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Hearing assessment in high-risk congenital diaphragmatic hernia survivors
International Journal of Pediatric Otorhinolaryngology 74 (2010) 1176–1179
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Hearing assessment in high-risk congenital diaphragmatic hernia survivors Carla Morando a,*, Paola Midrio b, PierGiorgio Gamba b, Marco Filippone a, Alberto Sgro` b, Eva Orzan c a
Neonatal Intensive Care Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, Italy Pediatric Surgery Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, Italy c Pediatric Audiology Unit, Otolaryngology and Otosurgery, Hospital of Padova, Via Giustiniani 3, Italy b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 25 June 2010 Accepted 9 July 2010 Available online 4 August 2010
Objective: To report results of audiometric evaluations in high-risk congenital diaphragmatic hernia survivors and their exposure to audiological risk factors (mechanical ventilation, high frequency oscillation, aminoglycoside therapy and neuromuscular blocking agents). Design: All newborns with high-risk congenital diaphragmatic hernia born between January 2003 and June 2009 were treated consecutively at the Neonatal Intensive Care Unit, Pediatric Hospital, University of Padova. Thirty-two survived and 26 of them underwent formal audiological evaluation (tonal and speech audiometry, otoacoustic emission, and immitance measurements) and follow up. Results: Twenty-one children had normal hearing; 4 had conductive hearing loss, which was successfully treated; and 1 had severe sensorineural hearing loss and suffers from Turner syndrome. Conclusions: Our series revealed a lower prevalence of sensorineural hearing loss in high-risk congenital diaphragmatic hernia survivors than in other studies, suggesting that the association between hearing loss and congenital diaphragmatic hernia has yet to be accurately defined and fully elucidated. ß 2010 Elsevier Ireland Ltd. All rights reserved.
Keywords: Hearing loss Congenital diaphragmatic hernia Follow up Audiological risk factors
1. Introduction Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that affects 1 in every 2500–3000 live births [1]. The hallmark of this pathology is a defect in the formation of the muscular or tendinous portion of the diaphragm; this condition allows abdominal viscera to protrude into the thoracic cavity during the fetal life. Fetuses and newborns with CDH have varying degrees of pulmonary parenchymal and vascular hypoplasia. Over the past two decades, antenatal diagnosis rates have improved, the related pathophysiology has been further clarified, and there have been advances in perinatal and perioperative management. Significant long-term sequelae have become apparent, and so has the need for long-term follow-up. Many survivors of CDH may have severe morbidities, e.g. neurocognitive delay, gastroesophageal reflux, hearing loss, chest wall deformity, growth impairment, recurrent hernia and other complications attributable to the associated congenital anomalies beyond the neonatal period [2]. Judging from the literature, sensorineural hearing loss (SNHL) occurs in 25–62% of CDH survivors, but the available studies differ in population, definition of hearing loss and use of extracorporeal membrane oxygenation (ECMO) [3–7]. Many risk factors have been associated with the onset of SNHL, including the duration of
* Corresponding author. Tel.: +39 3482524108; fax: +39 0498211994. E-mail address: [email protected] (C. Morando). 0165-5876/$ – see front matter ß 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2010.07.009
mechanical and high-frequency ventilation, and of loop diuretic therapy, and the use of pancuronium bromide (PB) [3–5], but the specific insult leading to SNHL remains unclear. This study aimed to assess the occurrence of hearing loss (HL) and describe its type (sensorineural and/or conductive) and severity, also assessing the impact of several risk factors on the development of SNHL in a population of children with high-risk CDH born between 2003 and 2009 and treated at the Neonatal Intensive Care Unit (NICU) of the Pediatrics Department in Padova, Italy. 2. Materials and methods High-risk CDH patients are defined as neonates with a prenatal diagnosis and/or symptoms within the first 2 h of life. The protocol for managing CDH requires sedation and ventilatory support (conventional and/or high-frequency ventilation), possibly also using neuromuscular blocking agents, and antibiotic therapy with ampicillin (25 mg/kg/dose) and gentamicin (2.5 mg/kg/dose), and surgical hernia repair once cardiac and respiratory functions have become stable. Survivors of CDH born between January 2003 and June 2009 underwent audiological evaluation at different ages. Those born in 2003 and 2004 were assessed yearly up until they were five years old. From 2005 onwards, a formal audiological follow-up was adopted, according to which all CDH survivors underwent newborn audiological screening using automated transient evoked otoacoustic emissions (A-TEOAE) and auditory brainstem response
C. Morando et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1176–1179
1177
Table 1 Population characteristics and exposure to audiological risk factors. Population Patient-related factors Males (%) Prenatal diagnosis (%) Gestational age (weeks) Birth weight (g) Side of hernia (right %) Sepsis or suspected sepsis (%) Age at audiological follow-up (years)
61 54 37.2 2.5 2857 680 22 42 2 (1–4.5)
Treatment-related factors Use of patch repair (%) Cumulative days on mechanical ventilation (days) Cumulative days of high-frequency ventilation (days) Inhaled nitric oxide (%) Cumulative days on gentamicin treatment (days) Use of neuromuscular blocking agents (%) Cumulative days on neuromuscular blocking agents (days)
31 5.5 (5–9) 2 (1–4) 11 5 (4–8) 81 1 (1–5)
Data are expressed as prevalence, mean SD, or median (interquartile range).
(A-ABR), followed by audiological evaluation twice a year. This audiological assessment included pure-tone threshold evaluation by testing air conduction (250–8000 Hz) and bone conduction (250–4000 Hz). Outer hair cell function was tested using distortion product otoacoustic emissions. Middle ear function was assessed by tympanometry and from the acoustic reflex thresholds. All tests were conducted and analyzed by audiologists with experience in pediatrics in an environment that assured reliable measurements. SNHL was defined as a unilateral or bilateral hearing threshold tested by air and bone conduction higher than 20 dB for at least two of the frequencies tested (from 250 to 4000 Hz) [8]. Sensorineural hearing loss was classified as follows: absent (average tone loss 0–20 dBHL), mild (average tone loss 21– 40 dBHL), moderate (1st degree: average tone loss 41–55 dBHL, 2nd degree: average tone loss 56–70), severe (1st degree: average tone loss 71–80 dBHL, 2nd degree: average tone loss 81–90 dBHL), very severe (1st degree: average tone loss 91–100 dBHL, 2nd degree: average tone loss 101–110, 3rd degree: average tone loss 111–119) and total hearing loss (average tone loss >120 dBHL) [8]. Conductive HL was diagnosed in children with normal bone conduction thresholds (<20 dB) and an air-bone gap 15 dB averaged over 0.5, 1 and 2 kHz. Potential audiological risk factors were extracted retrospectively from patients’ medical records (Table 1). This study was approved by the Padova University Hospital ethics committee and parents provided written consent.
Fig. 1. audiogram of the girl affected by sensorineural hearing loss.
One child had SNHL. While at the NICU, karyotype analysis revealed a monosomy 45,X0. Immediately after birth she presented pulmonary hypertension, she was sedated and pharmacologically paralyzed with pancuronium bromide, treated with high-frequency ventilation (HFOV) and inhaled nitric oxide. The intervention, performed when cardio-respiratory stabilization was reached, required positioning of patch to close the diaphragmatic defect. The post-operative course was complicated by pulmonary hemorrhage requiring again, ventilatory support with HFOV, inotropic agents, blood transfusions and a new course of antibiotic therapy with Vancomycin and Ceftazidime. As for all CDH patients, she followed a regular surgical follow up, during which, the recurrence of CDH was detected and the patient underwent a second surgical correction at three months of age. The girl had been screened at birth with A-TEOAE, which had suggested a normal cochlear function. The audiological evaluation at 4 years identified a bilateral, symmetrical, high-frequency, deeply sloping profound sensorineural hearing loss (Fig. 1). She
3. Results During the period considered, 55 children were born with highrisk CDH, 32 survived and 26 of them (81%) underwent a formal audiological evaluation. Fourteen patients had been diagnosed with CDH antenatally by ultrasound and 3 of them underwent fetal tracheal occlusion. The other 12 developed acute, severe respiratory distress within the first 2 h of life. Nineteen patients were at term, while 7 were born between 31 and 37 weeks of gestation. The birth weight was above 1500 g in all cases. Subjects did not have serious life-threatening chromosomal abnormalities, intracranial hemorrhage of grade II or greater, evidence of hypoxic-ischemic encephalopathy or severe congenital heart disease (e.g. tetralogy of Fallot). Twenty-two of the 26 children assessed underwent newborn hearing screening, 18 were tested with A-TEOAE and A-ABR while 4 were screened only with A-TEOAE. Twenty-one children had a normal hearing function. Four patients had a conductive hearing loss with an associated otitis media with effusion, which was treated successfully, and audiological assessment a few months later was within normal limits.
Fig. 2. results of audiomeric evaluation: youngest children have been submitted to the audiological screening and have made another test at six months, the other patients have been evaluated at different ages. Columns represent Pure Tone Average (0.5, 1 and 2 kHz) thresholds (dB HL) of the right and left ears.
C. Morando et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1176–1179
1178
Table 2 Comparison among different studies describing prevalence of sensorineural hearing loss in CDH survivors. PB: pancuronium bromide, VB: vecuronium bromide. Author
Population tested
SNHL definition
SNHL prevalence
Identified risk factors
Robertson, 1998 Cheung, 1999 Masumoto, 2007 Morini, 2008 Javidnia, 2009 Morando, 2010
37 37 16 82 17 26
>40 dB HL at any of the frequencies >40 dB HL at any of the frequencies >30 dB at any of the frequencies >20 dB at any of the frequencies Not defined >20 dB for at least 2 of the frequencies
22 27 4 40 6 1
Use of PB versus VB Length of ventilation, loop diuretics, use of PB versus VB Age at follow up Duration of intubation, lenght of hospital stay
began wearing hearing aids and attending auditory and speech rehabilitation. She is currently being assessed to receive a cochlear implant. Fig. 2 outlines the hearing test results for all the population studied. This study presents audiological outcome of high risk CDH survivors, nevertheless the follow-up was proposed to all CDH survivors. Among no high risk survivors, 9 out of 11 (81%) of patients have been tested. Four children were affected by diaphragmatic eventration and 5 children had CDH and presented respiratory symptoms beyond the first 2 h of life: one presented conductive hearing loss due to otitis media with effusion which has been treated and resolved, none of them has SNHL. 4. Discussion In our series, the prevalence of SNHL in high-risk CDH survivors was 3.8%, a figure comparable with the prevalence of SNHL in the population of newborns requiring intensive care [9]. This low prevalence of HL makes it impossible to discuss the role of audiological risk factors. The one child who developed SNHL had a normal cochlear function at birth, while her hearing impairment was diagnosed at the age of 4. She was negative on genetic testing for Connexin 26 and 30, and mitochondrial mutations, but karyotype analysis revealed that she has Turner syndrome. A recent study on 200 females with Turner syndrome ranging in age from 7 to 61 years found a 34% prevalence of SNHL [10]. Several studies have been published on SNHL in CDH survivors. Masumoto et al. [3] investigated NICU risk factors (use of loop diuretics and aminoglycosides, neuromuscular blocking agents, HFOV, ECMO, inhaled nitric oxide, duration of highly-concentrated oxygen inhalation, severe hypocapnia and severe hypoxia, severe acidosis and alkalosis, duration of mechanical ventilation) and their relationship with SNHL in a population of 16 survivors with severe CDH, all diagnosed antenatally, with a mortality rate of 34%. Four patients (25%) had a SNHL defined as a minimal response level higher than 30 dB for any of the octave frequencies from 500 to 4000 Hz. The prolonged use of PB and the duration of treatment with loop diuretics, mechanical ventilation and high-frequency oscillation have been suggested as possible risk factors for lateonset SNHL. Another paper [4] analyzed the same risk factors and found a robust association between SNHL among CDH survivors and the prolonged administration of PB during the neonatal period. On 38 CDH survivors, 36 audiologic information at 2 years or older was obtained from 37, SNHL was defined as a hearing level at 40 dB or higher in any of the octave frequencies from 250 to 4000 Hz and it was diagnosed in 23 patients (62%). Morini et al. [5] evaluated 82 of a series of 87 high-risk CDH survivors (mortality rate 29%). SNHL (a hearing level higher than 20 dB for at least one frequency tested) was detected in 40 (49%) patients. At logistic regression analysis, an evaluation of the NICUrelated risk factors only found age at audiological follow-up independently associated with the onset of SNHL. Another study [6] demonstrated that the length of intubation and the length of NICU stay are clear risk factors for the
(60%) (62%) (25%) (49%) (35%) (4%)
development of hearing loss. In this population of 17 CDH survivors SNHL was found in 6 (35%) cases: 1 was congenital while the others were diagnosed between 11 and 18 months of age. In a large CDH population, high prevalence of SNHL (60%) has been reported by Robertson et al. [7]: no difference has been demonstrated between those who require neonatal ECMO and those conventionally treated, most of them (77%) had normal responses to sound as newborns or in infancy. Table 2 compares the results of different studies. In the present study, the accurate audiological evaluation of a sample of high-risk CDH survivors identified a lower prevalence of SNHL than in other studies. The difference cannot be attributed entirely to a dissimilar surveillance rate. The population analyzed had not been treated with ECMO. Most of the patients (60%) had been treated with vecuronium bromide, so we can contribute nothing on the potential role of PB in the onset of HL claimed in other studies. During the period of intensive care before the extubation, the duration of both mechanical ventilation and HFOV usage was shorter than the one stated by other studies [3,4]. Our sample underwent audiological evaluation at different ages; the older children were tested up to five years of age, while the younger patients are still being followed up. Although a longer-term follow-up is warranted, CDH does not seem to add to the risk of SNHL due to NICU-related audiological risk factors (apart from ECMO treatment and the use of PB). Prospective, randomized studies on larger groups of patients would be needed to elucidate our hypothesis and provide more conclusive evidence. Conflict of interest statement None of the authors have any conflict of interest relevant to the content of this study. Acknowledgements There is no financial support to disclose. The authors are grateful to Maria De Benedittis, Rita Turato, Professor Lino Chiandetti and Professor Gregorio Babighian for their help in this study. References [1] J. Colvin, C. Bower, J.E. Dickinson, J. Sokol, Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia, Pediatrics 116 (2005) e356–e363. [2] Section on surgery and the committee on fetus and newborn postdischarge follow-up of infants with congenital diaphragmatic hernia, Pediatrics 121 (2008) 627–632. [3] K. Masumoto, K. Nagata, T. Uesugi, T. Yamada, T. Taguchi, Risk factors for sensorineural hearing loss in survivors with severe congenital diaphragmatic hernia, Eur. J. Ped. 166 (2007) 612–697. [4] P.Y. Cheung, J.M. Tyebkhan, A. Peliowski, W. Ainsworth, C.M.T. Robertson, Prolonged use of pancuronium bromide and sensorineural hearing loss in childhood survivors of congenital diaphragmatic hernia, J. Pediatr. 135 (1999) 233–239. [5] F. Morini, I. Capolupo, R. Masi, M.P. Ronchetti, M. Locatelli, C. Corchia, et al., Hearing impairment in congenital diaphragmatic hernia: the inaudible and noiseless foot of time, J. Pediatr. Surg. 43 (2008) 380–384. [6] H. Javidnia, J.P. Vaccani, Progressive sensorineural hearing loss in children with congenital diaphragmatic hernias, J. Otolaryngol. Head Neck Surg. 38 (2009) 29–31.
C. Morando et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1176–1179 [7] C.M.T. Robertson, P.Y. Cheung, M.M. Halushak, C.A. Elliott, N.J. Leonard, the Western Canadian ECMO Follow-up Group, High prevalence of sensorineural hearing loss among survivors of neonatal congenital diaphragmatic hernia, Am. J. Otol. 19 (1998) 730–736. [8] Bureau International d’AudioPhonologie Recommendation n 02/1 bis Audiometric classification of hearing impairments. http://www.biap.org/biapanglais/ rec021eng.htm.
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[9] E.T. Hille, H.I. van Straaten, P.H. Verkerk, The Dutch NICU neonatal hearing screening working group, Prevalence and independent risk factors for hearing loss in NICU infants, Acta Paediatr. 96 (2007) 1155–1158. [10] K.A. King, T. Makishima, C.K. Zalewski, V.K. Bakalov, A.J. Griffith, C.A. Bondy, et al., Analysis of auditory phenotype and karyotype in 200 females with Turner syndrome, Ear Hear 28 (2007) 831–841.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Hearing assessment in high-risk congenital diaphragmatic hernia survivors Carla Morando a,*, Paola Midrio b, PierGiorgio Gamba b, Marco Filippone a, Alberto Sgro` b, Eva Orzan c a
Neonatal Intensive Care Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, Italy Pediatric Surgery Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, Italy c Pediatric Audiology Unit, Otolaryngology and Otosurgery, Hospital of Padova, Via Giustiniani 3, Italy b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 25 June 2010 Accepted 9 July 2010 Available online 4 August 2010
Objective: To report results of audiometric evaluations in high-risk congenital diaphragmatic hernia survivors and their exposure to audiological risk factors (mechanical ventilation, high frequency oscillation, aminoglycoside therapy and neuromuscular blocking agents). Design: All newborns with high-risk congenital diaphragmatic hernia born between January 2003 and June 2009 were treated consecutively at the Neonatal Intensive Care Unit, Pediatric Hospital, University of Padova. Thirty-two survived and 26 of them underwent formal audiological evaluation (tonal and speech audiometry, otoacoustic emission, and immitance measurements) and follow up. Results: Twenty-one children had normal hearing; 4 had conductive hearing loss, which was successfully treated; and 1 had severe sensorineural hearing loss and suffers from Turner syndrome. Conclusions: Our series revealed a lower prevalence of sensorineural hearing loss in high-risk congenital diaphragmatic hernia survivors than in other studies, suggesting that the association between hearing loss and congenital diaphragmatic hernia has yet to be accurately defined and fully elucidated. ß 2010 Elsevier Ireland Ltd. All rights reserved.
Keywords: Hearing loss Congenital diaphragmatic hernia Follow up Audiological risk factors
1. Introduction Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that affects 1 in every 2500–3000 live births [1]. The hallmark of this pathology is a defect in the formation of the muscular or tendinous portion of the diaphragm; this condition allows abdominal viscera to protrude into the thoracic cavity during the fetal life. Fetuses and newborns with CDH have varying degrees of pulmonary parenchymal and vascular hypoplasia. Over the past two decades, antenatal diagnosis rates have improved, the related pathophysiology has been further clarified, and there have been advances in perinatal and perioperative management. Significant long-term sequelae have become apparent, and so has the need for long-term follow-up. Many survivors of CDH may have severe morbidities, e.g. neurocognitive delay, gastroesophageal reflux, hearing loss, chest wall deformity, growth impairment, recurrent hernia and other complications attributable to the associated congenital anomalies beyond the neonatal period [2]. Judging from the literature, sensorineural hearing loss (SNHL) occurs in 25–62% of CDH survivors, but the available studies differ in population, definition of hearing loss and use of extracorporeal membrane oxygenation (ECMO) [3–7]. Many risk factors have been associated with the onset of SNHL, including the duration of
* Corresponding author. Tel.: +39 3482524108; fax: +39 0498211994. E-mail address: [email protected] (C. Morando). 0165-5876/$ – see front matter ß 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2010.07.009
mechanical and high-frequency ventilation, and of loop diuretic therapy, and the use of pancuronium bromide (PB) [3–5], but the specific insult leading to SNHL remains unclear. This study aimed to assess the occurrence of hearing loss (HL) and describe its type (sensorineural and/or conductive) and severity, also assessing the impact of several risk factors on the development of SNHL in a population of children with high-risk CDH born between 2003 and 2009 and treated at the Neonatal Intensive Care Unit (NICU) of the Pediatrics Department in Padova, Italy. 2. Materials and methods High-risk CDH patients are defined as neonates with a prenatal diagnosis and/or symptoms within the first 2 h of life. The protocol for managing CDH requires sedation and ventilatory support (conventional and/or high-frequency ventilation), possibly also using neuromuscular blocking agents, and antibiotic therapy with ampicillin (25 mg/kg/dose) and gentamicin (2.5 mg/kg/dose), and surgical hernia repair once cardiac and respiratory functions have become stable. Survivors of CDH born between January 2003 and June 2009 underwent audiological evaluation at different ages. Those born in 2003 and 2004 were assessed yearly up until they were five years old. From 2005 onwards, a formal audiological follow-up was adopted, according to which all CDH survivors underwent newborn audiological screening using automated transient evoked otoacoustic emissions (A-TEOAE) and auditory brainstem response
C. Morando et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1176–1179
1177
Table 1 Population characteristics and exposure to audiological risk factors. Population Patient-related factors Males (%) Prenatal diagnosis (%) Gestational age (weeks) Birth weight (g) Side of hernia (right %) Sepsis or suspected sepsis (%) Age at audiological follow-up (years)
61 54 37.2 2.5 2857 680 22 42 2 (1–4.5)
Treatment-related factors Use of patch repair (%) Cumulative days on mechanical ventilation (days) Cumulative days of high-frequency ventilation (days) Inhaled nitric oxide (%) Cumulative days on gentamicin treatment (days) Use of neuromuscular blocking agents (%) Cumulative days on neuromuscular blocking agents (days)
31 5.5 (5–9) 2 (1–4) 11 5 (4–8) 81 1 (1–5)
Data are expressed as prevalence, mean SD, or median (interquartile range).
(A-ABR), followed by audiological evaluation twice a year. This audiological assessment included pure-tone threshold evaluation by testing air conduction (250–8000 Hz) and bone conduction (250–4000 Hz). Outer hair cell function was tested using distortion product otoacoustic emissions. Middle ear function was assessed by tympanometry and from the acoustic reflex thresholds. All tests were conducted and analyzed by audiologists with experience in pediatrics in an environment that assured reliable measurements. SNHL was defined as a unilateral or bilateral hearing threshold tested by air and bone conduction higher than 20 dB for at least two of the frequencies tested (from 250 to 4000 Hz) [8]. Sensorineural hearing loss was classified as follows: absent (average tone loss 0–20 dBHL), mild (average tone loss 21– 40 dBHL), moderate (1st degree: average tone loss 41–55 dBHL, 2nd degree: average tone loss 56–70), severe (1st degree: average tone loss 71–80 dBHL, 2nd degree: average tone loss 81–90 dBHL), very severe (1st degree: average tone loss 91–100 dBHL, 2nd degree: average tone loss 101–110, 3rd degree: average tone loss 111–119) and total hearing loss (average tone loss >120 dBHL) [8]. Conductive HL was diagnosed in children with normal bone conduction thresholds (<20 dB) and an air-bone gap 15 dB averaged over 0.5, 1 and 2 kHz. Potential audiological risk factors were extracted retrospectively from patients’ medical records (Table 1). This study was approved by the Padova University Hospital ethics committee and parents provided written consent.
Fig. 1. audiogram of the girl affected by sensorineural hearing loss.
One child had SNHL. While at the NICU, karyotype analysis revealed a monosomy 45,X0. Immediately after birth she presented pulmonary hypertension, she was sedated and pharmacologically paralyzed with pancuronium bromide, treated with high-frequency ventilation (HFOV) and inhaled nitric oxide. The intervention, performed when cardio-respiratory stabilization was reached, required positioning of patch to close the diaphragmatic defect. The post-operative course was complicated by pulmonary hemorrhage requiring again, ventilatory support with HFOV, inotropic agents, blood transfusions and a new course of antibiotic therapy with Vancomycin and Ceftazidime. As for all CDH patients, she followed a regular surgical follow up, during which, the recurrence of CDH was detected and the patient underwent a second surgical correction at three months of age. The girl had been screened at birth with A-TEOAE, which had suggested a normal cochlear function. The audiological evaluation at 4 years identified a bilateral, symmetrical, high-frequency, deeply sloping profound sensorineural hearing loss (Fig. 1). She
3. Results During the period considered, 55 children were born with highrisk CDH, 32 survived and 26 of them (81%) underwent a formal audiological evaluation. Fourteen patients had been diagnosed with CDH antenatally by ultrasound and 3 of them underwent fetal tracheal occlusion. The other 12 developed acute, severe respiratory distress within the first 2 h of life. Nineteen patients were at term, while 7 were born between 31 and 37 weeks of gestation. The birth weight was above 1500 g in all cases. Subjects did not have serious life-threatening chromosomal abnormalities, intracranial hemorrhage of grade II or greater, evidence of hypoxic-ischemic encephalopathy or severe congenital heart disease (e.g. tetralogy of Fallot). Twenty-two of the 26 children assessed underwent newborn hearing screening, 18 were tested with A-TEOAE and A-ABR while 4 were screened only with A-TEOAE. Twenty-one children had a normal hearing function. Four patients had a conductive hearing loss with an associated otitis media with effusion, which was treated successfully, and audiological assessment a few months later was within normal limits.
Fig. 2. results of audiomeric evaluation: youngest children have been submitted to the audiological screening and have made another test at six months, the other patients have been evaluated at different ages. Columns represent Pure Tone Average (0.5, 1 and 2 kHz) thresholds (dB HL) of the right and left ears.
C. Morando et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1176–1179
1178
Table 2 Comparison among different studies describing prevalence of sensorineural hearing loss in CDH survivors. PB: pancuronium bromide, VB: vecuronium bromide. Author
Population tested
SNHL definition
SNHL prevalence
Identified risk factors
Robertson, 1998 Cheung, 1999 Masumoto, 2007 Morini, 2008 Javidnia, 2009 Morando, 2010
37 37 16 82 17 26
>40 dB HL at any of the frequencies >40 dB HL at any of the frequencies >30 dB at any of the frequencies >20 dB at any of the frequencies Not defined >20 dB for at least 2 of the frequencies
22 27 4 40 6 1
Use of PB versus VB Length of ventilation, loop diuretics, use of PB versus VB Age at follow up Duration of intubation, lenght of hospital stay
began wearing hearing aids and attending auditory and speech rehabilitation. She is currently being assessed to receive a cochlear implant. Fig. 2 outlines the hearing test results for all the population studied. This study presents audiological outcome of high risk CDH survivors, nevertheless the follow-up was proposed to all CDH survivors. Among no high risk survivors, 9 out of 11 (81%) of patients have been tested. Four children were affected by diaphragmatic eventration and 5 children had CDH and presented respiratory symptoms beyond the first 2 h of life: one presented conductive hearing loss due to otitis media with effusion which has been treated and resolved, none of them has SNHL. 4. Discussion In our series, the prevalence of SNHL in high-risk CDH survivors was 3.8%, a figure comparable with the prevalence of SNHL in the population of newborns requiring intensive care [9]. This low prevalence of HL makes it impossible to discuss the role of audiological risk factors. The one child who developed SNHL had a normal cochlear function at birth, while her hearing impairment was diagnosed at the age of 4. She was negative on genetic testing for Connexin 26 and 30, and mitochondrial mutations, but karyotype analysis revealed that she has Turner syndrome. A recent study on 200 females with Turner syndrome ranging in age from 7 to 61 years found a 34% prevalence of SNHL [10]. Several studies have been published on SNHL in CDH survivors. Masumoto et al. [3] investigated NICU risk factors (use of loop diuretics and aminoglycosides, neuromuscular blocking agents, HFOV, ECMO, inhaled nitric oxide, duration of highly-concentrated oxygen inhalation, severe hypocapnia and severe hypoxia, severe acidosis and alkalosis, duration of mechanical ventilation) and their relationship with SNHL in a population of 16 survivors with severe CDH, all diagnosed antenatally, with a mortality rate of 34%. Four patients (25%) had a SNHL defined as a minimal response level higher than 30 dB for any of the octave frequencies from 500 to 4000 Hz. The prolonged use of PB and the duration of treatment with loop diuretics, mechanical ventilation and high-frequency oscillation have been suggested as possible risk factors for lateonset SNHL. Another paper [4] analyzed the same risk factors and found a robust association between SNHL among CDH survivors and the prolonged administration of PB during the neonatal period. On 38 CDH survivors, 36 audiologic information at 2 years or older was obtained from 37, SNHL was defined as a hearing level at 40 dB or higher in any of the octave frequencies from 250 to 4000 Hz and it was diagnosed in 23 patients (62%). Morini et al. [5] evaluated 82 of a series of 87 high-risk CDH survivors (mortality rate 29%). SNHL (a hearing level higher than 20 dB for at least one frequency tested) was detected in 40 (49%) patients. At logistic regression analysis, an evaluation of the NICUrelated risk factors only found age at audiological follow-up independently associated with the onset of SNHL. Another study [6] demonstrated that the length of intubation and the length of NICU stay are clear risk factors for the
(60%) (62%) (25%) (49%) (35%) (4%)
development of hearing loss. In this population of 17 CDH survivors SNHL was found in 6 (35%) cases: 1 was congenital while the others were diagnosed between 11 and 18 months of age. In a large CDH population, high prevalence of SNHL (60%) has been reported by Robertson et al. [7]: no difference has been demonstrated between those who require neonatal ECMO and those conventionally treated, most of them (77%) had normal responses to sound as newborns or in infancy. Table 2 compares the results of different studies. In the present study, the accurate audiological evaluation of a sample of high-risk CDH survivors identified a lower prevalence of SNHL than in other studies. The difference cannot be attributed entirely to a dissimilar surveillance rate. The population analyzed had not been treated with ECMO. Most of the patients (60%) had been treated with vecuronium bromide, so we can contribute nothing on the potential role of PB in the onset of HL claimed in other studies. During the period of intensive care before the extubation, the duration of both mechanical ventilation and HFOV usage was shorter than the one stated by other studies [3,4]. Our sample underwent audiological evaluation at different ages; the older children were tested up to five years of age, while the younger patients are still being followed up. Although a longer-term follow-up is warranted, CDH does not seem to add to the risk of SNHL due to NICU-related audiological risk factors (apart from ECMO treatment and the use of PB). Prospective, randomized studies on larger groups of patients would be needed to elucidate our hypothesis and provide more conclusive evidence. Conflict of interest statement None of the authors have any conflict of interest relevant to the content of this study. Acknowledgements There is no financial support to disclose. The authors are grateful to Maria De Benedittis, Rita Turato, Professor Lino Chiandetti and Professor Gregorio Babighian for their help in this study. References [1] J. Colvin, C. Bower, J.E. Dickinson, J. Sokol, Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia, Pediatrics 116 (2005) e356–e363. [2] Section on surgery and the committee on fetus and newborn postdischarge follow-up of infants with congenital diaphragmatic hernia, Pediatrics 121 (2008) 627–632. [3] K. Masumoto, K. Nagata, T. Uesugi, T. Yamada, T. Taguchi, Risk factors for sensorineural hearing loss in survivors with severe congenital diaphragmatic hernia, Eur. J. Ped. 166 (2007) 612–697. [4] P.Y. Cheung, J.M. Tyebkhan, A. Peliowski, W. Ainsworth, C.M.T. Robertson, Prolonged use of pancuronium bromide and sensorineural hearing loss in childhood survivors of congenital diaphragmatic hernia, J. Pediatr. 135 (1999) 233–239. [5] F. Morini, I. Capolupo, R. Masi, M.P. Ronchetti, M. Locatelli, C. Corchia, et al., Hearing impairment in congenital diaphragmatic hernia: the inaudible and noiseless foot of time, J. Pediatr. Surg. 43 (2008) 380–384. [6] H. Javidnia, J.P. Vaccani, Progressive sensorineural hearing loss in children with congenital diaphragmatic hernias, J. Otolaryngol. Head Neck Surg. 38 (2009) 29–31.
C. Morando et al. / International Journal of Pediatric Otorhinolaryngology 74 (2010) 1176–1179 [7] C.M.T. Robertson, P.Y. Cheung, M.M. Halushak, C.A. Elliott, N.J. Leonard, the Western Canadian ECMO Follow-up Group, High prevalence of sensorineural hearing loss among survivors of neonatal congenital diaphragmatic hernia, Am. J. Otol. 19 (1998) 730–736. [8] Bureau International d’AudioPhonologie Recommendation n 02/1 bis Audiometric classification of hearing impairments. http://www.biap.org/biapanglais/ rec021eng.htm.
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[9] E.T. Hille, H.I. van Straaten, P.H. Verkerk, The Dutch NICU neonatal hearing screening working group, Prevalence and independent risk factors for hearing loss in NICU infants, Acta Paediatr. 96 (2007) 1155–1158. [10] K.A. King, T. Makishima, C.K. Zalewski, V.K. Bakalov, A.J. Griffith, C.A. Bondy, et al., Analysis of auditory phenotype and karyotype in 200 females with Turner syndrome, Ear Hear 28 (2007) 831–841.