- Email: [email protected]
Screening for congenital heart disease with newborn pulse oximetry – Authors' reply
Correspondence
I declare that I have no conflicts of interest.
Krishnarajah Nirantharakumar [email protected] University of Birmingham, Birmingham B15 2TT, UK 1
Ewer AK, Middleton LJ, Furmston AT, et al. Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study. Lancet 2011; 378: 785–94.
Authors’ reply Differences in results between de-Wahl Granelli and colleagues’ study1 and ours are likely to have arisen because of antenatal screening and timing of pulse oximetry. Detection of critical congenital heart disease by antenatal ultrasound is very variable: we detected 50% of cases of critical congenital heart disease antenatally compared with only 3% in de-Wahl Granelli and colleagues’ study.1 Detection rates of between 15% and 50% have been reported among UK health regions.2 We noted a lower incremental value of pulse oximetry than did de-Wahl Granelli and colleagues, almost certainly because many more cases were identified by antenatal screening in our study hospitals. Our detection rate for critical congenital heart disease of 75% with pulse oximetry for the full cohort is higher than theirs. We agree that routine visualisation of the outflow tracts should further improve antenatal detection in isolated cardiac lesions; however, consistency of detection has yet to be shown. de-Wahl Granelli and colleagues screened at a median of 38 h after birth, compared with 12 h in our study, which might explain our higher false-positive rate. Discharge from UK hospitals is frequently within 24 h, so delayed pulse oximetry is not feasible and also increases risks of late diagnosis. Importantly, half (28/57) of eligible babies with critical congenital heart disease in de-Wahl Granelli and colleagues’ study required admission www.thelancet.com Vol 379 January 28, 2012
to intensive care before screening took place compared with none in our study. We confirm that all babies in our study were asymptomatic at testing, and the individual case highlighted by ÖstmanSmith and de-Wahl Granelli was not receiving prostaglandin or oxygen. We disagree that it is impossible to have saturations of 100% and 97% with hypoplastic left heart syndrome. Notably, since the initial examination for this baby was normal, the second test result would have passed according to the protocol described by de-Wahl Granelli and colleagues. We cannot deduce the value of screening where physical examination precedes pulse oximetry from our study, since the results of physical examination are likely to have been affected by the prior knowledge of the saturation result. We disagree that all cyanosed babies would be detected clinically, since the ability of clinicians to detect cyanosis is notably poor3—in the non-screening regions in de-Wahl Granelli and colleagues’ study, 44% of babies with transposition of great arteries were discharged without diagnosis. Our study, combined with the evidence of others,1 supports the introduction of routine pulse-oximetry screening for neonates. Introduction of pulse- oximetry screening will particularly improve detection rates in regions where antenatal diagnosis rates are lower. The optimum timing of screening requires careful consideration; delayed screening is likely to minimise false-positive rates, whereas earlier screening should improve timely diagnosis. We declare that we have no conflicts of interest.
*A K Ewer, L J Middleton, S Thangaratinam, K S Khan, J J Deeks [email protected] School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK (AKE); *Birmingham Women’s Healthcare NHS Foundation Trust, Birmingham B152TG, UK (AKE); Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK (LJM); Queen Mary University of London, Barts and the London School of Medicine, London, UK (ST, KSK); and Public Health,
Epidemiology and Biostatistics, University of Birmingham, Birmingham, UK (JJD) 1
2
3
de-Wahl Granelli A, Wennergren M, Sandberg K, et al. Impact of pulse oximetry screening on detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39 821 newborns. BMJ 2009; 338: A3037. National Institute for Cardiovascular Outcomes Research. Percentage of infants who required treatment who were antenatally diagnosed, analysed by year and by SHA/country. http://www.ccad.org. uk/002/congenital.nsf/vwContent/ Antenatal%20Diagnosis?Opendocument (accessed Jan 3, 2012). O’Donnell CPF, Kamlin COF, Davis PG, Carlin JB, Morley CJ. Clinical assessment of infant colour at delivery. Arch Dis Child 2007; 92: F465–67.
Coronary artery calcium for guiding statin treatment Although of interest and hypothesisgenerating, the MESA report by Michael Blaha and colleagues (Aug 20, p 684)1 is not a randomised trial and thus it is impossible to conclude that coronary artery calcification can be used to target patients who “derive the most and the least absolute benefit from statin therapy”. Four majortrials—AURORA,CORONA, 4-D, and GISSI-HF—did not show a benefit for statin therapy compared with placebo. What these four trials share is the enrolment of very high-risk individuals who are likely to have high coronary artery calcification scores. Moreover, heavily calcified plaques are not the most likely to rupture and cause infarction, nor do statins reduce coronary artery calcification. Therefore, until we have clear randomised evidence, the aggressive coronary artery calcification algorithm suggested by Axel Schmermund and Thomas Voigtländer in their accompanying Comment2 is premature and would deny treatment to individuals in whom completed trials have shown benefit, while providing it to groups never tested.
Science Photo Library
these issues and with the lower limit of the CI being 14·6% for sensitivity, I wonder how one can justify it as a screening instrument?
I am the principal investigator of the JUPITER trial, which was funded by AstraZeneca, and am listed as a co-inventor on patents held by the Brigham and
311
I declare that I have no conflicts of interest.
Krishnarajah Nirantharakumar [email protected] University of Birmingham, Birmingham B15 2TT, UK 1
Ewer AK, Middleton LJ, Furmston AT, et al. Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study. Lancet 2011; 378: 785–94.
Authors’ reply Differences in results between de-Wahl Granelli and colleagues’ study1 and ours are likely to have arisen because of antenatal screening and timing of pulse oximetry. Detection of critical congenital heart disease by antenatal ultrasound is very variable: we detected 50% of cases of critical congenital heart disease antenatally compared with only 3% in de-Wahl Granelli and colleagues’ study.1 Detection rates of between 15% and 50% have been reported among UK health regions.2 We noted a lower incremental value of pulse oximetry than did de-Wahl Granelli and colleagues, almost certainly because many more cases were identified by antenatal screening in our study hospitals. Our detection rate for critical congenital heart disease of 75% with pulse oximetry for the full cohort is higher than theirs. We agree that routine visualisation of the outflow tracts should further improve antenatal detection in isolated cardiac lesions; however, consistency of detection has yet to be shown. de-Wahl Granelli and colleagues screened at a median of 38 h after birth, compared with 12 h in our study, which might explain our higher false-positive rate. Discharge from UK hospitals is frequently within 24 h, so delayed pulse oximetry is not feasible and also increases risks of late diagnosis. Importantly, half (28/57) of eligible babies with critical congenital heart disease in de-Wahl Granelli and colleagues’ study required admission www.thelancet.com Vol 379 January 28, 2012
to intensive care before screening took place compared with none in our study. We confirm that all babies in our study were asymptomatic at testing, and the individual case highlighted by ÖstmanSmith and de-Wahl Granelli was not receiving prostaglandin or oxygen. We disagree that it is impossible to have saturations of 100% and 97% with hypoplastic left heart syndrome. Notably, since the initial examination for this baby was normal, the second test result would have passed according to the protocol described by de-Wahl Granelli and colleagues. We cannot deduce the value of screening where physical examination precedes pulse oximetry from our study, since the results of physical examination are likely to have been affected by the prior knowledge of the saturation result. We disagree that all cyanosed babies would be detected clinically, since the ability of clinicians to detect cyanosis is notably poor3—in the non-screening regions in de-Wahl Granelli and colleagues’ study, 44% of babies with transposition of great arteries were discharged without diagnosis. Our study, combined with the evidence of others,1 supports the introduction of routine pulse-oximetry screening for neonates. Introduction of pulse- oximetry screening will particularly improve detection rates in regions where antenatal diagnosis rates are lower. The optimum timing of screening requires careful consideration; delayed screening is likely to minimise false-positive rates, whereas earlier screening should improve timely diagnosis. We declare that we have no conflicts of interest.
*A K Ewer, L J Middleton, S Thangaratinam, K S Khan, J J Deeks [email protected] School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK (AKE); *Birmingham Women’s Healthcare NHS Foundation Trust, Birmingham B152TG, UK (AKE); Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK (LJM); Queen Mary University of London, Barts and the London School of Medicine, London, UK (ST, KSK); and Public Health,
Epidemiology and Biostatistics, University of Birmingham, Birmingham, UK (JJD) 1
2
3
de-Wahl Granelli A, Wennergren M, Sandberg K, et al. Impact of pulse oximetry screening on detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39 821 newborns. BMJ 2009; 338: A3037. National Institute for Cardiovascular Outcomes Research. Percentage of infants who required treatment who were antenatally diagnosed, analysed by year and by SHA/country. http://www.ccad.org. uk/002/congenital.nsf/vwContent/ Antenatal%20Diagnosis?Opendocument (accessed Jan 3, 2012). O’Donnell CPF, Kamlin COF, Davis PG, Carlin JB, Morley CJ. Clinical assessment of infant colour at delivery. Arch Dis Child 2007; 92: F465–67.
Coronary artery calcium for guiding statin treatment Although of interest and hypothesisgenerating, the MESA report by Michael Blaha and colleagues (Aug 20, p 684)1 is not a randomised trial and thus it is impossible to conclude that coronary artery calcification can be used to target patients who “derive the most and the least absolute benefit from statin therapy”. Four majortrials—AURORA,CORONA, 4-D, and GISSI-HF—did not show a benefit for statin therapy compared with placebo. What these four trials share is the enrolment of very high-risk individuals who are likely to have high coronary artery calcification scores. Moreover, heavily calcified plaques are not the most likely to rupture and cause infarction, nor do statins reduce coronary artery calcification. Therefore, until we have clear randomised evidence, the aggressive coronary artery calcification algorithm suggested by Axel Schmermund and Thomas Voigtländer in their accompanying Comment2 is premature and would deny treatment to individuals in whom completed trials have shown benefit, while providing it to groups never tested.
Science Photo Library
these issues and with the lower limit of the CI being 14·6% for sensitivity, I wonder how one can justify it as a screening instrument?
I am the principal investigator of the JUPITER trial, which was funded by AstraZeneca, and am listed as a co-inventor on patents held by the Brigham and
311