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.

Congenital disorders (CD) remain an unprioritized health care issue in South Africa with national surveillance underreporting by > 95%. This lack of empiric data contributes to an underestimation of the CD disease burden, resulting in a lack of services for those affected. Modelling offers estimated figures for policymakers to plan services until surveillance is improved. This study applied the Modell Global Database (MGDb) method to quantify the South African CD disease burden in 2012. The MGDb combines birth prevalence data from well-established registries with local demographic data to generate national baseline estimates (birth prevalence and outcomes) for specific early-onset, endogenous CDs. The MGBd was adapted with local South African demographic data to generate baseline (no care) and current care national and provincial estimates for a sub-set of early-onset endogenous CDs. Access to care/impact of interventions was quantified using the infant mortality rate as proxy. With available care in 2012, baseline birth prevalence (27.56 per 1000 live births, n = 32,190) decreased by 7% with 2130 less affected births, with 5400 (17%) less under-5 CD-related deaths and 3530 (11%) more survivors at 5 years, including 4720 (15%) effectively cured and 1190 (4%) less living with disability. Results indicate a higher proportion of CD-affected births than currently indicated by national surveillance. By offering evidence-based estimates, the MGDb may be considered a tool for policymakers until accurate empiric data becomes available. Further work is needed on key CD groups and costing of specific interventions.

Hemoglobinopathies are the most common monogenic disorders in humans; among them, thalassemia constitutes a serious medical and public health problem in high prevalence regions, in a geographical zone ranging from the Mediterranean Basin to China. In addition, migrations over the years have introduced thalassemia to many parts of the world. Although disease-specific programs are in place and accessible to most patients in prosperous countries, this is not the case in developing economies, where more than 75.0% of the patient population is born and lives; this concerns both prevention and treatment programs. In view of the significant improvements in public health and healthcare systems over the past few years, the Thalassemia International Federation has revisited the thalassemia prevention programs, initiatives and policies in some of its member countries, discussing their effectiveness and whether any changes in policy or public attitudes to thalassemia prevention have occurred through the recent years.

The importance of congenital disorders (also called birth defects) as a cause of early death and disability becomes increasingly apparent as countries pass through the development window and background mortality falls (Malherbe et al. 2015). Consequently, there is growing recognition of the need for their care and prevention, particularly in low- and middle-income countries. In 2010, the World Health Assembly (WHA) expressed concern that birth defects are still not recognised as a priority in public health, and called upon its member states to strengthen the prevention of congenital disorders and provision of care for those affected (World Health Assembly 2010). Nevertheless, the 2015 International Conference on Birth Defects and Disabilities in the Developing World concluded that “as the Sustainable Development Goals are adopted by United Nations member states, children with congenital disorders remain left behind in policies, programs, research, and funding” (Darmstadt et al. 2016). In fact, two WHO regional offices (those for the Eastern Mediterranean and South-East Asia) have responded to the call from World Health Assembly. In the process, both have encountered important barriers to the development of health policy in this area. Firstly, policy requires a sound epidemiological base, but in most middle- and low-income countries, the combination of (a) limited resources for the correct and accurate diagnosis of congenital disorders and (b) inadequate information systems leads to gross under-estimation of the contribution of congenital disorders to early death and disability (Christianson et al. 2006; Christianson and Modell 2004; World Health Organization 1999). Secondly, the extreme diversity of congenital disorders makes them difficult to grasp collectively at a strategic public health level. Thirdly, these problems are compounded by failure to agree and implement precise and rigorous technical terminology (World Health Organization 2006). The database described in the following articles—the Modell Global Database of Congenital Disorders (MGDb)—has been developed in order to overcome these barriers to service development.

Neural tube defects (NTDs) are associated with substantial mortality, morbidity, disability, and psychological and economic costs. Many are preventable with folic acid, and access to appropriate services for those affected can improve survival and quality of life. We used a compartmental model to estimate global and regional birth prevalence of NTDs (live births, stillbirths, and elective terminations of pregnancy) and subsequent under‐5 mortality. Data were identified through web‐based reviews of birth defect registry databases and systematic literature reviews. Meta‐analyses were undertaken where appropriate. For 2015, our model estimated 260,100 (uncertainty interval (UI): 213,800–322,000) NTD‐affected birth outcomes worldwide (prevalence 18.6 (15.3–23.0)/10,000 live births). Approximately 50% of cases were elective terminations of pregnancy for fetal anomalies (UI: 59,300 (47,900–74,500)) or stillbirths (57,800 (UI: 35,000–88,600)). Of NTD‐affected live births, 117,900 (∼75%) (UI: 105,500–186,600) resulted in under‐5 deaths. Our systematic review showed a paucity of high‐quality data in the regions of the world with the highest burden. Despite knowledge about prevention, NTDs remain highly prevalent worldwide. Lack of surveillance and incomplete ascertainment of affected pregnancies make NTDs invisible to policy makers. Improved surveillance of all adverse outcomes is needed to improve the robustness of total NTD prevalence estimation, evaluate effectiveness of prevention through folic acid fortification, and improve outcomes through care and rehabilitation.

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations.

In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, early death, or disability. Currently, lack of epidemiological data from many settings limits the understanding of the burden of these conditions, thus impeding health planning, policy-making, and commensurate resource allocation. The Modell Global Database of Congenital Disorders (MGDb) seeks to meet this need by combining general biological principles with observational and demographic data, to generate estimates of the burden of congenital disorders. A range of interventions along the life course can modify adverse outcomes associated with congenital disorders. Hence, access to and quality of services available for the prevention and care of congenital disorders affects both their birth prevalence and the outcomes for affected individuals. Information on this is therefore important to enable burden estimates for settings with limited observational data, but is lacking from many settings. This paper, the third in this special issue on methods used in the MGDb for estimating the global burden of congenital disorders, describes key interventions that impact on outcomes of congenital disorders and methods used to estimate their coverage where empirical data are not available.

Congenital disorders (often also called birth defects) are an important cause of mortality and disability. They encompass a wide range of disorders with differing severity that can affect any aspect of structure or function. Understanding their epidemiology is important in developing appropriate services both for their prevention and treatment. The need for epidemiological data on congenital disorders has been recognised for many decades. Here, we provide a historical overview of work that has led to the development of the Modell Global Database of Congenital Disorders (MGDb)-a tool that can be used to generate evidence-based country, regional and global estimates of the birth prevalence and outcomes of congenital disorders.

Neural tube defects (NTDs) are associated with substantial mortality, morbidity, disability, and psychological and economic costs. Many are preventable with folic acid, and access to appropriate services for those affected can improve survival and quality of life. We used a compartmental model to estimate global and regional birth prevalence of NTDs (live births, stillbirths, and elective terminations of pregnancy) and subsequent under-5 mortality. Data were identified through web-based reviews of birth defect registry databases and systematic literature reviews. Meta-analyses were undertaken where appropriate. For 2015, our model estimated 260,100 (uncertainty interval (UI): 213,800–322,000) NTD-affected birth outcomes worldwide (prevalence 18.6 (15.3–23.0)/10,000 live births). Approximately 50% of cases were elective terminations of pregnancy for fetal anomalies (UI: 59,300 (47,900–74,500)) or stillbirths (57,800 (UI: 35,000–88,600)). Of NTD-affected live births, 117,900 (∼75%) (UI: 105,500–186,600) resulted in under-5 deaths. Our systematic review showed a paucity of high-quality data in the regions of the world with the highest burden. Despite knowledge about prevention, NTDs remain highly prevalent worldwide. Lack of surveillance and incomplete ascertainment of affected pregnancies make NTDs invisible to policy makers. Improved surveillance of all adverse outcomes is needed to improve the robustness of total NTD prevalence estimation, evaluate effectiveness of prevention through folic acid fortification, and improve outcomes through care and rehabilitation.

Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these important conditions. We have developed methods, which overcome this lack of data and allow estimation of the burden of affected pregnancies and their outcomes in different settings worldwide. For example, the methods include a simple equation relating the percentage of mothers 35 and over to Down syndrome birth prevalence. The results obtained provide a starting point for consideration of services that can be implemented for the care and prevention of these disorders.

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families. When considered collectively, they account for an important public health burden, which is frequently under-recognised. To document the collective frequency and health burden of rare single gene disorders, it is necessary to aggregate them into large manageable groupings and take account of their family implications, effective interventions and service needs. Here, we present an approach to estimate the burden of these conditions up to 5 years of age in settings without empirical data. This approaches uses population-level demographic data, combined with assumptions based on empirical data from settings with data available, to provide population-level estimates which programmes and policy-makers when planning services can use.

Congenital disorders are an important cause of pregnancy loss, premature death and life-long disability. A range of interventions can greatly reduce their burden, but the absence of local epidemiological data on their prevalence and the impact of interventions impede policy and service development in many countries. In an attempt to overcome these deficiencies, we have developed a tool-The Modell Global Database of Congenital Disorders (MGDb) that combines general biological principles and available observational data with demographic data, to generate estimates of the birth prevalence and effects of interventions on mortality and disability due to congenital disorders. MGDb aims to support policy development by generating country, regional and global epidemiological estimates. Here we provide an overview of the concepts and methodological approach used to develop MGDb.

Background: In the last comprehensive review of the literature published in 2002, little information on the prevalence of orofacial clefts was available from low-and middle-income countries (LMICs).Objective: To analyze published data on the birth prevalence of cleft lip and/or palate (CL/P) from LMIC.Design: Systematic review of the literature and meta-analysis of data from original papers on the birth prevalence of cleft lip and/or cleft palate (CL/P) in LMICs between 1990 and 2014. Secondary inclusion criteria were developed to analyze lower-quality studies from countries with scarce data.Main Outcome Measure: Birth prevalence of undifferentiated CL/P (with or without associated syndrome or other anomaly).Results: Twenty-eight studies met strict inclusion criteria. Among 31,475,278 total births, the pooled birth prevalence of undifferentiated CL/P was 1.38 per 1000 births (95% confidence interval [CI]: 1.20 to 1.56). Four studies met criteria for secondary analysis, providing data on 75,627 births, with a pooled prevalence of 0.75 CL/P cases per 1000 births (95% CI: 0.56 to 0.95). Comparison of studies was limited by variable definitions of cases and of the reference population and by inconsistent reporting of outcomes. There is significant heterogeneity in the findings.Conclusions: In LMICs, approximately 1 in every 730 children is born with CL/P. To optimize comparability across settings, future research should use a standard classification system and standard criteria for data collection and presentation. As clefting is associated with deprivation, understanding the true scale, risks, and preventive measures for orofacial clefts in LMIC is a matter of both scientific and humanitarian importance.

Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families’ experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals’ views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information.

Background In 2010 the World Health Assembly called for action to improve the care and prevention of congenital disorders, noting that technical guidance would be required for this task, especially in low- and middle-income countries. Responding to this call, we have developed a freely available web-accessible Toolkit for assessing health needs for congenital disorders. Methods Materials for the Toolkit website (http://toolkit.phgfoundation.org) were prepared by an iterative process of writing, discussion and modification by the project team, with advice from external experts. A customized database was developed using epidemiological, demographic, socio-economic and health-services data from a range of validated sources. Document-processing and data integration software combines data from the database with a template to generate topic- and country-specific Calculator documents for quantitative analysis. Results The Toolkit guides users through selection of topics (including both clinical conditions and relevant health services), assembly and evaluation of qualitative and quantitative information, assessment of the potential effects of selected interventions, and planning and prioritization of actions to reduce the risk or prevalence of congenital disorders. Conclusions The Toolkit enables users without epidemiological or public health expertise to undertake health needs assessment as a prerequisite for strategic planning in relation to congenital disorders in their country or region.

The first epidemiological study for thalassemia in Cyprus was performed by Fawdry in 1946. The study determined that the frequency of β-thalassemia (β-thal) carriers was around 18.0% and that of α(0)-thal carriers (individuals with both cis α-globin genes inactive) at around 2.0%. In 1998, another study concluded that Cyprus had one of the highest frequencies of β-thal carriers worldwide (17.2%). Based on Haldane's hypothesis that malaria might be the selective agent responsible for the maintenance of high levels of thalassemia and sickle cell disease in many populations around the world, it is expected that following the eradication of the disease in Cyprus in 1948, the carriers of β-thal should decline with each generation. In order to determine whether this has been the case, we compiled frequency data for β-thal carriers from three separate surveys performed as part of the Cyprus National Thalassaemia Screening Programme (NTSP). The surveys were carried out in 1986, 2003 and 2010 involving 9622, 6711 and 5228 subjects, respectively. The expected drop in the prevalence of β-thal carriers for each successive generation following the eradication of malaria, i.e., in the absence of selection pressure, was calculated using the Hardy-Weinberg equation and the mathematical model of Hartl and Clark. The surveys provide supporting evidence for the decrease of the frequency of the β-thal carriers in the Greek Cypriot population, with a drop of 1.89% in 24 years.