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Augmentative and alternative communication in children with Down’s syndrome: a systematic review

BMC Pediatrics volume 18, Article number: 160 (2018) Cite this article

Abstract

Background

The use of technology to assist in the communication, socialization, language, and motor skills of children with Down’s syndrome (DS) is required. The aim of this study was to analyse research findings regarding the different instruments of ‘augmentative and alternative communication’ used in children with Down’s syndrome.

Methods

This is a systematic review of published articles available on PubMed, Web of Science, PsycInfo, and BVS using the following descriptors: assistive technology AND syndrome, assistive technology AND down syndrome, down syndrome AND augmentative and alternative communication. Studies published in English were selected if they met the following inclusion criteria: (1) study of children with a diagnosis of DS, and (2) assistive technology and/or augmentative and alternative communication analysis in this population.

Results

A total of 1087 articles were identified. Thirteen articles met the inclusion criteria. The instruments most used by the studies were speech-generating devices (SGDs) and the Picture Exchange Communication System (PECS).

Conclusion

Twelve instruments that provided significant aid to the process of communication and socialization of children with DS were identified. These instruments increase the interaction between individuals among this population and their peers, contributing to their quality of life and self-esteem.

Peer Review reports

Background

According to the World Health Organization (WHO), one in every 1100 children born worldwide harbours a chromosome 21 genetic abnormality. In the United States, 250,000 families are affected by Down’s syndrome (DS) [1] with a prevalence of one per 691 live births [2].

DS is a disorder caused by trisomy of human chromosome 21 (Hsa21) and presents various anomalies of the respiratory, cardiovascular, sensory (organs), gastrointestinal, haematological, immune, endocrine, musculoskeletal, renal, and genitourinary systems [3]. Furthermore, individuals with DS may have changes in body anatomy, such as different facial features with a rounded and flat face, an epicanthic fold, an oblique palpebral cleft, dysmotic ears, a flat and flattened nose, a short and wide neck, a small mouth with hypotonic tongue with tongue protrusion, brachycephaly, short stature, hands that may present clinodactyly or syndactyly, a single palmar fold, and small feet [3, 4]. With regard to development and cognitive aspects, this population can present difficulty in learning [5]. For example, the majority of children with DS exhibit a moderate degree of intellectual disability [4, 6], a low Intelligence Quotient (IQ), and low memory [7].

Considering the cognitive aspects, growth, and learning process associated with psychological, cultural, and environmental factors is especially important for children with DS because they need to be integrated into society and have autonomy and independence in their activities [8]. Given that DS is a common chromosomal alteration in humans and one of the leading causes of intellectual disability in the world population, it is extremely important to use tools that help in the development of communication to provide better socialization [9].

One possibility of supporting the communication process is through tasks that are fun and provide cognitive and motor stimuli, especially for those with communication deficits who often need to use complementary, additional or amplified communication systems to establish an interaction process [10]. Thus, one technology specifically designed to help individuals without functional speech or writing or with a gap between their communicative need and their actual ability to communicate (speak and/or write) is ‘augmentative and alternative communication’ (AAC) [11].

AAC includes aided communication modes that require additional materials or devices and is subdivided into high and low-technology AAC. Low-technology systems or devices encompass communication books or boards (non-powered), written words on paper, photographs, line drawings and pictograms. High-technology systems include voice output communication aids (VOCAs), which are known as ‘speech-generating devices’ in North America, and software on personal computers or laptops used as communication aid (providing recorded or synthesized voice or written output). Moreover, the concept includes technology that provides access to personal computers or laptops, enabling their use as communication aids [12].

According to Foreman and Crews [8], children with DS often present difficulties in ​​language and communication as well as visual and perceptual areas, thereby suggesting that they may potentially benefit from using AAC systems to improve language development, communication, and consequently the socialization process. In this context, AAC is a key area of research aimed at studying and developing mechanisms, tools, and methodologies to complement, supplement, or increase the potential for communication [10] and has been widely used with different disorders.

Some studies highlight the importance of the relevance of the intervention for the AAC. For example, Soto and Clarke [13] demonstrated the positive effects of the conversation-based intervention for improving the expressive vocabulary and grammatical skills of children with severe motor speech disorders and expressive language delay who use augmentative and alternative communication. Moreover, their study discusses clinical and theoretical implications of conversation-based interventions and identifies future research needs in the area. Finke et al. [14] studied school-age children with autism spectrum disorder (ASD) and identified benefits associated with the use of AAC with high-technology devices for multi-symbol messages. In a review with adults with post-stroke aphasia, Russo et al. [15] described a compensatory strategy to enhance communicative skills with AAC technology.

With regard to DS, several systemic reviews have been reported on observed reading skills [16], language and verbal short-term memory skills [17], and cognitive and behavioural functioning across the lifespan [18] as well as studies on reading comprehension in developmental disorders of language and communication [19]. However, no review studies have been found that observed the instruments used for AAC for DS.

Therefore, the aim of this study is to investigate the results presented in previous studies (i.e., clinical trials, case-control, cross-sectional, case reports, and case series) on AAC use in children with DS observing the different instruments used for communication. The presentation of existing knowledge about technological modernity and this new communication tool in DS can help in the organization of treatment programmes and benefits aimed at improving the communication and independence of this population.

Methods

Search strategy

This review was based on a systematic search conducted in August 2017 of published articles available on PubMed (http://www.ncbi.nlm.nih.gov/pubmed), Web of Science (https://webofknowledge.com/), BVS – Virtual Health Library (http://bvsalud.org/), and PsycInfo (http://www.apa.org/pubs/databases/psycinfo/index.aspx) using keywords obtained from the Health Sciences Descriptors (DeCS) of the Virtual Health Library. The searches were conducted thrice on each database (See Table 1). We used the descriptor ‘syndrome’ in all searches to ensure that all potential articles were obtained. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [20]. The use of checklists, e.g., PRISMA, improves the reporting quality of systematic reviews and provides substantial transparency in the article selection process [21, 22].

Table 1 Studies searches according to database, terms and quantity of returned studies
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Finally, reference lists of retrieved studies were hand-searched to identify additional relevant studies. Keywords and a combination of keywords were used to search the electronic databases. We organized the search and selection of studies following the Population Intervention Comparison Outcome Study Design (PICOS) strategy. As performed by Massetti et al. [23], Sampaio and Mancini [24], and Massetti et al. [25], we used the search strategy based on their composition according to the PICOS method to locate and compare different works (Fig. 1). In this model, the search strategy is based on the topics of population (P), intervention (I), control group (C), outcome (O), and study design (S) as well as several searches in the cited databases.

Fig. 1
figure 1

Population Intervention Comparison Outcome Study Design (PICOS) strategy

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Selection process

We used three steps to select the articles. The first step involved searching for the articles in the databases and reading the titles and abstracts. The second step involved the exclusion of works using the title or abstract and inclusion criteria analysis. The third and final step was to analyse the full text of the eligible works [26, 27]. After the removal of duplicates, two authors evaluated the titles, abstracts, and inclusion criteria independently.

Inclusion criteria

Studies published in English were eligible if they met the following criteria: (1) study of children with a diagnosis of DS, and (2) assistive technology and/or AAC analysis in this population. There were no restrictions regarding sample size. To determine the age range limit, we used the chronological limits of the child defined by the Brazilian Child and Adolescent Statute (ECA). This statute defines a typical child as a citizen under 12 years of age [28] and those between 12 and 18 years of age as adolescents. These guidelines also encompass the range limit proposed by the WHO of 9 years, 11 months, and 29 days [29].

In our study, we did not restrict the time of publication or the type of study design; all publications found, except for reviews, were included.

Exclusion criteria

Articles were excluded if they (1) were not databased (e.g., books, theoretical papers or secondary reviews, reviews, and meta-analyses), (2) were not published in English, or (3) used populations not explicitly identified with a diagnosis of DS.

Data extraction and study quality

Data from the included studies were extracted using Microsoft Excel 2010. The form included fields to be completed by a reviewer in the following order: (1) study identification (main author’s name, year, and country), (2) study method (type of study, blinding, and secret allocation), (3) target population aspects (age and sex), (4) aspects of the intervention performed (sample size, presence of supervision, frequency, session length, and follow-up), (5) presence of follow-up, (6) loss to follow-up, (7) studied outcomes, and (8) presented results (see Tables 2 and 3).

Table 2 Summary of selected studies using instruments to promote communication and socialization among Down’s syndrome children
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Table 3 Methods, main outcomes, and methodological score of reviewed studies
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After performing the initial literature searches, each study title and abstract was screened for eligibility by RTAB and JYFLA. The full text of all potentially relevant studies was subsequently retrieved and further examined for eligibility. To increase confidence in article selection, all potentially relevant articles were reviewed independently by two researchers (RTAB and JYFLA) [24]. In the case of disagreement between them, a third researcher (TBC) was approached for a solution.

The authors of the study had the following functions: RTAB structured the script and directed the work; RTAB and JYFLA collected the studies and organized the data; TM, TBC and CA structured the method and study analysis; ASBO, CBMM and LCA structured the introduction, discussion, and conclusion; CA and TPCA adapted the work to the English language; RG, TPCA and IMPB helped in the construction of the discussion; and LCA reviewed and generally organized the manuscript. It is important to emphasize that the list of articles from the references was analysed as described by Arab et al. [30]; however, this method did not change the results of the initial search.

Analyses

The study evaluation was performed using the PEDro scale (see Table 3), one of the most used scales in the rehabilitation area [31]. This scale was developed as a part of the Physiotherapy Evidence Database to evaluate experimental studies and has a total score of 10 points, including internal validity of evaluation criteria and presentation of statistical analysis [31]. These criteria are contained in the Delphi list developed by Verhagen et al. [32] and are used to evaluate items in systematic reviews. According to Maher et al. [33], PEDro score efficiency assesses the reliability of the total score based on judgements of acceptable consensus. We followed the methodological quality proposed by Snider et al. [34] and Massetti et al. [26], which ranked the study-level evidence using the following scoring scale: ‘Excellent’ 9–10, ‘Good’ 6–8, ‘Fair’ 4–5, and ‘Poor’ < 4.

Results

PubMed, Web of Science, PsycInfo, and BVS database searches resulted in 1087 articles. After filtering articles by reading titles and abstracts, we selected 17 articles for full-text reading. Of these, 13 articles fulfilled the inclusion criteria for this review (Fig. 2) (see Additional file 1, Additional file 2, Additional file 3, and Additional file 4).

Fig. 2
figure 2

Flow chart of search strategy and selection of the articles. Initialism: AAC: augmentative and alternative communication. Overview of the literature review process. Adapted from Moher et al. (2009)

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Discussion

The studies used predominantly visual and auditory instruments for communication to provide socialization. We identified twelve instruments used for communication for children with DS (see Table 4) as described below.

Table 4 Objectives and characteristics of the instruments used in included studies
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Primary and secondary outcomes

Given that individuals with Down’s syndrome (DS) have cognitive, language, and socialization deficits and motor delay, it is important to present augmentative and alternative communication (AAC) instruments to this population. The instruments found will be displayed in topics according to the frequency in which they appeared in the results sample. Thus, the instruments will be presented considering the number of studies identified, the number and age of participants with DS and the main improvements brought by the instrument used in DS.

Speech-generating devices (SGDs)

Four studies [35,36,37,38] used speech-generating devices (SGDs). These studies included a total of 29 children with DS from 3 to 12 years of age and reported similar results. The efficacy of these instruments in DS was demonstrated by improved communication due to speech improvement, cognition, and socializing. However, the findings from the study by Sigafoos et al. [39] demonstrated that intervention with these instruments only was not sufficient to promote the process of social interaction.

It is interesting to note that SGDs are more frequently used in other populations with developmental disabilities, such as severe apraxia [40] and ASD [41,42,43,44], providing communication development through progress in the variables of language, reduction of inappropriate vocalizations, improved social communication, and disruptive behaviour.

SGDs could probably be used more in DS; therefore, teachers should be trained and specialized. According to Barker et al. [36], the Picture Exchange Communication System (PECS) is the most commonly used AAC in DS, and teachers have a higher level of training. In contrast, only 25% of teachers have training in the use of SGDs.

Picture Exchange Communication System (PECS)

Three studies [36,37,38] used Picture Exchange Communication System (PECS). These studies included a total of 28 children with DS from 3 to 12 years old. These studies obtained satisfactory results after a follow-up study, and similar results regarding improvements in language skills and social communication were reported.

Converging these findings, the PECS was successfully used to increase interaction among individuals with DS and their peers with a consequent influence on their quality of life [45].

In studies with individuals diagnosed with autism spectrum disorder, the results using the PECS are similar in terms of improving communication and the socialization process [46]. In addition, among preschoolers diagnosed with pervasive developmental disorder not otherwise specified, improvements in spoken communication and an increased number of different words after intervention with the PECS were identified in a six-month follow-up [47].

Sign language system (MAKATON)

Two studies [8, 35] used a sign language system (MAKATON) with a total of 20 children with DS from 2 to 7 years old. Improvements in language development were noted.

This instrument is being investigated in children as well as adults [48]. Adults with learning disabilities aged 18 to 44 years interacted with researchers through MAKATON signs, assisting in systemic family therapy. Furthermore, the instrument is important in educational environments, i.e., students with difficulties in learning and socialization [49]. For typical individuals and individuals with developmental disabilities, MAKATON can aid in the communication and learning processes, providing educational value and fun [50].

PCS: Picture communication symbols

Two studies [51, 52] used Picture Communication Symbols (PCS) with a total of 22 people with DS ranging from 7 to 22 years old. This set of symbols is a communication tool that aims to verify the visual perception of the individual with a focus on speed and precision when the symbols are “distributed or grouped” (arrangement) with identical content. PCS is one on of the most widely used commercial AAC symbol sets proposed by Mayer Johnson [52].

Grouping symbols and maintaining their original colour increased the speed for target location (food, clothing, activities) in all the participants, including those with DS and those exhibiting typical development, and precision in children with DS [51]. In the construction of a display design, it is essential to consider visual and perceptual characteristics, especially in individuals with DS [53].

COMPIC: Computer-generated pictographs

One study [8] used computer-generated pictographs (COMPIC) with a total of 19 children with DS from 2 to 4 years old. This study focused on the domain symbols to help identify objects, increase social interaction and language development, and improve their understanding and communication.

In a case study with a 4-year-old child with multiple disabilities, specific COMPIC symbols of his leisure activities (toy cars, blocks, bubbles) were made ​​available. Decision-making and communication development were improved. In addition, an increase in the will to communicate was noted [54].

Web-based survey (joystick)

One study [55] used a web-based survey (Joystick), with 1 child with DS that was 9 years and 8 months old. It explored a means of retrieving general preferences from children regarding rehabilitation joysticks. The most effective method for designers to use such information remains a challenge (e.g., children’s responses outlining a favourite colour were often different to the colour of their preferred joystick design, so it is unclear how a designer should incorporate this potentially conflicting information).

In addition to children with DS, the joystick has also been used with other populations, such as adults suffering from strokes, resulting in improved functional and cognitive abilities [56].

Modified ride-on car

One study [57] used a modified ride-on car with 1 child with DS who was 1 year and 1 month old. The method resulted in improved communication and socialization. As noted with any single-subject research design, especially one involving an infant, it is difficult to conclude that changes were a result of the intervention and not simply the subject’s maturation. It is important to remember that outcome changes are likely due to multiple factors, and this study does not meet every criterion of the single-case study research design [57].

A study involving 6 children from 23 to 38 months old with various cognitive and motor deficits revealed that the subjects presented independent mobility and self-initiated interactions with educators and everyday objects [58].

Picture-based strategy

One study [59] used a picture-based strategy with 1 child with DS who was 7 years and 8 months old. The study established the performance of requests, including multiple opportunities for requesting behaviours in a reinforcing context, environmental arrangement to encourage spontaneous communicative attempts, and the use of prompting and modelling to establish the use of effective forms. This study demonstrates that children with DS can benefit from interventions that use images to facilitate the execution of requests [60].

Core vocabulary

One study [61] with a total of 30 children with DS from 2 to 7 years old used core vocabulary. The core vocabularies of children in the current study serve several syntactic, semantic, and pragmatic functions. Core vocabulary words contained demonstratives (that, these), verbs (to be, to want), pronouns (my), prepositions (on), and articles (the). Without any known focus on teaching core vocabulary within speech-language therapy, these core words seem to emerge in the spontaneous interactions of the children with DS in the current study either in spoken or signed modalities. This result may not occur in other children with complex communication needs who rely on significant others to add core vocabulary to their AAC devices.

An investigated instrument based on the spoken and signed modalities involving children with typical development [62, 63] had similar results for children with DS.

Input techniques

One study [64] with a total of 8 people with DS from 10 to 28 years old used input techniques. Computer devices (keyboard, mouse, speech device, and word prediction software) were used for vocabulary analysis, performance measurement (speed and error rate), and assessment of the child’s interaction with the computer [64]. These types of instruments require further analysis given that only a few individuals with DS have the skills/ability to enter a text at a productive speed and with acceptable accuracy. Most people with DS are very slow to enter data, and the generated text typically contains a substantial number of errors.

Children with other disabilities used different devices and showed benefits. Inputs (video cameras, head trackers, and gloves) and outputs (monitors and polarized glasses) attached to computers were also used in deaf children [65]. The focus was on cognitive development, resulting in improved visual and tactile perception. In addition, tetraplegic individuals and patients with neurodegenerative diseases, such as amyotrophic lateral sclerosis, also benefit from emulating the mouse to provide mechanical movements and transform them into electrical signals transmitted via a brain–computer interface [66].

Language signals system

One study [37] used a language signals system. The study included a total of 15 children with DS from 3 to 5 years old. Positive results were demonstrated with the use of sign language (American Sign Language) to assist with cognitive processes, social interaction, and language development (production of different words) [37]. Harris et al. [67] demonstrated that the use of signs significantly increased communication capacity during the development of children with DS and suggested that early association of signals and active communication by the child may have long-term benefits for development.

Digital interactive board

One study [68] with a total of 9 people with DS from 9 to 29 years old used a digital interactive board. The study demonstrated significant benefits in terms of socialization, autonomy, and consequently individual self-esteem. González et al. [68] used the Divermates prototype to solve a mathematical task. The results showed that touching the screen improves error correction compared with handwriting, which is especially helpful to individuals with DS given their motor difficulties. In addition to the motivational factor in using computer technology, educational tools with attractive designs enable adaptation according to language needs, colour, font size, organization, grouping, categorization of items, and navigation control. González et al. [69] explain that a customized education system has been created with characteristics that are useful to students with special needs, such as DS. This system assists cognitive and motor skills, playing a key role in the learning process.

Study limitations

This review employed search terms that exhaustively covered all relevant publications. The review also used structured data extraction and quality appraisal to add to the systematic reviewing methods. Nonetheless, limitations in this review must be acknowledged. For some of the identified studies, weak methodologies and few studies using some presented instruments limited the interpretations and conclusions. We believe that these limitations may be attributed to the fact that research in this area and with this population is still considered recent. The most common design flaws were a) the small number of participants and interventions, b) the lack of a control group, and c) the heterogeneity of the sample. Future research should focus on the gaps that these limitations potentially created in studies with this population. Analysis of the methodological quality of the studies using the PEDro scale reveals that many studies failed to perform randomization and simple blinding, which could make the results more consistent. Moreover, we did not identify studies that were rated as ‘good’ or ‘excellent’, which can be considered a limitation given that most of the included studies were rated as ‘poor’ (3) or ‘fair’ (10).

Applicability

Devices that help individuals with intellectual and developmental disabilities in schools, associations, or at home daily are important. A lack of support and insufficient training are factors related to the abandonment or limited use of a communication system [70]. Parents, care givers, and the professionals involved must have knowledge about the instrument being used, so they can assist and participate directly in the cognitive and motor development of the individual. Van der Meer et al. [35] noted the importance of taking into account the individual’s preference for different choices of AAC as this factor may influence the communication skills and the acquisition tasks. Foreman and Crews [8] suggest the possibility of combining various methods of communication to enable better development.

Future perspectives

Follow-up studies and better designed methods are needed so we can follow individuals with DS throughout their development. Furthermore, testing the applicability of various AAC devices is necessary to possibly measure effective perspectives that contribute to communication, socialization, language, and motor control.

Conclusion

Twelve instruments that significantly aided in the communication and socialization of children with DS were identified from this review. This study highlights that these instruments provide significant results for children with DS not only in terms of their interaction with each other but also their interactions with other people who coexist with this population, thereby improving interpersonal relationships. However, some key factors should be considered in using such technological devices, including preferences, professional and parent training, joint use of the devices, display design, and above all stratification of the cognitive level before any intervention. Future investigations in communication and socialization of children with DS should employ standardized methods.

Abbreviations

AAC:

Augmentative and Alternative Communication

ALS:

American Sign Language

ASD:

Autism Spectrum Disorder

COMPIC:

Computer-Generated Pictographs

CP:

Cerebral Palsy

DD:

Developmental Disability

DS:

Down’s Syndrome

F:

Female

ISF:

Intrinsic Symbolic Factor

M:

Male

MAKATON:

Sign Language System

MSSD:

Multisystem Developmental Disorder

PCS:

Picture Communication Symbols

PECS:

Picture Exchange Communication System

PEDI:

Pediatric Evaluation of Disability Inventory

ROCs:

Modified Ride-on Cars

SA:

Support Assistants

SD:

Standard Deviation

SGDs:

Speech-Generating Devices

TD:

Typical Development

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Acknowledgements

The authors would like to thank CAPES (Higher Education Personnel Training Coordination). Call Notice No. 59/2014 – PGPTA and the UNIEDU-SC postgraduate programme.

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Authors and Affiliations

  1. Laboratório de Delineamento de Estudos e Escrita Científica, Departamento de Saúde da Coletividade, Faculdade de Medicina do ABC (FMABC), Rua Fagundes Varela, 121. Vila Príncipe de Gales, 09060510, Santo André, SP, Brasil

    Renata Thaís de Almeida Barbosa, Jennifer Yohanna Ferreira de Lima Antão, Tânia Brusque Crocetta, Regiani Guarnieri, Thaiany Pedrozo Campos Antunes, Carlos Bandeira de Mello Monteiro & Luiz Carlos de Abreu

  2. Escola Paulista de Medicina, Disciplina de Neurologia Clínica. Setor de Doenças Neuromusculares, Universidade Federal de São Paulo (UNIFESP-EPM), Rua Botucatu, 740, Vila Mariana, 04023900, São Paulo, SP, Brasil

    Acary Souza Bulle de Oliveira

  3. Escola Paulista de Medicina. Disciplina de Cardiologia, Departamento de Medicina, Universidade Federal de São Paulo (UNIFESP), Rua Napoleão de Barros, 715, Vila Clementino, 04023062, São Paulo, SP, Brasil

    Claudia Arab

  4. Programa de Pós-Graduação em Ciências da Reabilitação, Faculdade de Medicina, Universidade de São Paulo (USP), Rua Cipotânea, 51, Cidade Universitária, 05360000, São Paulo, SP, Brasil

    Thaís Massetti & Carlos Bandeira de Mello Monteiro

  5. Escola Superior de Ciências da Santa de Misericórdia de Vitória (EMESCAM), Av. N.S da Penha, 2190, Santa Luiza, 29045402, Vitória, ES, Brasil

    Italla Maria Pinheiro Bezerra

  6. Escola de Artes, Ciências e Humanidades, Universidade de São Paulo (EACH-USP), Rua Arlindo Béttio, 1000, Ermelino Matarazzo, 03828000, São Paulo, SP, Brasil

    Carlos Bandeira de Mello Monteiro

  7. Departamento de Saúde Materno Infantil, Faculdade de Saúde Pública, Universidade de São Paulo (USP), Av. Dr. Arnaldo, 715, 01246904, São Paulo, SP, Brasil

    Luiz Carlos de Abreu

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Contributions

RTAB structured the script and directed the work; RTAB and JYFLA collected the studies and organized the data; TM, TBC and CA structured the method and study analysis; ASBO, CBMM and LCA structured the introduction, discussion, and conclusion; CA and TPCA adapted the work to the English language; RG, TPCA and IMPB helped in the construction of the discussion; and LCA reviewed and generally organized the manuscript. All authors have read and approved the manuscript.

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Correspondence to Renata Thaís de Almeida Barbosa.

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Extraction of data – worksheet – Web of Science. (XLSX 54 kb)

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Extraction of data – worksheet – PubMed. (XLSX 75 kb)

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Extraction of data – worksheet – BVS. (XLSX 315 kb)

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Extraction of data – worksheet – PsycInfo. (XLSX 14 kb)

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Barbosa, R.T.d., de Oliveira, A.S.B., de Lima Antão, J.Y.F. et al. Augmentative and alternative communication in children with Down’s syndrome: a systematic review. BMC Pediatr 18, 160 (2018). https://doi.org/10.1186/s12887-018-1144-5

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Keywords

BMC Pediatrics

ISSN: 1471-2431

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