Manvi Bansal ORCID iD: 0000-0002-3030-7754

Retrospective Analysis of Inpatient Polysomnogram

Characteristics and Discharge Outcomes in Infants with
Accepted Article
Bronchopulmonary Dysplasia Requiring Home Oxygen
Therapy
Nicole Flores-Fenlon, MD1; Noah Wright, MA2; Cheryl Lew, MD, MSEd, MSBioethics3;
Theodora A. Stavroudis, MD4; Choo Phei Wee, MS5; Sally L. Davidson Ward, MD3;
Manvi Bansal, MD3

Affiliations:
1
Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center, Keck
School of Medicine of USC, Los Angeles, CA, United States
2
Rocky Vista University College of Osteopathic Medicine, Parker, CO, United States
3
Division of Pediatric Pulmonology and Sleep Medicine, Children’s Hospital Los
Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern
California, Los Angeles, CA, United States
4
Fetal and Neonatal Institute, Division of Neonatology, Children's Hospital Los Angeles,

Department of Pediatrics, Keck School of Medicine, University of Southern California,

Los

Angeles, CA, United States

5
Southern California Clinical and Translational Science Institute (SC-CTSI) and The
Saban Research Institute (TSRI) Biostatistics Core, Children’s Hospital Los Angeles, Los
Angeles, California, United States

Address Correspondence To:

Manvi Bansal, MD

Division of Pediatric Pulmonology and Sleep Medicine

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1002/ppul.25129.

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 Children’s Hospital Los Angeles

4650 Sunset Boulevard, MS #83

Los Angeles, CA 90027

Accepted Article
323-361-3592

Email: mbansal@chla.usc.edu

Short Title: Polysomnography Findings in Infants with BPD

Abbreviations:

PSG = polysomnogram

BPD = bronchopulmonary dysplasia

NICU = neonatal intensive care unit

OAHI = obstructive apnea-hypopnea index

ODI = oxygen desaturation index

OSA = obstructive sleep apnea

CI = central apnea index

SpO2 = oxygen saturation measured by pulse oximeter

TIB = Total time in bed

TST = Total sleep time

Ar/Aw = Arousal/Awakening index

ACO2 = Average carbon dioxide level (in torr)

PCO2 = Peak carbon dioxide level (in torr)

MAI = Mixed apnea index

OAI = Obstructive apnea index

OHI = Obstructive hypopnea index

REM = Rapid Eye movement

PB = Periodic breathing

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 Keywords: inpatient, infant, polysomnography, polysomnogram, sleep study,
bronchopulmonary dysplasia, oxygen therapy, discharge

Funding Sources:
Accepted Article
TSRI Biostatistics Core at CHLA is partially funded by SC-CTSI. This publication,
therefore, was supported by NIH/NCRR SC-CTSI Grant Number UL1 TR000130. Its
contents are solely the responsibility of the authors and do not necessarily represent the
official views of the NIH.

Financial Disclosure: The authors have no financial relationships relevant to this article
to disclose.

Conflict of Interest: The authors have no conflict of interest to disclose.

Contributor’s Statement Page

Dr. Flores-Fenlon made substantial contributions to designing the study, analyzing the

data, and interpreting the results. Mr. Wright assisted with data collection. Ms. Wee
performed the statistical analyses. Drs. Lew, Stavroudis and Ward assisted with
manuscript preparation. Dr. Ward helped in assessing sleep study data as well. Dr. Bansal
made substantial contributions to designing the study, interpreting the results, collection
of some data and preparing the manuscript. All authors reviewed and approved the final
version of the manuscript.

Abstract

Rationale

Little is known about the polysomnogram characteristics in infants with BPD, especially

severe BPD, who do not need home ventilatory support but are at increased risk for

chronic hypoxia and are vulnerable to its effects.

Objective

To assess polysomnogram characteristics and change in discharge outcomes in premature

infants with bronchopulmonary dysplasia (BPD) who required oxygen therapy at

discharge.

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 Methods

This is a retrospective chart review of premature infants with BPD admitted to a

Accepted Article
quaternary newborn and infant intensive care unit from January 1, 2012 to December 31,

2015 and underwent polysomnography prior to discharge

Measurements and Main Results

Data from 127 patients was analyzed. The median gestational age of our patients was 26

weeks and 1 day (IQR 24.71, 28.86). The majority of the patients had moderate to severe

BPD. The median obstructive apnea-hypopnea index (OAHI) was 5.3 events per hour

(IQR 2.2, 10.1). The median oxygen desaturation index (ODI) was 15.7 events per hour

(IQR 4.7, 35). Nadir SpO2 was 81% (IQR 76-86), Ar/Aw index 21.9 (IQR13.3-30.9). No

statistically significant difference was noted between severe and non-severe BPD groups

for polysomnogram characteristics. However, average end tidal CO2 was significantly

higher in the severe BPD group (p = 0.0438). Infants in the severe BPD group were

intubated longer than infants with non-severe BPD (p = 0.0082). Corrected gestational

age (CGA) at the time of discharge (CGA-PSG) and polysomnogram (CGA-DC) were

higher in severe BPD patients but not statistically different. The majority of premature

infants that received a PSG were discharged home with oxygen. 69% required a titration

of their level of support based on results from the PSG.

Conclusion

Our results highlight the presence of abnormal polysomnogram characteristics in BPD

patients, as early as 43 weeks corrected gestational age. These findings have not been

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 previously described in this patient population prior to initial discharge home. A severe

BPD phenotype tends to be associated with higher respiratory morbidity compared to a

non-severe BPD phenotype for the comparable CGA. PSG, when available, may be
Accepted Article
helpful for individualizing and streamlining treatment in preparation for discharge home

and mitigating the effects of intermittent hypoxic episodes.

Introduction

Infants admitted to the NICU, whether term or preterm, are at risk for sleep

disordered breathing due to a variety of causes (1-3). In particular, infants with BPD are a

particularly fragile population that are at risk for sleep disordered breathing,

hypoventilation and hypoxemia (4). A study from the National Institute of Child Health

and Human Development Neonatal Research Network showed that 68% of infants born

at 22-28 weeks and with birthweight from 401-1500 g were diagnosed with BPD, using

the severity-based based definition proposed by Jobe et al (5, 6). This classification

scheme has been refined by Abman et al. from the Bronchopulmonary Dysplasia

Collaborative to distinguish between infants with severe BPD as having “type 1” disease

if they are receiving ≥30% O2 or nasal CPAP or high-flow nasal cannula at ≥36 wk post-

menstrual age, and “type 2” disease if they are receiving mechanical ventilation at this

age (7). Though more of these infants are surviving to childhood and beyond, they remain

at risk for life-threatening hypoxia secondary to their impaired lung mechanics (1, 8) and

immature respiratory control (4). In addition, chronic or intermittent episodes of

hypoxemia have been shown to have adverse effects on cognitive, academic

achievement, and behavioral outcomes (9). Providing an adequate regimen of respiratory

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 support is essential to a safe discharge to the home environment, and for optimizing

growth, as well as minimizing recurrent lung injury (7).

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Clinically unsuspected desaturations can occur frequently in preterm infants with

BPD (1). Lung function in these patients remains abnormal for years, and many continue

to require monitoring and supplemental oxygen following discharge (10). Though infants

may have appropriate oxygen saturations while awake, they can exhibit desaturation

events during sleep and feeding, thus prompting clinicians to initiate supplemental

oxygen. The Thoracic Society of Australia and New Zealand (TSANZ), the American

Thoracic Society (ATS), and the British Thoracic Society (BTS) recommend the use of

supplemental oxygen to maintain goal saturations and to facilitate discharge home (10-

12). While the TSANZ and ATS acknowledge the potential utility of polysomnography

(PSG) to wean infants off oxygen or to determine oxygen need in infants who are not

doing well, they do not currently make recommendations for completion of a PSG for all

infants with BPD (11, 12). The impact that a PSG, otherwise known as a sleep study, can

have on the management of these infants has not been demonstrated to date. It provides

data regarding central, mixed, obstructive apnea, hypoventilation information and allows

for more precise oxygen titration and provides objective data that can be used to tailor

management and optimize respiratory status for the individual patient (2).

However, little is known about the PSG characteristics of preterm infants with

BPD and the impact the results have on therapy. There are no studies to date that have

examined the results of PSG in these infants done prior to discharge or in infants at an

early post-menstrual age. Data supporting the routine use of polysomnography to assess

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 the need for supplemental oxygen support in these infants is also lacking (3). Further,

there are very few pediatric sleep labs with adequate expertise in infants. The aim of this

study is to define polysomnogram (PSG) characteristics in premature infants with

Accepted Article
bronchopulmonary dysplasia (BPD) and delineate its role in discharge planning.

Methods

Study Design and Patient Population

A retrospective chart review and descriptive study was conducted to identify premature

infants born at less than 37 weeks gestational age with BPD who were admitted to the

Neonatal Intensive Care Unit (NICU) of a quaternary urban children’s hospital from

January 1, 2012 to December 31, 2015 and underwent polysomnography prior to

discharge from the hospital. Not every premature infant with diagnosed BPD underwent

PSG. PSG was done on premature infants with diagnosed BPD as per the clinical

decision-making by the rounding pulmonologist to assist with oxygen titration or if the

infant had ongoing intermittent desaturations with feeding, sleeping or while awake

despite oxygen supplementation or while on room air. It was done as close to the

discharge as possible, when determination of oxygen needs was the last thing the patient

needed prior to discharge home. This hospital does not have an in-house delivery service;

therefore, all infants are out-born and transferred to the NICU. Patients were identified by

querying the Somnostar polysomnography database for infants who had a

polysomnography done during this time period. Total of 272 infants were pulled from the

database. Of these 133 were preterm infant who underwent sleep study prior to discharge.

4 infants were excluded from the study due to inadequate data being available when they

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 were transferred from the outside hospital and 2 were late preterm infants with complex

congenital cardiac abnormalities (hypoplastic left heart and Ebstein’s anomaly) who

underwent sleep study for other indications.

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Premature infants with BPD who did not have issues with desaturations did not

have a PSG done. Patients with type 2 severe BPD with tracheostomy or tracheostomy

and ventilator dependence did not undergo PSG and were not included in the study. All

PSGs were done at the patient’s bedside. Diagnosis of BPD was made by the

neonatologist, confirmed by the pediatric pulmonologist, and based on oxygen

dependency at 36 weeks post-menstrual age (5) per the criteria for “new BPD” (Jobe et

al. in the 2001 National Institutes of Health and Child Development (NICHD)/National

Heart, Lung, and Blood Institute (NHLBI) Workshop and as per Abman et al (7)). During

the analysis, a subset of infants was identified for whom documentation from the

referring hospital was inadequate for definite classification into type 1 or type 2 severe

BPD. These infants were deemed “unclassifiable” per our criteria due to inadequacy of

documentation.

Data Collection

We reviewed the electronic medical records of all patients who met the criteria for

our study. Demographic data including ethnicity and gender were collected. Gestational

age and birthweight were recorded. Maternal history as recorded in the admission history

and physical, surfactant and caffeine use, number of days intubated and number of days

on non-invasive positive-pressure ventilation (defined as use of nasal cannula intermittent

mandatory ventilation or nasal continuous positive airway pressure), use of respiratory

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 medications or diuretics for BPD (defined as albuterol, levalbuterol, budesonide,

furosemide, chlorothiazide, and spironolactone) and surgeries were abstracted. Number

of days intubated was calculated only for the admission at our institution, unless there
Accepted Article
was clear documentation from the transfer paperwork of the dates of invasive and non-

invasive ventilation. The presence of additional diagnoses including pulmonary

hypertension and gastroesophageal reflux, based on inclusion in the diagnosis list of the

patient’s medical record, were recorded. Any other significant co-morbidities noted in the

diagnosis list in the medical record and any surgeries performed during the admission

were also obtained. Infants who did not have continuing desaturations, born at greater

than 37 weeks gestation, did not complete a full PSG for any reason, or completed a PSG

as an outpatient, and infants who had craniofacial anomalies were excluded from

analysis.

Polysomnography

We used following equipment in sleep lab for performing PSG. Braebon thermal

airflow sensor (pediatric and adult), airflow and end tidal CO2 canula: PTAF, Pro-tech 2

from Respironics, BCI/Smith Medical Capnocheck, capnograph 9004, system was used

for monitoring CO2 and as Pulse oximeter with averaging set to 2 beats/ 8 seconds.

Respiratory inductive plethysmography belts used from years 2012-2013 were from

AMBU Sleepmate, piezoelectric belts, and from years 2013-2014 we used QDC-Pro

from Vyaire Medical/CareFusion.

PSG was performed when patients were on oxygen flow of 1 liter per minute or

less or who had intermittent desaturations who were otherwise medically stable and ready

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 for discharge home. Additionally, infants were off all sedation and narcotic medications

for at least 24 hours, unless the infant was to be discharged home with these medications.

PSGs were read by a board-certified pediatric sleep medicine attending and scored
Accepted Article
according to the American Academy of Sleep Medicine Manual for Scoring Sleep 2007

guidelines. As new amendments and versions/updates were available, they were

immediately applied to keep scoring guidelines current and up to date, including 2.0

version, then 2.3 versions and updates which happened during study period. The

following polysomnogram parameters were evaluated for the study: heart rate, respiratory

rate, obstructive apnea hypopnea index (OAHI; number of obstructive apneas and

hypopneas per hour of sleep), central apnea index (CI), oxygen desaturation index (ODI;

number of oxygen desaturations of 3% or more per hour of sleep), and baseline oxygen

saturation as measured by pulse oximetry (SpO2) and oxygen saturation nadir.. Studies

were commenced on room air with the addition of oxygen by nasal cannula for

desaturation events or baseline SpO2 of less than 89%, beginning at 0.25 liters per minute

and then oxygen was gradually increased to eliminate hypoxemia with a goal SpO2 ≥

94%. Patients who were unable to tolerate room air at the start of the study underwent

oxygen titration only.

Statistical Methods

Descriptive statistics are provided to describe the distribution of this study sample

characteristics. Continuous variables that are normally distributed are described in mean

and standard deviation (SD), whereas those that are not normally distributed are

described in median and interquartile range (IQR). Categorical variables are summarized

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 in frequency and percentage. Two-sample t-test and Wilcoxon rank-sum test were used to

examine the difference in continuous parameters between non-severe and severe BPD

groups. Chi-Square test and Fisher’s Exact test were used for comparing categorical
Accepted Article
variables between the non-severe and severe groups. Then, generalized linear model

based on gamma distribution was used to assess the relationship in days of intubation on

OAI, OAHI and MAI univariately. This is to examine the effect of days of intubation on

any possible anatomical changes resulting in increase in any obstructive PSG parameters.

The association in gestational age and corrected gestation age at the time of sleep study

with central apnea index was assessed with a similar statistical model to evaluate role of

progressive maturity of central control of respiration in relation to central apneas. Similar

model was used to assess the association of reflux on OAI, OAHI, and MAI.

Univariate linear regression model is used to assess the association of hemoglobin

(Hb) and pulmonary hypertension (PHTN) on nadir SpO2.. The results for OAI, MAI,

OAHI and central apnea index are described as percent change; beta estimate (β) is used

to describe the results for SpO2;. 95% confidence interval and p-value are included in

these estimates. Significance level is set at 5% with two-sided test throughout the

analyses. All statistical computations were done in Stata/SE 15.1 (StataCorp, College

Station, TX).

Results

A total of 127 infants met the criteria for this study. Fifty-seven percent of the

patients were male, about forty five percent were Hispanic, and about twenty five percent

were Caucasian/white (Table 1). Median gestational age of the patient population was 26

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 weeks and 1 day (IQR 24.71, 2.86) with a median birthweight of 0.76 kg (IQR 0.64,

1.05). Eighty-three percent of the patients received at least one dose of surfactant. Eighty-

one percent of the patients received caffeine during their hospital admission, but this was
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discontinued by the time of the PSG. Patients were intubated for a median of 41 days

(IQR 14, 67) and received non-invasive positive pressure ventilatory support for a

median of 25 days (IQR 9, 38). Ninety-six percent of the patients were started on

respiratory medications such as albuterol, budesonide, ipratropium and diuretics during

their hospital stay and were subsequently discharged home on these medications.

Twenty-eight percent of the patients were discharged home with aerosolized medications

only. With regards to associated co-morbidities, eighteen percent of infants had

pulmonary hypertension diagnosed by echocardiogram at some point during their

admission and forty-nine percent had clinical symptoms of gastroesophageal reflux.

Almost all the studies performed were titration studies with about 81% of the infants

spending median of 27.5 minutes of time on room air (IQR 7.25-63.5 minutes). This was

either spend in the beginning of the end of the sleep study as ordered by the physician.

The relative proportions of patients with mild, moderate, severe type 1 and severe

type 2 BPD are presented in Table 1. Most patients in the study had moderate (14%) to

severe (37% with type 1 and 41% with type 2) BPD. Of note, there were six patients with

severe BPD who were deemed “unclassifiable” for the reasons detailed above.

Table 2 shows the distribution of sleep study parameters between non-severe and

severe BDP groups. 93% of PSG in this study were oxygen titration studies. Median

sleep efficiency was 61%. The median OAHI was 5.3 events per hour (IQR 2.2, 10;

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 normal < 1.5 events per hour). The median CI and ODI were 3.4 events per hour (IQR

1.4, 7.2; normal < 5 events per hour) and 15.7 events per hour (IQR 4.5, 35; normal < 1.5

events per hour), respectively. There was no significant difference in these parameters
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between the non-severe and severe BPD groups. As shown in Table 2, there is a

differential distribution in aCO2 (p=0.0438) and days of intubations (p=0.0082) between

non-severe and severe BPD groups. REM sleep was detected in 65% of infants during

their PSG. The PSG was performed at a median age of 43 weeks and 1 day corrected

gestational age and the patients were discharged at a median age of 45 weeks 2 days

corrected gestational age. Eight percent of patients had concomitant hypoventilation

(defined as more than 25% of total sleep time with end-tidal CO2 more than 50 mm Hg).

72% of mothers had a pregnancy complicated by diagnoses such as preeclampsia,

PPROM, diabetes, oligohydramnios, infection, and substance use, in addition to preterm

labor.

We used a univariate generalized linear model based on gamma distribution that

evaluates the relationship in days of intubations with PSG parameters (OAI, MAI, OAHI)

(Table 3). Decrease in all of these parameters for every unit increase in days of intubation

was noted, but was not statistically significant. Neither of these PSG parameters are

significantly associated with intubation days (all p>0.05). Same model was used to

evaluate OAHI, MAI and OAI association with reflux. None were found significantly

associated with reflux (Table 3). We also used a univariate linear regression model to

evaluate the relationship in Hb and PHTN with nadir SpO2. Hb is marginally significantly

associated with nadir SpO2 (β=1.12, 95% CI=0.001, 2.24, p=0.050). For patients with and

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 without PHTN, there was no significant difference in nadir SpO2 (β=0.85, 95% CI=-3.06,

4.76, p=0.668).
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Univariate generalized linear model based on gamma distribution was also used to

assesses the association between gestational age and corrected gestational age at the time

of sleep study with central apnea index (Table 3). Though there was a 3.17% and 3.60%

decrease in central apnea index for every week increase in gestational age and corrected

gestational age respectively, neither of them is significantly associated (both p>0.05).

Ninety-eight percent of the patients were discharged home with supplemental

oxygen (Table 4). Sixty-nine percent of these patients required a change in their level of

supplemental oxygen support prior to discharge; of those infants requiring a change in

their oxygen support, 55% required an increase in oxygen support based on the PSG

results. Nineteen patients who were previously on room air were found to have abnormal

PSG results necessitating oxygen supplementation, whereas only two were found to no

longer need oxygen support. It is important to note that this change in level of oxygen

support is based solely on a comparison between the baseline level of oxygen the infant

was on prior to the PSG and the recommendations for oxygen support based on results

from the PSG.

Discussion

This study provides data on PSG characteristics on the largest cohort of premature

infants with moderate to severe BPD who had a PSG performed as an inpatient prior to

discharge home, a practice that is unique to very few medical centers. Our cohort had

predominantly severe BPD patients (82%) born around 26 weeks of gestation. All of

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 these infants had abnormal polysomnogram characteristics with lower sleep efficiency of

around 61%, elevated median OAHI (5.3 events/hour), ODI (15.7 event/hour), lower

nadir SpO2 (80%), elevated Ar/Aw index (22.25), and elevated OHI (3.25 events/hour).
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Considering that almost all these studies were titration studies done for clinical purposes,

they are not truly comparable to indices obtained and reported from diagnostic studies. It

is thence likely that indices such as OAHI, OHI, MAI, nadir SpO2, end tidal CO2 etc. can

potentially be much more severe than obtained. End tidal CO2 can be inaccurate due to

faster respiratory rate and washing of CO2 with supplemental oxygen. Supplemental

oxygen in addition prevents significant desaturation events thus leading to underscoring

of the respiratory events. These are significant limitations of performing sleep studies,

especially titration studies in this age group. Future designed prospective studies could

consider diagnostic studies only rather titration studies and could potentially add

transcutaneous CO2 monitoring for more accurate measurements. Regardless, these

indices were abnormal not only when compared to children at one year of age and older,

but some were also abnormal when compared to those reported by Daftary et al in their

study of 30 normal neonates born at 37-42 weeks of gestation (14). These results identify

a population of infants that are at increased risk for hypoxemia and its consequences and

represent a potential target for improving neonatal outcomes though provision of

supplemental oxygen tailored to the individual infant’s needs. The median nadir oxygen

saturation was 80%. Further, we found that 87 infants (69%) who had a PSG required

adjustment of their supplemental oxygen as compared to the clinical assessment of

oxygen needs based on bedside monitoring, with 50 of those patients requiring an

increase in oxygen support, and the rest requiring a decrease in support. Ensuring that

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 infants with BPD are discharged home safely with adequate oxygenation is critical.

Frequent episodes of hypoxia in infants with BPD may affect growth, cardiac functions

and long term neurodevelopmental outcomes (15). Further, infants with BPD are
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vulnerable to episodes of hypoxemia and hypoventilation, which may be clinically

inapparent, particularly during sleep (1, 16).

TSANZ, ATS, and BTS have made recommendations regarding target saturation,

supplemental oxygen need, determination of oxygen need, and discharge home with

oxygen (10-12). All three groups recommend use of supplemental oxygen to maintain

saturations within goal and to facilitate discharge home and affirm the adequacy of

continuous pulse oximetry to assess the need for and level of supplemental oxygen

support. The ATS makes the additional recommendation in its practice guideline on

home oxygen therapy for children that oximetry measurements should include the

infant’s awake, sleeping and feeding states to adequately capture desaturation episodes

(13). The TSANZ and ATS acknowledge the potential utility of PSG to wean infants off

oxygen or to determine oxygen need in infants who are not doing well, but do not make

recommendations for completion of a PSG for all infants with BPD (11, 12). At our

institution, we use pulse oximetry as outlined in the above society guidelines to monitor

saturations but use PSG when an infant who is otherwise approaching discharge home is

having ongoing oxygen desaturations. We use the information from the PSG for oxygen

titration and to determine the presence of apnea, its type (central, mixed or obstructive)

and its severity. This allows us to titrate the level of oxygen support the infant needs to

ensure a safe discharge home or pursue investigations like brain imaging, bronchoscopy

or optimizing respiratory support if hypoventilation is present.

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 Completion of an inpatient infant PSG when possible should be considered in

premature infants with severe BPD for several reasons. In its 2018 Clinical Practice

Guideline regarding Home Oxygen Therapy for Children, the ATS strongly recommends
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that home oxygen therapy be prescribed for infants with BPD complicated by chronic

hypoxemia, with chronic hypoxemia defined as ≥ 5% of the recording time spent with

SpO2 ≤ 93% if measurements are obtained continuously, or three separate readings of

SpO2 ≤ 93% if measurements are obtained intermittently (13). They note that assessment

of oxygen saturation using pulse oximetry is enough to diagnose chronic hypoxemia in

infants. However, hospital cardiorespiratory monitors can detect some, but not all,

episodes of hypoxia in infants. The pulse oximetry output on hospital monitors represents

the average of the patient’s oxygen saturation over 10-15 seconds, whereas the pulse

oximetry probe used during a PSG averages a patient’s oxygen saturation every three

seconds, thereby providing much greater resolution and detail to the information it

provides. Additionally, oxygen saturations while the infant is awake may not be

predictive of desaturations during sleep, and more effective management of oxygen

treatment may be done with more continuous monitoring during sleep (17).

This has important implications particularly for infants with BPD who seem

stable without oxygen support even on conventional unit monitoring, but on further study

are found to require oxygen supplementation to maintain adequate saturations. There

were eighteen of such infants in our study. PSG provides a wide range of objective and

physiologic data that can direct individualized medical management in both the short-

term, while the infant is admitted and monitored, and long-term, when the infant is at

home (18). The results can also complement findings from direct visualization of the

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 airway via bronchoscopy and thereby provide a full picture of the pathophysiologic

processes contributing to sleep-disordered breathing in preterm infants (18). Our practice

is to complete an inpatient PSG in a select group of patients with moderate to severe BPD
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to streamline clinical management and facilitate safe discharge home. The infant’s

healthcare team, both neonatologists and pulmonologists, interpret the PSG findings in

the context of the infant’s clinical picture to ensure that adequate oxygenation, and

therefore safety, is optimized prior to discharge. We have found that using a portable

PSG system and completing the full technician-attended PSG at the bedside to be safe

and minimally disruptive to the care of the infant.

Ensuring that an infant is discharged home with adequate and optimal oxygen

saturation is an important continuation of the practice of keeping premature infants at

relatively higher oxygen saturation targets, as data from the BOOST-II and SUPPORT

trials suggested increased mortality among infants in the lower oxygen saturation target

group (19, 20). Maintaining oxygen saturations between 92-96% can improve growth,

pulmonary hypertension, neurodevelopmental and behavioral outcomes, and decrease

risk of sudden death (21-23). Infants with BPD are at increased risk for adverse

neurodevelopmental and motor outcomes, and this risk appears to be positively correlated

with the severity of BPD (15, 24).

Given the incidence of BPD in premature infants, we recognize that performing a

PSG in all infants with BPD is resource-intensive and not feasible. The resources to

perform inpatient infant PSG is not readily available in most centers but should be

considered a helpful adjunct in individualizing therapy in particularly vulnerable patients

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 such as those with severe BPD. Available literature supports pulse oximeter is sufficient

to determine oxygen need in infants with BPD. Statements and guidelines from the

Thoracic Society of Australia and New Zealand, the American Thoracic Society (ATS),
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and the British Thoracic Society all affirm the adequacy of continuous pulse oximetry to

assess the need for and level of supplemental oxygen support (10-12). An alternative

approach to performing an inpatient infant PSG is to obtain overnight pulse oximetry data

download to assess the requirement for oxygen or to determine if the level oxygen being

provided is optimal. This strategy has its own challenges, in that oxygen titration may not

be done as accurately while the study is in process and no other data can be accurately

obtained as in a PSG. If it is not possible to obtain any concrete data as an inpatient, the

patient can be discharged on supplemental oxygen and complete the PSG study in the

outpatient setting based on need and the judgement of the treating pulmonologist. Thus, a

close follow-up with a pediatric primary care provider or pulmonologist is an important

component to a safe discharge home, regardless of whether a PSG is performed or not, in

order to monitor oxygen saturations, titrate the level of support, and provide further

management. At our institution, we use PSG to ensure adequacy of respiratory support to

this vulnerable patient population. Further, patients who continue to be followed at this

institution undergo serial PSG as per their outpatient pulmonologist. The findings allow

for individualized titration of oxygen therapy as well as a better understanding of degree

of obstructive, mixed and central apnea in this vulnerable population who is at risk of

adverse neurodevelopmental outcomes as well. This is additional information beyond

what pulse oximetry can provide and may be helpful in the management of preterm

infants with severe BPD.

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 A large multi-center cohort study found that tracheobronchomalacia is a common

finding in neonates with BPD who undergo bronchoscopy (36% of infants in the study)

and was associated with longer admissions and more complicated hospitalizations (25).
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Infants with tracheobronchomalacia often require CPAP to minimize airway collapse and

obstruction (26). We did not routinely perform or examine bronchoscopy findings (if

done) in our patient population, but it is plausible that a portion of our population likely

has tracheobronchomalacia, which may contribute to the degree of OSA that we observe

here. Additionally, studies have found evidence of upper airway remodeling in preterm

infants that may result in OSA and contribute to an increased OAHI (27, 28). While

infants with BPD may have a component of OSA, this elevated OAHI may not be solely

due to airways obstruction secondary to altered anatomy. Of note, as discussed earlier

OAHI can very well be under-estimated as almost all of the studies were titration studies.

Since the index is related to desaturations of 3% or more from baseline that occur during

both central and obstructive apneas, the score may be also an indication of the degree to

which the lungs remain immature and injured, and not entirely reflect airways obstruction

but may be a consequence of poor pulmonary reserve.

Few studies have investigated the PSG characteristics of preterm infants with

BPD. To our knowledge, there are no studies to date that have studied the results of

inpatient PSGs in preterm infants with moderate to severe BPD as young as our

population. McGrath-Morrow et al. performed a retrospective study to determine the

utility of overnight polysomnography to assess pulmonary reserve in infants with BPD.

The mean age at which the PSG was done in this group of patients was ten months, they

found that the respiratory disturbance index (RDI), defined as the number of hypopneas,

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 obstructive, mixed and central apneas per hour of total sleep time, oxygen saturation

nadir did not correlate with outpatient clinic measures of respiratory rate or oxygen

saturation. Therefore, in order to help prevent some of the long-term complications of

Accepted Article
BPD in these infants, it may provide extra benefit to the patient to complete an overnight

PSG and allow for a full assessment of oxygen needs prior to discharge home.

Underdevelopment of the lungs in premature infants leads to impaired respiratory

mechanics, which should improve over time as these infants continue to grow and

develop (29). Our median nadir SpO2 was 80%, lower than the mean nadir SpO2 of 86%

in the study by McGrath-Morrow. Our patient population was younger at the time of their

PSG (43 weeks corrected gestation age or approximately 4 months of age in our

population versus ten months of age), and therefore their lungs are likely not at the same

level of development and growth as in McGrath-Morrow’s study.

Our study is the earliest assessment to date that examines the characteristics of

inpatient PSG done prior to the initial hospital discharge of infants with BPD. It is also

the largest study to date in terms of the number of infants that were eligible for our study.

Our institution is unique in our practice of completing a relatively large number of

inpatient infant PSG prior to discharge home, which provides us with a robust number of

patients from which to collect data.

There are important limitations to note in our study. This is a retrospective study,

so we are unable to draw any conclusions of causality from our results. There is

inadvertent selection bias that exists due to retrospective nature of the study. Titration

studies have limitations and can underestimate many PSG indices as discussed above.

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 The adequacy of documentation can also impact the quality of the analysis, as evidenced

by the group of “unclassifiable” patients. This is also a descriptive study, and we did not

include premature infants without BPD as controls with which to compare our study
Accepted Article
group to. Due to the nature of being a tertiary referral center for the region and being

situated in an urban setting, our patient population may be at higher risk for respiratory

morbidity and have more severe BPD than other populations. In addition, not every infant

diagnosed with BPD was followed by a pulmonologist, which may further limit our

population to patients with more severe disease. Due to the variability in documentation

practices and in level of detail in the records received from the referring hospitals, data on

exact number of days on invasive or non-invasive ventilation was not available for some

of our patients. We did not record whether infants received post-natal steroids for

prevention of BPD. We also did not collect data on Apgar scores, oxygen dependence at

twenty-four hours of age or administration of antenatal steroids, all of which are factors

that are associated with the development of BPD but may or may not affect the severity

of sleep disordered breathing. Given that our study focused on a subset of premature

infants with moderate to severe BPD, our results may not be representative or

generalizable to all infants with BPD, and outcome data to validate our approach is

needed.

Further studies are needed to address the questions that remain from this current

study. While we have provided demographic information, general clinical descriptors,

and co-morbidities of our study population, further analysis can be done to examine for

any relationships between these parameters and PSG findings. A study that includes a

diagnostic PSG component, larger number of BPD patients and if possible control group

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 should be considered. An analysis of airway exams in this population of infants along

with correlation with PSG results may yield further insights. Long-term outcomes such as

neurodevelopmental impairment, degree of respiratory morbidities, and pulmonary

Accepted Article
function, should also be further explored.

Conclusion

Results from the largest cohort to date of inpatient PSGs in infants with BPD

show several abnormal PSG characteristics. Most infants required an alteration in the

oxygen therapy as compared to their baseline oxygen support prior to the PSG.

Performing a PSG during the index hospital admission and prior to discharge may be

helpful for individualizing and optimizing inpatient treatment and planning for a safe

discharge home. Further studies into the use of PSG in this vulnerable population are

needed. It is possible that with more available data, a set of guidelines pertaining to use of

PSG in infants with BPD may be developed.

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 Table 1: Study Population (n=127)

Gender % (n)
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Male 57% (72)

Female 43% (55)

Ethnicity

Hispanic 44.9% (57)

Non-Hispanic 44.9% (57)

Unknown 10.2% (13)

Race

Asian/Pacific Islander 4.7% (6)

African American/Black 17.3% (22)

White/Caucasian 25.2% (32)

Unknown/other/2 or more race 52.7% (67)

BPD classification

Mild 3% (4)

Moderate 14% (18)

Severe, type 1 37% (47)

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 Severe, type 2 41% (52)

Unclassifiable severe BPD 5% (6)

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Table 2. Polysomnogram and clinical characteristics comparison: severe and non-
severe BPD groups

BPD severity

Total (N=127) Non-severe Severe (n=105) P-value

(n=22)

OAHIa 5.3 (2.2, 10) 6.3 (3.6, 11.6) 4.7 (2.1, 9.8) 0.23101

CIa 3.4 (1.4, 7.2) 3.4 (1.4, 7.2) 3.4 (1.3, 7.1) 0.86841

ODIa 15.7 (4.7, 35) 26.5 (9.8, 35) 13.55 (4.1, 0.32581
33.8)

Nadir SpO2b 80 ± 8.46 79.5 ± 9.09 80.10 ± 8.46 0.76392

Hypoventilationc

No 119 (93.70) 21 (95.45) 98 (93.33) 1.0003

Yes 8 (6.30) 1 (4.55) 7 (6.67)

TIB (hour)a 5.18 (3.82, 5.76) 5.49 (4.64, 5.74) 5.16 (3.82, 0.52201
5.76)

TST (hour)a 3.16 (2.07, 3.58) 3.38 (2.2, 3.5) 3.11 (2.04, 0.44651
3.69)

Ar/Awa 22.25 ± 13.88 20.56 ± 14.94 22.60 ± 13.70 0.53222

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 aCO2b 36.56 ± 6.75 33.86 ± 5.92 37.10 ± 6.80 0.04382

pCO2b 47.94 ± 7.35 45.05 ± 8.11 48.52 ± 7.35 0.05442

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MAIa 1.15 (0.47, 2) 1.51 (0.59, 2) 1.06 (0.43, 0.58691
2.03)

OHIa 3.25 (1.41, 6.34) 5.31 (2.02, 7.94) 3.14 (1.35, 0.28871
5.77)

OAIa 1.18 (0.47, 3.34) 1.34 (0.36, 4.04) 1.01 (0.50, 0.93341
3.34)

GA (week)b 27.04 ± 3.25 27.79 ± 3.64 26.88 ± 3.16 0.23692

BW (kg)ad 0.76 (0.64, 1.05) 0.81 (0.67, 1.38) 0.76 (0.63, 0.15851
1.03)

RRb 56.98 ± 12.92 56.45 ± 15.71 57.10 ± 12.35 0.83352

HRa 148 (137, 156) 148 (137, 153) 148 (138, 157) 0.24601

D-Intuba 41 (14, 67) 22 (6, 46) 43 (18, 71) 0.00821

PHTNC

No 104 (81.89) 18 (81.82) 86 (81.90) 1.0003

Yes 23 (18.11) 4 (18.18) 19 (18.10)

Refluxc

No 65 (51.18) 10 (45.45) 55 (52.38) 0.5554

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 Yes 62 (48.82) 12 (54.55) 50 (47.62)

Hb (g/dL)bc 10.83 ± 1.33 10.40 ± 1.41 10.91 ± 1.30 0.10212

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CGA-PSGb 43.60 ± 5.33 41.84 ± 4.84 43.97 ± 5.38 0.08852

CGA-DCa 45.29 (41.43, 43.64 (40.29, 45.86 (42.43, 0.06191

50) 47.14) 50.57)

a
Median (Interquartile range); bMean ± SD; cFrequency (Percentage) c Hemoglobin data not available for
three patients (CBC not done during admission); dBW not documented for two patients
1
Mann-Whitney Ranksum Test; 2Two-sample T-test; 3Fisher’s Exact Test; 4Chi-Square Test

Table 3.

Gestational age and corrected gestation age in relation to CIa

% change 95% CI P-value

Gestational age (GA) -3.17 (-9.88, 4.05) 0.380

Corrected gestational age -3.60 (-7.86, 0.85) 0.112

(CGA)

The effect of days of intubation on OAI, OAHI, and MAI univariatelya

% Change 95% CI P

OAI -0.22 (-1.24, 0.81) 0.680

MAI -0.28 (-0.99, 0.43) 0.440

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 AHI -0.26 (-0.69, 0.17) 0.234
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The effect of reflux on OAI, OAHI, and MAI univariatelya

% Change 95% CI P

OAI -31.49 (-64.54, 32.33) 0.260

MAI -27.50 (-54.94, 16.64) 0.185

AHI -23.96 (-43.62, 2.54) 0.073

a
Univariate generalized linear model based on gamma distribution

Table 4. Adjustments to oxygen support based on sleep study results and discharge
planning

% (n)

Required adjustment of supplemental oxygen 69% (95)

- Room air to supplemental oxygen - 20% (19)

- Supplemental oxygen to room air
- Required increase in oxygen support* - 2% (2)
- Required decrease in oxygen support*
- 55% (52)

- 45% (43)

Discharge home with oxygen 98% (134)

*from baseline prior to sleep study, based on sleep study recommendations

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