Mandibular advancement appliances for sleep-disordered breathing in children: A randomized crossover clinical trial

Abstract

Objective

To test the short-term effectiveness of a mandibular advancement splint (MAS) for the management of sleep-disordered breathing (SDB) in children.

Methods

Eighteen SDB children were enrolled in a crossover randomized clinical trial and assigned to a treatment sequence starting either with an Active or a Sham MAS. Each appliance was worn for three weeks and treatment periods were separated by a two-week washout. Home-based polysomnographic data were collected before and after each treatment period. In addition, blood samples were collected at the end of each treatment period to assess serum levels of insulin-like growth factor-1 (IGF-1).

The apnea-hypopnea index (AHI) and snoring time represented the main outcome variables. Secondary outcomes included IGF-1 levels, and questionnaire scores for quality of life and behavior.

Results

Compared to the Sham MAS, the wearing of the Active MAS resulted in a significant reduction in overall AHI (-37%; 95% CI = 15–53%; p = 0.002) and supine AHI (−4.1 events per hour; 95% CI = 1.8–6.4; p < 0.001). Mean snoring time per night was shorter with the Active MAS than with the Sham MAS (−46.3 min; 95% CI = 14.5–78.1; p = 0.004). Wearing of the Active MAS improved the ratings of quality of life and behavior (P ≤ 0.028), but there was no evidence that it influenced IGF-1 levels (P = 0.172).

Conclusion

Wearing an Active MAS overnight, over a short period can be beneficial for SDB children, resulting in a clinically relevant reduction of supine AHI.

Introduction

Sleep-disordered breathing (SDB) encompasses a continuous spectrum of disorders, ranging from primary snoring to obstructive sleep apnea (OSA). The health impact of SDB in children has become increasingly recognised [ ]. Whilst most authors report a 10% prevalence of habitual snoring in children [ ], the prevalence of OSA in children ranges from 1 to 4% [ ]. SDB has been associated with growth disorders, daytime sleepiness, educational and behavioral problems, and nocturnal enuresis [ ]. In the most severe cases, OSA may have life-threatening consequences, such as cardiorespiratory failure [ ].

Enlarged adenoids and tonsils are the most common cause of OSA in children therefore the first line and most common treatment for pediatric OSA is adenotonsillectomy [ ]. The incidence of adenotonsillectomy has increased in the past few decades, as the indication for surgery has markedly shifted from recurrent infection to upper airway obstruction [ ]. Although significant improvements in SDB are observed following adenotonsillectomy, the cure rate of OSA after operation (defined as a post-adenotonsillectomy AHI < 1 event/h) ranges from 27% to 60% [ ].

Orthodontic and craniofacial anomalies have often been reported in pediatric OSA. A mutual interaction has been reported between the nasopharyngeal airway and the craniofacial complex [ ]. Jaw malposition and anomalies are associated with changes in airway morphology and respiratory problems [ ]. Reciprocally, obstruction of the airways has an influence on the development of the stomatognathic system [ ]. Because of this association, oral appliances, such as mandibular advancement splints have also been widely used for the treatment of OSA in patients with dentofacial anomalies [ ]. These appliances increase the posterior oropharyngeal airway and reduce the upper airway collapsibility by holding the mandible in a protruded position during sleep. Furthermore, the appliance may trigger stretch receptors, which in turn activate the airway supporting muscles [ ] increasing airway patency.

Previous studies have shown that oral appliances are better tolerated than continuous positive air pressure (CPAP), which is currently considered the first-line treatment option for adult OSA, due to improved comfort, quietness, and portability [ ]. Mandibular advancement splints (MAS) are the most widely used oral appliance for treating SDB in adults. In children, they are widely used to improve facial appearance in growing children with retruded mandible [ ] but they are hardly used for SDB treatment [ ]. To date, there are only few studies testing the efficacy of MAS in children, which suffer from methodological flaws, including lack of randomisation and lack of adequate control conditions, such as the use of a placebo-like or sham appliance. A Cochrane review [ ] concluded that there is not enough evidence to support the use of oral appliances and functional orthopedic appliances for the treatment of OSA in children. This conclusion was also reached by two recent systematic reviews and a meta-analysis, confirming that the current evidence is limited, but the potential for MAS to be effective for treating pediatric OSA was indicated [ ]. Thus there is a strong need to carry out well-designed randomized controlled trials (RCTs) to investigate both the efficacy and effectiveness of mandibular advancement appliances in children affected with SDB [ ].

The aims of this study were to test the short-term effectiveness of MAS appliances for the management of SDB in children and their effect on quality of life, behavior, and growth hormone levels.

Materials and methods

Study design

This study was carried out as a crossover randomized clinical trial. Each participant wore an Active and a Sham MAS appliance overnight for three weeks. Treatment periods were separated by a two-week washout period.

Participants and setting

This study took place between May 2014 and December 2015, and was conducted at the Discipline of Orthodontics, School of Dentistry, University of Otago, Dunedin, New Zealand. Ethical approval was granted by the University of Otago Human Ethics Committee [H14/054]. The trial was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12614001013651). The full protocol including sample size estimation has been published elsewhere [ ]. We aimed to recruit at least 18 participants.

Recruitment

Advertisements were placed in local newspapers and on community noticeboards to invite children whose parents reported their child snored regularly and loudly to participate in the study. Thirty-one parents contacted the research team with expressions of interest, and were sent information sheets by mail. Twenty-two respondents presented to the Dental School for a clinical screening, and their parents were asked to complete the Pediatric Sleep Questionnaire (PSQ). Individual height and weight measurements were taken at the first appointment to calculate the body mass index (BMI), and an oral examination was performed. Tonsil size and oropharyngeal patency were visually inspected and scored according to Mallampati [ ]. Dental impressions were taken using alginate impression material (Orthotrace, Cavex Holland BV, Haarlem, The Netherlands), and poured with stone (Ortho Stone & Ortho Plaster, Nobilium Company, New York, USA) to obtain study and work models. Additional records that were collected included intra-oral and extra-oral photographs and lateral cephalograms (Carnex Tome Ceph, SOREDEX, Tuusula, Finland) in maximum intercuspal position. The cephalometric landmarks and measurements assessed are illustrated in Fig. 1 .

Fig. 1
Cephalometric measures used in the study.
Cephalometric landmarks and measurements used to describe the dentofacial features of participants enrolled in the trial.
SNA (deg) the angle formed by the planes sella-nasion and nasion-point ASNB (deg) the angle formed by the planes sella-nasion and nasion-point BANB (deg) the angle formed by the planes nasion-point A and nasion-point BWits appraisal (mm) distance between the projection of points A and B on the occlusal planeSN-MP (deg) the angle between the mandibular plane and sella-nasionMMPA (deg) the angle formed between the palatal (ANS-PNS) and mandibular planesLower face height (LFH) (ANS-Me) (mm) measured by the distance from ANS to mentonTotal face height (TFH) (N-Me) (mm) measured by the distance from N to mentonUIA the angle formed by the long axis of the upper incisor and the maxillary planeLIA the angle formed by the long axis of the lower incisor and the mandibular planeLi-APog (mm) distance between the tip of the lower incisor (Li) and (A-Pog)Interincisal angle (deg) the angle formed by the long axis of the upper and lower incisorUpper lip relation to Ricketts E line (mm) measured by the distance between labrale superius (Ls) to Ricketts E lineLower lip relation to E line (mm) measured by the distance between labrale inferius (lower lip) to Ricketts E line

Eligible participants had to meet the following inclusion criteria: age range from 8 to 12 years, and; parental report of loud snoring for three or more nights per week.

Exclusion criteria were: previous orthodontic treatment, craniofacial and genetic syndromes ( e.g. cleft lip and/or palate), neuromuscular disorders, and Class III incisor and/or skeletal relationship as confirmed by lateral cephalometric radiograph (ANB angle ≤0°) [ ].

Randomization

Participants enrolled in the trial were randomly assigned to one of two sequences involving either the Active MAS treatment being delivered first followed by the Sham MAS, or the opposite order.

Randomization was performed using computer-generated blocks of size 4 for the two treatments. Allocation was concealed using opaque envelopes, which were only disclosed immediately after enrolment by a member of the research team (MF). Participant flow is illustrated in Fig. 2 .

Fig. 2
Participants’ flow in the study.
Eighteen patients were included in the study and were randomly allocated to the treatment sequences.

Participants were not made aware of whether the appliance they received was the Active or the Sham appliance.

Oral appliances

Clark’s Twin-Block [ ] was chosen as the active intervention for this RCT to be used as an Active MAS, based on the results of a pilot study, which aimed to compare the retention and comfort of different MAS designs [ ]. Treatment was always provided by the same member of the research team (GI).

Twin-Block MAS design

This consisted of two removable upper and lower acrylic plates, each with matching surfaces, which encourage the lower jaw to posture forward as the upper and lower teeth come together [ ]. Bilateral hooks were added to the appliance in order to insert vertical elastics. The purpose of these elastics was to hold the mouth closed during sleep, and to keep the mandible in a forward position [ ]. The construction bite was taken by advancing the mandible to 75% of the maximum jaw protrusion with minimum bite opening [ ]. This was performed by using a commercially available bite registration kit [ ] (George Gauge™, Scheu Dental Technology, Brussels, Belgium).

Sham MAS design

This consisted of two upper and lower acrylic plates, resembling the design of the active MAS, but without any component to protrude the mandible.

Primary outcomes

Apnea-hypopnea index and snoring

Level 3 home-based abbreviated polysomnography data [ ] were collected using a portable sleep monitoring unit (Embletta MRP PG-XS-ENU, Natus Neurology Incorporated, Ontario, Canada). The following variables were assessed: oxygen saturation and heart rate (pulse oximetry), nasal pressure (using a nasal pressure catheter), nasal and mouth thermistry, thoracic and abdominal respiratory movement (inductance plethysmography), position (gravity sensor), and activity (actigraphy). Snoring sounds were recorded by a microphone attached to the nasal cannula extension. This equipment has previously been validated for the diagnosis of SDB [ ]. EMG activity from the masseter muscles was also collected, but data are not presented in this report.

The portable unit and the recording time (on/off times) were set by software (RemLogic-E version 3.4, Embla system, Natus Europe, Planegg, Germany). PSG signals were acquired at 24-bit resolution and sampled up to 8000 Hz (snoring sounds). Nasal pressure was sampled at 250 Hz, whereas the respiratory signals recorded by inductance bands were sampled at 100 Hz.

For each participant, home-based PSG data were collected four times before and after each treatment period with the Twin-Block or the Sham appliance. The AHI scoring also included sleep position, because sleep related obstructive respiratory events in children are more common in the supine sleep position [ ]. The AHI was calculated according to the American Academy of Sleep Medicine (AASM) criteria for scoring pediatric respiratory sleep studies [ ].

Snoring was assessed by audio recordings, which is one of the recommended methods to aid visualising snoring oscillations [ ]. The Embletta MPR microphone used to record snoring is an analogue omnidirectional condenser microphone, which was attached to the nasal cannula. For optimal visualization of snoring, a high-pass filter was used to remove very low frequencies (20 Hz), and a low-pass filter to remove high frequencies (3 kHz). This allowed researchers to acquire relevant information on the sound of snoring.

Subjective reports of snoring frequency and wearing of appliances ( i.e. treatment adherence) were recorded in diaries, to be filled in by parents every night throughout each treatment period. Snoring was scored as a polychotomous variable (yes, no, don’t know), while the wearing of appliances was scored as a dichotomous variable (full-night, less than full-night).

Sleep study scoring

Recorded data from the Level 3 Sleep Studies was analyzed automatically using custom RemLogic-E software (version 3.4, Embla system, Natus Europe, Planegg, Germany). Respiratory events and snoring periods were then manually edited over generally 2-min epochs by a registered respiratory/sleep physiologist. The sleep physiologist was blind to patient information, including appliance worn and treatment sequence. An obstructive apnea was defined as a decrease ≥90% of the pre event baseline measured by thermistor or a valid alternative sensor for at least 2 breaths and associated with continued respiratory effort [ ]. An hypopnea was defined as a decrease ≥30% from pre event baseline measured by nasal pressure sensor or a valid alternative sensor, lasting at least 2 breaths with a corresponding decrease in oxygen saturation ≥3% or arousal indicated by surrogate measures including movement measured by actigraphy, changes in snoring sounds, >10% increase in heart rate or abrupt changes in thoracoabdominal effort [ ]. A central apnea was defined as a decrease ≥90% of the pre event baseline measured by thermistor or a valid alternative sensor, lasting 20 s or at least the duration of two breaths and associated with a ≥3% oxygen desaturation or arousal indicated by surrogate measures as above, or lasts at least the duration of two breaths and is associated with a decrease in heart rate to <50 beats per minutes for 5 s. The apneas are associated with absence of inspiratory effort. A mixed apnea was defined if it met the two breath apnea criteria and was associated with absence of effort during one portion of the event and the presence of inspiratory effort in another portion [ ]. Snoring was scored manually by listening to the recordings in synchrony with the respiratory variables. Snoring events were tagged on the recorded audio graph. The occurrence of snoring was assessed as total snoring time per night and the number of snoring episodes over the entire duration of the recorded sleep period.

Secondary outcomes

Growth hormone levels

Blood samples were taken from all participants by a certified phlebotomist in a specialized laboratory (Southern Community Laboratories, Dunedin, New Zealand). Growth hormone levels were indirectly assessed by determining the levels of insulin-like growth factor 1 (IGF-1) [ ].

Two samples were collected from each participant in a non-fasting state at the end of each treatment period in the morning to early afternoon. IGF-1 concentrations were assayed using a human IGF-1 Quantikine ELISA Kit (PDG100, R&D Systems, Minneapolis, USA). The human IGF-1 immunoassay employs the quantitative sandwich enzyme technique [ ]. Samples were stored in a freezer at −80 °C until batch assayed in the Southern Community Laboratories (Dunedin, New Zealand) by a technician who was blinded to the treatment period.

SDB symptoms and daytime sleepiness questionnaires

SDB associated symptoms were assessed using the sleep related breathing disorder subscale of the Pediatric Sleep Questionnaire (PSQ) [ ]. The PSQ-SRDB cut-off to indicate the presence of SDB is 0.33 ( i.e. positive answers on ≥33% of the 22 question items) [ ].

The questionnaire was completed by parents/caregivers. PSQ questionnaires were administered four times during the study, before and after each treatment period.

Quality of life

The OSA-18 instrument is a quality-of-life questionnaire with a focus on pediatric sleep-disordered breathing. It has been used as a screening tool for pediatric OSA [ ]. This questionnaire consists of 18 questions about sleep and respiratory disturbance, as well as other symptoms caused by OSA. The total symptom score (TSS) resulting from this questionnaire may vary from 18 to 126 points. A TSS at or above 60 is considered abnormal, and is associated with SDB. Scores of 60–80 suggest a moderate impact on the disease-specific quality of life, and a score above 80 suggests a large impact [ ].

The OSA-18 questionnaire was administered four times, and parents/caregivers rated the frequency of symptoms before and at the end of each treatment period.

Behavioral assessment

The Behavioral and Emotional Screening System (BESS) is a recently developed set of measures consisting of 30 items derived from the Behavior Assessment System for Children, Second Edition (BASC-2) [ ]. This BASC-2 tool has been widely used in studying behavioral differences in pediatric SDB patients [ ]. The shorter BESS questionnaire is designed to quickly screen children and adolescents from preschool to high school for current or future emotional or behavioral problems. Parent rating scale questionnaires for ages 6–11 years, were used in the study to measure both adaptive and maladaptive behaviors. The BASC-2 BESS was administered before and at the end of each treatment period.

Parent report of nocturnal enuresis

Since around 24% of children with sleep apnea report nocturnal enuresis [ ], the frequency of bed-wetting was recorded by parents/caregivers using written diaries (yes/no question), and completed throughout the study period.

Statistics

PSG and questionnaire data were analyzed using linear mixed-effect models, with baseline values included as a covariate along with effects for treatment and period (first or second) and a random effect for participant to accommodate the repeated measures due to the crossover design. Carry-over effects were tested for to ensure there was no evidence that the washout period was not sufficient. Model residuals were checked for normality and homoscedasticity, and where this improved satisfaction of model assumptions, data were log-transformed and ratios of geometric means reported rather than differences in arithmetic means. The results are presented as mean ± standard deviation of the mean, unless otherwise stated in the tables. IGF-1 and diary data were analyzed in the same way but without adjusting for baseline values. Intraclass correlation coefficients (ICC) were calculated using a set of 10 duplicate measurements carried out by the same rater. The two assessments were made at least one-month interval apart and were used to estimate intra-examiner reliability of AHI. The significance level was set at P < 0.05 (two-sided). Data were analyzed using Stata Statistical Software ( Stata 14, StataCorp LP, Texas, USA).

Materials and methods

Study design

This study was carried out as a crossover randomized clinical trial. Each participant wore an Active and a Sham MAS appliance overnight for three weeks. Treatment periods were separated by a two-week washout period.

Participants and setting

This study took place between May 2014 and December 2015, and was conducted at the Discipline of Orthodontics, School of Dentistry, University of Otago, Dunedin, New Zealand. Ethical approval was granted by the University of Otago Human Ethics Committee [H14/054]. The trial was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12614001013651). The full protocol including sample size estimation has been published elsewhere [ ]. We aimed to recruit at least 18 participants.

Recruitment

Advertisements were placed in local newspapers and on community noticeboards to invite children whose parents reported their child snored regularly and loudly to participate in the study. Thirty-one parents contacted the research team with expressions of interest, and were sent information sheets by mail. Twenty-two respondents presented to the Dental School for a clinical screening, and their parents were asked to complete the Pediatric Sleep Questionnaire (PSQ). Individual height and weight measurements were taken at the first appointment to calculate the body mass index (BMI), and an oral examination was performed. Tonsil size and oropharyngeal patency were visually inspected and scored according to Mallampati [ ]. Dental impressions were taken using alginate impression material (Orthotrace, Cavex Holland BV, Haarlem, The Netherlands), and poured with stone (Ortho Stone & Ortho Plaster, Nobilium Company, New York, USA) to obtain study and work models. Additional records that were collected included intra-oral and extra-oral photographs and lateral cephalograms (Carnex Tome Ceph, SOREDEX, Tuusula, Finland) in maximum intercuspal position. The cephalometric landmarks and measurements assessed are illustrated in Fig. 1 .

Fig. 1
Cephalometric measures used in the study.
Cephalometric landmarks and measurements used to describe the dentofacial features of participants enrolled in the trial.
SNA (deg) the angle formed by the planes sella-nasion and nasion-point ASNB (deg) the angle formed by the planes sella-nasion and nasion-point BANB (deg) the angle formed by the planes nasion-point A and nasion-point BWits appraisal (mm) distance between the projection of points A and B on the occlusal planeSN-MP (deg) the angle between the mandibular plane and sella-nasionMMPA (deg) the angle formed between the palatal (ANS-PNS) and mandibular planesLower face height (LFH) (ANS-Me) (mm) measured by the distance from ANS to mentonTotal face height (TFH) (N-Me) (mm) measured by the distance from N to mentonUIA the angle formed by the long axis of the upper incisor and the maxillary planeLIA the angle formed by the long axis of the lower incisor and the mandibular planeLi-APog (mm) distance between the tip of the lower incisor (Li) and (A-Pog)Interincisal angle (deg) the angle formed by the long axis of the upper and lower incisorUpper lip relation to Ricketts E line (mm) measured by the distance between labrale superius (Ls) to Ricketts E lineLower lip relation to E line (mm) measured by the distance between labrale inferius (lower lip) to Ricketts E line

Eligible participants had to meet the following inclusion criteria: age range from 8 to 12 years, and; parental report of loud snoring for three or more nights per week.

Exclusion criteria were: previous orthodontic treatment, craniofacial and genetic syndromes ( e.g. cleft lip and/or palate), neuromuscular disorders, and Class III incisor and/or skeletal relationship as confirmed by lateral cephalometric radiograph (ANB angle ≤0°) [ ].

Randomization

Participants enrolled in the trial were randomly assigned to one of two sequences involving either the Active MAS treatment being delivered first followed by the Sham MAS, or the opposite order.

Randomization was performed using computer-generated blocks of size 4 for the two treatments. Allocation was concealed using opaque envelopes, which were only disclosed immediately after enrolment by a member of the research team (MF). Participant flow is illustrated in Fig. 2 .

Fig. 2
Participants’ flow in the study.
Eighteen patients were included in the study and were randomly allocated to the treatment sequences.

Participants were not made aware of whether the appliance they received was the Active or the Sham appliance.

Oral appliances

Clark’s Twin-Block [ ] was chosen as the active intervention for this RCT to be used as an Active MAS, based on the results of a pilot study, which aimed to compare the retention and comfort of different MAS designs [ ]. Treatment was always provided by the same member of the research team (GI).

Twin-Block MAS design

This consisted of two removable upper and lower acrylic plates, each with matching surfaces, which encourage the lower jaw to posture forward as the upper and lower teeth come together [ ]. Bilateral hooks were added to the appliance in order to insert vertical elastics. The purpose of these elastics was to hold the mouth closed during sleep, and to keep the mandible in a forward position [ ]. The construction bite was taken by advancing the mandible to 75% of the maximum jaw protrusion with minimum bite opening [ ]. This was performed by using a commercially available bite registration kit [ ] (George Gauge™, Scheu Dental Technology, Brussels, Belgium).

Sham MAS design

This consisted of two upper and lower acrylic plates, resembling the design of the active MAS, but without any component to protrude the mandible.

Primary outcomes

Apnea-hypopnea index and snoring

Level 3 home-based abbreviated polysomnography data [ ] were collected using a portable sleep monitoring unit (Embletta MRP PG-XS-ENU, Natus Neurology Incorporated, Ontario, Canada). The following variables were assessed: oxygen saturation and heart rate (pulse oximetry), nasal pressure (using a nasal pressure catheter), nasal and mouth thermistry, thoracic and abdominal respiratory movement (inductance plethysmography), position (gravity sensor), and activity (actigraphy). Snoring sounds were recorded by a microphone attached to the nasal cannula extension. This equipment has previously been validated for the diagnosis of SDB [ ]. EMG activity from the masseter muscles was also collected, but data are not presented in this report.

The portable unit and the recording time (on/off times) were set by software (RemLogic-E version 3.4, Embla system, Natus Europe, Planegg, Germany). PSG signals were acquired at 24-bit resolution and sampled up to 8000 Hz (snoring sounds). Nasal pressure was sampled at 250 Hz, whereas the respiratory signals recorded by inductance bands were sampled at 100 Hz.

For each participant, home-based PSG data were collected four times before and after each treatment period with the Twin-Block or the Sham appliance. The AHI scoring also included sleep position, because sleep related obstructive respiratory events in children are more common in the supine sleep position [ ]. The AHI was calculated according to the American Academy of Sleep Medicine (AASM) criteria for scoring pediatric respiratory sleep studies [ ].

Snoring was assessed by audio recordings, which is one of the recommended methods to aid visualising snoring oscillations [ ]. The Embletta MPR microphone used to record snoring is an analogue omnidirectional condenser microphone, which was attached to the nasal cannula. For optimal visualization of snoring, a high-pass filter was used to remove very low frequencies (20 Hz), and a low-pass filter to remove high frequencies (3 kHz). This allowed researchers to acquire relevant information on the sound of snoring.

Subjective reports of snoring frequency and wearing of appliances ( i.e. treatment adherence) were recorded in diaries, to be filled in by parents every night throughout each treatment period. Snoring was scored as a polychotomous variable (yes, no, don’t know), while the wearing of appliances was scored as a dichotomous variable (full-night, less than full-night).

Sleep study scoring

Recorded data from the Level 3 Sleep Studies was analyzed automatically using custom RemLogic-E software (version 3.4, Embla system, Natus Europe, Planegg, Germany). Respiratory events and snoring periods were then manually edited over generally 2-min epochs by a registered respiratory/sleep physiologist. The sleep physiologist was blind to patient information, including appliance worn and treatment sequence. An obstructive apnea was defined as a decrease ≥90% of the pre event baseline measured by thermistor or a valid alternative sensor for at least 2 breaths and associated with continued respiratory effort [ ]. An hypopnea was defined as a decrease ≥30% from pre event baseline measured by nasal pressure sensor or a valid alternative sensor, lasting at least 2 breaths with a corresponding decrease in oxygen saturation ≥3% or arousal indicated by surrogate measures including movement measured by actigraphy, changes in snoring sounds, >10% increase in heart rate or abrupt changes in thoracoabdominal effort [ ]. A central apnea was defined as a decrease ≥90% of the pre event baseline measured by thermistor or a valid alternative sensor, lasting 20 s or at least the duration of two breaths and associated with a ≥3% oxygen desaturation or arousal indicated by surrogate measures as above, or lasts at least the duration of two breaths and is associated with a decrease in heart rate to <50 beats per minutes for 5 s. The apneas are associated with absence of inspiratory effort. A mixed apnea was defined if it met the two breath apnea criteria and was associated with absence of effort during one portion of the event and the presence of inspiratory effort in another portion [ ]. Snoring was scored manually by listening to the recordings in synchrony with the respiratory variables. Snoring events were tagged on the recorded audio graph. The occurrence of snoring was assessed as total snoring time per night and the number of snoring episodes over the entire duration of the recorded sleep period.

Secondary outcomes

Growth hormone levels

Blood samples were taken from all participants by a certified phlebotomist in a specialized laboratory (Southern Community Laboratories, Dunedin, New Zealand). Growth hormone levels were indirectly assessed by determining the levels of insulin-like growth factor 1 (IGF-1) [ ].

Two samples were collected from each participant in a non-fasting state at the end of each treatment period in the morning to early afternoon. IGF-1 concentrations were assayed using a human IGF-1 Quantikine ELISA Kit (PDG100, R&D Systems, Minneapolis, USA). The human IGF-1 immunoassay employs the quantitative sandwich enzyme technique [ ]. Samples were stored in a freezer at −80 °C until batch assayed in the Southern Community Laboratories (Dunedin, New Zealand) by a technician who was blinded to the treatment period.

SDB symptoms and daytime sleepiness questionnaires

SDB associated symptoms were assessed using the sleep related breathing disorder subscale of the Pediatric Sleep Questionnaire (PSQ) [ ]. The PSQ-SRDB cut-off to indicate the presence of SDB is 0.33 ( i.e. positive answers on ≥33% of the 22 question items) [ ].

The questionnaire was completed by parents/caregivers. PSQ questionnaires were administered four times during the study, before and after each treatment period.

Quality of life

The OSA-18 instrument is a quality-of-life questionnaire with a focus on pediatric sleep-disordered breathing. It has been used as a screening tool for pediatric OSA [ ]. This questionnaire consists of 18 questions about sleep and respiratory disturbance, as well as other symptoms caused by OSA. The total symptom score (TSS) resulting from this questionnaire may vary from 18 to 126 points. A TSS at or above 60 is considered abnormal, and is associated with SDB. Scores of 60–80 suggest a moderate impact on the disease-specific quality of life, and a score above 80 suggests a large impact [ ].

The OSA-18 questionnaire was administered four times, and parents/caregivers rated the frequency of symptoms before and at the end of each treatment period.

Behavioral assessment

The Behavioral and Emotional Screening System (BESS) is a recently developed set of measures consisting of 30 items derived from the Behavior Assessment System for Children, Second Edition (BASC-2) [ ]. This BASC-2 tool has been widely used in studying behavioral differences in pediatric SDB patients [ ]. The shorter BESS questionnaire is designed to quickly screen children and adolescents from preschool to high school for current or future emotional or behavioral problems. Parent rating scale questionnaires for ages 6–11 years, were used in the study to measure both adaptive and maladaptive behaviors. The BASC-2 BESS was administered before and at the end of each treatment period.

Parent report of nocturnal enuresis

Since around 24% of children with sleep apnea report nocturnal enuresis [ ], the frequency of bed-wetting was recorded by parents/caregivers using written diaries (yes/no question), and completed throughout the study period.

Statistics

PSG and questionnaire data were analyzed using linear mixed-effect models, with baseline values included as a covariate along with effects for treatment and period (first or second) and a random effect for participant to accommodate the repeated measures due to the crossover design. Carry-over effects were tested for to ensure there was no evidence that the washout period was not sufficient. Model residuals were checked for normality and homoscedasticity, and where this improved satisfaction of model assumptions, data were log-transformed and ratios of geometric means reported rather than differences in arithmetic means. The results are presented as mean ± standard deviation of the mean, unless otherwise stated in the tables. IGF-1 and diary data were analyzed in the same way but without adjusting for baseline values. Intraclass correlation coefficients (ICC) were calculated using a set of 10 duplicate measurements carried out by the same rater. The two assessments were made at least one-month interval apart and were used to estimate intra-examiner reliability of AHI. The significance level was set at P < 0.05 (two-sided). Data were analyzed using Stata Statistical Software ( Stata 14, StataCorp LP, Texas, USA).

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Jun 17, 2018 | Posted by in General Dentistry | Comments Off on Mandibular advancement appliances for sleep-disordered breathing in children: A randomized crossover clinical trial
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