December 20, 2023
The right to good nutrition is out of reach for over 16 million children under 5 years old in the MENA region. Despite some improvements, trends in children’s nutrition have stagnated or worsened since 2000. More than 7 million (7.1) children suffer from chronic malnutrition (short for their age or stunted), and 3.7 million children suffer from acute malnutrition and are too thin for their height (wasted). Among them, 1.6 million children are severely wasted. Sudan accounts for the highest percentage of low birth-weight newborns (32%), wasting (16%), and stunting (38 %). Other countries such as Egypt and Oman also register worrying levels of stunting at 21% and 11%, respectively.
Children and young people from the poorest and most marginalized communities account for the largest share of all children suffering from malnutrition, perpetuating poverty across generations. An estimated 2 million children in Yemen are acutely malnourished, including nearly 360,000 children under the age of 5 suffering from severe acute malnutrition who are fighting to survive and are 11 times more likely to die if they do not receive treatment. Other countries such as Egypt and Oman also register worrying levels of stunting at 21% and 11%, respectively.
Growth hormone deficiency (GHD) may occur in childhood or adulthood. Childhood-onset GHD may be of all three types – congenital, acquired, or idiopathic. It causes small stature, growth retardation, and maturation delays that are unsuitable for the child’s chronological age, as indicated by the delayed lengthening of the extremity bones. Adult-onset GHD can also be idiopathic but is most frequently acquired by a pituitary tumor or brain injury. Although several reasons might lead to growth hormone deficiency, improper nutrition or diet is one of the major reasons resulting in GHD. Different levels of development are another factor associated with unequal stunting among children living in the MENA region. Oil-rich countries, e.g., Saudi Arabia, Kuwait, and Qatar, have fewer stunted children than population-rich countries, e.g., Egypt, Algeria, and Turkey.
El Mouzan et al. (2008) estimated the overall prevalence in children and adolescents with moderate and severe short stature, found in boys at 11.3% and 1.8%, respectively, and in girls, 10.5% and 1.2%, respectively. The national prevalence of short stature in Saudi children and adolescents is intermediate compared with the international level. In both school-age children and adolescents, there was a significantly higher prevalence of short stature in the MENA region compared to LATAM and APAC.
Diagnosing growth hormone deficiency typically starts with a physical exam. This can help show the doctor if there are any signs of slowed growth and has several types of diagnostic tests to make further inquiries once any physical abnormality is identified.
- Physical examination – It involves weight, height, and body proportions. This is especially important in diagnosing a child with growth hormone deficiency. A child with growth hormone deficiency does not typically follow the normal growth charts: Their growth rate is typically very slow, and the child is usually much shorter than other children of the same age. Other than a physical exam, many other tests and exams are used to diagnose growth hormone deficiency in children and adults.
- Blood tests for growth hormone deficiency – Diagnosing growth hormone deficiency (GHD) involves a multifaceted approach, with clinicians relying on a combination of clinical evaluation and specific blood tests. A primary marker for assessing GH activity is Insulin-like Growth Factor-1 (IGF-1), a protein whose levels offer a more stable indicator compared to GH. GH stimulation tests, utilizing stimuli such as insulin, arginine, clonidine, or growth hormone-releasing hormone (GHRH), directly measure the pituitary gland’s ability to release GH. Conversely, GH suppression tests, involving glucose administration, assess the negative feedback loop controlling GH secretion. Baseline GH levels, taken at various times, and specialized GHRH and GH-IGF axis testing further contribute to the diagnostic process. It’s crucial to emphasize that these tests must be considered within the broader clinical context, including a patient’s medical history and overall health. Furthermore, growth hormone deficiency might be an isolated condition or part of a more extensive hormonal deficiency, necessitating the evaluation of other pituitary hormones. Individuals suspecting GHD should consult healthcare professionals for a comprehensive assessment tailored to their specific health circumstances.
Other tools used for the diagnosis of GHD include auxology, radiographic assessment of bone age, measurement of insulin-like growth factor 1 (IGF-I) and IGF binding protein 3 (IGFBP-3), provocative growth hormone (GH) testing, cranial magnetic resonance imaging (MRI), and, in certain cases, genetic testing.
Children with GHD should be started on recombinant human growth hormone supplements when the disorder is recognized to optimize growth potential. To avoid adverse effects caused by fluid retention, good practice is to initiate treatment at low doses (0.2–0.4 mg per day by subcutaneous injection), with dose titration at 6–8 week intervals based on serum IGF1 levels together with clinical assessment for symptomatic response and adverse effects. The dosage is gradually increased to its highest dose during puberty and discontinued at or near completion of skeletal maturation when the patient may require retesting to see if GH is needed as an adult.
Three peptides regulate GH secretion: GH-releasing hormone (GHRH), ghrelin stimulating GH release and somatostatin (SS) inhibiting GH release. In circulation, GH stimulates the liver and other peripheral tissues to produce insulin-like growth factor-1 (IGF-1). When linear growth is no longer possible, GH has many important effects on lipids, body composition, strength, aerobic capacity, and quality of life in patients with adult GH deficiency.
The FDA has approved the use of Somatropin (Nutropin [Genentech)], Humatrope [Lilly], Genotropin [Pfizer], Saizen [EMD Serono], Norditropin [Novo Nordisk], TevTropin [Teva], and Omnitrope [Sandoz] for the treatment of growth hormone deficiency. Somatropin is one of the most utilized treatments for growth hormone deficiency, as it is a biosynthetic human growth hormone. Apart from Somatropin, emerging therapies like Sogroya, NGENLA, TransCon hGH, and Eftansomatropin alfa are expected to hit the markets of interest in the upcoming years and gain a patient share of growth hormone deficiency.
Patient Population of GHD in the MENA Region
GH deficiency is much evident in the MENA region due to many underlying reasons such as genetic defects, severe brain injury, being born without a pituitary gland or non-functional pituitary gland, improper nutrition, etc. Adult GH deficiency has been estimated to affect 1 in 100,000 people annually, whereas its incidence is approximately 2 cases per 100,000 population when childhood-onset GH deficiency patients are considered. About 15–20% of the cases represent the transition of childhood GH deficiency into adulthood.
- Saudi Arabia – As per Delveinsight estimates, the total patient population of GHD is expected to increase to 273,394 cases by 2032, and the total patient population of CO-GHD and AGHD is expected to increase to 263,974 and 9,420 cases, respectively.
- Kuwait – As per Delveinsight estimates, the total patient population of CO-GHD and AGHD is expected to increase to 28,138 cases and 767 cases, respectively, by 2032.
- Egypt – As per Delveinsight estimates, the total patient population of GHD is expected to increase to 282,296 cases by 2032, and the total diagnosed patient population to be increased to 641,148 cases.
Healthcare in the MENA Region
Over the last decades, healthcare expenditure has been increasing in many countries, and the Middle East and North Africa (MENA) region follows the same pattern mainly because of the high price of health technology, increased awareness about health, and lifestyle changes. As a result, healthcare systems in the MENA region face a huge challenge to keep up with the increasing demand for healthcare due to rapid population growth, a steady increase in the elderly population, and an increased prevalence of chronic, non-communicable diseases.
With a combined population of less than 400 million, the Center of Arab Genomic Studies estimates about 2.8 million patients are suffering from a rare disease in the Middle East. The region has one of the highest prevalence rates in the world for rare diseases, especially genetic diseases. This has been related to the higher rates of consanguineous marriages and advanced maternal and paternal age. To promote the treatment of these diseases, Middle Eastern governments need to improve the infrastructure for diagnosing and treating rare diseases, prioritize diseases with higher public health implications, increase awareness amongst patients and physicians, and improve access to new innovative drugs.
Market Access and Reimbursement of Growth Hormone Deficiency in the MENA Region
The huge variation of cost elements and prices of supportive care regimens, as well as the accessibility of specialized drugs, are key challenges for policymakers to make value-based judgments regarding funding and reimbursement of rare disorders. Only the most innovative and cost-effective new treatments are now considered for reimbursement. Therefore, pharmaceutical companies need to be aware of new health initiatives, to understand and cope with these differences, and to work within the new, evolving structures unlike those that have been in place at any time in the recent past. There is no indication of reimbursement for Growth Hormone Deficiency treatment.
Unfortunately, no studies or reports estimate the cost of orphan drugs in the Middle East or the Kingdom of Saudi Arabia, which will be challenging for policymakers and researchers to implement policies regarding funding and reimbursement of gene therapy and orphan drugs. The struggle to balance social values and the cost-effectiveness of costly treatments in reimbursing orphan drugs and new technologies in many disease areas is still controversial.
There is no indication of reimbursement for Growth Hormone Deficiency treatment.
Prices of orphan drugs are regulated like other drugs by the Pharmaceutical Products Pricing Committee established at the Ministry of Health by Ministerial Decree No 66 dated July 11, 2012, modified and completed, published in the Ministry of Health Official Bulletin. A new product cannot be launched on the market without a prior agreement on price. Ministry of Health grants list price attestation at the same time as the market authorization.
Orphan drugs marketed under the regimen of a temporary authorization for use (“ATU” – “Autorisation Temporaire d’Utilisation”) do not have a list price. Therefore, negotiation is directly conducted between the manufacturer and the hospital’s central pharmacy (“PCH” – “Pharmacie Centrale des Hôpitaux”), responsible for purchasing orphan drugs, to determine the transaction price.
Growth Hormone Deficiency – Challenges, Actions, and Initiatives3
Challenges Leading to GHD
- Low- and middle-income nations in the MENA area struggle with the dual burden of malnutrition (including stunting, wasting, and micronutrient deficiencies) and overnutrition (including overweight and obesity), as well as the related chronic, non-communicable diseases (NCDs).
- The nutritional condition of young children in the MENA region demonstrates disparities between and within individual countries for children under 5. The region has also long been plagued by ongoing hostilities, which has worsened the nutrition status of the most vulnerable population, women and children.
- In addition to death and injury, the effects of ongoing violence in the MENA region also include secondary indirect effects such as a worsening of social, economic, and health situations in both conflict-affected and neighboring nations. Conflict-affected nations appear to have nutrition programs more focused on treating acute malnutrition and preserving lives than non-conflict-affected nations. Additionally, these nations see greater sub-national inequality, particularly in wealth quintiles and geographic regions.
Challenges in Addressing Rare Diseases in the MENA Region4
- Low priority of rare diseases given by governments and key stakeholders.
- Low awareness amongst patients and doctors.
- Inadequate infrastructure for diagnosis and treatment of rare diseases.
- Lack of access to new innovative drugs to treat rare disease conditions.
- Diseases with higher public health implications take precedence.
- Sociocultural factors such as issues of shame and social stigma
Solutions to Overcome GHD5
- For a child’s brain to develop normally and build the groundwork for developing cognitive, motor, and socioemotional skills throughout childhood and adulthood, adequate nutrition is required during pregnancy and the first 2 years of life. Appropriate breastfeeding methods might benefit a child’s emotional and cognitive development.
- Investment in stunting is key to achieving Sustainable Development Goals such as the demand to end poverty in all its forms everywhere, end hunger, achieve food security and improved nutrition, promote sustainable agriculture, ensure healthy lives, and promote well-being for all at all ages.
Initiatives by UNICEF – Nutrition-related GHD5
Across the region, UNICEF is working to ensure that by 2030, all forms of malnutrition are eliminated. There will be a focus on nutrition for growth and development. They will recast the narrative of Nutrition in UNICEF, linking nutrition to the growth and development of children and nations.
UNICEF aims to put greater focus on:
- Complementary foods in early childhood (diet quality/diversity)
- Nutrition of school-age children and adolescents
- Prevention of overweight/obesity
- Maternal nutrition
- Food systems for children and women
- Scale up of CMAM as part of routine services for children
UNICEF will prioritize investing in stunting reduction, given its critical link to child development and overall national development and a greater recognition that stunting in near life could lead to overweight and NCDS later in life.
They also plan to use stunting as a key indicator for monitoring maternal, infant, and young child nutrition, as well as indicators relating to anemia in women of reproductive age, low birth weight, child overweight, exclusive breastfeeding, and wasting.
UNICEF will support adopting multisectoral approaches combining nutrition-specific and nutrition-sensitive interventions to bring about a more holistic, sustainable response to improved child nutrition.
MENA region is at greater risk of attaining rare diseases like growth hormone deficiency and has the highest prevalence rates in the world for rare diseases. Amongst several underlying reasons, genetic disturbances are the major reason for growth hormone deficiency in the MENA region. MENA still holds a scope for improvement in its diagnosis and treatment for GH deficiency. Despite their prevalence, rare diseases in the Middle East receive very little attention among policymakers and other stakeholders. However, there has been increased attention on orphan diseases by large Pharma companies looking to commercialize new drugs in the Middle East markets.