Abstract
Birth defects, also known as congenital disorders, are a significant health issue impacting at least five million births annually worldwide. For policymakers to mount a relevant healthcare response to care for those affected, the burden of disease of these conditions must be quantified. Estimates of the contribution of birth defects to under-5 child mortality and morbidity are generated by several groups globally. These estimates often differ, causing confusion for policymakers. While some differences may be attributed to the data sources and methods used, much is due to a lack of clarity in the terminology used for the group of disorders classed as “congenital”. This study aimed to gain insight into the diversity of terms and definitions for birth defects, including those used routinely by relevant international/national organisations and in the peer-reviewed literature. This two-part study included (1) scoping review of peer-reviewed literature to identify terms and definitions in use for birth defects and (2) review of key websites and grey literature to identify terms and definitions used. The results of this study indicate a wide variety of terms being used, often interchangeably and undefined, in peer-reviewed publications, on institutional websites and related literature. This suggests a lack of clarity related to terminology and sets the scene for further discussion, recommending that the community of practice working on birth defects comes to a consensus on standard terminology and definitions for global uptake and implementation. Such standardisation will facilitate a common understanding of the burden of these disorders globally, regionally and within countries so that action can be taken to support affected children and their families.
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Introduction
The heterogenous collective of congenital disorders (also known as birth defects) includes a diverse range of conditions present from birth as well as minor conditions (e.g. polydactyly) that do not pose a significant health issue. Some disorders, such as cleft lip and spina bifida, are obvious at birth while other serious conditions, such as congenital heart defects and inborn errors of metabolism, are less easily detected. Other conditions may only manifest later in life, for example, Huntington’s disease. The aetiology of these conditions varies, ranging from genetic or partially genetic, sporadic, or environmental causes. Serious congenital disorders, defined as those resulting in death or disability in the absence of intervention, are an important cause of early death and life-long disability (Christianson et al. 2006; Modell et al. 2016). The collective of congenital disorders represents a significant health issue impacting at least five million births annually across the globe (World Health Organization 2006, Modell et al. 2016).
While congenital disorders impact all populations, their occurrence varies across and between populations, with the majority of disorder-related deaths occurring in low- and middle-income countries (LMIC) (Christianson et al. 2006; Perin et al. 2023). While some conditions vary in their occurrence geographically, the prevalence of others is predictable between populations (Moorthie et al. 2018). Their birth prevalence is affected by various factors, including the degree of development of healthcare infrastructure and capacity (e.g. antenatal and perinatal care, vaccination programmes, diagnostic capacity, availability of primary and secondary preventative measures), prevalence of risk factors (poverty, maternal age at conception, frequency of consanguineous unions) and environmental exposures. Factors such as protection of carriers of haemoglobin disorders and glucose-6-phosphate dehydrogenase (G6PD) deficiency against death from malariaFootnote 1 must also be considered (Christianson et al. 2006).
While under-5 survival has improved over the past two decades globally, the proportion of child deaths due to congenital disorders has increased, from 4.6% of under-5 deaths in 2000 to 7.6% in 2019 (Perin et al. 2022, 2023). This is most prominent in countries with the lowest under 5 mortality rates, where congenital disorders account for 20–30% of under-5 deaths (Draper et al. 2021; Ely and Driscoll 2021; Perin et al. 2023). This includes many high-income countries (HIC) that have completed epidemiological transition (Omran 1971). The proportion of child deaths due to congenital disorders is also set to increase in low-income countries, as parallel and persisting infectious diseases (e.g. acute respiratory infections, diarrhoea and malaria) are better managed and eradicated (Christianson and Modell 2004; Kahn et al. 2007; Malherbe et al. 2015; Kabudula et al. 2017).
Estimates of the contribution of congenital disorders to these adverse outcomes (mortality and morbidity) generated by several groups globally differ, causing confusion for policymakers. While some differences are attributed to the use of different data sources and methods, much of the difference is due to the use of different terminology for the conditions classed as “congenital”. This article addresses the need for an agreed terminology related to congenital disorders, to enable professional and public perception of the true scale of the problem.
Why is consensus on terminology important?
Early, optimal services and interventions can prevent death and mitigate disability for 70% of those affected by congenital disorders (Czeizel et al. 1993; Christianson and Modell 2004, World Health Organization 2006). However, the planning and provision of appropriate health services for those affected requires detailed, accurate and reliable epidemiologic data to quantify this burden of disease in different settings (World Health Organization 1996, 2006). A first step to obtaining such agreement is to clearly define and classify the collective and conditions for inclusion and review in the burden of disease (World Health Organization 1996, 2006). Consensus on global, uniform definitions and terminology related to congenital disorders and consistent implementation of these agreed terms is currently lacking. When the concept of community geneticsFootnote 2 was introduced in 1992, it was recognised that “to create the scientific basis that we need,—principles and methods must be clearly enunciated, gain wide acceptance and be applied in practice” (Modell 1992). This applies today for the terms used to describe the collective, and sub-sets, of congenital disorders.
Several key challenges arise from the continued use of diverse terminology and differences in the range of conditions included in the collective by stakeholders. Perhaps of greatest concern is the impact of this ambiguity on the perception of the burden of disease by policymakers. For example, congenital disorders are defined by the World Health Organization (WHO) as “any potential pathological conditions arising before birth, whether they are evident at birth or become manifest later in life” (World Health Organization 1985, 2000, 2006, World Health Assembly 2010)—but undefined sub-sets of disorders representing only a portion of this disease burden are regularly presented by stakeholders and may be misinterpreted as the totality of the burden due to the use of non-synonymous terms (Malherbe et al. 2016; Modell et al. 2016, 2018). The estimated global live birth prevalence of congenital anomalies (structural anomalies only) is 22 per 1 000 live births, but this is often taken to represent total congenital disorders (structural and functional anomalies), which affect at least 36 per 1 000 births (Czeizel and Sankaranarayanan 1984; Christianson et al. 2006; Modell et al. 2016). In a population experiencing a million births per year, this equates to 20 000 births affected by congenital anomalies versus 39 000 affected by the larger collective of congenital disorders (Statistics South Africa 2021). If policymakers perceive structural anomalies to represent the total burden of congenital disorders, 19 000 affected births remain unaccounted for and underserved by appropriate health care in the country. This issue is relevant to health care in all populations but is most marked in extremely resource-constrained populations in LMIC (Christianson et al. 2006). It is vital that the congenital disorder-related burden of disease is accurately and comprehensively reported in these countries (Malherbe et al. 2015, 2016).
Current terminology
Comprehensive evaluation and consensus of terms and definitions related to congenital disorders has not been undertaken in the scientific literature and has received limited attention at international fora (Brisson 2000, Malherbe et al. 2016, Malherbe et al. 2018, Darlison and Malherbe 2020). The 2006 March of Dimes (MOD) Global Report on Birth Defects (Christianson et al. 2006) made use of the Modell Global Database (MGDb), to produce country-level estimates for early-onset, congenital disorders. Later, the MGDb was further developed at the request of WHO/MOD to expand these estimates (World Health Organization 2006, Modell et al. 2016). The MGDb developed a glossary of definitions to explain the ill-defined and often overlapping terms (Fig. 1).
Single gene disorders are excluded from the congenital anomaly grouping in Fig. 1. Most single gene disorders are also considered rare diseases. While individually rare, collectively, rare diseases are common, with over 7 000 characterised to date, accounting for a third of congenital disorders (Haendel et al. 2020). This descriptive, desktop study was designed to gain insight into the diversity of terms and definitions currently in use for congenital disorders, including those used routinely by relevant international and national organisations and in the peer reviewed literature, and set the scene for further discussion aiming to achieve consensus on standardised terminology and definitions for global uptake and implementation.
Method
This study was undertaken in two parts: (1) review of peer-reviewed medical literature using components of scoping review methodology to identify terms and definitions in use for congenital disorders and (2) review of key websites and grey literature to identify terms and definitions used.
Peer-reviewed literature
The preliminary steps of a scoping review as described by Arksey and O’Malley (2005) were followed. This included the following:
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Term identification: development of list of key terms and relevant synonyms, including MeSH terms (Table 1).
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Eligibility criteria: Peer-reviewed articles of all types (i.e. conference-proceedings, systematic and other reviews, clinical trials, case studies) excluding books and book sections. Published between 2002 and 2022 to differentiate terms used prior- and post-2006 consensus meeting (World Health Organization 2006). Articles published in English only (due to limited resources) were searched on title and abstract (tiab).
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Information sources: a single electronic database, PubMed, was used due to its broad clinical focus. PubMed searches were undertaken on 17 and 23 August 2022.
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Search terms: terms, including MeSH terms, were compiled by two authors (HM and CA) following preliminary searches. A total of 251 terms and phrases were identified. An individual search (on title and abstract—tiab) was undertaken for each of the 251 terms using quotation marks for terms of more than one word, and wild card (*) was used with root words to retrieve all term suffixes and variations, e.g. “Birth defect*” [tiab] and “Congenital disorder*” [tiab]. For examples of the terms searched, see Table 1, and for a complete list of the Boolean strings in all PubMed searches and results, see Supplementary File 1.
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Screening and study selection: individual search results were imported into Endnote reference manager software (version 20, Clarivate). Duplicates were removed from results of each individual term search.
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Data abstraction and data synthesis: due to the high volume of searches (251) and results, a sample of 20 articles from each search term that returned > 100 results were identified using an online, random number generator (www.random.org) after sorting records by year and alphabetically by surname. Results of three specific search terms (congenital anomal/anomalies, birth defects and congenital disorders) were further evaluated following earlier WHO recommendations (World Health Organization 2006). The full text of sample articles was coded and evaluated using NVivo software (QSR International Pty Ltd, March 2022 release 1.6.2) to identify the definition or context of the terms use. For each randomly selected sub-set of 20, the 10 articles with the highest number of different terms coded during analysis were described in further detail.
Website review
A list of key international organisations primarily involved in the field of congenital disorders were identified through the application of the combined authors knowledge and a Google search (https://www.google.com/) undertaken in Johannesburg, South Africa, in August 2022 and January 2023 using three specific terms: birth defects, congenital disorders and congenital anomalies. Key international organisations identified by the authors found in the first 20 results returned for each search term were included. To better understand national-level use of terminology, searches were undertaken for a limited number of English-speaking high-income countries (Australia, Canada, New Zealand, the UK and the USA). Examples from different stakeholder groups were sought (i.e. government, registries and patient support organisations) in these countries, where available. Terms relating to congenital disorders on the websites included from the Google searches were recorded together with their definition (when provided) and evaluated.
Results
Peer-reviewed literature
Of the 251 PubMed searches undertaken, over a third (n = 88, 35%) returned zero articles meeting the inclusion criteria. A fifth of searches (n = 52, 21%) returned results for over 100 articles, and of these, the top 20 search terms (i.e. returning the most articles) are presented in Fig. 2. Duplicates (n = 705) were removed for synonymous terms, including single gene/single-gene defect* (n = 141), single gene/single-gene disorder (n = 354) and single gene/single-gene mutation (n = 207). Duplicate articles recorded between searches were not deleted since this indicated the use of multiple terms in one article.
The top five terms identified were “complex disease*” (n = 3848 articles), “genetic risk*” (n = 3830), “genetic predispose*” (n = 3338), “genetic mutation*” (n = 3103) and “genetic disease*” (n = 2928).Footnote 3 The first four of these terms were excluded from further analysis as they are broadly used across different fields of medicine and not solely applicable to congenital disorders.
Of the three specific terms—congenital anomaly/anomalies, birth defects and congenital disorders—further evaluated, “congenital anomaly/anomalies” returned 2118 articles, ranking 3rd overall (following abovementioned exclusions). Both “birth defects” and congenital disorders” were included in the top 20 searches, returning 1533 and 699 articles and ranking 6th and 15th respectively.
Figure 3 shows the number of peer-reviewed articles found in the 20-year study period in searches using the terms birth defects, congenital disorders and congenital anomalies. While there is an overall increase in the number of articles found for all three terms over the period, particularly from 2013, congenital anomalies resulted in the most articles, both prior to and after 2006 (Fig. 3). Further analysis of the sub-set of articles found for these three search terms indicate that clear definitions of these terms are rarely provided, and in many cases, these three terms are used inconsistently and often synonymously with other terms (Table 2). Of the 20 articles detailed in Table 2, 17 (70%) did not define any terms used and six (30%) defined some terms used but not all.
Website review
The terminology used on the websites reviewed was notably less technical with less terms used than that in the peer-reviewed literature. The terms birth defect and congenital anomaly are most commonly used and often used interchangeably. Many websites did not define the term(s) used, and others offered different, conflicting definitions for the same term on different pages of the same website. Definitions of terms also varied between websites. See Table 3 and Table 4 for details.
Discussion
The aim of this study was to demonstrate the variety of collective terms and definitions related to congenital disorders used in both the peer-reviewed literature and on websites of key international and national initiatives. The review results show a wide variety of different terms in use, often interchangeably, in both settings. Definitions are rarely provided, and in some cases, particularly in the website review, different definitions are used interchangeably, for example, on the WHO website. Three specific terms, congenital anomal/anomalies, birth defects and congenital disorders, were also further evaluated following recommendations related to these terms in 2006 (World Health Organization 2006), and results indicated poor uptake of terms recommended for use. The inconsistent use of terms and definitions highlights the need for development of defined, uniform terms and consistent implementation of both terminology and definitions.
Previous consensus efforts
The MOD and WHO made a concerted effort to achieve global consensus on birth defect terminology in 2006, when a meeting involving 18 global experts from both LMIC and HIC was convened following the publication of the March of Dimes global report on birth defects (Christianson et al. 2006). One aim of this WHO/MOD meeting was to reach agreement on the definition of terms related to congenital disorders (Christianson et al. 2006, World Health Organization 2006).
Participants at the meeting achieved consensus, proposing synonymous use of the terms “birth defects” and “congenital disorders” (World Health Organization 2006). Estimates of congenital disorders for 190 countries published in the MOD global report (Christianson et al. 2006) were also endorsed at the meeting, with data differences between these and WHO childhood death estimates for congenital anomalies thought to be, in part, due to the difference in terminologies used (World Health Organization 2006). MOD representatives preferred the broader and more accepted term birth defects, defined as “abnormalities in structure or function, including metabolism, which are present from birth” (World Health Organization 2006)—recognising that some conditions are obvious at birth while others manifest later in life. While this term was preferred due to its broad use and acceptance, MOD acknowledged that it is not universally accepted (World Health Organization 2006). They also suggested grouping according to aetiology including as follows:
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Genetic disorders, including single gene defects and chromosomal abnormalities
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Partially genetic disorders, including multifactorial congenital malformations
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Non-genetic disorders, due to abnormalities of the foetal environment, including teratogens, mechanical forces (e.g. constraint), vascular accidents and unknown causes (Christianson et al. 2006)
In contrast, WHO representatives preferred the term “congenital disorders” (World Health Organization 2006). MOD/WHO representatives advised against the use of the term congenital anomalies, as described in the 10th revision of the International Classification of Diseases (ICD-10) (Shibuya and Murray 1998, World Health Organization 1992, 2006). The ICD codes are used extensively to gather and exchange data on birth defects and for assigning cause of death. However, this sub-set of disorders excludes “functional birth defects including non-syndromic, congenital disability…common single gene disorders… inborn errors of metabolism” and “many teratogen-induced birth defects, including congenital syphilis, congenital rubella syndrome and iodine deficiencies (World Health Organization 2006). Today this would include TORCH congenital infections, including Toxoplasma gondii, other agents, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). Collectively, these excluded conditions account for more than a third of congenital disorders in ICD-10 (Christianson and Modell 2004; Malherbe et al. 2016; Modell et al. 2016).
A further recommendation from the 2006 MOD meeting was for the WHO ICD team to engage relevant organisations to develop a “universally acceptable classification of birth defects”. The most recent revision, ICD-11, has implemented an updated, more sophisticated structure and invited evidence-based proposals to promote openness and transparency—which has included the incorporation of inputs relevant to congenital disorders and the use of the collective term “developmental anomalies” (World Health Organization 2019, 2022, Drösler et al. 2021, Harrison et al. 2021).
The consensus achieved at the 2006 WHO/MOD meeting was thought to have ended “over two decades of uncertainty” (World Health Organization 2006). However, the recommendations were not widely publicised in other formats or to other audiences, and the evidence indicates little uptake of uniform, consistent terminology globally (Modell et al. 2016), both in the literature and websites reviewed. This may also account for the continued preferred use of the term congenital anomaly/anomalies observed in both reviews.
General observations
This review shows that despite the recommendations of the 2006 MOD/WHO meeting (World Health Organization 2006), there is still no global consensus on birth defect terminology. This may be partly because sustained advocacy and awareness around congenital disorders have waned in recent years due to resource restrictions and changes in focus (e.g. shift in focus by MOD to preterm births), despite the increasing proportion of child deaths related to these disorders. This has resulted in congenital disorders being under-prioritised within the broad mandate of many health organisations.
Community genetic services
The historic challenge of finding an appropriate “home” for congenital disorders has also contributed to loss of momentum in the field of community genetics. The unique characteristics of congenital disorders, including diverse natural histories, varying impact across the lifespan and diverse aetiologies, make them difficult to place. Little traction has been gained by placing these conditions under the umbrella of non-communicable diseases (NCDs)—where almost exclusive focus remains upon adult-onset disorders. A more suitable placement for congenital disorders, particularly early onset conditions, may be within maternal, child, adolescent and reproductive health programmes, rather than NCDs—but this requires further discussion and debate within the global public health community.
Historically, governments began to recognise the need for community genetic services once the infant mortality rate (IMR) dropped below 40–50 per 1 000 live births—and significant further reductions could only be achieved by comprehensively addressing congenital disorders (Modell and Kuliev 1998; Christianson and Modell 2004, World Health Organization 1999). In many LMIC, the need for community genetic services is being recognised later due to the continued burden of infectious diseases of childhood and as NCDs gain increasing recognition (Kerber et al. 2013). In the interim, many of those affected by congenital disorders do not receive a diagnosis or the care required after diagnosis. This is contrary to the underlying philosophy of the Sustainable Development Goals (SDG) “to leave no one behind” and the 2030 SDG3 target to “end preventable deaths of newborns and children under five years of age” (United Nations 2015). It also echoes the consensus of the 2015 International Conference on Birth Defects and Disabilities in the Developing World (ICBD) that “children with congenital disorders remain left behind in policies, programmes, research and funding” (Darmstadt et al. 2016; Modell et al. 2018). For true inclusivity, global efforts must incorporate integrated programmes combining care and prevention, on the principle that “care is an absolute and prevention is the ideal” (Christianson et al. 2000).
Endogenous versus environmental congenital disorders
The need to distinguish between environmental congenital disorders caused by maternal exposure to teratogens (alcohol, recreational and prescription drugs, tobacco, occupational exposure, infection malnutrition), and congenital disorders arising from endogenous causes, was recognised both by MOD at the 2006 joint meeting with WHO (World Health Organization 2006) as outlined above and during the subsequent development of the MGDb. This clear distinction has not been made by other key initiatives or programmes but has important implications for policy development and implementation. The majority of environmental congenital disorders are preventable and may even be eliminated through existing, traditional public health measures such as immunisation, food fortification, sanitation and community information. However, this does not apply to disorders with internal (endogenous) causes such as most congenital malformations, chromosomal disorders, single gene disorders and disorders due to common genetic risk factors (Modell et al. 2016). The endogenous disordersFootnote 4 included in the MGDb may be treatable or correctable, or life-limiting and incurable, and present health services providers, especially those in LMIC, with a difficult challenge. It is proposed that the terms endogenous and environmental congenital disorders are more widely used to differentiate between these aetiologies.
Implications for data sharing and policy development
The inconsistent use of undefined terms makes it difficult to compare data sets both within and between populations, inviting the reader to make assumptions based on previous knowledge and experience which may differ from that intended by the authors. Some established registries, such as the umbrella registry EUROCAT, enable valid comparisons by clearly defining a core dataset to be collected by all participating registries, supported by detailed guidelines for case reporting and ascertainment (EUROCAT 2018). In other regions and countries, especially LMIC where registries are under-developed or non-existent and there is a lack of detail on congenital disorders, terms and definitions are often adopted ad hoc with little or no evidence-base and bundling and grouping for presentation to policymakers is often unplanned and unstandardised.
The provision of standardised, accessible and reliable output data for congenital disorders associated with structural abnormality (ICD-10 Chapter XVII) by congenital anomaly registries may account for the extensive use of, and preference for, the term congenital anomalies across both the scientific literature and public websites. Unfortunately, as programmes expand to include additional, less obvious, functional congenital disorders, the terminology often remains unchanged, leading to difficulties in comparing data from different sources. Without standardisation to ensure accuracy, comparisons across and between countries and regions will not be possible and some important conditions will remain unrecognised and underserviced by health services.
Limitations of the study
A robust scoping review methodology was employed in this study, and 20 articles were evaluated per specific search term due to resource constraints and the high number of articles identified. Similarly, the website review was preliminary, with the inclusion of a single source for a term and definition used by an individual entity. Both reviews in this study were limited in scope to the English language and in the number of studies that could be evaluated due to resource constraints. Nevertheless, the results revealed the range of terms and definitions used globally. Support for the call for standard terminology and definitions will be enhanced by a broader search which also includes additional languages.
Recommendations for future standardisation efforts
Tailoring of terms for specific audiences
Terminology development and usage should consider the audience being addressed. As demonstrated by the use of different terms in the literature as compared to key websites in this review, different audiences require and prefer the use of specific terms, such as “congenital disorders of glycosylation” identified for papers related to this specific field (Freeze and Aebi 2005). The scientific literature is mainly aimed at specialists, but many other target audiences are multidisciplinary, including a combination of public health directors, primary health care practitioners, politicians and policymakers, the media and patient support associations with varying levels of genetic expertise. If genetic information and services are to be made available to all who may benefit, then agreed, clear and simple terms must be used and pitched appropriately for a general audience. This would both facilitate communication among health professionals working in different disciplines and support them in providing correct and consistent information to others.
The understanding of the lay population, including patients, patient organisations and the general public, is equally important. Some terms may have negative connotations or be considered derogatory by those living with congenital disorders, as highlighted by Mai et al. (2012) in relation to the use of birth “defects”. While the present review focused solely on English terminology, translation into vernacular language requires careful consideration since a suitable term in one country may not be deemed appropriate in another.
Role of international organisations
Key international and regional initiatives working in the fields of congenital disorders and community genetics should address the issue of terminology and lead by example through collaborating on the global harmonisation of uniform terms and their implementation. Such organisations have an opportunity to set the tone through the development and consistent implementation of uniform terms for congenital disorders, underpinned by a companion glossary.
Need for wider consultation
Recent work undertaken by the global rare disease community and sponsored by Rare Diseases International (RDI) to develop operational definitions for these conditions offers insight into the development of uniform terms and definitions for congenital disorders. A group of 18 experts from six continents participated in a series of three online workshops and two surveys to review and reach agreement on key statements related to rare diseases. The group agreed that the operational definition of rare diseases “must be clear and practical to implement, with defined parameters that permit a uniform, unambiguous, objective interpretation of the definition by a wide range of stakeholders across the world” (Rare Diseases International 2022). The results of this work have been actively and widely shared across a range of stakeholders (Rare Diseases International 2022) and in a forthcoming scientific publication (Wang et al., unpublished).Footnote 5
Recommendations for future work to develop and advocate for standard definitions include the following:
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Agreement on terms and definitions that are precise, comprehensible and uniform across the full spectrum of congenital disorders. Such terms should be transparent and accurate in their clinical implications and also reflect the changes made in ICD-11.
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Agreed terms should be sensitive to the preferences and tailored to the pitch, of the users, especially patients and lay-audiences. To ensure effective communication to both specialist and lay audiences, two-tiers of terms could be considered to meet the needs of both the specialist and non-specialist, e.g. haemoglobinopathies/haemoglobin disorders.
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Use of developed terms should be accompanied by the definition to optimise their understanding by the reader, minimise ambiguity and promote consistent implementation.
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Terms and definitions could be condensed into an online, WHO-endorsed glossary for global dissemination.
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Implementation of a robust, transparent consultative process followed by wide dissemination of the results in a variety of formats to promote optimal uptake.
Conclusion
The quantity and diversity of terms used to describe congenital disorders and the lack of standardised definitions highlight the need for concerted, international efforts to develop uniform terms for consistent use. This is a critical issue, both in LMIC where empirical data on congenital disorders is lacking and also in the HIC that host key funding sources and major research centres. To ensure that those affected by congenital disorders are not left behind, they must be diagnosed and counted. For this to be undertaken comprehensively and accurately, the components of this burden of disease must be clearly defined in a language understood by all.
Notes
Malaria infection strongly influences the birth prevalence of haemoglobin disorders and G6PD.
Community genetics is defined as “the art and science of the responsible and realistic application of health and disease-related genetics and genomics knowledge and technologies in human populations (communities) to the benefit of individual persons.” (Ten Kate et al. 2010).
Wild card (*) used in search phrase with root words in PubMed search to identify all suffix variations of terms.
The term “constitutional” has been replaced by “endogenous” in a recent application of the MGDb in South Africa (Malherbe et al. 2021) with regard to conditions with a genetic/partially genetic aetiology and may be more preferable for future use.
Wang C, Whiting A, Rath A, et al. A reference to improve the recognition and visibility of rare diseases (Submitted: Orphanet Journal of Rare Diseases, March 2023).
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Acknowledgements
The authors would like to sincerely thank Prof. Arnold Christianson, Wits Centre for Ethics, University of Witwatersrand, South Africa, and Dr Mathew Darlison, University College London, UK, for their contributions to the initial thinking and conceptualisation of this study.
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Open access funding provided by North-West University. This study and open access publication was funded by the World Health Organization through Rare Diseases South Africa NPC.
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Helen Malherbe and Collen Aldous. The first draft of the manuscript was written by Helen Malherbe, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Bernadette Modell, Hannah Blencowe, Kathleen Strong and Colleen Aldous have no conflicts of interest. Helen Malherbe is a part-time consultant and board member (uncompensated) for Rare Diseases South Africa NPC.
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B Modell is an Emeritus Professor of Community Genetics.
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Malherbe, H., Modell , B., Blencowe , H. et al. A review of key terminology and definitions used for birth defects globally. J Community Genet 14, 241–262 (2023). https://doi.org/10.1007/s12687-023-00642-2
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DOI: https://doi.org/10.1007/s12687-023-00642-2