Voice related quality of life in pediatric patients with a history of prematurity

International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx

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PEDOT-7053; No. of Pages 5

Voice related quality of life in pediatric patients witha history of prematurity

Patrick C. Walz a,c,d,*, Michael P. Hubbell b, Charles A. Elmaraghy c,d

a Ann and Robert H. Lurie Children’s Hospital, McGaw Medical Center, Northwestern University, Chicago, IL, United Statesb Rockwood Clinic, Spokane, WA, United Statesc Nationwide Children’s Hospital, Columbus, OH, United Statesd Wexner Medical Center at the Ohio State University, Columbus, OH, United States

A R T I C L E I N F O

Article history:

Received 5 February 2014

Received in revised form 16 March 2014

Accepted 18 March 2014

Available online xxx

Keywords:

Prematurity

Dysphonia

Voice-related quality of life

A B S T R A C T

Objective: To determine incidence of dysphonia in patients with history of prematurity and evaluate the

correlation between dysphonia and risk factors unique to premature infants. The aim of this study is to

determine parent-perceived vocal quality in patients with history of prematurity and whether duration

of intubation, number of intubations, and incidence of patent ductus arteriosus repair were correlated

with these perceptions.

Methods: Cohort study of premature patients presenting to outpatient clinics from January 2010 to

January 2013 in tertiary care center. Patients gestational age �37 weeks at birth without history of

tracheostomy or known vocal fold pathology were eligible. A volunteer sample was obtained from

patients presenting in Otolaryngology clinics from January 2010 to January 2013 whose parents agreed

to complete surveys. Outcomes were assessed via parental completion of pediatric voice outcomes score

(pVOS) and pediatric voice-related quality of life (pVRQOL) instruments. The primary outcome assessed

was the incidence of dysphonia in infants with a history of prematurity without known vocal pathology.

Additionally, patient factors associated with dysphonia were evaluated. The hypothesis tested was

formulated prior to data collection.

Results: Sixty-nine participants were included. Mean age at follow-up was 28 (3–197) months. Mean

gestational age was 29 (23–37) weeks. Mean intubation duration was 3 (0–22) weeks and median

number of intubations was 1 (range 0–5). Voice outcome scores varied widely with pVRQOL scores

demonstrating a mean of 89.2 � 18.1 (25–100) and pVOS with a mean of 11.4 � 2.2 (0–13). Univariate

analysis utilized Spearman correlation coefficients for continuous variables and Wilcoxon Two-sample test

for categorical groups. Significance was set at p < 0.05. All significant univariate associations were placed in a

multivariate model. Duration of intubation �4 weeks was the only factor which correlated with dysphonia on

multivariate analysis (p = 0.0028, OR = 6.4, 95% CI = 1.9–21.6).

Conclusions: The data suggest that prolonged intubation is associated with poorer long term parent-

perceived voice quality in premature patients. Further study is required to correlate parent perceptions

with objective vocal quality data and physical findings of vocal pathology. These data may increase the

clinician’s suspicion for and evaluation of dysphonia in this population.

� 2014 Elsevier Ireland Ltd. All rights reserved.

Contents lists available at ScienceDirect

International Journal of Pediatric Otorhinolaryngology

jo ur n al ho m ep ag e: ww w.els evier . c om / lo cat e/ i jp o r l

1. Introduction

In the United States, over half a million children are bornprematurely each year [1]. The incidence of prematurity has

* Corresponding author at: 225 East Chicago Avenue, Box 25, Chicago, IL 60611,

United States. Tel.: +1 317 679 0423; fax: +1 312 227 9414.

E-mail address: [email protected] (P.C. Walz).

Please cite this article in press as: P.C. Walz, et al., Voice related qualiPediatr. Otorhinolaryngol. (2014), http://dx.doi.org/10.1016/j.ijporl.2

http://dx.doi.org/10.1016/j.ijporl.2014.03.023

0165-5876/� 2014 Elsevier Ireland Ltd. All rights reserved.

steadily increased by 36% since the early 1980s [1]. With theincrease in prematurity, there have been advances in the care ofpremature infants and improved long-term survival. Due tomyriad medical problems including pulmonary disease, prematureinfants are at risk for respiratory failure requiring prolongedintubation and mechanical ventilation. Additionally, this groupmay also require multiple surgical interventions or suffer episodicrespiratory distress requiring multiple intubations early in life. Therisk to the pediatric airway with prolonged and multiple

ty of life in pediatric patients with a history of prematurity, Int. J.014.03.023


mailto:[email protected]


http://www.sciencedirect.com/science/journal/01655876

www.elsevier.com/locate/ijporl


Table 1Patient background information. Values listed are mean � standard

deviation (range) for continuous variables and number (percentage) for

categorical variables. Age indicates age of the patient (in months) at time of

study enrollment. Gestational age indicates age (in weeks) at birth.

Patient background information

Age (months) 27.8 � 35.8 (3–197)

Gestational age (weeks) 29.4 � 4.1 (23–37)

Gender (M/F) 40 (58)/29 (42)

Intubation length (weeks) 2.99 � 5.2 (0–22)

Number of intubations 1.1 � 1.1 (0–5)

NICU stay (weeks) 9.16 � 8.5 (0–36)

Weight (kg) 1.48 � 0.9 (0.51–4.48)

Bronchopulmonary dysplasia 25 (37.3)

GERD 28 (40.6)

History of cardiac surgery 9 (13.8)

PDAL 8 (11.6)

NICU – neonatal intensive care unit; GERD – gastroesophageal reflux

disease; PDAL – patent ductus arteriosus ligation.

P.C. Walz et al. / International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx2

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intubations is well known and significant progress in the preventionof airway sequelae has been made in the last 3 decades [2–10].

As these previously premature patients mature and develop,they face significant physical and psychosocial challenges [11–14].Of these challenges, recent reports have also begun to cite voicedisturbances in premature patients [15,16]. As previous literaturehas supported a link between voice, quality of life, and evenoccupation choice [17], the impact of vocal quality, though of lessurgency in the setting of multiple complex medical concerns thatcan be associated with prematurity, does deserve considerationdue to its potential long-term impact.

Several instruments have been designed in the past decadespecifically to evaluate outcomes in voice related problems andtreatments. The most utilized and best validated surveys are theVoice Handicap Index (VHI) [18], the Voice Outcomes Survey (VOS)[19], and the Voice-Related Quality of Life (VRQOL) [20]. Theseinstruments were designed to be used in the care of laryngologypatients and were validated in adult populations. Since theirdissemination, each of these instruments has spawned a pediatricanalog, namely the pediatric VHI (pVHI) [21], pediatric VOS (pVOS)[22], and pediatric VRQOL (pVRQOL) [23]. Validation of both thepVRQOL[23] and the pVOS [22,23] have been performed in thepediatric population. Normative data from a healthy populationhas also been published [24].

Only one previous investigation has utilized any quality of lifeinstrument to investigate voice outcomes in pediatric patients witha history of prematurity [25], identifying a link between gestationalage at birth <25 weeks and moderate to severe voice disturbance inchildhood. In this population where patients can spend weeks tomonths on respiratory support, the larynx is susceptible to injuryfrom prolonged intubation, multiple intubations, or prolonged non-invasive ventilation. French et al. identified female gender andincreased number of intubations as significant risk factors formoderate to severe dysphonia in the premature patient [25].

The present study seeks to identify the association betweenairway management and other potentially confounding factors andcomorbid conditions on voice outcomes in the pediatric populationwith a history of prematurity by surveying parents of patients with ahistory of prematurity using the pVRQOL and the pVOS instruments.

2. Patients and methods

This study was a prospective observational study withretrospective chart analysis. Patients were prospectively accruedand surveys were obtained with subsequent retrospective chartreview for additional data. Institutional Review Board approvalwas obtained from the Nationwide Children’s Hospital IRB(IRB10-00161).

2.1. Inclusion criteria

Patients with a history of prematurity, defined as gestationalage at birth of 37 weeks or less, who presented for routine care tothe Neonatology or Otolaryngology outpatient clinic for routinecare between January 2010 and January 2013 were eligible forinclusion. Participation was voluntary, so a consecutive sample ofall patients was not able to be obtained. Parents of patientsmeeting these criteria were informed of the observational natureof the study and given the pVOS and pVRQOL instruments. Patientsmeeting criteria with returned surveys and consent for inclusionwere ultimately included in the analysis.

2.2. Exclusion criteria

Patients without consent for inclusion or who were not bornprematurely were excluded from the analysis. Additionally,


patients with a history of tracheostomy or known vocal pathologyand those presenting with voice complaints were excluded.

2.3. Data analysis

After accruing pVOS and pVRQOL scores as well as demographicdata for each patient, statistical analysis was performed.

2.4. Univariate analysis

The association between pVOS, pVRQOL, and patient demo-graphic and clinical factors was assessed. Spearman correlationswere used to identify associations between outcomes andcontinuous variables, and Wilcoxon Two-sample test was usedto compare pVOS and pVRQOL scores between categorical groups.P value <0.05 was considered significant. All tests were conductedin SAS 9.3 (by SAS Institute Inc., Cary, NC, USA).

2.5. Multivariate analysis

After identifying associated factors by univariate analysis,multivariate analysis was then undertaken to identify factors withindependent association to pVOS and pVRQOL. The pVOS andpVRQOL scores were not normally distributed, and there was noimprovement in the distribution with logarithmic or square roottransformation, so linear regression was not able to be applied. Assuch, the pVOS and pVRQOL outcomes were converted to binarydata reflecting a score either greater than or less than the medianscore (12 for pVOS, 100 for pVRQOL). Two separate models ofmultivariable logistic regression were then used to model the twoseparate outcome scores: pVOS and pVRQOL. Independentvariables were chosen from previous univariate analysis with pvalue <0.05. Backward stepwise selection method was then usedto select the best model. P value <0.05 was considered significant.All tests were conducted using SAS 9.3 (by SAS Institute Inc., Cary,NC, USA).

3. Results

Sixty-nine participants were identified meeting inclusioncriteria and were included in the analysis. Mean age at followup was 28 months (range 3–197 months). Mean gestational agewas 29 weeks (range 23–37 weeks). Mean length of intubation was3 weeks (range 0–22 weeks) and median number of intubationswas 1 (range 0–5). Patient demographics are further summarizedin Table 1 pVRQOL and pVOS scores varied widely, demonstrating



Table 2Spearman Correlations between voice outcome scores and continuous variables. Spearman correlation coefficients (r) are listed in the columns headed by r. N indicates total

number of observations for a given variable.

Spearman correlation coefficients (r)

pVOS score pVRQOL score

r p-value N r p-value N

Age (mo) �0.0793 0.5172 69 �0.14833 0.2844 54

Gestational age (wk) 0.34495 0.0037 69 0.2786 0.0414 54

Intubation length (wk) �0.52023 <0.0001 69 �0.29512 0.0303 54

Number of intubations �0.41013 0.0006 66 �0.20994 0.1392 51

NICU stay (mo) �0.42526 0.0003 69 �0.29915 0.028 54

Weight (kg) 0.32473 0.0065 69 0.2553 0.0624 54

GERD duration (mo) �0.2081 0.2976 27 �0.08865 0.7182 19

NICU – neonatal intensive care unit; GERD – gastroesophageal reflux disease; Pvos – pediatric voice outcomes scale; pVRQOL – pediatric voice related quality of life.

P.C. Walz et al. / International Journal of Pediatric Otorhinolaryngology xxx (2014) xxx–xxx 3

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dysphonia that ranged from severe to absent based upon parentalresponses (Table 2).

3.1. Spearman correlation between outcomes and continuous

variables

Continuous variables were then evaluated for their correlationwith the pVOS and pVRQOL outcomes (Table 2). pVOS score wassignificantly positively correlated with gestational age (r = 0.34,p = 0.0037) and birth weight (r = 0.32, p = 0.0065). Patients closerto term and patients with higher birth weights had better pVOSscores. pVOS score was significantly negatively correlated withlength of intubation (r = �0.52, p < 0.0001), number of intuba-tions (r = �0.41, p = 0.0006) and length of NICU stay (r = �0.42,p = 0.0003). Patients with longer length of intubation, increasednumber of intubations, and longer NICU stays have poorer pVOSscores. pVRQOL score was significantly positively correlated with

Table 3Univariate analysis of categorical variables relative to pVOS and pVRQOL.

Variable N Mean (std. de

Gender F

pVOS score 69 11.45 (2.15)

pVRQOL score 54 88.88 (18.80)

BPD No

pVOS score 67 11.93 (1.20)

pVRQOL score 52 92.80 (12.61)

GERD No

pVOS score 69 11.32 (1.88)

pVRQOL score 54 91.16 (14.85)

History of heart surgery No

pVOS score 65 11.64 (1.75)

pVRQOL score 50 92.06 (14.69)

PDA No

pVOS score 65 11.79 (1.84)

pVRQOL score 50 92.26 (14.79)

CPAP No

pVOS score 62 12.09 (1.20)

pVRQOL score 48 90.97 (16.01)

Treatment of PDA PDAL

pVOS score 21 9.50 (4.11)

pVRQOL score 14 63.84 (31.27)

Intubation (weeks) >0

pVOS score 69 10.98 (2.40)

pVRQOL score 54 87.20 (20.17)

Intubation (weeks) �4

pVOS score 69 9.75 (3.14)

pVRQOL score 54 75.54 (25.06)

Intubation (weeks) �8

pVOS score 69 10.31 (1.32)

pVRQOL score 54 77.79 (20.67)

N – number included in analysis. pVOS – pediatric voice outcome study, pVRQOL – p

gastroesophageal reflux disease, PDA – patent ductus arteriosus, CPAP – continuous po


gestational age (r = 0.28, p = 0.0414) and significantly negativelycorrelated with length of intubation (r = �0.30, p = 0.0303) andlength of NICU stay (r = �0.30, p = 0.0280).

3.2. Analysis of voice outcome scores by categorical groups

Categorical variables were then correlated to voice outcomes asoutlined in Table 3. pVOS score was significantly higher in patientswithout BPD (11.93 � 1.2) than patients with BPD (10.40 � 3.07)(p = 0.0126). pVOS score was significantly higher in patients withoutPDA (11.79 � 1.84) than patients with PDA (10.65 � 2.71)(p = 0.0124). pVOS score was significantly higher in patients withoutintubation (12.24 � 1.26) than patients with any intubation(10.98 � 2.40) (p = 0.0036). Additionally, pVOS score was significant-ly higher in patients with <4 week intubation length (12.02 � 1.16)than patients with �4 week intubation length (9.75 � 3.14)(p < 0.0001). Furthermore, pVOS score was significantly higher in

v) Mean (std. dev) p-value (2-sided)

M

11.30 (2.24) 0.5705

89.52 (17.80) 0.5633

Yes

10.40 (3.07) 0.0126

83.03 (24.18) 0.2003

Yes

11.43 (2.62) 0.3168

85.97 (22.61) 0.5521

Yes

9.78 (3.93) 0.0556

69.45 (31.17) 0.0232

Yes

10.65 (2.71) 0.0124

83.16 (24.10) 0.3299

Yes

11.18 (2.56) 0.0866

90.35 (19.21) 0.9534

Indocin

11.46 (1.13) 0.2037

94.24 (12.81) 0.0323

0

12.24 (1.26) 0.0036

93.00 (13.10) 0.3146

<4

12.02 (1.16) <0.0001

94.51 (11.05) 0.0026

<8

11.61 (2.29) 0.0005

91.23 (17.07) 0.0165

ediatric voice-related quality of life, BPD – bronchopulmonary dysplasia, GERD –

sitive airway pressure, PDAL – PDA ligation.



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patients with <8 week intubation length (11.61 � 2.29) than patientswith �8 intubation length (10.31 � 1.32) (p = 0.0005).pVRQOL scorewas significantly higher in patients without cardiac surgery(92.06 � 14.69) than patients with any history of cardiac surgery(69.45 � 31.17) (p = 0.0232). pVRQOL score was significantly lowerfor patients with patent ductus arteriosus (PDA) who were managedwith PDA ligation than those managed medically (p = 0.0323).pVRQOL score was significantly higher in patients with <4 weekintubation length (94.51 � 11.05) than patients with �4 weekintubation length (75.54 � 25.06) (p = 0.0026). pVRQOL score wassignificantly higher in patients with <8 week intubation length(91.23 � 17.07) than patients with �8 week intubation length(77.79 � 20.67) (p = 0.0165).

3.3. Multivariate logistic regression for outcome pVOS and pVRQOL

Variables included in multivariate analysis of pVOS score weregestational age, number of intubations, length of NICU stay,weight, presence of bronchopulmonary dysplasia (BPD), presenceof PDA, and length of intubation (<4 vs. �4 weeks). Whenassessing the impact of multiple variables on pVRQOL score,gestational age, length of NICU stay, history of cardiac surgery, andlength of intubation (<4 vs. �4 weeks) were included. On initialevaluation, under the control of other covariances, each factor didnot play a significant role in either model. By using the Backwardstepwise selection method the best model for both pVOS andpVRQOL were chosen and one significant factor was identified:intubation length (<4 weeks vs. �4 weeks). Patients intubated for<4 weeks had a significantly higher probability of having a higherthan median pVOS score (p = 0.0028, OR = 6.4, 95% CI = 1.9–21.6).There was no significant difference in comparison of the pVRQOLanalysis.

4. Discussion

Premature infants are subjected to myriad interventions inorder to assist with vital functions as they continue to grow anddevelop. The long-term effects – both intended and unintended –of the measures undertaken to ensure the long term health of thesepatients are beginning to be understood. When considering airwayinterventions, the primary focus in long-term studies has longbeen airway patency, but in recent years, the impact of prolongedintubation and multiple intubations on voice outcomes has beenconsidered. Our data support the commonly held notion that theduration of intubation is negatively correlated with parent-perceived voice outcomes in premature patients independent ofother potential confounding variables.

While previous authors have identified the frequency ofintubations as a risk factor for decreased vocal quality andvoice-related quality of life, their investigation focused on ex-25week premature infants, effectively excluding a portion of thepremature population. This difference in inclusion criteria mayhave contributed to the disparate findings between theirinvestigation and the current study, with the Australian cohortselecting a more severely compromised cohort.

The strengths of this preliminary investigation include pro-spective collection of quality of life data, diverse populationincluding both extremely premature infants and near term infants,and assessment of potentially confounding variables. Weaknessesinclude the retrospective nature of comorbidity identification,relatively small sample size, and lack of correlation of voice qualityof life measures with standardized objective vocal quality scores orlaryngeal findings. Another weakness of the study was thevoluntary nature of recruitment, potentially leading to a reportingbias. Another interesting finding leading to challenges with data


analysis was the relatively good voice quality reported overall,with median pVOS and pVRQOL scores at or near normal.

Areas for future research include the identification of objectivevocal quality measures to validate the perceptual findings andcorrelation of vocal quality and voice-related quality of lifemeasures with pathologic changes. While the current study aidsin selecting patients at increased risk for any dysphonia, furtherinvestigations will ideally correlate physical findings withperceived dysphonia, enabling providers to identify at-riskpatients sooner with the hope for early intervention and improvedoutcomes.

5. Conclusion

The data suggest that independent of comorbidities commonlyassociated with poor vocal quality of life, duration of intubation inthe neonatal period is associated with poorer parent-perceivedvoice quality in premature patients. As a result, the clinician shouldmaintain an increased suspicion for dysphonia in this populationand a low threshold for evaluating the larynx to assess for vocalpathology.

Funding source

No specific funding source.

Conflict of interest

None.

Acknowledgements

The authors would like to acknowledge Wei Wang and Dr. IgorDvorchik at the Biostatistics Core Division of the NationwideChildren’s Hospital for their assistance with statistical analysis.

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Voice related quality of life in pediatric patients with a history of prematurity