Polysomnography in infants with clinical suspicion of sleep-related breathing disorders

Abstract

Study Objectives:

Limited data exist concerning the indications, parameters, utility of daytime polysomnography, and treatment of infants with suspected sleep-related breathing disorders.

Methods:

We retrospectively reviewed all polysomnography undertaken in a quaternary pediatric hospital for term infants up to 6 months of age between January 2017 and December 2019. Outcomes were evaluated, including a comparison among diagnostic groups.

Results:

Of 161 infants (58% male), 77 (48%) were ≤ 2 months old, and 103 (61%) were referred for either craniofacial abnormalities or an airway malformation. Daytime (n = 100) vs nighttime (n = 61) studies showed no differences in sleep architecture or treatment rates. Apnea-hypopnea index was > 10 events/h in 137 (85%) and was similar across different diagnostic groups, and 97 (78%) were prescribed noninvasive ventilation, with a mean treatment duration of 13.4 ± 9 months. Of the infants who were commenced on noninvasive ventilation 75% did not require it beyond 24 months.

Conclusions:

Polysomnographic sleep parameters and the number of treatments prescribed were equivalent whether the polysomnography was performed during daytime or nighttime. Treatment with noninvasive ventilation was required in the short term for most infants with sleep-related breathing disorders, regardless of the indication for referral.

Citation:

Singh J, Yeoh E, Castro C, Uy C, Waters K. Polysomnography in infants with clinical suspicion of sleep-related breathing disorders. J Clin Sleep Med. 2022;18(12):2803–2812.

BRIEF SUMMARY

Current Knowledge/Study Rationale: Few studies describe the clinical course for infants with sleep-related breathing disorders. This study is the first to evaluate a diverse population of high-risk infants ≤ 6 months of age undergoing polysomnographic studies for suspected sleep-related breathing disorders.

Study Impact: This study demonstrated the equivalence of daytime vs night polysomnography in young infants and the short-term nature of noninvasive ventilation therapy for most infants regardless of their underlying condition. It supports the use of daytime polysomnography which may provide earlier diagnostic access and treatment for young infants in institutions where the availability of nighttime studies may be limited.

INTRODUCTION

Sleep-related breathing disorders (SRBD)¹ can occur in children of all ages, including infants. In older children, sequelae of SRBD include adverse effects on growth, development, and behavior.^2–5 Studies evaluating the natural course and prognosis for SRBD in infancy, including treatment outcomes, remain limited.²

Polysomnography (PSG) in infants is an important and evolving field of study that was originally attempted to identify risks for sudden infant death syndrome.^6,7 Normative data that evaluated healthy infants have been established to guide research into PSG performed during infancy.^8–11 Additionally, the American Academy of Sleep Medicine recently updated the scoring guidelines for sleep studies of infants aged 0–2 months to standardize testing and reporting and, thus, has provided a framework for research into this area.^12,13

At present, studies on PSG largely describe separate groups of infants with specific comorbidities.^14–17 Additionally, there is a paucity of studies on the utility of daytime studies in infants in contrast to the better-established nighttime studies.

To address the limited data on PSG in infants with suspected SRBD, the spectrum of comorbidities of infants, outcomes of PSG, treatment, and prognoses, we designed this study to evaluate (1) the clinical indications for PSG referral and their corresponding PSG results, (2) the parameters of daytime vs nighttime studies, and (3) the number of infants who required treatment, types of treatments prescribed following the PSG, and the duration of the requirement for noninvasive ventilation (NIV).

METHODS

This retrospective longitudinal study was approved by the ethics committee of the Sydney Children’s Hospital Network (2019/ETH00036). The electronic medical records of all infants ≤ 6 months corrected gestational age, referred to the David Read Sleep Laboratory in the Children’s Hospital at Westmead for PSG from January 2017 to December 2019, were reviewed. Data obtained from the electronic medical records included age during which a PSG was performed, underlying diagnosis, and initial and follow-up PSG results.

All PSG were conducted using Compumedics Grael PSG (Melbourne, Australia) and studies were scored on the Profusion 4.5 software (Compumedics, Melbourne Australia). The PSG included 10-leads recording electroencephalogram, electrooculography, electrocardiogram, submental electromyogram, with respiratory outcomes measured using nasal airflow (pressure), oro-nasal thermistor, pulse oximetry, transcutaneous CO₂ (tcCO₂) with respiratory effort determined using thoracic and abdominal plethysmography bands, and surface electromyogram of the diaphragm and abdominal muscles. Sleep studies were scored using the American Academy of Sleep Medicine scoring criteria (< 2 months of age scoring criteria) for all infants to capture indeterminate sleep that may persist in infants beyond 2 months of age.¹²

PSG features and results analyzed included: day or night-time study, total sleep time (TST), sleep efficiency, arousal index (the number of arousals ×60/TST), sleep architecture, rapid eye movement (REM), nonrapid eye movement (NREM), and indeterminate stages of sleep, baseline oxygen and carbon dioxide levels, maximum tcCO₂ during REM and NREM sleep, saturation nadir, oxygen desaturation index (the number of oxygen desaturations ≥ 3% ×60/TST), apnea-hypopnea index (AHI; the number of obstructive apneas and hypopnea ×60/TST), obstructive apnea-hypopnea Index (OAHI; the number of obstructive apneas, mixed apneas and obstructive hypopneas ×60/TST) and central apnea index (CAI; the number of central apnea ×60/TST).¹⁸

Comparisons (unpaired) were made between daytime vs nighttime studies. Four age groups were defined: < 6 weeks, 6 weeks to 2 months, 2–4 months, and 4–6 months. Comorbidities were grouped into 6 categories according to the primary abnormality noted by the pediatric sleep physician requesting the study as follows: craniofacial abnormalities, neurological conditions, premature infants (< 36 weeks) with a history of apnea of prematurity or bronchopulmonary dysplasia (prematurity),¹⁹ airway or lung malformations, infants with witnessed apnea or brief resolved unexplained event (BRUE), and infants with cardiac conditions. Features of PSG in these different groups were compared.

Interventions that followed PSG were categorized to include: no treatment, initiation of NIV in the form of continuous positive airway pressure (CPAP) or bilevel positive airway pressure, home oxygen, caffeine, surgical intervention, or home monitoring (SmartMonitor 2; Circadiance, Pittsburgh, PA) alone. Growth parameters (weight-for-length percentile) and the duration of treatment, when prescribed, were also reviewed.

Statistical calculations were performed using SPSS Statistic Data Editor (IBM 2020 Build 1.0.0.1406) and presented as mean ± standard deviation. Chi-square test (categorical variables comparison) and one-way analysis of variance (continuous variables comparison) were applied. Statistical comparison of respiratory parameters in different age groups was controlled for the underlying condition using analysis of variance. Statistical significance was accepted at P < .05.

RESULTS

Infant characteristics

A total of 161 infants underwent PSG during the study period (Figure 1). Most infants were referred for craniofacial abnormalities (n = 61, 38%) with Pierre-Robin sequence being the most common abnormality (n = 27, 44%). Infants with airway or lung malformation were the second largest group (n = 42, 26%) with laryngomalacia being the most common indication for referral within this group (n = 17, 40%). In the group of infants who presented with witnessed apnea or BRUE (n = 28, 17%), 1 infant underwent a PSG for a family history of sudden infant death syndrome while the rest were referred for BRUE or witnessed apneas. These infants were otherwise healthy without any clinical suspicion of a structural, syndromic, or neurological cause. Infants referred for neurological reasons (n = 13, 8%) included those with Arnold-Chiari malformation, brainstem abnormalities, spinal muscular atrophy, and hypoventilation. Ten (6%) infants in the cardiac condition group were referred for congenital heart diseases, including infants with patent ductus arteriosus, and septal defects. There were seven (4%) infants who were referred for a history of apnea of prematurity or bronchopulmonary dysplasia with gestational age ranging between 25 and 32 weeks. Infants from this group underwent PSG between 38 to 41 weeks of corrected gestational age (Figure 1).

Figure 1. Infants undergoing PSG grouped based on the clinical indications for the initial referral.

BRUE = brief resolved unexplained event, PSG = infant polysomnography.

The mean age of infants undergoing PSG was 10 ± 7 weeks. Distribution among the 4 age categories were 56 (34%) < 6 weeks, 21 (13%) 6 weeks to 2 months, 55 (34%) age 2–4 months, and 29 (17.9%) age 4–6 months (P = .30). Infants with a history of witnessed apnea or BRUE underwent their first PSG at 12.22 ± 7.44 weeks of age, while those who were premature underwent their first PSG at 1.01 ± 1.9 weeks of corrected gestational age (P = .35) (Table 1). A total of 152 (94.4%) infants were studied completely in the supine position.

Table 1.

Changes in sleep study parameters according to overall cohort, daytime vs nighttime study, and 4 age groups.

	Overall	Type of Study			Age Group
	Mean ± SD	Daytime (n = 100)	Nighttime (n = 61)	P	Under 6 weeks (n = 56)	6 weeks to 2 months (n = 21)	2 to 4 months (n = 55)	4 to 6 months (n = 29)	P
		Mean ± SD	Mean ± SD		Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD
Sleep Characteristics
Total sleep time (minutes)	297 ± 107	238 ± 63	393 ± 93	< 0.001	255 ± 83	294 ± 104	301 ± 107	355 ± 107	< 0.001
Sleep efficiency (%)	70.7 ± 11.9	67.7 ± 11.2	75.8 ± 11.5	< 0.001	68.3 ± 11.3	73.9 ± 11.1	69.5 ± 12.6	75.7 ± 10.4	0.919
Onset latency (minutes)	9.9 ± 19.2	8.3 ± 16.1	12.4 ± 23.3	0.884	9.8 ± 18.6	3.8 ± 7.8	15.1 ± 25.3	4.9 ± 7.4	0.048
Total arousal index (events/h)	21.1 ± 7.3	21.9 ± 7.2	19.8 ± 7.4	0.525	21.8 ± 6.7	20.8 ± 8.8	20.3 ± 7.5	21.5 ± 6.9	0.919
Sleep Stages
Active/REM sleep (%)	46.1 ± 11.8	45.5 ± 10.3	46.9 ± 13.8	0.466	44.8 ± 10.7	43.2 ± 9.1	45.5 ± 11.1	51.6 ± 15.1	0.440
Quiet/NREM sleep (%)	44.7 ± 10.6	44.1 ± 10.4	44.8 ± 10.9	0.928	44.9 ± 10.6	49.2 ± 9.3	44.8 ± 9.8	39.9 ± 11.9	0 .043
Indeterminate sleep (%)	11.1 ± 12.1	11.1 ± 12.6	9.9 ± 11.2	0.369	11.4 ± 12.5	11.0 ± 15.7	11.9 ± 9.9	8.9 ± 12.6	0.836
Oximetry Parameters
Baseline saturation (%)	97 ± 2	97 ± 2	96 ± 3	0.081	97 ± 2	97 ± 2	96 ± 3	97 ± 2	0.366
Saturation nadir (%)	85 ± 9	86 ± 9	82 ± 10	0.23	89 ± 5	81 ± 18	84 ± 7	84 ± 8	0.079
Desaturation index	14.5 ± 14.2	12 ± 11	18 ± 18	0.016	8.3 ± 8.5	14.8 ± 10.2	17.8 ± 15.4	19.4 ± 19.4	*0.47
Carbon Dioxide Parameters
Baseline tcCO2 (mm Hg)	44.6 ± 6.7	43.8 ± 6.7	45.9 ± 6.4	0.047	43.3 ± 5.16	44.5 ± 4.0	45.6 ± 5.6	46.8 ± 6.6	0.98
Maximum tcCO2 (mm Hg)	52.4 ± 7.4	51.7 ± 6.8	53.6 ± 8.14	0.115	49.9 ± 5.3	53.5 ± 7.1	53.1 ± 8.1	54.8 ± 8.5	0.419
Mean tcCO2 in active sleep (mm Hg)	44.3 ± 5.9	43.2 ± 4.5	46.0 ± 7.4	0.007	42.5 ± 4.5	43.9 ± 4.1	45.4 ± 6.7	46.3 ± 7.4	0.134
Mean tcCO2 in quiet sleep (mm Hg)	45.1 ± 5.7	44.1 ± 4.5	46.8 ± 6.9	0.007	43.5 ± 5.3	44.6 ± 4.6	46.0 ± 5.7	47.2 ± 6.6	0.431
Mean tcCO2 in indeterminate sleep (mm Hg)	44.7 ± 5.6	43.6 ± 4.5	46.6 ± 6.5	0.005	42.8 ± 4.1	44.4 ± 4.1	46.2 ± 6.4	46.4 ± 6.4	0.723
Apnea-hypopnea index (events/h)	29.9 ± 25.6	27.7 ± 24.9	33.5 ± 26.6	0.161	27.1 ± 24.1	22.2 ± 17.6	32.8 ± 26.4	35.5 ± 30.7	0.267
Obstructive apnea- hypopnea index (events/h)	21.8 ± 24	19.9 ± 23.6	24.8 ± 24.7	0.223	19.3 ± 24.3	16.3 ± 15.8	23.5 ± 24.4	27.1 ± 27.3	0.001
Central apnea index	7.87 ± 7.6	8.5 ± 8.4	6.7 ± 6.4	0.094	9.5 ± 9.0	7.7 ± 7.4	7.9 ± 7.0	5.3 ± 4.8	0.32

NREM = non-REM, REM = rapid eye movement, tcCO₂ = transcutaneous carbon dioxide, SD = standard deviation.

Overall sleep study results

The mean TST of the 161 infants undergoing PSG was 297 ± 107 minutes with an average sleep efficiency of 70.7 ± 11.9%. For the entire cohort, the distribution of sleep stages was: 46.1 ± 11.1% REM sleep, 44.6 ± 10.6% NREM, and 11.1 ± 12.1% indeterminate sleep. Baseline saturation was 97 ± 2% with a saturation nadir of 85 ± 9% and a desaturation index of 14.5 ± 14.2 events/h. Twenty-nine (18.2%) infants had a baseline saturation of < 95% and 6 (3.8%) below 90%. Baseline tcCO₂ was 44.6 ± 6.7 mm Hg with a maximum tcCO₂ of 52.4 ± 7.4 mm Hg. Sixty-five (40%) infants had a baseline tcCO₂ above 45 mm Hg, and 17 (11%) exceeded 50 mm Hg.

There were 92 (57%) infants who had periods of tcCO₂ above 50 mm Hg, with a mean percentage of TST spent with tcCO2 > 50 mm Hg/TST of 11.7 ± 2.1% (range 0.1%–97.8%). Differences among the diagnostic groupings were not significant: craniofacial abnormalities, 12.22 ± 3.9%; neurological conditions, 15.33 ± 8.3%; prematurity, 1.47 ± 1.2%; infants with airway malformations, 15.81 ± 4.9%; infants with a history of apnea or BRUE, 11.93 ± 6.4%; and cardiac conditions, 6.73 ± 2.9% (P = .55).

Total AHI was 29.9 ± 25.6 events/h with an OAHI of 21.8 ± 24 events/h and central apnea index of 7.87 ± 7.6 events/h (Table 1).

Analysis of the PSG parameters performed based on the 4 age groups showed that sleep was longer and more efficient in infants > 4 months. Sleep onset latency was longest in infants between 2 and 4 months at 15 ± 25 minutes (P = .05), % REM was highest in infants age 4–6 months at 51 ± 15.1% (P = .44), % NREM was longest in infants < 4 months at 44%–49% (P = .04) (Table 1).

Desaturation index, saturation nadir, and baseline saturations were worse in infants first studied at an older age. Among other respiratory parameters, the only difference of significance was higher obstructive apnea-hypopnea indices in older infants.

Baseline tcCO₂ for infants < 6 weeks was 43 ± 5.2 mm Hg vs 46.8 ± 6.6 mm Hg for infants 4–6 months (P = .37). Maximum tcCO₂ for infants < 6 weeks was 49.9 ± 5 mm Hg vs 54 ± 8.4 mm Hg for infants 4–6 months (P = .42). Similar patterns were also seen for tcCO₂ levels during specific sleep stages (REM, NREM, and indeterminate) (Table 1).

Mean AHI was 27.1 ± 24.1 events/h for infants < 6 weeks vs 35.5 ± 30.7 events/h for infants 4– 6 months (P = .27). Obstructive apnea-hypopnea index was 19.3 ± 24.3 events/h for infants < 6 weeks vs 27.1 ± 27.3 events/h for infants 4–6 months (P = .001). Central apnea index was 9.5 ± 9.0 events/h for infants < 6 weeks vs 5.3 ± 4.8 events/h for infants 4–6 months old (P = .32).

Analysis performed based on the different clinical categories demonstrated that infants in the craniofacial group had the highest AHI value of 34.9 ± 28 events/h, while those who presented with apnea, BRUE, or had a risk of sudden infant death syndrome demonstrated the lowest AHI values of 21.5 ± 13.7 events/h (P = .24) (Table 2).

Table 2.

Changes in sleep parameters according to clinical grouping.

	Diagnostic Group
	Craniofacial (n = 61)	Neurological (n = 13)	Prematurity (n = 7)	Airway or Lung Malformation (n = 42)	Apnea/BRUE (n = 28)	Cardiac Conditions (n = 10)
	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD
Age (in weeks)	10.92 ± 7.89	8.68 ± 6.55	*1.01 ± 1.9	9.72 ± 6.14	12.22 ± 7.44	9.02 ± 5.67
Sleep Characteristics
Total sleep time (minutes)	280 ± 94	271 ± 92	247 ± 94	324 ± 123	321 ± 120	284 ± 72
Sleep efficiency (%)	67.1 ± 12.0	67.3 ± 14.1	71.3 ± 8.3	74.8 ± 12.2	73.3 ± 10.6	72.8 ± 6.2
Onset latency (minutes)	9.9 ± 2.8	3.5 ± 1.9	6.3 ± 3.7	12.7 ± 3.3	10.7 ± 3.9	5.9 ± 2.0
Total arousal index (events/h)	21.7 ± 7.3	20.2 ± 8.7	23.8 ± 8.9	19.8 ± 7.1	21.2 ± 5.9	22.2 ± 8.9
Sleep Stages
Active/REM sleep (%)	47.3 ± 14.5	47.8 ± 7.5	47.8 ± 8.9	43.6 ± 10.2	44.7 ± 9.4	49.8 ± 10.2
Quiet/NREM sleep (%)	45.7 ± 11.4	45.2 ± 7.5	40.1 ± 11.2	42.7 ± 11.5	46.9 ± 8.2	45.2 ± 9.1
Indeterminate sleep (%)	8.8 ± 8.7	6.5 ± 4.9	15.9 ± 13.3	18 ± 17.6	8.4 ± 5.0	6.7 ± 2.4
Oximetry parameters
Baseline saturation (%)	97 ± 2	97 ± 3	97 ± 2	97 ± 2	97 ± 2	95 ± 4
Saturation nadir (%)	85 ± 8	85 ± 7	76 ± 25	87 ± 8	86 ± 6	85 ± 8
Desaturation index	15.2 ± 14.9	13 ± 13	13.2 ± 11.8	12.9 ± 12.6	15.1 ± 12.5	22.6 ± 18.9
Carbon Dioxide Parameters
Baseline tcCO2 (mm Hg)	44.8 ± 5.3	42.9 ± 5.7	43.1 ± 5.6	45.4 ± 4.3	45.3 ± 8.5	45.4 ± 2.9
Maximum tcCO2 (mm Hg)	53.3 ± 7.2	50.4 ± 7.5	51.9 ± 9.1	52.0 ± 6.4	52.3 ± 10.0	51.9 ± 4.0
Mean tcCO2 in active sleep (mm Hg)	44.2 ± 5.7	42.5 ± 6.3	43.0 ± 5.8	45.6 ± 4.1	45.2 ± 7.9	45.2 ± 2.6
Mean tcCO2 in quiet sleep (mm Hg)	44.7 ± 5.4	43.9 ± 6.2	43.5 ± 5.6	45.6 ± 4.1	45.2 ± 7.9	48.1 ± 6.8
Mean tcCO2 in indeterminate sleep (mm Hg)	44.7 ± 5.5	44.0 ± 6.3	43.7 ± 6.1	45.0 ± 4.4	45.0 ± 7.9	45.2 ± 2.6
Apnea-hypopnea index (events/h)	34.9 ± 28.0	26.5 ± 19.4	25.3 ± 15.2	30.4 ± 30.0	21.5 ± 13.7	28.5 ± 21.7
Obstructive apnea- hypopnea index (events/h)	28.8 ± 25.7	15 ± 13.9	15.0 ± 12.2	23.7 ± 22.6	11.4 ± 8.3	23.7 ± 21.6
Central apnea index	6.1 ± 5.8	11.3 ± 11.0	10.3 ± 14.1	7.1 ± 6.5	10.4 ± 10.0	4.5 ± 2.3

BRUE = brief resolved unexplained event, CLD = chronic lung disease, NREM = non-REM, REM = rapid eye movement, SD = standard deviation, tcCO₂ = transcutaneous carbon dioxide.

All 161 infants demonstrated mild to severe OSA (AHI > 1 event/h). The distribution of OSA severity was 9 (5.6%) with mild (AHI 1–5 events/h), 16 (9.9%) moderate (AHI 5–10 events/h), and 136 (84%) had severe OSA (AHI > 10 events/h). Severe OSA was demonstrated most frequently in the craniofacial abnormality group (n = 51, 37.5%) followed by infants in the airway or lung malformation group (n = 34, 25%) (P = .59).

Daytime and nighttime studies

One-hundred infants underwent daytime studies and 61, nighttime studies. This included 23 (23%) daytime studies and 15 (24%) nighttime studies with both diagnostic and NIV titration components (Figure 1). Infants who underwent daytime studies were 8.3 ± 6.6 weeks of age, while those who underwent nighttime studies had a mean age of 13.9 ± 6.2 weeks (Figure 2).

Figure 2. Number of infants undergoing polysomnography based on age group and daytime or nighttime studies.

`The majority of daytime studies were performed in infants with craniofacial abnormalities (n = 44, 44%), followed by airway or lung malformation (n = 20, 20%), history of witnessed apnea or BRUE (n = 17, 17%), cardiac conditions (n = 7, 7%), and neurological conditions and prematurity (n = 6, 6%). The majority of nighttime studies were performed in infants with airway and lung malformation (n = 22, 36.1%), followed by craniofacial abnormalities (n = 17, 27.9%), history of apnea/BRUE (n = 11, 18%), neurological conditions (n = 7, 11.5%), cardiac conditions (n = 3, 4.9%), and prematurity (n = 1, 1.6%) (Figure 3 and Figure 4).

Figure 3. AHI based on clinical grouping comparing daytime vs nighttime studies.

AHI = apnea-hypopnea index, BRUE = brief resolved unexplained event.

Figure 4. Prevalence of severe sleep-related breathing disorder (AHI, apnea-hypopnea index exceeding 10 events/h) based on the diagnostic grouping comparing daytime (D) vs nighttime studies (N).

BRUE = brief resolved unexplained event, SIDS = sudden infant death syndrome.

Treatment

Of the infants studied, 124 (77%) were prescribed treatment following the initial PSG. Seventy-eight (78%) of infants who underwent daytime studies were prescribed treatment, while 46 (75%) of infants who underwent nighttime studies were prescribed treatment. In terms of the number of infants prescribed treatment, no difference was seen between infants undergoing either daytime or nighttime studies (P = .91) (Figure 4).

Out of the 124 infants who were prescribed treatments, 97 (78%) were prescribed with NIV support, 90 (72%) required CPAP, and 7 (6%) required bilevel positive airway pressure. Other treatment groups were: 8 (4.9%) infants who were commenced on oxygen, 5 (3.1%) who underwent surgery, 4 (2.5%) were prescribed caffeine, and 10 (6.2%) were commenced at-home cardiorespiratory monitoring (SmartMonitor 2).

In terms of treatment in the different age groups, 43 (77%) infants < 6 weeks, 17 (81%) 6 weeks to 2 months, 42 (76%) 2–4 months, and 22 (75%) 4–6 months were prescribed treatment.

Most treatments were prescribed to children with craniofacial abnormalities (n = 53, 42.7%) and those with airway or lung malformation (n = 30, 24.2%) followed by infants with a history of witnessed apnea or BRUE (n = 17, 13.7%), neurological conditions (n = 10, 8.1%), cardiac conditions (n = 8, 6.5%), and prematurity (n = 6, 4.8%) (P = .11).

Repeat PSG and treatment outcomes

One-hundred and eight (68%) infants had at least 1 follow-up PSG (range 1–3 studies, 3–32 months apart). For this subgroup with follow-up studies, the diagnostic component of AHI scores was reviewed. Diagnostic AHI values demonstrated a nonsignificant trend that was 74% lower at follow-up PSG (initial study 29.9 ± 25.6 events/h vs follow-up study 7.9 ± 7.6 events/h in the overall cohort) (P = .19). This decline in AHI values was comparable regardless of the age at first study: < 6 weeks, 71% (27.1 ± 24.1 vs 7.9 ± 7.1 events/h for initial vs follow-up); at 6–8 weeks, 62% improvement (22.2 ± 17.6 vs 8.4 ± 7 events/h, initial vs follow-up); at 2–4 months, 77% improvement, (32.8 ± 26 vs 7.5 ± 5.8 events/h; initial vs follow-up); and at 4–6 months, 35.5 ± 30.7 vs 8.6 ± 11.3 events/h (initial vs follow-up) (P = .25).

The mean weight-for-length of the infants who were prescribed treatment was on the 22.12 ± 21.45 percentile at baseline, increasing to 53.57 ± 29.06 percentile at their follow-up study (P < .001). The weight-for-length of the infants who did not require treatment was on the 45.25 ± 29.82 percentile at baseline, increasing to 48.89 ± 31.42 percentile at their follow-up study (P = .45). Among the diagnostic groups, in terms of infants who received treatment, those with cardiac issues had the highest increase in weight-for-length parameters (48.01 ± 26.95 percentile) followed by craniofacial (32.99 ± 25.26 percentile), neurology (30.18 ± 22.51 percentile), airway (26.73 ± 25.49 percentile), premature infants (21.68 ± 15.65 percentile), and apnea or BRUE (19.64 ± 24.88 percentile).

Infants who required treatment following a repeat PSG (n = 32, 25%) included 22 (69%) infants who continued the same prescribed modality and pressure, 7 (22%) who required an increase in pressure, and 3 (9%) who required lower NIV pressures. Of the infants who required a continuation of treatment, 16 (25%) were from the craniofacial group (Pierre-Robin syndrome and micro- or retrognathia alone), 10 (31%) from the airway and lung malformation group (laryngomalacia, congenital diaphragmatic hernia), 2 (6%) each from the apnea or BRUE and infants with cardiac conditions, and 1 (3%) each from infants born prematurely or those with a neurological condition (spinal muscular atrophy).

The overall mean duration of treatment was 13.4 ± 9 months, while according to the diagnostic groupings: craniofacial abnormalities, 16.1 ± 8.2 months; neurological conditions, 19 ± 13.7 months; prematurity, 12.6 ± 8.2 months; infants with airway malformations, 11.3 ± 9.4 months; and infants with a history of apnea or BRUE, 15.3 ± 9.2 months (P = .35).

DISCUSSION

To our knowledge, this is the largest study evaluating a diverse population of infants with suspected SRBD undergoing PSG, the differences between daytime and nighttime study, and the treatment provided. Our study builds on growing data and interest in infants undergoing PSG.^20,21 The majority of the available literature focuses on individual conditions, whereas our cohort included groups with a variety of pathologies, evaluated parameters of PSG, the differences in sleep and respiratory parameters among infants of different age groups and conditions, and daytime vs nighttime studies.³

In terms of the etiology of SRBD, it has been reported that craniofacial abnormalities are the most common underlying cause of obstructive sleep apnea,²² as they are frequently associated with anatomic features such as nasal obstruction, micrognathia, anomalies of the cranial base, maxillary or mandibular hypoplasia, crowded oropharynx, or macroglossia. Such abnormalities predispose these infants to upper airway compromise, as evidenced by the high frequency of SRBD in several syndromes with craniofacial involvement, including almost 50% of children with Apert, Crouzon, or Pfeiffer syndromes, during the first 6 years of life,^23,24 or those with Treacher Collins or Goldenhar syndromes.²⁵ We found that in addition to craniofacial abnormalities, airway or lung malformations form a substantial group of infants referred for PSG and subsequently diagnosed with SRBD. Together, infants referred for cranial, facial, and airway malformation form almost two-thirds of infants who undergo PSG and, by extension, were diagnosed with and required treatment for SRBD.

Despite the high prevalence of SRBD and different clinical pathologies in this study group, we found that many sleep parameters were within those reported for healthy infants. The sleep data obtained were equivalent to published norms, suggesting that most infants maintain their sleep architecture despite the presence of significant SRBD. Although infants < 6 weeks had longer mean TST (300 minutes) compared to 260 minutes in a healthy infant cohort, sleep efficiency was similar (70.7% vs 71.9%) and the proportions of REM, NREM, and indeterminate sleep stages were comparable.¹¹ Our infants had a mean percentage of TST in REM of 46.1%, NREM of 44.7%, and indeterminate phase of 11.1% compared to 40.6%, 43.3%, and 16.1% in the healthy infant cohort.¹¹ The TST was lower in the older infants in our cohort, consistent with longitudinal studies.²⁶ Unsurprisingly, we found a higher total arousal index in our cohort of infants with suspected SRBD compared to data published on normal infants (21.1 events vs 14.7 events).¹¹

The mean tcCO₂ level in our cohort was 9.2 mm Hg higher than the value published for normal infants (44.6 vs 35.4 mm Hg). The tendency for gas exchange and respiratory abnormalities to become more pronounced in older infants also contrasts with data from normal infants.²⁷ These abnormal tcCO₂ and desaturation events correlated with higher arousal indices and have the theoretical potential for contributing to sequelae such as blunting of ventilatory responses and contributing to life-threatening apnea.²⁸ By demonstrating that the respiratory variables in our cohort were markedly different from the published normal values,^9,10,29 we infer that (1) infants referred based on clinical suspicion of SRBD in a tertiary center are likely to show abnormalities in their PSG and (2) worsening gas exchange in older infants who underwent PSG suggests that early polysomnography can be a valuable tool in the diagnosis of SRBD in very young infants.

To provide earlier access to PSG in infants with suspected SRBD, our institution has implemented daytime sleep studies for infants particularly infants under 2 months who may not yet have an established circadian rhythm.³⁰ Daytime PSG testing permits more rapid access to diagnostic facilities in an age group for which the studies are time-critical, and when the long wait times for nighttime studies may lead to significant delays in diagnosis and treatment implementation. The protocol for daytime studies uses a minimum of 6 hours of study time and allows us to expedite the studies for these very young infants. It has allowed us to perform bedside, portable PSG testing of these high-risk infants in the neonatal intensive care unit environment instead of transferring them to our sleep unit. In our study, a majority of infants undergoing daytime sleep study were under the age of 2 months with a small proportion of infants between 2 and 4 months. Despite the younger age of the infants in this study, we found no difference between daytime and nighttime PSG in terms of sleep architecture and the ability to detect SRBD. This contrasts with older children described in the literature undergoing a 1-hour daytime nap study where analysis demonstrated poor sensitivity and specificity for detecting SRBD.^31,32

The differences in oxygen desaturation index and baseline tcCO₂ levels between daytime and nighttime studies may suggest that daytime studies are less sensitive compared to nighttime studies. However, differences in respiratory parameters could be explained by other factors such as the age of the infants and underlying pathologies in the 2 groups. Equivalency of the daytime and nighttime testing was supported by the lack of difference in sleep parameters, and that an equivalent proportion of infants were treated between the 2 study types (78% requiring treatment in those who were studied using daytime PSG vs 75% in those who were studied using nighttime studies).

In terms of severity of AHI and OAHI, we found no statistical difference between age groups or clinical pathologies, regardless of whether they included structural or nonstructural disorders or whether infants underwent daytime or nighttime studies. Interestingly, we did not find any significant difference in terms of infants in different diagnostic groups requiring treatment. Based on a clinical suspicion of a pediatric sleep physician, 4 out of 5 infants undergoing a PSG required treatment whether the study was performed during the day or night. We suggest that an infant’s requirement for treatment relates strongly to characteristics detectable on clinical evaluation.

In terms of treatment duration, existing pediatric studies report a wide range of treatment duration from 1 month to 5 years.^33–36 Bedi et al reported that 13 (72%) of 18 airway studies reported improvements in respiratory parameters, yet the only study with longitudinal, diagnostic PSG data included only 3 infants.³ The mean duration of therapy in our larger cohort was 13 months with only 25% of infants requiring treatment beyond this. Half of the infants who required treatment beyond the duration of the study had either craniofacial or airway and lung malformations, particularly Pierre Robin sequence, or laryngomalacia. Admittedly, the shorter duration of treatment may be influenced by intolerance to therapy. We found that infants with SRDB who required treatment had a trend toward a lower weight at baseline and a larger increase in weight at their follow-up studies, suggesting another potential benefit from NIV treatment in infants with SRDB. These outcomes of the average duration, the conditions of persistent treatment, and improved weight trend will permit a more informed discussion of the prognosis with the families of affected infants.

The limitations of this study include: (1) its retrospective nature and therefore susceptibility to all the inherent flaws of a retrospective study, (2) all infants who underwent PSG were already prescreened clinically by a pediatric sleep physician making the data subject to selection bias and consequently skewed toward a high number of infants with abnormal PSG results, (3) the comparison of daytime vs nighttime studies was not paired during the analysis, (4) when assessing therapy, we did not record compliance and tolerance of NIV or other prescribed therapies, and (5) the timing of follow-up studies was not standardized and depended on the infant tolerance, clinical indications, and physician preference.

Our study has raised multiple questions warranting future research in this understudied area, including (1) performance of crossover studies in infants to compare daytime vs nighttime studies to confirm equivalency of the 2 methods, (2) assessment of growth and development in infants who have been diagnosed with SRDB in the first 5 years of life and whether treatment affects growth trajectories, and (3) the prevalence of SRDB in infants and whether SRDB in infants is self-limiting and resolving.³⁷ Evaluation of these outcomes would require prospective studies with a larger cohort or multicentered studies targeting infants with SRDB.

In conclusion, this study provides data that supports the usefulness of daytime PSG to identify SRBD and provide earlier diagnostic access and treatment for young infants. In a specialist pediatric center: (1) the majority of PSG undertaken for suspicion of SRBD will have abnormal results that require treatment intervention, (2) both daytime vs nighttime studies were able to identify SRBD in infancy, (3) treatment was required for a relatively short period for most infants diagnosed with SRBD, regardless of the indication for referral.

DISCLOSURE STATEMENT

All authors have reviewed and approved the manuscript for submission. This study was performed in the Children’s Hospital at Westmead, Sydney, Australia. The authors report no conflicts of interest.

ABBREVIATIONS

BRUE

brief resolved unexplained event

CPAP

continuous positive airway pressure

NIV

noninvasive ventilation

NREM

non–rapid eye movement

OAHI

obstructive apnea-hypopnea index

PSG

polysomnography

REM

rapid eye movement

SRBD

sleep-related breathing disorders

TcCO₂

transcutaneous CO₂

TST

total sleep time