Available via license: CC BY 4.0
Content may be subject to copyright.
Page 1/13
A Policy Analysis of the National Phenylketonuria Screening
Program in Iran
Alireza Heidari ( alirezaheidari7@gmail.com )
Golestan University of Medical Sciences and Health Services
Mohammad Arab
Tehran University of Medical Sciences
Behzad Damari
Tehran University of Medical Sciences
Research article
Keywords: Policy Analysis, Phenylketonuria (PKU), Neonatal Screening, Policy Triangulation Framework, National PKU screening (NaPS)
DOI: https://doi.org/10.21203/rs.2.22558/v3
License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License
Page 2/13
Abstract
Background: Phenylketonuria (PKU) screening is a public health measure taken to diagnose and treat the patients with PKU to prevent
severe neurological disorders in them. The present study was aimed at analyzing the policies of the national PKU screening (NaPS)
program in Iran.
Methods: PKU screening program policies were analyzed in compliance with the policy triangle model. Document review and 38 semi-
structured interviews were used for data collection. Document review data were analyzed using content analysis, and interview data were
analyzed using framework analysis.
Results: The national PKU screening (NaPS) program was a decision made at the genetics department of Ministry of Health and Medical
Education (MOHME) in Iran. Many internal and external stakeholders were involved in it and valid evidence was used to formulate the
policies. Despite some opposition and insucient support, the program was implemented due to the continuous persistence of parents,
interested executives, formulated valid content and a top-down approach. The main barriers included rapid substitution of managers,
shortage of Phe-free milk, little awareness of patients’ families, social stigma, and inadequate co-operation of some hospital
administrators.
Conclusions: The policy triangle framework contributed to explaining the different components of the PKU screening program. A
successful PKU screening program requires more stability of senior managers in MOHME, enough human resources and Phe-free milk,
educating patients’ families, and commitment of hospitals administrators. Meanwhile, all the stakeholders need to be involved in the
program effectively.
Background
Phenylketonuria (PKU) is the most common hereditary metabolic disorder in the world [1]. Patients with PKU show high levels of
phenylalanine in the blood serum, and thus develop neurological disorders such as mental retardation, seizures, behavioral problems,
and developmental delays [2–4]. The prevalence of the disease is reported to be 1 in 10,000 in whites and 1 to 6,000 - 8,000 in the
Iranian population [5]. Other domestic studies have also reported a high incidence of the disease among people with mental retardation
from 2.1% to 5% [6-7]. If the disease is not diagnosed and treated within the rst year of birth, the child's IQ capacity may be reduced by
50%. Irreversible effects on the brain can be prevented by timely detection and control of phenylalanine levels in the blood [8].
Neonatal screening is a population-based public health screening program implemented for early detection [9]. PKU screening is a
prerequisite for early implementation of the Phe restricted diet, which is essential to prevent severe neurological disorders in patients with
PKU [10]. Nowadays, most developed countries carry out PKU screening, and any newborn with PKU is immediately exposed to a Phe-
restricted diet to lower plasma Phe concentrations. This combination of early diagnosis and initiation of treatment results in normal IQ
for most PKU patients [11].
The PKU screening program in Iran launched in 2006. In this program blood samples were taken from all infants on day 3 to 5 after birth
for colorimetric screening. And people with phenylalanine levels of 4 mg/dl or higher were referred to be conrmed by HPLC test. Then
regular follow-up is performed for people who have phenylalanine levels equal to or greater than 4 mg/dl, and if the phenylalanine levels
are 7 mg/dl or more, the diet begins with restricted phenylalanine. Dietary supplements of Iron, zinc, selenium, carnitine, vitamins and
essential fatty acids are prescribed for all children up to 2 years of age [12].
Policy analysis includes plans and actions aimed at achieving health care goals by dening a vision for the future, setting goals and
objectives, setting priorities, and identifying the roles of different groups. Health policy analysis helps to understand the success or
failure in implemented policies so that they can be useful for planning future policies. Health policy analysis helps policymakers to
improve their successful implementation of future policies and provide opportunities to produce policy documents [13]. Policy analysis
can help to understand the complexity of the policy process as well as its nature and provide policy-related evidence [14]. Policy analysis
helps to understand why policymakers pay attention to certain issues in the health system and disregard other issues, also to identify
stakeholders who agree or disagree with the policies and the reasons why they agree or disagree with it, as well as to identify undesirable
consequences of policies implementation and future problems in implementing policies and achieving their goals [15-16]. Since,
studying the role of evidence in policymaking helps to better understand the contribution of research to policy formation and to identify
the factors that inuence it [17] and no sucient works have been conducted on policy analysis of the phenylketonuria screening, the
present study is aimed at analyzing the policies of the national phenylketonuria screening (NaPS) program in Iran.
Page 3/13
Methods
Study design
This qualitative study was conducted from May 2015 to January 2016 using the Walt and Gilson triangle Kingdon’s multiple streams
models. Kingdon model is an instrument for understanding the policies agenda-setting. Based on this model, the interaction of three
streams problem, policy and politics will result in a policy window and policy entrepreneurs can use the opportunities for policy
development [18]. The triangle model covers four general areas: content, context, actors, and the decision-making process (Fig. 1). The
content
includes policy goals, operational policies, and so on. The word “
actors
” refers to executives and inuential organizations. The
context
refers to social, economic, political, cultural and other environmental conditions. The
process
consists of four parts: agenda
setting, policy formulation, policy implementation, and policy evaluation [19].
Study population and selection of participants
Study participants included 38 individuals from different sectors related to the study in Iran:
the Health Commission of the Islamic Consultative Assembly,
Ministry of Health and Medical Education (MOHME) (deputies of health and treatment, food and drug administration),
the Iranians Health Insurance organization,
the policymaking council,
faculty members in universities of medical sciences,
children's specialized hospitals,
Pasteur Institute,
Welfare Organization, and
PKU Patients Support Association.
Target groups were selected based on purposive sampling. Their selection criteria included knowledge and experience in phenylketonuria
screening programs, active participation in phenylketonuria screening programs, and interest in research participation.
Data collection
Semi-structured interviews were conducted to collect data using the interview guideline. Credibility, transferability, dependability, and
conformability were used such as criteria of rigor and trustworthiness of this study [20-22]. Interviews were conducted face-to-face at a
designated time and place. The interviews lasted between 30 and 65 minutes. At the beginning of each interview, the participants were
provided with a summary of the research topic and the method of using the data. The written consent was obtained to conduct the
interview. Note taking was also used during the recording of the interviews. The audio les were transcribed at the earliest opportunity.
Data analysis
Framework Analysis was used to analyze the data, which included ve basic steps: Familiarization, Identifying a Thematic Framework,
Indexing, Charting and Mapping and Interpretation. In addition, Document Analysis was used to validate the ndings of the interviews
and to benet from the evidence available in the policy process. Documents were collected purposefully by referring to the organizations
involved in NaPS program and reviewing relevant internet sites. The content analysis method was used for data analysis of documents.
Results
Findings were reported based on four categories of policy triangle framework (context, content, process, and actors). These categories
are explained as follows (Fig. 2):
Context
Content included three factors: political, economic, and social and cultural factors.
Page 4/13
Political factors
Political commitment and stability of top-level healthcare administrators of MOHME will contribute to the continuity of the approach of
fair access to health services for all. According to Article 89 of Iran's Fourth Development Plan (1963-1972), the MOHME was required to
design a system of minimum standardization of health services based on the levels of services in order to ensure fair access to health
services. In this regard, the NaPS program with specic level was launched at the lowest levels of the network, was fairly implemented in
cities and villages. But the long-term plan for the future has not been dened. Because of the political changes in government, the
minister, his deputies and other senior managers of the MOHME change relatively fast.
"The system should not change with the change of managers. It must be stable. After the management changes, specialized staff also
change. Then the problem emerges "
(P.19).
Economic factors
Economic sanctions will exert the most pressure on the needy and less privileged /under-privileged and susceptible patients- those who
cannot afford the diagnostic and therapeutic costs of PKU. The economic sanctions restricted the currency exit from country and the
imports of drugs and Phe-free milk and even publication of scientic articles related to the PKU program in foreign journals. Because
most families could not afford the diagnostic and therapeutic costs of the disease, the cost of screening and Phe-free milk was
subsidized by government.
"Iran sanctions face us with limited drug access and low access to technology"
(P.17).
“
Sanctions have had a major impact on the import of Phe-free milk for patients
"(P.4).
"We had trouble publishing the article on this project, so one of the journals responding to our article replied:” we cannot publish your
article because you are under sanctions"
(P.24).
Social and cultural factors
Adequate public education on PKU- e.g. mental retardation, prevention, and follow up- and knowledge of healthcare providers on the
PKU-associated social stigma will help decrease the impacts of the disorder and achieve the goals of the program. People welcomed the
diagnosis program as it dealt with concerns about the likelihood of mental retardation and the possibility of preventing the disease, but
some families do not regularly follow up on treatment regimens. Parenting skills of patients’ parents and self-care of patients are poor.
Patients and their families have little knowledge of the disease, and they are not provided with adequate education. The tendency for
family marriages in Iran leads to an increased risk of the disease. The social stigma associated with disease has made it dicult to
advance the program.
"With age, withdrawal from treatment increases and disease control becomes more dicult. Many patients develop seizures because
they have not followed the diet and phenylalanine levels in their blood have risen."
(P.28)
"Disease-related social stigma makes it dicult to care and follow up. The parents of one of the patients moved and they would not be
followed up as they do not provide their new address. A person who has a child with PKU doesn't even tell his sister and brother that his
child has PKU"
(P.36)
Policy content
To help NaPS program to be effective, different specialized and administrative departments at country, provincial and national levels and
universities need to full their duties, responsibilities, and follow regulations in this regard. The purpose of NaPS program was to reduce
physical disability, mental retardation and family damage. PKU screening is not just a test, but it is a system designed to identify, treat,
and fully care for patients. Therefore, the program was organized at county, provincial, and national levels.
The genetics department of the MOHME and medical sciences universities were determined as responsible for implementing the
program in national and provincial levels. In health part, health houses, urban and rural health centers, district health centers and disease
prevention and control unit in the deputy of health of the medical sciences universities were considered to provide health services. In
treatment part, blood sampling centers, provincial health reference laboratory and selected PKU hospitals were considered to provide
diagnostic and therapeutic services.
Page 5/13
Chief among the duties of genetics department are:
drafting the national program guidelines,
developing the monitoring checklists,
forming the national technical committees,
notifying all universities in the country of the program,
collecting the annual reports from medical sciences universities,
evaluating implemented programs,
following up the necessary facilities,
engaging relevant organizations and departments and making coordination with them,
following up laws and approvals,
developing the educational packages,
anticipating funding for program implementation and reporting to high level ocials.
Chief among the duties of medical sciences universities are:
planning and discussing the program at the genetics committee,
organizing meetings of the PKU academic committee,
monitoring implementation of approvals,
monitoring performance, and
periodically reporting to health and treatment deputies.
The duties of the provincial health reference laboratory are:
receiving and registering all screening samples,
performing all screening tests,
reporting positive screening tests (initial suspected) and
requiring re-testing (technical and medical) to the “disease prevention and control unit” in the province.
The number of patients in each province is relatively limited, so such a large system cannot be implemented in all cities. In this way, at
least one children's specialized hospital as PKU selected hospital in each province provides all required services to patients. In PKU
selected hospitals, all required services are provided:
specialist physician periodic visit,
laboratory services for treatment control,
expert nutrition services,
pharmaceutical services (delivery of Phe-free milk and other nutrition items to patients),
clinical psychology and social care services, and
parents’ education.
The duties of the health centers and health houses include:
immediate referral of newly-diagnosed patients to the selected hospitals,
follow-up in absence of treatment, collection, registration and transmission of information,
participation in educational programs, and
educating pregnant mothers.
In order to implement the program, guidelines of laboratory, care, clinical, nutritionist, genetic diagnosis and prevention, non-classic
sampling guidelines and supplementary regulations of clinical psychologists were developed.
Policy process
Page 6/13
The results of policy process of PKU program consists of ve sections: 1) Agenda setting, 2) Formulation of PKU screening policies, 3)
Implementation of PKU screening policies, 4) Evaluation of PKU screening policies, and 5) Challenges of implementing a PKU screening
program.
Agenda setting
Three different streams are needed to set up an agenda for the policy process of PKU program:
1. Problem Stream: Identifying the problems behind the necessity of implementing a national PKU screening program;
2. Policy Stream: Support of insurance organizations and treatment department of MOHME; and
3. Political Stream: Adequate support of patients’ families and members of the Iranian Society of Pediatrics to implement NaPS
program.
During 1997-2010, the outbreak ratio of PKU was calculated 1:8000 in three big provinces of Tehran, Fars, and Mazandaran in Iran [23].
Following the implementation of the Iranian NaPS in 2013, the incidence rate of this disease was decreased to 1:4166 [24]. If the disease
is not diagnosed in a timely manner and the treatment process is not initiated, physical, mental and intellectual disabilities will occur for
the patient and these problems are irreversible. The medical costs and problems of keeping a disabled child in the family are also other
problems (
First Stream
).
"
There was a problem. Every year a number of patients were added to PKU patients. They suffered from severe physical and mental
disabilities, reduced IQs and complications such as seizures and increased nancial burden for the families and health system. On the
other hand, the disease could be diagnosed early and be cared for
" (P.1).
The above-mentioned problems have led health policymakers to explore ways to solve these problems. Therefore, with the successful
implementation of the hypothyroid screening program and the use of infrastructure of this program for phenylketonuria screening, as
well as executive and scientic efforts, PKU screening program was developed (
Second stream
).
"We had already experienced congenital hypothyroidism screening. Sampling time, sampling method and sending to the lab are the
same as phenylketonuria screening"
(P.14).
Although, there were some problem and policy streams, factors such as lack of prioritization of the program by the MOHME top
executives, the limited capacity of the health system, the inability to increase health personnel in accordance with national
administrative regulations and laboratory equipment problems, caused the policy window to remain closed and program implementation
stopped.
Despite the opposition of the Network Development Oce with regard to integrating the program, insucient support of insurance
organizations and deputy of treatment of MOHME, the NaPS program was implemented due to the continuous persistence of patients’
families and members of the Iranian Society of Pediatrics to initiate screening and therapeutic interventions and formulated content, and
talented and interested executives who convinced the policymakers (
Third stream
)
"
We, patients' families, corresponded with the Vice-Chancellor of Health Minister. We met him. We talked to him about our problems. He
was very upset about our situation. He instructed the relevant organizations to serve all PKU patients”
(P.22).
One of the reasons for the success of this program was the presence of a capable, interested, and persistent responsible person
" (P.16).
Problems associated with the disease (
rst stage
), successful implementation of the hypothyroid screening program and ability to run
the program based on the created infrastructure at national level (
second stage
), exerting pressure on the patients’ families, members of
the Scientic Committee on Children and following up by executives (
third stage
) concurrently led to agreement of health policy makers
with the program, and policy window was opened.
Formulation of PKU screening policies
To formulate the policies of PKU screening, various departments need to implement different administrative, scientic and executive
measures to achieve this goal. Executives sought to involve all stakeholders prior to launching the program. The scientic proposal for
the implementation of the screening program was formulated by two faculty members. A services package to be provided to patients
with hereditary metabolic diseases was developed by faculty members working with various medical sciences universities in Iran. The
Page 7/13
Genetics Department used the Thalassemia Genetics Program as the infrastructure and model of the PKU program and utilized
thalassemia genetic consultants. The standards were extracted from the review of scientic references, valid guidelines and evidences
from leading countries and then localized in the national committee.In order to formulate policies, numerous meetings were held with
the participation of academics and stakeholders to engage them to advance the program. WHO observers attended some of these
meetings. The program was presented in the Provincial Health and Food Security Council by health administrators. In order to ensure
the feasibility of implementing the program, diagnostic and therapeutic facilities were checked out by different groups of genetic experts,
physicians, and health reference laboratory experts.
Implementation of PKU screening policies
Different approaches should be used to implement the PKU screening policies. The approach for implementing PKU screening policies
was a top-down approach. The pilot program was conducted in 2007 at Universities of Medical Sciences in Shiraz, Mazandaran and 3
Universities of Medical Sciences in Tehran, i.e. Shahid Beheshti, Tehran and Iran University of Medical Sciences. The screening program
was nationwide following the implementation of the pilot one in early 2013. Organizing the laboratory tests, transferring the specimens
and conrming the tests were done by the Health Reference Laboratory. In the capital of each province, a children's specialized hospital
was organized as PKU's selected hospital. A treatment team consisting of a pediatrician, a nutritionist, a psychologist, a social worker,
and a secretary was formed in these hospitals. Patients’ dietary milk was distributed by the selected hospital pharmacy. At the beginning
of the program, a liaison was selected from among the patients’ parents, but after a while, this role was assigned to the hospital staff.
The follow-up of the newborn baby was monitored by health center experts. Detailed statistics of treatment and absence of treatment
from the selected hospital were provided to the MOHME. Malignant and non-classic diagnostic tests were conducted at the Pasteur
Institute of Iran.
Evaluation of PKU screening policies
Provincial experts' performance was evaluated by the Genetic Department of MOHME. In this way, periodic monitoring and completing
checklists and providing statistics and documentation was done.
Challenges of Implementing a PKU Screening Program
Different sections of a health care system should actively cooperate to full the successful implementation of PKU screening program. A
national screening decision was made in 2011, but was delayed due to laboratory equipment problems in medical sciences universities
in 2012. Monitoring and follow-up of PKU patients have lower priority than other programs in some selected hospitals. Selected
hospitals suffered from a shortage of milk powder. It was not appropriate to record hospital and non-hospital information. Qualitative
evaluation of selected hospitals was not performed well due to inadequate co-operation of some hospital administrators and the lack of
a supervisory system for providing PKU services in hospitals.
"
From the year 2007 to 2011, when we wanted to start a national screening program, during these four years, the most important
problems were laboratory diagnostic problems
"(P.3).
One of the problems is that hospital information is not recorded very well
" (P.2).
Actors
Internal stakeholders involved in the NaPS program include:
Genetics department,
Health Network Development Center,
Oce of Population & Family Health,
Health Reference Laboratory,
Children Health Department,
Deputies of Health Universities of Medical Sciences,
Deputies of treatment Services,
Selected Hospitals of PKU,
Pasteur Institute of Iran,
Page 8/13
Food and Drug Administration,
and related research centers
External stakeholders involved were:
the Welfare Organization,
Health Insurance Organization,
PKU Patient Support Association,
the Post oce and
the Registration Oce.
Discussion
The purpose of the Phenylketonuria screening program in Iran was to reduce physical disability and mental retardation and medical and
nonmedical costs. Given the relatively high prevalence of PKU [24] compared to that of other countries [25-29], high rates of familial
marriages in Iran [30-31]and mental retardation in patients with PKU [32-33] highlighted the role of early diagnosis of disease and the
need for timely medical interventions. Establishing a specic mechanism for the care and control of PKU patients was also the main
demand of the patients' families, but despite the problems related to the disease and its consequences, due to the limited capacity of the
health system, the inability to increase the number of human resources in accordance with national administrative regulations and lack
of laboratory equipment, the policymakers and senior managers at the MOHME were not convinced to integrate the program into the
health system and to implement the program at the national level. Eventually, after pressure from the demand and follow-up by patients’
parents and members of the Pediatric Medical Association, policy makers and senior executives were persuaded to implement the
program. The results of Barojo study in 2007 also showed that policymakers' willingness and pressure of families with affected children
led to a particular disease being selected for the neonatal screening program in Latin American countries without any appropriate basis
or the use of a national standard [34]. In this regard, in the United States, legal pressure from parents and the legislature was the main
driving force behind the widespread screening [35].
Based on the results of the present study, to implement the program nationwide, provincial laboratories were equipped. The surveillance
system for the affected patients was organized in health networks. PKU selected hospitals were designated in the capital of each
province and a treatment team consisting of a pediatrician, a nutritionist, a psychologist, a social worker and a secretary was formed in
these hospitals. There are some differences between Iranian structure of human resources for PKU screening and that of the other
countries. New Zealand, which launched the Metabolic Disorders Screening Program since 2005, used a consulting group including
pediatricians, patients' families and other medical teams before implementing the program [36]. The results of the Hanley study in
Canada in 2005 showed that health care workers for the phenylketonuria screening program were physicians, nutritionists, nurses, social
workers, biochemists, genetic counselors, and psychologists [37]. Midwives, neonatal unit staff, health visitors and health team
members, nursing specialist consultants, pediatric nurses in the pediatric nursing team, child health team, public health staff, general
practitioners and pediatricians are involved in the implementation of the UK Neonatal Screening Program [38]. Benetting from nurses
and midwives in the care team of patients with PKU in Canada and the United Kingdom was a distinction between their human resources
structure and the one practiced in Iran.
Based on the results, a “top-down” approach for policy implementation was adopted. Ham and Hill have considered two approaches for
policy implementation; the main difference between these approaches is the degree of actors’ involvement in the policy cycle [39]. In the
bottom-up approach, eld actors can inuence performance through negotiation and engagement, and in the “top-down” approach,
bargaining and interaction between different levels of the policy cycle are low [40]. The “top-down” approach, i.e. the approach used in
policy implementation, focuses on a small group of high-level policymakers at the MOHME, and policies are seen as high-level orders of
the high-level authorities that the low-level authorities are forced to implement. Although periodic visits and reporting occur at different
levels of the health care system, these interactions are not sucient and may reduce the long-term participation of actors at lower levels.
Inadequate co-operation of hospital administrators seems to be one of the consequences of applying this approach.
The results of the study indicated the impact of political changes in the country and consequently structural and managerial changes in
the health system which have an adverse impact on the implementation of NaPS policies and programs. This result is in line with the
results of the studies by Romain et al. in 2015 in Tunisia [41]. Managers and policies changes that occur after political changes may
Page 9/13
cause confusion and lead to halting the programs. Therefore, development of a long-term plan and the commitment of all managers to it
will help to sustain the plan.
Another political factor was the impact of international sanctions on imports of dietary milk and medicine. Studies by Masoumi et al. in
2015 [42], Georgia et al. in 2014 [43] and Shahabi et al. in 2015 [44] have also addressed the impact of sanctions on health. The
sanctions have had a negative impact on the country's treatment system, which includes the provision of drugs and medical equipment.
In many cases, it has impeded the entry of certain drugs and has also caused slow entry of drugs and equipment, the introduction of
counterfeit and inappropriate drugs, and increased prices for other drugs [45].
One of the important cultural factors was the family's lack of awareness of PKU. This result is consistent with the results of a study by
Hong et al. in Southern Taiwan in 2005 [46] and Barojo study [33], but it was inconsistent with the results of Campbell and Ross's study
in the US in 2003 [47]. Parents' ignorance of the disease can be due to their poor health literacy. Since the rst step towards behavior
change about a subject is to obtain awareness about it [48], therefore, parents knowledge should be increased based on the content of
scientic guidelines to lead to effective care.
Strengths and limitation of the study
This study had some strength. To use a qualitative approach, internal and external stakeholders participated in the study with different
backgrounds and explained their own professional experience individually. Two well-known conceptual framework (policy analysis
triangle and Kingdon’s multiple streams models) used were able to collect relevant data including process, content and context and
actors to interpret development policies.
Nonetheless, this study suffers from some limitations. The study, rather than being longitudinal was a cross-sectional study. Since this
study was the rst research to analyze the PKU screening policies, other restrictions of the study was limited access to documents.
Conclusion
The present study was conducted to analyze the policies of PKU Screening in Iran. The analysis helped to identify the different
components of policymaking cycle and effective factors on formulation, implementation, and evaluation of policies. A successful PKU
Screening program requires more stability of senior managers in the MOHME, enough human resources and Phe-free milk, educating
patients’ families, and commitment of hospitals administrators and also, all of the stakeholders should be involved in the program
effectively.
Abbreviations
HPLC: High performance liquid chromatography
IQ: Intelligence Quotient
MOHME: Ministry of Health and Medical Education
NaPS: National Phenylketonuria Screening
PKU: Phenylketonuria
Declarations
Ethics approval and consent to participate
The present study received ethical approval from the Ethics Committee of Tehran University of Medical Sciences (TUMS), le number
142135. Before beginning interviews, written informed consent was obtained from all participants.
Consent for publication
Not Applicable.
Availability of data and materials
Page 10/13
In order to preserve the anonymity of participants transcripts are not available
Competing interests
There is none to declare.
Funding
The present study was funded by Tehran University of Medical Sciences (TUMS). The funding body had no role in the design of the
study, data collection and analysis of the data.
Conicts of interest
There are no conicts of interest.
Authors’ contributions
AH and MA conceptualized the study. AH collected the data and performed data analysis. MA and BD reviewed the analysis. AH wrote
the manuscript and edit it. All authors read and approved the nal manuscript.
Acknowledgment
The present study was part of a thesis for a PhD degree in health policy and was funded by Tehran University of Medical Sciences
(TUMS). The authors would like to express their appreciation to all participants who shared their valuable experience.
References
1. Gunduz M, Arslan N, Unal O, Cakar S, Kuyum P, Bulbul SF. Depression and anxiety among parents of phenylketonuria children.
Neurosciences 2015; 20(4):350-6.
2. Purevsuren J, Bolormaa B, Narantsetseg C, Batsolongo R, Enkhchimeg O, Bayalag M, et al. The rst Mongolian cases of
phenylketonuria in selective screening of inborn errors of metabolism. Molecular Genetics and Metabolism Reports 2016; 9:71-74.
3. Soleymani Z, Keramati N, Rohani F, Jalaei S. Factors Inuencing Verbal Intelligence and Spoken Language in Children with
Phenylketonuria. Indian Pediatr 2015; 52(5):397-401.
4. Etemad K, Heidari A, Setoodeh A, Shayeganrad A, Akhlaghi A, Azizi M et al. Health-related quality of life of parents of children with
phenylketonuria in Tehran Province, Islamic Republic of Iran. East Mediterr Health J 2020;26(3):331–339.
5. Binnafar S, Mahdieh N. genetics of Phenylketonuria in Iran: A Review study. J Mazandaran Univ Med Sci 2017; 27(147): 446-455.
6. Vallian S, Barahimi E, Moeini Phenylketonuria in Iranian population: a study in institutions for mentally retarded in Isfahan.
Mutat Res 2003; 15 (1-2): 45-52.
7. Golbahar J, Honardar Selective Screening of Phenylketonuria, Tyrosinemia and Maple Syrup Urine Disease in Southern Iran. Iran
J Med Sci 2002; 27: 134-135.
8. Ganji F, Naseri H, Rostampour N, Sedighi M, Lotzadeh M. Assessing the Phenylketonuria Screening Program in Newborns, Iran
2015-2016. Send to Acta Med Iran. 2018 Jan; 56(1):49-55.
9. El-Metwally A, Yousef Al-Ahaidib L, Ayman Sunqurah A, Al-Surimi K, Househ M, Alshehri A, Da'ar OB, Abdul Razzak H, AlOdaib AN.
The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review. Biomed Res Int 2018; 2018:7697210.
10. Zerjav Tansek M, Groselj U, Angelkova N, et al. Phenylketonuria screening and management in southeastern Europe - survey results
from 11 countries. Orphanet J Rare Dis. 2015; 10:68.
11. Van Vliet D, van Wegberg AMJ, Ahring K, et al. Can untreated PKU patients escape from intellectual disability? A systematic review.
Orphanet J Rare Dis 2018; 13(1):149.
12. Aghasi P, Setoodeh A, Sayarifard A, et al. Intellectual and Developmental Status in Children With Hyperphenylalaninemia and PKU
Who Were Screened in a National Program. Iran J Pediatr. 2015; 25(6):e3033.
13. Yousenezhadi T, Mosadeghrad AM, Arab M, Ramezani M, Sari AA. An Analysis of Hospital Accreditation Policy in Iran. Iran J Public
Health. 2017; 46(10):1347-1358.
14. Fischer F, Miller GJ. Handbook of public policy analysis: Theory, Politics, and Methods. CRC Press, 2006.
Page 11/13
15. Brugha R, Varvasovszky Z. Stakeholder analysis: A review. Health policy and planning 2000. 15(3): 239-246.
16. Gilson L, Buse K, Murray SF, Dickinson C. Future directions for health policy analysis: A tribute to the work of Professor Gill Walt.
Health policy and planning 2008; 23(5): 291-293
17. El-Jardali F, Jamal D, Ataya N, et al. (2011). Health Policy and Systems Research in Twelve Eastern Mediterranean Countries: a
stocktaking of production and gaps (2000–2008). Health Res Policy Syst, 9: 39.
18. Kingdon JW. Agendas, Alternatives, and Public Policies. 2nd ed. New York: Longman; 2011.
19. Walt G, Gilson L. Reforming the health sector in developing countries: the central role of policy analysis. Health policy and planning.
1994 1;9(4):353-70.
20. .Cypress BS. Rigor or reliability and validity in qualitative research: Perspectives, strategies, reconceptualization, and
recommendations. Dimens Crit Care Nurs 2017; 36(4): 253-63.
21. Eri M, Jafari N, Kabir M J, Mahmoodishan G, Moghassemi M J, Tahanian M, et al . Concept and Challenges of Delivering Preventive
and Care Services in Prehospital Emergency Medical Service: A Qualitative Study. J Mazandaran Univ Med Sci. 2015; 25 (126) :42-
57.
22. Damari B, Hajebi A, Bolhari J, Heidari A. Developing a Training Course for Spiritual Counselors in Health Care: Evidence from Iran.
Indian J Palliat Care. 2018; 24(2):145–149.
23. Ganji F, Naseri H, Rostampour N, Sedighi M, Lotzadeh M. Assessing the Phenylketonuria Screening Program in Newborns, Iran
2015-2016. Acta Med Iran 2018; 56(1):49-55.
24. Heidari A, Arab M, Damari B. Estimation of Economic Cost in Patients with phenylketunoria in Iran. J Manage Med Inform Sch 2018;
3(3):7-14.
25. Gu X, Wang ZG. Screening for phenylketonuria and congenital hypothyroidism in 5.8 million neonates in China. Zhonghua yu fang
yi xue za zhi 2004; 38(2):99-102. 26.
26. Lugovska R, Vevere P, Andrusaite R, Kornejeva A. Newborn screening for PKU and congenital hypothyroidism in Latvia. Southeast
Asian J Trop Med Public Health 1998; 30(Suppl 2):52-3. 27.
27. Oddason KE, Eiriksdóttir L, Franzson L, Dagbjartsson A. Phenylketonuria (PKU) in Iceland. Laeknabladid 2011; 97(6):349-52. 28.
28. Pangkanon S, Charoensiriwatana W, Janejai N, Boonwanich W, Chaisomchit S. Detection of phenylketonuria by the newborn
screening program in Thailand. Southeast Asian J Trop Med Public Health 2009;40(3):525-9. 29.
29. Han YJ, Lee DH. Measures to Improve Newborn Screening System in Korea. Health and Social Studies 2002; 22(1):175-95.
30. Senemar S, Ganjekarimi H, Fathzadeh M, Tarami B, Barzgar M. Epidemiological and clinical study of phenylketonouria (PKU)
disease in the national screening program of neonates, Fars Province, Southern Iran. Iranian J Publ Health 2009; 38:58-64. 39.
31. Habib A, Fallahzadeh MH, Kazeroni HR, Ganjkarimi AH. Incidence of Phenylketonuria in Southern Iran. Iran J Med Sci 2010;35:137-9
32. Holmgren G, Larsson A, Palmstierna H, Alm J. The frequency of PKU and hyperphenylalaninemia in Sweden-a study in institutions
for the mentally retarded as well as in neonates. Clin Genet 1976;10:313
33. DiLella AG, Woo SL. Molecular basis of phenylketonuria and its clinical applications. Mol Biol Med1987;4:183-92
34. Borrajo GJC. Newborn screening in Latin America at the beginning of the 21st century. Journal of inherited metabolic disease 2007;
30(4):466-481.
35. Soltani M. Metabolic diseases screening in newborns. Laboratory & Diagnosis 2009: 17-20.
36. Padilla CD, Therrell BL. Newborn screening in the Asia Pacic region. Journal of inherited metabolic disease 2007; 30(4):490-506.
37. Hanley WB. Newborn screening in Canada–Are we out of step? Paediatrics & child health 2005; 10(4):203-207.
38. Newborn Bloodspot Screening Programme Policy. Available from:
http://www.nelft.nhs.uk/_documentbank/Whipps_Cross_and_Waltham_Forest_Newborn_Bloodspot_Policy_FINAL___June_2013.pdf.
39. Ham C, Hill MJ. The policy process in the modern capitalist state: Harvester Wheatsheaf; 1993.
40. Buse K, Mays N, Walt G. Making health policy (understanding public health). UK: Bell & Brain Ltd. 2005.
41. Ben Romdhane H, Tlili F, Skhiri A, Zaman S, Phillimore P. Health system challenges of NCDs in Tunisia. International journal of
public health 2015; 60(1): 39-46.
42. Massoumi, R.L. and S. Koduri, Adverse effects of political sanctions on the health care system in Iran. Journal of global health,
2015. 5(2):020302.
43. Gorji A. Sanctions against Iran: the impact on health services. Iranian journal of public health 2014; 43(3):381-382.
Page 12/13
44. Shahabi S, Fazlalizadeh H, Stedman J, Chuang L, Shariftabrizi A, Ram R. The impact of international economic sanctions on Iranian
cancer healthcare. Health policy 2015; 119(10): 1309-1318.
45. Alekajbaf H, Ansariyan M. Impact of unilateral and multilateral sanctions on Iran Perspective on the health rights of the citizens of
Iran. The Iranian Journal of Medical Law 2014; 8(29):11-50.
46. Huang MC, Lee CK, Lin SJ, Lu IC. Parental consent for newborn screening in southern Taiwan. Journal of medical ethics 2005;
31(11): 621-624.
47. Campbell E, Ross LF. Parental attitudes regarding newborn screening of PKU and DMD. American Journal of Medical Genetics Part
A, 2003; 120(2):209-214.
48. Etemad K, Eftekhar Ardabili H, Rahimi A, Gouya M, Heidari A, Kabir M. Attitudes and Knowledge of HIV Positive Persons and High
Risk Behaviors Groups in Golestan, Iran. Iranian Journal of Epidemiology 2011; 7 (1) :23-31.
Figures
Figure 1
The policy framework of National Phenylketonuria Screening (NaPS) Program in Iran based on Walt & Gilson Triangle Framework
Page 13/13
Figure 2
Basic health policy analysis model based on Walt and Gilson triangle framework
