mandibular distraction for micrognathia in neonates · 2019-06-15 · quires mandibular osteotomies...
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Mandibular Distraction for Micrognathiain Neonates
Carrie E. Zimmerman, BS,* Laura S. Humphries, MD,* Tulsi Roy, MD,* Russell R. Reid, MD, PhD*
*Department of Surgery, Section of Plastic Surgery, University of Chicago Medical Center, Chicago, IL
Education Gaps
1. Pierre Robin sequence (PRS) comprises the clinical triad of micrognathia,
glossoptosis, and upper airway obstruction. The severity of micrognathia
and airway obstruction among neonates with PRS varies. The evaluation of
neonates with micrognathia is not standardized across neonatal units,
which may result in delayed referral to and, therefore, delayed evaluation
and care by appropriate specialists.
2. Airway management for neonates with PRS ranges from noninvasive airway
support to surgical intervention for mandibular lengthening. The gold
standard surgical intervention is mandibular distraction osteogenesis (MDO),
the goal of which is to anteriorly reposition the mandible and tongue base
away from the posterior pharynx to relieve upper airway obstruction. The
ideal anatomic endpoint of mandibular distraction is not yet known.
3. Surgical intervention for treatment of upper airway obstruction in patients
with PRS carries a risk of complications and long-term effects. With the
introduction of MDO for PRS less than 2 decades ago, long-term clinical
outcomes data with MDO are currently lacking.
Abstract
Pierre Robin sequence (PRS) comprises the clinical triad of micrognathia,
glossoptosis, and upper airway obstruction, with a reported incidence of 0.5
to 2.1 per 10,000 live births. The mainstay of management involves prompt
diagnosis of airway obstruction and airway management. The gold standard
surgical intervention for management of symptomatic micrognathia is
mandibular lengthening by distraction osteogenesis (MDO) to anteriorly
reposition a retroflexed tongue and relieve obstruction. Although MDO is
often successful in the short-term in relieving upper airway obstruction and/
or avoiding the need for permanent tracheostomy, the long-term effects of
MDO are not yet elucidated.
Objectives After completing this article, readers should be able to:
1. Describe the initial diagnostic evaluation, airway analysis and evaluation,
and necessary referrals for neonates with Pierre Robin sequence.
AUTHOR DISCLOSURE Ms Zimmerman, DrsHumphries, Roy, and Reid have disclosed nofinancial relationships relevant to this article.Dr Reid has disclosed receipt of lab royaltiesfrom Applied Biologicals, Inc., from sales of ICAL cells. This commentary does not contain adiscussion of an unapproved/investigativeuse of a commercial product/device.
ABBREVIATIONS
HRQOL health-related quality of life
MDO mandibular distraction
osteogenesis
PEBP pre-epiglottic baton plate
PRS Pierre Robin sequence
PSG polysomnography
TLA tongue-lip adhesion
UAO upper airway obstruction
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2. Describe the indications for and technical aspects of mandibular
distraction osteogenesis (MDO), along with its complications.
3. Recognize the importance of appropriate patient selection for MDO.
4. Recognize the psychological and quality-of-life implications of MDO.
5. Identify treatment alternatives to MDO.
INTRODUCTION
Micrognathia is defined as a developmentally small man-
dible withmarkedly posterior positioning of themandibular
alveolus relative to the maxillary alveolus. (1) Micrognathia
has an incidence of 1 in 1,000 births. (2) This condition
presents with a broad clinical range of severity, from asymp-
tomatic presentation to severe upper airway obstruction
(UAO), the treatment of which involves airway stabilization
with or without surgical intervention to lengthen the man-
dible (Fig 1).
Pierre Robin sequence (PRS) includes the clinical triad
of micrognathia, glossoptosis (ie, posterior displacement
of the tongue), and UAO. Though not typically described
as part of the triad, cleft palate is frequently associated
with PRS, which can compound difficulties with feeding
and speech both in the short- and long-term. Microgna-
thia can be diagnosed with imaging during the prenatal
period, while the PRS triad is identified at birth. (3)(4) The
prevalence of PRS has been cited as being between
0.5 and 2.1 per 10,000 live births, with the highest
incidence among whites and the lowest incidence among
non-Hispanic African Americans. (5) Tongue base pro-
lapse and UAO in PRS may result in feeding difficulty,
failure to thrive, brain damage, and sudden death. (1)(3)
(6)(7) Mortality in PRS has been cited to range between
2.2% and 26%, most commonly because of obstructive
apnea and cardiac failure as a result of severe airway
obstruction. (8)
Furthermore, patients with PRSmay be classified into
“syndromic” or “isolated” groups. Patients with “syn-
dromic PRS” have a concomitant syndrome or anatomic
abnormalities. Syndromic PRS occurs in 45% to 80% of
cases (Table 1). Patients with “isolated PRS” do not have
other associated abnormalities. (3)(6)(8) Because of the
frequent association with multilevel airway obstruction
in syndromic PRS, achieving and maintaining an un-
obstructed airway in children with syndromic PRS tends
to be more difficult than in children with isolated
PRS. (3)
EVALUATION AND MANAGEMENT OF PRS
A systematic approach to the clinical evaluation and treat-
ment of neonates with micrognathia is essential to provide
comprehensive care (Fig 2). Asymptomatic micrognathia
may require multidisciplinary input, but often, outpatient
referral and follow-up are adequate. Alternatively, in a
symptomatic patient with micrognathia and UAO, initial
stabilization of the airway is an essential first step. Following
stabilization, patients with micrognathia should undergo
further evaluation to first establish whether the microgna-
thia is isolated or part of a syndrome. Patients identified as
having PRS should undergo an extensive multidisciplinary
evaluation that may include neonatology/pediatrics, sleep
medicine, otolaryngology, plastic surgery, genetics, speech
pathology, and nutrition services.
The primary objective of PRS treatment is securing a
safe airway to improve oxygenation, and consequently
improve feeding, speech, and developmental outcomes.
Airway evaluation and stabilization should begin promptlyFigure 1. Decision tree for evaluation and management of infants withmicrognathia.
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TABLE 1. Common Syndromes Associated with Pierre Robin Sequence
SYNDROME INCIDENCE ANATOMIC CHARACTERISTICS PHYSIOLOGIC CHARACTERISTICS
Velocardiofacialsyndrome
1:4,000 live births Found in most patients with DiGeorge sequenceand conotruncal anomaly face syndrome.
Speech abnormalities (hypernasal)
Includes:• Breathing difficulty
Craniofacial anomalies
• Chronic otitis media
• Retrognathia
• Transient neonatal hypocalcemia
• Long face with prominent nose
• Mild intellectual impairment
• Velopharyngeal weakness
• Psychiatric disorders
• Submucous or overt cleftsCardiovascular anomalies• Congenital heart defects• Carotid artery anomalies
Craniofacial orhemifacialmicrosomia(39)(40)
1:4,000–5,500 livebirths
A variable presentation including: • Hearing impairmentCraniofacial anomalies • Airway compromise• Mandibular hypoplasia• Microtia• Orbital distortion• Hypoplasia of facial muscles, parotid gland,and muscles of mastication
Cardiac anomalies• Septal and outflow tract heart defectsGoldenhar syndrome is within the spectrum of
this disorder. Additional characteristics includeepibulbar dermoids and vertebral defects
Stickler (41)(42)and Marshallsyndromes (43)(44)
1:7,500–9,000(Stickler)
Overlapping connective tissue disorders with: • Airway compromiseCraniofacial anomalies • Sensorineural deafness• Flat midface with depressed nasal bridge,short nose, anteverted nares
• Myopia
• Micrognathia• May have soft palate cleftEye anomalies• Abnormal vitreous gel in eye• Retinal detachment (Stickler)• CataractsMusculoskeletal anomalies• Joint hypermobility• Arthritis• Osteoarthritis in 3rd or 4th decade• Spinal abnormalities• Spondyloepiphyseal abnormalities (Marshall)• Anhidrotic ectodermal dysplasia (Marshall)Cardiac anomalies• Mitral valve prolapse (Stickler)
Treacher-Collinssyndrome (45)
1:25,000–50,000live births
Variable presentation but always bilateral. • Conductive hearing lossIncludes: • Airway difficulty and respiratory
compromise• Malar and mandibular hypoplasia• Speech and feeding difficulty• Zygomal cleft
• Antimongoloid slanted eyes with eyelid notch(colobomas)
• Retrusive jaw and chin• External ear abnormalities• Absence of eyelashes in medial third oflower eyelid
• Cleft lip and choanal atresia may be present
Continued
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after a diagnosis of PRS, beginning with conservative and
noninvasive measures such as continuous pulse oximetry
monitoring and prone or side positioning. Approximately 70%
of patients can be stabilizedwith positioning changes alone. (8)
(9) If repositioning does not adequately relieve obstruction,
nasopharyngeal airway placementmay be temporarily used for
up to 2 to 4 months. Patients may also be treated with non-
invasive continuous positive airway pressure therapy; however,
large cohort data for its long-term effectiveness among patients
with PRS are lacking. (10) Patients who fail less invasive
airway support may require endotracheal intubation or even
tracheostomy placement. If advanced airway support is
required, or if patients demonstrate significant obstruction
during oral feedings, nasogastric tube feedings may be nec-
essary for nutrition.Genetic evaluation andneonatal screening
in patients with PRSmay identify the presence of concurrent
congenital anomalies and syndromes (Table 1). A geneticist
can help guide further evaluation. If more anomalies are
identified, the infant may require additional evaluation by
subspecialists (eg, neurology, cardiology, ophthalmology).
Polysomnography (PSG), or a “sleep study,” determines
the presence and severity of UAO and may identify
TABLE 1. (Continued)
SYNDROME INCIDENCE ANATOMIC CHARACTERISTICS PHYSIOLOGIC CHARACTERISTICS
Nagar syndrome(acrofacialdystosis)(46)
Rare Similar characteristics to Treacher-Collinssyndrome, with noted differences
• Hearing impairment
• Absence of colobomas• Secondary speech and language delays
• Severe, wide cleft palate seen in all cases• Respiratory and feeding difficulty
• Limb anomalies including hypoplasiaof thumbs, radius, metacarpals
• Short stature
Figure 2. University of Chicago Hospital clinical evaluation and management guidelines for patients with Pierre Robin sequence (PRS). BMP¼basicmetabolic panel; CBC¼complete blood cell count; ECHO¼echocardiography.
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concomitant central apnea by monitoring for specific respi-
ratory events, including apneic and hypopneic events, and
oxygen desaturations. The 2012 American Academy of
Sleep Medicine guidelines delineate obstructive severity
with an apnea-hypopnea index and with the lowest associ-
ated oxygen saturation (Table 2). (10)(11)(12)(13) Serial cap-
illary blood gases with increasing carbon dioxide levels,
respiratory acidosis with metabolic compensation, and oxy-
gen desaturations at rest and during feedings can all support
the diagnosis of chronic airway obstruction. (1)(3)(13)
Nasopharyngeal endoscopy should be routinely per-
formed to identify concomitant upper airway pathology,
including subglottic airway obstruction, which may occur
in up to 23% of patients with PRS. (14) The identification of
additional airway pathology is important, because its pres-
ence may influence the definitive management of PRS. (14)
Combining PSG and nasopharyngeal endoscopy results
is useful to identify suitable candidates for mandibular
distraction osteogenesis (MDO). Although the presence
of central sleep apnea and/or concomitant airway pathology
does not preclude the use of MDO to address UAO, patients
may continue to have airway, breathing, and oxygenation
problems given their comorbidities. Thus, patients with
evidence of UAO on PSG with few or no central sleep
apneas, along with absence of concomitant airway pathology
may benefit the most from MDO.
SURGICAL MANAGEMENT OF PRS
Mandibular Distraction OsteogenesisAlthough conservative noninvasive measures are typically
effective to relieve airway obstruction, 23% of patients with
PRS will require surgical intervention. (3)(8)(9) MDO has
become the preferred surgical option at many institutions
for neonates and infants with PRS-associated UAO who
would otherwise require tracheostomy. (7)(15) MDO re-
quires mandibular osteotomies and placement of distrac-
tors that allow for gradual lengthening of the mandible in
an anterior-posterior direction. Anterior advancement of the
mandible promotes anterior repositioning of the tongue
relative to the oropharynx, with the goal of relieving tongue-
based airway obstruction. McCarthy et al published the first
clinical report ofmandibular distraction with a rigid external
distractor device for congenital mandibular deformities in
1992. (16) Since that time, both resorbable and nonresorb-
able internal distractor devices have been developed and are
commercially available. (8)
The MDO process is invasive and the treatment regimen
is intensive, spanning several weeks. The treatment involves
an initial surgery to place the device, followed by a 3-phase
distraction period. Figure 3 displays the authors’ institu-
tional timeline and protocol for the use ofMDO in neonates.
For neonates, the distraction period includes: 1) a latency
phase, which is the 24-hour period after distractor place-
ment and the start of distraction; 2) a distraction phase,
wherein the anterior mandible segment is advanced a
specific distance per day (typically 1 mm/day in a 0.5-mm
twice-daily regimen), which may last up to 2 to 3 weeks
depending on the rate of distraction and goal distraction
length; and 3) a consolidation phase, a period ranging from
6 to 8 weeks after distraction completion to allow for bone
healing. The devices are removed after the consolidation
phase. (17)(18)(19)
At the authors’ institution, PSG guides the endpoint of
mandibular distraction. After the distraction phase of
MDO is completed, PSG is performed to confirm reso-
lution of the UAO. (20) The appropriate anatomic end-
point of mandibular distraction beyond the relief of UAO
is unknown. While some advocate for overdistraction or
“overcorrection” of the mandible, this practice may result
in a severe underbite or class III malocclusion and have a
long-term impact on maxillary-mandibular relationships.
Recently, the concept of using airway volume and mor-
phology to guide mandibular distraction endpoint was
introduced. (15)(21) Preoperative virtual surgical plan-
ning using patient 3-dimensional computed tomography
for skeletal reconstruction and soft-tissue airway volume
calculations is useful and may serve as an objective ad-
junct in preoperative guidance and postoperative follow-
up. (8) Figure 4 exhibits a clinical example.
TABLE 2. Severity of Obstructive Sleep Apnea in Children (11)(12)(13)
CATEGORY OF SEVERITY APNEA-HYPOPNEA INDEX MINIMUM OXYGEN SATURATION
Mild <5 <90% for 2%–5% of sleep time
Moderate 5 to <10 <90% for 5%–10% of sleep time
Severe >10 <90% for >10% of sleep time
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MDO OUTCOMES
Reported clinical outcomes of MDO are varied. Metrics
include avoiding a tracheostomy or performing successful
decannulation of the tracheostomy, meeting normal growth
and developmental milestones, weaning from continuous
positive airway pressure, and/or alleviating or significantly
improving obstructive sleep apnea symptoms. Data com-
piled from systematic reviews and meta-analyses demon-
strate that 82% to 100% of patients had an overall positive
outcome fromMDO. In particular, normal oral feeding was
achieved in 86% to 100% of patients, and the axial skeleton
growth curve normalized after 1 year in almost all cases. (8)
(18)(22)(23) MDO is more likely to be successful in relieving
UAO and result in tracheostomy avoidance in patients with
nonsyndromic PRS compared with syndromic PRS with
cognitive comorbidities; those with a syndromic condi-
tion with a disrupted mandibular growth center; and those
without mandibular condyles, coronoid processes, or mal-
formed glenoid fossas. (3) A previously mentioned litera-
ture review found a success rate of avoiding tracheostomy
or achieving successful decannulation in 97.6% of pa-
tients with isolated PRS who underwent MDO compared
with 94% in patients with syndromic PRS in subgroup
analysis. (18)
High success rates fromMDO depend on proper patient
screening and selection. In addition to assessing for con-
comitant central sleep apneas and/or airway pathology
with PSG and nasopharyngeal endoscopy, it is important
to consider other systemic comorbidities that may affect
MDO outcome. Specifically, if MDO is performed on patients
with neurologic comorbidities, the surgery will not address
underlying conditions such as chronic aspiration, hypotonia,
and poor oral coordination, thus unnecessarily exposing the
patient to surgical complications without achieving significant
improvement in airway obstruction. (3)
MDO COMPLICATIONS
Short-term and long-term risks and complications associ-
ated with MDO are listed in Table 3. The overall complica-
tion rate of MDO is between 20.5% and 35.6%. (8)(17)(18)
(24)
Commonly cited short-term complications include infec-
tion, inappropriate vectors of distraction (ie, direction or
differential length of distraction between sides) resulting in
malocclusion, device malfunction, fusion error (eg, prema-
ture bony healing or nonunion of bone segments), and
nerve damage or palsy of the inferior alveolar nerve and/
or the marginal mandibular nerve. The long-term compli-
cations attributable to MDO are not yet fully elucidated, but
include malocclusion, relapse, tooth injury or abnormality,
hypertrophic scarring, and limited mandibular range of
motion. (1)(8)(17)(18)(24)(25) Data on complications include
the following:
• Infections: Infections from MDO vary in their severity
from superficial cellulitis to deep infections or osteo-
myelitis requiring device removal (incidence of 0.5%–
0.9%). (24)• Tooth abnormalities: The tooth-related injuries seen in 1.3%
to 22.5% of patients are mainly caused by damage to un-
erupted molar buds during the MDO procedure. (24) A
retrospective study of 10 infants with PRS treated with
Figure 3. University of Chicago Hospital mandibular distraction osteogenesis timeline and protocol for patients with Pierre Robin sequence (PRS).CT¼computed tomography; MDO¼mandibular distraction osteogenesis; OSA¼obstructive sleep apnea.
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MDO and followed for over 5 years demonstrated
statistically significant position changes, shape anomalies,
and root malformations of molars compared with matched
controls. (22)
• Hypertrophic scarring: Hypertrophic scarring of the
submandibular skin incisions, seen in 2.1% to 16.6% of
patients, can necessitate scar revision. (1)(24) In 1 study,
scar revision was recommended for 15% of patients. (3)
• Inferior alveolar nerve damage: The inferior alveolar
nerve may be damaged during the MDO procedure and
further aggravated by stretching during the distraction
phase. Distraction rates over 1 mm/day are associated
with a greater incidence of inferior alveolar nerve tran-
sient hypesthesia. (24)(26) There is a need for more
investigation into the permanency of nerve damage from
MDO.
There is some disagreement over whether relapse,
defined as an increase in the sagittal overbite from its
measurement immediately after MDO, should be consid-
ered a surgical complication or a normal postoperative
phenomenon observed after MDO in skeletally immature
patients with developmentally abnormal mandibles. (24)
Relapse has been estimated to occur in up to 64.8% of
patients who have undergone MDO. (24) Recurrence of
significant UAO may require a second MDO procedure
(w2.2% of patients) or tracheostomy placement for persis-
tent obstruction (w2.2%). (18)
The ideal age at which to undertake MDO is worthy of
discussion. It has been shown that MDO can treat patients
Figure 4. Clinical case. A 3-day-old female neonate with isolated Pierre Robin sequence (PRS), and wide Veau II cleft palate underwent multidisciplinaryevaluation. She was found to have severe obstructive sleep apnea on polysomnography (PSG) (preoperative apnea-hypopnea index 35.91, nadiroxygen saturation high 80s), and deemed a surgical candidate for mandibular distraction osteogenesis. She underwent virtual surgical planning (VSP)preoperatively. A) Preoperative computed tomography scan with oblique orientation of mandibular osteotomies. B) VSP-calculated simulatedplacement of a 70-degree curvilinear distractor, with planned total advancement of 14.7 mm bilaterally. C) VSP-calculated preoperative airway volume(1,065 mm3). D) VSP-simulated postoperative airway volume (1,497 mm3) with planned mandibular distraction. At age 3 months and weight 3.0 kg,she underwent placement of the planned distractors. The latency phase was 24 hours, and distraction phase was 26 days with total mandibularadvancement of 14 mm on the right and 10 mm on the left. Postdistraction PSG showed apnea-hypopnea index to be 2.6, and nadir oxygen saturationof 71%. The consolidation phase was 6 weeks. E) Soft tissue and F) bone changes after consolidation phase, before distractor removal.
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with PRS who are only days old, but the smaller mandible
size and lack of mineralization compounds the surgical
complexity of distractor placement in this patient popula-
tion. (27) One study found that patients older than 5 months
had relatively fewer major postoperative complications;
however, no statistically significant difference was found
between overall complication rates in newborns and older
infants. (27) Of note, adult patients have a worse prognosis
after MDO, perhaps because of the reduced ability of adult
mesenchymal stem cells to differentiate under the mechan-
ical stress of distraction. (28)
Experience of the operating surgeon is another factor that
affects MDO success. Surgeons who perform 10 or fewer
craniofacial distractions per year have a complication rate as
high as 55.6%, compared with the average 35.6% reported for
MDO surgeries performed by experienced practitioners. (29)
MDO DEVICES—EXTERNAL AND INTERNAL
Mandibular distractors are available in 2 main categories:
internal (Fig 4) and external devices (Fig 5). The most
apparent difference between the external and internal dis-
traction devices is their visibility and amount of facial
obstruction. Internal devices, with no visible external hard-
ware, have been cited to reduce parental anxiety, allow faster
return to school or daycare, and facilitate breastfeeding. (8)
(30) In addition, because the average distraction phase for
internal devices is shorter, children undergoing internal
distractor placement also experience reduced hospital
length of stay. (8) Internal distractors have a lower risk of
pin site–associated infections and by their nature, necessitate
less wound care. The potential downside of internal devices is
the inability to modify the vector of distraction after implan-
tation; however, with virtual surgical planning and the ability
to place internal devices more precisely, the aforementioned
concern is mitigated. Both internal and external distractors
require a second operation to remove the hardware, though on
occasion, external distractors can be removed under sedation.
Long-term injury of themarginalmandibular branch as well as
greater hypertrophic scarring is cited more frequently with
external distractors. Indications for the external distraction
device have historically included the need for a multiplanar
distraction and ability to immediately address mandibular
asymmetries and open bite deformities during the surgery.
To place internal distractors precisely, computed tomography is
required, which necessitates additional radiation exposure.
(1) However, in the last decade, the development of internal,
multivector, and curvilinear models have facilitated a similar
fine tuning ofmandibular segments compared with that in the
external models. (17)
A comprehensive literature review analyzing 711 pediat-
ric patients younger than 18 years with craniofacial abnor-
malities who underwent MDO between 1992 and 2013
found that when distractor type was specified, a slightly
higher percentage of internal distractors was used by sur-
geons (53.4% to 46.6%), particularly in more recent pub-
lications. The complication rate in this study was 22.1%with
external distractors and 8.3% with internal distractors. (18)
POST-MDO MANAGEMENT
In light of the paucity of data on the long-term stability of
MDO and the concern for tooth injury and long-term mal-
occlusion, routine follow-up with dentistry, orthodontics, oral
TABLE 3. Rate of Complications Associated withMandibular Distraction Osteogenesis
SHORT-TERMCOMPLICATIONS
LONG-TERMCOMPLICATIONS
Infection Malocclusion
• 6% (17) • 2.4% (17) “skeletal openbite”
• 6.3% (18) Relapse
• 9.5% (3) • 64.8% (24)
• 11.8% internal non-resorbable, 12.8% externaldevice, 18.5% resorbable (8)
Tooth injury/abnormalities
• 22% (25) • 1.3% (18)
Inappropriate vector ofdistraction
• 21% (3) molar damage
• 0.67–8.8% (24) • 22.5% (24)
Device malfunction Scarring
• 1.5% (18) • 2.1% (17)
• 2.9% internal nonresorbable,6.4% external device (8)
• 2.3% (18)
• 7.3% (17) • 15.6% (24)
• 7.5–7.9% (24) Limited mandibular rangeof motion
Fusion error • 1.1% (18)• 2.4% (24) premature
consolidation andfibrous nonunion
Nerve damage/palsy• 2% (25)• 2.5% (18)• 5.5% external device, 5.9%internal nonresorbable (8)
• 11.4% (24)
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surgery, plastic surgery, and otolaryngology is critical to
achieve sustained success after MDO. As patients age after
MDO, they may require further orthodontic care, aesthetic
surgical procedures such as upper jaw or chin reposition-
ing (genioplasty [cutting and repositioning the chin] or Le
Fort osteotomy [cutting and repositioning the upper jaw]),
and in some cases, repeat MDO. (1)(9)
At the authors’ institution, patients with PRS with cleft
palates typically undergo another PSG before cleft palate
closure to ensure the absence of airway obstruction, because
cleft palate repair, in and of itself, is pro-obstructive. (31) After
cleft repair, these patients may develop abnormal speech
because of velopharyngeal insufficiency leading to nasal air
emission. (32) Some of the abnormal speech processes ob-
served include hypernasality, hyponasality, velopharyngeal
hypodynamism (functional impairment of the velopharyngeal
apparatus), and replacement of oral sounds with glottal stop
(consonant sound formed by air escape after closed glottis) or
pharyngeal fricatives (sound formed by constricting airflow in
the pharynx). (33) In these cases, early intensive speech therapy
is recommended to correct these issues. Children as young as 1
year old can begin performing exercises to strengthen their
velopharyngealmuscles. If speech therapy alone is insufficient,
surgical interventions should be considered, including enlarge-
ment of the posterior pharyngeal wall, pushback palatoplasty
to lengthen the palate, and pharyngeal flaps. (32) In addition,
children with cleft palates are at increased risk for otitis media
leading to conductive hearing loss. (34) Some institutional
protocols suggest a hearing assessment every 6 months for
patients between 1 and 4 years of age as well as otoscopic
assessment for otitis media. Children with conductive hearing
loss may benefit from insertion of tympanostomy tubes. (34)
MDO—QUALITY OF LIFE IMPLICATIONS
The term “health-related quality of life” (HRQOL) describes
a metric that allows objective evaluation of a treatment’s
impact on the physical, psychological, and social aspects of a
patient’s day-to-day life. HRQOL is an important factor to
include in the outcome metrics of a particular treatment. A
survey study given to caregivers of children who previously
underwent MDO demonstrated a benefit in HRQOL after
MDO. (35) Caregivers felt that MDO provided the largest
benefit in the physical domain, specifically the profile of the
lower face. (35) Generalizability of these data is limited,
given the small sample size (n¼21) and retrospective nature
of this study (with a time gap of 1–4 years). Thus, additional
data are needed on the HRQOL benefit of MDO compared
with other PRS interventions in children. In contrast, data
from an HRQOL study on adult patients undergoing MDO in
France showed that 43% of patients found the treatment
painful, 19% of patients felt some degree of stress during
the course of the procedure, and 17% of patients experienced
sleep alterations. Patients were better able to persevere through
treatments when they had hope for improvement. (36)
SURGICAL ALTERNATIVES TO MDO
TracheostomyTracheostomy has been described as the definitive treatment
for correcting UAO and is considered when other options
fail, in cases of underlying neurologic conditions causing
central apnea, or in cases of subglottic obstruction. Trache-
ostomy is a necessary treatment in approximately 10% of
patients with PRS. (9) In some cases, a tracheostomy is used
as a temporary measure with the goal of decannulation after
the child grows and develops. Tracheostomies are associated
with amorbidity of 43% to 65%,mortality of up to 6%, and the
need for skilled nursing care and additional medical equip-
ment at home. Complications associated with tracheostomy
use include accidental decannulation or mucous plugging
leading to sudden UAO, airway infections, bleeding, stomal
maintenance problems, speech and swallowing delay, granu-
lations, and laryngeal/tracheal stenosis. (3)(8)(37)
Figure 5. External mandibular distractors. Example of external mandibular distractor system in an 8-week old child with severe obstructive sleep apneaassociated with Pierre Robin sequence. A) Frontal view; B) right lateral view.
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Tongue-Lip AdhesionTongue-lip adhesion (TLA) is a variant of the glossopexy
procedure. It involves releasing the genioglossus muscle
of the tongue in an attempt to bring the tongue forward
and open the pharyngeal airway to relieve UAO. The
TLA is typically released by 12 months of age. Although
this procedure works well for managing UAO, it tends
to exacerbate dysphagia. Children often have diffi-
culty maintaining adequate nutritional intake with this
procedure and may require prolonged nasogastric or
gastrostomy tube feedings. Over 80% of institutions
have stopped using this procedure, turning more to-
ward alternative methods of nasopharyngeal airway
stabilization. (3)
NONSURGICAL ALTERNATIVES TO MDO
Given the morbidity associated with surgical treatment of
UAO, there is great interest in developing nonsurgical alter-
natives to relieving the obstruction, particularly when conser-
vative measures such as prone positioning, nasopharyngeal
intubation, and continuous positive airway pressure are
inadequate. Nonsurgical treatment of UAO in patients
with PRS should be aimed at pharyngeal wall stabilization
and hypopharynx widening by shifting the tongue ante-
riorly to attenuate the effects of glossoptosis.
In Germany, several studies have demonstrated success
with the use of a removable orthodontic pre-epiglottic baton
plate (PEBP) with a velar extension to treat PRS-associated
UAO (Fig 6). The device is custom made from a patient
maxillary castmodel and is composed of compound soft and
hard acrylic. The device covers the palate and the alveolar
ridges and contains a velar extension, the position of which
is modified under endoscopy. (6) The device is held in place
with suction adhesion, and sometimes requires the addition
of an external wire structure to be secured via adhesive to the
patient’s face.
In patients with isolated UAO who underwent preinter-
vention PSG, the use of a PEBP device significantly im-
proved mixed-airway obstruction index scores 3 months
after application without adverse effects. (38) In many
infants, the use of a PEBP not only significantly improves
UAO, but with reliable therapy, also promotes sucking
and feeding without significant morbidity compared with
a similar device without velar extension. (6) By stimulat-
ing weight gain and improving overall nutritional status,
the use of PEBP in this patient population may obviate the
need for supplemental enteral nutrition.
Figure 6. Pre-epiglottic baton plate (PEBP) with velar extension. A) Diagram representation of the PEBP with velar extension, with each of the alveolar,cleft palate and velar extension components. B) Diagram of a patient with Pierre Robin sequence (PRS), including micrognathia, glossoptosis, cleftpalate, and posterior oropharyngeal narrowing. C) Diagram of PEBP with velar extension demonstrating anterior repositioning of posterior tongue basein a patient with PRS, thus increasing the posterior oropharyngeal space.
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By precluding the need for prolonged general anesthesia
and surgical intervention, such as tracheostomy and MDO,
the use of PEBP is an attractive option to address isolated
UAO in patients with PRS. Although data from the German
experience are promising, the use of PEBPs has not yet been
described in the United States.
CONCLUSIONS
Standardized clinical evaluation and management guide-
lines in pediatric units and NICUs are essential to ensure
timely diagnosis, evaluation, and management of UAO in
patients with micrognathia and in those with PRS. Specif-
ically, a multidisciplinary care team is required to ensure
that patients receive proper airway evaluation, necessary
surgical treatments, genetic consultations and subsequent
referrals, and continuous nutrition and speech therapy.
We herein present a flow management algorithm to aid in
identifying and treating patients with PRS.
MDO remains the gold standard surgical treatment
available to definitively relieve UAO in select patients with
PRS. However, it carries morbidity and risk in both the early
and late postoperative period. The exploration of less inva-
sive treatment options, such as the PEBP with velar exten-
sion, may avoid the risks and complications associated with
surgical intervention in a subset of patients with PRS.
References1. Scott AR. Surgical management of Pierre Robin sequence: usingmandibular distraction osteogenesis to address hypoventilation andfailure to thrive in infancy. Facial Plast Surg. 2016;32(2):177–187
2. NemecU, Nemec SF, Brugger PC, et al. Normal mandibular growthand diagnosis of micrognathia at prenatal MRI. Prenat Diagn.2015;35(2):108–116
3. Scott AR, Tibesar RJ, Sidman JD. Pierre Robin sequence:evaluation, management, indications for surgery, and pitfalls.Otolaryngol Clin North Am. 2012;45(3):695–710, ix
4. Kooiman TD, Calabrese CE, Didier R, et al. Micrognathia andoropharyngeal space in patients with Robin Sequence: prenatal MRImeasurements. J Oral Maxillofac Surg. 2018;76(2):408–415. doi:10.1016/j.joms.2017.07.163
5. Genisca AE, Frías JL, Broussard CS, et al; National Birth DefectsPrevention Study. Orofacial clefts in the National Birth DefectsPrevention Study, 1997-2004. Am J Med Genet A. 2009;149A(6):1149–1158
6. Buchenau W, Wenzel S, Bacher M, Müller-Hagedorn S, Arand J,Poets CF. Functional treatment of airway obstruction and feedingproblems in infants with Robin sequence. Arch Dis Child FetalNeonatal Ed. 2017;102(2):F142–F146
7. Dennison WM. The Pierre Robin syndrome. Pediatrics. 1965;36(3):336–341
8. Paes EC,Mink van derMolenAB,MuradinMSM, et al. A systematicreview on the outcome of mandibular distraction osteogenesis ininfants suffering Robin sequence. Clin Oral Investig. 2013;17(8):1807–1820
9. Mackay DR. Controversies in the diagnosis and management of theRobin sequence. J Craniofac Surg. 2011;22(2):415–420
10. Berry RB, Budhiraja R, Gottlieb DJ, et al. Rules for scoringrespiratory events in sleep: update of the 2007 AASM Manual forthe Scoring of Sleep and Associated Events. J Clin Sleep Med. 2012:8(5):597–619. doi: 10.5664/jcsm.2172.
11. Roland PS, Rosenfeld RM, Brooks LJ, et al; American Academyof Otolaryngology—Head and Neck Surgery Foundation. Clinicalpractice guideline: polysomnography for sleep-disorderedbreathing prior to tonsillectomy in children. Otolaryngol Head NeckSurg. 2011;145(1 suppl):S1–S15
12. Katz ES, Mitchell RB, D’Ambrosio CM. Obstructive sleep apnea ininfants. Am J Respir Crit Care Med. 2012;185(8):805–816
13. Garg RK, Afifi AM, Garland CB, Sanchez R, Mount DL. Pediatricobstructive sleep apnea: consensus, controversy, andcraniofacial considerations. Plast Reconstr Surg. 2017;140(5):987–997
14. Cruz MJ, Kerschner JE, Beste DJ, Conley SF. Pierre Robinsequences: secondary respiratory difficulties and intrinsic feedingabnormalities. Laryngoscope. 1999;109(10):1632–1636
15. Zellner EG, Mhlaba JM, Reid RR, Steinbacher DM. Doesmandibular distraction vector influence airway volumes andoutcome? J Oral Maxillofac Surg. 2017;75(1):167–177
16. McCarthy JG, Schreiber J, Karp N, Thorne CH, Grayson BH.Lengthening the human mandible by gradual distraction. PlasticReconstr Surg. 1992;89(1):1–10
17. Verlinden CRA, van de Vijfeijken SECM, Tuinzing DB, Jansma EP,Becking AG, Swennen GRJ. Complications of mandibulardistraction osteogenesis for developmental deformities: asystematic review of the literature. Int J Oral Maxillofac Surg.2015;44(1):44–49
18. Tahiri Y, Viezel-Mathieu A, Aldekhayel S, Lee J, Gilardino M. Theeffectiveness of mandibular distraction in improving airwayobstruction in the pediatric population. Plast Reconstr Surg. 2014;133(3):352e–359e
19. Hong P. A clinical narrative review of mandibular distractionosteogenesis in neonates with Pierre Robin sequence. Int J PediatrOtorhinolaryngol. 2011;75(8):985–991
20. Mhlaba JM, Talmage GD, Baroody FM, Bandla HP, Reid RR.Polysomnographic titration of mandibular lengthening bydistraction in tongue-based airway obstruction. J Am Soc MaxillofacSurg. 2017;1(4):11–16.
21. Mhlaba JM, ChenML, Bandla HP, Baroody FM, Reid RR. Predictivesoft tissue airway volume analysis in mandibular distraction:pushing the envelope in surgical planning for obstructive sleepapnea. J Craniofac Surg. 2016;27(1):181–184
American Board of PediatricsNeonatal-Perinatal ContentSpecification• Know the associations and clinical features and management ofmacroglossia and hypoplastic mandible, including the PierreRobin syndrome.
Vol. 19 No. 5 MAY 2018 e287 by guest on May 1, 2018http://neoreviews.aappublications.org/Downloaded from
22. Paes EC, BittermannGKP, BittermannD, et al. Long-term results ofmandibular distraction osteogenesis with a resorbable device ininfants with Robin Sequence: effects on developing molars andmandibular growth. Plast Reconstr Surg. 2016;137(2):375e–385e
23. Ow ATC, Cheung LK. Meta-analysis of mandibular distractionosteogenesis: clinical applications and functional outcomes. PlastReconstr Surg. 2008;121(3):54e–69e
24. Master DL, Hanson PR, Gosain AK. Complications of mandibulardistraction osteogenesis. J Craniofac Surg. 2010;21(5):1565–1570
25. Murage KP, Costa MA, Friel MT, Havlik RJ, Tholpady SS, Flores RL.Complications associated with neonatal mandibular distractionosteogenesis in the treatment of Robin sequence. J Craniofac Surg.2014;25(2):383–387
26. Mofid MM, Manson PN, Robertson BC, Tufaro AP, Elias JJ, VanderKolk CA. Craniofacial distraction osteogenesis: a review of 3278cases. Plast Reconstr Surg. 2001;108(5):1103–1107.
27. Kolstad CK, Senders CW, Rubinstein BK, Tollefson TT. Mandibulardistraction osteogenesis: at what age to proceed. Int J PediatrOtorhinolaryngol. 2011;75(11):1380–1384
28. Tan J, Xu X, Tong Z, et al. Decreased osteogenesis of adultmesenchymal stem cells by reactive oxygen species under cyclicstretch: a possible mechanism of age related osteoporosis. Bone Res.2015;3:15003–15006
29. Oktay H, Baydas B, Ersöz M. Using a modified nutrition plate forearly intervention in a newborn infant with Pierre Robin sequence: acase report. Cleft Palate Craniofac J. 2006;43(3):370–373
30. Mandell DL, Yellon RF, Bradley JP, Izadi K, Gordon CB.Mandibulardistraction for micrognathia and severe upper airway obstruction.Arch Otolaryngol Head Neck Surg. 2004;130(3):344–348
31. Jackson O, Basta M, Sonnad S, Stricker P, Larossa D, Fiadjoe J.Perioperative risk factors for adverse airway events in patientsundergoing cleft palate repair.Cleft Palate Craniofac J. 2013;50(3):330–336
32. de Buys Roessingh AS, Herzog G, Cherpillod J, Trichet-Zbinden C,Hohlfeld J. Speech prognosis and need of pharyngeal flap for nonsyndromic vs syndromic Pierre Robin Sequence. J Pediatr Surg.2008;43(4):668–674
33. Pinto MDB, Pegoraro-Krook MI, Andrade LKF, Correa APC, Rosa-Lugo LI, Dutka JCR. Intensive treatment of speech disorders inrobin sequence: a case report. CoDAS. 2017;29(5):e20160084
34. Glynn F, Fitzgerald D, EarleyMJ, RowleyH. Pierre Robin sequence:an institutional experience in the multidisciplinary management ofairway, feeding and serous otitis media challenges. Int J PediatrOtorhinolaryngol. 2011;75(9):1152–1155
35. Hong P, McNeil M, Kearns DB, Magit AE. Mandibular distractionosteogenesis in children with Pierre Robin sequence: impact onhealth-related quality of life. Int J Pediatr Otorhinolaryngol. 2012;76(8):1159–1163
36. Castry G, Ella B, Emparanza A, Siberchicot F, Zwetyenga N.[Psychological impact of alveolar mandibular distraction]. RevStomatol Chir Maxillofac. 2009;110(5):251–255
37. Serra A, Cocuzza S, Longo MR, Grillo C, Bonfiglio M, Pavone P.Tracheostomy in childhood: new causes for an old strategy. Eur RevMed Pharmacol Sci. 2012;16(12):1719–1722
38. Bacher M, Sautermeister J, Urschitz MS, Buchenau W, Arand J,Poets CF. An oral appliance with velar extension for treatment ofobstructive sleep apnea in infants with Pierre Robin sequence. CleftPalate Craniofac J. 2011;48(3):331–336
39. Kelberman D, Tyson J, Chandler DC, et al. Hemifacial microsomia:progress in understanding the genetic basis of a complexmalformation syndrome. Hum Genet. 2001;109(6):638–645
40. Horgan JE, Padwa BL, LaBrie RA, Mulliken JB. OMENS-Plus:analysis of craniofacial and extracraniofacial anomalies inhemifacial microsomia. Cleft Palate Craniofac J. 1995;32(5):405–412
41. Vilaplana F, Muiños SJ, Nadal J, Elizalde J, Mojal S. Sticklersyndrome. Epidemiology of retinal detachment. Arch Soc EspOftalmol. 2015;90(6):264–268 [English Edition]
42. Richards AJ, McNinch A, Martin H, et al. Stickler syndrome and thevitreous phenotype: mutations in COL2A1 and COL11A1. HumMutat. 2010;31(6):E1461–E1471
43. Shanske AL, Bogdanow A, Shprintzen RJ, Marion RW. TheMarshall syndrome: report of a new family and review of theliterature. Am J Med Genet. 1997;70(1):52–57
44. Genetics Home Reference Stickler syndrome. November 2017:1-8.
45. Dixon J, Trainor P, Dixon MJ. Treacher Collins syndrome. OrthodCraniofac Res. 2007;10(2):88–95
46. Hunt JA, Hobar PC. Common craniofacial anomalies: the facialdysostoses. Plast Reconstr Surg. 2002;110(7):1714–1728.
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1. A newborn patient presents with the clinical triad of micrognathia, glossoptosis, and upperairway obstruction (UAO) and is identified as having Pierre Robin sequence (PRS). Theincidence of PRS varies by race and ethnicity and has been found to be highest in patientswith which of the following background?
A. Asian/Pacific Islander.B. White.C. African American.D. American Indian/Alaska Native.E. Hispanic.
2. The newborn patient with PRS has signs of respiratory distress including grunting andsubcostal retractions. The primary objective of PRS treatment is to secure a safe airwaybeginningwith conservative and noninvasivemeasures such as continuous pulse oximetrymonitoring, and prone or side positioning. What is the proportion of infants that canbe stabilized with positioning changes alone?
A. 10%.B. 25%.C. 50%.D. 70%.E. 90%.
3. The newborn patient with PRS has been stabilized and management plans are beingdiscussed with the parents. Mandibular distraction osteogenesis (MDO) has become thepreferred surgical option atmany institutions for neonates and infants with PRS-associatedUAO. The treatment involves an initial surgery to place the device, followed by a 3-phasedistraction period that includes a latency phase, a distraction phase, and a consolidationphase. Which of the following statements regarding MDO is CORRECT?
A. During the distraction phase, the mandibular segment is typically advanced by1 mm daily.
B. The latency phase is typically is a 48- to 72-hour period after distractor placementand before the start of distraction.
C. A 12-week consolidation phase is necessary to allow for complete bone healing.D. Mandibular distraction is considered complete once the mandible is advanced
beyond a standardized anatomic endpoint.E. Overcorrection of themandible is recommended to ensure appropriate relief of the
UAO.
4. The patient with PRS is preparing for the MDO procedure. While data from systematicreviews and meta-analyses indicate that 82% to 100% of patients have an overall positiveoutcome from MDO, short- and long-term complications have been described. Whichof the following statements is CORRECT regarding MDO complications?
A. The overall complication rate of MDO is 10%.B. Osteomyelitis requiring device removal is the most common infection following
MDO with an incidence of 1.8%.C. The tooth-related injuries seen in as many as 22.5% of patients are mainly caused
by damage to unerupted molar buds during the MDO procedure.D. Hypertrophic scarring of the submandibular skin incisions is uncommon, occurring
in less than 1% of patients.E. Inferior alveolar nerve damage only occurs in overaggressive distraction rates over
1.5 mm/day.
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5. A newborn patient with PRS is noted to have evidence of UAO. Various surgicaland nonsurgical options are available for patients with UAO not responding toposition changes alone, including tracheostomy and the tongue-lip adhesion (TLA)procedure. Which of the following statements is CORRECT regarding these alternativemethods of treatment?
A. A tracheostomy is a necessary treatment in approximately 25% of patients withPRS.
B. Tracheostomies are associated with mortality rates as high as 10%.C. The TLA procedure works well for managing UAO, but is no longer performed in a
majority of centers because of the high incidence of feeding difficulties associatedwith it.
D. The TLA is typically released by 6 months of age.E. A custom-made orthodontic pre-epiglottic baton plate has been shown to improve
UAO but is associated with poor feeding outcomes.
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DOI: 10.1542/neo.19-5-e2772018;19;e277NeoReviews
Carrie E. Zimmerman, Laura S. Humphries, Tulsi Roy and Russell R. ReidMandibular Distraction for Micrognathia in Neonates
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DOI: 10.1542/neo.19-5-e2772018;19;e277NeoReviews
Carrie E. Zimmerman, Laura S. Humphries, Tulsi Roy and Russell R. ReidMandibular Distraction for Micrognathia in Neonates
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