- Email: [email protected]
Pulse oximetry screening for critical congenital heart defects
Correspondence
1
2
Ma C, An Z, Hao L, et al. Progress toward measles elimination in the People’s Republic of China, 2000–2009. J Infect Dis 2011; 204: S447–54. De Serres G, Boulianne N, Defay F, et al. Higher risk of measles when the first dose of a 2-dose schedule of measles vaccine is given at 12–14 months versus 15 months of age. Clin Infect Dis 2012; 55: 394–402.
Pulse oximetry screening for critical congenital heart defects Shakila Thangaratinam and colleagues (June 30, p 2459)1 report a systematic review to assess pulse oximetry as a screening method for critical congenital heart defects (CCHD) in asymptomatic newborn babies. They found that pulse oximetry was highly specific and moderately sensitive in the detection of CCHD, and this they cite as compelling evidence to introduce pulse oximetry as a screening test in asymptomatic newborn babies. We agree that the introduction of such screening would lead to a reduction in morbidity and mortality associated with CCHD. These disorders accounted for an estimated 219 000 deaths in 20042—about 2% of child deaths worldwide (and a higher proportion in rich countries where child mortality rates are lower). However, this point raises the issue that many disorders characterised by hypoxaemia have a higher burden of neonatal and child mortality and morbidity than do CCHD, but are not screened for with pulse oximetry. Globally 64% of the 7·6 million deaths in children younger than 5 years are due to infectious causes, most of which involve hypoxaemia—notably pneumonia (18% of child deaths), diarrhoea (11%), malaria (7%), and neonatal sepsis (5%).3 There are an estimated 1·5–2·7 million cases of hypoxaemic pneumonia annually.4,5 Additionally, preterm birth is the second leading cause of child death (1·1 million per year),3 mainly through respiratory distress syndrome, which requires oxygen therapy and has a www.thelancet.com Vol 380 October 13, 2012
narrow therapeutic index necessitating pulse oximetry to minimise the risk of retinopathy of prematurity. If hypoxaemia is missed in these patients, treatment and referral can be delayed, and mismanagement of oxygen therapy can lead to continued morbidity or irreversible damage. In prioritising a global reduction in neonatal and child mortality, an effort needs to be made to target the major killers and to ensure that pulse oximetry is available to identify all who would benefit from oxygen therapy and to monitor those receiving such therapy. Poorer countries have a greater need for appropriate pulse oximetry than do rich ones, and further research and innovation is also required in these settings. We are all involved with Powerfree Education and Technology—a not-for-profit organisation to test robust, low-cost health-care devices.
*Sarah Crede, Joy Lawn, David Woods, John Wyatt [email protected] Powerfree Education and Technology, Cape Town, South Africa (SC, JL, DW, JW); Saving Newborn Lives/Save the Children, London, UK (JL); University of Cape Town, Cape Town, South Africa (DW); and University College London, London, UK (JW) 1
2
3
4
5
Thangaratinam S, Brown K, Zamora J, Khan KS, Ewer AK. Pulse oximetry screening of critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012; 379: 2459–64. WHO. The global burden of disease: 2004 update. Geneva: World Health Organization, 2008. Liu L, Johnson HL, Cousens S, et al, for the Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 379: 2151–61. Duke T, Graham SM, Cherian MN, et al. Oxygen is an essential medicine: a call for international action. Int J Tuberc Lung Dis 2010; 14: 1362–68. Subhi R, Adamson M, Campbell H, Weber M, Smith K, Duke T. The prevalence of hypoxaemia among ill children in developing countries: a systematic review. Lancet Infect Dis 2009; 9: 219–27.
in a universal newborn screening programme. The role of hereditary variant haemoglobins in artifactually low SpO2 is worthy of mention. Artifactually low SpO2 is attributed to altered light absorption properties of the variant haemoglobins at 660 nm and 940 nm (the two wavelengths used to calculate estimated SaO2 by pulse oximetry). A review2 has reported 45 patients with 21 different hereditary variant haemoglobins that were associated with asymptomatic low SpO2. 11 of the index cases were infants. Lowoxygen-affinity variant haemoglobins such as haemoglobin Bassett3 cause true hypoxaemia and low SpO2. However, most variant haemoglobins associated with asymptomatic low SpO2 have normal arterial oxygen saturation (SaO2) by co-oximetry. In one report,4 a neonate had SpO2 of 85% and was investigated extensively. The baby’s mother and grandmother also had asymptomatic low SpO2. They were later found to be heterozygous for an α-globin chain variant, haemoglobin Titusville. Although hereditary variant haemoglobins are likely to be rare causes of asymptomatic low SpO2 in neonates, they should be included in the diagnostic work-up of these infants if universal newborn screening is implemented. In one survey,5 in 40 neonates found to have low SpO2 but no congenital heart defect, 12 were healthy. Measurement of SpO2 in parents, haemoglobin analysis by highperformance liquid chromatography, and, when indicated, measurement of SaO2 can be helpful to rule out artefactually low SpO2 caused by variant haemoglobins. We declare that we have no conflicts of interest.
Shakila Thangaratinam and colleagues1 report that measurement of oxygen saturation (SpO2) by pulse oximetry is highly specific for the detection of critical congenital heart defects and should be included
*Madeleine M Verhovsek, David H K Chui [email protected] Department of Medicine, McMaster University, Hamilton, ON L8N 4A6, Canada (MMV); and Department of Medicine, Boston University, Boston, MA, USA (DHKC)
1305
Correspondence
1
2
3
4
5
Thangaratinam S, Brown K, Zamora J, et al. Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012; 379: 2459–64. Verhovsek M, Henderson MPA, Cox G, et al. Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: a systematic review. Am J Hematol 2011; 86: 722–25. Das A, Sinha S, Hoyer JD. Hemoglobin Bassett produces low pulse oximeter and co-oximeter readings. Chest 2007; 131: 1242–44. Luo HY, Irving I, Prior J, et al. Hemoglobin Titusville, a low oxygen affinity variant hemoglobin, in a family of northern European background. Am J Hematol 2004; 77: 384–86. Riede FT, Wörner C, Dähnert I, et al. Effectiveness of neonatal pulse oximetry screening for detection of critical congenital heart disease in daily clinical routine—results from a prospective multicenter study. Eur J Pediatr 2010; 169: 975–81.
Authors’ reply The main aim of our systematic review was to assess the accuracy of pulse oximetry screening in detecting critical congenital heart defects (CCHD) in asymptomatic neonates. Our primary test accuracy study1 and the studies of others have consistently shown that additional non-cardiac disorders could also be identified during routine newborn screening. Non-cardiac disorders commonly identified by low oxygen saturations in the newborn period include congenital pneumonia and septicaemia, pulmonary hypertension of the neonate, meconium aspiration syndrome, and pneumothorax.2 These disorders can be as life-threatening as CCHD and so their early recognition and treatment after pulse oximetry screening is an additional benefit of the procedure. Careful assessment and consideration of a non-cardiac cause for hypoxaemia should be an essential part of the management algorithm for test-positive cases. We have shown that, in a UK setting, the screening is cost-effective for detection of cardiac defects.3 The additional non-cardiac diagnoses can only improve the cost-effectiveness. We acknowledge the call by Sarah Crede and colleagues for 1306
the assessment of newborn pulse oximetry screening in low-income and middle-income countries. If newborn pulse oximetry screening were a routine procedure worldwide, we have no doubt that it would have a huge effect not just on the early diagnosis of CCHD but on neonatal respiratory and infectious disorders. Early detection of hypoxaemia by pulse oximetry screening in lowincome and middle-income countries will allow judicious allocation of scarce resources towards the management of the above disorders that substantially contribute to neonatal mortality and morbidity. The availability of pulse oximeters in hospitals would also facilitate the assessment of hypoxaemia in patients beyond the newborn period. We thank Madeleine Verhovsek and David Chui for describing their experience with low-affinity variant haemoglobins as a cause of low oxygen saturations in neonates. Although these disorders are extremely rare, with screening now being implemented across the USA and considered in other countries including the UK, we agree that consideration of variant haemoglobin should also be part of the management algorithm of unexplained persistent low oxygen saturations. We declare that we have no conflicts of interest.
*S Thangaratinam, K S Khan, A K Ewer [email protected] Queen Mary University of London, London E1 4NS, UK (ST, KSK); and University of Birmingham, Birmingham, UK (AKE) 1
2
3
Ewer AK, Middleton LJ, Furmston AT, et al. Pulse oximetry as a screening test for congenital heart defects in newborn infants (PulseOx): a test accuracy study. Lancet 2011; 378: 785–94. Ewer AK, Furmston AT, Middleton LJ, et al. Pulse oximetry as a screening test for congenital heart defects in newborn infants: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess 2012; 16: 1–184. Roberts TE, Barton P, Auguste P, Middleton LJ, Furmston AT, Ewer AK. Pulse oximetry as a screening test for congenital heart disease in newborn infants: a cost effectiveness analysis. Arch Dis Child 2012; 97: 221–26.
Healthy Cities deserve better It seems a significant moment in the life of Healthy Cities that The Lancet published a Commission on the accomplishments of that very movement (June 2, p 2079).1 But, oddly, there is a strong disconnect between the materials presented and analysed by Yvonne Rydin and colleagues in the Commission and the realities of the international Healthy Cities movement. In essence, the five case studies do not add substantially to the problem analyses found in comprehensive texts on urban health.2 In the introduction to the Commission, there is explicit reference to the international Healthy Cities movement started by WHO, first in Europe and the Americas, and with increasing popularity around the world. What sets this Healthy Cities movement apart from other urban health initiatives is an unequivocal commitment to a set of values that would govern health development in the urban context.3 These values (relating to community development, equity, social inclusion, intersectoral management, and policy development) explicitly refer to the fact that urban health development is everyone’s business. The Commission’s analyses seem to look at Healthy Cities through an entirely different lens, applying a frame of reference that is grounded in a biomedical and pathological paradigm of health, rather than a sociological and salutogenic paradigm. For that reason, the Commission’s recommendations do not seem to add much to the operational basis and ambitions of the thousands of Healthy Cities around the world. Community leaders, political representatives, and urban social and policy entrepreneurs need handson, politically astute research for change. Corburn4 has shown that such research should rely on community engagement much more than on the academic enterprise. www.thelancet.com Vol 380 October 13, 2012
1
2
Ma C, An Z, Hao L, et al. Progress toward measles elimination in the People’s Republic of China, 2000–2009. J Infect Dis 2011; 204: S447–54. De Serres G, Boulianne N, Defay F, et al. Higher risk of measles when the first dose of a 2-dose schedule of measles vaccine is given at 12–14 months versus 15 months of age. Clin Infect Dis 2012; 55: 394–402.
Pulse oximetry screening for critical congenital heart defects Shakila Thangaratinam and colleagues (June 30, p 2459)1 report a systematic review to assess pulse oximetry as a screening method for critical congenital heart defects (CCHD) in asymptomatic newborn babies. They found that pulse oximetry was highly specific and moderately sensitive in the detection of CCHD, and this they cite as compelling evidence to introduce pulse oximetry as a screening test in asymptomatic newborn babies. We agree that the introduction of such screening would lead to a reduction in morbidity and mortality associated with CCHD. These disorders accounted for an estimated 219 000 deaths in 20042—about 2% of child deaths worldwide (and a higher proportion in rich countries where child mortality rates are lower). However, this point raises the issue that many disorders characterised by hypoxaemia have a higher burden of neonatal and child mortality and morbidity than do CCHD, but are not screened for with pulse oximetry. Globally 64% of the 7·6 million deaths in children younger than 5 years are due to infectious causes, most of which involve hypoxaemia—notably pneumonia (18% of child deaths), diarrhoea (11%), malaria (7%), and neonatal sepsis (5%).3 There are an estimated 1·5–2·7 million cases of hypoxaemic pneumonia annually.4,5 Additionally, preterm birth is the second leading cause of child death (1·1 million per year),3 mainly through respiratory distress syndrome, which requires oxygen therapy and has a www.thelancet.com Vol 380 October 13, 2012
narrow therapeutic index necessitating pulse oximetry to minimise the risk of retinopathy of prematurity. If hypoxaemia is missed in these patients, treatment and referral can be delayed, and mismanagement of oxygen therapy can lead to continued morbidity or irreversible damage. In prioritising a global reduction in neonatal and child mortality, an effort needs to be made to target the major killers and to ensure that pulse oximetry is available to identify all who would benefit from oxygen therapy and to monitor those receiving such therapy. Poorer countries have a greater need for appropriate pulse oximetry than do rich ones, and further research and innovation is also required in these settings. We are all involved with Powerfree Education and Technology—a not-for-profit organisation to test robust, low-cost health-care devices.
*Sarah Crede, Joy Lawn, David Woods, John Wyatt [email protected] Powerfree Education and Technology, Cape Town, South Africa (SC, JL, DW, JW); Saving Newborn Lives/Save the Children, London, UK (JL); University of Cape Town, Cape Town, South Africa (DW); and University College London, London, UK (JW) 1
2
3
4
5
Thangaratinam S, Brown K, Zamora J, Khan KS, Ewer AK. Pulse oximetry screening of critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012; 379: 2459–64. WHO. The global burden of disease: 2004 update. Geneva: World Health Organization, 2008. Liu L, Johnson HL, Cousens S, et al, for the Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 379: 2151–61. Duke T, Graham SM, Cherian MN, et al. Oxygen is an essential medicine: a call for international action. Int J Tuberc Lung Dis 2010; 14: 1362–68. Subhi R, Adamson M, Campbell H, Weber M, Smith K, Duke T. The prevalence of hypoxaemia among ill children in developing countries: a systematic review. Lancet Infect Dis 2009; 9: 219–27.
in a universal newborn screening programme. The role of hereditary variant haemoglobins in artifactually low SpO2 is worthy of mention. Artifactually low SpO2 is attributed to altered light absorption properties of the variant haemoglobins at 660 nm and 940 nm (the two wavelengths used to calculate estimated SaO2 by pulse oximetry). A review2 has reported 45 patients with 21 different hereditary variant haemoglobins that were associated with asymptomatic low SpO2. 11 of the index cases were infants. Lowoxygen-affinity variant haemoglobins such as haemoglobin Bassett3 cause true hypoxaemia and low SpO2. However, most variant haemoglobins associated with asymptomatic low SpO2 have normal arterial oxygen saturation (SaO2) by co-oximetry. In one report,4 a neonate had SpO2 of 85% and was investigated extensively. The baby’s mother and grandmother also had asymptomatic low SpO2. They were later found to be heterozygous for an α-globin chain variant, haemoglobin Titusville. Although hereditary variant haemoglobins are likely to be rare causes of asymptomatic low SpO2 in neonates, they should be included in the diagnostic work-up of these infants if universal newborn screening is implemented. In one survey,5 in 40 neonates found to have low SpO2 but no congenital heart defect, 12 were healthy. Measurement of SpO2 in parents, haemoglobin analysis by highperformance liquid chromatography, and, when indicated, measurement of SaO2 can be helpful to rule out artefactually low SpO2 caused by variant haemoglobins. We declare that we have no conflicts of interest.
Shakila Thangaratinam and colleagues1 report that measurement of oxygen saturation (SpO2) by pulse oximetry is highly specific for the detection of critical congenital heart defects and should be included
*Madeleine M Verhovsek, David H K Chui [email protected] Department of Medicine, McMaster University, Hamilton, ON L8N 4A6, Canada (MMV); and Department of Medicine, Boston University, Boston, MA, USA (DHKC)
1305
Correspondence
1
2
3
4
5
Thangaratinam S, Brown K, Zamora J, et al. Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis. Lancet 2012; 379: 2459–64. Verhovsek M, Henderson MPA, Cox G, et al. Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: a systematic review. Am J Hematol 2011; 86: 722–25. Das A, Sinha S, Hoyer JD. Hemoglobin Bassett produces low pulse oximeter and co-oximeter readings. Chest 2007; 131: 1242–44. Luo HY, Irving I, Prior J, et al. Hemoglobin Titusville, a low oxygen affinity variant hemoglobin, in a family of northern European background. Am J Hematol 2004; 77: 384–86. Riede FT, Wörner C, Dähnert I, et al. Effectiveness of neonatal pulse oximetry screening for detection of critical congenital heart disease in daily clinical routine—results from a prospective multicenter study. Eur J Pediatr 2010; 169: 975–81.
Authors’ reply The main aim of our systematic review was to assess the accuracy of pulse oximetry screening in detecting critical congenital heart defects (CCHD) in asymptomatic neonates. Our primary test accuracy study1 and the studies of others have consistently shown that additional non-cardiac disorders could also be identified during routine newborn screening. Non-cardiac disorders commonly identified by low oxygen saturations in the newborn period include congenital pneumonia and septicaemia, pulmonary hypertension of the neonate, meconium aspiration syndrome, and pneumothorax.2 These disorders can be as life-threatening as CCHD and so their early recognition and treatment after pulse oximetry screening is an additional benefit of the procedure. Careful assessment and consideration of a non-cardiac cause for hypoxaemia should be an essential part of the management algorithm for test-positive cases. We have shown that, in a UK setting, the screening is cost-effective for detection of cardiac defects.3 The additional non-cardiac diagnoses can only improve the cost-effectiveness. We acknowledge the call by Sarah Crede and colleagues for 1306
the assessment of newborn pulse oximetry screening in low-income and middle-income countries. If newborn pulse oximetry screening were a routine procedure worldwide, we have no doubt that it would have a huge effect not just on the early diagnosis of CCHD but on neonatal respiratory and infectious disorders. Early detection of hypoxaemia by pulse oximetry screening in lowincome and middle-income countries will allow judicious allocation of scarce resources towards the management of the above disorders that substantially contribute to neonatal mortality and morbidity. The availability of pulse oximeters in hospitals would also facilitate the assessment of hypoxaemia in patients beyond the newborn period. We thank Madeleine Verhovsek and David Chui for describing their experience with low-affinity variant haemoglobins as a cause of low oxygen saturations in neonates. Although these disorders are extremely rare, with screening now being implemented across the USA and considered in other countries including the UK, we agree that consideration of variant haemoglobin should also be part of the management algorithm of unexplained persistent low oxygen saturations. We declare that we have no conflicts of interest.
*S Thangaratinam, K S Khan, A K Ewer [email protected] Queen Mary University of London, London E1 4NS, UK (ST, KSK); and University of Birmingham, Birmingham, UK (AKE) 1
2
3
Ewer AK, Middleton LJ, Furmston AT, et al. Pulse oximetry as a screening test for congenital heart defects in newborn infants (PulseOx): a test accuracy study. Lancet 2011; 378: 785–94. Ewer AK, Furmston AT, Middleton LJ, et al. Pulse oximetry as a screening test for congenital heart defects in newborn infants: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess 2012; 16: 1–184. Roberts TE, Barton P, Auguste P, Middleton LJ, Furmston AT, Ewer AK. Pulse oximetry as a screening test for congenital heart disease in newborn infants: a cost effectiveness analysis. Arch Dis Child 2012; 97: 221–26.
Healthy Cities deserve better It seems a significant moment in the life of Healthy Cities that The Lancet published a Commission on the accomplishments of that very movement (June 2, p 2079).1 But, oddly, there is a strong disconnect between the materials presented and analysed by Yvonne Rydin and colleagues in the Commission and the realities of the international Healthy Cities movement. In essence, the five case studies do not add substantially to the problem analyses found in comprehensive texts on urban health.2 In the introduction to the Commission, there is explicit reference to the international Healthy Cities movement started by WHO, first in Europe and the Americas, and with increasing popularity around the world. What sets this Healthy Cities movement apart from other urban health initiatives is an unequivocal commitment to a set of values that would govern health development in the urban context.3 These values (relating to community development, equity, social inclusion, intersectoral management, and policy development) explicitly refer to the fact that urban health development is everyone’s business. The Commission’s analyses seem to look at Healthy Cities through an entirely different lens, applying a frame of reference that is grounded in a biomedical and pathological paradigm of health, rather than a sociological and salutogenic paradigm. For that reason, the Commission’s recommendations do not seem to add much to the operational basis and ambitions of the thousands of Healthy Cities around the world. Community leaders, political representatives, and urban social and policy entrepreneurs need handson, politically astute research for change. Corburn4 has shown that such research should rely on community engagement much more than on the academic enterprise. www.thelancet.com Vol 380 October 13, 2012