Kinderen die uitvallen op de neonatale gehoorscreening (NGS) of met op latere leeftijd (een vermoeden van) gehoorverlies, worden doorverwezen naar een Audiologisch Centrum voor diagnose en interventie. Het draaiboek NGS schrijft voor dat audiologische centra de kinderen binnen drie weken na verwijzing zien voor audiologische diagnostiek. Het streven is om uiterlijk met een à terme leeftijd van 3 maanden de diagnose rond te hebben en bij een à terme leeftijd van 6 maanden met passende interventies (zoals hoorrevalidatie en vroegbehandeling) gestart te zijn (genoemde termijnen in vervolg van deze module hebben betrekking op de à terme leeftijd). Voor kinderen die later verwezen zijn geldt dat zo snel mogelijk na de verwijzing het gehooronderzoek, de diagnose en een passende interventie zal moeten starten.

Uit de monitoring van de NGS (Monitor NGS, 2021) blijkt jaarlijks dat de norm van toegangstijd tot het Audiologisch Centrum van maximaal drie weken na verwijzing niet overal wordt gehaald. Soms liggen hier praktische bezwaren van ouders aan ten grondslag, soms ook logistieke/inhoudelijke redenen van het Audiologisch Centrum. De norm van een tijdige diagnose binnen 3 maanden wordt niet altijd gehaald. Kortom: er is praktijkvariatie binnen de uitvoering van de follow-up van de NGS. Tegelijkertijd is er een trend om het tijdspad nog verder te verkorten. In het geval van congenitale cytomegalievirusinfectie (CMV) is tijdige diagnostiek belangrijk ten einde tijdige antivirale behandeling (voor de leeftijd van 3 maanden) mogelijk te maken. Daarnaast pleit de Joint Committee on Infant Hearing (JCIH, 2019) voor diagnose bij 2 maanden en start interventie bij 3 maanden. Gezien het feit dat de huidige termijnen niet gehaald worden, is vervroegen van deze termijnen een grote uitdaging. Wat is een optimaal en haalbaar tijdspad om het risico op ontwikkelingsachterstanden te verkleinen?

Description of studies

Ching (2020) performed a prospective cohort study using data from the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study, to investigate the impact of universal newborn hearing screening and early intervention on language outcomes for children with congenital hearing loss. Children were included if they had mild to profound hearing loss and received hearing aids (HA) or cochlear implants (CI) before the age of 3 years. Patients were screened at 6 and 12 months after hearing aid fitting, and at the age of 3, 5 and 9 years. This paper focusses on outcomes in 5-year-olds. In total, 168 children were included for hearing aids. Outcome of interest was labeled by Ching (2020) as global language score, which was an aggregated score of: total language (measured with Pre-school Language Scale version 4 (PLS-4)), receptive vocabulary score (measured with Peabody Picture Vocabulary Test 4th edition (PPVT-4)), articulation score (measured with Diagnostic Evaluation of Articulation and Phonology (DEAP)), Woodcock Diagnostic Reading Battery (WDRB), non-verbal cognitive ability (measured with Wechsler Nonverbal Scale of Ability (WNV)), PEACH, Child Development Inventory (CDI), and the Strengths and Difficulties Questionnaire (SDQ). Although Ching (2020) labeled the outcome as global language score, due to the diversity of included scores, the guideline working group labeled the outcome as global development score. The global development score has a normative mean of 100 and a standard deviation (SD) of 15. Standard multiple regression analyses with the global development score as a dependent variable were conducted to determine the effect of exposure to newborn hearing screening and the effect of age at intervention on outcomes respectively, while controlling for a range of potential confounders.

Meinzen-Derr (2020) created a comprehensive longitudinal population-based cohort linking hearing screening and diagnostic data of 1746 infants identified with permanent hearing loss born from January 1, 2008, to December 31, 2014, with early intervention (EI) data and educational records. The aim of the study was to investigate kindergarten readiness in children who are deaf or hard of hearing who received EI. EI was defined by using the national EHDI benchmark of enrollment into EI before the age of 6 months. Children were classified as entering EI early if they enrolled before the age of 6 months and classified as entering EI later if they enrolled at or after the age of 6 months. In total, 385 children were included. Of those, 222 children were in the EI-early group (age (months, IQR): 3.4 (2.4 to 4.3); 118 (53.2%) male) and 163 children were in the EI late group (age (months, IQR): 9.2 (7.5 to 15.4); 85 (52.2%) male). The outcome measure of interest was kindergarten readiness assessment (KRA). The KRA consists of 50 questions designed to address a child’s growth and development in four areas of early learning: 1) social foundations, 2) mathematics, 3) language and literacy, and 4) physical wellbeing and motor development.

Meinzen-Derr (2022) reported on the same longitudinal cohort as Meinzen-Derr (2020) to evaluate the association between age of early intervention (EI) enrollment for DHH children and emergent literacy in preschool. In this article, emergent literacy was measured during preschool using the Get it! Got it! Go! (GGG) assessment. The GGG is composed of three individual indicators in children’s language and literacy development: Picture Naming (measuring expressive language development), Rhyming, and Alliteration (measures of phonological awareness associated with early literacy development).

Vohr (2008) performed a prospective longitudinal cohort study to determine the early language outcomes of children with mild to profound hearing loss, compared with hearing control children, at 12 to 16 months of age and to examine the effects of “very early” enrollment (≤3 months) in early intervention (EI). Of the 31129 infants screened for HL in Rhode Island during the enrollment period, 64 infants were diagnosed as having congenital HL, 720 infants had false-positive results, and 30345 passed the screening test. 33 (52%) of the 64 infants identified as having HL were enrolled in the initial study and were seen at 6 to 10 months; 30 of 33 were seen at 12 to 16 months. All infants were screened with a 2-step protocol that included otoacoustic emission testing followed by automated auditory evoked response testing, with outpatient rescreening in cases of hospital testing failure. All patients who experienced screening failure were referred for comprehensive diagnostic testing, which included auditory brainstem response testing, tympanometry, otoacoustic emission testing, and, by 6 months of age, visual reinforcement audiometry. matches for the infants with confirmed HL were in 2 categories, namely, subjects with false-positive hearing screening results and control subjects with hearing screening pass results. Matches were based on a hierarchical matching procedure using the following characteristics: gender, date of birth (±90 days), hospital of birth, normal nursery versus NICU, maternal education, race/ethnicity, and health insurance. Matching criteria were relaxed when necessary to find sufficient matches. Exceptions were necessary for matching of multiple births. Outcomes of interest include auditory brainstem response testing, tympanometry, otoacoustic emission testing, visual reinforcement audiometry; Family Support Scale, Family Resource Scale, Impact on the Family-Adapted Version G, Parenting Stress Index; MacArthur-Bates Communicative Development Inventory (CDI), Words and Gestures. Multivariate models were built, and additional regression analyses were performed to test the effects of age of enrollment in EI for the children with HL included degree of HL, NICU versus well-infant nursery care, and entry into EI at ≤3 months versus >3 months.

Results

Due to heterogeneity in participants, methods, and results, pooling of data (meta-analysis of data) was not possible.

Ching (2020) reported that overall, ‘global development scores’ were higher when intervention was started earlier, for children with moderate or severe hearing loss. However, the absolute difference between >3 months, >6 months, and >9 months was small and did not exceed the threshold of clinical relevance for moderate hearing loss. For severe hearing loss, there were clinically relevant differences noted, but these latter findings should be interpreted with caution as the comparator group did not specify the outer boundary of timing of intervention (could be several months to years). In addition, none of these findings were adjusted for confounding, which may be due to small numbers especially in the Severe group. However, the results indicate that the benefit of earlier intervention is greater for hearing loss that is more severe.

Meinzen-Derr (2020) reported an adjusted odds ratio (n=385) for early EI entry (<6 months) vs late entry (> 6 months) of 2.16 (95% CI: 1.33-3.50) using multiple logistic regression analysis (adjusting for disability diagnosis while in EI; Mother education level; type of insurance; and type of hearing loss). This means that children from early EI entry (<6 months) are 2.16 times more likely to achieve on track language and literacy compared to children with late entry (>6 months). This result did exceed the threshold of clinical relevance and was statistically significant but should be viewed with caution due to potential of confounding by indication (non-randomized study).

Meinzen-Derr (2022) reported that children who enrolled in EI early (<6 months) had higher mean scores (mean, 95% CI) over time compared to children who enrolled later for the emergent literacy assessment domains of picture naming (2.42, (0.47, 4.37), approximately 2.4-word difference), rhyming (1.2, (0.35, 2.06), approximately 1-word difference) and alliteration (0.61, (0.15, 1.07)). These results did not exceed the threshold of clinical relevance.

Vohr (2008) reported that overall, CDI scores were higher for children with hearing loss at EI ≤3 months, compared to >3 months. Results are shown in underlying table. Percentile scores for phrases understood, words produced, words understood, and gestures (early, later and total) all exceeded the threshold of clinical relevance. Please note that numbers were small, findings were not adjusted for confounding and that the study was non-randomized, making that these findings should be interpreted with caution.

Table 1: CDI scores at 12 to 16 months for children with HL in EI at ≤3 or>3 months (from Vohr 2008)

1. Speech (perception)

No studies were found reporting speech perception.

2. Auditory development

No studies were found reporting auditory development.

3. Auditory discrimination

No studies were found reporting auditory discrimination.

Level of evidence of the literature

Summary

The level of evidence (GRADE method) is determined per comparison and outcome measure and is based on results from 4 observational studies and starts at level “low”. Subsequently, the level of evidence was downgraded if there were relevant shortcomings in one of the several GRADE domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Observational data evaluating the optimal timeline for screening, diagnostics and start of intervention in children aged 0-4 years with hearing loss were limited to 30-385 participants per study. All observational studies do suggest clinically relevant improvements in language but did not assess other study outcomes that were considered as crucial by the working group (i.e., speech perception, auditory development, auditory discrimination). Therefore, an overall assessment on the question if early intervention (EI) minimizes the risk of delays in development is incomplete. In addition, findings on language development, where better outcomes were found through early intervention, and which follows clinical practice (where intervention is offered as soon as possible), should be viewed with caution. Not only are these results potentially confounded as shown by Vohr [2008], where moderate/profound hearing loss was more often found in infants who were preterm born, stayed at ICU, while these infants were less often offered EI at ≤3 months), they are also non-randomized, riddling outcomes with potential confounding (by indication), immortal time bias and selection bias (Vandenbroucke, 2004). The study question is difficult to answer through randomization from an ethical viewpoint and such studies were likely for that reason not found. Although confounding might be present in the current studies, we did not downgrade the level of evidence since the confounding is only weakening the observed effect. Meaning that the real effect might be even stronger.

The level of evidence regarding the outcome measure language started at GRADE low was not downgraded.

A systematic review of the literature was performed to answer the following question: what is the optimal timeline for screening, diagnostics and start of intervention in children aged 0-4 years with hearing loss to minimize the risk of delays in development?

Relevant outcome measures

The guideline development group considered development (including language development, speech (perception), auditory development, and auditory discrimination measured at an older age) as a critical outcome measure for decision making.

A priori, the working group did not define the outcome measures listed above but used the definitions used in the studies. The working group defined a limit of 25% difference for dichotomous outcomes (RR < 0.8 or > 1.25), and 10% for continuous outcomes as a minimal clinically (patient) important difference.

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until 30-03-2023. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 575 hits. Studies were selected based on the following criteria:

• Systematic review (detailed search strategy, risk of bias assessment, and results of individual comparative studies available), randomised control trial or observational comparative study;
• Research question includes all elements of the PICO;
• Full text available;
• Full text written in English or Dutch.

Twenty-eight studies were initially selected based on title and abstract screening. After reading the full text, 24 studies were excluded (see the table with reasons for exclusion under the tab Methods), and four studies were included.

This guideline is developed for children with hearing loss aided with hearing aids or children with mild hearing loss who need monitoring. Hence, publications describing children who received cochlear implants, were excluded from the literature selection. We are aware of the fact that this might be a limitation for answering the current question. This is because children who are possibly in need of a cochlear implant clearly benefit from timely completion of diagnostics and early rehabilitation with hearing aids. On the other hand, these children are a distinct population due to their large hearing loss and receive a different rehabilitation program which both may influence their outcomes. Because of this we have chosen to exclude this group.

Results

Four studies were included in the analysis of the literature. 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.