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Feeding and reflux in children after mandibular distraction osteogenesis for micrognathia: A systematic review
Accepted Manuscript Title: Feeding and reflux in children after mandibular distraction osteogenesis for micrognathia: a systematic review Author: Omar Breik Kandiah Umapathysivam David Tivey Peter Anderson PII: DOI: Reference:
S0165-5876(16)30026-X http://dx.doi.org/doi:10.1016/j.ijporl.2016.03.033 PEDOT 8025
To appear in:
International Journal of Pediatric Otorhinolaryngology
Received date: Revised date: Accepted date:
3-2-2016 21-3-2016 24-3-2016
Please cite this article as: O. Breik, K. Umapathysivam, D. Tivey, P. Anderson, Feeding and reflux in children after mandibular distraction osteogenesis for micrognathia: a systematic review, International Journal of Pediatric Otorhinolaryngology (2016), http://dx.doi.org/10.1016/j.ijporl.2016.03.033 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Feeding and reflux in children after mandibular distraction osteogenesis for micrognathia: a systematic review Authors:
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Omar Breik1, 2 BDSc(Hons) MBBS MClinSc
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Kandiah Umapathysivam2
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BSc(Hons) MSc GradDip (Business Admin) PhD David Tivey2
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BSc(Hons) PhD Peter Anderson3 4
Oral and Maxillofacial Surgery Registrar, Royal Melbourne Hospital, Melbourne,
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DSc MD(Edin) PhD FDSRCS(Ed) FRCS(Eng) FRCS(Plast) FACS FRACS
Victoria
Joanna Briggs Institute, School of Translational Science, University of Adelaide,
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2
Adelaide, South Australia
Consultant, Australian Craniofacial Unit, Women’s and Children’s Hospital,
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3
Adelaide, South Australia 4
Visiting Professor, Oral & Maxillofacial Surgery Unit, Universiti Sains Malaysia, Kota Bharu
Corresponding Author:
Dr Omar Breik MBBS BDSc(Hons) MClinSc Oral and Maxillofacial Surgery Registrar Royal Melbourne Hospital 300 Grattan Street, Parkville Melbourne, Victoria 3050 [email protected]
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Short Title: Feeding and reflux after mandibular distraction Abbreviations in the text: MDO – mandibular distraction osteogenesis
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GERD – Gastro-esophageal reflux PRS – Pierre Robin Sequence
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iPRS – isolated Pierre Robin Sequence sMicro – syndromic micrognathia
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RR – retrospective review CR – Case report
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TMJ – Temporomandibular Joint
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Funding: None
Financial Disclosure: The authors have no financial relationships relevant to this
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article to disclose
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disclose
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Conflicts of interest: The authors have no conflicts of interest relevant to this article to
Contributor’s Statement:
Dr Breik designed the study, performed the analyses, drafted the initial manuscript and approved the final manuscript
Dr’s Umapathysivam and Tivey reviewed results and assisted with statistical analysis. They also reviewed and revised the manuscript and approved the final manuscript as submitted
Prof Anderson helped conceptualize the study, reviewed and revised the manuscript and approved the manuscript as submitted
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Abstract
Mandibular distraction osteogenesis (MDO) is becoming increasingly more commonly used as in neonates and infants with upper airway obstruction secondary to
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micrognathia. A significant number of these children are dependent on nasoenteric feeding or gastrostomies after birth for adequate nutrition and often suffer from gastro-esophageal reflux (GERD).
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Objective
determine the effects of MDO on feeding and GERD. Data Sources
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This analysis is a subset of a larger systematic review. The objective of this study is to
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The databases searched included PubMed, Embase, Scopus, Web of Knowledge and grey literature sources. Study Selection
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The inclusion criterion included studies in children with clinical evidence of micrognathia/Pierre Robin Sequence (PRS) who have failed conservative treatments, including both syndromic (sMicro) and non-syndromic (iPRS) patients. 21 studies
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relevant to feeding and 4 studies relevant to GERD outcomes were included. All
Results
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studies included were case series and case reports.
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MDO leads to a significant improvement in feeding, with 82% of children feeding exclusively orally after surgery. The overall percentage of children with iPRS who were feeding orally was 93.7% compared with only 72.9% in the sMicro group (p<0.004). A growth decline within the first six weeks after surgery was observed in multiple studies. Overall, out of 70 patients with pre-operative GERD, only four had evidence of GERD after surgery. Conclusions
Considering the limitations of this systematic review, this study found that successful relief of airway obstruction by MDO leads to improvement of feeding and improvement in symptoms of GERD in children with upper airway obstruction secondary to micrognathia. Clinicians need to be aware of the risk of growth decline in the initial post-operative period.
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Introduction
In 1923, the French stomatologist Pierre Robin was the first to describe a
constellation of symptoms associated with upper airway obstruction in neonates now
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known as Pierre Robin Sequence (PRS).(1) This sequence is a craniofacial anomaly characterized by mandibular micrognathia, glossoptosis, and in most cases a ‘U’
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shaped cleft palate. Micrognathia is a congenital condition characterized by an abnormally small mandible. This condition tends to occur in conjunction with
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posterior tongue displacement (glossoptosis), which can lead to physical obstruction of the oropharyngeal and hypopharyngeal regions on inspiration. There is only limited epidemiological data, but the incidence has been reported to range from
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approximately 1 in 8500 live births in Merseyside(2) to 1 in 14,000 live births in Denmark.(3) The most recent study from Germany reported an incidence of approximately 1 in 8000 births.(4) This variation in incidence is related in part to the
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inconsistent definition of PRS in the literature.
Diagnosis of patients with PRS is challenging due to the wide spectrum of
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PRS phenotypes, variation in degree of airway obstruction, feeding difficulties and the need for treatment. This has led to some authors only characterizing those with airway obstruction needing treatment as having PRS(5), others will include all patients
with micrognathia and glossoptosis, or limit the PRS diagnosis to those with associated cleft palates as having PRS.(6) Although these clinical features are most commonly seen in isolation (7), they can also occur in association with other clefting conditions of the craniofacial skeleton; for example, Treacher Collins Syndrome, Stickler syndrome and Nager syndrome. Such co-occurrences further complicate the diagnosis. For simplicity, in this review, those without an associated syndrome have been referred to as isolated PRS (iPRS) and those with an associated syndrome referred to as syndromic micrognathia (sMicro).
The micrognathia and upper airway obstruction contribute to a wide range of clinical problems in these children(8, 9). These infants have significant feeding and 5
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swallowing problems. During the normal swallowing process, breathing is suppressed and a decrease in ventilation occurs during the sucking process.(10) In contrast to normal infants, infants with upper airway obstruction may have to increase the efforts to breathe even at rest, and hence may lack the pulmonary reserve necessary to
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support the additional respiratory effort required for oral feeding. In addition to this, these children also tend to have higher caloric consumption due to their repeated
attempts to clear their upper airway. All of these factors may cause failure to thrive.(11, These children are often dependent on long-term nasoenteric feeding or
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12)
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gastrostomy feeding due to these issues (13).
Another significant complication is the increased incidence of gastro-
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esophageal reflux (GERD) in children with PRS. It is hypothesized that upper airway obstruction results in an increased inspiratory effort to overcome the obstruction, which results in a negative intra-thoracic pressure that can cause a suction type effect
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on the gastric contents.(14)
All of these complications are believed to be secondary to the upper airway
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obstruction; therefore the priority is to treat the upper airway obstruction. However, it
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is yet to be determined if relieving the upper airway obstruction will also resolve these complications. The purpose of this systematic review was to identify and
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synthesize the best available evidence on the effect of MDO on feeding and gastroesophageal reflux in children with upper airway obstruction secondary to micrognathia. This paper reports a sub-set of the results of a larger systematic review, which also evaluated the overall effectiveness of MDO at relieving airway obstruction(15).
Methods
This systematic review was conducted as part of fulfillment of a Masters of Clinical Science degree at the University of Adelaide. The review was conducted according to a peer reviewed protocol prepared a priori (16). The PICO (Participants, Intervention, Comparator, Outcomes) criteria used for this review are included in table 1. All the studies included were children with clinical evidence of micrognathia who underwent 6
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bilateral MDO. All studies needed to have included the conservative treatment options attempted, reasons for failure, and minimum of 1 year follow up. Syndromic and non-syndromic children were included if there was clinical evidence of glossoptosis and upper airway obstruction, but some particular conditions were
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excluded. These include bilateral TMJ ankylosis, unilateral hemifacial microsomia or other conditions that may be contributing to the airway obstruction for reasons other than the micrognathia alone. Also, children with known lower airway abnormalities
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prior to treatment were also excluded.
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The types of studies considered included both experimental and epidemiological study designs including randomized control trials, quasi-experimental studies,
considered case series and case reports.
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prospective and retrospective cohort and case control studies. The review also
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The search strategy included both published and unpublished studies in English from 1990 to November 2013. The databases searched included PubMed, CINAHL, EMBASE, SCOPUS, Web of knowledge and other grey literature databases such as
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Scirus and Mednar. The search strategy optimized for PubMed is detailed in figure 1.
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Search terms and strategy were translated for use with alternative databases.
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Papers selected for retrieval were assessed by two independent reviewers for methodological validity and quality and critically appraised using standardized critical appraisal instruments from the Joanna Briggs Institute’s Met Analysis of statistics assessment and review instrument (JBI-MAStARI). Any disagreements that arose between the reviewers were resolved through discussion, or with a third reviewer. Data was extracted from papers included in the review independently, and included in tables. The data collected was checked by the second reviewer. Where available, individual patient data was collected. If this was not possible the authors of primary studies were contacted for missing information or to clarify unclear data. Follow up periods were also recorded. Data parameters were recorded for the feeding and reflux outcomes as illustrated in table 2. The categorical data retrieved was cross tabulated and expressed as odds ratios with 95% confidence intervals. The cross tabulation method allows for comparison of 1 or 7
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more variables. Statistical significance was determined at P < 0.05 after a chi squared test. Comprehensive meta-analysis software (Version 2.2.064; Biostat, Englewood, NJ) was used to establish odds ratios and statistical significance. When statistical pooling was not possible, the findings are presented in narrative form including tables
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and figures to aid in data presentation.
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Results
The search identified a total of 4815 studies. Out of these, the total retrieved based on
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title was 801. Following removal of duplicates, studies not in English, or studies outside the date criteria, there were only 382 studies. The abstracts were then
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reviewed to determine their relevance to the review question and objectives. During this process, 258 studies were excluded, leaving 124 studies that were retrieved for
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detailed full text critical evaluation.
Following the review of the full text, an additional 38 studies were excluded as they did not fully meet the inclusion criteria resulting in 86 studies that were subjected to
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critical appraisal resulting in 66 included in the final analysis (Figure 2). Amongst
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these papers, there were 21 papers relevant to the feeding outcomes and 4 papers relevant to the GERD outcomes. The findings from these studies are analyzed in this
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paper.
Feeding Outcomes
This primary outcome is concerned with assessing growth and feeding methods after successful relief of upper airway obstruction despite mandibular distraction. The data collected was feeding method after surgery. In some studies the feeding method preoperatively was also reported and that data was collected where available for comparison. Where available, the weight centiles pre and post-operatively were also collected. Overall, 21 studies(13, 17-36) included adequate information related to feeding (Table 3).
Five of these were case studies while the remaining 16 were case series. All 21 studies were included in the overall analysis. One author was contacted for further
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information regarding feeding, and provided feeding outcome of patient 2 in their series(19). Five of these studies were excluded in the syndromic vs non-syndromic analysis due to inadequate distinction between syndromic and non-syndromic patients. Inadequate information was provided for an age-based analysis to be
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performed. Table 4 consists of demographic data and the included information from
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the individual studies.
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Overall feeding outcomes analysis
Twenty-one studies were included in this analysis. The total numbers of patients included in this analysis were 300. Overall, 246 of the 300 children (82%) were
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feeding completely orally (PO feeding) within 12 months of mandibular distraction over a mean follow up period of 3 years (ranging from 12 months-7 years). The
remaining 54 still required feeding adjuncts and could not be fed exclusively orally in
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the short term. Of these children, 13 still had NG tubes and 41 still had gastrostomy tubes for feeding in the short term (Table 5). Most of the children who were able to
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feed orally were weaned off gastrostomy tubes or NG tubes pre-operatively. Two patients were reported to have been fed with total parenteral nutrition (TPN) before
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MDO(21). One of these children was then able to feed orally, and the other required
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NG feeding post-operatively.
When evaluating the available pre and post-operative centiles, a general trend was observed which showed a decline in centiles in the immediate post-operative period.
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For the first 6-8 weeks post-operatively, there was a general decline by one or two
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centiles in weight. After the consolidation period, there was a general improvement in centiles with an average increase of two centiles compared to the pre-operative
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centiles.
The presence of a cleft palate may also affect feeding in these patients. The majority of larger included studies did not include the number of patients with cleft palates; repaired or unrepaired. The small case series and case reports (18) (19) (20) (21) (24) (13) (25) (26) (36)
included whether the patients had an associated cleft palate, but this data
was not amenable to further analysis.
Feeding subgroup analysis: syndromic vs non-syndromic
Sixteen studies were included in this subgroup analysis. The main reason for exclusion was due to inadequate distinction between syndromic and non-syndromic children with PRS. The objective of this analysis was to identify if having PRS as part 10
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of a syndrome affects the feeding outcome after MDO. A total of 122 patients were included in this subgroup analysis. Among these children 102 were able to exclusively feed orally (PO feeding) after MDO, giving an overall percentage of 83.6%. When comparing syndromic and isolated PRS patients, most of the patients
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who needed adjuncts were within the syndromic micrognathia group (16/20). The overall percentage of children with iPRS who were feeding orally was 93.7%
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compared with only 72.9% in the sMicro group (table 6).
Results of statistical analysis show that there is a statistically significant difference
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between success rates of iPRS and sMicro patients. For syndromic patients with micrognathia, there is a five times greater chance that they will require feeding
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adjuncts despite successful relief of the airway obstruction by MDO.
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Gastro-esophageal reflux outcomes
This outcome is concerned with the relief of gastro-esophageal reflux in children with PRS after MDO. Only four studies (13, 21, 23, 37) reported the presence of GERD pre and
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monitoring.
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post-MDO. These studies reported the GERD outcomes were based on pH
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Out of 70 patients with reported pre-operative GERD, only four had persistent reflux on pH monitoring post-MDO. No syndromic or age-based subgroup analysis was possible in these studies due to lack of distinction between syndromes and minimal age based data.
Discussion
Feeding abnormalities in children with micrognathia appear to be closely related to the upper airway obstruction. In this review, four out of five patients were able to feed exclusively orally after MDO. Most of these children were weaned from gastrostomy or enteric feeding before MDO to oral feeding after MDO. It is hypothesized that this outcome is due to improvement in the upper airway caliber, allowing the child to breathe adequately and maintain oxygenation while feeding. In addition the improved
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facial skeletal profile will improve lip approximation, facilitating a better sucking reflex after the healing phase is complete. Syndromic patients were more likely to require feeding adjuncts despite MDO compared with non-syndromic children with micrognathia and upper airway obstruction. This may be due to concomitant subtle
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neurological or swallowing abnormalities that syndromic patients may have which contribute to the feeding difficulties (34, 38). Overall, micrognathic children managed
with distraction have improved outcomes in oral feeding and many patients can avoid
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the need for long term enteral feeding via nasogastric or gastrostomy tubes.
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When evaluating pre and post-operative growth centiles, a general trend was observed which showed a decline in centiles in the immediate post-operative period in several
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studies. (21, 25, 34) The consequences of this early growth decline are not yet known. The reasons for this immediate decline may be related to the abnormal sucking and swallowing reflex due to daily movement of the mandible and tongue structures. The
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anatomical changes caused by MDO to the tongue base and pharyngeal wall position may precipitate a feeding disorder due to a dysfunctional and disorganized feeding mechanism.(34) It may also be caused by increased metabolic demands after surgery.
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Although most of the studies reported complete oral feeding post-operatively, it is
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important for clinicians to be aware of this potential early growth decline. Clinicians should consider continuing feeding with the pre-operative feeding adjuncts initially,
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until after completing the consolidation period or until removal of the distractors to avoid this decline in growth. Also, involvement of dietitians during the healing phase is also imperative, as increasing caloric intake during this period of increased physiological stress may be considered.
Although the swallowing functional improvement after MDO was not specifically included in this review, the findings support other studies that have demonstrated significant improvement in swallowing function after MDO. In the study by Hong et al., 2012 significant improvements in feeding and swallowing function were observed in all of their patients after MDO and this was confirmed by video fluoroscopic swallow studies(13).
The contribution of an associated cleft palate in the feeding difficulties in these patients remains unclear. The presence of a cleft palate alone is associated with a lag 12
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in growth in the first few years of life compared to noncleft children(39, 40). In children with PRS however, it is presumed that airway obstruction is the main reason for the feeding difficulties(41, 42). The studies included in this systematic review often did not report the number of patients with cleft palates, repaired or unrepaired. In the study by
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Hong et al., 2012(13), all 6 patients had a cleft palate, and the authors reported that all children had attempted standard cleft palate feeding strategies such as the use of
nipples and bottles. These children had no significant improvements in feeding until
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after relief of the airway obstruction by mandibular distraction. The study by Spring et al.,(34) reported that the 3 patients who had growth decline after MDO had an
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associated cleft palate and this may have contributed to their persistent feeding
difficulty. However the study did not report if the other 7 patients had cleft palates
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and so it is difficult to determine the association of the cleft palate to the persistent feeding difficulties in those patients. Overall, this systematic review supports the hypothesis that the airway obstruction is the main cause of feeding difficulties in
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children with micrognathia. However, it is important for clinicians managing these children to consider the role of the cleft palate during treatment and early involvement
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of a paediatric dietitian and speech pathologist is imperative.
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The age at the time of MDO may also affect feeding outcomes, but due to the lack of adequate reporting in the included studies, it was not possible to do an age related
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analysis on outcomes. The mean age of patients included in this study was 7 months with ages ranging from 5 days of age at the time of surgery to 6 years of age. It can be extrapolated however from our findings that early MDO was successful at improving feeding, and this in turn may affect long term growth of the child. This is consistent with another study by Lidsky et al.,(38) 2008 which found that children who underwent early airway interventions (less than 3 months of age) were less likely to need feeding assistance compared to those who underwent delayed airway intervention despite syndromic status.
It is important to note here that these findings do not advocate a predominantly surgical treatment plan for all patients with upper airway obstruction secondary to micrognathia. Where possible, the relief of the airway obstruction with conservative methods is advocated, and surgical intervention is reserved for those who have failed
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conservative treatments such as prone positioning, nasopharyngeal tubes and other non-invasive techniques.
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Gastro-esophageal reflux outcomes
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Gastro-esophageal reflux is common in infants and is becoming increasingly more
recognized as a possible cause of distress and failure to thrive in infants(43). Studies on
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infants with PRS have shown that the prevalence of GERD is higher in patients with PRS than normal controls with prevalence rates of up to 83%(37, 44). Although the occurrence of GERD is likely to be multifactorial in these patients, several studies
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have suggested that the most important factor in the occurrence of GERD in these patients is the upper airway obstruction(14, 44). These studies found that relief of the
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upper airway obstruction via nasopharyngeal tubes, or other surgical interventions reduced the severity of reflux on pH monitoring. It is hypothesized that the airway
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gastric contents.
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obstruction leads to a negative intrathoracic pressure causing a suction effect on
This review aimed to evaluate the effect of MDO on reflux. The review found that the
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majority of patients with confirmed pre-operative GERD had significant improvement in reflux based on pH monitoring after MDO. These findings are consistent with the hypothesis that the cause of GERD in these patients is the airway obstruction. This improvement in reflux may be a contributing factor to the improvement in feeding as well. The improvement in reflux may also be related to the ability to remove feeding tubes from these patients after MDO. The contribution of these feeding tubes to reflux in these patients is yet to be determined. However, in the study by Marques et al., 2009, they found no statistically significant correlation between the length of time of use of feeding tubes and the improvement in reflux index values. They concluded that respiratory obstruction was a more important predisposing factor than feeding tubes in infants with PRS(44).
Recent studies have suggested that GERD and the need for Nissen fundoplication are associated with failure of distraction osteogenesis.(45) The findings of the airway
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outcomes of the larger systematic review were not consistent with this observation for primary MDO(15). The presence of severe GERD; however, was associated with increased risk of failure of decannulation of tracheostomy dependent patients after MDO. Often these children can be decannulated after Nissen fundoplication.
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Tracheostomy dependent patients who are being considered for MDO should have formal pH monitoring pre-operatively. If severe reflux is diagnosed, referral to a
reflux. Ideally, this should be performed before MDO.
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pediatrician is required for consideration of medical or surgical management of the
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Apart from the findings in this review, there were other relevant factors to feeding and reflux that were noted during review of the literature. Respiratory tract infections in
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tracheostomy dependent children are common, and are likely secondary to aspiration. Children who undergo MDO seem to have a reduction in aspiration. The study by Monasterio 2004(37) and Hong 2012(13) included details about aspiration pre and post-
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operatively. Monasterio 2004 reported in a retrospective series of 18 patients, 66% had barium penetration into laryngeal vestibule, 50% had stasis of residual material in the pharyngeal recess, 28% had pharyngeal transit of >1 second and 5.5% had
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bronchial aspiration on barium swallow pre-operatively. Post-MDO, none of the
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patients demonstrated barium aspiration and there was normal pharyngeal transit of <1 second in all patients.(37) Despite MDO significantly disrupting the tongue and
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oropharyngeal musculature, these patients tended to have a reduction in aspiration and hence respiratory infections. This may also be related to alleviation of the reflux by reversing the upper airway obstruction.
Limitations
Systematic reviews, by nature are retrospective and observational. They are heavily reliant on the data reporting of others, and hence are at risk of replicating biased results.
The quality of the included studies overall were poor. They were all case reports or case series, with no prospective trials, quasi-randomized or randomized control trials. Often the studies included had incomplete data, making the specific inclusion for each individual analysis more complex as can be seen in the results section. The heterogeneity within both the syndromic and isolated PRS groups creates an inherent 15
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difficulty in trying to group them into single groups. Hence, the syndromic analysis needs to be interpreted with caution. The findings of this review only provide a guide to what factors are associated with higher chance of failure, and which overall groups
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of patients are at risk of further problems
There are currently no long-term studies evaluating the feeding outcomes or GERD
outcomes in children who underwent MDO for upper airway obstruction secondary to
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micrognathia. Further research is needed to evaluate long term improvement and
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interventions that may be needed in these patients.
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Conclusion
After MDO, 4 out of 5 patients could be exclusively orally fed within 12 months of MDO. Those with associated syndromes tended to have a 5 times higher rate of
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requiring feeding adjuncts after MDO and hence should be monitored closely by a dietitian if the feeding adjuncts are removed. Several studies have reported the
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observation that some children suffer from a decline in their growth parameters in the first 6-8 weeks post-operatively. We recommend that children should continue on
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feeding adjuncts during this period to ensure appropriate nutritional status during this period of potential growth decline. Despite the few studies available, relief of the
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upper airway obstruction with MDO appears to reduce GERD in affected children. Further research is needed to determine if resolution of GERD and improvement in feeding in these patients persists in the long term.
References 16
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6. 7. 8. 9. 10.
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cr
Ac ce p
11.
us
5.
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4.
M
3.
d
2.
Robin P. Glossoptosis due to atresia and hypotrophy of the mandible. Am J Dis Child. 1934;48:541-7. Bush PG, Williams AJ. Incidence of the Robin Anomalad (Pierre Robin syndrome). Br J Plast Surg. 1983 Oct;36(4):434-7. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J. 2004;41:47-52. Vatlach S, Maas C, Poets CF. Birth prevalence and initial treatment of Robin sequence in Germany: a prospective epidemiologic study. Orphanet J Rare Dis. 2014;9:9. Cole A, Lynch P, Slator R. A new grading of Pierre Robin sequence. Cleft Palate Craniofac J. 2008 Nov;45(6):603-6. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J. 2004 Jan;41(1):47-52. Evans AK, Rahbar R, Rogers GF, Mulliken JB, Volk MS. Robin sequence: A retrospective review of 115 patients. Int J Pediatr Otorhinolaryngol. 2006;70(6):973-80. Denny AD, Talisman R, Hanson PR, Recinos RF. Mandibular distraction osteogenesis in very young patients to correct airway obstruction. Plast Reconstr Surg. 2001 Aug;108(2):302-11. Hong P, Bezuhly M. Mandibular distraction osteogenesis in the micrognathic neonate: A review for neonatologists and pediatricians. Pediatr Neonatol. 2013;54(3):153-60. Mathew OP, Clark ML, Pronske ML, Luna-Solarzano HG, Peterson MD. Breathing pattern and ventilation during oral feeding in term newborn infants. J Pediatr. 1985 May;106(5):810-3. Dinwiddie R. Congenital upper airway obstruction. Paediatr Respir Rev. 2004 Mar;5(1):17-24. Hong P, Bezuhly M, Mark Taylor S, Hart RD, Kearns DB, Corsten G. Tracheostomy versus mandibular distraction osteogenesis in Canadian children with Pierre Robin sequence: a comparative cost analysis. J Otolaryngol Head Neck Surg. 2012 Jun 1;41(3):207-14. Hong P, Brake MK, Cavanagh JP, Bezuhly M, Magit AE. Feeding and mandibular distraction osteogenesis in children with Pierre Robin sequence: a case series of functional outcomes. Int J Pediatr Otorhinolaryngol. 2012 Mar;76(3):414-8. Dudkiewicz Z, Sekula E, Nielepiec-Jalosinska A. Gastroesophageal reflux in Pierre Robin sequence--early surgical treatment. Cleft Palate Craniofac J. 2000 Mar;37(2):205-8. Breik O, Tivey D, Umapathysivam K, Anderson P. Mandibular distraction osteogenesis for the management of upper airway obstruction in children with micrognathia: a systematic review. Int J Oral Maxillofac Surg. 2016 Feb 8. Breik O, Umapathysivam K, Tivey D, Anderson PJ. Mandibular distraction osteogenesis in the management of airway obstruction in children: A
te
1.
12.
13.
14. 15.
16.
17
Page 16 of 27
22. 23. 24. 25.
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cr
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26.
us
21.
an
20.
M
19.
d
18.
te
17.
systematic review protocol. The JBI Database of Systematic Reviews and Implementation Reports 2013;11(10): 16-29. The JBI Database of Systematic reviews and Implementation Reports. 2013;11(10):16-29. Al-Samkari HT, Kane AA, Molter DW, Vachharajani A. Neonatal outcomes of Pierre Robin sequence: an institutional experience. Clin Pediatr (Phila). 2010 Dec;49(12):1117-22. Breugem C, Paes E, Kon M, van der Molen AB. Bioresorbable distraction device for the treatment of airway problems for infants with Robin sequence. Clin Oral Investig. 2012 Aug;16(4):1325-31. Brevi B, Lagana F, Piazza F, Sesenna E. Mandibular distraction osteogenesis with a small semiburied device in neonates: report of 2 cases. Ear Nose Throat J. 2006 Feb;85(2):102-5. Chigurupati R, Massie J, Dargaville P, Heggie A. Internal mandibular distraction to relieve airway obstruction in infants and young children with micrognathia. Pediatr Pulmonol. 2004 Mar;37(3):230-5. Dauria D, Marsh JL. Mandibular distraction osteogenesis for Pierre Robin sequence: what percentage of neonates need it? J Craniofac Surg. 2008 Sep;19(5):1237-43. Denny A, Amm C. New technique for airway correction in neonates with severe Pierre Robin sequence. J Pediatr. 2005 Jul;147(1):97-101. Genecov DG, Barcelo CR, Steinberg D, Trone T, Sperry E. Clinical experience with the application of distraction osteogenesis for airway obstruction. J Craniofac Surg. 2009 Sep;20 Suppl 2:1817-21. Griffiths AL, Heggie A, Holman S, Robertson SP, White SM. Obstructive Sleep Apnea Successfully Treated by Mandibular Distraction Osteogenesis in a Rare Skeletal Dysplasia. J Craniofac Surg. 2013 Mar;24(2):508-10. Howlett C, Stavropoulos MF, Steinberg B. Feeding complications in a sixweek-old infant secondary to distraction osteogenesis for airway obstruction: a case report. J Oral Maxillofac Surg. 1999 Dec;57(12):14658. Iatrou I, Theologie-Lygidakis N, Schoinohoriti O. "Mandibular distraction osteogenesis for severe airway obstruction in Robin Sequence. Case report". J Craniomaxillofac Surg. 2010 Sep;38(6):431-5. Izadi K, Yellon R, Mandell DL, Smith M, Song SY, Bidic S, et al. Correction of upper airway obstruction in the newborn with internal mandibular distraction osteogenesis. J Craniofac Surg. 2003 Jul;14(4):493-9. Looby JF, Schendel SA, Lorenz HP, Hopkins EM, Aizenbud D. Airway analysis: With bilateral distraction of the infant mandible. J Craniofac Surg. 2009;20(5):1341-6. Miller JJ, Kahn D, Lorenz HP, Schendel SA. Infant mandibular distraction with an internal curvilinear device. J Craniofac Surg. 2007 Nov;18(6):1403-7. Miloro M. Mandibular distraction osteogenesis for pediatric airway management. J Oral Maxillofac Surg. 2010 Jul;68(7):1512-23. Mudd PA, Perkins JN, Harwood JE, Valdez S, Allen GC. Early intervention: distraction osteogenesis of the mandible for severe airway obstruction. Otolaryngol Head Neck Surg. 2012 Mar;146(3):467-72.
27. 28. 29. 30. 31.
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37. 38. 39. 40.
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41.
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36.
an
35.
M
34.
d
33.
Olson TP, McMurray JS, Mount DL. Endoscopic changes in the upper airway after mandibular distraction osteogenesis. J Craniofac Surg. 2011 Jan;22(1):105-9. Scott AR, Tibesar RJ, Lander TA, Sampson DE, Sidman JD. Mandibular distraction osteogenesis in infants younger than 3 months. Arch Facial Plast Surg. 2011 May-Jun;13(3):173-9. Spring MA, Mount DL. Pediatric feeding disorder and growth decline following mandibular distraction osteogenesis. Plast Reconstr Surg. 2006 Aug;118(2):476-82. Tibesar RJ, Scott AR, McNamara C, Sampson D, Lander TA, Sidman JD. Distraction osteogenesis of the mandible for airway obstruction in children: long-term results. Otolaryngol Head Neck Surg. 2010 Jul;143(1):90-6. Zenha H, Azevedo L, Rios L, Pereira A, Pinto A, Barroso ML, et al. Bilateral mandibular distraction osteogenesis in the neonate with pierre robin sequence and airway obstruction: a primary option. Craniomaxillofacial trauma & reconstruction. 2012 Mar;5(1):25-30. Monasterio FO, Molina F, Berlanga F, Lopez ME, Ahumada H, Takenaga RH, et al. Swallowing disorders in Pierre Robin sequence: its correction by distraction. J Craniofac Surg. 2004 Nov;15(6):934-41. Lidsky ME, Lander TA, Sidman JD. Resolving feeding difficulties with early airway intervention in Pierre Robin Sequence. Laryngoscope. 2008 Jan;118(1):120-3. Felix-Schollaart B, Hoeksma JB, Prahl-Andersen B. Growth comparison between children with cleft lip and/or palate and controls. Cleft Palate Craniofac J. 1992 Sep;29(5):475-80. Ranalli DN, Mazaheri M. Height-weight growth of cleft children, birth to six years. Cleft Palate J. 1975 Oct;12:400-4. Evans KN, Sie KC, Hopper RA, Glass RP, Hing AV, Cunningham ML. Robin sequence: from diagnosis to development of an effective management plan. Pediatrics. 2011 May;127(5):936-48. Maas C, Poets CF. Initial treatment and early weight gain of children with Robin Sequence in Germany: a prospective epidemiological study. Arch Dis Child Fetal Neonatal Ed. 2014 Nov;99(6):F491-4. Hyman PE. Gastroesophageal reflux: one reason why baby won't eat. J Pediatr. 1994 Dec;125(6 Pt 2):S103-9. Marques IL, Monteiro LCS, De Souza L, Bettiol H, Sassaki CH, Costa RDA. Gastroesophageal reflux in severe cases of Robin sequence treated with nasopharyngeal intubation. Cleft Palate Craniofac J. 2009 //;46(4):44853. Murage KP, Tholpady SS, Friel M, Havlik RJ, Flores RL. Outcomes analysis of mandibular distraction osteogenesis for the treatment of Pierre Robin sequence. Plast Reconstr Surg. 2013 Aug;132(2):419-21.
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32.
42. 43. 44.
45.
Figures and tables legend Tables 19
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Table 1: PICO criteria for the systematic review Table 2: Data items collected and recorded for each outcome studied. Table 3: Studies included in different analyses for feeding outcomes and reasons for exclusion
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Table 4: Collected data from the included studies consisting of demographics, feeding outcomes and centile data
exclusively fed orally or needed adjuncts following MDO.
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Table 5: Illustrates the feeding outcomes in terms of whether the patients could be
Figures
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Figure 1: The search strategy optimized for PubMed.
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Table 6: Results of syndromic vs non-syndromic subgroup analysis.
Figure 2: Flow diagram demonstrating the numbers of studies screened, assessed for
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eligibility and included in the review
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Page 19 of 27
Table(s)
Table 1: PICO criteria for the systematic review Participants
- Male and female children from birth with clinical evidence of micrognathia - Clinical evidence of upper airway obstruction
- Syndromic and non-syndromic children
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- Bilateral mandibular distraction
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with failed conservative treatments
Exclusion
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- Children who underwent unilateral distraction - Children with known pre-operative central
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apnea/lower airway abnormalities
Outcomes
Feeding
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Intervention
- TMJ ankylosis/hemifacial microsomia or other Bilateral mandibular mandibular conditiondistraction leading to osteogenesis airway obstruction
ed
Gastro-esophageal reflux
Outcome
Ac ce
Feeding
pt
Table 2: Data items collected and recorded for each outcome studied.
Gastro-esophageal reflux
Data items recorded Method of feeding after MDO: 1. Exclusively orally fed 2. Feeding adjuncts – Enteric feeding/gastrostomy Weight growth centiles and trends
Results of pH monitoring pre and post-MDO Need for treatment of GERD
Page 20 of 27
Table 3: Studies included in different analyses for feeding outcomes and reasons for exclusion Overall
Syndromic vs Non-
Design
Analysis
Syndromic
Al-Samkari 2010 (17)
RR
Included
Included
Breugem 2012 (18)
RR
Included
Included
Brevi 2006 (19)*
CR
Included
Included
Chigurupati 2004 (20)
RR
Included
Included
Dauria 2008 (21)
RR
Included
Included
Denny and Amm 2005 (22)
RR
Included
Included
Genecov 2009 (23)
RR
Included
Excluded – inadequate
cr
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Study
us
Article
Griffiths 2013 (24)
CR
Included
Hong 2012 (13)
RR
Included
Included
Howlett 1999 (25)
CR
Included
Included
Iatrou 2010 (26)
CR
Included
Included
Izadi 2003 (27)
RR
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distinction
Included
Included
Looby 2009 (28)
RR
Included
Included
RR
Included
Included
RR
Included
Excluded – inadequate
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Mudd 2012 (31) Olson 2011 (32) Scott 2011
(33)
an
ed
Miloro 2010 (30)
pt
Miller 2007 (29)
Included
RR
distinction Included
Excluded – inadequate distinction
RR
Included
Included
RR
Included
Excluded – inadequate distinction
Spring 2006 (34)
RR
Included
Included
Tibesar 2010 (35)
RR
Included
Excluded – inadequate distinction
Zenha 2012 (36)
CR
Included
Included
21 included
16 included
RR – retrospective review, CR – Case report
*Contacted author for further information
Page 21 of 27
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Country/U nit
RR
St Louis
No. of patients
Age (months) mean
7
Neonates
5
Neonates
Age Ranges
Breugem 2012
Brevi 2006
(19)
Chigurupati 2004 (20)
Netherlands
6
1
5
1
NG tube (2)
2
0
4
iPRS
NG tube
1
0
4
iPRS
NG tube
1
0
39
TCS
Gastrostomy
1
0
1
10
TCS
Gastrostomy
0
1
1
20
sMicro
Gastrostomy
1
0
1
0.5
iPRS
TPN
0
1
11-25th
5-10th
1
iPRS
Gastrostomy
0
1
11-25th
11-25th
1
iPRS
Gastrostomy
0
1
11-25th
5-10th
1
iPRS
TPN
1
0
26-50th
51-75th
Improved (but 1)
(10) - >50th centile
<3
12 months 25th
1
ce pt
Ac Texas
Griffiths 2013
CR
Melbourne
7-71 days
4
0.5
7-36 days
iPRS
-
4
0
7
0.6
sMicro
-
6
1
67
16
3-45 days 5days-6 years
Mixture
-
61
6
1
5
Skeletal
Haberman feeder
1
0
Genecov 2009 RR
3
iPRS
Australia
(23)
2
1
RR
Wisconsin
sMicro
4
1
RR
1
NG tube (5)
1
Denny and Amm 2005 (22)
6
Centile Post MDO (>6 weeks)
sMicro
2
St Louis
iPRS
Immed iate Improv ed Improv ed
0
Italy
RR
Centile pre
6
1
(21)
Feeding adjuncts
NG tube (6)
CR
Dauria 2008
Pre-MDO feeding
PO feed s
iPRS
ed
RR
(18)
Syndrom e
M an
Article Al-Samkari 2010 (17)
Study Design
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Table 4: Collected data from the included studies consisting of demographics, feeding outcomes and centile data
9/12 -
Page 22 of 27
Nova Scotia Canada
2
2
4
2.5
(25)
CR
Florida
1
2
Iatrou 2010 (26)
CR
1
8
Izadi 2003 (27)
RR
Greece Los Angeles
7
0.25
8
0.25
RR
Israel
12 5
(29)
RR
Stanford
7
Miloro 2010 (30) Mudd 2012 (31)
RR RR
Chicago
Colorado
35 25
iPRS
28 - 94
sMicro
3.5 1
NG tubes (2)
2
0
NG tubes (4)
4
0
iPRS
-
1
0
iPRS
Gastrostomy
1
0
iPRS
NG tube (7)
7
0
sMicro
NG tube (7)
6
1
iPRS
Gastrostomy (8)
12
0
4
1
11-310 days
<8 months
ce pt
3
3.5
32-78 days
ed
Looby 2009 (28) Miller 2007
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RR
10th
M an
Hong 2012 (13)
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Dysplasia
(24)
0-4 years
sMicro iPRS
NG tube (2)
7
0
sMicro
NG tube (3) Gastrostomy (13), NG tube (18), PO (4)
0
3
35
0
Mixture
11-76 days
Mixture
-
13
12
5 days-6 years
iPRS
-
6
0
sMicro
-
6
2
Mixture
-
13
6
iPRS
-
1
0
sMicro
-
1
3
sMicro
-
5
0
25 4.8kg at 8 months
3/52 <5
8/52 - 25th 13.5kg at 22 months
Improved Just above 5
first 10/52 5
between 5-25
8
RR
Scott 2011 Spring 2006
RR
(34)
RR
(33)
Wisconsin
Ac
Olson 2011 (32)
Boston
Wisconsin
6
8
8 19
1.25
1
0.25
4
3
5
63
0.25 months 1,25-5.5 months 36.6-98 months
Have individual centile charts Have individual centile charts Have individual centile charts
Page 23 of 27
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Mineapolis
CR
Portugal
32
10.4
1
0.3
1
0.3 Mean 7 months
5 days - 67 months
Mixture
Zenha 2012
Total
300
RR – Retrospective review CR – Case report
sMicro
22
10
Orogastric tube
1
0
PO
1
0
246
54
Ac
ce pt
ed
TCS – Treacher Collins Syndrome
iPRS
Gastrostomy (17), PO (15)
M an
(36)
cr
(35)
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Tibesar 2010
Page 24 of 27
Table 5: Illustrates the feeding outcomes in terms of whether the patients could be exclusively fed orally or needed adjuncts following MDO.
Outcome
Total
PO feeds
Adjuncts
% PO feeds
needed 300
246
54
82%
PO feeds
Adjuncts
(%)
needed(%)
246 (82)
iPRS sMicro
ll patients
Total
Odds ratio (95% CI)
p-value
54 (18)
300
-
-
59 (93.7)
4 (6.3)
63
43 (72.9)
16 (27.1)
59
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Variable
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Table 6: Results of syndromic vs non-syndromic subgroup analysis.
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Feeding
1
-
5.49 (1.71, 17.58)
0.004
Ac ce
pt
ed
M
an
Syndromic analysis
Page 25 of 27
Ac
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pt
ed
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i
Figure(s)
Page 26 of 27
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Figure(s)
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S0165-5876(16)30026-X http://dx.doi.org/doi:10.1016/j.ijporl.2016.03.033 PEDOT 8025
To appear in:
International Journal of Pediatric Otorhinolaryngology
Received date: Revised date: Accepted date:
3-2-2016 21-3-2016 24-3-2016
Please cite this article as: O. Breik, K. Umapathysivam, D. Tivey, P. Anderson, Feeding and reflux in children after mandibular distraction osteogenesis for micrognathia: a systematic review, International Journal of Pediatric Otorhinolaryngology (2016), http://dx.doi.org/10.1016/j.ijporl.2016.03.033 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Feeding and reflux in children after mandibular distraction osteogenesis for micrognathia: a systematic review Authors:
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Omar Breik1, 2 BDSc(Hons) MBBS MClinSc
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Kandiah Umapathysivam2
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BSc(Hons) MSc GradDip (Business Admin) PhD David Tivey2
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BSc(Hons) PhD Peter Anderson3 4
Oral and Maxillofacial Surgery Registrar, Royal Melbourne Hospital, Melbourne,
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1
M
DSc MD(Edin) PhD FDSRCS(Ed) FRCS(Eng) FRCS(Plast) FACS FRACS
Victoria
Joanna Briggs Institute, School of Translational Science, University of Adelaide,
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2
Adelaide, South Australia
Consultant, Australian Craniofacial Unit, Women’s and Children’s Hospital,
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3
Adelaide, South Australia 4
Visiting Professor, Oral & Maxillofacial Surgery Unit, Universiti Sains Malaysia, Kota Bharu
Corresponding Author:
Dr Omar Breik MBBS BDSc(Hons) MClinSc Oral and Maxillofacial Surgery Registrar Royal Melbourne Hospital 300 Grattan Street, Parkville Melbourne, Victoria 3050 [email protected]
1
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Short Title: Feeding and reflux after mandibular distraction Abbreviations in the text: MDO – mandibular distraction osteogenesis
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GERD – Gastro-esophageal reflux PRS – Pierre Robin Sequence
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iPRS – isolated Pierre Robin Sequence sMicro – syndromic micrognathia
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RR – retrospective review CR – Case report
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TMJ – Temporomandibular Joint
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Funding: None
Financial Disclosure: The authors have no financial relationships relevant to this
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article to disclose
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disclose
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Conflicts of interest: The authors have no conflicts of interest relevant to this article to
Contributor’s Statement:
Dr Breik designed the study, performed the analyses, drafted the initial manuscript and approved the final manuscript
Dr’s Umapathysivam and Tivey reviewed results and assisted with statistical analysis. They also reviewed and revised the manuscript and approved the final manuscript as submitted
Prof Anderson helped conceptualize the study, reviewed and revised the manuscript and approved the manuscript as submitted
2
Page 2 of 27
Abstract
Mandibular distraction osteogenesis (MDO) is becoming increasingly more commonly used as in neonates and infants with upper airway obstruction secondary to
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micrognathia. A significant number of these children are dependent on nasoenteric feeding or gastrostomies after birth for adequate nutrition and often suffer from gastro-esophageal reflux (GERD).
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Objective
determine the effects of MDO on feeding and GERD. Data Sources
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This analysis is a subset of a larger systematic review. The objective of this study is to
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The databases searched included PubMed, Embase, Scopus, Web of Knowledge and grey literature sources. Study Selection
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The inclusion criterion included studies in children with clinical evidence of micrognathia/Pierre Robin Sequence (PRS) who have failed conservative treatments, including both syndromic (sMicro) and non-syndromic (iPRS) patients. 21 studies
d
relevant to feeding and 4 studies relevant to GERD outcomes were included. All
Results
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studies included were case series and case reports.
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MDO leads to a significant improvement in feeding, with 82% of children feeding exclusively orally after surgery. The overall percentage of children with iPRS who were feeding orally was 93.7% compared with only 72.9% in the sMicro group (p<0.004). A growth decline within the first six weeks after surgery was observed in multiple studies. Overall, out of 70 patients with pre-operative GERD, only four had evidence of GERD after surgery. Conclusions
Considering the limitations of this systematic review, this study found that successful relief of airway obstruction by MDO leads to improvement of feeding and improvement in symptoms of GERD in children with upper airway obstruction secondary to micrognathia. Clinicians need to be aware of the risk of growth decline in the initial post-operative period.
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Introduction
In 1923, the French stomatologist Pierre Robin was the first to describe a
constellation of symptoms associated with upper airway obstruction in neonates now
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known as Pierre Robin Sequence (PRS).(1) This sequence is a craniofacial anomaly characterized by mandibular micrognathia, glossoptosis, and in most cases a ‘U’
us
shaped cleft palate. Micrognathia is a congenital condition characterized by an abnormally small mandible. This condition tends to occur in conjunction with
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posterior tongue displacement (glossoptosis), which can lead to physical obstruction of the oropharyngeal and hypopharyngeal regions on inspiration. There is only limited epidemiological data, but the incidence has been reported to range from
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approximately 1 in 8500 live births in Merseyside(2) to 1 in 14,000 live births in Denmark.(3) The most recent study from Germany reported an incidence of approximately 1 in 8000 births.(4) This variation in incidence is related in part to the
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inconsistent definition of PRS in the literature.
Diagnosis of patients with PRS is challenging due to the wide spectrum of
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PRS phenotypes, variation in degree of airway obstruction, feeding difficulties and the need for treatment. This has led to some authors only characterizing those with airway obstruction needing treatment as having PRS(5), others will include all patients
with micrognathia and glossoptosis, or limit the PRS diagnosis to those with associated cleft palates as having PRS.(6) Although these clinical features are most commonly seen in isolation (7), they can also occur in association with other clefting conditions of the craniofacial skeleton; for example, Treacher Collins Syndrome, Stickler syndrome and Nager syndrome. Such co-occurrences further complicate the diagnosis. For simplicity, in this review, those without an associated syndrome have been referred to as isolated PRS (iPRS) and those with an associated syndrome referred to as syndromic micrognathia (sMicro).
The micrognathia and upper airway obstruction contribute to a wide range of clinical problems in these children(8, 9). These infants have significant feeding and 5
Page 4 of 27
swallowing problems. During the normal swallowing process, breathing is suppressed and a decrease in ventilation occurs during the sucking process.(10) In contrast to normal infants, infants with upper airway obstruction may have to increase the efforts to breathe even at rest, and hence may lack the pulmonary reserve necessary to
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support the additional respiratory effort required for oral feeding. In addition to this, these children also tend to have higher caloric consumption due to their repeated
attempts to clear their upper airway. All of these factors may cause failure to thrive.(11, These children are often dependent on long-term nasoenteric feeding or
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12)
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gastrostomy feeding due to these issues (13).
Another significant complication is the increased incidence of gastro-
an
esophageal reflux (GERD) in children with PRS. It is hypothesized that upper airway obstruction results in an increased inspiratory effort to overcome the obstruction, which results in a negative intra-thoracic pressure that can cause a suction type effect
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on the gastric contents.(14)
All of these complications are believed to be secondary to the upper airway
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obstruction; therefore the priority is to treat the upper airway obstruction. However, it
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is yet to be determined if relieving the upper airway obstruction will also resolve these complications. The purpose of this systematic review was to identify and
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synthesize the best available evidence on the effect of MDO on feeding and gastroesophageal reflux in children with upper airway obstruction secondary to micrognathia. This paper reports a sub-set of the results of a larger systematic review, which also evaluated the overall effectiveness of MDO at relieving airway obstruction(15).
Methods
This systematic review was conducted as part of fulfillment of a Masters of Clinical Science degree at the University of Adelaide. The review was conducted according to a peer reviewed protocol prepared a priori (16). The PICO (Participants, Intervention, Comparator, Outcomes) criteria used for this review are included in table 1. All the studies included were children with clinical evidence of micrognathia who underwent 6
Page 5 of 27
bilateral MDO. All studies needed to have included the conservative treatment options attempted, reasons for failure, and minimum of 1 year follow up. Syndromic and non-syndromic children were included if there was clinical evidence of glossoptosis and upper airway obstruction, but some particular conditions were
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excluded. These include bilateral TMJ ankylosis, unilateral hemifacial microsomia or other conditions that may be contributing to the airway obstruction for reasons other than the micrognathia alone. Also, children with known lower airway abnormalities
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prior to treatment were also excluded.
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The types of studies considered included both experimental and epidemiological study designs including randomized control trials, quasi-experimental studies,
considered case series and case reports.
an
prospective and retrospective cohort and case control studies. The review also
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The search strategy included both published and unpublished studies in English from 1990 to November 2013. The databases searched included PubMed, CINAHL, EMBASE, SCOPUS, Web of knowledge and other grey literature databases such as
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Scirus and Mednar. The search strategy optimized for PubMed is detailed in figure 1.
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Search terms and strategy were translated for use with alternative databases.
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Papers selected for retrieval were assessed by two independent reviewers for methodological validity and quality and critically appraised using standardized critical appraisal instruments from the Joanna Briggs Institute’s Met Analysis of statistics assessment and review instrument (JBI-MAStARI). Any disagreements that arose between the reviewers were resolved through discussion, or with a third reviewer. Data was extracted from papers included in the review independently, and included in tables. The data collected was checked by the second reviewer. Where available, individual patient data was collected. If this was not possible the authors of primary studies were contacted for missing information or to clarify unclear data. Follow up periods were also recorded. Data parameters were recorded for the feeding and reflux outcomes as illustrated in table 2. The categorical data retrieved was cross tabulated and expressed as odds ratios with 95% confidence intervals. The cross tabulation method allows for comparison of 1 or 7
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more variables. Statistical significance was determined at P < 0.05 after a chi squared test. Comprehensive meta-analysis software (Version 2.2.064; Biostat, Englewood, NJ) was used to establish odds ratios and statistical significance. When statistical pooling was not possible, the findings are presented in narrative form including tables
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and figures to aid in data presentation.
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Results
The search identified a total of 4815 studies. Out of these, the total retrieved based on
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title was 801. Following removal of duplicates, studies not in English, or studies outside the date criteria, there were only 382 studies. The abstracts were then
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reviewed to determine their relevance to the review question and objectives. During this process, 258 studies were excluded, leaving 124 studies that were retrieved for
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detailed full text critical evaluation.
Following the review of the full text, an additional 38 studies were excluded as they did not fully meet the inclusion criteria resulting in 86 studies that were subjected to
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critical appraisal resulting in 66 included in the final analysis (Figure 2). Amongst
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these papers, there were 21 papers relevant to the feeding outcomes and 4 papers relevant to the GERD outcomes. The findings from these studies are analyzed in this
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paper.
Feeding Outcomes
This primary outcome is concerned with assessing growth and feeding methods after successful relief of upper airway obstruction despite mandibular distraction. The data collected was feeding method after surgery. In some studies the feeding method preoperatively was also reported and that data was collected where available for comparison. Where available, the weight centiles pre and post-operatively were also collected. Overall, 21 studies(13, 17-36) included adequate information related to feeding (Table 3).
Five of these were case studies while the remaining 16 were case series. All 21 studies were included in the overall analysis. One author was contacted for further
8
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information regarding feeding, and provided feeding outcome of patient 2 in their series(19). Five of these studies were excluded in the syndromic vs non-syndromic analysis due to inadequate distinction between syndromic and non-syndromic patients. Inadequate information was provided for an age-based analysis to be
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performed. Table 4 consists of demographic data and the included information from
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the individual studies.
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Overall feeding outcomes analysis
Twenty-one studies were included in this analysis. The total numbers of patients included in this analysis were 300. Overall, 246 of the 300 children (82%) were
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feeding completely orally (PO feeding) within 12 months of mandibular distraction over a mean follow up period of 3 years (ranging from 12 months-7 years). The
remaining 54 still required feeding adjuncts and could not be fed exclusively orally in
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the short term. Of these children, 13 still had NG tubes and 41 still had gastrostomy tubes for feeding in the short term (Table 5). Most of the children who were able to
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feed orally were weaned off gastrostomy tubes or NG tubes pre-operatively. Two patients were reported to have been fed with total parenteral nutrition (TPN) before
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MDO(21). One of these children was then able to feed orally, and the other required
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NG feeding post-operatively.
When evaluating the available pre and post-operative centiles, a general trend was observed which showed a decline in centiles in the immediate post-operative period.
d
For the first 6-8 weeks post-operatively, there was a general decline by one or two
te
centiles in weight. After the consolidation period, there was a general improvement in centiles with an average increase of two centiles compared to the pre-operative
Ac ce p
centiles.
The presence of a cleft palate may also affect feeding in these patients. The majority of larger included studies did not include the number of patients with cleft palates; repaired or unrepaired. The small case series and case reports (18) (19) (20) (21) (24) (13) (25) (26) (36)
included whether the patients had an associated cleft palate, but this data
was not amenable to further analysis.
Feeding subgroup analysis: syndromic vs non-syndromic
Sixteen studies were included in this subgroup analysis. The main reason for exclusion was due to inadequate distinction between syndromic and non-syndromic children with PRS. The objective of this analysis was to identify if having PRS as part 10
Page 9 of 27
of a syndrome affects the feeding outcome after MDO. A total of 122 patients were included in this subgroup analysis. Among these children 102 were able to exclusively feed orally (PO feeding) after MDO, giving an overall percentage of 83.6%. When comparing syndromic and isolated PRS patients, most of the patients
ip t
who needed adjuncts were within the syndromic micrognathia group (16/20). The overall percentage of children with iPRS who were feeding orally was 93.7%
cr
compared with only 72.9% in the sMicro group (table 6).
Results of statistical analysis show that there is a statistically significant difference
us
between success rates of iPRS and sMicro patients. For syndromic patients with micrognathia, there is a five times greater chance that they will require feeding
an
adjuncts despite successful relief of the airway obstruction by MDO.
M
Gastro-esophageal reflux outcomes
This outcome is concerned with the relief of gastro-esophageal reflux in children with PRS after MDO. Only four studies (13, 21, 23, 37) reported the presence of GERD pre and
te
monitoring.
d
post-MDO. These studies reported the GERD outcomes were based on pH
Ac ce p
Out of 70 patients with reported pre-operative GERD, only four had persistent reflux on pH monitoring post-MDO. No syndromic or age-based subgroup analysis was possible in these studies due to lack of distinction between syndromes and minimal age based data.
Discussion
Feeding abnormalities in children with micrognathia appear to be closely related to the upper airway obstruction. In this review, four out of five patients were able to feed exclusively orally after MDO. Most of these children were weaned from gastrostomy or enteric feeding before MDO to oral feeding after MDO. It is hypothesized that this outcome is due to improvement in the upper airway caliber, allowing the child to breathe adequately and maintain oxygenation while feeding. In addition the improved
11
Page 10 of 27
facial skeletal profile will improve lip approximation, facilitating a better sucking reflex after the healing phase is complete. Syndromic patients were more likely to require feeding adjuncts despite MDO compared with non-syndromic children with micrognathia and upper airway obstruction. This may be due to concomitant subtle
ip t
neurological or swallowing abnormalities that syndromic patients may have which contribute to the feeding difficulties (34, 38). Overall, micrognathic children managed
with distraction have improved outcomes in oral feeding and many patients can avoid
cr
the need for long term enteral feeding via nasogastric or gastrostomy tubes.
us
When evaluating pre and post-operative growth centiles, a general trend was observed which showed a decline in centiles in the immediate post-operative period in several
an
studies. (21, 25, 34) The consequences of this early growth decline are not yet known. The reasons for this immediate decline may be related to the abnormal sucking and swallowing reflex due to daily movement of the mandible and tongue structures. The
M
anatomical changes caused by MDO to the tongue base and pharyngeal wall position may precipitate a feeding disorder due to a dysfunctional and disorganized feeding mechanism.(34) It may also be caused by increased metabolic demands after surgery.
d
Although most of the studies reported complete oral feeding post-operatively, it is
te
important for clinicians to be aware of this potential early growth decline. Clinicians should consider continuing feeding with the pre-operative feeding adjuncts initially,
Ac ce p
until after completing the consolidation period or until removal of the distractors to avoid this decline in growth. Also, involvement of dietitians during the healing phase is also imperative, as increasing caloric intake during this period of increased physiological stress may be considered.
Although the swallowing functional improvement after MDO was not specifically included in this review, the findings support other studies that have demonstrated significant improvement in swallowing function after MDO. In the study by Hong et al., 2012 significant improvements in feeding and swallowing function were observed in all of their patients after MDO and this was confirmed by video fluoroscopic swallow studies(13).
The contribution of an associated cleft palate in the feeding difficulties in these patients remains unclear. The presence of a cleft palate alone is associated with a lag 12
Page 11 of 27
in growth in the first few years of life compared to noncleft children(39, 40). In children with PRS however, it is presumed that airway obstruction is the main reason for the feeding difficulties(41, 42). The studies included in this systematic review often did not report the number of patients with cleft palates, repaired or unrepaired. In the study by
ip t
Hong et al., 2012(13), all 6 patients had a cleft palate, and the authors reported that all children had attempted standard cleft palate feeding strategies such as the use of
nipples and bottles. These children had no significant improvements in feeding until
cr
after relief of the airway obstruction by mandibular distraction. The study by Spring et al.,(34) reported that the 3 patients who had growth decline after MDO had an
us
associated cleft palate and this may have contributed to their persistent feeding
difficulty. However the study did not report if the other 7 patients had cleft palates
an
and so it is difficult to determine the association of the cleft palate to the persistent feeding difficulties in those patients. Overall, this systematic review supports the hypothesis that the airway obstruction is the main cause of feeding difficulties in
M
children with micrognathia. However, it is important for clinicians managing these children to consider the role of the cleft palate during treatment and early involvement
d
of a paediatric dietitian and speech pathologist is imperative.
te
The age at the time of MDO may also affect feeding outcomes, but due to the lack of adequate reporting in the included studies, it was not possible to do an age related
Ac ce p
analysis on outcomes. The mean age of patients included in this study was 7 months with ages ranging from 5 days of age at the time of surgery to 6 years of age. It can be extrapolated however from our findings that early MDO was successful at improving feeding, and this in turn may affect long term growth of the child. This is consistent with another study by Lidsky et al.,(38) 2008 which found that children who underwent early airway interventions (less than 3 months of age) were less likely to need feeding assistance compared to those who underwent delayed airway intervention despite syndromic status.
It is important to note here that these findings do not advocate a predominantly surgical treatment plan for all patients with upper airway obstruction secondary to micrognathia. Where possible, the relief of the airway obstruction with conservative methods is advocated, and surgical intervention is reserved for those who have failed
13
Page 12 of 27
conservative treatments such as prone positioning, nasopharyngeal tubes and other non-invasive techniques.
ip t
Gastro-esophageal reflux outcomes
cr
Gastro-esophageal reflux is common in infants and is becoming increasingly more
recognized as a possible cause of distress and failure to thrive in infants(43). Studies on
us
infants with PRS have shown that the prevalence of GERD is higher in patients with PRS than normal controls with prevalence rates of up to 83%(37, 44). Although the occurrence of GERD is likely to be multifactorial in these patients, several studies
an
have suggested that the most important factor in the occurrence of GERD in these patients is the upper airway obstruction(14, 44). These studies found that relief of the
M
upper airway obstruction via nasopharyngeal tubes, or other surgical interventions reduced the severity of reflux on pH monitoring. It is hypothesized that the airway
te
gastric contents.
d
obstruction leads to a negative intrathoracic pressure causing a suction effect on
This review aimed to evaluate the effect of MDO on reflux. The review found that the
Ac ce p
majority of patients with confirmed pre-operative GERD had significant improvement in reflux based on pH monitoring after MDO. These findings are consistent with the hypothesis that the cause of GERD in these patients is the airway obstruction. This improvement in reflux may be a contributing factor to the improvement in feeding as well. The improvement in reflux may also be related to the ability to remove feeding tubes from these patients after MDO. The contribution of these feeding tubes to reflux in these patients is yet to be determined. However, in the study by Marques et al., 2009, they found no statistically significant correlation between the length of time of use of feeding tubes and the improvement in reflux index values. They concluded that respiratory obstruction was a more important predisposing factor than feeding tubes in infants with PRS(44).
Recent studies have suggested that GERD and the need for Nissen fundoplication are associated with failure of distraction osteogenesis.(45) The findings of the airway
14
Page 13 of 27
outcomes of the larger systematic review were not consistent with this observation for primary MDO(15). The presence of severe GERD; however, was associated with increased risk of failure of decannulation of tracheostomy dependent patients after MDO. Often these children can be decannulated after Nissen fundoplication.
ip t
Tracheostomy dependent patients who are being considered for MDO should have formal pH monitoring pre-operatively. If severe reflux is diagnosed, referral to a
reflux. Ideally, this should be performed before MDO.
cr
pediatrician is required for consideration of medical or surgical management of the
us
Apart from the findings in this review, there were other relevant factors to feeding and reflux that were noted during review of the literature. Respiratory tract infections in
an
tracheostomy dependent children are common, and are likely secondary to aspiration. Children who undergo MDO seem to have a reduction in aspiration. The study by Monasterio 2004(37) and Hong 2012(13) included details about aspiration pre and post-
M
operatively. Monasterio 2004 reported in a retrospective series of 18 patients, 66% had barium penetration into laryngeal vestibule, 50% had stasis of residual material in the pharyngeal recess, 28% had pharyngeal transit of >1 second and 5.5% had
d
bronchial aspiration on barium swallow pre-operatively. Post-MDO, none of the
te
patients demonstrated barium aspiration and there was normal pharyngeal transit of <1 second in all patients.(37) Despite MDO significantly disrupting the tongue and
Ac ce p
oropharyngeal musculature, these patients tended to have a reduction in aspiration and hence respiratory infections. This may also be related to alleviation of the reflux by reversing the upper airway obstruction.
Limitations
Systematic reviews, by nature are retrospective and observational. They are heavily reliant on the data reporting of others, and hence are at risk of replicating biased results.
The quality of the included studies overall were poor. They were all case reports or case series, with no prospective trials, quasi-randomized or randomized control trials. Often the studies included had incomplete data, making the specific inclusion for each individual analysis more complex as can be seen in the results section. The heterogeneity within both the syndromic and isolated PRS groups creates an inherent 15
Page 14 of 27
difficulty in trying to group them into single groups. Hence, the syndromic analysis needs to be interpreted with caution. The findings of this review only provide a guide to what factors are associated with higher chance of failure, and which overall groups
ip t
of patients are at risk of further problems
There are currently no long-term studies evaluating the feeding outcomes or GERD
outcomes in children who underwent MDO for upper airway obstruction secondary to
cr
micrognathia. Further research is needed to evaluate long term improvement and
us
interventions that may be needed in these patients.
an
Conclusion
After MDO, 4 out of 5 patients could be exclusively orally fed within 12 months of MDO. Those with associated syndromes tended to have a 5 times higher rate of
M
requiring feeding adjuncts after MDO and hence should be monitored closely by a dietitian if the feeding adjuncts are removed. Several studies have reported the
d
observation that some children suffer from a decline in their growth parameters in the first 6-8 weeks post-operatively. We recommend that children should continue on
te
feeding adjuncts during this period to ensure appropriate nutritional status during this period of potential growth decline. Despite the few studies available, relief of the
Ac ce p
upper airway obstruction with MDO appears to reduce GERD in affected children. Further research is needed to determine if resolution of GERD and improvement in feeding in these patients persists in the long term.
References 16
Page 15 of 27
6. 7. 8. 9. 10.
ip t
cr
Ac ce p
11.
us
5.
an
4.
M
3.
d
2.
Robin P. Glossoptosis due to atresia and hypotrophy of the mandible. Am J Dis Child. 1934;48:541-7. Bush PG, Williams AJ. Incidence of the Robin Anomalad (Pierre Robin syndrome). Br J Plast Surg. 1983 Oct;36(4):434-7. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J. 2004;41:47-52. Vatlach S, Maas C, Poets CF. Birth prevalence and initial treatment of Robin sequence in Germany: a prospective epidemiologic study. Orphanet J Rare Dis. 2014;9:9. Cole A, Lynch P, Slator R. A new grading of Pierre Robin sequence. Cleft Palate Craniofac J. 2008 Nov;45(6):603-6. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J. 2004 Jan;41(1):47-52. Evans AK, Rahbar R, Rogers GF, Mulliken JB, Volk MS. Robin sequence: A retrospective review of 115 patients. Int J Pediatr Otorhinolaryngol. 2006;70(6):973-80. Denny AD, Talisman R, Hanson PR, Recinos RF. Mandibular distraction osteogenesis in very young patients to correct airway obstruction. Plast Reconstr Surg. 2001 Aug;108(2):302-11. Hong P, Bezuhly M. Mandibular distraction osteogenesis in the micrognathic neonate: A review for neonatologists and pediatricians. Pediatr Neonatol. 2013;54(3):153-60. Mathew OP, Clark ML, Pronske ML, Luna-Solarzano HG, Peterson MD. Breathing pattern and ventilation during oral feeding in term newborn infants. J Pediatr. 1985 May;106(5):810-3. Dinwiddie R. Congenital upper airway obstruction. Paediatr Respir Rev. 2004 Mar;5(1):17-24. Hong P, Bezuhly M, Mark Taylor S, Hart RD, Kearns DB, Corsten G. Tracheostomy versus mandibular distraction osteogenesis in Canadian children with Pierre Robin sequence: a comparative cost analysis. J Otolaryngol Head Neck Surg. 2012 Jun 1;41(3):207-14. Hong P, Brake MK, Cavanagh JP, Bezuhly M, Magit AE. Feeding and mandibular distraction osteogenesis in children with Pierre Robin sequence: a case series of functional outcomes. Int J Pediatr Otorhinolaryngol. 2012 Mar;76(3):414-8. Dudkiewicz Z, Sekula E, Nielepiec-Jalosinska A. Gastroesophageal reflux in Pierre Robin sequence--early surgical treatment. Cleft Palate Craniofac J. 2000 Mar;37(2):205-8. Breik O, Tivey D, Umapathysivam K, Anderson P. Mandibular distraction osteogenesis for the management of upper airway obstruction in children with micrognathia: a systematic review. Int J Oral Maxillofac Surg. 2016 Feb 8. Breik O, Umapathysivam K, Tivey D, Anderson PJ. Mandibular distraction osteogenesis in the management of airway obstruction in children: A
te
1.
12.
13.
14. 15.
16.
17
Page 16 of 27
22. 23. 24. 25.
ip t
cr
Ac ce p
26.
us
21.
an
20.
M
19.
d
18.
te
17.
systematic review protocol. The JBI Database of Systematic Reviews and Implementation Reports 2013;11(10): 16-29. The JBI Database of Systematic reviews and Implementation Reports. 2013;11(10):16-29. Al-Samkari HT, Kane AA, Molter DW, Vachharajani A. Neonatal outcomes of Pierre Robin sequence: an institutional experience. Clin Pediatr (Phila). 2010 Dec;49(12):1117-22. Breugem C, Paes E, Kon M, van der Molen AB. Bioresorbable distraction device for the treatment of airway problems for infants with Robin sequence. Clin Oral Investig. 2012 Aug;16(4):1325-31. Brevi B, Lagana F, Piazza F, Sesenna E. Mandibular distraction osteogenesis with a small semiburied device in neonates: report of 2 cases. Ear Nose Throat J. 2006 Feb;85(2):102-5. Chigurupati R, Massie J, Dargaville P, Heggie A. Internal mandibular distraction to relieve airway obstruction in infants and young children with micrognathia. Pediatr Pulmonol. 2004 Mar;37(3):230-5. Dauria D, Marsh JL. Mandibular distraction osteogenesis for Pierre Robin sequence: what percentage of neonates need it? J Craniofac Surg. 2008 Sep;19(5):1237-43. Denny A, Amm C. New technique for airway correction in neonates with severe Pierre Robin sequence. J Pediatr. 2005 Jul;147(1):97-101. Genecov DG, Barcelo CR, Steinberg D, Trone T, Sperry E. Clinical experience with the application of distraction osteogenesis for airway obstruction. J Craniofac Surg. 2009 Sep;20 Suppl 2:1817-21. Griffiths AL, Heggie A, Holman S, Robertson SP, White SM. Obstructive Sleep Apnea Successfully Treated by Mandibular Distraction Osteogenesis in a Rare Skeletal Dysplasia. J Craniofac Surg. 2013 Mar;24(2):508-10. Howlett C, Stavropoulos MF, Steinberg B. Feeding complications in a sixweek-old infant secondary to distraction osteogenesis for airway obstruction: a case report. J Oral Maxillofac Surg. 1999 Dec;57(12):14658. Iatrou I, Theologie-Lygidakis N, Schoinohoriti O. "Mandibular distraction osteogenesis for severe airway obstruction in Robin Sequence. Case report". J Craniomaxillofac Surg. 2010 Sep;38(6):431-5. Izadi K, Yellon R, Mandell DL, Smith M, Song SY, Bidic S, et al. Correction of upper airway obstruction in the newborn with internal mandibular distraction osteogenesis. J Craniofac Surg. 2003 Jul;14(4):493-9. Looby JF, Schendel SA, Lorenz HP, Hopkins EM, Aizenbud D. Airway analysis: With bilateral distraction of the infant mandible. J Craniofac Surg. 2009;20(5):1341-6. Miller JJ, Kahn D, Lorenz HP, Schendel SA. Infant mandibular distraction with an internal curvilinear device. J Craniofac Surg. 2007 Nov;18(6):1403-7. Miloro M. Mandibular distraction osteogenesis for pediatric airway management. J Oral Maxillofac Surg. 2010 Jul;68(7):1512-23. Mudd PA, Perkins JN, Harwood JE, Valdez S, Allen GC. Early intervention: distraction osteogenesis of the mandible for severe airway obstruction. Otolaryngol Head Neck Surg. 2012 Mar;146(3):467-72.
27. 28. 29. 30. 31.
18
Page 17 of 27
37. 38. 39. 40.
ip t
cr
Ac ce p
41.
us
36.
an
35.
M
34.
d
33.
Olson TP, McMurray JS, Mount DL. Endoscopic changes in the upper airway after mandibular distraction osteogenesis. J Craniofac Surg. 2011 Jan;22(1):105-9. Scott AR, Tibesar RJ, Lander TA, Sampson DE, Sidman JD. Mandibular distraction osteogenesis in infants younger than 3 months. Arch Facial Plast Surg. 2011 May-Jun;13(3):173-9. Spring MA, Mount DL. Pediatric feeding disorder and growth decline following mandibular distraction osteogenesis. Plast Reconstr Surg. 2006 Aug;118(2):476-82. Tibesar RJ, Scott AR, McNamara C, Sampson D, Lander TA, Sidman JD. Distraction osteogenesis of the mandible for airway obstruction in children: long-term results. Otolaryngol Head Neck Surg. 2010 Jul;143(1):90-6. Zenha H, Azevedo L, Rios L, Pereira A, Pinto A, Barroso ML, et al. Bilateral mandibular distraction osteogenesis in the neonate with pierre robin sequence and airway obstruction: a primary option. Craniomaxillofacial trauma & reconstruction. 2012 Mar;5(1):25-30. Monasterio FO, Molina F, Berlanga F, Lopez ME, Ahumada H, Takenaga RH, et al. Swallowing disorders in Pierre Robin sequence: its correction by distraction. J Craniofac Surg. 2004 Nov;15(6):934-41. Lidsky ME, Lander TA, Sidman JD. Resolving feeding difficulties with early airway intervention in Pierre Robin Sequence. Laryngoscope. 2008 Jan;118(1):120-3. Felix-Schollaart B, Hoeksma JB, Prahl-Andersen B. Growth comparison between children with cleft lip and/or palate and controls. Cleft Palate Craniofac J. 1992 Sep;29(5):475-80. Ranalli DN, Mazaheri M. Height-weight growth of cleft children, birth to six years. Cleft Palate J. 1975 Oct;12:400-4. Evans KN, Sie KC, Hopper RA, Glass RP, Hing AV, Cunningham ML. Robin sequence: from diagnosis to development of an effective management plan. Pediatrics. 2011 May;127(5):936-48. Maas C, Poets CF. Initial treatment and early weight gain of children with Robin Sequence in Germany: a prospective epidemiological study. Arch Dis Child Fetal Neonatal Ed. 2014 Nov;99(6):F491-4. Hyman PE. Gastroesophageal reflux: one reason why baby won't eat. J Pediatr. 1994 Dec;125(6 Pt 2):S103-9. Marques IL, Monteiro LCS, De Souza L, Bettiol H, Sassaki CH, Costa RDA. Gastroesophageal reflux in severe cases of Robin sequence treated with nasopharyngeal intubation. Cleft Palate Craniofac J. 2009 //;46(4):44853. Murage KP, Tholpady SS, Friel M, Havlik RJ, Flores RL. Outcomes analysis of mandibular distraction osteogenesis for the treatment of Pierre Robin sequence. Plast Reconstr Surg. 2013 Aug;132(2):419-21.
te
32.
42. 43. 44.
45.
Figures and tables legend Tables 19
Page 18 of 27
Table 1: PICO criteria for the systematic review Table 2: Data items collected and recorded for each outcome studied. Table 3: Studies included in different analyses for feeding outcomes and reasons for exclusion
ip t
Table 4: Collected data from the included studies consisting of demographics, feeding outcomes and centile data
exclusively fed orally or needed adjuncts following MDO.
cr
Table 5: Illustrates the feeding outcomes in terms of whether the patients could be
Figures
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Figure 1: The search strategy optimized for PubMed.
us
Table 6: Results of syndromic vs non-syndromic subgroup analysis.
Figure 2: Flow diagram demonstrating the numbers of studies screened, assessed for
Ac ce p
te
d
M
eligibility and included in the review
20
Page 19 of 27
Table(s)
Table 1: PICO criteria for the systematic review Participants
- Male and female children from birth with clinical evidence of micrognathia - Clinical evidence of upper airway obstruction
- Syndromic and non-syndromic children
cr
- Bilateral mandibular distraction
ip t
with failed conservative treatments
Exclusion
us
- Children who underwent unilateral distraction - Children with known pre-operative central
an
apnea/lower airway abnormalities
Outcomes
Feeding
M
Intervention
- TMJ ankylosis/hemifacial microsomia or other Bilateral mandibular mandibular conditiondistraction leading to osteogenesis airway obstruction
ed
Gastro-esophageal reflux
Outcome
Ac ce
Feeding
pt
Table 2: Data items collected and recorded for each outcome studied.
Gastro-esophageal reflux
Data items recorded Method of feeding after MDO: 1. Exclusively orally fed 2. Feeding adjuncts – Enteric feeding/gastrostomy Weight growth centiles and trends
Results of pH monitoring pre and post-MDO Need for treatment of GERD
Page 20 of 27
Table 3: Studies included in different analyses for feeding outcomes and reasons for exclusion Overall
Syndromic vs Non-
Design
Analysis
Syndromic
Al-Samkari 2010 (17)
RR
Included
Included
Breugem 2012 (18)
RR
Included
Included
Brevi 2006 (19)*
CR
Included
Included
Chigurupati 2004 (20)
RR
Included
Included
Dauria 2008 (21)
RR
Included
Included
Denny and Amm 2005 (22)
RR
Included
Included
Genecov 2009 (23)
RR
Included
Excluded – inadequate
cr
ip t
Study
us
Article
Griffiths 2013 (24)
CR
Included
Hong 2012 (13)
RR
Included
Included
Howlett 1999 (25)
CR
Included
Included
Iatrou 2010 (26)
CR
Included
Included
Izadi 2003 (27)
RR
M
distinction
Included
Included
Looby 2009 (28)
RR
Included
Included
RR
Included
Included
RR
Included
Excluded – inadequate
Ac ce
Mudd 2012 (31) Olson 2011 (32) Scott 2011
(33)
an
ed
Miloro 2010 (30)
pt
Miller 2007 (29)
Included
RR
distinction Included
Excluded – inadequate distinction
RR
Included
Included
RR
Included
Excluded – inadequate distinction
Spring 2006 (34)
RR
Included
Included
Tibesar 2010 (35)
RR
Included
Excluded – inadequate distinction
Zenha 2012 (36)
CR
Included
Included
21 included
16 included
RR – retrospective review, CR – Case report
*Contacted author for further information
Page 21 of 27
ip t cr
Country/U nit
RR
St Louis
No. of patients
Age (months) mean
7
Neonates
5
Neonates
Age Ranges
Breugem 2012
Brevi 2006
(19)
Chigurupati 2004 (20)
Netherlands
6
1
5
1
NG tube (2)
2
0
4
iPRS
NG tube
1
0
4
iPRS
NG tube
1
0
39
TCS
Gastrostomy
1
0
1
10
TCS
Gastrostomy
0
1
1
20
sMicro
Gastrostomy
1
0
1
0.5
iPRS
TPN
0
1
11-25th
5-10th
1
iPRS
Gastrostomy
0
1
11-25th
11-25th
1
iPRS
Gastrostomy
0
1
11-25th
5-10th
1
iPRS
TPN
1
0
26-50th
51-75th
Improved (but 1)
(10) - >50th centile
<3
12 months 25th
1
ce pt
Ac Texas
Griffiths 2013
CR
Melbourne
7-71 days
4
0.5
7-36 days
iPRS
-
4
0
7
0.6
sMicro
-
6
1
67
16
3-45 days 5days-6 years
Mixture
-
61
6
1
5
Skeletal
Haberman feeder
1
0
Genecov 2009 RR
3
iPRS
Australia
(23)
2
1
RR
Wisconsin
sMicro
4
1
RR
1
NG tube (5)
1
Denny and Amm 2005 (22)
6
Centile Post MDO (>6 weeks)
sMicro
2
St Louis
iPRS
Immed iate Improv ed Improv ed
0
Italy
RR
Centile pre
6
1
(21)
Feeding adjuncts
NG tube (6)
CR
Dauria 2008
Pre-MDO feeding
PO feed s
iPRS
ed
RR
(18)
Syndrom e
M an
Article Al-Samkari 2010 (17)
Study Design
us
Table 4: Collected data from the included studies consisting of demographics, feeding outcomes and centile data
9/12 -
Page 22 of 27
Nova Scotia Canada
2
2
4
2.5
(25)
CR
Florida
1
2
Iatrou 2010 (26)
CR
1
8
Izadi 2003 (27)
RR
Greece Los Angeles
7
0.25
8
0.25
RR
Israel
12 5
(29)
RR
Stanford
7
Miloro 2010 (30) Mudd 2012 (31)
RR RR
Chicago
Colorado
35 25
iPRS
28 - 94
sMicro
3.5 1
NG tubes (2)
2
0
NG tubes (4)
4
0
iPRS
-
1
0
iPRS
Gastrostomy
1
0
iPRS
NG tube (7)
7
0
sMicro
NG tube (7)
6
1
iPRS
Gastrostomy (8)
12
0
4
1
11-310 days
<8 months
ce pt
3
3.5
32-78 days
ed
Looby 2009 (28) Miller 2007
cr
ip t Howlett 1999
RR
10th
M an
Hong 2012 (13)
us
Dysplasia
(24)
0-4 years
sMicro iPRS
NG tube (2)
7
0
sMicro
NG tube (3) Gastrostomy (13), NG tube (18), PO (4)
0
3
35
0
Mixture
11-76 days
Mixture
-
13
12
5 days-6 years
iPRS
-
6
0
sMicro
-
6
2
Mixture
-
13
6
iPRS
-
1
0
sMicro
-
1
3
sMicro
-
5
0
25 4.8kg at 8 months
3/52 <5
8/52 - 25th 13.5kg at 22 months
Improved Just above 5
first 10/52 5
between 5-25
8
RR
Scott 2011 Spring 2006
RR
(34)
RR
(33)
Wisconsin
Ac
Olson 2011 (32)
Boston
Wisconsin
6
8
8 19
1.25
1
0.25
4
3
5
63
0.25 months 1,25-5.5 months 36.6-98 months
Have individual centile charts Have individual centile charts Have individual centile charts
Page 23 of 27
ip t RR
Mineapolis
CR
Portugal
32
10.4
1
0.3
1
0.3 Mean 7 months
5 days - 67 months
Mixture
Zenha 2012
Total
300
RR – Retrospective review CR – Case report
sMicro
22
10
Orogastric tube
1
0
PO
1
0
246
54
Ac
ce pt
ed
TCS – Treacher Collins Syndrome
iPRS
Gastrostomy (17), PO (15)
M an
(36)
cr
(35)
us
Tibesar 2010
Page 24 of 27
Table 5: Illustrates the feeding outcomes in terms of whether the patients could be exclusively fed orally or needed adjuncts following MDO.
Outcome
Total
PO feeds
Adjuncts
% PO feeds
needed 300
246
54
82%
PO feeds
Adjuncts
(%)
needed(%)
246 (82)
iPRS sMicro
ll patients
Total
Odds ratio (95% CI)
p-value
54 (18)
300
-
-
59 (93.7)
4 (6.3)
63
43 (72.9)
16 (27.1)
59
us
Variable
cr
Table 6: Results of syndromic vs non-syndromic subgroup analysis.
ip t
Feeding
1
-
5.49 (1.71, 17.58)
0.004
Ac ce
pt
ed
M
an
Syndromic analysis
Page 25 of 27
Ac
ce
pt
ed
M
an
us
cr
i
Figure(s)
Page 26 of 27
Ac ce p
te
d
M
an
us
cr
ip t
Figure(s)
Page 27 of 27