Mandibular Distraction Osteogenesis as a Primary Intervention in Infants With Pierre Robin Sequence

Abstract

Background:

Pierre Robin sequence (PRS) is a triad of congenital facial abnormalities that can present as a syndrome (syndromic PRS [sPRS]) or an isolated entity (isolated PRS [iPRS]). Patients with PRS can develop airway and feeding problems that may result in failure to thrive. Mandibular distraction osteogenesis (MDO) is a method for improving the functional issues associated with breathing and feeding. There is a Paucity of literature evaluating the outcomes of MDO between sPRS and iPRS patients.

Methods:

An institutional review board–approved retrospective review of PRS patients managed by a single surgeon and treated with MDO between January 2015 and December 2019 at a tertiary referral hospital was performed. The patients were stratified into iPRS or sPRS based on gene testing. Airway outcome measures included avoidance of tracheostomy, relief of sleep apnea, and oxygen saturation improvement. Primary feeding measures included achievement of full oral feeds and growth/weight gain. Statistical analysis included t tests and χ² tests where appropriate using SPSS.

Results:

Over the study period, of the 29 infants with PRS, 55% identified as iPRS and 45% as sPRS. There were no significant differences in the patient characteristics, apnea-hypoxia index (22.27 ± 12.27) and laryngeal view (3 ± 0.79) pre-MDO. After MDO, 83% of the subjects achieved a positive feeding outcome and 86% achieved a positive airway outcome with no statistical significance between sPRS and iPRS (P = 0.4369). There was a statistically significant change post-MDO in apnea-hypoxia index (5.24 ± 4.50, P = 0.02) and laryngeal view (1.59 ± 1.00, P = 0.01).

Conclusions:

Our recent experience would lead us to believe that sPRS patients have greater morbidities and challenging clinical developments that, when properly evaluated, can be managed by MDO. There is a potential role for MDO in reducing the need for traditional surgical interventions for respiratory and feeding problems in both iPRS and sPRS patients.

Pierre Robin sequence (PRS) is a triad of congenital facial abnormalities that includes micrognathia, glossoptosis, and upper airway obstruction (AO) with or without U-shaped cleft palate.¹ The PRS sequence begins with the failure of the mandible to grow anteriorly (micrognathia), which reduces the oropharyngeal space² and causes posterior displacement of the tongue (glossoptosis)³ leading to AO. Respiratory dysfunction due to AO is the main cause of feeding difficulties leading to poor growth.^4–6 Furthermore, PRS can present as one component of a known or suspected syndrome (syndromic PRS [sPRS]) or as an isolated finding (isolated PRS [iPRS]). Pierre Robin sequence can potentially lead to life-threatening obstructive apnea and feeding difficulties during the neonatal period. Current evidence suggests that the incidence of PRS varies between 1 in 8500 and 1 in 14,000 live births in the United States.^7,8 A variety of studies have reported the mortality rate of PRS patients to vary between 10% and 30%.^3,9–11 In the absence of treatment, children with PRS may succumb to obstructive sleep apnea (OSA), asphyxia, hypoxia, respiratory failure, cor pulmonale, malnutrition, and death.^2,12 Respiratory dysfunction due to AO is the main cause of feeding difficulties leading to poor growth.^4–6 In addition to feeding and growth issues associated with isolated PRS, children with sPRS can develop other related problems due to an underlying syndrome or associated anomalies, respectively. A combination of these factors may result in failure to thrive.¹² Furthermore, the OSA leads to cardiovascular problems, metabolic syndromes, and delays in development into adulthood.

Pierre Robin sequence patient management is focused on improving functional status associated with airway and feeding.¹³ Nonsurgical management involves positioning the patient, nasopharyngeal airway, or nasal continuous positive airway pressure.⁶ Surgical management can involve tongue-lip adhesion, tracheostomy, or mandibular distraction osteogenesis (MDO).^3,10 MDO lengthens the mandible and positions the patient’s tongue anteriorly to relieve AO. Previous studies have shown that MDO relieves AO,⁴ reduces the need for tracheostomy,¹⁴ and leads to decreased length of hospital stay and cost savings.¹⁵ MDO can be chosen as a primary management option for AO in patients with micrognathia. These data have largely focused on nonsyndromic patients as there is minimal information comparing syndromic and nonsyndromic cases.¹⁶ There is a paucity of studies that report on the success of MDO in relieving AO and improving feeding outcomes on sPRS patients. The numerous associated phenomena associated with sPRS patients leads us to hypothesize that MDO would be less successful. A review of the literature would also lead us to believe that sPRS patients have greater morbidities and challenging clinical developments and poorer MDO outcomes. The primary aim of this study was to investigate the efficacy of primary MDO as the treatment for feeding and airway complications in sPRS and iPRS patients.

METHODS

This study presents an institutional review board–approved retrospective review of a single surgeon’s patients and experience treating PRS with MDO (Current Procedural Terminology code 21194, 20690) at a tertiary children’s referral center. We identified 29 patients diagnosed with PRS who underwent MDO from January 1, 2015, to December 30, 2019. Patients who were lost to follow-up within 1 year of MDO or had incomplete medical records were excluded. All patients with PRS were managed in a single pediatric specialty hospital by a multidisciplinary craniofacial team, which included plastic surgery, otolaryngology, medical genetics, speech-language pathology, occupational therapy, and critical care. Mandibular distraction osteogenesis candidacy requirements included sufficient bone matter, morphology that allowed for sufficient mandibular vector, and absence of any other major airway anomaly. Clinical workup included 3-dimensional computed tomography, polysomnogram, and upper airway endoscopy. All patients were evaluated by a clinical geneticist who assessed for a possible genetic syndrome and ordered additional testing as indicated. All patients underwent MDO using the senior author’s technique as outlined in Figure 1.

FIGURE 1.

Top row: a 15-day-old adolescent boy diagnosed with iPRS who, after preoperative evaluation, was found to meet the criteria for bilateral MDO. A, Lateral view of intubation before osteotomy procedure with skin incision marked. B, Identification of the right side of the mandible at the osteotomy site. C, Placement of the distractor. Bottom row: a female diagnosed with iPRS at 21 days old and 6 months old. Comparison of change in mandible preoperatively at 21 days old (D) and postoperatively at 6 months old after distraction hardware removal (E).

Patient variables recorded included sex, race, gestational age, age at time of initial distraction, data from baseline apnea-hypoxia index (AHI), type of syndrome, presence of tracheotomy, length of distraction, number of distraction procedure attempts, and follow-up time. In addition, records were analyzed for occurrence of Gastrostomy tube (g-tube) placement, Nasogastric (NG) tube placement, time to MDO intervention, duration of each MDO intervention, and any additional airway intervention including the following: tracheotomy, repositioning, Nasopharyngeal (NP) tube, and Continuous positive airway pressure (CPAP) use. Patients were then separated into two groups based on the genetic information: patients with iPRS and patients with syndromic PRS who had additional syndromes or genetic anomalies.

During the study period 29 patients were identified with PRS that were treated with MDO and were not lost to follow-up. Of the 29 patients, 16 were grouped into iPRS and 13 were grouped into sPRS. All MDO surgeries were completed in 5 stages: osteotomy, latency (as shown in computed tomography scan on Fig. 2), distraction, consolidation, and remodeling phase

FIGURE 2.

Different views of distraction hardware in place in a 23-day-old iPRS patient during latency phase.

For data analysis, surgical success of MDO included positive airway and feeding outcomes. The positive airway outcome measure included avoidance of tracheostomy (primary airway measure), decannulation, and relief of OSA. Relief of OSA was monitored via AHI and sleep efficiency using polysomnography. Residual moderate OSA is considered when AHI is 5 or greater. Improvement in airway was monitored via Cormack-Lehane system classification of laryngoscopy view. We evaluated feeding surgical outcomes by measuring achievement of full oral feeds at latest follow-up (primary feeding measure), growth/weight gain, and improvement in gastroesophageal reflux. Failure to thrive was defined as any instance where the age-adjusted weight percentile was less than 5%. The repeat of MDO procedure was considered a failed attempt. Complications of the distraction process included external scarring, infection, hardware exposure, device dislodgement, injuries to various branches of the facial nerve, and complications specific to the osteotomy such as dental and neurovascular injuries.

Patient demographics and outcomes were statistically analyzed based on PRS syndrome status. Study interventions for continuous variables were compared using a t test, and categorical data were compared using a χ² or Fisher exact test in the presence of small cell counts (<5). Data were summarized using standard descriptive statistics including the mean, standard deviation, median, quartiles and range for continuous variables, and counts and percentages for categorical data. A P value of 0.05 or less was considered statistically significant for all comparisons. Statistical analysis was conducted in R (R Core Team, 2014), and figures were produced using the package ggplot2.

RESULTS

Our study cohort was composed of 29 patients who were diagnosed either with iPRS (16 patients) or sPRS (13 patients) based on genetic evaluation. All of the 29 patients had had primary bilateral MDO for decannulation or in lieu of an impending tracheostomy. Demographic data for these patients are summarized in Table 1. Of the sPRS group, the majority (46%) were diagnosed as a variety of atypical syndromic PRS, followed by Stickler syndrome (31%), Moebius sequence (15%), and Treacher Collins (8%). There was no significant difference in patient age at primary mandibular distractor placement (78.10 days), birth weight (3.204 lb), presence of cleft palate, or race/ethnicity demographics between the sPRS and iPRS groups (Table 1).

TABLE 1.

Patient Demographic Data

	Total (N = 29)	iPRS (n = 16)	sPRS (n = 13)	P
Sex, n (%)				0.588*
Male	14 (48)	7 (57)	7 (33)
Female	15 (52)	9 (36)	6 (67)
Age at MDO procedure, mean (range), d	78.10 (2–712)	60.94 (16–237)	99.23 (2–712)	0.904†
Birth weight, mean ± SD, lb	3.16 ± 0.41	3.31 ± 0.39	2.95 ± 0.33	0.616†
Race/ethnicity, n (%)				0.984*
White	20 (69)	11 (69)	9 (69)
African American	7 (24)	4 (25)	3 (23)
Latino	2 (7)	1 (6)	1 (8)
Syndrome diagnosis
Stickler	—	—	4 (31%)
Treacher Collins	—	—	1 (8%)
Atypical syndromic PRS	—	—	6 (46%)
Moebius	—	—	2 (15%)
Cleft palate, n (%)				0.525*
No	6 (21)	4 (25)	2 (15)
Yes	23 (79)	12 (75)	11 (85)

^*χ² with P < 0.05 indicating statistical significance.

^†Two-sample, 2-tailed t test with P < 0.05 indicating statistical significance.

Laryngeal view, Cormack-Lehane grade.

Characteristics of MDO

For our study population before the operation to install the distraction device (pre-MDO), there was no significant difference between the sPRS or iPRS groups for PO use (3, P = 0.111), pre-MDO AHI (22.27 ± 12.27, P = 0.50), or pre-MDO laryngeal view (±0.79, P = 0.65; Table 2). After the operation, there was no significant difference between the cohorts in distraction technique with PRS patients having an average of 9.19 ± 10.15 (P = 0.60) days to extubation, average latency and activation period of 10.24 ± 1.36 days (P = 0.42), total hospital stay of 28.55 ± 25.40 (P = 0.51), and consolidation period of 68.83 ± 16.17 (P = 0.50; Table 3). However, the total number of patients requiring corrections to mandibular device placement was 23% in the sPRS group and 0% in the iPRS group (P = 0.042; Table 3).

TABLE 2.

Baseline and Post-MDO Data of sPRS Versus iPRS Patients

Patient	Group Pre-MDO AHI	Post-MDO AHI	Pre-MDO Laryngeal View	Post-MDO Laryngeal View	Pre-MDO Non-PO, n (%)	Post-MDO Non-PO, n (%)	Post-MDO Decannulation, n (%)
Total	22.27 ± 12.27	5.24 ± 4.50	3 ± 0.79	1.59 ± 1.00	27 (93)	5 (17)	25 (86)
iPRS	23.08 ± 21.68	5.64 ± 4.49	3 ± 0.82	1.38 ± 0.72	12 (75)	1 (6)	15 (93)
sPRS	21.02 ± 16.33	4.28 ± 2.85	4 ± 1	1.11 ± 1.12	13 (100)	4 (30)	10 (77)
P	0.5024†	0.5879†	0.6564*	0.136*	0.111*	0.082*	0.153*

Data are presented as mean ± SD, unless otherwise indicated.

^†Two-sample, 2-tailed t test with P < 0.05 indicating statistical significance.

^*χ² with P < 0.05 indicating statistical significance.

Laryngeal view, Cormack-Lehane grade; Non-PO, NG tube or G tube.

TABLE 3.

Clinical Characteristics of Mandibular Distraction Osteogenesis

	Total (N = 29)	iPRS (n = 16)	sPRS (n = 13)	P
Days to extubation, mean ± SD	9.10 ± 9.604	10.81 ± 12.46	7.00 ± 3.54	0.6006*
Latency, mean ± SD, d	10.24 ± 1.36	10.06 ± 1.57	10.54 ± 0.83	0.4248*
Total hospital stay, mean ± SD, d	28.55 ± 25.40	25.00 ± 22.37	32.92 ± 20.60	0.5135*
Consolidation, mean ± SD, d	68.83 ± 16.17	68.94 ± 15.82	68.69 ± 17.23	0.5028*
Methadone wean use	4 (14%)	3 (19%)	1 (8%)	0.390†
Failed MDO (ie, required second distraction), n (%)				0.042†
No	26 (90)	16 (100)	10 (77)
Yes	3 (10)	0 (0)	3 (23)

^*Two-sample, 2-tailed t test with P < 0.05 indicating statistical significance.

^†χ² with P < 0.05 indicating statistical significance.

Laryngeal view, Cormack-Lehane Grade.

Outcomes of Post-MDO

After the consolidation period and the removal of the hardware, there was a similar change in the sPRS and iPRS groups in AHI of 5.24 ± 4.50 (P = 0.58), postoperative weight percentile (P = 0.281), and laryngeal view of 1.59 ± 1.00 (P = 0.136; Table 2). There was no significant difference in avoidance of tracheostomy with 93% of iPRS patients and 77% of sPRS (P = 0.153). In addition, there was no significant difference in avoidance of feeding tube with 93% of iPRS and 71% of sPRS (P = 0.083) not having a gastronomy tube in place after mandibular distraction hardware removal. Airway surgical success, defined as avoidance of impending tracheostomy or successful tracheostomy removal within 1 year of MDO, was achieved in 91% of the patient cohort. Feeding surgical success, defined as avoidance of impending gastronomy tube or starting oral feeds within 1 year of MDO, was achieved in 86% of the patients (Fig. 1). A distraction hardware realignment was needed in 23% of the sPRS patients (P = 0.042). Finally, for the entire study population, there was a significant difference change post-MDO in AHI (P = 0.02) and laryngeal view (P = 0.01) when compared with the pre-MDO numbers.

DISCUSSION

In PRS patients, the posterior displacement of the tongue in the pharynx due to a micrognathic mandible is classically the cause of the AO and the subsequent feeding difficulties. Mandibular distraction is the current mainstay of treatment for tongue-based AO due to the anatomical correction. Our study aimed to clarify the effects of mandibular distraction on syndromic and nonsyndromic PRS patients over a retrospective longitudinal period.

Our finding that mandibular distraction yielded an improvement in AO and feeding difficulties is not surprising and is consistent with traditional models in which relieving the airway leads to a reduction in failure to thrive.¹⁷ What was surprising was the magnitude of the impact with both sPRS and iPRS cohorts. The success rate of MDO in our sPRS and iPRS study population was 86% for airway and 83% for feeding end points, which compares favorably with the current PRS literature that reports overall success rates of 84% to 100%. To our knowledge, this is the largest retrospective comparison of MDO in PRS patients by sPRS and iPRS. The total number of repeat distraction attempts was significantly higher than expected in the sPRS group (3 sPRS patients and 0 iPRS, P = 0.042). However, 2 of the 3 distraction patients required a repair of the mandible, but this still led to improvements to their predistraction numbers. These data suggest that although sPRS patients present with similar clinical morphology as iPRS patients (ie, retrognathia and glossoptosis), they are more complex than iPRS patients and may require additional interventions to relieve airway and feeding obstructions. More than 50 syndromes have been associated with PRS, some of which can have only subtle presenting findings, which is why genetics evaluation was performed for each case to accurately identify sPRS versus iPRS. Nonetheless, surgical success was not statistically different between the 2 groups (for iPRS cohort vs for sPRS cohort, P = 0.0) and demonstrates that although the iPRS group has a higher success rate, the success rate for the sPRS group is still highly acceptable (Table 3). That said, the efficacy of distraction is less clear in sPRS patients with more severe syndromes with additional comorbidities such as Smith-Lemli-Optiz or otopalatodigitial syndrome.^13,18,19

Furthermore, there were no statistically significant differences between our 2 cohorts in terms of age at time of distraction, AO, etc (Table 1), factors that may have confounded analysis were controlled for. Results regarding the quantification of mandibular morphology and airway morphological changes, palatoplasty, or other medical comorbidities were beyond the scope of this analysis. Unlike previous reports by Zhang et al¹⁰ and Lee et al,²⁰ sPRS or iPRS did not directly correlate with complications. In our study, mandibular distraction yielded an improvement in AO. Specifically, AHI decreased from 20.86 to 5.15 and laryngeal view grade decreased from 2.91 to 1.59; this represents a decrease in OSA type from severe or moderate to mild.¹⁹ In addition, Humphries et al²¹ studied airway morphological changes in PRS and saw a similar improvement in the airway in their cohort of 20 patients. Their perspective of airway shape suggests that MDO success can be attributed to correction of the multifactorial morphologic problems in the sequence. Meanwhile, da Costa et al⁴ and other studies^19,22 have demonstrated that the highest predictive factor of surgical intervention was a high obstructive index on preintervention sleep study, as was found with all our patients (Table 3). Grades of retrognathia and glossoptosis are not predictive of respiratory and feeding disorders although it was in our protocol to note the grade before decannulation.⁶ In addition, although the primary goal of MDO is to improve AOs and breathing difficulties, there seems to be a relationship between the airway intervention and feeding difficulties. Feeding difficulty in PRS patients, characterized by low oral intake, feeding times of greater than 30 minutes, fatigue, and coughing, gagging, and vomiting with intake have been hypothesized to occur secondary to upper AO.¹⁷ This study showcased the ability for MDO to relieve UAO and prevent tracheostomy while also permitting appropriate weight gain without the use of feeding tubes. Findings from 2 other retrospective studies suggest that MDO may promote normal feeding by relieving gastroesophageal reflux disease and swallowing function.^23,24 Moreover, the avoidance of an additional surgical intervention and decreased time needed for a feeding tube are potential benefits for quality of life.^1,17

Traditionally, managing AO conservatively with CPAP or prone positioning is prioritized over addressing feeding dysfunction. This strategy is the cornerstone of treatment because PRS tends to achieve normal or near-normal mandibular size within a few years of birth.^3,11,15 However, Ching et al¹⁴ and Lee et al²⁰ showed that this non-intervention method can result in significant morbidity and mortality with complication rate as high as a 43%. Those patients, who fail conservative management, generally require surgical intervention, with tracheostomy being the preferred long-term airway stabilization. Furthermore, children with PRS who undergo tracheostomy are not typically decannulated until approximately the age of 3 years, which is correlated to delays in speech production and language development.^10,14,25 Tongue-lip adhesion is another surgical technique used to prevent occlusion of the upper airway, but patients are typically anchored in the first month of life and reversed at approximately the age of 1 year. Tongue-lip adhesion also has been correlated with delays in speech and language production. Our multidisciplinary team uses MDO to primary surgical treatment because it addresses a multifaceted dysfunction in the sequence.^4,5,21 Furthermore, studies have shown that this strategy has a lower cost burden to the system as well with estimated cost saving of US $300,000 over tracheostomy in a 3-year period and a lower cost than tongue-lip adhesion when associated procedures and outpatient care for PRS are taken into account.²⁶

The limitations of this study are as follows: exclusion of 1 patient due to incomplete data, the inherent limitation of retrospective investigation, and the relatively small number of patients. Future studies can expand on the preliminary findings of this study with computed tomography and upper airway endoscopy to quantify the morphology of AOs and its contribution to the unique pathophysiology of sPRS and iPRS. In addition, longitudinal investigations could also include speech outcomes and resonance outcomes after palatoplasty in this cohort to determine the contribution of MDO in the natural course of PRS. This study cohort can be followed longitudinally as most of them are still seen by the same multidisciplinary cleft-craniofacial team.

CONCLUSIONS

Mandibular distraction osteogenesis as a primary approach to PRS patients allows for relieving airway and feeding obstructions without the delay in speech and language associated with other surgical methods. Respiratory and feeding complications are frequent and severe in pediatric patients with anomalies or syndromes. This study showcases that in a multidisciplinary team setting, MDO is a reliable and effective strategy to address the airway and feeding obstruction of a syndromic PRS patient. Although prior studies indicate that syndromic PRS patients experience higher complications and morbidity from surgical treatment, the recent advances in MDO allow for improved development outcomes. Mandibular distraction osteogenesis as primary intervention in PRS patients is a reliable and extremely effective method to relieve a lifetime of airway and feeding complications.