Scholarly article on topic 'Barriers to implementing sustainable national newborn screening in developing health systems'

Barriers to implementing sustainable national newborn screening in developing health systems Academic research paper on "Economics and business"

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Abstract of research paper on Economics and business, author of scientific article — Bradford L. Therrell, Carmencita D. Padilla

Abstract Newborn screening is a comprehensive public health prevention system that seeks to identify newborns at increased risk for certain inherited congenital conditions. Institutionalizing and sustaining this system presents a formidable challenge within developing public health systems often competing with other healthcare priorities and political agendas. We review some of our experiences in overcoming newborn screening implementation challenges and discuss recent efforts to encourage increased newborn screening through support networking and information exchange activities in the Middle East/North Africa and in the Asia Pacific Regions.

Academic research paper on topic "Barriers to implementing sustainable national newborn screening in developing health systems"

International Journal of Pediatrics and Adolescent Medicine (2014) 1, 49-60

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Barriers to implementing sustainable national newborn screening in developing health systems*

Bradford L. Therrell Jra b *, Carmencita D. Padillacd

a National Newborn Screening and Global Resource Center, Austin, TX, USA

b Department of Pediatrics, University of Texas Health Center at San Antonio, San Antonio, TX, USA c Department of Pediatrics, College of Medicine, University of the Philippines — Manila, Manila, Philippines

d Newborn Screening Reference Center, National Institutes of Health (Philippines), Ermita, Manila, Philippines

Received 9 February 2014; accepted 28 April 2014 Available online 13 November 2014

Abstract Newborn screening is a comprehensive public health prevention system that seeks to identify newborns at increased risk for certain inherited congenital conditions. Institutionalizing and sustaining this system presents a formidable challenge within developing public health systems often competing with other healthcare priorities and political agendas. We review some of our experiences in overcoming newborn screening implementation challenges and discuss recent efforts to encourage increased newborn screening through support networking and information exchange activities in the Middle East/North Africa and in the Asia Pacific Regions.

Copyright © 2014, King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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KEYWORDS

Newborn screening; Barriers; Sustainable; Developing countries

* Submitted from: National Newborn Screening and Global Resource Center, University of Texas Health Science Center at San Antonio (Department of Pediatrics), Austin, TX, USA.

* Corresponding author: National Newborn Screening and Global Resource Center, 3907 Galacia Drive, Austin, TX 78759, USA. Tel.: +1 512 921 1400.

E-mail addresses: therrell@uthscsa.edu (B.L. Therrell), cdpadilla@upm.edu.ph (C.D. Padilla).

Peer review under responsibility of King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia.

1. Introduction

The term 'newborn screening' generally describes various tests that can occur during the first few hours or days of a newborn's life. These screening tests have the potential for preventing catastrophic health outcomes to newborns and their family when they are properly timed and performed. Newborn dried bloodspot screening (NDBS) is one type of

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2352-6467/Copyright © 2014, King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

screening that uses blood collected from the baby's heel, placed onto special absorbent paper, air dried, and transported to a screening laboratory for analysis. The presence of abnormal concentrations of certain biochemical markers can indicate increased risks for the condition of interest and must be confirmed through further diagnostic testing. Other types of NBS include hearing loss and congenital heart defects, among others, but this manuscript focuses on NDBS screening.

To provide national uniformity and equality, NDBS programs are generally part of the national public health prevention system. While in their initial phase, NDBS programs may exist in academic or private settings, and their institutionalization and sustainability at the national level require recognition by the health ministry and integration into the public health system. This recognition can take different forms in different settings ranging from simple recognition statements to full-scale program implementation and support. Although government financing is ideal and assures sustainability, there are successful programs in which full or partial payment is made by the family obtaining the screening service.

NDBS programs function within a comprehensive system that includes education, screening, short-term follow-up, diagnosis, treatment/management, and long-term follow-up/evaluation [1]. The NDBS system is often challenged by economic, political, and cultural considerations. The initiation of NBS in developing health systems, such as many in the Middle East and North Africa (MENA) and the Asia Pacific (AP) regions, has been slow for various reasons, including lack of understanding by the individual as well as family, societal, and financial benefits. All countries with NDBS either have faced or will face challenges in implementing NBS; however, many developing health systems face additional challenges related to the economy, government stability, culture/religion, geography, and health/political priorities [2—6].

The countries in the MENA and AP regions vary widely in size from small countries (e.g., Bahrain, Lebanon, Qatar, Kuwait, New Zealand, and Singapore) to large countries (e.g., Saudi Arabia, Egypt, Iran, Libya, Algeria, China, and Mongolia). Some countries are economically advanced (e.g., Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Australia, Japan, New Zealand, and Singapore), whereas others are economically developing (e.g., Iraq, Iran, Syria, Jordan, Morocco, Libya, Algeria, Yemen, Philippines, Indonesia, Sri Lanka, and Vietnam). Out-of-hospital births remain a challenge in Bangladesh (80%), India (61%), Philippines (62%), Pakistan (80%), Laos (85.7%), Iran (34.4%), Palestine (38.8%) and Yemen (50%) [3,4,6]. Written languages that use character sets not readily understood by outsiders (e.g., Arabic, Chinese, and Thai) also present special challenges, particularly to experts on developed programs who cannot easily communicate their experiences or share educational materials. Despite these variabilities and challenges, NDBS champions continue to press for progress in the more progressive developing health systems in both regions [2—6].

Historically, successful NDBS has developed from the efforts of an interested individual or group of individuals concerned with improving the health outcomes for new-borns and their families. In limited cases (usually in small

countries, such as Singapore and Hong Kong), the NDBS program has developed as a government service. However, academic and hospital initiatives have become more common. Without recognition of the importance of NDBS by the health ministry, these initiatives have often remained isolated and have exhibited slow progress. Their institutionalization at the national level invariably requires intersection with government public health activities. Sometimes, these efforts have taken years to develop into a comprehensive system that adequately serves all newborns. Success in the development and institutionalization of NDBS has typically resulted from the perseverance of dedicated leaders who work to gain the required expertise in NDBS medical and laboratory science and whose perseverance results in overcoming the political, cultural and economic challenges [7].

Through our efforts in working with individuals and groups seeking to begin and improve NDBS in both developed and developing health systems, we have identified four strategic elements useful for developing a successful and sustainable NDBS program. These include the following: (1) identifying and nurturing strong leadership with the goal of educating others, designing and carrying out pilot studies to obtain data for health policy development, and gathering program support from potential stakeholders (parents, professionals, and policymakers); (2) initiating strategic advocacy initiatives targeted at providing policymakers, health professionals and the general public with a basic understanding of the operation and value of NDBS; (3) developing and maintaining strong collaborations between NDBS stakeholder groups (government organizations, non-government organizations, and individuals) in planning and implementation; and (4) developing innovative and sustainable financing strategies.

In this manuscript, we briefly summarize the current status of NBS efforts in a large part of the developing world (MENA and AP), review some of the challenges associated with implementing and sustaining NDBS in a developing healthcare environment, and discuss some example approaches and experiences in overcoming internal barriers to NBS implementation. Whenever possible, we provide examples of successful NDBS program activities, acknowledging that there are many other examples of success that are not noted here.

2. Screening in the Middle East/North Africa and the Asia Pacific regions

Table 1 summarizes selected demographic data for the countries in the MENA and AP regions with developing NDBS systems. These data are the latest available from the World Health Organization (WHO) and provide comparisons of population totals, annual births, gross national income, fertility rates, infant mortality rates and percentages of government budgets allocated for health [8—10]. A summary of published NDBS screening data in the two regions is also given. Accurate data from developing programs are sparse, and the data listed may not be current, particularly that for MENA [2—4,6].

It is interesting to compare the percentages of government expenditures for health in 2000 and 2008 because this

Table 1 Selected demographics for countries with developing NDBS programs in MENA and AP regions.

Country Total population Annual births Infant mortality GNI per Total % Central government Percentage of

(thousands)a (thousands)a (per 1000 live capita fertility expenditures expended newborns

births)a (US$)a'b ratec on healthd screened annuallye

2011 2011 1990 2011 2011 2011 2000 2008

Middle East and North Africa

Algeria 35,980 712 54 26 4470 2 9.0 10.6 —

Bahrain 1324 23 18 9 15,920 3 10.2 10.3 —

Egypt 82,537 1886 63 18 2600 3 7.5 5.9 94.4

Iran (Islamic 74799 1255 47 21 4520 2 8.4 8.7 84.4

Republic of)

Iraq 32,665 1144 37 31 2640 5 1.3 3.1 —

Jordan 6330 154 31 18 4380 3 11.0 16.3 —

Kuwait 2818 50 14 9 48,900 2 5.5 6.1 —

Lebanon 4259 65 27 8 9110 2 8.0 12.3 31.4

Libyan Arab 6423 144 33 13 12,320 3 6.0 5.5 —

Jamahiriya

Morocco 32,273 620 64 28 2970 2 4.0 6.6 —

Occupied 4147 148 — 24 1230 5 — — —

Palestinian

Territory

Oman 2846 50 36 7 19,260 2 7.1 4.9 98.9

Qatar 1870 21 17 6 80,440 2 5.0 6.8 100.0

Saudi Arabia 28,083 605 34 8 17,820 3 9.2 8.4 13.7

Syrian Arab 20,766 466 30 13 2750 3 6.5 4.6 —

Republic

Tunisia 10,594 179 40 14 4070 2 8.1 10.4 —

United Arab 7891 94 19 6 40,760 2 7.6 8.9 100.0

Emirates

Yemen 24,800 940 89 57 1070 5 8.3 4.3 —

East Asia and the Pacific

Cambodia 14,305 317 85 36 830 3 8.7 9.0 —

China 1,347,565 16,364 39 13 4930 2 11.1 10.3 -59

Indonesia 242,326 4331 54 25 2940 2 4.5 6.2 <1

Korea (North) — No data available —

Lao People's 6288 140 102 34 1130 3 5.1 3.7 -7

Democratic

Republic

Malaysia 28,859 579 15 6 8420 3 6.2 6.9 >95f

Mongolia 2800 65 76 26 2320 2 10.7 7.5 -6

Nepal 30,486 722 94 39 540 3 7.7 11.3 —

Palau 21 <1 27 14 7250 — 12.0 16.6 >70

Philippines 94,852 2358 40 20 2210 3 7.0 6.1 - 28

Vietnam 88,792 1458 36 17 1260 2 6.6 9.3 -7

South Asia

Bangladesh 150,494 3016 97 37 770 2 7.6 7.4 <5

India 1,241,492 27,098 81 47 1410 3 3.9 4.4 <1

Pakistan 176,745 4764 95 59 1120 3 2.3 3.1 <1

Sri Lanka 21,045 373 24 11 2580 2 6.9 7.9 -3

a The data are from Ref. [8] with the exception of the data for Occupied Palestinian Territory, which were obtained from Ref. [9]. b GNI per capita - The gross national income (GNI) is the sum of value added by all resident producers plus any product taxes (less subsidies) not included in the valuation of output and any net receipts of primary income (compensation of employees and property income) from abroad. The GNI per capita is the gross national income divided by the midyear population. The GNI per capita in US dollars is converted using the World Bank Atlas method Ref. [8].

c Total fertility rate - Number of children who would be born per woman if she lived to the end of her childbearing years and bore children at each age in accordance with prevailing age-specific fertility rates Ref. [8]. d The data are from Ref. [10].

e The data for MENA countries are from Refs. [2,3], and the data for Asia Pacific countries were obtained from Refs. [4,6]. f The percentage of infants screened refers to G6PD only, as reported in Ref. [6]; the extent of coverage for congenital hypothyroidism is not known.

can serve as an imperfect indicator of a governments' potential for supporting a new program, such as NDBS. The infant mortality rates (IMR) in 1990 and 2011 are provided to emphasize the trends and improvements over time across the two regions and to emphasize the growing importance of establishing NDBS as a public health prevention program. The March of Dimes' Global Report on Birth Defects notes that genetic and congenital conditions are increasingly important in the overall public health impact once the infant mortality falls below 50 per 1000 births [11]. There have been significant improvements in the infant mortality rates in the MENA and AP regions over the past two decades. With the exception of Yemen and Pakistan, all of the countries in these two regions reported infant mortality rates in 2011 that were lower than 50/1000 births.

In the MENA region, larger percentages of consanguineous marriages are known to contribute to an increased number of problematic genetic conditions in newborns [12—15]. For this reason, it may be argued that NDBS for inborn errors in the metabolism is more important in MENA than in many other parts of the world. Previous NDBS data from the MENA region and recent pilot NDBS studies in Bahrain and Oman tend to confirm this argument [2,16,17]. Similarly, screening for congenital hypothyroidism is generally accepted to be a universal problem that affects approximately 1:2500 newborns worldwide, with higher prevalence in iodine-deficient areas, which exist within MENA and AP [7]. Certain hemoglobin disorders, such as thalassemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency, are also present in many parts of both regions, and sickle cell anemia is even found in some locations [18—22]. Thus, the consideration of NDBS programs for multiple conditions (sometimes called 'expanded screening') is increasingly important.

For the development of a new NDBS programs, it is critical to gain knowledge from developed programs and to be aware of successful development strategies in neighboring countries. Thus, several knowledge-sharing conferences and implementation workshops have been conducted in both the MENA and AP regions. These conferences have provided opportunities to develop communications networks within the two regions and to learn from international experts, who provide a knowledgebase on which to build stronger program infrastructures. The results of some of these meetings have been published, and other reports are in development [3,6]. Three MENA regional meetings have been held in Marrakech, Morocco (2006), Cairo, Egypt (2008) and Doha, Qatar (2011). A fourth is being organized as a collaboration between local NDBS advocates and the International Society for Neonatal Screening (ISNS) but a date and location have not yet been determined. The first three meetings were primarily supported with funding from the U.S. National Institutes of Health (NIH) and, as such, included significant emphasis on possible research initiatives that may assist in NDBS program development (research is the primary mission of NIH). Workshops were also part of the conferences and focused on local NDBS program development and quality improvement with country progress reports and goal setting as the primary discussions.

The AP meetings were organized under slightly different circumstances. Building on previous regional conferences as part of an International Atomic Energy Agency (IAEA) project, the Philippine Newborn Screening Reference Center took the lead in organizing a continuing string of conferences/workshops for NDBS programs within the AP with national coverages of less than 50% of all newborns. Funding support was obtained from both commercial and noncommercial sources. To date, there have been four regional NDBS meetings: Cebu, Philippines (2008), Manila, Philippines (2010 and 2012), and Cebu, Philippines (2013). The conference attendees requested and received official acknowledgment as a working group of the Asia Pacific Society of Human Genetics. As with MENA, these meetings have included experts from developed screening programs and representatives from national screening projects and health ministries within the AP region. The programs have focused on identifying and overcoming internal barriers to national NDBS program implementation, infrastructure development and quality assurance. Continuous reviews/ updates of each country's NDBS 'plan of action' are available. Future meetings are anticipated at approximately two-year intervals.

Participants from 18 MENA countries at the first MENA conference developed an output document, the 'Marrakech Declaration,' noting that, "Newborn screening is an important tool in the prevention of disease and disability in our children and thus should be a key part of a comprehensive public health system in all of our countries." To emphasize the importance of NBS to health ministry officials and other stakeholders, the conference participants recommended that "... all countries in the region should screen for at least one condition and develop a national model program that takes into account all aspects for post-testing care." [3] At the first AP conference, the participants from 11 countries developed the 'Cebu Declaration' as an output document with a similar intent [6]. Despite the relatively simple goal of screening one condition in each country, many of the low-and middle-income countries in each region still face significant implementation challenges, particularly in countries in which health systems are stressed.

3. Challenges associated with implementing NDBS in a developing healthcare system

Experiences in the implementation of successful NDBS programs in both developed and developing healthcare systems appear to focus on addressing the following ten challenges to successfully implement a sustainable NDBS program:

(1) Planning — NDBS momentum is created through visionary ideas that can be molded into a systematic approach to a sustainable national NDBS program. Once logically developed, the program plan provides a foundation on which to establish the other elements necessary for success.

(2) Leadership — Successful program implementation usually requires passionate leadership (individual or group) with an ability to understand and address

challenges. Leaders must clearly convey ideas and successfully motivate others. The initiation of a new program or new ideas usually requires time, and leaders must be willing to make the required time investment.

(3) Education — New ideas result from the accumulation and transfer of new knowledge. The education of professionals, policymakers and the public must be provided in a carefully thought-out way that addresses stakeholder concerns that may adversely affect successful program implementation.

(4) Medical support — For a new or expanded medical program, such as NDBS, to succeed, the medical community must accept it. Program leaders must have sufficient knowledge and vision to address medical questions in a manner that builds confidence and collaboration among peers. Successful NDBS requires timely and appropriate diagnosis and treatment, which requires the cooperation of primary care and specialty healthcare providers.

(5) Technical support — Because NDBS analytical protocols are micro-techniques that differ from routine medical laboratory tests, implementation usually requires some technical training and knowledge sharing. Similarly, specimen collection and transport as well as the post-analytical processes of result reporting and follow-up (including clinical and laboratory confirmation) are essential pre-analytical processes that must be properly executed. Analytical technical support is often available from product vendors specializing in NDBS, and pre- and post-analytical support can be obtained from other more developed NDBS programs.

(6) Logistical support — Mechanisms must be developed for obtaining and distributing blood collection supplies, training the testing and follow-up personnel, transporting specimens to the screening labo-ratory(ies), providing for screening laboratory operations (equipment, supplies and maintenance), maintaining appropriate records, and reporting the screening results quickly while addressing cultural and other sensitivities.

(7) Protocol/policy development — Institutionalized policies and protocols addressing all NDBS system components prevent confusion and unnecessary overlap. Six system components should be addressed: education, screening (including considerations of consent/ dissent for testing, data sharing, and residual specimen storage and use), follow-up/tracking, diagnosis, treatment/management, and evaluation/quality improvement. A comprehensive listing of possible program elements that may be included in policy/ protocol development [Program Evaluation and Assessment Scheme (PEAS)] has been published and may provide a useful planning tool. [23]

(8) Administration — Strong leadership, planning and policy development should lead to efficient and effective program administration/management. Successful patient outcomes will be achieved with properly functioning program components and timely and optimized medical management. Good program

administration should ensure that improved newborn health is attainable within the confines of the healthcare system.

(9) Evaluation — Outcome monitoring by observation of disorder-specific sentinel events provides a means for NDBS system evaluation and should be designed to assist with continuing program improvements. Similarly, indicators of the successful function of other NDBS system components, including external laboratory proficiency testing, should be monitored as part of an overall quality assurance program. The PEAS tool noted earlier has been modified for this purpose in at least one NDBS program [23,24].

(10) Sustainability — To become sustainable, the NDBS system must be integrated into a functioning public health system and be adequately financed. Some countries have been successful in obtaining approval for financing through national public health insurance programs, but this process is often slow and incomplete. As a result, other financing schemes, including a fee system, should be considered. Many developed programs implore a system in which birthing facilities purchase screening kits (collection cards) and are responsible for their own reimbursement. In such cases, care must be taken to limit the administrative/collection charges that may be added to the test cost to the patient; otherwise, the patient charges will become excessive and counterproductive. When fees are considered, all program costs, including both laboratory and non-laboratory screening elements (i.e., program administration, equipment, education, public relations, follow-up, and specimen storage), must be considered [25,26].

4. Elements in overcoming NBS implementation challenges

The ten challenges previously listed have been successfully dealt with to varying degrees in all developed and developing NDBS programs. The identification of local champions for NDBS who are willing to spend the necessary time to achieve successful implementation is essential to success. In most cases, the impetus for NDBS has originated from local champions who have learned of the importance of screening from the experiences of other countries. The ability of NDBS champions to obtain support from and involvement of the health ministry directly impacts the speed of NDBS implementation and its subsequent expansion. Expert advice from both within and external to a developing NDBS program is also essential to successful program development. Collaborations between government and non-government organizations (including religious leaders) offer unique opportunities that can result in quantifiable population health benefits. Ultimately, NDBS must be embraced by a knowledgeable public intent on improving child health and society, and the successful involvement of supportive media representatives (press, radio, television) can often assist in providing this knowledge.

4.1. Acknowledging the rights of the child

The UN Declaration of the Rights of the Child and The UN Convention on the Rights of the Child have been particularly useful for approaching government policymakers in the developing world regarding NDBS [27,28]. Recognizing the 'Rights of the Child' has often been used as part of the argument for persuading government policymakers of their responsibilities in providing NDBS as a preventative measure for improved newborn and child health. Both the Marrakech and Cebu Declarations make reference to these UN activities [3,6]. Most countries are now signatories to the Convention, which requires signatories to "recognize the right of the child to the enjoyment of the highest attainable standard of health" [Art. 24(1)]. In ensuring these rights, parties are to take appropriate measures to "diminish infant and child mortality" [Art. 24(2a)] and to "ensure the provision of necessary medical assistance and healthcare to all children with emphasis on the development of primary healthcare" [Art. 24(2)] [28].

4.2. Leveraging government resources

Often, NDBS champions are not government employees (public servants), and their knowledge of NDBS originates from training or research experiences in more developed settings. In some cases, their initial intent is to establish a small NDBS program to the benefit of a local group of patients in a limited setting, such as a private hospital of an academic center. In developing national health systems, it is thus not surprising to find that more than one effort may be ongoing to establish a NDBS program. This sometimes results in unnecessary competitions that slow the progress of a sustainable national NDBS system.

For a national NDBS program to succeed, there ultimately must be intersection with the national public health system/health ministry. A coordinated effort that has government support is an important step to sustainability because there are usually many government services and networks that can be leveraged to the benefit of NDBS. For example, an existing maternal and child health infrastructure within the health ministry has the potential for rapidly spreading knowledge of NDBS activities throughout the country (including remote areas). Nurses, clinics and other service delivery systems that are already in place can provide the needed logistical support, and policies and procedures already in place may provide a foundation on which to quickly establish the new program.

Other components of a government health system infrastructure also have been useful in NDBS infrastructure development. As one example, government hospitals have provided successful models for NDBS program implementation. Their closely regulated activities offer a convenient means for implementing program protocols in a controlled manner, which may provide a model for other hospitals as the program proceeds. Similarly, government health clinics and birthing centers also may provide a controlled environment in which to pilot screening services.

National government-run immunization programs have provided support capabilities to some developing programs. In programs requiring early immunization for certain

conditions, such as hepatitis, immunization personnel have sometimes collected NDBS specimens as an additional responsibility. In cases in which vaccination schedules do not provide timely patient contact sufficient for satisfactory NDBS, the population-based nature of most public health immunization systems can still be useful for parent and community education. Organized immunization programs can provide follow-up tracking and other program assistance in remote areas for newborns with positive or unsatisfactory screening results. Some programs also have utilized the immunization supply delivery system for logistical support to provide NDBS specimen collection kits to birthing facilities.

The government public health systems often employ professional health educators (or other professional staff with health educator responsibilities) and maintain public health information offices that may provide professional media support (the ability to produce pamphlets, posters, videos, etc.). In cases in which such capabilities and personnel exist, they have usually been available for a wider range of health-related educational activities, including NDBS. In many public health education systems, there are material-distribution capabilities and evaluation systems that can monitor material usage. By taking advantage of the existing capabilities, developing or expanding NDBS systems may quickly, efficiently and inexpensively provide the needed public education.

4.3. Leveraging resources from non-government organizations (NGOs)

In addition to the benefits obtained from existing government programs, developing NDBS systems have also been successful in leveraging capabilities present in NGOs. Some of the organizations that have played significant roles in developing NDBS systems include academic institutions, professional societies, private insurers, civic organizations, and sectarian and religious groups. Although statements of support from the government are essential for sustainability, positive reinforcement from professional societies is also useful in advancing NDBS activities. Support statements from local organizations can be combined with those from organizations in countries that have long-standing and successful NDBS to achieve stronger impact [29,30]. Support from and through major academic centers are often crucial for diagnosing, managing and treating at-risk patients identified through NDBS. Expertise from interested academicians has proven useful for not only monitoring treatment and/or compliance with treatment but also policy development and supporting training and educational activities.

In some countries, public service organizations, such as Lions Club International and Rotary International, have provided funding support for various items, such as informational materials, laboratory equipment, laboratory facilities, and services for charity patients. The UN Children's Fund (UNICEF) has provided funding support for the production and distribution of informational brochures on NDBS in some developing countries. The March of Dimes Birth Defects Foundation has assisted with financial support for expert speakers at national and regional meetings. Sectarian and religious groups also have been helpful in certain populations, particularly those with beliefs that can

significantly impact health and newborn care. For example, sectarian and religious pre-nuptial couple's conferences may include mention of the value of NDBS.

4.4. Developing protocol and policy

NBDS protocol and policy development require individuals with sufficient technical knowledge and experience to guide a consensus-building process. Many models of successful NDBS systems exist, and their successes should be utilized whenever possible to avoid wasted effort in reinvention. Technical screening protocols are well developed and are often available through companies that supply laboratory supplies and through publications describing the activities of developed programs. In contrast, NDBS program policies in developing programs, while similar to those in developed programs, usually require customization to meet local needs. When creating policies, multi-disciplinary input and consensus development are encouraged such that stakeholder acceptance can be maximized. Properly developed and administered policies should include responsibilities for program implementation and administration at all levels of operation. It is important that contingency planning be included in protocol and policy development to address actions that should be taken in cases of natural or man-made disasters [31]. Well-thought-out contingency plans exist in some developed programs and are available on the Internet along with instructions for plan development [32,33].

4.5. Considering legislation

Health ministries may administer public health policy in different manners, including proclamations, laws, policies, administrative orders, and policy-related rules and regulations. In most countries, NDBS is successfully administered as a medical 'best practice', and a law requiring its implementation is not necessary. However, in some countries, the force of a legal mandate has been necessary as an aid to ensure universal implementation and equality. Two developing programs, China and the Philippines, provide examples of how legislative language has been used. In China, Presidential Order No 33, Article 24 (1994) states that ". medical and health institutions shall gradually develop medical and healthcare services such as the screening of newborn babies." [34] In the Philippines, Republic Act 9288, Article 1, Section 3 (2004) states that "... every newborn must be given access to newborn screening", and Article 3 states that "... any health practitioner who delivers, or assists in the delivery, of a newborn in the Philippines shall, prior to delivery, inform the parents or legal guardian of the newborn of the availability, nature, and benefits of newborn screening" [35].

4.6. Organizing an advisory committee

Successful NDBS programs usually have an advisory committee of some type for not only advice but also professional assistance and advocacy [7,23,36]. In addition to medical experts, advisory committees often include members representing professional and community groups interested in

or impacted by NDBS. In this way, as program policies are debated and developed, members of the advisory committee can become advocates in their respective disciplines. In cases in which program managers cannot lobby policymakers, advisory committee members may fulfill that role. Because the committee approach is often slow and deliberate, particularly when it is multi-disciplinary and the knowledge level is low, most developing programs have found it expeditious to use advisory groups sparingly until the foundation for the program has been established.

4.7. Creating advocacy/public relations

The timely education of consumers, healthcare professionals and policymakers is essential for both establishing and expanding NDBS. Similarly, a well-thought-out advocacy campaign has often been found to aid in gaining public acceptance of a new or expanding NDBS program. Support from the local medical/paramedical community and medical specialists is also essential for the program to succeed. Health professionals play a key role in educating and motivating families and others in the community regarding the importance of NDBS. Families, in turn, can assist health professionals in convincing policymakers to sustain NBS at the national level.

Successful developing programs must be creative in their educational approaches and must be careful to be culturally sensitive and present material at a sufficiently low educational level to meet local needs. Some programs have found it useful to provide educational videos, books and/or compact discs to educate various stakeholders (for example, see information on manuals in the Philippine NDBS program) [37]. Comic books in local languages have been used to help educate low-literacy mothers in Mexico and the Philippines. Posters illustrating proper specimen collection techniques in the local languages are widely distributed to specimen collection facilities in both developed and developing programs. For metabolic conditions requiring special nutritional diets, cookbooks using local food products and written in local dialects have also been widely created and distributed.

4.8. Using expert assistance

Because NDBS programs have existed in most parts of the developed world for 40—50 years, there are many well-established systems from which to draw expertise. To speed the development process, newly developing and expanding NDBS programs are encouraged to collaborate with acknowledged international experts. Experts often have been used for the development of NDBS programs to aid program design and present educational seminars to professionals, policymakers and consumers. Policymakers have acknowledged the value of information exchanges with 'outside' experts to add legitimacy to internal deliberations on NDBS. As part of the activities of the MENA NDBS conferences, participants and thyroid NDBS experts have prepared flip chart educational materials to use for convincing government policymakers of the importance of screening and to answer their basic questions about program development. A reference book based on experiences in the AP region has also been produced [7].

4.9. Obtaining health ministry support

NDBS programs have often been initiated by individuals or groups as academic or private projects. No NDBS project has been universally accessible and institutionalized at the national level without some support from the health ministry. Occasionally, private entrepreneurs have begun NDBS programs in an effort to reach selected portions of the population (usually the private pay clients), but full population screening, including the indigent population, requires government support. Although health ministries are sometimes reluctant to take the lead in implementing NDBS, their reluctance diminishes as programs show success in reducing childhood morbidity and mortality. For this reason and for the fact that public policy development usually requires valid supporting data, pilot screening projects are usually necessary. These projects should be focused on statistically valid case detection projections in limited settings that can be completed in comparatively short periods of time. Reaching adequate health ministry support requires political awareness and perseverance. As examples, NBS programs in the Philippines, Egypt, Qatar and United Arab Emirates, among others, now have full government support. Although coverage in the latter three countries is essentially 100%, government support in the Philippines is relatively recent, and coverage expanded from 5.2% to 30% in its first five years as part of the public health system [3,35,38].

4.10. Gaining health professional and hospital support

With beginning NDBS programs, it is important to have support from general physicians, pediatricians, obstetricians, and specialty care providers to both educate parents and meet the medical needs of a newborn and its family. Because births most often occur in hospitals, it is also necessary to have support from the hospitals' administration. Experience has shown that these stakeholders most often desire information on the history of NDBS, rationales for its existence, benefits to individual newborns, families and society, financial strategies, and future plans. The goal of transferring this knowledge is to make every healthcare practitioner and hospital administrator into passionate advocates for the NDBS program. Some programs have found that simple performance rewards for reaching program milestones are effective for obtaining individual participation and support. For example, inexpensive but tasteful recognition plaques and framed certificates have been periodically presented to hospital administrators and physicians to acknowledge their contributions to increased newborn screening acceptance and coverage. Contests (with appropriate prizes) encouraging advocacy through posters in hospital waiting areas and banners outside of hospitals have been successful for increasing program use. Billboards have also been used to advertise the importance of NBS, and videotaped advocacy and information messages have been widely used in hospital waiting areas [39,40].

4.11. Media

Multi-pronged media campaigns have proven extremely useful for accelerating community support for NDBS in

developing health systems. Most of the population is accessible through various public media, i.e., radio, television and newspaper. For this reason, advocates of developing health systems have successfully used opportunities to explain NDBS on television and radio talk shows. Public service announcements and magazine and newspaper articles have also been shown to be successful public relations strategies. Although health professionals are often useful for explaining the medical implications of NDBS, parents are important for explaining the real impact of screening from a personal and family perspective. It is particularly impactful when contrasting cases can be illustrated (i.e., one child with a condition detected and successfully treated as a result of screening versus one who was affected with the condition as a result of not having been screened). The media have also played roles in tracking down patients for follow-up in situations in which it was difficult to locate a family following a positive screening test. Smartphone technologies are providing additional capabilities for NDBS education and tracking.

4.12. Maintaining records

Lessons learned from and models of developed NDBS programs provide a wealth of materials from which developing NBS programs can profit. One such example involves the creation and maintenance of records. It is essential that accurate records be kept regarding the offering of screening tests, their results, and subsequent related activities. Furthermore, these results must be carefully controlled such that patient and family privacy is protected. A number of models exist pertaining to computerized record keeping, including examples of integrated systems that allow access to other health records, such as immunizations and birth records. Integrated systems allow the utilization of other programs as an aid to tracking and compliance monitoring [41,42]. For example, integrated data between NDBS and immunizations can allow confirmation of screening at the time of immunization such that infants who have not been screened may be provided the service. Similarly, birth certificates can be used to record a NDBS kit number for use in compliance monitoring [43]. To simplify electronic health records in the U.S., the Library of Medicine is currently creating a computerized coding and language infrastructure to aid in the standardization of electronic records and result transfer, and this may ultimately prove beneficial for future NDBS systems outside of the U.S. [44].

The residual blood that remains on the NDBS specimen card following screening is another type of record that requires consideration. These unique specimens have the potential to generate population-based information that could have significant health benefits. These specimens contain extractable DNA from a newborn who has not yet been subjected to environmental factors. Whether these specimens are stored for research beyond newborn screening is a subject for extended debate at the program policy level. All NDBS programs are encouraged to consider this topic and develop a realistic policy for the storage and use of residual specimens [45-47]. If stored, the governing policy should promote public trust. The program must assure that the confidentiality and privacy of families is respected and that the specimens are protected.

5. Institutionalization

It is important to note that the U.S. Association of State and Territorial Public Health Officials (ASTHO) has recently recognized NDBS as a "core" public health function [48]. The Centers for Disease Control and Prevention (CDC) has also listed newborn screening expansion as one of the "Ten Great Public Health Achievements in the U.S. from 2001 to 2010." [49] The formal recognition and institutionalization of NDBS as a public health prevention program is a critical step in implementing and sustaining NBS. To be sustainable, NDBS must exist as a six-part comprehensive system, and each component must be carefully considered in its institutionalization [1].

The timely recall of patients identified as 'at increased risk' for disorders identified through screening is one of the most challenging parts of the NDBS system. Most NDBS programs, whether developed or developing, acknowledge that the location of patients who were screened as positive is severely impacted by the inability of the system to maintain accurate information of the patients' addresses and the failure of parents to identify a physician who will serve as the newborn's primary care provider following discharge from the newborn nursery. Public health clinics and outreach programs in developing and developed health systems have provided an important means for contacting patients who were screened as positive in both rural and urban settings. In the urban environment, government clinics and government hospitals have provided follow-up clinical and laboratory services as part of the NDBS system. In rural areas, public health nurses, local clinics, and an informal health network have assisted with difficult follow-up cases. As systems mature, it becomes increasingly feasible to establish regional follow-up centers that can provide comprehensive follow-up care, including genetic counseling.

Specialty care (i.e., pediatric endocrinologists, pediatric hematologists, and metabolic physicians) must be available and accessible to assist with proper clinical diagnoses and patient management. Such specialty care is often limited in developing settings and may be available only in one or two locations. There may be limited availability in both the public and private sectors. In locations in which specialty providers are not readily available, it may be necessary to rely on a physician with a special interest in a particular disorder who may be knowledgeable but is not a trained specialist. Telehealth is an increasing priority in both developed and developing healthcare settings and, in some cases, may prove useful for NDBS specialty care.

The availability of specialty care treatment supplies in developing countries may also prove challenging. Medical foods, formulas, and pharmaceuticals may be difficult to routinely obtain or expensive. Suppliers outside of the country may be necessary for initiating and sustaining some of the treatments for certain screened conditions, in which cases cordial relationships with supplier representatives may prove beneficial. Parent advocates in developed countries have also assisted in providing limited supplies and drawing attention to national needs.

Once an NDBS program has been implemented, continuing education should be a priority. Human resources are limited and may preclude the extended training of large

numbers of workers. Workshops that provide education in a 'train the trainer' mode have been found to be an efficient and effective model. For example, the IAEA sponsored regional workshops in the AP region to train laboratory specialists in testing procedures for congenital hypothyroid screening. Similar types of workshops were held for program administrators and follow-up coordinators [50]. This model has been effectively used in both developed and developing NDBS systems. The Japanese International Cooperation Agency (JICA) also has provided basic education and training with ongoing support to developing NBS programs, including many in both the MENA and AP regions [51]. Many educational resources are available from developed and more mature developing programs, and immature developing programs have found it prudent to supplement their training activities with these materials (videotapes, various books and pamphlets, and protocols). Once training materials are developed locally, it is a simple matter to update and redistribute them periodically.

Specimen transport and test result communications have required special attention in many developing programs. Local mail delivery systems are often not reliable and cannot be used for specimen transport. Additionally, some of the screening tests may require rapid specimen delivery (1-2 days) such that analyses and results are available in time for interventions to be medically successful (sometimes within five days after birth). It therefore becomes necessary to work locally with organizations that specialize in transport services to develop usable systems. In some cases, special shipping arrangements have been made with couriers, bus companies, air delivery services, and private postal services. In climates where heat and humidity may compromise specimen integrity, transport in air-conditioned vehicles or special packaging may be required. The screening test results must also be available in a timely manner, and positive results are usually reported by telephone, telefax, or other rapid special telecommunication arrangements. Due to the difficulty associated with finding patients, the communication of test results requiring immediate (emergency) follow-up have sometimes required the involvement of government police and media announcements to locate families. In at least one case in a remote area, the local taxi company was aware of the family's location and was used to assist in locating the child for follow-up.

6. Financing

Ideally, the financial sustainability of NDBS programs requires full government support. However, because of other competing health priorities, full government support of NDBS is usually not possible. As a result, almost all NDBS programs face financing challenges. Out of necessity, developing NDBS programs have been particularly innovative in approaching financing. Often, small grants have been used for initial planning and pilot testing, but this has not been practical for the long term. In some developing programs, initial screening services have been paid for through small fees paid by the family or other benefactors. Unfortunately, there is extensive poverty in many countries where NDBS is developing, and small fees may appear to

pose an insurmountable hardship. However, NDBS fees are usually substantially less than those of other prenatal medical services and are bargains compared with other healthcare costs.

Once implemented, NDBS is usually viewed as a routine health necessity, and most programs (developed and developing) plan ways to ensure that screening is accessible to the entire newborn population, regardless of their ability to pay. As a matter of equitable healthcare delivery, NDBS planning should include financial support for those who cannot pay. To offset screening fees (where they exist), some programs, most notably the Philippines, have developed model financing strategies and educational programs to encourage parents to save for this expense [35]. In some cases, altruistic organizations and local governments have provided financial assistance through gifts or loans to lower or eliminate costs. To be totally sustainable at the national level, NBS must ultimately be part of government and private insurance.

Adequate program funding is essential, and considerable time and effort should thus be expended in developing appropriate costing data and planning program finances. If fees are necessary, a sound billing and collection system must exist, and the fee must be comprehensive (i.e., it must include the items necessary for sustainability — education, screening, and follow-up). Two primary monetary flow mechanisms exist: (1) direct billing to the birthing facility following testing and (2) billing for NBS collection cards purchased prior to screening. The former requires the program to front its costs to recover expenses after the fact, whereas the latter allows advance payment. Both systems have been used in developed and developing programs. In cases in which government funds pay for the program, the costs must also be carefully documented, and a sound mechanism for receiving and spending funds must exist. In either case, a sound accounting system and careful record keeping are required.

7. Program quality

The importance of high-quality screening services cannot be overstated. Public confidence and confidence from the medical community rely on the assumption that screening results are valid and indicate increased risk when positive screening results are reported and a lack of risk when negative screening results are reported. An internal quality assurance program, coupled with periodic external evaluation and laboratory proficiency testing, has been effective in meeting most NDBS program needs. Laboratory quality management has generally utilized assay controls and standards supplied by the reagent kit manufacturers and external proficiency testing from various sources, such as the U.S. CDC [52—54]. Diagnostic laboratories are also part of the NDBS system and should be included in quality considerations. Non-laboratory components of the NDBS system are equally important, and an active self-evaluation system is encouraged. The U.S. PEAS provides a comprehensive evaluation model that has been translated into Persian and Chinese, and has been modified for evaluation of the three separate components of the Philippine NDBS program [23,24].

8. Conclusions

Continuing emphasis on improving the health of mothers and children and an expanding knowledge of the success of NDBS in reducing morbidity and mortality in newborns have led to increased interest in initiating NDBS programs in developing healthcare systems. This interest has been particularly evident in the MENA and AP regions, where NDBS Champions have successfully begun screening in over 30 countries in recent years. Varied experiences exist within both regions as a result of the population heterogeneity, health ministry priorities, poverty, geography, politics, and other factors affecting the development of sustainable NDBS programs. Regional meetings in both the MENA and AP regions have led to commitments to increase screening activities that were formalized in the Marrakech and Cebu Declarations, respectively [3,6]. These declarations provided a valuable first step toward the implementation and sustainment of NDBS programs in countries in both regions. To date, a limited number of countries in the MENA and AP regions report the existence of universally available national NDBS programs that screen for at least one condition, although many limited coverage screening projects exist. In several countries with and without national coverage, multiple conditions are screened. Various implementation strategies, including collaborations with countries outside of the respective regions as a means of obtaining start-up laboratory and administrative support, have been employed. In successful screening programs in Qatar, Lebanon, Laos and the Philippines, the start-up activities involved sending specimens to developed screening laboratories in Germany and Australia [35,38,55,56].

Although most programs have focused on initial screening for congenital hypothyroidism, which is known to be cost-effective in most screening settings, tandem mass spectrometry (MS/MS) for metabolic conditions has also been embraced by some developing programs. Although MS/MS screening is relatively expensive and technically challenging, its use in screening for metabolic conditions in countries where consanguinity leads to increased incidence of metabolic conditions will likely prove to be cost-effective. Ongoing MS/MS studies in Lebanon, Qatar, and Saudi Arabia should provide useful information for countries in the MENA region, and similarly, data from projects in China, Japan, and other countries should provide information for the large AP screening population [2,38,55,57,58].

In addition to the regional meetings noted in this manuscript, other international collaborations have provided opportunities for expanding knowledge and meeting the other challenges encountered when establishing and strengthening NDBS programs. Although it is no longer a viable funding source, the IAEA provided start-up assistance (technical training and administrative support) for congenital hypothyroidism screening in many MENA and AP countries [6,50]. Similarly, JICA has provided (and continues to provide) NDBS training courses for developing programs in the MENA and AP regions in addition to selected programs in Latin America [51]. Initiatives from commercial vendors have provided innovative purchasing strategies and pricing for reagents and equipment that have encouraged

NDBS growth and expansion. Experts from developed programs continue to contribute both time and energy to training and transferring knowledge to developing programs. Progressive health ministry officials overseeing developing healthcare systems have provided support in some countries, and their interest appears to be increasing (as their knowledge increases), indicating that more national NDBS programs may profit from ministry support in the near future.

In the future, expanding communication technologies will likely play a larger role in educating parents and professionals regarding NDBS. In developing healthcare systems, communication technologies should be particularly useful for data and result transfer and for improved vendor support of testing equipment and other supplies critical to the screening process. Strategic planning as well as multi-national collaborations will continue to be critical to sustainable NBS. Necessary information for policy decisions originate from data, and it is important that national and regional data be standardized, collected centrally and periodically analyzed. Programs should be aware of developing international information technology standards and definitions such that they may be considered during planning deliberations. New technologies continue to be developed to result in an increased number of screening possibilities, and efforts must be made in developing programs to stay abreast of technological changes that may affect screening protocols and policies.

In this manuscript, we have attempted to outline some of the ways in which NDBS programs are meeting the system development challenges faced in developing health systems. Institutionalizing NDBS for a single condition in countries with little or no previous newborn screening activity or expanding to meet the growing health needs in others requires dedication and perseverance. Leaders in establishing NDBS programs must provide health ministries with sufficient knowledge and understanding to gain their support if the programs are to become sustainable at the national level.

Conflict of Interest

Neither author has any conflicts of interest to disclose.

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