The Cleft Palate–Craniofacial Journal 52(2) pp. e23–e31 March 2015 Ó Copyright 2015 American Cleft Palate–Craniofacial Association

ORIGINAL ARTICLE Hearing Outcomes in Patients With Cleft Lip/Palate Hildur Skuladottir, M.D., Ase Sivertsen, M.D., Ph.D., Jorg Assmus, Ph.D., Asa Rommetveit Remme, R.N., Marianne Dahlen, R.N., Hallvard Vindenes, D.D.S., M.D., Ph.D. Objective: Children with cleft lip and palate or cleft palate only have a high incidence of conductive hearing loss from otitis media with effusion. Studies demonstrating longitudinal results are lacking. This study was undertaken to investigate long-term longitudinal hearing outcomes of children with cleft lip and/or cleft palate and cleft palate only. Design: Retrospective chart review. Setting: Clinical charts of patients born with cleft lip and palate or cleft palate only in 1985 to 1994 who were referred to the cleft team in Bergen, Norway. Study findings include 15 years of follow-up. Participants: The study population consisted of 317 children of whom 159 had nonsyndromic cleft lip and palate and 158 had nonsyndromic cleft palate. Main Outcome Measures: Pure tone average calculated from pure tone audiometry at ages 4, 6, and 15 years. Results: The median pure tone average significantly improved with increasing age. For the cleft lip and palate group, the median pure tone average at ages 4, 6, and 15 years was 16 dB hearing level (HL), 13 dB HL, and 9 dB HL, respectively (P  .001). In the cleft palate group the median pure tone average at ages 4, 6, and 15 years was 15 dB HL, 12 dB HL, and 9 dB HL, respectively (P  .001). There was no significant difference in the hearing levels between the two groups. Patients who had surgical closure of the palate at age 18 months had a significantly better pure tone average outcome at age 15 compared with patients who had surgery at 12 months. Conclusions: Hearing improves significantly from childhood to adolescence in patients with cleft lip and palate and cleft palate only. KEY WORDS:

cleft lip/palate, hearing, longitudinal outcomes, long-term outcomes

Nonsyndromic cleft lip and/or cleft palate (CL/P) are among the most common birth defects in the head and neck in humans (Mossey et al., 2009). The prevalence in Norway is 2.2 per 1000 live births (Sivertsen et al., 2008). Treatment of CL/P is a challenging task due to the complexity of problems that arise from birth to adulthood. In Norway treatment is handled by two interdisciplinary teams. The treatment involves plastic surgeons; orthodontists; ear, nose, and throat (ENT) specialists; speech-language pathologists; and nurses. All patients referred to the cleft team in Bergen receive a standardized treatment and follow-up, which has been documented in a structured manner since 1968 (Sivertsen et al., 2008; Tindlund et al., 2009). A recent review of the scientific knowledge base for treatment of patients with CL/P concluded that existing research does not meet the criteria needed to offer evidencebased treatment (Forsetlund et al., 2009). When studying outcomes, special attention needs to be paid to the two major cleft subgroups: cleft lip and palate (CLP) and cleft

Dr. Skuladottir is Resident Physician, Department of Plastic Surgery, Haukeland University Hospital, and PhD candidate, Department of Global Public Health and Primary Care, University of Bergen; Dr. Sivertsen is Consultant Plastic Surgeon, Department of Plastic Surgery, Haukeland University Hospital, and Postdoctoral researcher, Department of Global Public Health and Primary Care, University of Bergen; Dr. Assmus is Biostatistician, Center for Clinical Research; Mr. Remme is Registrated Nurse, Department of Plastic Surgery, Haukeland University Hospital; Ms. Dahlen is Registrated Nurse, Haukeland University Hospital; and Dr. Vindenes is Consultant Plastic Surgeon, and Professor, Department of Plastic Surgery, Haukeland University Hospital, and Department of Clinical Dentistry, University of Bergen, Bergen, Norway. This manuscript was presented orally at the 9th European Craniofacial Congress, September 14 to 17, 2011, in Salzburg. Submitted January 2013; Revised September 2013; Accepted December 2013. Address correspondence to: Dr. Hildur Skuladottir, 20202 Spring Meadow Drive, Durham, NC 27517. Department of Plastic Surgery, Haukeland University Hospital, Jonas Lies vei 65, 5021 Bergen, Norway. Department of Global Public Health and Primary Care, University of Bergen, Kalfarveien 31, 5020 Bergen, Norway. E-mail [email protected].

DOI: 10.1597/13-009 23

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palate only (CP), which have distinct causalities (FoghAndersen, 1942). Cleft lip and palate and CP are described in a number of known syndromes, and the association differs in the two categories of clefts (for further information, visit the OMIM website: http://www.ncbi. nlm.nih.gov/omim). Otology Cleft palate laterally displaces the musculus tensor veli palatini and musculus levator veli palatini, which are responsible for the opening of the eustachian tube and thus cause dysfunction. This dysfunction leads to poor ventilation of the middle ear cavity, which in turn leads to negative pressure and results in a retracted tympanic membrane and mucous secretion (Broen et al., 1996). Eventually, this results in otitis media with effusion (OME), which is defined as middle ear effusion for 3 or more months (Kuo et al., 2013). Previous studies have found that the prevalence of OME in patients with CL/P is more than 90% (Ponduri et al., 2009). Otological complications of OME include cholesteatoma and chronic otitis (Møller, 1981). Since Paradise et al. (1969) described a universal prevalence of OME in children with CL/P, grommets have been become a standard procedure in many cleft centers, including those in Norway (Ponduri et al., 2009). One study found that 98% of 5-year-old children with CL/P have had at least one set of grommets (Szabo et al., 2010). The most common complications due to grommet insertions are persistent eardrum perforation and tympanosclerosis (Lous et al., 2005).

However, there are additional anatomical differences such as an altered cranium base and pharyngeal anatomy, a more collapsible eustachian tube, and ossicular malformations that may also cause hearing loss in patients with CL/P (Tuncbilek et al., 2003; Chen et al., 2008). Recent studies have indicated that patients with bilateral cleft lip and palate (BCLP) have poorer hearing outcomes than patients with unilateral cleft lip and palate (UCLP) (Handzic-Cuk et al., 1996; Flynn et al., 2013). In addition, there is inconsistent evidence that timing of the surgical closure of the palate might influence hearing outcomes (Watson et al., 1986; Rohrich and Byrd, 1990; Robinson et al., 1992). Studies on long-term outcomes indicate that although the hearing outcomes improve into adolescence (Bardach et al., 1992; Handzic-Cuk et al., 1996; Koempel and Kumar, 1997; Yang and McPherson, 2007; Flynn et al., 2013), many patients have permanent hearing loss (Yules, 1970; Bennett, 1972; Paradise, 1975; Møller, 1981; Gordon et al., 1988). In this study we investigated longitudinal hearing outcomes, presenting follow-up to the age of 15. We explored the relationship among timing of palatal closure, morphology, and hearing outcomes. Unilateral cleft lip and palate is more prevalent on the left-hand side (Paulozzi and Lary, 1999; Mittwoch, 2008; Dixon et al., 2011), and we wanted to investigate whether there was a difference in the pure tone average (PTA) outcomes on the right versus left ear. We also investigated whether there was a difference between UCLP and BCLP. Finally, we investigated whether poor hearing outcomes in childhood (at age 4) are a prognostic factor for outcomes in midadolescence (at age 15).

Audiology MATERIALS Children with CL/P have a high incidence of conductive hearing loss from OME (Paradise, 1969; Møller, 1975; Hubbard, 1985; Grant et al., 1988; Robinson et al., 1992; Hornigold et al., 2008; Flynn et al., 2009). Despite the fact that most newborns with CL/ P (82%) pass the newborn hearing screening (Szabo et al., 2010), the majority (82%) present with hearing loss in early infancy (Viswanathan et al., 2008). The three main categories of hearing loss are conductive, sensorineural, and mixed hearing loss. Conductive hearing loss is characterized by a faulty transmission of airwaves through either the outer or middle ear and usually affects the low frequencies. Sensorineural hearing loss is characterized by an impaired reception of the sound waves and often affects the high frequencies (Niskar et al., 1998). Mixed hearing loss refers to a combination of conductive and sensorineural hearing loss. The most common type of hearing loss in children with CL/P is conductive hearing loss caused by OME (Kuo et al., 2013). Otitis media with effusion functionally leads to a hearing loss of about 25 to 30 dB (Lous et al., 2005).

AND

METHODS

From January 1985 through December 1994, a total of 570 children were referred to the cleft team in Bergen. In the study period 18 (3%) patients died, and these patients were excluded from the study. Of the remaining 552 patients, 98 (18%) had additional malformations or known syndromes. These patients were excluded because many of these conditions can also affect hearing. This resulted in 454 isolated cases of cleft lip and/or palate (CL/P). A total of 296 (65%) had cleft lip with or without cleft palate CL6P and 158 (35%) had isolated CP (Table 1). Due to the common assumption that the involvement of the palate is responsible for otological problems, 137 (30%) patients with cleft lip only (CL) did not receive ENT follow-up and were excluded from the study (Graham 1963). This resulted in a study population of 317 nonsyndromic children with CLP (n ¼ 159) and CP (n ¼ 158), illustrated in Figure 1. The ENT protocol involves otoscopy, tympanometry, and audiological examination using standard pure tone audiometry at 4, 6, and 15 years of age. Ear-specific measurements were performed at 500, 1000, and 2000 Hz

Skuladottir et al., HEARING OUTCOMES IN PATIENTS WITH CLEFT LIP/PALATE

TABLE 1 Distribution in Terms of Cleft Type, Gender, and Additional Malformations/Syndromes Total, n All clefts CLP Nonsyndromic Syndromes/malformations

552 328 296 32

CP Nonsyndromic Syndromes/malformations

224 158 66

Male, n (%) 324 229 209 20

(59) (70) (71) (63)

95 (42) 64 (41) 31 (47)

Female, n (%) 228 99 87 12

(41) (30) (29) (38)

129 (58) 94 (59) 35 (53)

* CLP ¼ cleft lip and palate; CP ¼ isolated cleft palate.

and registered in dB hearing level (HL) by trained audiologists using headphones. For children aged 4 to 6 years conditioned-play audiometry was used, where the child indicates hearing a sound by a repetitive play task (such as placing a peg on a pegboard). A three-frequency PTA was calculated for each ear. The right ear was always tested before the left ear. In our clinic there has been a low threshold for treating children with CL/P with myringotomy and grommets. All children undergo an ENT examination prior to closure of the palate. Although myringotomy and grommet insertions are typically performed at the time of palatal closure, many patients have already been treated at that point. From 1985 to 1990 all patients with clefts affecting the palate were prophylactically treated in both ears at the time of palatal closure, but in the early 1990s the protocol was changed to treat only one ear (usually the most affected ear). These changes were instigated to minimize potential complications arising from the myringotomy/grommets. From 1985 to 1994 surgical closure of the palate was performed using the modified von Langenbeck technique (Smith and Ugalde, 2009). From 1985 to 1988 the timing was at 24 months of age. From 1989 to 1992, the timing of the procedure was gradually reduced to 12 months of age. During the transition patients were treated at 18 months of age. To investigate the effect of timing on later audiological outcomes we grouped the patients according to timing of closure as follows: 12 months (patients who had surgery performed from 9 to 15 months), 18 months (patients who had surgery performed from 15 to 21 months), and 24 months (patients who had surgery performed from 21 to 27 months). At ages 6 and 15, the ENT examination is a part of a battery of examinations performed in one day on the socalled clinical conference days (CCD). The CCDs are held twice a year for patients aged 6 and 15 that year. The whole cleft team gathers to perform joint examinations of the patients who undergo ENT examinations, a speechlanguage pathology evaluation, a clinical examination by a plastic surgeon, and an orthodontic examination. Following the CCDs the cleft team meets to evaluate the results and give each patient an individual follow-up plan.

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Audiological examination can be challenging in children. In the ENT department in Bergen the cutoff for satisfactory hearing is 15 dB HL, however a 20 dB HL is frequently used in the literature (Browning et al., 2010). The audiologist might accept an incomplete result so as not to stress the child further. Thus, an absolute PTA level might not be the true threshold. The ability to comply with testing often changes with age. To address this potential bias, we divided the scores into 15 dB HL and .15 dB HL at each test interval to investigate whether there was a difference in the number of patients with poor outcomes in each age group. This was also done with 20 dB HL as the cutoff. Statistics We calculated median and range values for the PTA level at ages 4, 6, and 15 years and compared the results at 4 and 6, 4 and 15, and 6 and 15 years, respectively, using the Wilcoxon signed-rank test. The same test was used to compare differences between CLP (including differences between UCLP and BCLP) and CP at all ages and to compare outcomes on right versus left ears. For the effects of timing of palatal closure on hearing, the median PTA at ages 4, 6, and 15 years was compared between the different age groups of intervention (12, 18, and 24 months), also using the Wilcoxon signed-rank test. The McNemar test was used to compare the differences between the different age groups after categorizing patients into a dichotomous variable using 15 and 20 dB as the cutoff. A one-way analysis of variance was used to compare the PTA score for the different morphological subgroups. P values of .05 were considered statistically significant. For statistical analysis we used Predictive Analytics Software (PASW, SPSS Inc. Released 2009. PASW Statistics

FIGURE 1 Morphological distribution among 454 nonsyndromic cases of CL/P. Abbreviations: CLP ¼ cleft lip and/or palate; CL ¼ cleft lip without cleft palate; CLP ¼ cleft lip and palate; B ¼ bilateral; U ¼ unilateral; CP ¼ isolated cleft palate.

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TABLE 2 Pure Tone Average (PTA) Outcomes at Ages 4, 6, and 15 Years in 159 Patients With CLP and 158 Patients With CP (Participation Differs Between Age Groups); Outcomes Compared Between Ages 4 and 6 Years, 6 and 15 Years, and 4 and 15 Years† PTA (dB HL) 4y

Comparing Outcomes at

6y

15 y

Ages (P Values)

n

Median (Range)

n

Median (Range)

n

Median (Range)

4 Versus 6 y

6 Versus 15 y

4 Versus 15 y

CLP All Right Left

167 90 77

16 (5–52) 17 (5–48) 15 (5–52)

224 112 112

13 (2–48) 13 (2–48) 12 (2–48)

267 134 133

9 (3–60) 10 (0–40) 8 (3–60)

.001* .001* .002*

.001* .001* .001*

.001* .001* .001*

CP All Right Left

167 86 81

15 (2–58) 15 (7–58) 15 (2–52)

226 113 113

12 (0–53) 12 (0–53) 13 (2–50)

256 128 128

9 (0–68) 10 (0–47) 8 (0–68)

.001* .001* .019*

.001* .001* .001*

.001* .001* .001*

† CLP ¼ cleft lip and palate; CP ¼ isolated cleft palate, n ¼ number of observations (ears). * Indicates a statistically significant result. P values calculated by using Wilcoxon signed rank test. Statistically significant if P  .05.

for Windows, Version 18.0. Chicago: SPSS Inc.) version 18.0 and STATA version 12 (StataCorp. 2011. Stata Statistical Software: Release 12. College Station, TX: StataCorp LP). Graphics were created using Matlab version 7.10 (MATLAB version 7.10.0. Natick, Massachusetts: The MathWorks Inc., 2010). Ethics The Regional Ethical Board classified the study as quality control and hence regulated by the hospitals’ regulations. Formal ethical approval was given by the data protection officials for research at Haukeland University Hospital. Principles outlined in the Declaration of Helsinki were followed. RESULTS The demographic distribution in terms of gender and additional associated malformations and syndromes is presented in Table 1. The study population shows a similar distribution as previously described in Norway (Sivertsen et al., 2008). This is also true for the morphological distribution (Fig. 1) that illustrates the higher frequency of CLP (65%) compared with CP (35%).

Table 2 illustrates the median PTA scores for right and left ears and the range of observations at ages 4, 6, and 15 years. For CLP the PTA decreases with age as follows: from 16 dB HL at age 4 to 13 dB HL at age 6 and 9 dB HL at age 15 years. For CP the results are as follows: from 15 dB HL at age 4 to 12 dB HL at age 6 and 9 dB HL at age 15. When comparing the outcomes between the different age groups (age 4 versus 6 years, age 6 versus 15 years, and age 4 versus 15 years), there was a significant improvement with age between all age groups for both CLP and CP. When using 15 dB HL as a cutoff there was significant improvement in CLP and CP in all age groups (Table 3). When using PTA 20 dB HL as a cutoff, there was a significant improvement in CLP when comparing the outcomes between ages 4 and 15 years (P  .001) and ages 4 and 6 years (P¼.02), but not between ages 6 and 15 years (P ¼ .07). For CP there was a significant improvement between ages 6 and 15 years (P ¼ .008) and 4 and 15 years (P  .001), but not between ages 4 and 6 years (P¼.22). At the age of 4 years there were more assessments of the right ear than the left. This is due to the fact that the right ear was examined first, and the youngest patients sometimes refused to proceed with examinations in the left ear. However, there was no significant difference between right and left ears at any age.

TABLE 3 Pure Tone Average (PTA) Outcomes .15 and 20 dB at the Ages 4, 6, and 15 in 159 Patients With CLP and 158 Patients With CP (Participation Differs Between Age Groups); Outcomes Compared Between Ages 4 and 6 Years, 6 and 15 Years, and 4 and 15 Years† n (%)

Comparing Outcomes at Ages (P Values)

4y

6y

15 y

4 Versus 6

6 Versus 15

4 Versus 15

CLP PTA . 15 dB HL PTA  20 dB HL

79 (47) 66 (40)

77 (34) 56 (25)

42 (16) 30 (11)

.004* .02*

.001* .07

.001* .001*

CP PTA . 15 dB HL PTA  20 dB HL

78 (47) 54 (32)

87 (38) 60 (27)

59 (23) 41 (16)

.03* .22

.001* .008*

.001* .001*

† n ¼ number of patients; CLP ¼ cleft lip and palate; CP ¼ isolated cleft palate. * Indicates a statistically significant result. P values calculated by using the McNemar test. Statistically significant if P  .05.

Skuladottir et al., HEARING OUTCOMES IN PATIENTS WITH CLEFT LIP/PALATE

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TABLE 4 Comparing Mean Pure Tone Average (PTA) Outcomes at Ages 4, 6, and 15 Years in Patients With UCLP Versus BCLP in 115 Patients With UCLP and 44 With BCLP (Participation Differs Between Age Groups)* PTA Results in dB HL UCLP

BCLP

Age, y

n

Mean (95% CI)

n

Mean (95% CI)

Difference

P Value

4 6 15

114 162 193

18.1 (15.7–20.4) 16.0 (13.7–18.2) 10.7 (9.30–12.1)

53 62 74

19.6 (16.0–23.2) 15.0 (12.2–17.9) 11.8 (8.70–15.0)

1.1 1.0 1.5

.16 .61 .19

* UCLP ¼ unilateral cleft lip and palate; BCLP ¼ bilateral cleft lip and palate; n ¼ number of observations (ears); CI ¼ confidence interval.

There was no significant difference between the PTA score in patients with CP compared with CLP in any age group. For 4 years the difference was 0.6 dB HL (P ¼ .57), for 6 years the difference was 0.8 dB HL (P ¼ .29), and for 15 years the difference was 0.1 dB HL (P ¼ .87). We found no difference between UCLP and BCLP (Table 4). Figure 2a and 2b illustrates the median PTA level in dB HL at ages 4, 6, and 15 years for the right and left ears. To investigate the prognostic importance of a poor audiological outcome at 4 years, we identified the patients who had PTA .15 dB HL at 4 years of age with complete data at 4, 6, and 15 years. Figure 2c and 2d illustrates that a PTA level .15 dB HL at 4 years does not have a negative prognostic effect and that the majority of patients with poor outcomes in childhood have good outcomes in adolescence. Figure 3 illustrates the timing of surgical closure. In the isolated CLP group, 21 (13%) patients had palatal closure at 12 months, 76 (48%) at 18 months, and 42 (26 %) at 24 months. Twenty (13%) patients had surgery elsewhere or at a different timing. In the CP group, 10 (6%) patients had palatal closure at 12 months, 56 (35%) at 18 months, and 53

(34%) at 24 months. Of the patients, 39 (25%) had surgery elsewhere or at a different timing. Table 5 outlines the mean PTA by timing of surgical closure of the palate. Table 6 illustrates the comparison of PTA outcomes at ages 4, 6, and 15 years by timing of surgical closure of the palate; there was a statistically significant difference at 15 years between the patients who had surgery at 18 compared with those who had surgery at 12 months (13.1 dB HL versus 10.1 dB HL, P ¼ .03). There were no other significant differences in PTA outcomes by timing of surgery. A total of 24 patients (18% of the patients, a total of 30 ears) with CLP and 27 patients (21% of the patients, a total of 41 ears) with CP had PTA scores equal to or above 20 dB HL at 15 years of age (Table 7). Otitis media with effusion was present in nine (38%) patients in the CLP group and seven (26%) patients with CP. Grommets were present in five (21%) patients with CLP and two (7%) patients with CP. Tympanosclerosis was present in four (17%) patients with CLP and five (19%) patients with CP. Perforation was present in three (13%) patients with CLP and five (19%) patients with CP group.

FIGURE 2 Four graphs demonstrating median pure tone average (PTA) outcome, interquartile range, and minimum to maximum range. Graph: a: PTA outcomes for left ear according to cleft type at ages 4, 6, and 15 years. b: PTA outcomes for right ear according to cleft type at ages 4, 6, and 15 years. c: Illustrates the progression of PTA outcomes (left ear) in patients according to whether their initial PTA score was .15 dB or 15 dB. d: Illustrates the progression of PTA outcomes (right ear) in patients according to whether their initial PTA score was .15 dB or 15 dB.

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TABLE 6 Difference in Pure Tone Average (PTA) Outcomes at Ages 4, 6, and 15 Years by Timing of Surgical Closure of the Palate (at 12, 18, and 24 Months) in 159 Patients With CLP and 158 Patients With CP (Participation Differs Between Age Groups)† Difference in Timing of Surgery (P Value) PTA (dB HL) at age, y

12 Versus 18 mo

12 Versus 24 mo

18 Versus 24 mo

4 6 15

0.2 (.27) 1.8 (.24) 3.0 (.03)*

1.3 (.79) 1.3 (.38) 1.7 (.28)

1.5 (.18) 0.5 (.83) 1.3 (.21)

† CLP ¼ cleft lip and palate; CP ¼ isolated cleft palate. * Indicates a statistically significant result. Groups are compared using Wilcoxon rank-sum test, and the results were considered statistically significant when P  .05.

factor for later outcomes. All of the patients were treated with a low-threshold protocol for early treatment and prevention of OME with myringotomy and grommets. The strengths of this study are the unique set of longitudinal data and the relatively large number of patients. The association of hearing loss and CL/P was first noted in 1893 (Gutzmann, 1893). This was followed by studies confirming this association; however, there was a large discrepancy in the incidence of hearing loss, ranging from 3% to 74% in different studies (Graham, 1963). Graham (1963) attributed this to differences in definitions of hearing loss, testing procedures, and age at testing. Furthermore, he mentions the great heterogeneity of patients with CL/P as a possible source of bias, showing that the incidence of ear disease is lower in patients with CL compared with CLþP and CP. Skolnik (1958), in his study of 401 patients with CL/P, reported that the incidence of ear disease increased from 1 year of age (6%) to 8 years (68%) and then leveled off. Shortly thereafter, two separate studies found a higher incidence of ear disease in children aged 3 to 6 years that decreased into adulthood (Goetzinger et al., 1960; Spriestersbach et al., 1962). In 1969 Paradise and Felder described the universality of OME in 50 children with CL/P. Since then, OME (including complications of it or its treatment) has been considered the leading cause of hearing loss in CL/ P, as reported in numerous publications (Hubbard, 1985; Grant et al., 1988; Hornigold et al., 2008; Flynn et al., 2009; Gani, 2012). There have been several cross-sectional studies showing that hearing outcomes improve with increasing age (Bennett, 1972; Møller, 1975; Gordon et al., 1988; Handzic-Cuk et al., 1996; Koempel and Kumar, 1997);

FIGURE 3 Timing of surgical closure of the palate by type of cleft. Abbreviations: CLP ¼ cleft lip and palate, CP ¼ isolated cleft palate. * Other includes patients who had surgery elsewhere or at a different timing.

Otosclerosis was present in three (13%) patients with CLP and three (11%) patients with CP. In the CP group, four (15%) patients had sensorineural hearing loss and one (4%) had a cholesteatoma; six patients only had the audiograms recorded, without further information. DISCUSSION Our results show PTA scores significantly improving with age in both CLP and CP. There was no significant difference between the two groups and they showed almost identical progress. When looking at BCLP and UCLP, we found no significant difference in PTA outcomes at any age. Furthermore, there was no difference between the right and left ears. Patients who had surgical closure of the palate at age 18 months had a better PTA outcome at age 15 compared with patients who had surgery at 12 months. A poor PTA outcome at 4 years of age was not a negative prognostic

TABLE 5 Pure Tone Average (PTA) Outcomes at Ages 4, 6, and 15 Years by Timing of Surgical Closure of the Palate (at 12, 18, and 24 Months) in 159 Patients With CLP and 158 Patients With CP (Participation Differs Between Age Groups)* Pure Tone Average (PTA) dB HL 4y

6y

15 y

Age at Surgery, mo

n

Mean (95% CI)

n

Mean (95% CI)

n

Mean (95% CI)

12 18 24

23 89 54

18.5 (15.9–21.1) 18.3 (16.2–20.4) 19.8 (17.4–21.1)

27 105 73

16.7 (13.6–19.7) 14.9 (13.4–16.3) 15.4 (13.5–17.32)

29 110 77

13.1 (9.4–16.8) 10.1 (8.9–11.5) 11.4 (9.7–13.0)

* CLP ¼ cleft lip and palate; CP ¼ isolated cleft palate; n ¼ number of patients; CI ¼ confidence interval.

Skuladottir et al., HEARING OUTCOMES IN PATIENTS WITH CLEFT LIP/PALATE

TABLE 7 Characteristics of Otological Status Among Patients With Pure Tone Average (PTA) 20 n (%) Otological Status Patients Ears OME Ear tubes Tympanosclerosis Perforation Otosclerosis Sensorineural hearing loss Cholesteatoma Missing

CLP* 24 30 9 5 4 3 3 0 0 2

(18) (11) (38) (21) (17) (13) (13)

(8)

CP 27 41 7 2 5 5 3 4 1 4

(21) (16) (26) (7) (19) (19) (11) (15) (4) (15)

* CLP ¼ cleft lip and palate; CP ¼ isolated cleft palate; OME ¼ otitis media with effusion.

however, there are few studies that present longitudinal data, and the ones that do are limited by a much smaller sample size than that in our study. A recent study by Flynn et al. (2013) looked at audiological outcomes in 58 patients at ages 7, 10, 13, and 16 years and found an improved PTA outcome with increasing age (however, not in the highfrequency PTA) and a poorer outcome for BCLP than for the other groups in the high-frequency PTA (Flynn et al., 2013). Timmermans et al. (2006) compared otological findings at age 3 years with outcomes at over 10 years of age in 20 patients with CP and found a reduced incidence in OME with age. Smith et al. (1994) studied eustachian tube function in 81 patients longitudinally, after surgical repair of the palate, and found that most patients recovered function at an average of 6 years after surgery. Whether the improvement of hearing levels is due to medical interventions, simply a result of the natural history of OME, or both remains unanswered. Otitis media with effusion is a common condition in children in general. The prevalence is 10% to 30% between the ages of 1 and 3 years, and the cumulative incidence is 80% at the age of 4 years (Tuncbilek et al., 2003). The observation that OME often resolves without intervention and that grommets do not result in long-term benefits has led to a more conservative approach in current ENT guidelines (American Academy of Family Physicians, American Academy of Otolaryngology–Head Neck Surgery, American Academy of Pediatrics Subcommittee on Otitis Media With Effusion, 2004). A recent Cochrane review concluded that the benefits of grommets is small and advocated watchful waiting as a management strategy for OME in otherwise healthy children (Browning et al., 2010). How this applies to children with CL/P, who face additional challenges with speech and language that might be affected by OME, is uncertain (Ponduri et al., 2009). For patients at particular risk of adverse effects by reduced hearing, an alternative to watchful waiting and grommets could be hearing aids (Maheshwar et al., 2002; Gani, 2012).

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Morphology did not have a significant impact in our study. This is in contrast to other studies that have indicated that patients with BCLP have a higher incidence of otological problems (Handzic-Cuk et al., 1996; Flynn et al., 2013). Although our results show a positive progression of the hearing outcomes for most patients, 11% of the patients with CLP and 16% of the patients with CP still have poor outcomes at 15 years of age. The most common cause was OME (38% CLP and 26% CP), but they also present findings that indicate complications due to grommets such as persistent perforations and tympanosclerosis (Sheahan and Blayney, 2003). Flynn et al. (2013) found abnormal outcomes in 19% at age 16 years, which is quite comparable with our results. Viewed in the light of the early studies that reported poor long-term outcomes in about 50% of the patients (Graham, 1963; Yules, 1970; Bluestone et al., 1975), there seems to be a positive trend toward better longterm outcomes. Some of this, however, might be explained by the exclusion of syndromic patients in the more recent studies. Patients who had surgical closure of the palate at 18 months had a significantly better PTA outcome at 15 years compared with the patients who had surgery at 12 months. There were no other significant differences in PTA outcomes by timing of surgery. Given the coarse grouping of surgical timing in the study, these results should be interpreted with caution. Furthermore, we do not have estimates of other outcomes that could be affected by timing of surgery such as speech, fistulae rate, and maxillary growth (Rohrich et al., 1996; Liao et al., 2006; Chapman et al., 2008). Theoretically, the surgical closure of the palate might affect hearing in several ways. First, different surgical techniques might affect the functionality of the soft palate in different ways and hence have an effect on the ventilation of the eustachian tube. There is recent evidence that technique does have an effect on hearing outcomes (Carroll et al., 2013); although, other studies have not found this (Dhillon, 1988; Antonelli et al., 2011). Second, if surgical closure affects the incidence of OME, then the timing would either reduce or increase the exposure to OME and affect the frequency of complications. Rohrich and Byrd (1990) did not find any effect of timing on hearing outcomes or maxillary growth; however, there were better speech outcomes and lower fistulae rates in the patients who had early repair. This finding is supported by another study that did not find any differences in hearing outcomes by age of palatal repair (Robinson et al., 1992). However, Watson et al. (1986) found a higher prevalence of sensorineural hearing loss in patients with late palatal closure compared with early palatal closure. When assessing the optimal timing of palatal closure, several outcomes other than hearing such as speech, fistulae rate, orthognathic outcomes, and maxillary growth need to be considered. Overall, the findings on the effects of palatal closure, in terms of timing or technique, on hearing outcomes are

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Cleft Palate–Craniofacial Journal, March 2015, Vol. 52 No. 2

inconsistent (Watson et al., 1986; Dhillon, 1988; Rohrich, 1990; Robinson et al., 1992; Sheahan and Blayney, 2003). Our study is not without its limitations. First, the study is a retrospective chart review with inherent limitations in data, and we do not have a control group. Second, the study has revealed weaknesses in the documentation of ENT procedures. Although all audiological data were well documented, we lack reliable data on the surgical ENT procedures. Furthermore, we lack audiological recordings at 4000 Hz in the early PTA assessments; recent studies indicate that high frequencies are affected in patients with CL/P (Flynn et al., 2013). Initially the aim was to assess the effect of grommets, but this turned out to be impossible because we lacked information on the procedures performed in other hospitals. Moreover, we do not have complete assessments for all age groups. This is due partly to a lower participation rate in our youngest patients, but we also found that of the 91% of the patients who participated on the 15-year CCD, we only had PTA assessments for 84% of patients with CLP and 81% of the patients with CP. Consequently, this study has led to better methods of documentation. Third, the participation differs between the age groups, with the lowest participation rate at 4 years to the highest at 15 years. This may be because at the 4-year review the patients attend only for an ENT examination, in contrast to the other time points when there is a comprehensive team review. Because most patients also attend local ENT clinics, they might not make the effort to travel long distances for just one examination. Notwithstanding, this is a potential bias because the 4-year-olds who attended might have a higher prevalence of OME and ENT symptoms than those who did not attend. In conclusion, our results show a significant improvement in hearing from childhood to adolescence in patients with cleft palate, treated by the cleft team in Bergen. Patients who had surgical closure of the palate at 18 months of age had better PTA outcomes at 15 years than the patients who had surgery at 12 months of age. Further prospective studies are required in order to assess the impact of ENT treatment and closure of the palate on hearing outcomes in patients with CL/P. Acknowledgments. The study is supported by grant from the Western Norway Regional Health Authority. We would especially like to thank Dr. Jens Christian Eriksson for his good advice. We also would like to thank Dr. Richard Kwok and Dr. Robert McConnaughey for helpful comments.

REFERENCES American Academy of Family Physicians, American Academy of Otolaryngology–Head Neck Surgery, American Academy of Pediatrics, Subcommittee on Otitis Media With Effusion. Otitis media with effusion. Pediatrics. 2004;113:1412–1429. Antonelli PJ, Jorge JC, Feniman MR, Piazentin-Penna SH, DutkaSouza JC, Seagle MB, Williams WN, Nackashi JA, Boggs S, Graciano MI, et al. Otologic and audiologic outcomes with the Furlow and von Langenbeck with intravelar veloplasty palatoplas-

ties in unilateral cleft lip and palate. Cleft Palate Craniofac J. 2011;48:412–418. Bardach J, Morris HL, Olin WH, Gray SD, Jones DL, Kelly KM, Shaw WC, Semb G. Results of multidisciplinary management of bilateral cleft lip and palate at the Iowa Cleft Palate Center. Plast Reconstr Surg. 1992;89:419–432, discussion 433–415. Bennett, M. (1972). Symposium on ear diseases. III. The older cleft palate patient. (A clinical otologic-audiologic study.). Laryngoscope. 82:1217–1225. Bluestone CD, Beery QC, Cantekin EI, Paradise JL. Eustachian tube ventilatory function in relation to cleft palate. Ann Otol Rhinol Laryngol. 1975;84:333–338. Broen PA, Moller KT, Carlstrom J, Doyle SS, Devers M, Keenan KM. Comparison of the hearing histories of children with and without cleft palate. Cleft Palate Craniofac J. 1996;33:127–133. Browning GG, Rovers MM, Williamson I, Lous J, Burton MJ. Grommets (ventilation tubes) for hearing loss associated with otitis media with effusion in children. Cochrane Database Syst Rev. 2010;(10):CD001801. doi:10.1002/14651858.CD001801.pub3. Carroll DJ, Padgitt NR, Liu M, Lander TA, Tibesar RJ, Sidman JD. The effect of cleft palate repair technique on hearing outcomes in children. Int J Pediatr Otorhinolaryngol. 2013;77:1518–1522. Chapman KL, Hardin-Jones MA, Goldstein JA, Halter KA, Havlik RJ, Schulte J. Timing of palatal surgery and speech outcome. Cleft Palate Craniofac J. 2008;45:297–308. Chen JL, Messner AH, Curtin G. Newborn hearing screening in infants with cleft palates. Otol Neurotol. 2008;29:812–815. Dhillon RS. The middle ear in cleft palate children pre and post palatal closure. J Royal Soc Med. 1988;81:710–713. Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12:167–178. Flynn T, Lohmander A, Moller A, Magnusson L. A longitudinal study of hearing and middle ear status in adolescents with cleft lip and palate. Laryngoscope. 2013;123:1374–1380. Flynn T, Moller C, Jonsson R, Lohmander A. The high prevalence of ¨ ¨ otitis media with effusion in children with cleft lip and palate as compared to children without clefts. Int J Pediatr Otorhinolaryngol. 2009;73(10):1441–1446. Fogh-Andersen P. Inheritance of Harelip and Cleft Palate. Copenhagen: Munksgaard; 1942. Forsetlund L, Semb G, Farah MG, Flottorp S. The Scientific Knowledge Base for Treatment of Patients With Cleft Lip, Alveolus and Palate. Oslo: Norwegian Knowledge Centre for the Health Services; 2009. Report No. 29. Gani B. A review of hearing loss in cleft palate patients. Int J Otolaryngol. 2012. Article ID 548698, 6 pages. doi:10.1155/2012/ 548698. Goetzinger CP, Embrey JE, Brooks R, Proud GO. Auditory assessment of cleft palate adults. Acta Otolaryngol. 1960;52:551– 557. Gordon ASD, Jean-Louis F, Morton RP. Late ear sequelae in cleft palate patients. Int J Pediatr Otorhinolaryngol. 1988;15:149–156. Graham MD. A longitudinal study of ear disease and hearing loss in patients with cleft lips and palates. Trans Am Acad Ophthalmol Otolaryngol. 1963;67:213–222. Grant HR, Quiney RE, Mercer DM, Lodge S. Cleft palate and glue ear. Arch Dis Child. 1988;63:176–179. Gutzmann A. Zur Prognose und Behandlung der Angeborenen Gaumdefekte. Berlin: Mscher Sprachheilk; 1893:26–27. Handzic-Cuk J, Cuk V, Risavi R, Katusic D, Stajner-Katusic S. Hearing levels and age in cleft palate patients. Int J Pediatr Otorhinolaryngol. 1996;37:227–242. Hornigold R, Morley A, Glore RJ, Boorman J, Sergeant R. The longterm effect of unilateral t-tube insertion in patients undergoing cleft

Skuladottir et al., HEARING OUTCOMES IN PATIENTS WITH CLEFT LIP/PALATE

palate repair: 20-year follow-up of a randomised controlled trial. Clin Otolaryngol. 2008;33:265–268. Hubbard T. Consequences of unremitting middle-ear disease in early life. N Engl J Med. 1985;312:1529–1534. Koempel J, Kumar A. Long-term otologic status of older cleft palate patients. Indian J Pediatr. 1997;64:793–800. Kuo CL, Lien CF, Chu CH, Shiao AS. Otitis media with effusion in children with cleft lip and palate: a narrative review. Int J Pediatr Otorhinolaryngol. 2013;77:1403–1409. Liao Y-F, Cole TJ, Mars M. Hard palate repair timing and facial growth in unilateral cleft lip and palate: a longitudinal study. Cleft Palate Craniofac J. 2006;43:547–556. Lous J, Burton MJ, Felding JU, Ovesen T, Rovers MM, Williamson I. Grommets (ventilation tubes) for hearing loss associated with otitis media with effusion in children. Cochrane Database Syst Rev. 2005(1):CD001801. doi:10.1002/14651858.CD001801.pub2. Maheshwar AA, Milling MAP, Kumar M, Clayton MI Thomas A. Use of hearing aids in the management of children with cleft palate. Int J Pediatr Otorhinolaryngol. 2002;66:55–62. Mittwoch U. Different gene expressions on the left and the right: a genotype/phenotype mismatch in need of attention. Ann Hum Genet. 2008;72:2–9. Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet. 2009;374:1773–1785. Møller P. Long-term otological features of cleft palate patients. Arch Otolaryngol. 1975;101:605–607. Møller P. Hearing, middle ear pressure and otopathology in a cleft palate population. Acta Otolaryngol. 1981;92:521–528. Niskar A, Kieszak SM, Holmes A, Esteban E, Rubin C, Brody DJ. Prevalence of hearing loss among children 6 to 19 years of age: the third national health and nutrition examination survey. JAMA. 1998;279:1071–1075. Paradise JL, Felder H. The universality of otitis media in 50 infants with cleft palate. Pediatrics. 1969;44(1):35–42. Paradise JL. Middle ear problems associated with cleft palate. An internationally-oriented review. Cleft Palate J. 1975;12:17–22. Paulozzi LJ, Lary JM. Laterality patterns in infants with external birth defects. Teratology. 1999;60:265–271. Ponduri S, Bradley R, Ellis PE, Brookes ST, Sandy JR, Ness AR. The management of otitis media with early routine insertion of grommets in children with cleft palate—a systematic review. Cleft Palate Craniofac J. 2009;46:30–38. Robinson PJ, Lodge S, Jones BM, Walker CC, Grant HR. The effect of palate repair on otitis media with effusion. Plast Reconstr Surg. 1992;89:640–645. Rohrich RJ, Byrd HS. Optimal timing of cleft palate closure. Speech, facial growth, and hearing considerations. Clin Plast Surg. 1990;17:27–36.

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Rohrich RJ, Rowsell AR, Johns DF, Drury MA, Grieg G, Watson DJ, Godfrey AM, Poole MD. Timing of hard palatal closure: a critical long-term analysis. Plast Reconstr Surg. 1996;98:236–246. Sheahan P, Blayney AW. Cleft palate and otitis media with effusion: a review. Rev Laryngol Otol Rhinol (Bord). 2003;124:171–177. Sivertsen A, Wilcox A, Johnson GE, Abyholm F, Vindenes HA, Lie RT. Prevalence of major anatomic variations in oral clefts. Plast Reconstr Surg. 2008;121:587–595. Sivertsen A, Wilcox AJ, Skjaerven R, Vindenes HA, Abyholm F, Harville E, Lie RT. Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives. BMJ. 2008;336:432–434. Skolnik EM. Otologic evaluation in cleft palate patients. Laryngoscope. 1958;68:1908–1949. Smith KS, Ugalde CM. Primary palatoplasty using bipedicle flaps (modified Von Langenbeck technique). Atlas Oral Maxillofac Surg Clin. 2009;17:147–156. Smith TL, DiRuggiero DC, Jones KR. Recovery of eustachian tube function and hearing outcome in patients with cleft palate. Otolaryngol Head Neck Surg. 1994;111:423–429. Spriestersbach DC, Lierle DM, Moll KL, Prather WF. Hearing loss in children with cleft palates. Plast Reconstr Surg Transplant Bull. 1962;30:336–347. Szabo C, Langevin K, Schoem S, Mabry K. Treatment of persistent middle ear effusion in cleft palate patients. Int J Pediatr Otorhinolaryngol 2010;74:874–877. Timmermans K, Vander Poorten V, Desloovere C, Debruyne F. The middle ear of cleft palate patients in their early teens: a literature study and preliminary file study. B-ENT. 2006;4(suppl 2):95–101. Tindlund RS, Holmefjord A, Eriksson JC, Johnson GE, Vindenes H. Interdisciplinary evaluation of consecutive patients with unilateral cleft lip and palate at age 6, 15, and 25 years: a concurrent standardized procedure and documentation by plastic surgeon; speech and language pathologist; ear, nose, and throat specialist; and orthodontist. J Craniofac Surg. 2009;2(suppl 2):1687–1698. Tuncbilek G, Ozgur F, Belgin E. Audiologic and tympanometric findings in children with cleft lip and palate. Cleft Palate Craniofac J. 2003;40:304–309. Viswanathan N, Vidler M, Richard B. Hearing thresholds in newborns with a cleft palate assessed by auditory brain stem response. Cleft Palate Craniofac J. 2008;45:187–192. Watson DJ, Rohrich RJ, Poole MD, Godfrey AM. The effect on the ear of late closure of the cleft hard palate. Br J Plast Surg. 1986;39:190–192. Yang FF, McPherson B. Assessment and management of hearing loss in children with cleft lip and/or palate: a review. Asian J Oral Maxillofac Surg. 2007;19:77–88. Yules RB. Hearing in cleft palate patients. Arch Otolaryngol. 1970;91:319–323.