Original Article Twelve-Month Prospective Study of Oxygen Saturation Measurements among Term and Preterm Infants Michael W. Beresford, PhD Heather Parry, RGN, RSCN Nigel J Shaw, MD BACKGROUND: Optimising home oxygen delivery in infants has important logistical and safety implications. This can be aided by having a suitable reference range of normal values for arterial oxygen saturation using pulse oximetry (SpO2). OBJECTIVES: To describe oxygenation profiles in healthy preterm and term infants in relation to gestational and postnatal age, to extend reference values to guide home oxygen therapy. STUDY DESIGN: Prospective monitoring of SpO2 for 4 hours at 3 monthly intervals of 34 term, and 53 preterm healthy infants, took place over a 12-month period using an Ohmeda Biox 3700e pulse oximeter and data logger. RESULTS: Group mean and 5th percentiles were used to construct cumulative frequency curves at each time interval, representing the normal reference range of SpO2 profiles for term and preterm infants over time. CONCLUSIONS: These data may be used to test the benefits in the home or hospital of having a reference range of normal values for cumulative SpO2. Journal of Perinatology (2005) 25, 30–32. doi:10.1038/sj.jp.7211206 Published online 14 October 2004 INTRODUCTION Pulse oximetry (SpO2) has become the mainstay of assessment of oxygenation in preterm infants who have prolonged oxygen dependency. In the absence of randomized-controlled trials Liverpool Women’s Hospital, Liverpool, UK. Address correspondence and reprint requests to Ben Shaw, Neonatal Unit, Liverpool Women’s Hospital, Liverpool L8 7SS, UK. comparing the safety and efficacy of different SpO2 levels, a pragmatic approach is to aim for normal SpO2 levels. Using a convenient system that can analyse the infant’s oxygenation profile and compare it to a reference range for SpO2, we have previously reported such a reference range in a group of 33 infants born between 30 and 34 weeks gestation in the immediate postnatal period.1 It is possible that this reference range could change, as the infant gets older. However, there are no longitudinal studies of SpO2 in infants and children from birth to investigate this possibility. The aims of this study were to describe oxygenation profiles in healthy preterm and term infants in relation to gestational and postnatal age and therefore to extend reference values to guide home oxygen therapy. METHODS Infants were recruited to the study between July 1998 and July 1999 at Liverpool Women’s Hospital, UK, after local regional ethics committee approval had been granted. Infants who had received no mechanical ventilation or supplemental oxygen therapy were recruited after parental consent had been obtained. Infants with known congenital anomalies or cardio-respiratory disorders were excluded. Gestational age was determined from maternal dates and/or early antenatal ultrasound examination. All infants were studied for a continuous period of 4 hours following a feed, while asleep, or during a period of quiet wakefulness. Infants studied were grouped into the following gestational age bands: term infants Z37 weeks; preterm infants: <37 weeks. Initial monitoring took place in term infants at least 48 hours postdelivery and after 1 week for the preterm infants. Subsequent monitoring took place in the infant’s home at approximately 3, 6, 9 and 12 months postdelivery. The monitoring of SpO2 took place using a standard Ohmeda Biox 3700e pulse oximeter using an averaging interval of 3 seconds. A data-logging device and dedicated software, developed at the Department of Clinical Engineering, University of Liverpool, was used to record the data. Initial measurements took place on the neonatal unit or postnatal wards before discharge. Parents agreed to be contacted following discharge at the appropriate time intervals. At a convenient time, a dedicated research nurse (HP) visited the family, and instructed the parents in operating and recording oxygen saturations. Parents recorded four hours of data while the infant slept, generally at night time. Measurements on Journal of Perinatology 2005; 25:30–32 r 2005 Nature Publishing Group All rights reserved. 0743-8346/05 $30 30 www.nature.com/jp Prospective Study of Oxygen Saturation Profiles in Infants SpO2: Post-delivery 100.0 Cumulative oxygen saturation (%) infants who were thought, in the opinion of the nurse, to have an acute respiratory illness were postponed until the child had clinically improved. Analyses of raw data were performed blind to the infant’s gestational or postnatal age. Using the group mean and lower 5th percentile, a cumulative frequency curve was constructed for each of the five recorded time intervals over the first year postdelivery. Descriptive statistics and graphs were generated using Microsoft Excel statistical software. Beresford et al. Term mean Preterm mean Reference mean Term Lower Preterm Lower Reference Lower 75.0 50.0 25.0 85 87 89 91 93 95 97 99 SpO2 (%) SpO2: 6 months post-delivery Cumulative oxygen saturation (%) A total of 87 infants were recruited to the study and had baseline measurements performed. Median (range) gestational age for the term infants (n ¼ 34) was 40 weeks (37 to 41) and for the preterm infants (n ¼ 53) was 33 weeks (29 to 36). In all, 19 term infants and 23 preterm infants were male. Median (interquartile, IQR) age for the initial recording of term and preterm infants was 2 days (2 to 3) and 8 days (8–10), respectively. Median (IQR) age for each of the subsequent recordings for all infants postdelivery was: 14 weeks (13–16); 27 weeks (26 to 28); 40 weeks (39 to 42); and 52 weeks (51 to 53). During the course of the study, 11 (13%) parents asked for their infant to be withdrawn from further follow-up. In addition, 46 (53%) of families, at some point over the next 12 months failed to respond to an initial attempt to contact them and a subsequent reminder. These families were deemed to have withdrawn themselves from the study from that time point onwards. The numbers of infants and median (range) gestational age of infants on whom follow-up data were obtained at 6 and 12 months for the term and preterm groups, respectively, was as follows. At 6 months, term group (n ¼ 15): 39 weeks (37 to 41); preterm group (n ¼ 32): 33 weeks (30 to 36). At 12 months, term group (n ¼ 11): 39 weeks (37 to 41); preterm group (n ¼ 19): 33 weeks (31 to 35). Figures 1 to 3 show the cumulative frequency for SpO2 for term and preterm infants (along with the existing reference range) postdelivery, and at 6 and 12 months, respectively (curves for 3 and 9 months not shown). The mean and lower 5th centile are shown for each group, and similar data are shown of the reference data.1 Figure 1. Mean and lower 5th centile for the cumulative frequency for SpO2 for term and preterm infants (along with the existing reference range) postdelivery. 100.0 Term mean Term Lower Preterm mean Preterm Lower Reference Lower Reference mean 75.0 50.0 25.0 85 87 89 91 93 95 97 99 SpO2 (%) Figure 2. Mean and lower 5th centile for the cumulative frequency for SpO2 for term and preterm infants (along with the existing reference range) 6 months postdelivery. SpO2: 12 months post-delivery Cumulative oxygen saturation (%) RESULTS 100.0 Term mean Term Lower Preterm mean Preterm Lower Reference mean Reference Lower 75.0 50.0 25.0 85 87 89 91 93 95 97 99 SpO2 (%) CONCLUSIONS In this study, we have prospectively followed a healthy term and preterm population of infants over a 12-month period and observed their SpO2. We have extended our reference range for increasing postnatal age using a data-logging device and dedicated software that is relatively simple and practical for routine use at home and in the nursery. Journal of Perinatology 2005; 25:30–32 Figure 3. Mean and lower 5th centile for the cumulative frequency for SpO2 for term and preterm infants (along with the existing reference range) 12 months postdelivery. Published data of SpO2 reference ranges in term and preterm infants over time have been limited, having: included preterm infants with significant neonatal respiratory disease;2 performed follow-up measurements within a laboratory setting;3 studied 31 Beresford et al. infants only on a single occasion over the first 9 months postdelivery4 or during childhood;5,6 measured SpO2 levels only during apnoeas or bradycardias;7 or only performed repeat measures over the first four postnatal weeks.8 Mean cumulative SpO2 frequency for term and preterm infants were very similar over the initial 6-month follow-up, and corresponded to our existing reference range.1 They diverged somewhat at 9 months and a year, where study numbers are reduced. Of note, the 5th centiles are markedly variable between groups, and compared to the existing reference range, particularly after the initial 3-month follow-up. The reasons for variation between curves may include: a fall in sample numbers over time; increasing movement artefact not detected with increasing postnatal age; difference in clinical characteristics between groups and with the original cohort; or some real differences between groups over time. Other factors that may contribute to variation in profiles include: idiopathic pulmonary hypertension; on-going alveolar development in preterm infants producing aberration in an otherwise healthy population; circadian rhythm; and sleep stage. In this pragmatic study, we think it appropriate to use these postnatal reference ranges for preterm infants in optimising home oxygen parameters rather than simply a postdelivery cohort, as it will allow for the possibility of differences due to artefact or otherwise. The cumulative frequency curve of oxygen saturations represents the range of SpO2 profiles in normal term and preterm infants. Such curves are helpful in guiding supplemental oxygen treatment as they provide a more visual, user-friendly display of the normal range than a single figure a mean (SD) SpO2 does.1 For example, by monitoring oxygen saturations over time in room air of an infant in whom it is thought that supplemental oxygen may be required, an individual SpO2 profile can be constructed. This can be superimposed on the term or preterm reference curve for the appropriate postnatal age, and any deviation from the normal SpO2 profile be assessed. Equally, a child on home oxygen could be monitored for ongoing requirement by comparing their SpO2 profile in room air to the appropriate reference curve. A shift to the left (with a greater proportion of time spent at SpO2 levels below the normal values) would indicate an ongoing oxygen requirement. Repeating the process in oxygen could confirm that the infants are receiving sufficient oxygen to ensure their oxygen saturation profile is within the normal range for healthy, gestational, age-matched infants. This study has underlined the difficulty of following up a cohort longitudinally, with 22/34 (65%) of term infants and 25/53 (47%) of preterm infants dropping out over a 12-month period. It was thought withdrawal from the study was lower in the preterm group because the infant had initially been in hospital longer and had been more familiar with oxygen saturation monitoring as an in- 32 Prospective Study of Oxygen Saturation Profiles in Infants patient, while the term infants were discharged much sooner, and had had less contact with staff. Monitoring infants while undisturbed reflected our clinical practice of over-night saturation monitoring in children on home oxygen. Recording SpO2 levels during activities such as feeding and handling may have increased inaccuracies related to movement artefact. It is acknowledged that with the advent of newer technology, motion tolerant low perfusion capable oximeters might have been able to produce more reproducible results. Restricting the duration of recording to 4 hours permitted a reasonable period of study, while maintaining the practicality of the methodology, and reducing the potential for added movement artefact.9 The effects of prodromal illness on measurements were not excluded, as only those infants with actual symptoms had their date of monitoring postponed. Having defined our criteria for detecting major movement artefact, we cannot be certain of having excluded minor artefacts resulting in transient desaturation. The most likely effect of not detecting these events would have been to lower marginally the overall mean SpO2. In summary, we have constructed normal reference ranges for cumulative SpO2 for healthy term and preterm infants over a 12month period. These data could be used to test the benefits in the home or hospital of having a reference range of normal values for cumulative SpO2. References 1. Ng A, Subhedar N, Primhak RA, Shaw NJ. Arterial oxygen saturation profiles in healthy preterm infants. Arch Dis Child Fetal Neonatal Ed 1998;79: F64–F66. 2. Poets CF, Stebbens VA, Alexander JR, Arrowsmith WA, Salfield SAW, Southall DP. Arterial oxygenation in preterm infants at discharge from the hospital and six weeks later. J Pediatr 1992;120:447–54. 3. Hoppenbrouwers T, Hodgman JE, Arakawa K, Durand M, Cabal LA. Transcutaneous oxygen and carbon dioxide during the first half year of life in preterm and normal term infants. Pediatr Res 1992;31:73–9. 4. Horemuzova E, Katz-Salamon M, Milerad J. 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