El ámbito cultural de la ERE en los jóvenes

The Metabolic Services of the Medical Genetics Department at King Faisal Specialist Hospital and Research Centre (KFSH&RC) in Riyadh, Saudi Arabia, is one of the major tertiary care referral centres for metabolic disorders in the region of Saudi Arabia and some neighbouring countries. It has always collaborated with other health care centres in Bahrain, Kuwait, Qatar, Oman, and United Arab Emirates for the diagnosis of genetic disorders (Al-Odaib et al., 2003; and Therrell, 2003).

The disorders seen at KFSH&RC include organic acidaemias, amino acidaemias, fatty acid oxidation defects, and lysosomal storage and peroxisomal disorders among others. In the past the affected infants were identified through diagnosis after

symptomatic presentation or through selective screening at KFSH&RC and affiliated hospitals. Selective screening included infants born at these hospitals and infants born

to families with known history of any of the disorders. A newborn screening

programme started in 2005 as a pilot, and gradually increased the number of screened newborns each year becoming a national programme in 2011 (more details in the following section).

2.5.1 Incidence of IEM in Saudi Arabia

The true incidence of each metabolic disorder in Saudi Arabia is yet to be identified.

There are a few small studies conducted to measure the incidence of metabolic disorders in different regions of the country.

Rashed and colleagues (1999) carried a pilot study of newborn screening using MS/MS at KFSH&RC. They screened 27,624 samples from KFSH&RC and two other Saudi hospitals, and diagnosed 20 cases of metabolic disorders. They reported that this yielded a frequency of 1:1381 live births for a collection of 10 metabolic disorders. This newborn screening continued on a small scale until the start of the national newborn screening pilot programme in 2005 (Saadallah & Rashed, 2007).

However, these results need to be interpreted with caution. The study was carried out in hospitals catering for high risk patients; mothers of previously diagnosed children with any metabolic disorder are followed-up here during pregnancy until they give birth to test the new baby. Additionally, KFSH&RC is a tertiary hospital, many infants with unknown diagnoses are referred to it.

Moammar and colleagues (2010) carried out a retrospective study in the Saudi Aramco Medical Centre, a major hospital at the Eastern Province of Saudi Arabia.

They reviewed the medical records of Saudi patients at the hospital from 1983 up to 2008, in an effort to measure the incidence of metabolic disorders in that region. They identified 248 patients, who had 55 different metabolic disorders, yielding a

prevalence of 1:667. The most commonly seen disorders were lysosomal storage disorders, organic acidopathies, and aminoacidopathies. Nearly all the patients in the study were children from consanguineous marriages. The authors believe that this warrants a prompt expansion of the newborn screening programme. They recommend providing regional treatment and follow-up care facilities with the availability of genetic counselling for the families.

Another retrospective study was conducted by Al Bu Ali and colleagues (2011) in AlAhsa city of the Eastern Province in Saudi Arabia. They reviewed the files of all the babies born in the AlAhsa Maternity and Children hospital from April 2006 till 2009. They identified 43 patients, who had 14 different metabolic disorders, reporting a prevalence of 1:774. The most common metabolic disorders found in this population were 3-methylcrotonyl-CoA carboxylase deficiency and biotinidase deficiency, followed by medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glutaric acidemia type II.

The Saudi Ministry of Health has reported the rate of metabolic disorders among newborns as 1:1000 (Afifi & Abdul-Jabbar, 2007). This early information from the pilot newborn screening programme speculated that there will be approximately 500 new cases of metabolic disorders each year. This validated the necessity of having a national newborn screening programme, to help reduce harm and disability in the community.

The most recent report about the progress of the newborn screening programme in Saudi was published on the PSCDR website describing progress up to the end of the year 2010 (Al-Odaib et al., 2011). It summarises the expansion plans for the

programme, and states that the rate of the 16 disorders screened for is 1:1000 live births after 5 years of increased screening.

The incidence of metabolic disorders in Saudi Arabia is comparable to the reported incidence from the Arab Gulf region, as reviewed in the previous section. However, it is higher than what is reported from Europe and Canada. The overall incidence of metabolic diseases in British Columbia was approximately 1:2500 (Applegarth, Toone, & Lowry, 2000). In Italy the incidence of approximately 200 diseases was reported as 1:2555 (Dionisi-Vici et al., 2002). An incidence of 1:2517 was reported from Germany (Lindner et al., 2007). While in the West Midlands, UK, the overall birth prevalence of metabolic disorders was 1:784 live births (Sanderson, Green, Preece, & Burton, 2006).

One reason for the higher incidence of metabolic disorders in the West Midlands is thought to be the high ethnic diversity of the study population (Sanderson et al., 2006). The other studies reported low ethnic minority groups in their study

populations. Although these studies have included different disorders in their

calculations, but they give an understanding of the disease burden in each area. In a previous study in the West Midlands metabolic disorders were reported to be 1:2691 for Whites and 1:318 for Pakistanis (Hutchesson, Bundey, Preece, Hall, & Green, 1998). This demonstrates the variation of incidence among different ethnic groups and the importance of knowing the prevalent disorders in each community to provide adequate services.

In an important step towards obtaining the epidemiological data needed for service planning and provision of care, the Saudi National Genetic and Birth Defects Registry (NGBDR) project started in January 2003. It is funded by the Prince Salman Centre for Disability Research (PSCDR) in collaboration with the KFSH&RC toestablish and maintain a national registry of genetic disorders, birth defects, and developmental disabilities in Saudi Arabia (PSCDR, 2012).

2.5.2 Newborn screening in Saudi Arabia

Health care is considered a right for Saudi citizens, thus health services and medications are provided nationally for free. There are ample private health care providers as well. Health services have improved vastly during the past 30 years in Saudi Arabia, but establishing preventative medicine was slow. Services such as premarital screening and newborn screening took a long time to develop, in spite of the high incidence of manageable metabolic disorders in Saudi Arabia. Since 1993 researchers from the KFSH&RC have asserted that the use of new technology such as MS/MS for newborn screening in Saudi Arabia is efficient, cost-effective, and

prevents the community from dealing with the emotional and financial burden of caring for many disabled children. They have highly recommended it, especially because KFSH&RC have acquired the technology for diagnostic and selective screening purposes (Nasserullah et al., 1998; Rashed & Ozand, 1993; and Ozand, 1998). Yet it was not until 2005 that a pilot for a national newborn screening programme started in Saudi Arabia.

The pilot started with the aim of screening 50,000 newborns per year from 24 hospitals in the main cities of Saudi Arabia, and gradually involving more hospitals and increasing the number of screened newborns. The disorders screened for are:

Phenylketonuria (PKU), Maple Syrup Urine Disease (MSUD), Arginosuccinase Deficiency (ASL), Citrullinemia (ASD), HMG-CoA Lyase Deficiency (HMG), Isovaleric Acidaemia (IVA), Methylmalonic Acidaemia (MMA), Propionic Acidaemia (PA), Beta-ketothiolase Deficiency (BKT), Methylcrotonyl-CoA

Carboxylase Deficiency (3MCC), Glutaric Acidaemia type-I (GA-I), Medium-chain acyl-CoA dehydrogenase deficiency (MCAD), Galactosemia (GAL), Congenital Hypothyroidism (CH), Congenital Adrenal Hyperplasia (CAH), and Biotinidase Deficiency (BD) (Afifi & Abdul-Jabbar, 2007; and Ministry of Health, 2012).

The programme has expanded gradually, screening 130,000 newborns in the year 2011. Samples were sent from 86 hospitals around the country. They predict that by the end of the year 2014 they would be screening all newborns (S. Alabdulmunem, personal communication, May 16, 2012). The latest statistics show that Saudi Arabia has a total of 408 government and private hospitals, more than two thirds with maternity and child services. The number of newborns in Saudi Arabia in the year 2010 was estimated to be just over 600,000 live births (Ministry of Health, 2010).

The Saudi newborn screening programme, now named “The National Programme for Reducing Disability through Early Examination of Infants”, is a collaboration

between the Ministry of Health (MOH), KFSH&RC, and PSCDR. Administration is by the PSCDR, supervision and finance are by the MOH, and The National

Laboratory for Newborn Screening (NLNBS) is housed at the KFSH&RC and equipped to screen all newborns in the country (Afifi & Abdul-Jabbar, 2007; and Al-Odaib et al., 2011).

The programme was not mandatory, but rather a collaborative effort, where hospitals were asked to collaborate in sending the samples to the NLNBS. It has been

announced that in 2012 the programme has become mandatory and all public, military, and private hospitals were urged to ensure their readiness for participation (Ministry of Health, 2011).

The PSCDR has established a secure web portal, to allow direct access for hospitals to the results of newborns screened at their facilities. The aim is to expedite and

facilitate the process of conveying the results to the families and their health care providers as quick as possible (Al-Odaib et al., 2011). This is a crucial measure to

employ early in the programme, as timely reporting of positive results is one of the main challenges to newborn screening programmes as discussed by Downing et al (2010). They advocate the use of electronic health information technology to advance the quality and effectiveness of newborn screening.

Abhyankar and colleagues (2010) describe the development of a template for an electronic message to report the results of newborn screening to hospitals and care providers. Several states in the US are implementing this technology, which made communicating results more rapid and effective. Making use of existing technologies would benefit the developing Saudi newborn screening programme. Such

technologies could in addition facilitate the dissemination of educational material for the health care providers and the families regarding newborn screening and

interpretation of results (Downing, Zuckerman, Coon, & Lloyd-Puryear, 2010).

The PSCDR has also started building a database for the newborn screening results (Al-Odaib et al., 2011). This is important for long-term surveillance of services, quality improvement, and research (Berry et al., 2010; and Kemper et al., 2008).

Recording all results in one database will give a true measure of the incidence of each disorder within the screening programme.

With the high incidence of metabolic disorders in Saudi Arabia there are evidently commendable efforts for expanding the newborn screening programme to all newborns in the country. It is crucial to implement a public health education programme to increase the level of public awareness about newborn screening, metabolic disorders, and their management. This is elemental for the understanding and acceptance of a new programme by the community, and ultimately its success (Afifi & Abdul-Jabbar, 2007; and Moammar, Cheriyan, Mathew, & Al-Sannaa, 2010).

Educating parents should start before the birth of their infants. Primary health care providers, midwives, and obstetrics need to be educated and involved in educating parents about newborn screening and its importance (Downing et al., 2010). Davis and colleagues (2006) discovered through interviewing new parents and health care providers that they had inadequate information about newborn screening. Parents and providers wanted concise and brief information on newborn screening and agreed that

it should be given before the birth of the baby. The availability of trained health care providers to cater for diagnosed patients from recall after positive results, to

education, to follow-up, and management are essential for the success of the

programme (Burgard et al., 2011; Howell & Lloyd-Puryear, 2010; and Therrell et al., 2010).

Newborn screening should not be viewed as an end in itself. It should be part of a comprehensive public health programme encompassing follow-up, confirmatory diagnosis, family education, counselling, management, and provision of various services for affected individuals and their families, including continuous evaluation (Kaye & the Committee on Genetics, 2006; and Pass et al., 2000).

Researchers affirm the importance of a timely and well planned follow-up system for the well-being of the patients detected by newborn screening programmes (Downing et al., 2010; and Kuroda & Ito, 1999). Long-term follow-up needs systemic and comprehensive planning to ensure seamless high quality care and treatment throughout life for the patients. This needs continuous staff training, quality

assurance, care coordination, updated treatments, and research (Berry et al., 2010; and Kemper et al., 2008).

One of the challenges for the newborn screening programme in Saudi Arabia could be the limited health personnel and resources in small towns and remote villages.

Difficulties in managing cases from remote areas were in reaching them and in

persuading their families to follow up at specialised centres (Nasserullah et al., 2003).

This highlights the need for public education about the newborn screening programme and the disorders, and the need for more specialised health care providers. Many workshops have been organised and training programmes are being developed to improve the knowledge and expertise of health care providers (S. Alabdulmunem, personal communication, May 16, 2012).

Cultural issues, politics, education, technology, and financing will always be

challenging obstacles to implementing newborn screening programmes (Saadallah &

Rashed, 2007; and Therrell, 2003). Educating policy and decision makers about the benefits of the programme, setting laws and regulations to govern important issues such as confidentiality and accessibility, continuous training for professionals, and

instituting public health education programmes about newborn screening can

positively help overcome these challenges (Therrell, 2003; and Therrell et al., 2010).

Quality development and evaluation have been part of the Saudi newborn screening programme due to its participation in the Newborn Screening Quality Assurance Programme (NSQAP) since 2004. The programme is sponsored by the Centres for Disease Control and Prevention (CDC) and the Association of Public Health

Laboratories (APHL), and housed in the CDC. The programme provides guidelines, training, consultation, technical assistance, and quality control material for newborn screening laboratories, to help improve their screening accuracy and reliability (Centers for Disease Control and Prevention, 2013; and De Jesús, Mei, Bell, &

Hannon, 2010). The Saudi newborn screening programme is also a member of a member of the European Research Network for Evaluation and Improvement of screening, Diagnosis and Metabolism (ERNDIM) Quality Assurance Programme (Al-Odaib et al., 2011).

All the components may not be fully ready in the Saudi newborn screening

programme. Nonetheless, it is improving and steadily heading towards reaching the goal of screening all newborns in the country.

2.5.3 Schemes implemented in Saudi Arabia to reduce the burden of genetic diseases

Premarital screening

Premarital carrier detection for sickle-cell disease and thalassaemia has been implemented in Saudi Arabia since 2002. The Saudi MOH instituted legislation mandating premarital screening from 2004, but it does not prevent identified at risk couples from choosing to take the risk and marry (Al-Odaib et al., 2003; and El-Hazmi, 2004b). Testing for the human immunodeficiency virus (HIV), and the hepatitis viruses B and C (HBV and HCV) was added to the programme in 2008 (Alswaidi & O'Brien, 2009). It was accepted by the community as a step towards prevention, as it enables would-be couples to make informed decisions about marriage and the risks involved (Al-Aama, 2010; Alam, 2006; and Meyer, 2005).

Memish and Saeedi (2011) evaluated the effects of the Saudi premarital screening programme after six years of its implementation. The number of couples who were found to be carriers of sickle-cell or thalassaemia traits and cancelled their marriage plans increased five folds, from only 9% at the start of the programme in 2004 to 52%

in 2009. The remaining 48% of couples still went ahead with their wedding plans even though they were carriers and at high risk of having affected children.

Several researchers believe that the timing of the screening test is not optimum. It is usually done after the couple’s engagement and just before issuing the marriage certificate; therefore the couple’s commitment to each other or their worry of social stigma may be the reason for not cancelling their marriage plans. Other reasons could be the failure of proper referral of carrier couples to genetic counselling, or the couples have been given inadequate information about the risk factors (Aama, Al-Nabulsi, Alyousef, Asiri, & Al-Blewi, 2008; Alhamdan, Almazrou, Alswaidi, &

Choudhry, 2007; and Memish & Saeedi, 2011).

The effects of this programme can be improved through providing more information in the media, including information about it in high school and college curriculums, strengthening education about the disease for at-risk couples, encouraging couples to test early on before any wedding plans, and by offering singles the screening test right after high school (Al-Aama et al., 2008; Alhamdan et al., 2007; Ibrahim et al., 2011;

and Memish & Saeedi, 2011). Screening could also be offered to the extended family of patients before any plans of marriage (Al-Shahrani, 2009; and Ozand, Odaib, Sakati, & Al-Hellani, 2005).

Prenatal diagnosis

Prenatal diagnosis has been well received among Muslims in many countries, as Islam allows pregnancy termination in the first trimester for health reasons (Modell & Darr, 2002). In Islam, pregnancy termination is permitted if the foetus is diagnosed with a severe and untreatable condition, and both parents agree. This must be carried out before the pregnancy reaches 120 days from conception (Albar, 2002).

Saudi parents accept prenatal diagnosis, and many are starting to accept the idea of pregnancy termination after understanding that religiously it is permitted for severe conditions (Alkuraya & Kilani, 2001; Alsulaiman & Hewison, 2007; and Alsulaiman

et al., 2012). Families affected by a serious condition had more favourable views towards abortion than families who didn’t. However, induced abortion is rarely practised in Saudi hospitals. Religious interpretations are strong in the Saudi culture, and abortion conveys ethical dilemmas for many families (Al-Odaib et al., 2003; and Alsulaiman & Abu-Amero, 2013).

Pre-implantation genetic diagnosis (PGD)

PGD is a procedure used for couples at high risk of having children with genetic disorders. It is best suited for monogenic disorders and structural chromosome abnormalities (Geraedts & De Wert, 2009). PGD involves testing of embryos, produced through in-vitro fertilization (IVF), for the genetic disorder. One or two of the unaffected embryos are then implanted into the uterus. It has almost universally assured the delivery of a healthy infant and is recognized as a significant alternative to prenatal diagnosis. It eliminates the dilemma of terminating an affected pregnancy. It has been accepted by families and applied around the world in IVF and PGD centres (Harper & SenGupta, 2012; and Lavery et al., 2002). Nonetheless, it is a challenging procedure, and patients need to understand that risk of misdiagnosis cannot be

eliminated (Harton et al., 2011; and Wilton, Thornhill, Traeger-Synodinos, Sermon, &

Harper, 2009).

With PGD there is a need for IVF and embryo testing, both are invasive procedures not free from risk. Risks include high patient discomfort, stress and anxiety, reaction to fertility drugs, some embryos may be damaged by the process of cell removal for testing, failure of procedure, miscarriage, ectopic pregnancy, and ovarian

hyperstimulation syndrome (Bhattacharya, 2003; El-Hazmi, 1999; Heijnen, Macklon,

& Fauser, 2004; and Olivennes, 2003). In addition, there are risks to the infant. These include low birth weight, congenital abnormalities, and peri-natal mortality (Harton et al., 2011).

A few studies have examined the acceptance of PGD among Saudi couples. Most welcomed the idea as a way of preventing the birth of an affected child (Alkuraya &

Kilani, 2001; Alsulaiman, Al-Odaib, Al-Rejjal, & Hewison, 2010; and Alsulaiman &

Hewison, 2006). Families who had undergone PGD report experiencing more ethical and psychological stress than anticipated (Alsulaiman et al., 2010). PGD is a complex

procedure that continues to evolve and develop with new tools and approaches. It is not an easy process for the families, therefore counselling services should be an integral part of care to help the families through the difficult stages of this technology

procedure that continues to evolve and develop with new tools and approaches. It is not an easy process for the families, therefore counselling services should be an integral part of care to help the families through the difficult stages of this technology