Universal pulse oximetry screening for critical congenital heart disease is a simple cheap addition to universal hearing and metabolic screening with undeniable benefits. Infants with undiagnosed life threatening congenital heart disease can be detected prior to closure of the ductus arteriosus, and prior to discharge from hospital. Infants who have such critical disease can have intervention, including surgery, with a lower mortality compared to infants who present after discharge who are often in shock at the time of diagnosis. Many bodies, including the Canadian Pediatric Society have come out in favour of universal pulse oximetry screening as a result.

Despite all of the data about the beneifts of screening, in the UK the National Screening Committee has just recommended against inclusion of pulse oximetry screening in the national program of neonatal screening, which basically means the neonatal physical exam.

The main justification of this decision appears to be their evaluation of evidence about “harms” of screening. Potential harms are listed in the following way:

• A positive result from pulse oximetry will generate some harms, including: parental anxiety, a longer stay in hospital, possible transfer to the neonatal unit, further tests to assess for non-symptomatic conditions.
• For many of these babies the further investigations will be unnecessary and the baby will be identified as healthy. This is a false positive result.

They also seem to doubt the benefits of a true-positive screen:

• For babies with CHD or other non-cardiac condition it is not clear that investigations and identification of these conditions will lead to any better outcome than a diagnosis at the time the baby becomes symptomatic.

I find this decision bizarre given that the preferred method of the committee is therefore physical examination, which has a false negative rate in the UK of over 50%, and a false positive rate of about 50%. Those data are referred to in this report, as the best studies were performed in the UK, but the potential harms of physical examination (false positive rate high) and false reassurance of negative physical examinations is not considered. I think the routine physical examination is therefore far more questionable than routine pulse oximetry, for the detection of congenital heart disease.

In some studies, in fact, referral for neonatal cardiac ultrasound is not increased by routine pulse oximetry screening. It is just more appropriately targeted. As about 4 to 5% of newborn infants will have a murmur, referral based on the clinical exam leads to many more false positives, especially when the target condition is critical heart disease, than oximetry.

What I find most bizarre, is that between the actual report of the literature review, and the chapter which compares the findings of that review to the criteria for institution of a screening program, there is a huge disconnect. The addition of pulse oximetry screening to the neonatal exam seems to fulfill all the criteria in the list.

Criterion 5

This risk of discharge home without a diagnosis or of severe acidosis has been estimated to be reduced by around 60% with pulse oximetry.
The benefit of newborn screening will be reduced if antenatal detection increases significantly, however current models suggest that newborn screening will remain clinically effective and cost-effective for life-threatening or critical CHDs until antenatal detection rates are above 85-90%…
Non-cardiac conditions leading to low oxygen saturation, such as respiratory or infective illness, may be found in infants with low oxygen saturations (false positive screening results). The benefits and costs of further investigation and early diagnosis of such conditions requires further investigation before these diagnoses can be considered a benefit of screening.

I do agree with that last paragraph, babies with lowish saturations who have, for example, increased pulmonary vascular resistance may do well without intervention, just being the slowest percentiles for the resolution of their fetal pulmonary vasoconstriction. Some probably do benefit from finding low saturations, such as those with sepsis, but it isn’t clear from the literature exactly how many “false positives” actually have conditions that need, and benefit from, intervention. But I also don’t think you can write all the ‘false positives’ off as an undue risk of screening, at least some of the babies will benefit.

The consultation process included an in-depth examination of the ‘false positives’ from the UK pilot study. you can see that if you click on the ‘Notes from the Pulse Oximetry workshop’ on this page. That review examined what happened to the 239 babies with a positive screen (0.73% of the screens performed); there were 14 babies with congential heart disease. Being fairly conservative in their opinions, there were another 36 babies who had conditions requiring treatment. 32 babies had discharge delayed despite not having a treatable condition, and the remaining false positives went home as planned anyway.

Criterion 8

A pathway for clinical investigation after a positive screen result on pulse oximetry has not been clearly established or evaluated in practice. Essential considerations prior to implementation of pulse oximetry in a national screening programme would therefore be to agree a policy for
investigation to identify cardiac and non-cardiac causes of low oxygen saturation, including consideration of the resource implications and acceptability to parents.

Not really in agreement here, the first stage of evaluation of a baby with a confirmed positive screen should be a rapid expert cardiac ultrasound, if there is no structural heart disease, then the second step is not entirely clear, I would agree. Who needs evaluation in what order for what conditions? Do they all need a chest x-ray? Or blood culture) But eliminating critical congential heart disease is a clear priority as the first step on the pathway.

Criterion 10

…Early detection of life-threatening CHDs in asymptomatic newborns allows management aimed at preventing cardiovascular collapse before intervention, a particular risk for duct-dependent cardiac defects, and there is some evidence that this can lead to improved short and long-term outcomes after surgery.

Yep.

Criterion 14

Antenatal ultrasound, newborn clinical examination and pulse oximetry appear acceptable as  screening tests. However the acceptability of high false positive rates (which may raise anxiety) and  false negative rates (leading to false reassurance) requires further exploration for all screening modalities.

I don’t know the literature about parental anxiety from false positive oximetry screening, but there are several studies about parental impacts of false positive hearing screens, which are very reassuring. They show that false positive screens are not a major burden to families, and that they appreciate the value of screening despite the false positive test of their child. It is important to have good communication with the parents prior to or during the screen, with written and/or verbal information. The experience from the Birmingham study seems to show the same thing. (Powell R, et al. Pulse oximetry screening for congenital heart defects in newborn infants: an evaluation of acceptability to mothers. Archives of disease in childhood Fetal and neonatal edition. 2013;98(1):F59-63).

Most neonatal screening tests are trying to detect relatively rare phenomena, and false postives for almost everything (which may cause stress) are more common than true positives. In this light, the ratio of true positives to false positives for pulse oximetry screening is similar to many of the things we already screen for. For example for neonatal hypothyroidism screening there are between 2 to 3 times as many false positives as true positives, and if your program starts with T4 screens that ratio is even higher. The benefits of hypothyroidism screening are so evident that we accept a substantial number of false positives, and so do the parents.

As for false negatives, this is also an issue with other screens, such as hearing screening, and parental information is key. But is it truly an issue? If a child has critical congenital heart disease which is missed by a falsely negative oximetry screen, and then presents with a serious deterioration later on, are they worse off than if they had not had a screen at all? Are parents likely to say “he had a normal oximetry screen, so we won’t take him to the emergency room?” I think kids with a false negative screen will likely be in exactly the same position as non-screened kids, therefore without an adverse impact.

Criterion 15

Existing evidence suggests that the benefits outweigh the harms for newborn screening, when the screening test is clinical examination with or without pulse oximetry, and for antenatal screening, when the screening test is antenatal ultrasound.

Agreed

Criterion 16

The existing evidence strongly suggests that pulse oximetry in conjunction with clinical examination is more cost-effective than clinical examination alone. Further evidence, including estimation of  QALYs, continues to support this.

Strongly agreed!

The literature review does have a couple of strange features, including a figure showing a list of congenital heart diseases causing death in the first year of life, which is headed by ventricular septal defect. They don’t give the correct reference for the data from which the data are derived, and I can’t find any data in the references by Wren, that they seem to be referring to, that supports that figure. If the quality of the understanding of the problem is reflected by that figure (when did you last see an infant with a VSD die? Before 1 year of age? After excluding complex cardiac malformations which happen to include a VSD?) A fairly recent study from France, for example put VSD as the least likely to cause death before 1 year of age.

Overall I think the recommendation of this committee doesn’t follow from their review of the literature and their own pilot project. If you are in the UK you can make a comment before this is finalized, go the university of Birmingham website here, and follow the links.