. Children with this mutation who will never be symptomatic cannot benefit from their diagnosis of MCADD, but may be harmed by acquiring this label and receiving its treatment. While some children undoubtedly benefit from an MCADD diagnosis, we agree with the USPSTF, that the harms of expanded newborn screening, including diagnosing MCADD, are poorly characterized and deserve more investigation.3
1. Andresen BS, Lund AM, Hougaard DM, et al. MCAD deficiency in Denmark. Molecular genetics and metabolism. Jun 2012;106(2):175-188. 2. Heptinstall LE, Till J, Wraith JE, Besley GT. Common MCAD mutation in a healthy parent of two affected siblings. Journal of inherited metabolic disease. 1995;18(5):638-639. 3. Moyer VA, Calonge N, Teutsch SM, Botkin JR. Expanding newborn screening: process, policy, and priorities. The Hastings Center report. May-Jun 2008;38(3):32-39.
Conflict of Interest:
None declared
Consider effect of computers on over diagnosis
The authors have done an excellent analysis of the overdiagnosis problem. Many of the same reasons for excessive testing among trainees were documented years ago in "To be complete" (1) and remain valid today; physician factors like intolerance of ambiguity and avoidance of omission errors have been accelerated with the use of electronic health software. Boolean logic and checklists require yes or no decisions despite the uncertainty of many steps in primary care pediatric encounters. The "checklist mentality" (2) and the "iPatient" (3) are illustrative of medical students and residents learning in a model where decision making more attuned to engineering problems has been adopted. Engineering checklists and aviation analogies, both used as examples that may improve medical care, only go so far; landing a plane and evaluating and treating self-limited problems are quite different. Although medicine borrows from many fields in approaches to quality and organization, i.e. sports, engineering, law, business, etc., at its core, medicine is different. The authors should consider the influence of electronic health record software on overdiagnosis.
References
1- Hardison JE. To be complete. NEJM 1979; 300: 193-194.
2- McMahon GT, Ashida R. The checklist mentality. Hektoen International: A journal of medical humanities. 6:4 (2014) ISSN 2155- 3017.
3- Verghese, A. Culture shock -Patient as icon, icon as patient. NEJM 2008; 359:2748-2751.
Conflict of Interest:
None declared
Under-treatment, not over-diagnosis, of MCAD Deficiency poses a greater harm to children.
I read with interest the article by Coon et al entitled "Overdiagnosis: How Our Compulsion for Diagnosis May Be Harming Children" in this most recent issue of Pediatrics. The authors thoroughly and clearly describe several medical conditions, which, when detected and treated, may lack benefit or result in harm to the patient. One example given is medium-chain Acyl-CoA dehydrogenase deficiency (MCADD), the most common fatty acid oxidation defect, occurring as frequently as 1:4,900 to 1: 17,000. Prior to its inclusion on newborn screening, MCADD has been implicated in cases of sudden infant death (Yang et al, 2007; Korman et al, 2004; Gregersen et al, 2010).
The disease results in the inability to mobilize fatty acids during periods of fasting, potentially resulting in hypoglycemia, a Reye-like syndrome with hepatic failure and death. Some children who are found to be carnitine deficient may require small amounts (5mg/kg) of supplementation. Management in the first decade of life involves frequent feeds which become less frequent as the child ages, avoidance of prolonged fasting, and vigilance during periods of intercurrent illness or hypermetabolic states. While it is true that a percentage of individuals have enough residual enzyme to avoid metabolic crises, the risk of not treating a potentially asymptomatic child with the disorder significantly outweighs the benefit of identifying over-diagnosis. A review article in 2002 by Rinaldo et al discusses this idea of a "mild" phenotype but emphasized that until fasting studies are performed, the individual should be treated as if they have the disorder and are at risk for decompensation. Personally, I do not check enzyme levels in children detected by newborn screening to modify my subsequent management. The majority of parents whose children I treat would likely be much more comfortable "treating" their child rather than relying on the enzyme analysis which may predict their infant to be asymptomatic. When in doubt, the primary care clinician should consult a metabolic specialist for management recommendations. Underestimating the possible complications of this disorder can be lethal.
1. Yang ZI, Lantz PE, Ibdah JA (2007). "Post-mortem two prevalent ?- oxidation mutations in sudden infant death". Pediatrics International 49 (6): 883-887. 2. Korman, S. H.; Gutman, A.; Brooks, R.; Sinnathamby, T.; Gregersen, N.; Andresen, B. S. (2004). "Homozygosity for a severe novel medium-chain acyl -CoA dehydrogenase (MCAD) mutation IVS3-1G>C that leads to introduction of a premature termination codon by complete missplicing of the MCAD mRNA and is associated with phenotypic diversity ranging from sudden neonatal death to asymptomatic status". Molecular Genetics and Metabolism 82 (2): 121-129. 3. Gregersen, N.; Winter, V.; Jensen, P. K.; Holmskov, A.; K?lvraa, S.; Andresen, B. S.; Christensen, E.; Bross, P.; Lundemose, J. B.; Gregersen, M. (1995). "Prenatal diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood". Prenatal diagnosis 15 (1): 82-86. 4. Rinaldo P, Matern D, and Bennett MJ. 2002. Fatty Acid Oxidation Disorders. Anny Rev. Physiol. 64:477-502.
Conflict of Interest:
Dr. Schrier Vergano is a member of the scientific advisory board for Ambry Genetics.
Regarding your interesting article on overdiagnosis
Dear Authors, Thank you very much for your interesting article on overdiagnosis. I wished to discuss two issues in addition. Firstly, one of the diagnoses you mentioned is ADHD. I fully agree that this diagnosis is particularly prone to overdiagnosis, and this diagnosis is often made without understanding the long term consequences for the patient as he/she enters adult life. Patients may find it harder or more expensive to find life insurance, disability insurance and even a mortgage, because this diagnosis, as do many others, triggers the financial institutions to assess their potential client to be of increased risk. Secondly, the use of diagnostic tools without appropriate rationale may lead to the same issue, even if an abnormal finding is later revoked or disproved by additional diagnostics. The mentioning of such findings on applications is often necessary, and therefore conclusions by the physicians about these findings in correspondence to other physicians and insurance companies should be very carefully worded.
Conflict of Interest:
None declared