Achieving the targets of sustainable development goals (2030 agenda) for congenital disorders in Asia: Bottlenecks and interventions

1 INTRODUCTION

The Millennium Development Goals (MDG) Report in 2015 by the United Nations showed that it was successful in reducing poverty and mortality globally (United Nations Millennium Development Goals Report, 2015). The global under-five mortality rate has declined by more than half, dropping from 90 to 43 deaths per 1,000 live births from 1990 to 2015. Since the early 1990s, the rate of reduction in under-five mortality has more than tripled globally and in Asia, reduction of 60–78% was reported. The majority of these deaths were prevented due to improvements in hygiene, immunization, and treatment of infectious diseases. In particular, measles vaccination helped to prevent nearly 15.6 million deaths between 2000 and 2013. Despite these successes, the report also showed there were gaps or disparities. Much of the achievements tended to bypass women and those who are in the lowest socioeconomic group or disadvantaged because of their condition, disability or age.

In 2015, the 2030 Agenda for sustainable development goals (SDG 2030) were adopted post-MDG with 17 sustainable development goals as its targets (United Nations, 2017). The focus is on continuing the progress made in MDGs as well as to reduce noncommunicable diseases (NCDs). This focus on NCDs meant that congenital disorders and genetic conditions will be included for prevention and control globally. In particular, the SDG three included targets to end preventable deaths of newborns and children under 5 years of age by 2030, universal health care coverage, reduction of premature mortality from NCDs by 33% as well as support the development and research for medicines for both communicable and NCDs. These new targets meant that both curative and preventive strategies are needed to prevent congenital disorders.

The World Health Assembly reported concerns that birth defects were not recognized as a priority in public health (World Health Assembly, 2010). During the seventh international conference on birth defects and disabilities in the developing world (ICBD7) in Dar-es-Salaam in 2015, experts and stakeholders from 37 countries reported that children with congenital disorders continued to be left behind in policies, programs, research, and funding (Darmstadt, et al., 2016). The ICBD7 identified several major hurdles and proposed some recommendations to overcome these limitations and discussed plans on how to accelerate the prevention of congenital disorders and the improvement of care of affected children, especially in high burden, low-resource settings globally. It was reported that a review showed the rate of progress in many areas is far slower than needed to meet the targets by 2030. Some of the issues identified that needed urgent attention included the need to improve healthcare data quality and availability, reducing inequalities within and among countries, renewed efforts to reduce infant mortality rate and a critical shortage of skilled manpower and healthcare funding (United Nations, 2017).

2 CONGENITAL DISORDERS: THE NEED FOR COMMON DEFINITION AND ACCURATE DATA

Congenital disorders (also known as birth defects or congenital anomalies) were defined by the World Health Organization as any potential pathological conditions arising before birth, whether evident at birth or manifesting later in life (March of Dimes, World Health Organization., 2006). Modell divided congenital disorders into two broad groups. The first group consisted of congenital disorders due to environmental exposure to teratogens. The second group was constitutional congenital disorders due to various endogenous causes such as chromosomal disorders, single gene disorders, and disorders due to genetic risk factors (Modell et al., 2018). Earlier publications found there was lack of accurate information on the number of children born with a serious congenital disorder and the collection of data on the global burden of mortality and morbidity due to congenital disorders was recommended (Christianson, Howson, & Modell, 2006).

As a result of limited resources for the correct and accurate diagnosis of congenital disorders and inadequate information systems, these shortcomings led to gross underestimation of the contribution of congenital disorders to early death and morbidity. To overcome the limitations due to the extreme heterogeneity of congenital disorders as well as the need for a common set of precise terminology for congenital disorders, the Modell global database of congenital disorders (MGDb) was developed (Modell et al., 2016). There was wide differences between current calculations of mortality and morbidity due to congenital disorders produced by the global burden of disease study (GBD) and WHO compared to the report by the March of Dimes (MOD) and MGDb on the other (Liu, Cousens, Lawn, & Black, 2012; Lozano et al., 2012; Modell et al., 2012). Analysis showed that the major cause of the difference was due to the lack of agreed technical terminology for reporting. (Liu et al., 2015; Modell et al., 2018).

This situation is not surprising as the classification of congenital disorders have been challenging due to the heterogeneity and its classification under various medical or surgical disciplines. The international classification of diseases 10th edition (ICD10) is arguably the most widely used disease nomenclature world-wide. The availability of a standardized disease classification for rare congenital disorders is extremely vital for epidemiological study and comparison, for research as well as used for allocation of healthcare resources. In addition, the online Mendelian inheritance in man (OMIM) catalog for human genes and genetic disorders (Amberger, Bocchini, Schiettecatte, Scott, & Hamosh, 2014) and Orphanet rare disease database are also widely used in some countries and academic circles (Rath et al., 2012). In 2015, when a comparison study (or cross-referencing) was made using the 2010 online version of the ICD10 and Orphanet which has over 6,954 clinical entities listed, only 355 were found to have a unique specific code in ICD10 and a mere 162 can be specifically mapped to a set of ICD10 codes (Aymé, Bellet, & Rath, 2015). In 2007, the WHO started the revision process of the ICD10, whereby a topic advisory group (TAG) for rare diseases was set-up, managed by Orphanet and funded by the European commission (EC) with the proposed adoption of the new codes in ICD11 by the World Health Assembly in 2017. It was reported that over 5,400 rare diseases which were listed in the Orphanet database have an endorsed representation in the foundation layer of ICD11, and were provided with a unique identifier in the beta version of ICD11. Nonetheless, there were significant technical challenges, delays, and lack of funding which resulted in the EC expert group on rare diseases to recommend ORPHA codes in addition to ICD10 codes for rare diseases having no specific ICD10 codes (www.orphadata.org.).

The 2016 WHO Global Health estimates reported that congenital anomalies or birth defects are amongst the top 20 causes of deaths amongst the NCDs globally (WHO, 2016). The joint WHO-MOD report estimated that 7.9 million children are born each year with a genetic or multifactorial congenital disorder. In addition, of the 2.7 million newborns that die annually, more than 10% of the deaths are due to congenital disorders. In addition, this number is likely an under estimation as many deaths due to congenital disorders, such as congenital heart defects and inherited metabolic disorders, are not diagnosed or remain undetected at birth. A systematic review analysis on global, regional, and national causes of child mortality in 2000–2013 showed that deaths due to congenital disorders, preterm births, and neonatal sepsis showed the slowest progress and improvements (Liu et al., 2015). Survivors with a serious congenital disorder will encounter a lifetime of severe disability (Vos et al., 2017). It was also estimated that up to 70% of congenital disorders are preventable or their effect can be reduced and their quality of life improved. While the past healthcare efforts were focused on reducing mortality due to congenital disorders, there is a need to shift focus to the needs of survivors with disability, to access disability services and to improve quality of life, education, and job opportunities (Darmstadt, et al., 2016). MGDb estimated there were more than two million survivors with significant disability at 5 years, globally and confirmed interventions could both reduce adverse outcomes of constitutional congenital disorders by 50–80% as well as the birth prevalence of environmental congenital disorders to a very low level (Modell et al., 2018).

3 CONGENITAL DISORDERS REGISTRY: PROVIDING TIMELY EPIDEMIOLOGICAL DATA

Accurate information on congenital disorders from population-based studies originating from low and middle-income countries in the Asia region is lacking (WHO Regional Office for South East Asia., 2013). There is a perception that congenital disorders are not a priority area in many health jurisdictions due to lack of data, lack of professional input from healthcare providers and not enough clinical geneticists caring for families with congenital disorders from this region and lack of representations in groupings and academic centers that published data on birth defects (Vos et al., 2017). Some of the major hurdles identified in the establishment of a congenital disorder registry in this region include lack of common terminology, paucity of population-based data, insufficient specialists to make the diagnosis, and maintain the registry. Above all, there is limited governmental funding or public health expenditure for prevention and care of patients with congenital disorders. Often health care authorities need evidence of cost-effectiveness of sustaining a registry before funding is allocated (Darmstadt, et al., 2016).

It is vital that quality data are made available for governments, international organizations, healthcare authorities, the private sector, patients' support groups, and the lay public to make informed decisions and accurate projections on the needs and services required. Increasingly there is a shift to genetic testing and genomics study of congenital disorders. Many of the low- and middle-income countries (LMICs) of the Asia region were found to have unsuitable service delivery models and weak health information systems (Samb et al., 2010). Moorthie et al. (2018) summarized that congenital anomalies registries have two main surveillance purposed. First, the registry must define baseline epidemiological data on important congenital anomalies and the second, to help identify clusters of cases and any other epidemiological changes that could trigger alerts on potential teratogenic hazards. The setting up of a sustainable program is resource-intensive requiring national infrastructure for recording all cases, diagnostic facilities and imaging to identify internal malformations. The International Collaborative Group on Global Epidemiology of Congenital Disorders developed the MGDb of congenital disorders that reported many novel recommendations based on their studies and analysis (Moorthie et al., 2018).

Many national birth defects registries in the Asia region used hospital-based reporting systems on sentinel disorders in live births by primary care doctors or nurses using local or research funding. Most of the congenital disorders were classified according to the ICD-10 and the reports are not mandated by law or legislations; hence, many do not publish their data or findings and accessibility of their data is limited. These limitations were previously discussed in other reports (Thong, 2014). In most countries, birth certificates do not routinely list birth defects or congenital disorders. The reason for this was unclear. It was possible that in LMICs, some deliveries were attended by nonmedical doctors and the diagnoses of birth defects were not made. To standardize the terminology and definitions, it is worthwhile to note that The March of Dimes and the WHO Human Genetics Programme had reached an understanding on the use of “birth defects” and “congenital disorder.” As mentioned earlier, the WHO burden of disease unit uses “congenital anomalies” that was defined as macroscopic morphological anomalies present from birth which excluded functional birth defects, disability, common single gene disorders such as cystic fibrosis, and glucose-6-phosphate dehydrogenase deficiency and inborn errors of metabolism. It was hoped that future reports on Global Burden of Disease will take this into account (Modell et al., 2018).

Ascertainment of infants with multiple birth defects remains a continuing challenge in the Asia region. This may require the assessment of a clinical geneticist familiar with Asian dysmorphology to make a syndromic diagnosis or to perform the appropriate investigations. Most of the earlier reports on dysmorphology were based on patients from Western countries. Fortunately, many dysmorphologists and clinical geneticists are aware of the need to be inclusive of all the major ethnic groups globally in their assessment of syndromes. It is encouraging to note that many major journals had taken steps to overcome these shortcomings (Koretzky et al., 2016) as well as dysmorphology databases that included patients from diverse populations (Vorravanpreecha, Lertboonnum, Rodjanadit, Sriplienchan, & Rojnueangnit, 2018). In addition, due to lack of facilities such as imaging and diagnostic laboratories, many patients with multiple birth defects were wrongly diagnosed. While patient with unique syndromes are individually rare, collectively they constitute an important public health burden. Therefore under-recognition of these conditions may lead to misallocation of resources. Increasingly, prenatal diagnosis and elective termination of pregnancies were performed in many communities, thus reducing the births of newborns with congenital disorder. However, the true prevalence remained the same as these procedures and stillbirths with congenital disorders might not be reported to the registries in some countries. Thus baseline data in these countries on congenital disorders may be inaccurate (Thong, 2012).

In order for some countries to produce estimates of prevalence of congenital disorders as a starting point for evaluation of disease burden and service implications needs, Moorthie et al. (2018) proposed an innovative method whereby reliable and validated registry data from high income settings was used to produce reference rates that can be used as provisional estimates on non-syndromic congenital malformations for countries with little or no observational data. Their analysis of EUROCAT registry data showed little significant country differences in the baseline birth prevalence of non-syndromic congenital malformations, other than neural tube defects and orofacial clefts (Boyd et al., 2011). They proposed the use of methods based on rates observed in high-income European settings, to obtain provisional global, regional and country estimates for the birth prevalence of these malformation groups in settings with no data, as a starting point (EUROCAT, 2015). They cautioned that while these methods do not provide precise estimates, but may be sufficient for policy purposes, until more robust data become available through dedicated and sustainable surveillance systems. For documentation on frequency and healthcare burden of rare single gene disorders, Blencowe et al. (2018) proposed that it was necessary to aggregate them into large manageable groupings, effective interventions and service needs required and to take account of their psychosocial implications (Blencowe, Kancherla, Moorthie, et al., 2018). Their approach to estimate the burden of these disorders up to 5 years of age in settings without empirical data was to use 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 of healthcare planning services can utilize. The authors reported that besides estimating the birth prevalence and outcomes of rare monogenic disorders, it was possible to estimate the effects of consanguinity-related congenital disorders, the effects of paternal age as well as the potential effect of prospective carrier detection for the purposed of genetic counseling, family planning and control of these conditions. These non-ICD approaches may help to overcome current challenges in LMICs in the Asia region and to provide information on the effect of available interventions on their birth prevalence and outcomes. Some of the key interventions that impact on outcomes of congenital disorders and methods used to estimate their coverage were identified where empirical data are not available (Blencowe, Moorthie, Darlison, et al., 2018).

There is a paucity of studies on congenital disorders in LMICs in the Asia region and the cost effectiveness of a birth defects or congenital disorders registry (Thong, Ho, & Noor Khatijah, 2005). Many health care planners and governments are hesitant to commit public funds for these registers due to the lack of definitive evidence of cost-effectiveness. There may be underutilisation of the data from the registries due to lack of confidence in the findings or concerns related to their accuracy to serve as a teratogen warning system. Certainly, there is a need to increase professional and lay public awareness on congenital disorders and to enhance research collaboration in this region. Hence there is strong need for all registries of congenital disorders to publish their findings and methodology of data collection on a regular basis. With greater awareness, accurate information, provision of genetic services and genetic counseling, it is hoped that stigmatization and marginalization of individuals with congenital disorders may be further reduced (Laurino et al., 2018).

4 CONGENITAL DISORDERS OR BIRTH DEFECTS REGISTRIES IN THE ASIAN REGION

A review of literature on birth defects or congenital disorders registries in the Asia region showed paucity of reliable epidemiological data in the region published in the English language. Many health authorities recognized the need for a national birth defects or congenital disorders registry in their respective countries (Gupta, Kabra, & Kapoor, 2014; Padilla, Cutiongco, & Sia, 2003). Some countries published specific birth defects (Bermejo-Sánchez et al., 2011; Shapira, Hakla, Blum, Shpack, & Amitai, 2014) or pilot studies (Hoang et al., 2013). In the Republic of Korea, data were obtained from a pilot study based on the medical insurance claims database of the National Health Insurance Corporation and the conclusion, there was a need to establish a registry system of birth defects in Korea (Kim, Yee, Choi, Choi, & Seo, 2012) The international clearinghouse for birth defects surveillance and research (ICBDSR) was established in 1974 and published annual global epidemiological data on birth defects from 42 surveillance programs originating from 36 countries. It also prepared guidelines for data collection, coding, process, analysis, use, and evaluation of the system. Of the 42 surveillance programs, only Japan and Iran were regular contributing birth defects monitoring systems in Asia, while India (Chennai), Israel and Saudi Arabia were listed as “monitoring systems, not contributing with annual data.” No other Asian countries were listed in the ICBDSR website (Annual Report 2014, ICBDSR). It is possible that various Asian countries prepared their national data on birth defects for their respective health authorities but these reports are not routinely available for analysis.

It was reported in 2014 that the Queen Sirikit National Institute of Child Health initiated and established the Thailand Birth Defects Registry to capture birth defects among newborn infants with the aim to determine the burden of birth defects in Thailand. The registry collected data from four databases which were contributed by 20 participating hospitals. Hence, the registry was hospital-based using a hybrid reporting system and included only live births whose information was collected up to 1 year of age. The prevalence rate of major anomalies was 26.12 per 1,000 live births and the five most common birth defects were congenital heart defects, limb anomalies, cleft lip/cleft palate, Down syndrome, and congenital hydrocephalus, respectively (Pangkanon, Sawasdivorn, Kuptanon, Chotigeat, & Vandepitte, 2014). In Iran, the Tabriz Registry of Congenital Anomalies (TRoCA) was established using guidelines provided by the ICBDSR for data collection, coding, process, analysis, use, and evaluation of the system. The authors stated that TRoCA has successfully achieved its main objective as a pilot model for setting up a nationwide registry of congenital anomalies in Iran (Stone et al., 2017).

The Ministry of Health of China initiated a national hospital-based birth defects monitoring system in the 1980s which involved nearly every province in the country. The Chinese Birth Defects Monitoring Network (CBDMN) is a nationwide and hospital-based birth defects surveillance network covering a total of 450–471 hospitals (county level, city level, and provincial level) in China which monitored about 8–10% of the annual births in China (Dai et al., 2011; Li, Zheng, & Li, 1996). The CBDMN used the passive case ascertainment method to identify congenital malformations, including live births, stillbirths, and termination of pregnancy in the member hospitals. The surveillance period for each abnormality was from 28 weeks of gestation to the first 7 days after birth. These cases were recognized through physical examination by trained obstetric and pediatric clinicians postnatally. Cases diagnosed by prenatal ultrasonography were also confirmed by the postnatal records after delivery. A “Birth Defects Register Form” will be submitted and an online reporting is conducted quarterly. Pregnancies ending in stillbirth or elective termination of pregnancies (TOPs) including an autopsy report when available were reviewed to confirm or amend the final diagnosis. Written informed consent was obtained from the parents of neonates before they were discharged from the hospital. The consent mainly included the aims and importance of monitoring birth defects. The international classification of diseases, 10th revision, was used to code the diagnosis. In addition, a regional population-based system established and maintained by Beijing University in collaboration with the Centers for Disease Control and Prevention (CDC) of the United States of America (Li et al., 2003). This regional population-based system is a member of the ICBDSR. The main focus of earlier international policy recommendations was on prevention of congenital disorders due to teratogenic effects of environmental factors. These public health measures included vaccination programs for rubella and screening for syphilis, avoidance of alcohol intake and appropriate pregnancy care. It was estimated that these steps reduced the effects of these teratogens to about 15% of total congenital disorders. Conversely, constitutional congenital disorders were the secondary focus of public health policy recommendations, though these disorders have become prominent as other causes of early mortality and morbidity were gradually brought under control. (United Nations Millennium Development Goals Report (2015). In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, neonatal death, and chronic disability.

5 PREVENTION AND CONTROL OF THALASSEMIA IN THE ASIAN REGION

Some of the early efforts for prevention and planning of control programs of congenital disorders in Asian countries were focused on thalassemia and neutral tube defects. Thalassemia is a congenital disorder of hemoglobin manifested by the absence or decrease production of one or more of the globin chains in erythrocytes, resulting in chronic anemia and hypoxia as well multiple complications from the disease itself and from the regular blood transfusions that are needed to keep the patient alive. While sickle cell disease is more common in the Africa and west Asia, alpha and beta thalassemia are the main types of hemoglobinopathies in South, Southeast, and East Asia (Weatherall, 2010). Over 56,000 infants are affected annually and at least 5.2% of the global populations are carriers. Countries in the tropics have the highest incidence due to its association with malaria infections, where 7% of pregnant women are carriers (Williams & Weatherall, 2012).

In view of the serious ramifications to global health, the 63rd World Health Assembly In May 2010 adopted an additional resolution on the prevention and management of birth defects and the thalassemias. The WHO committed to increase awareness among the international community of the global burden of these disorders, promote equitable access to health services, provide technical support to countries for the prevention and management of these disorders as well as promote and support research to improve the quality of life of those affected. The global burden of disease (GBD 2010) was the first GBD to include the inherited disorders of hemoglobin in its assessment of disease burden where sickle cell disorders and the thalassemias were ranked 70th and 68th in terms of DALYs across all ages, respectively. For children in the 1- to 4-years age group, they ranked 17th and 24th, respectively. GBD 2010 estimated that thalassemias alone resulted in 17,860 (confidence interval, 15,071–20,430) deaths per year (Vos et al., 2017).

The prevention and control of thalassemias in any national program require a planned program and consultations with all the major stakeholders to establish the various components needed to ensure its success. The program must include an education component for the professionals and public, optimal treatment of the affected patient including safe blood transfusion and iron chelation therapy, cascade screening of the family and population-wide screening, a registry to provide epidemiological data and a preventive program that may include genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis (Monni, Peddes, Iuculano, & Ibba, 2018). This holistic approach is cost-effective and had proven to be successful in reducing the frequency of thalassaemia in many countries such as Cyprus and Greece (Kyrri et al., 2013; Ladis, Karagiorga-Lagana, Tsatra, & Chouliaras, 2013). The cost of a total prevention program has been demonstrated to be 10–20% of the cost of treating the existing affected patients.

Following the success of some countries in the Mediterranean region such as Cyprus, Italy, and Greece, several Asian countries including China, India, Lebanon, Pakistan, and Iran are running prospective programs for the prevention of thalassaemia. More than 85% of all pregnant women in Thailand were reportedly screened for thalassaemia trait. A pilot study at Chiangmai University, North Thailand where thalassemia is most prevalent, showed a reduction of all new cases of severe thalassaemia diseases (Fucharoen, Sanchaisuriya, Sae-ung, Dangwibul, & Fucharoen, 2004). In the last two decades, many Asian hematologists and geneticists collaborated as the Asian Network for Thalassaemia Control to disseminate good practice in the control and management of thalassaemia in Asia and to provide a central forum for interacting with individual governments and international health agencies to provide support. The main aims of this network included the development and dissemination of adequate screening techniques to determine the frequency of the different forms of thalassaemia in Asian countries, education and screening programs, discussions about the possibility of prenatal diagnosis in view of cultural and religious sensitivities and the need to have a complete profile of genotype–phenotype correlation information and the development of appropriate approaches to treatment (Fucharoen & Winichagoon, 2011). Many areas hitherto not studied before in Asia were investigated for the molecular basis of thalassemia. For example, a study on beta thalasaemia major amongst the Kadazandusun population in remote areas in Sabah, Malaysia, revealed that the Filipino deletion was the most common mutation of the beta globin gene, suggesting a founder effect. Hence the molecular basis for beta thalassemia in North Borneo was elucidated resulting in detailed information been available for genetic counseling and prenatal diagnosis (Thong et al., 1999). Another notable achievement was the effort to provide health education for control and prevention of thalassemia in Cambodia which never had any past education programs on thalassemia. Following a health education program held in Phnom Penh, it was found from the study that the level of knowledge and the intention to undergo screening was significantly higher in the intervention group than the control group. The authors concluded that health education clearly heightens awareness and improves consideration of screening for prevention and control of severe thalassemia (Cheng et al., 2018).

6 PREVENTION AND CONTROL OF NEURAL TUBE DEFECTS (NTDS)

In contrast to the progress made in thalassemia in Asian countries, prevention and control of NTDs had been rather muted. The NTDs consist of two major forms of malformations: anencephaly which is life-limiting and spina bifida which may cause serious brain and spinal cord malformations leading to life-long disabilities as well as severe socioeconomic hardships and reduced quality of life. World-wide, the birth prevalence of NTDs is reported to be 18.6/10,000 live births with the highest number found in Southern Asia and East Asia regions with live birth prevalence of NTDs of 31.2 and 19.4/10,000, respectively. About 50% of cases were elective terminations of pregnancy for fetal anomalies or stillbirths while 75% of affected livebirths with NTDs resulted in under-five deaths (Atta et al., 2016; Blencowe, Kancherla, Moorthie, et al., 2018). The majority of cases can be prevented by ensuring adequate blood folate concentrations in the mother before conception and during early pregnancy (Kancherla, 2018). Hence, all women in their child-bearing age are recommended to take at least 400 μg of folic acid daily at least 1 month before conception (Crider et al., 2014). Despite these achievements and knowledge of prevention of NTDs using folic acid in food fortification program, NTDs continue to be highly prevalent globally. A systematic review showed a paucity of high-quality data in the regions of the world with the highest burden. (Blencowe, Kancherla, Moorthie, et al., 2018; Blencowe, Moorthie, Petrou, et al., 2018).

The Food Fortification Initiative (FFI) is an international partnership that collects data from various country leaders on grain fortification legislation, national industrial milling capabilities, and national fortification status. The FFI reported that only 81 countries currently have mandatory wheat and/or maize flour fortification legislation that include folic acid. Over 100 countries, including many LMICs in Africa and Asia, as well as some high-income countries in Europe, have yet to implement fortification. Kancherla (2018) reported a novel approach in trying to encourage countries to implement a mandatory fortification of wheat flour with folic acid. The authors applied several evidence-based criteria on the current fortification status for these countries. Among the criteria used were whether the country provided full fortification or only fortified less than 50% of industrially milled wheat flour, whether the country's existing industrial capacity of producing at least 30% of its flour production, and whether the fortified wheat flour available for human consumption amounted exceeded 75 g per person per day. These were employed to provide a comprehensive assessment of fortification potential in each country. They identified 71 countries with an immediate potential for mandatory fortification of wheat flour with folic acid. Out of these, seven countries from Asia fulfilled the requirements. These are China, Mongolia, South Korea, Japan, Malaysia, Brunei, Sri Lanka. Further analysis showed that post-fortification with folic acid will save 16,500 live births from NTDs annually assuming a post-fortification prevalence of 0.5 NTDs per 1,000 births globally. The folic acid fortification of food will increase global prevention from the current rate of 13% to a new rate of 34%. This fortification with folic acid can be achieved immediately in these countries within their existing centralized milling infrastructure (Kancherla, 2018).

The fortification of food with folic acid is safe and it was established that mandatory fortification alone does not contribute to exceeding the upper limit of daily folic acid intake in our diet (Orozco, Yeung, Guo, Carriquiry, & Berry, 2016). It was also estimated that the actual benefit of folic acid fortification may be higher due to various reasons. For example, the country specific prevalence estimates derived from the March of Dimes Global Report on Birth Defects are known to be conservative, and likely to be an underestimation (Christianson et al., 2006). In addition, most of the estimates are potential based on live births data and did not include stillbirths or termination of pregnancies. Even among countries with mandatory fortification, it has been established that fortified foods may not reach all of the target population (Rosenthal et al., 2016). A study in Malaysia showed that the birth prevalence of NTDs varies according to the ethnic groups and locations in the country (Boo, et al., 2013). Hence any food fortification must be targeted to the appropriate high-risk groups in that country. In addition, appropriate enforcement and quality assurance mechanisms must be in place to stimulate compliance by food producers (van den Wijngaart, Begin, Codling, Randall, & Johnson, 2013). In the case of NTDs, there is an urgent need for sustained political will to ensure governments and food producers work together to ensure folic acid fortification.

7 CONCLUSIONS

There are concerns that the SDG (2030 Agenda) for congenital disorders in Asia may not be achieved due to various bottlenecks in the healthcare delivery systems. Hence, there is an urgent need to identify these challenges and to recommend evidence-based data and relevant interventions to achieve these targets. Although some successes were achieved in combating communicable diseases and improving childhood mortality rates, there were a number of obstacles and bottlenecks in the health systems in Asia. These included the lack of accurate epidemiological information on congenital disorders, lack of human and financial resources, inadequate focus on public health strategies to ensure targeted interventions, low level knowledge on congenital disorders amongst the community and healthcare providers and the difficulty managing rare congenital disorders in an environment of low national health expenditures. The examples given of thalassaemia and neural tube defects showed the limitations and at the same time, the possibilities that may be achieved in line with the goals of SDG2030. The bottlenecks above needed to be addressed systematically and appropriate interventions must be identified and implemented. These included innovative epidemiological tools to overcome lack of data in LMICs, efforts to standardize rare disease nomenclature and classification and the renewed interest in birth defects registries in the region. While some successes were achieved in prevention and control of hemoglobinopathies and neural tube defects in a few Asian countries, more sustained efforts were required by public health experts and healthcare providers to ensure both curative and preventive approaches are used optimally for these and other conditions. Finally, there must be a concerted effort by all health authorities to relook at achieving the targets of SDG (2030 Agenda) for congenital disorders in Asia as part of their national health care agenda. The implementation of congenital disorders-related research, prevention, care, and treatment delivery services must be integrated into existing health systems in order to be effective.

CONFLICT OF INTEREST

The author declares no conflict of interest.