Universal Newborn Screening for Congenital Heart Disease Using Pulse Oximetry: Has the Time Come?
Pub Date: Monday, July 6, 2009
Author: Daphne T. Hsu, MD and Waldemar A. Carlo, MD
Mahle WT, Newburger JW, Matherne GP, et al. Role of pulse oximetry in examining newborns for congenital heart disease: a scientific statement from the American Heart Association and American Academy of Pediatrics. Circulation 2009:120.
With the widespread availability of a safe, noninvasive method of determining systemic oxygen saturation, there has been enthusiasm within the pediatric community in support of the use of pulse oximetry to screen normal newborns for the presence of cyanotic congenital heart disease. This enthusiasm has been tempered by the worry that a high false-positive rate would have the untoward result of substantially increasing both parental anxiety and the use of costly resources such as echocardiography. The American Heart Association (AHA) and American Academy of Pediatrics (AAP) have published a joint scientific statement that evaluates the state of the evidence available to support screening with pulse oximetry to identify neonates with critical congenital heart disease (heart disease requiring intervention in the first year of life). In this statement, the authors present a systematic compilation of data from 51,098 neonates who underwent pulse oximetry measurement more than 24 hours after birth. In this combined dataset, the false positive rate was 0.035%, the negative predictive value was 99.9%, and the sensitivity was 69%. Despite these relatively compelling data, the authors conclude that the routine screening of newborns with pulse oximetry cannot be recommended based on the current level of evidence (Class IIb, level of evidence C), and they state that “further studies in large populations and across a broad range of delivery systems are needed.” Given the lack of randomized controlled trials and better controlled studies in large populations and across a broad range of health-care facilities, the conclusions and recommendations are reasonable. However, other experts may interpret the same data as evidence for a stronger class of recommendation in favor of universal newborn screening. A review of the principles of screening seems appropriate to address potential differences in expert opinion.
Principles of Screening
Although the AHA classification of recommendations and level of evidence has proven to be an important tool in the development of practice guidelines, this classification scheme has largely been applied to specific diseases, not to the evaluation of universal screening processes. In a 1968 document for the World Health Organization, Wilson and Jungner set out the following principles of early disease detection that continue to be relevant today [2,3]:
- The condition sought should be an important health problem.
- There should be an accepted treatment for patients with recognized disease.
- Facilities for diagnosis and treatment should be available.
- There should be a recognizable latent or early symptomatic stage.
- There should be a suitable test or examination.
- The test should be acceptable to the population.
- The natural history of the condition, including development from latent to declared disease, should be adequately understood.
- There should be an agreed policy on whom to treat as patients.
- The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.
- Case-finding should be a continuing process and not a “once and for all” project.
Although the Wilson and Jungner principles are commonly used in discussions of newborn screening for heritable diseases, a strong argument can be made that these principles should also be applied to the evaluation of methods used to screen for critical congenital heart disease. Several of the studies cited in the statement have used this approach and it is informative to look at the current statement in light of these principles.[4,5]
Mahle et al. have provided strong evidence that pulse oximetry is an accurate, reliable, and reproducible method to measure hypoxemia in neonates more than 24 hours of age. The natural history of congenital heart disease is well characterized, and the vast majority of critical congenital heart disease lesions have accepted treatments. Facilities that offer diagnosis and treatment are available throughout the United States, and many of the lesions have a latent phase prior to the development of overt heart failure or circulatory collapse. Critical congenital heart disease is an important health problem. The incidence of critical congenital heart disease among neonates is 2.5 of 1,000, which is substantially higher than the incidence of one per 10,000 live births found for infants with phenylketonuria, the first disease to be included in a universal neonatal screening protocol. Although the number of infants with critical congenital heart disease may be considered to be relatively small, Centers for Disease Control and Prevention infant mortality statistics from 2004-2005 (PDF) indicate that congenital heart disease is one of the leading causes of mortality in infants less than 1 year of age.
As Wilson and Jungner realized in 1968, an important principle in the consideration of a screening test is that the cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care. This principle is even more relevant today as the availability of diagnostic modalities has multiplied and health-care costs have increased. The lack of accurate data regarding the financial and psychological costs of universal pulse oximetry screening in neonates could be considered by some to be a barrier. Thus, the majority, if not all, of the Wilson and Jungner principles are fulfilled by pulse oximetry as a screening tool.
The purpose of a screening tool is to identify patients at risk for disease. Thus, an ideal screening tool is one with a high negative predictive value and a low false positive rate. In the systematic review presented in the statement, the negative predictive value and specificity were both 99.9% and the false positive rate was 0.035%. The sensitivity and positive predictive values were somewhat disappointing, 69% and 47%, respectively. These low values can be in part attributed to the authors' decision to perform the analysis using a definition of critical congenital heart disease that included all lesions that require catheter or surgical intervention in the first year of life. In 50% of the lesions in this definition, hypoxemia is present only some of the time. Table 4 of the statement demonstrates that pulse oximetry identified 33 of 35, or 94%, of the neonates who had critical congenital heart lesions always associated with hypoxemia in the first few days of life. As expected, pulse oximetry is less successful in identifying neonates with lesions not always associated with hypoxemia, such as tetralogy of Fallot, atrioventricular septal defect, coarctation, and pulmonary stenosis. Thus, it must be clear to those using pulse oximetry as a screening tool that sensitivity and positive predictive value for noncyanotic critical congenital heart disease are relatively low.
Outstanding Questions/Next Steps
In January, 2009 a multicenter study conducted in the United Kingdom entitled "Pulse oximetry as a screening test for congenital heart disease in newborn babies" completed its planned enrollment of 20,000 neonates. The aims of this study are:
- to develop pulse oximetry as a feasible screening tool for congenital heart disease in newborn babies,
- to determine the accuracy (sensitivity, specificity, predictive values, and likelihood ratios) of pulse oximetry for diagnosing critical and serious CHD in newborns using echocardiography, clinical follow-up, and congenital malformation registries' data as reference standards,
- to determine the psychosocial effect of pulse oximetry as a screening method among parents and acceptability to health professionals, and
- to compare the cost and cost effectiveness of pulse oximetry and other screening tests (routine neonatal clinical examination and antenatal screening) for improving outcomes of congenital heart disease in the newborn using model based economic evaluation.
With this scientific statement, the authors have presented the state of the evidence for the role of routine pulse oximetry in the detection of critical heart disease in the newborn. Although there is substantial evidence that pulse oximetry can identify the vast majority of neonates with cyanotic critical congenital heart disease, the use of universal pulse oximetry screening in clinical practice is less well established. Using the AHA classification of recommendations and levels of evidence for practice guidelines, the authors conclude that screening pulse oximetry may be considered because the benefits appear to exceed the risk but cannot be recommended (Class IIb, Level of Evidence C). The data provided in the statement demonstrates that pulse oximetry fulfills many of the principles used to determine the suitability of a diagnostic modality as a screening tool. An ongoing large study is designed to answer many outstanding questions regarding universal pulse oximetry screening, including determining the additional diagnostic benefit, quantifying the health-care costs and evaluating the psychological impact on the families. The protocol developed for this United Kingdom study is an excellent framework from which to design studies that evaluate how pulse oximetry performs as a screening tool in the varied health care-delivery systems that exist in the United States. If this and other future evidence show benefits from pulse oximetry screening for critical congenital heart disease, the recommendations will have to be revised. In the meantime, we concur with the present recommendations.
- Mahle W, Newburger J, Matherne G, et al. Role of pulse oximetry in examining newborns for congenital heart disease: a scientific statement from the American Heart Association and American Academy of Pediatrics. Circulation 2009.
- Wilson JM, Jungner YG. Principles and practice of mass screening for disease. Bol Oficina Sanit Panam 1968;65:281-393.
- Pellegrino E. The changing moral focus of newborn screening: an ethical analysis by the President's Council on Bioethics. 2008.
- Koppel RI, Druschel CM, Carter T, et al. Effectiveness of pulse oximetry screening for congenital heart disease in asymptomatic newborns. Pediatrics 2003;111:451-455.
- Liske MR, Greeley CS, Law DJ, et al. Report of the Tennessee Task Force on Screening Newborn Infants for Critical Congenital Heart Disease. Pediatrics 2006;118:1250-1256.
- Birmingham Clinical Trials Unit University of Birmingham. Pulse oximetry as a screening test for congenital heart disease in newborn babies. PulseOx Website 2008. Available at: www.pulseox.bham.ac.uk.
-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --