Received: 5 October 2018 | Accepted: 20 January 2019

DOI: 10.1002/ppul.24275

ORIGINAL ARTICLE: OUTCOMES

Oxygen saturations and neurodevelopmental outcomes in

single ventricle heart disease

Kelly R. Wolfe PhD1 | John Brinton PhD2 | Michael V. Di Maria MD3 |

Maxene Meier MS2 | Deborah R. Liptzin MD4

1 Pediatric
Neurology, University of Colorado
School of Medicine and Children's Hospital, Abstract
Aurora, Colorado
Objectives: To evaluate whether the degree of hypoxemia following stage-I and stage-
2 Department of Biostatistics and Informatics,
Colorado School of Public Health, University
II palliative surgeries predicts neurodevelopmental outcomes at 14 months of age in
of Colorado, Aurora, Colorado children with single ventricle congenital heart disease (SVCHD).
3 HeartInstitute, University of Colorado
Design: We analyzed longitudinal data from two Pediatric Heart Network (PHN)
School of Medicine and Children's Hospital
Colorado, Aurora, Colorado randomized controlled trials, with a total of 328 subjects. Oxygen saturations,
4 Pediatric
Pulmonary Medicine, University of measured via pulse oximetry, at time of discharge from stage-I and stage-II surgeries
Colorado School of Medicine and Children's
were the primary predictors of interest, and Bayley Scales of Infant Development-II
Hospital Colorado, Aurora, Colorado
(BSID-II) scores at 14 months old were the primary outcome measure. Relevant
Correspondence
Kelly R. Wolfe, PhD, Assistant Professor of
covariates from previously-published PHN studies were also included in regression
Pediatrics, Children's Hospital Colorado and models.
University of Colorado School of Medicine,
13123 East 16th Avenue, Box 395, Aurora,
Results: Oxygen saturations at time of discharge from stage-I and stage-II surgeries
CO 80045. were not related to BSID-II scores. Having one or more oxygen saturation
Email: kelly.wolfe@childrenscolorado.org
measurements below 80% was also not associated with BSID-II scores, and neither
Funding information was change in oxygen saturations over time. These relationships were not altered by
Children's Hospital Colorado Neurosciences
Administrative Research Team
inclusion of relevant covariates.
Conclusions: In this large cohort of children with SVCHD, oxygen saturations post-
stage-I and post-stage-II palliation surgeries as measured via pulse oximetry were not
associated with neurodevelopmental outcomes at 14 months of age. The relationship
between oxygen saturations and neurodevelopment in SVCHD is likely complex, and
neurodevelopment is known to be affected by a number of factors. Pulse oximetry may
also be an insufficient proxy for cerebral oxygen delivery. Clinically, pulse oximetry
readings during the interstage and post-stage-II surgery periods are not a reliable
predictor of future neurodevelopmental risk.

KEYWORDS
blood oxygenation, neurodevelopment, pulse oximetry, pediatric heart network, single
ventricle

Abbreviations: BSID-II, Bayley Scales of Infant Development-Second Edition; ISV, Infant Single Ventricle trial; NHLBI, National Heart Lung and Blood Institute; PHN, Pediatric Heart
Network; SAS, Statistical Analysis Software; SPO2, venous blood oxygen saturation levels; SVCHD, single ventricle congenital heart disease; SVR, Single Ventricle Reconstruction trial.

Pediatric Pulmonology. 2019;1–6. wileyonlinelibrary.com/journal/ppul © 2019 Wiley Periodicals, Inc. | 1

2 |
1 | INTRODUCTION
Survival rates for children with single ventricle congenital heart disease
(SVCHD) have improved dramatically over recent decades, related to
advances in surgical care and medical management.1–3 As a result,
increased attention has been given to outcomes such as quality of life,
end organ function, and neurodevelopment.4
Various predictors of neurodevelopmental outcomes in SVCHD
have been established, including sociodemographic variables, disease
5–7
characteristics, and aspects of the child's clinical course. One such
clinical characteristic hypothesized to relate to subtle brain injury and
associated neurodevelopmental abnormalities is the lower blood
oxygen saturations that children with SVCHD experience from the
prenatal period until the time of their Fontan operation and often,
beyond.8 Hypoxemia is hypothesized to slow the pace of brain growth,
particularly with regards to white matter, during gestation in
SVCHD9,10 and contribute to increased inflammation and apoptosis
11
as the brain develops during infancy, childhood, and adolescence.
While hypoxemia during the stage-I palliation perioperative period has
been shown to relate to poorer neurodevelopment in SVCHD12–14 the
unique contribution of chronic hypoxemia to altered neurodevelop-
ment has been understudied in SVCHD. As a result, practitioners lack
empirical guidelines to guide clinical management of chronic hypox-
emia during the pre-Fontan period. The present study aims to address
this gap in the literature.
The Pediatric Heart Network (PHN) is a consortium of clinical
research sites established in 2001 by the National Heart Lung and
Blood Institute (NHLBI). The present study combines data from two
PHN randomized controlled trials to investigate the effects of oxygen
saturation (SpO2) measured at the time of discharge following stage I
and stage II palliative surgeries, on neurodevelopment at 14 months of
age. We hypothesized that higher SpO2 Levels during the interstage
and post-stage-II surgery periods would be related to higher neuro-
developmental scores at 14 months of age in the SVCHD population.
2 | M ATERIA LS AN D METH ODS
2.1 | Study design
The study was designed as a retrospective cohort study of de-
identified data from two previous randomized controlled trials: (1) The
NHLBI Single Ventricle Reconstruction (SVR) Trial conducted by the
PHN at 15 centers from 2005 to 2009 15
and (2) the NHLBI Infant
Single Ventricle (ISV) Trial conducted by the PHN at 10 centers in the
United States and Canada, enrolling patients from 2003 to 2007. 16
The
data from both trials are de-identified and publicly available for re-
analysis. The University of Colorado Institutional Review Board
approved this retrospective study.
2.2 | Data collection
Statistical Analysis Software (SAS) datasets from each study were
merged. The primary predictors of interest were SpO2 levels measured
WOLFE ET AL.
via pulse oximetry at two time points: hospital discharge following
stage-I and stage-II surgeries. The patient would typically be around 1
month of age at the time discharge from Stage I surgery, and around
four to 6 months of age at the time of discharge from Stage II surgery.
The primary outcomes of interest were the Bayley Scales of Infant
and Toddler Development-Second Edition (BSID-II) Mental Develop-
ment Index (MDI) and the Psychomotor Development Index (PDI),
obtained at 14 months of age.17 These scores are standardized according
to the child's age. The primary predictor (SpO2) was summarized in three
ways based on longitudinal measures: (1) mean SpO2 levels between the
two hospital discharge time points; (2) An SpO2 level below 80% at either
time point; and (3) Change in oxygen saturations of more than 2%
between the two time points. These three methods for summarizing
SpO2 were chosen from a clinical rationale, as we sought to understand
the relative importance of a patient's general SpO2 level over time, having
one or more SpO2 measurements below the clinical cutoff for concern,
and variability versus stability in SpO2 levels.
A priori, investigators identified covariates of interest for
adjustment in regression models. Covariates were considered if they
were found to be significant predictors in the regression analyses
predicting BSID-II scores in manuscripts published from the two
original trials.6,7,18–22 The final model used to estimate the association
of SpO2 with neurodevelopment was adjusted for maternal education
level, days on ventilator post-stage-I surgery, birthweight, total stage-I
surgery length of stay and total number of complications during stage-I
and stage-II surgery admissions.
2.3 | Statistical analysis
The frequencies of missing data, as well as potential differences in key
characteristics due to exclusion and missing covariate information were
examined using Fisher's exact, Chi-square, and t-tests. The distributions
of the primary outcome of interest (BSID-II scores at 14 months old)
were examined via histograms, and tests of the normality assumption
were conducted using the Shapiro-Wilks test statistics.
Multiple linear regression models examined the association
between SpO2 and neurodevelopment. Assumptions of linear
regression including Gaussian distribution of the outcome and
homoscedasticity were assessed using residual plots and Levine's
Test respectively. Type 3 F-tests were used to assess statistical
significance of the association between SpO2 and neurodevelopment
in a series of nested models. Model 1 was a univariate model, with
BSID-II scores at 14 months old as the outcome, and SpO2 as the
predictor. Model 2 was a multivariable model adjusting for covariates,
reported above. Significance was set at the alpha = 0.05 level. All
analyses were conducted using R version 3.3.1 software.23 Post hoc
analysis examined the interaction between SpO2 and all of the
covariates, reported above.
3 | RESULTS
A combined total of 2165 participant records came from the data
consolidation. After excluding participants with missing data for the
WOLFE ET AL.
| 3

predictors, outcomes, or a priori covariates, a total of 328 participants
(35 from the ISV Trial and 293 from the SVR Trial) were included in the
analytic cohort. Excluded participants tended to have a lower
birthweight, fewer diagnoses of HLHS, and more complications
(ps <.05); however, they did not differ from included participants on
SpO2 levels. Basic summary statistics describing the analytic cohort in
terms of demographic and clinical variables are presented in Table 1.
Overall, the cohort's mean SpO2 levels were around 81-82% at both
time points. BSID-II index mean scores were generally in the low-
average to below-average range (BSID-II Mental Development Index
SS mean = 89.38; Psychomotor Development Index SS mean = 75.10),
but with substantial variability (SDs of 17.56 and 19.61, respectively,
as opposed to SDs of 15 in the normative distribution).
Results from the regression analyses are presented in Tables 2
and 3 and Figure 1. SpO2 levels were not directly related to BSID-II
MDI or PDI scores, whether examined via mean SpO2 level over time,
the presence of an SpO2 level below 80% (a dichotomous variable;
yes/no) or whether SpO2 was consistent (within +/− 2%) between the
two time points. Inclusion of covariates in the models with SpO2 levels
did not change the non-significance of SpO2 as a predictor of
neurodevelopmental outcomes. Regarding the covariates, as in
previously-published studies with the PHN cohorts, predictors of
higher BSID-II MDI scores included higher maternal education level,
higher birthweight, fewer days on the ventilator post-stage-I surgery,
and shorter length of stay post-stage-I surgery (all ps <.05). Predictors
of higher BSID-II PDI scores included higher birthweight and fewer
days on the ventilator post-stage-I surgery (all ps <.05).
The post hoc analysis indicated a statistically significant interac-
tion between average SpO2 level and site and average SpO2 level and
length of stay when predicting BSID-II MDI score (P < .05). No other
interactions were significant.
4 | DISCUSSION
SpO2 levels at the time of discharge from stage-I and stage-II palliation
surgeries were not related to neurodevelopment at 14 months of age
in children with SVCHD. This was surprising, considering previous
studies documenting relationships between stage-I palliation surgery
perioperative oxygen saturation levels with neurodevelopmental
outcomes in SVCHD; however, these studies used more direct
methods of monitoring hemodynamics, such as SaO2 during cardiac

TABLE 1 Descriptive data for analytic cohort

N = 329
Sex (Male) 207 (63%)
Ethnicity (Hispanic) 60 (18%)
Race
White 278 (85%)
Black or African American 37 (11%)
Asian 3 (1%)
Other Race 8 (2%)
Birth Weight (g) 3171.56 ± 518.41
Maternal Education
<High School 43 (13%)
High School/GED 63 (19%)
Some College/2-year Degree 102 (31%)
4-year College Degree 83 (25%)
Graduate Degree 38 (12%)
Diagnosis of HLHS 284 (86%)
a
Stage-I Surgery Length of Stay (days) 24 (17, 37)
Number of Complications (Stage I and Stage II Surgeries)a 0 (0, 1)
SpO2 post stage-I surgery 82.33 ± 4.64 (Range: 67–92)
SpO2 post stage-II surgery 81.21 ± 4.59 (Range: 67–92)
SpO2 average level across timepoints>80 178/329 (54%)
SpO2 Level consistent (within +/−2 across timepoints) 217/329 (66%)
BSID-II Mental Development Index SS 89.38 ± 17.56 (Range: 50-122)
BSID-II Psychomotor Development Index SS 75.10 ± 19.61 (Range: 50-120)

g, grams; GED, general education diploma; SpO2, oxygen saturation measured via pulse oximetry; SS, standard score (mean = 100; standard deviation = 15).
a
Median and interquartile range.
4 | WOLFE ET AL.

TABLE 2 Univariate analysis predicting BSID-II mental development index

Model estimate 95%CI P-value
Mean SpO2 Level Post-Stage-I and Post-Stage-II Surgeries 0.36 −0.19, 0.91 0.2019
Any SpO2 Level under 80% 2.25 −1.55, 6.06 0.2471
SpO2 Change of more than 2% between Post-Stage-I and Post-Stage-II Surgeries −3.12 −7.11, 0.88 0.1273

Model estimates are Beta values. BSID, Bayley Scales of Infant and Toddler Development-Second Edition; SpO2, oxygen saturations via pulse oximetry.

catheterization12 and monitoring regional cerebral oxygen delivery
directly with near-infrared spectroscopy (NIRS) during and immedi-
ately after surgeries with cardiopulmonary bypass.14,24 Post hoc
analyses suggested that the effect of average SpO2 level on mental
development may be moderated by site and length of stay. This finding
should be interpreted cautiously in light of several factors including the
high number and exploratory nature of post hoc comparisons, the
substantial variability of sample sizes across sites, and the present
study's inability to investigate site differences (eg, in standard care)
that might contribute to this interaction effect.
Pulse oximetry, as was utilized in the present studies, is less
reliable compared to other methods of assessing oxygen saturations,
particularly for saturation levels below 80% or under conditions of
lower cardiac output.25–28 Pulse oximetry is also vulnerable to
additional sources of error, including motion artifacts, irregular heart
rhythms, skin pigmentation, and calibration assumptions.26 Arterial
oxygen saturation (SaO2) is less susceptible than SpO2 to confounders
like motion, skin pigmentation, nail polish, etc.; however, it still
depends on calculations using the oxyhemoglobin dissociation curve.
Patients with congenital heart disease may have altered oxyhemoglo-
bin dissociation curves that would affect how oxygen saturation (both
SaO2 and SpO2) reflects oxygen content.29,30 Oxygen content
evaluates the amount of oxygen in the blood and is related to the
partial pressure of oxygen, hemoglobin, and saturation. As patients
with CHD are typically polycythemic to increase their oxygen carrying
capacity,31 their oxygen content may be higher than suspected by
SpO2. Therefore, monitoring SpO2 may underestimate oxygen
content and cerebral oxygen delivery and help explain the lack of
relationship between SpO2 and neurodevelopmental outcomes.
Direct monitoring of systemic oxygen levels may be more important
than SpO2 measurements for predicting an infant with SVCHD's level
of future neurodevelopmental risk.
Another potential avenue of inquiry into our surprising findings
lies with the method of neurodevelopmental assessment. Evaluating
neurodevelopment in infants and toddlers is notoriously challenging,
and the BSID-II is generally considered to be a more specific, but less
sensitive, instrument for predicting long-term neurodevelopmental
impairment.32 Indeed, BSID-II scores at 14 months old did not predict
parent-reported neurodevelopment at 3 years of age in the PHN SVR
follow-up trial,18 and in the extremely low birthweight population,
BSID-II scores at 20 months old were not found to predict cognitive
functioning at eight years old.33 Neurodevelopmental assessments of
infants and toddlers provide broad estimates of neurodevelopment in a
few domains, and can be complicated by factors such as stranger
anxiety, fatigue (eg, testing during nap time) and unfamiliarity with the
testing setting, which tends to be school-like in nature. As children get
older, these potential confounds are reduced; additionally, neuropsy-
chological assessments can evaluate more specific areas of cognition
(eg, executive functions) once children reach school-age, and the
results become more predictive of long-term functioning. Follow-up
studies using multiple methods of assessing oxygen saturations will be
helpful in clarifying whether systemic oxygen levels during the
interstage and post-stage-II palliation surgery period are related to
long-term neurodevelopment in SVCHD. It is conceivable that chronic
hypoxia may specifically affect certain aspects of neurocognitive
functioning, such as executive functioning, processing speed, or long-
term memory, which develop and can be better assessed over the
course of childhood and adolescence.
A limitation that may influence the generalizability of our study is
that only 328 of 2165 original study participants had complete data
available, and when we compared the groups of participants who had
complete data versus those who did not, a number of clinical
characteristics differed between the two groups, including mean
BSID-II MDI and PDI scores, with the excluded participant group
retaining slightly higher BSID-II MDI (mean SS = 94.66, SD = 14.58)
and PDI (mean SS = 79.64, SD = 17.86) scores (Supplemental Table S1,
online only). Mean SpO2 levels did not differ between include and
excluded participant groups, and the BSID-II MDI and PDI scores from
the subjects used in our analyses demonstrated relationships in
expected directions with most of the demographic and medical

TABLE 3 Univariate analysis predicting BSID-II psychomotor development index

Model estimate 95%CI P-value
Mean SpO2 Level Post-Stage-I and Post-Stage-II Surgeries 0.45 −0.17, 1.06 0.1557
Any SpO2 Level under 80% 1.91 −2.36, 6.17 0.3815
SpO2 Change of more than 2% between Post-Stage-I and Post-Stage-II Surgeries 0.52 −3.98, 5.01 0.8223

Model estimates are Beta values. BSID, Bayley Scales of Infant and Toddler Development-Second Edition; SpO2, oxygen saturations via pulse oximetry.
WOLFE ET AL.
FIGURE 1 Scatterplots of SpO2 levels and neurodevelopmental outcomes. SpO2 Levels by BSID-II Mental Development B. SpO2 Levels
by BSID-II Psychomotor Development. Index (MDI) Standard Scores Index (PDI) Standard Scores. SpO2, oxygen saturations via pulse
oximetry; BSID-II, Bayley Scales of Infant and Toddler Development-Second Edition
covariates that were significantly related to these variables in studies
using the larger cohort6,7,18–22 (Tables 2 and 3). Additionally, Figure 1
demonstrates that our study cohort still retained a wide range of BSID-
II scores for both MDI and PDI indices, and the distributions show the
expected “leftward shift” (ie, the mean scores for our cohorts are below
normative means). As such, it appears our sample was adequately
representative of the larger study cohort.
In conclusion, results of the present study indicate that pulse
oximetry at the time of discharge from stage-I and stage-II palliation
surgeries does not predict short-term neurodevelopment in SVCHD.
Evaluation of cerebral oxygen delivery (eg, using NIRS, oxygen
content) should be prioritized for future research studies on
neurodevelopment in SVCHD. Clinically, pulse oximetry readings
during the interstage and post-stage-II surgery period should not be
relied upon as an indicator of future neurodevelopmental risk in
SVCHD.
ACKNOWLEDGMENTS
The NIH/NHLBI Pediatric Heart Network Infant Single Ventricle trial
dataset was used in preparation of this work. Data were downloaded
from https://www.pediatricheartnetwork.org//pud_login.asp?
study_id=ISV on 09/16/16 and 04/07/17. We are grateful to the
Children's Hospital Colorado Neurology Administration Research
Team for providing financial support for biostatistics for this project.
Funding for biostatistics support provided by the Children's Hospital
Colorado Neurosciences Administrative Research Team. There are no
real or perceived conflicts of interest. The study sponsor did not have
influence over the study design; collection, analysis, or interpretation
of data; writing of the manuscript; or decision to submit the manuscript
for publication.
| 5
ORCID
Kelly R. Wolfe http://orcid.org/0000-0003-4754-4577
Deborah R. Liptzin http://orcid.org/0000-0002-3667-1856
REFERENCES
1. Stasik CN, Gelehrter S, Goldberg CS, Bove EL, Devaney EJ, Ohye RG.
Current outcomes and risk factors for the Norwood procedure.
J Thorac Cardiovasc Surg. 2006;131:412–417. Erratum appears in J
Thorac Cardiovasc Surg (2007) 133:602.
2. Tweddell JS, Hoffman GM, Mussatto KA, et al. Improved survival of
patients undergoing palliation of hypoplastic left heart syndrome:
lessons learned from 115 consecutive patients. Circulation. 2002;106:
I82–I89.
3. Tweddell JS, Nersesian M, Mussatto KA, et al. Fontan palliation in the
modern era: factors impacting mortality and morbidity. Ann Thorac
Surg. 2009;8:1291–1299.
4. Marino BS, Lipkin PH, Newburger JW, et al. Neurodevelopmental
outcomes in children with congenital heart disease: evaluation and
management. Circulation. 2012;126:1143–1172.
5. Goldberg CS, Lu M, Sleeper LA, et al. Factors associated with
neurodevelopment for children with single ventricle lesions. J Pediatr.
2014;165:490–496.
6. Gaynor JW, Stopp C, Wypij D, et al. Neurodevelopmental outcomes
after cardiac surgery in infancy. Pediatrics. 2015;135:816–825.
7. Mahle WT, Lu M, Ohye RG, et al. A predictive model for neuro-
developmental outcome following the Norwood procedure. Pediatr
Cardiol. 2013;34:327–333.
8. Fogel MA, Li C, Elci OU, et al. Neurological injury and cerebral blood
flow in single ventricles throughout staged surgical reconstruction.
Circulation. 2017;135:671–682.
9. Limperopoulos C, Tworetzky W, McElhinney DB, et al. Brain volume
and metabolism in fetuses with congenital heart disease: evaluation
with quantitative magnetic resonance imaging and spectroscopy.
Circulation. 2010;121:26–33.
6 |
10. Morton PD, Korotcova L, Lewis BK, et al. Abnormal neurogenesis and
cortical growth in congenital heart disease. Sci Transl Med. 2017;9:
eaah7029.
11. Cordina R, Grieve S, Barnett M, Lagopoulos J, Malitz N, Celermajer DS.
Brain volumetrics, regional cortical thickness, and radiographic
findings in adults with cyanotic congenital heart disease. Neuro-
Image:Clinical. 2014;319–325.
12. Hoffman GM, Mussatto KA, Brosig CL, et al. Systemic venous oxygen
saturation after the Norwood procedure and childhood neurodeve-
lopmental outcome. J Thorac Cardiovasc Surg. 2005;130:1094–1100.
13. Simons J, Sood ED, Derby CD, Pizarro C. Predictive value of near-
infrared spectroscopy on neurodevelopmental outcome after surgery
for congenital heart disease in infancy. J Thorac Cardiovasc Surg. 2012;
143:118–125.
14. Sood ED, Benzaquen JS, Davies RR, Woodford E, Pizarro C. Predictive
value of perioperative near-infrared spectroscopy for neurodevelop-
mental outcomes after cardiac surgery in infancy. J Thorac Cardiovasc
Surg. 2013;145:438–445.
15. Ohye RG, Gaynor JW, Ghanayem NS, et al. Design and rationale of a
randomized trial comparing the Blalock-Taussig and right ventricle-
pulmonary artery shunts in the Norwood procedure. J Thorac
Cardiovasc Surg. 2008;136:968–975.
16. Hsu D, Mital S, Ravishankar C, et al. Rationale and design of a trial of
angiotensin converting enzyme inhibition in infants with single
ventricle. Am Heart J. 2009;157:37–45.
17. Bayley N. Bayley Scales of Infant Development, Second Edition San
Antonio, TX: The Psychological Corporation; 1993.
18. Goldberg CS, Lu M, Sleeper LA, et al. Factors associated with
neurodevelopment for children with single ventricle lesions. J Pediatr.
2014;165:490–496.
19. Williams IA, Fifer C, Jaeggi E, Levine JC, Michelfelder EC, Szwast AL.
The association of fetal cerebrovascular resistance with early neuro-
development in single ventricle congenital heart disease. Am Heart J.
2013;165:544–550.
20. Ravishankar C, Zak V, Williams IA, et al. Association of impaired linear
growth and worse neurodevelopmental outcome in infants with single
ventricle physiology: a report from the Pediatric Heart Network Infant
Single Ventricle Trial. J Pediatr. 2013;162:250–256.
21. Miller TA, Zak V, Shrader P, et al. Growth asymmetry, head
circumference, and neurodevelopmental outcomes in infants with
single ventricles. J Pediatr. 2016;168:220–225.
22. Newburger JW, Sleeper LA, Bellinger DC, et al. Early developmental
outcome in children with hypoplastic left heart syndrome and related
anomalies: the single ventricle reconstruction trial. Circulation.
2012;125:2081–2091.
23. R, Version 3.3.1. Vienna, Austria: R Foundation for Statistical
Computing http://www.R-project.org/.
WOLFE ET AL.
24. Hovels-Gurich HH, Seghaye MC, Schnitker R, et al. Long-term
neurodevelopmental outcomes in school-aged children after neonatal
arterial switch operation. J Thorac Cardiovasc Surg. 2002;124:
448–458.
25. Sinha IP, Mayell SJ, Halfhide C. Pulse oximetry in children. Arch Dis
Child Educ Practice Ed. 2014;99:117–118.
26. Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric
practice. Pediatrics. 2011;128:740–752.
27. Lee WW, Mayberry K, Crapo R, Jensen RL. The accuracy of pulse
oximetry in the emergency department. Am J Emerg Med. 2000;18:
427–431.
28. Hannhart B, Haberer J-P, Saunier C, Laxenaire M-C. Accuracy and
precision of fourteen pulse oximeters. Eur Respir J. 1991;4:115–119.
29. Woodson RD, Torrance JD, Shappell SD, Lenfant C. The effect of
cardiac disease on hemoglobin-oxygen binding. J Clin Invest. 1970;
49:1349–1356.
30. Morse M, Cassels DE, Holder M. The position of the oxygen
dissociation curve of the blood in cyanotic congenital heart disease.
J Clin Invest. 1950;29:1098–1103.
31. Gidding SS, Bessel M, Liao YL. Determinants of hemoglobin
concentration in cyanotic heart disease. Pediatr Cardiol. 1990;11:
121–125.
32. Spittle AJ, Spencer-Smith MM, Eeles AL, et al. Does the Bayley-III
Motor Scale at 2 years predict motor outcome at 4 years in very
preterm children? Dev Med Child Neurol. 2013;55:448–452.
33. Hack M, Taylor HG, Drotar D, et al. Poor predictive validity of the
bayley scales of infant development for cognitive function of
extremely low birth weight children at school age. Pediatrics.
2005;116:333–341.
SUPPORTING INFORMATION
Additional supporting information may be found online in the
Supporting Information section at the end of the article.
How to cite this article: Wolfe KR, Brinton J, Di Maria MV,
Meier M, Liptzin DR. Oxygen saturations and
neurodevelopmental outcomes in single ventricle heart
disease. Pediatric Pulmonology. 2019;1–6.
https://doi.org/10.1002/ppul.24275