Otitis media met effusie (OME) en acute otitis media (OMA) komen bij kinderen veel voor. Met name recidiverende OMA (rOMA), gedefinieerd als drie of meer episodes in zes maanden, of vier of meer episodes in één jaar, kan tijdelijk grote gevolgen hebben voor het dagelijks leven van kinderen en hun ouders. Deze groep kinderen ervaart een grote ziektelast door frequente perioden van oorpijn, algemene ziekte, slapeloze nachten en verloren tijd op de crèche of school (Venekamp et al., 2018). Hun ouders kunnen zich gestrest voelen, omdat hun kind veel huilt, uit zijn doen is en ouders niet goed weten hoe ze hun kind het beste kunnen steunen. Het gezin kan hieronder lijden. Persisterende OME (pOME) kan zorgen voor tijdelijk verminderd gehoor wat weer invloed kan hebben op de spraak-taalontwikkeling en het gedrag.

Er heerst grote praktijkvariatie rondom de richtlijn otitis media. De huidige richtlijnen geven geen handvatten om de negatieve invloed van het gehoorverlies op het functioneren en de taal- en spraakontwikkeling vast te stellen. Uit het onderzoek naar praktijkervaringen blijkt dat de deelnemende KNO-artsen een eigen inschatting maken van de eventuele achterstand in de taal- en spraakontwikkeling van het kind (Equalis. Ervaringen ouders, huisartsen en KNO-artsen met het zorgtraject middenoorontsteking. Utrecht, Equalis 2020). De variatie in inschatting van de taal- en spraakontwikkeling en het functioneren zou kunnen betekenen dat het indicatiecriterium ‘negatieve invloed van het gehoorverlies op het functioneren of de ontwikkeling’ in de praktijk divers wordt gehanteerd.

Daarnaast is het onduidelijk wat de effecten zijn van otitis media op de auditieve ontwikkeling en taal- en spraakontwikkeling op latere leeftijd. Omdat deze effecten van otitis media een belangrijke indicatie vormen voor het plaatsen van buisjes bij otitis media, is een aanbeveling hierover zeer gewenst. Ook is het onbekend wat de gevolgen van rOMA en pOME zijn voor de kwaliteit van leven van kind en ouders en wat de effecten van rOMA en pOME zijn  op het gedrag en de emotionele ontwikkeling van het kind.

Language and speech development

Hearing loss

Reading and Writing skills

Behavior

Quality of Life

Description of studies

Observational studies

Bell (2021) studied the association between secondary care episodes of otitis media (OM) and literacy and numeracy skills in a retrospective cohort. Children born in Western Australia during July 2003 to June 2004, who subsequently participated in the grade 3 annual national assessment of children’s academic performance (NAPLAN test) in 2012, were included in the cohort (seven – nine years during study period). Exclusion criteria were missing all NAPLAN scores, multiple births, or diagnosed with intellectual disability. The final cohort included 19,262 children. Within this cohort, data on secondary care episodes of OM were assessed by analyzing hospital records. In this study, secondary care episodes were defined as admissions to hospital or presentation to an emergency department. In total 2,666 (13.8%) children were diagnosed with at least one OM episode (before the age of nine) or had symptoms indicative of OM. These diagnoses included acute OM, OM with effusion, conductive hearing loss, chronically discharging perforations, cholesteatoma, and mastoiditis. Children without secondary care episode of OM were classified as ‘no OM’. Data on secondary care episodes of OM were compared to scores on the NAPLAN test for reading, writing and numeracy. A multivariate regression model was used to calculate the associations between OM episodes and NAPLAN scores, adjusted for multiple confounders. These variables were selected a priori on evidence and obtained from registration data and equally distributed among the groups. The variable “day care attendance” was not considered as a confounder in the multivariable analysis. Since this is thought to be a relevant confounder this might introduce bias.

Fougner (2017) used data from a prospective birth cohort (Danish National Birth Cohort) to determine whether there is an association between (number of) OM episodes in childhood and self-rated school performance. The study sample consisted of 35,946 children. Children born with congenital malformations, genetic disorders, or anatomical abnormalities were excluded. Exposure was assessed with interviews at six and eighteen months of the child by asking mothers if, and how many times, their child suffered from middle ear infection. This data was categorized in “no episodes of OM” (n = 21,941) “1-3 episodes of OM” (n = 11,034) “4-6 episodes of OM” (n = 1,989) or “7 or more episodes of OM” (n = 982). The type of OM was not further specified. At eleven years of age, outcomes were assessed by asking children three questions regarding their school performance. One of these questions focused on Danish literacy skills. Only participants who had data on OM episodes and school performance were included in the sample. Ten potential confounders were identified based on literature. The association between OM and self-rated literacy skills were assessed with proportional odds regression adjusted for these confounders. Since OM-status was determined via parent-recall and literacy skills were evaluated by the children themselves, there might be recall bias regarding the exposure and outcome assessment.

Gouma (2011) performed a case-control study to investigate the behavioral trends of children with otitis media with effusion (OME). In total, 183 children, aged six to eight were included in the study. Children with a positive hospital record of recurrent acute OME or OME at the age of four or five were selected as cases (n = 117). Children without history of OME or complaints of hearing loss were selected as controls (n = 66) and recruited via the orthopedics department where they were hospitalized for minor injuries. Matching of cases and controls did not take place. Exclusion criteria were episodes of OME in the past 6 weeks, sensorineural hearing loss, ear malformations, or presence of psychiatric diseases in either child or parent. Outcomes included hearing ability and behavioral trend, assessed with the Child Behavior Checklist (CBCL). The CBCL questionnaire was given under controlled with cooperation of a child psychiatrist to ensure the correct application and evaluation of the CBCL questionnaire. In the article it was not indicated how the CBCL scores should be interpreted. The lack of matching between cases and controls could introduce some bias.

Grindler (2014) performed a prospective cross-sectional study to quantitate the average burden of OM. In total, data from 1,208 patients was analyzed. Children aged six – twenty-four months, with chief complaints of recurrent or chronic OM, who presented at the participating pediatric otolaryngology sites were selected as cases. Controls without recurrent or chronic OM were selected from family practice or pediatric sites. There were no other inclusion and exclusion criteria. Matching of cases and controls did not take place. On average, children selected as cases experienced 1.14 ± 0.99 episode of OM in a 1-month period and 2.67 ± 1.79 episodes of OM in a 3-month time period (physician evaluated). The controls experienced respectively 0.24 ± 0.51 episodes and 0.44 ± 0.94 episodes respectively. Outcome of the study was quality of life (QoL), measured with the Otitis Media-6 (OM-6) survey and the PedsQL Infant Impact Module (PedsQL). The lack of matching between cases and controls could introduce some bias.

Herzog (2020) used data from a prospective birth cohort (Danish National Birth Cohort) to investigate whether OM in early childhood is associated with long-term consequences of psychosocial development and if ventilation tubes insertion (VTI) prevents the possible negative consequences of OM. The study sample consisted of 52,877 children. Children born with congenital malformation, genetic disorders, or anatomical abnormalities were excluded. Exposure was OM-episodes and VTI. The children were categorized according to their OM status: “no episodes of OM” (n = 20818, 29.4%), “1-3 OM episodes without VTI” (n = 15460, 29.2%), “1-3 OM episodes with VTI” (n = 3979, 7.5%), “4+ OM episodes without VTI” (n = 3773, 7.1%), “4+ OM episodes with VTI” (n = 8847, 16.7%). Exposure status was parent-reported and assessed at 7-years of age. Outcome was behavioural and emotional difficulties, assessed with the Strenghts and Difficulties questionnaire (SDQ). Eight potential confounders were identified a priori, which was adjusted for in the multivariate analysis. The OM-status of the children was determined by parent reporting, which might introduce some recall bias regarding the exposure assessment.

Jafari (2016) examined the possible effects of recurrent otitis media in early childhood on binaural processing and verbal memory in school-aged children in a retrospective cohort. In total, 211 children aged six to twelve years from 22 primary schools in Teheran, Iran were included in the study sample. To reduce variability among the participants in terms of demographic factors, primary schools from similar geographic regions were selected. To be included in the sample, children had to be right-handed, monolingual native speakers, have an IQ between 90 and 115 in the Wechsler Intelligence Scale for Children-Revised (WISC-R), and pure-tone hearing thresholds equal or better than 20 dB (in frequencies ranging from 250 to 8000 Hz). Exclusion criteria were a history of neurological problems, medical diseases, preterm birth history, or absence of a good cooperation. For this study sample, history of OM episodes was assessed by a parent-survey. Children with a mean rate of three or more annual episodes of OM per year and recurrent otitis media confirmed and treated by a specialist were selected for the OM-positive sample (n = 31, 14.7%), the other children were in the OM-negative group (n = 180, 85.3%). Outcomes included binaural processing and verbal memory. The tests were conducted in a quiet room and executed by an audiologist who was blinded for each child’s history of OM. The lack of direct matching between exposed and non-exposed patients and determination of exposure status via parent-reporting could introduce some recall bias regarding the exposure assessment.

Niclasen (2016) used data from a prospective birth cohort (Aarhus Birth Cohort in Denmark) to investigate associations between OM in early childhood and later behavioral and learning difficulties. Children from the cohort aged nine to eleven years in 2001 were eligible to participate. Parents of the children were asked to report history episodes of OM and ventilation tubes insertion. All children with information on OM were included in the analysis (n = 7,578). Parent-reported episodes of OM and ventilation tubes were categorized in four categories: no OM episodes (n = 3,585), 1-3 incidences of OM irrespective of treatment with ventilation tubes (n = 2,425), 4 or more incidences of OM without ventilation tubes (n=569), 4 or more incidences of OM with ventilation tubes (n = 999). Outcomes variables included reading and spelling problems, assessed via a questionnaire to parents and behavior, assessed with the Strengths and Difficulties questionnaire (SDQ). The OM-status of the children was determined by parent reporting, which might introduce recall bias, regarding the exposure assessment. Moreover, there was no adjustment for the variable “day care attendance” in the multivariable model. Since this is thought to be a relevant confounder this might also introduce bias.

Results

Language, speech, and hearing development

Two of the included cohort studies reported the outcome language, speech, and hearing development. In Gouma (2011) hearing ability was presented as the air conduction hearing thresholds (in decibel; dB) at different frequencies. In Jafari (2016) binaural processing and verbal memory was assessed with the Dichotic Digit Test (DDT) and forward- and backward Digit Memory Span Test (DMST). Mean scores on both tests were presented for the otitis media (OM) and no-OM group. Lower scores indicate weakness in dichotic listening and verbal memory.

Otitis media with effusion (OME)

In the children with a history of OME, at 500 and 1000 Hz a mean hearing threshold of 25 dB was reported, compared to a mean hearing threshold of 10 dB in the children without history of OME (Table 1). According to the author, this difference was significant (p < 0.01). The author did not report standard deviations; therefore, we were not able to calculate whether this difference is clinically relevant. Gouma (2011) mentioned that there was no statistically significant difference regarding the hearing threshold at 2000 and 4000 Hz between the study and control group.

Recurrent otitis media

The standardized mean differences (SMD) on the DDT, DMST-forward and DMST-backward test (Jafari 2016) between children with and children without history of OME were considered small (Table 1). This indicates that children with a history of OM might have some weaknesses in binaural processing and verbal memory skills as compared to children without history of OM.

Table 1 overview of the results of studies on Otitis Media and language, speech, and hearing development

SD = standard deviation; OM = otitis media; OME = otitis media with Effusion; ROM = recurrent otitis media; DDT = Dichotic Digit Test; DMST = Dichotic Memory Span Test; dB = Decibel; Hz = Hertz

Reading and writing skills

Three of the included cohort studies reported the outcome reading and writing skills (Bell 2021; Fougner 2017; Niclasen 2016). Due to study heterogeneity, the results were not pooled. In the cohort study of Bell (2021), the national NAPLAN test was used to measure reading and spelling problems. In the study of Fougner (2014) children were asked to rate their own Danish literacy skills on a 4-point Likert scale with answers: “excellent”, “good”, “fair”, and “poor”. In the study of Niclasen (2016), reading and spelling problems were assessed via a questionnaire to parents with the following questions: “does your child find it difficult to read/spell?” Answers were categorized in “no”, “yes, a little/somewhat” and “yes, a lot”.

Recurrent otitis media

In the cohort study of Bell (2021), elevated Ors were reported for problems with reading and writing skills (Table 2). This indicates that children with a history of repeated episodes of OM on average had a higher risk of scoring below the benchmark for reading and writing skills, compared with children without history of OM. Both differences were considered clinically relevant.

In the study of Fougner (2014) it was reported that the proportion of children rating their own reading and writing scales as either excellent, good, fair, or poor were within similar ranges for children with a history of OM episodes and children without history of OM episodes. These differences were considered clinically not relevant (Table 2).

In the study of Niclasen (2016) elevated Ors were reported for reading and spelling problems for girls, and spelling problems for boys (Table 2). This indicates that girls with a history of 4+ episodes of OM, with ventilation tubes have a higher risk of developing reading and spelling problems, compared to children without history of OM. Boys with a history of 4+ episodes of OM with ventilation tubes, have a higher risk of developing spelling problems. These differences were considered clinically relevant. For children who suffered from 1-3 episodes of OM, or children who suffered from 4+ episodes of OM but were not treated with ventilation tubes no clinically relevant differences were found (Table 2).

Table 2 Overview of the results of studies on otitis media and reading and writing skills

OM = otitis media; OR = Odds Ratio; 95% CI = 95% confidence interval; ref = reference

Behavior / emotional development

Three of the included studies (Gouma 2011; Herzog 2020; Niclasen 2016) reported the outcome behavior. Due to study heterogeneity, the results were not pooled. In the study of Gouma (2011) behavior was assessed with the Child Behavior Checklist (CBCL). The mean total score for competence scales (social, academic, and overall activity) and syndrome scales (internalizing and externalizing syndromes) were presented. In the studies of Herzog (2020) and Niclasen (2016) behavior was assessed with the Strengths and Difficulties Questionnaire (SDQ). This questionnaire contains 25 questions about different positive and negative aspects of the child’s behavior which can eventually be categorized into an internalizing scale (representing peer problems and emotional problems) and an externalizing scale (representing hyperactivity and conduct). Additionally, a score for prosocial behavior can be assessed. A higher SDQ-score indicates difficulties within the different subcategories.

Otitis media with effusion (OME)

In the case-control study of Gouma (2011), the CBCL score was found to assess the effect of OM on behavior. The scores for different subscales of this score (competence scale and syndrome scale) for children with a history of OM and children without a history of OM appear to be in a similar range (Table 3). This suggests that there are no clinically relevant differences in behavior between these two groups. Due the lack of SDs in the article, it is not possible to exactly identify whether the differences were clinically relevant.

Recurrent otitis media

In the cohort study of Herzog (2020), mean SDQ-scores were reported. The scores for the different subscales of this score (externalizing scales, internalizing scales, pro-social scales) were reported.

• On the SDQ externalizing subscales (sum of hyperactivity and conduct scores) scores were reported to be increased for children with 1-3 episodes of OM, children with 4+ episodes of OM (without ventilation tubes), and children with 4+ episodes of OM (with ventilation tubes tubes), when compared to children without history of OM (Table 3).
• On the SDQ internalizing subscales (sum of emotional and peer problem scores) scores were reported to be increased for children with 1-3 episodes of OM, children with 4+ episodes of OM (without ventilation tubes) and children with 4+ episodes of OM with ventilation tubes, when compared with children without history of OM (Table 3)
• On the pro-social scales scores were reported to be higher for girls with 1-3 episodes of OM, children with 4+ episodes (without ventilation tubes) and children with 4+ episodes of OM, (with ventilation tubes), when compared with children without history of OM (Table 3)

The differences for the different questionnaire scores appear to be in a similar range and not differ substantially, suggesting no clinically relevant differences. Due to the lack of SDs in the article, it is not possible to exactly identify whether the differences were clinically relevant.

In the cohort study of Niclasen (2016) Ors were reported indicating a score above the cut-off scores for the different SDQ scales.

• On the SDQ externalizing subscales (sum of hyperactivity and conduct scores), elevated Ors were reported for boys and girls with a history of 4+ episodes of OM (without ventilation tubes) and boys and with a history of 4+ episodes of OM (with ventilation tubes). The differences for these subgroups were considered clinically relevant, indicating a higher risk of having difficulties in externalizing behavior domains. In the other subgroups no clinically relevant differences were reported (Table 3)
• On the SDQ internalizing subscales (sum of emotional and peer problem scores), elevated Ors were reported for boys with 4+ episodes of OM (with and without ventilation tubes). The differences for these subgroups were considered clinically relevant, indicating a higher risk of having difficulties in the internalizing behavior domains. For girls, no clinically relevant differences in one of the internalizing domains was found between children with and children without history of OR. (Table 3)

Between children with a history of 1-3 episodes of OM and children without history of OM, no clinically relevant differences were found for having a score above the 10% threshold of the different behavior scales.

Table 3 Overview of the results of studies on otitis media and behavior

OM = otitis media; OME = otitis media with effusion OR = Odds Ratio; 95% CI = 95% confidence interval; ref = reference; SDQ = Strengths and Difficulties Questionnaire

Quality of life

One of the included studies reported quality of life, assessed with the OM-6 survey and the PedsQL questionnaires (Grindler 2014). The OM-6 survey is a 6-item disease specific tool to measure health related quality of life (QoL) in children with OM. Elevated OM-6 scores correlate to increased burden of disease and impact of OM on the child. The PedsQL is a validated instrument that measures overall health related QoL and disease specific symptoms. The PedsQL scoring results in a scale of 1 to 100 with higher scores indicating better HR-QoL.The questionnaires are age-specific with one form for infants aged 1 to 12 months and one form for children aged 13-24 months.

Recurrent otitis media and chronic OM

On the OM-6 questionnaire, the SMD between children with and children without history of OM was considered moderate, indicating a greater burden of disease on QoL (Table 4). On the PedsQl scores the SMDs between children with and children without history of OM were considered moderate, indicating a worse health related QoL in children with a history of OM at different ages (Table 4).

Table 4 overview of the results of studies on otitis media and quality of life

SD = standard deviation; OM = otitis media; 95% CI = 95% Confidence Interval

Level of evidence of the literature

The level of evidence regarding the outcome measure language, speech and hearing development was derived from observational studies and therefore started low. The level of evidence was downgraded by 2 levels because of study limitations including the exposure assessment risk of bias) and number of included patients (imprecision). The final level of evidence for the outcome measure ‘language, speech and hearing development’ was ‘very low’.

The level of evidence regarding the outcome measure reading and writing skills was derived from observational studies and therefore started low. The level of evidence was downgraded by 3 levels because of study limitations including the exposure assessment and not corrected for all relevant confounders (risk of bias), conflicting results (inconsistency) and the 95% confidence intervals crossing the boundaries of clinical relevance (imprecision). The final level of evidence for the outcome measure ‘reading and writing skills’ was ‘very low’.

The level of evidence regarding the outcome measure behavior was derived from observational studies and therefore started low. The level of evidence was downgraded by 2 levels because of study limitations including lack of matching between cases and controls and limitation in the exposure assessment (risk of bias), conflicting results (inconsistency) and the 95% confidence intervals crossing the boundaries of clinical relevance (imprecision). The final level of evidence for the outcome measure ‘behavior was ‘very low’.

The level of evidence regarding the outcome measure quality of life was derived from observational studies and therefore started low. The level of evidence was downgraded by 1 level because of study limitations including lack of matching between cases and controls risk of bias) The final level of evidence for the outcome measure ‘quality of life’ was ‘very low’.

Search and select

A systematic review of the literature was performed to answer the following question:

What are the differences in speech, language and hearing development, behavior, and quality of life in children with a history of (repeated) episodes of otitis media (OM; pOME/rOMA/ACMOM) compared to children without a history of OM (pOME/rOMA/ACMOM)?

P: Children aged 0 – 12 year.

I: Children with a history of (repeated) episodes of otitis media (pOME/rOMA/ACMOM).

C: Children without a history of OM (pOME/rOMA/ACMOM).

O: Language, speech and hearing development, reading and writing skills at school, emotional development and behavior, quality of life of child and parent.

It was decided to limit the search to children aged up to twelve years old, since the effects on language- and speech development  are not expected to be present at older ages (up to 18 years old).

Relevant outcome measures

The guideline development group considered all predefined outcomes as a critical outcome measure for decision making. A priori, the guideline development group did not define the outcome measures listed above but used the definitions used in the studies.

The guideline development group defined a threshold of 25% for continuous outcomes and a threshold of <0.80 and >1.25 for dichotomous outcomes (Relative Risk; RR or Odds Ratio; OR) as a minimal clinically (patient) important difference. Standardized mean differences (SMD) were interpreted as a trivial effect (SMD = 0 to 0.2), a small effect (SMD = 0.2 to 0.5), a moderate effect (SMD = 0.5 to 0.8), and a large effect (SMD >0.8).

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms for articles published between 2009 until 16 November 2021. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 1113 hits. Studies were selected based on the following criteria: systematic reviews, RCTs and observational studies on the effects of otitis media on speech- and language development, behavior, and quality of life. For observational studies, an additional criterium was used: inclusion of at least 100 patients/controls. In total, 29 studies were initially selected based on title and abstract screening. After reading the full text, seven studies were included (see the table with reasons for exclusion under the tab Methods), and 22 studies were excluded.

An earlier performed search on articles describing the effect of otitis media on speech and language development, behavior and quality of life was executed in March 2009. The studies from this earlier performed search all had a (very) low level of evidence. Therefore, the results from this search were not included in the summary of literature. Relevant passages are included in the recitals.

Results

Seven studies were included in the analysis of the literature, these were all observational studies. No relevant systematic reviews or RCTs were found. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.