Dr. Mitchell Goldstein, Editor, Neonatology Today 

To the Editor 

I write in reference to the recently published study by Khoury R et al., which I have reviewed in detail, in which the authors compared the times taken to achieve stable heart rate readings for Masimo and Nellcor pulse oximeters in neonates immediately after delivery (1). Pulse rate stability was compared using a qualitative measure (looking at it and writing the number down). 

The 60 babies studied were all healthy, and they cannot be compared to a manuscript I authored (2) and this is the basis for this letter, where I will summarize the major limitations and differences between previous publications and the current findings in Khoury’s paper. 

The manuscript used interchangeably several aspects – “during delivery room transition,” “neonatal transition,” and “an uncomplicated resuscitation setting,” and this has led to confusion. Furthermore, I believe that the findings are of no clinical significance and could not support any changes in the current clinical guidelines of neonatal resuscitation. 

In many places of the world, there remains a significant need for education in order to improve the skill and training so that care of sick newborns after birth is improved. Adequate auscultation of the heart and palpation of the base of the umbilical cord have a more significant clinical impact than spending precious time and resources trying to apply ECG electrodes that have been shown to have reduced function in ill babies before 60 seconds of life. The scant resources in many areas should be diverted to neonates at risk due to gestational age or clinical condition to ensure the required clinical interventions are instituted in a timely manner. 

This study was conducted in healthy babies born by cesarean section who did not require resuscitation with Apgar scores of 8-9 at 1 minute; 91.7% of them were born by elective Cesarean-section. None of the infants required resuscitation, and comparisons were made after the healthy babies were placed on a warmer. Pulse rate stability was compared using a qualitative measure (looking at it and writing the number down). 

As mentioned by Khoury, the findings of his study cannot (and should not) be extrapolated to other groups of newborns, like those who are ill, premature, or have potentially serious conditions. 

I would also like to share a concept in relation to the Masimo sensor that was used. In response to the 2015 American Academy of Pediatrics Newborn Resuscitation Protocol (NRP) to address the measurement conditions during the first few minutes after birth (3), Masimo optimized the sensor in 2016 to provide stable pulse rate readings earlier. This sensor, which upon application automatically set the Masimo oximeter settings to 2-4 second (fast) averaging time and maximal sensitivity, was not utilized in the study cohort. Matching technology is essential for performance as approved by the FDA. Additionally, many published clinical studies in preterm and term infants in the delivery room report SpO₂ nomograms in thousands of babies using Masimo SET technology (4-6). What is reported in Khoury’s study cannot be extrapolated to what happens in the NICU in critically ill babies. SET technology use in thousands of babies (including many studies and all recent publications with ventilators with closed-loop technology) (7-10) led to a significant reduction in severe ROP and the need for laser therapy. Pulse oximetry selection is important in managing critically ill infants. 

Lastly, Khoury’s study mentions using the electrocardiogram (ECG) heart rate as a “gold standard” for pulse rate from pulse oximetry. Pulseless Electrical Activity (PEA, also known as Electro-Mechanical Dissociation or EMD) is not rare during the first minutes after birth, especially during asphyxia, as is clearly mentioned in NRP documents of AAP. The ECG can display heart rates far greater than the actual pulse rate in this situation. Several studies affirm this fact (11, 12). This is a possible explanation of some of the “low pulse rate” data points shown in Khoury’s Figure 2 when the actual peripheral pulse rate can be significantly lower than the ECG rate. 

In summary, I consider the statistically significant difference reported in this study to be clinically insignificant and do not provide any basis for the improvement of clinical care and outcomes of sick babies in the delivery room and in the NICU, and could actually distract clinicians from the first important steps that are essential during neonatal resuscitation. 

References: 

1. Khoury R, Klinger G, Shir Y, Osovsky M, Bromiker R. Monitoring Oxygen Saturation and Heart Rate During Neonatal Transition,” J Perinatol. 2020 November 30. Doi: 10.1038/s41372-020-00881-y. Online ahead of print. PMID: 33250516 
2. Baquero H, Alviz R, Castillo A, Neira F, Sola A. Avoiding hyperoxemia during neonatal resuscitation: time to response of different SpO2 monitors. Acta Paediatr. 2011;100(4):515-8. Doi: 10.1111/j.1651-2227.2010.02097.x 
3. American Academy of Pediatrics, Neonatal Resuscitation Program: https://www.aap.org/en-us/continuing-medical-education/life-support/NRP/Pages/NRP.aspx 
4. White LN, Thio M, Owen LS, Kamlin CO, Sloss S, Hooper SB, Davis PG, Dawson JA. Achievement of saturation targets in preterm infants <32 weeks’ gestational age in the delivery room. Arch Dis Child Fetal Neonatal Ed. 2017;102(5):F423-F427. doi: 10.1136/archdischild-2015-310311. Epub 2017 March 16. PID: 28302696. 
5. Dawson JA, Kamlin CO, Vento M, Wong C, Cole TJ, Donath SM, et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics. (2010) 125:e1340–7. doi: 10.1542/peds.2009-1510 
6. Dawson JA, Kamlin CO, Wong C, te Pas AB, O’Donnell CP, Donath SM, et al. Oxygen saturation and heart rate during delivery room resuscitation of infants <30 weeks’ gestation with air or 100% oxygen. Arch Dis Child Fetal Neonatal Ed. (2009) 94:F87– 91. doi: 10.1136/adc.2008.141341 
7. Castillo A, Deulofeut R, Critz A, Sola A. Prevention of retinopathy of prematurity in preterm infants through changes in clinical practice and SpO2 technology. Acta Paediatr. 2011 Feb;100(2):188- 92. doi: 10.1111/j.1651-2227.2010.02001.x. Epub 2010 October 15. PMID: 20825604; PMCID: PMC3040295. 
8. Bizzarro MJ et al. Temporal quantification of oxygen saturation ranges: an effort to reduce hyperoxia in the neonatal intensive care unit. J Perinatol 2014; 34(1):33-38 
9. Askie LM, Darlow BA, Finer N, Schmidt B, Stenson B, Tarnow- Mordi W, Davis PG, et al. Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration. Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA. 2018 June 5;319(21):2190-2201. doi: 10.1001/jama.2018.5725. 
10. Maiwald CA, Niemarkt HJ, Poets CF, Urschitz MS, König J, Hummler H, Bassler D, Engel C, Franz AR; FiO2-C Study Group. Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcome of extremely preterm infants – study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy. BMC Pediatr. 2019 October 21;19(1):363. doi: 10.1186/s12887-019-1735-9. PMID: 31630690; PMCID: PMC6802113. 
11. Patel S, Cheung PY, Solevåg AL, et al. “Pulseless electrical activity: a misdiagnosed entity during asphyxia in newborn infants?” Arch Dis Child Fetal Neonatal Ed. 2019;104(2):F215- F217. 
12. Luong D, Cheung PY, Barrington KJ, et al. “Cardiac arrest with pulseless electrical activity rhythm in newborn infants: a case series,” Arch Dis Child Fetal Neonatal Ed. 2019;104(6):F572-F574. 

Hernando Baquero Latorre, MD 
Coordinador de Neonatología 
Universidad del Norte 
Barranquilla Colombia 
+57 53 509 280 
hbaquero@uninorte.edu.co 

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Dear Dr. Latorre: 

As noted in my previous response to Dr. Barker, “comparison trials of relevant devices define usage parameters.” Further, as you have noted, the populations studied must be complementary to justify conclusions. Health newborns in the delivery room are different from those who are sick in the NICU. Speed of response, notwithstanding, the technology is not just about speed alone. Accuracy, precision, and reproducibility are a sine qua non. Early pulse oximetry was neither designed to work on NICU patients nor any sick patients for that matter. The pulse oximeter was referred to as a “fair-weather friend.” (1) We were taught that reliance on a pulse oximeter was problematic when a patient was moving or had low perfusion. Signal Extraction technology (SET) is an entirely different technology. Comparing SET to other technologies is like comparing a late model semiautonomous electric vehicle to a 1950s gas guzzler. However, shut down the electric grid, take away the software innovation, and provide only fossil fuel, and the 1950s gas guzzler will win every race. The innovative modes, software, sensors, and usage should have been included in the study. The fact remains that although the authors of the study have reached statistical significance, there is no clinical relevance because the Masimo devices were not used in their most optimized settings and did not have the latest software revision. (2, 3) 

Pulseless Electrical Activity (PEA) is definitively an issue. Earlier AAP resuscitation guidance questioned whether pulse oximetry might “falsely” indicate that there was no pulse when there was sufficient EKG activity resulting in unnecessary resuscitation. Although there is no substitute for a full exam, the reverse is undoubtedly true and much more dangerous should a “reassuring” EKG lead to a resuscitation delay. (4-6) Arguably, the EKG is analogous to “fool’s gold.” It seems like the real thing (i.e., pulse), but it’s not. 

Your concerns are well stated and essential. Khoury et al. should have incorporated these considerations into the initial study design. 

References: 

1. Barker SJ. “Motion-resistant” pulse oximetry: a comparison of new and old models. Anesth Analg. 2002;95(4):967-72, table of contents. Epub 2002/09/28. doi: 10.1097/00000539-200210000-00033. PubMed PMID: 12351278. 
2. Khoury R, Klinger G, Shir Y, Osovsky M, Bromiker R. Monitoring oxygen saturation and heart rate during neonatal transition. comparison between two different pulse oximeters and electrocardiography. J Perinatol. 2020. Epub 2020/12/01. doi: 10.1038/s41372-020-00881-y. PubMed PMID: 33250516. 
3. Hay WW, Jr., Rodden DJ, Collins SM, Melara DL, Hale KA, Fashaw LM. Reliability of conventional and new pulse oximetry in neonatal patients. J Perinatol. 2002;22(5):360-6. Epub 2002/06/26. doi: 10.1038/sj.jp.7210740. PubMed PMID: 12082469. 
4. Sillers L, Handley SC, James JR, Foglia EE. Pulseless Electrical Activity Complicating Neonatal Resuscitation. Neonatology. 2019;115(2):95-8. Epub 2018/10/24. doi: 10.1159/000493357. PubMed PMID: 30352434. 
5. Patel S, Cheung PY, Solevag AL, Barrington KJ, Kamlin COF, Davis PG, et al. Pulseless electrical activity: a misdiagnosed entity during asphyxia in newborn infants? Arch Dis Child Fetal Neonatal Ed. 2019;104(2):F215-F7. Epub 2018/06/14. doi: 10.1136/archdischild-2018-314907. PubMed PMID: 29895572.
6. Luong D, Cheung PY, Barrington KJ, Davis PG, Unrau J, Dakshinamurti S, et al. Cardiac arrest with pulseless electrical activity rhythm in newborn infants: a case series. Arch Dis Child Fetal Neonatal Ed. 2019;104(6):F572-F4. Epub 2019/02/24. doi: 10.1136/archdischild-2018-316087. PubMed PMID: 30796058.