Abstract
Objectives
Early diagnosis of childhood growth disorders, their timely and proper treatment are important for better outcomes.The aim of the present study was to assess the results of the first 18 months of the growth disorders related twinning programme “Partners4Growth” implemented at all tertiary university pediatric endocrinology clinics in Bulgaria.
Methods
In 2019, Partners4Growth started operation at 7 centres (4 experienced and 3 twin centres) with the main aim of aligning their practices in the shortest possible time. Education of twin centres’ personnel was organized, equipment and methods for growth evaluation and follow-up were standardized. The approach was tested initially at one centre. At baseline and at the 18th month a questionnaire concerning diagnosis and management of recombinant human growth hormone (rhGH) requiring disorders was applied.
Results
A total of 104 new patients were diagnosed compared to 30 in the previous year. Of those, 91 started rhGH treatment – 65 (64 %) GH deficient, 12 (12 %) Turner syndrome, 7 (7 %) Prader–Willi syndrome patients, and 7 (7 %) born small for gestational age without postnatal catch-up, representing 35.8 % of all currently rhGH treated Bulgarian children. A better geographical coverage and more advanced diagnostic and management practices were achieved.
Conclusions
Partners4Growth facilitated the alignment of the tertiary pediatric endocrinology centres competences thus leading to an improved diagnosis and treatment of growth disorders as well as better patients’ access. For its short existence, the Programme increased significantly the number of new patients in the difficult times of COVID-19 pandemic thus justifying its continuation.
Funding source: The Program is run by the Bulgarian Pediatric Association with the support of an unrestricted educational grant from the Pfizer company
Acknowledgments
The authors would like to acknowledge the contribution of Vladimir Pilosoff, former BPA Chair, for his devotion and contribution to the Partners4Growth Programme. They will also like to thank all past, current and future pediatric endocrinologists, nurses and non-medical staff at the tertiary clinics who are devoted to the development of the patient care and treatment. We are also indebted to our patients and their families who follow our advice.
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Research funding: The Program is run by the Bulgarian Pediatric Association with the support of an unrestricted educational grant from the Pfizer company.
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Author contributions: Stanimira Elkina – Wrote the first draft of the paper and subsequent revised drafts with the help and supervision of Violeta Iotova. Irina Halvadzhiyan – Collected data and contributed to the analysis of data, read, revised, and approved the paper drafts. Galina Popova – Contributed data, read, revised, and approved the paper drafts. Daniela Avdjieva-Tzavella – Contributed data, read, revised, and approved the paper drafts. Elisaveta Stefanova (deceased) – Contributed data. Nartzis Kaleva – Contributed data, read, revised and approved the paper drafts. Iva Stoeva – Conceived and designed the research, read, revised and approved the paper drafts. Chayka Petrova – Contributed data, read, revised, and approved the paper drafts. Violeta Iotova – Conceived and designed the research, Contributed data, participated in drafting the paper, revised, and approved the paper drafts as well as the final draft.
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Competing interests: Authors declare an educational grant by Pfizer provided to the Bulgarian Pediatrics Association. The funding organization played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Informed consent: Not applicable.
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Ethical approval: This type of audit study does not imply for an ethical clearance per se.
Appendix 1. Questionnaire addressed to Bulgarian pediatric endocrinologists from tertiary centers participating in the Programme “Partners4Growth”
At baseline of the Programme
In which year was your Centre for diagnostics and treatment of children suffering from growth hormone deficiency (GHD) and related conditions established?
How many children needing treatment with recombinant human growth hormone (rhGH) have you diagnosed during the last year?
How many children, girls and boys, respectively, with GHD (isolated and combined) are you currently treating? What is their age range?
What technical anthropometric equipment are you using to examine your patients? Do you take height measurements of both parents?
What auxological methods for assessment of your patients are you using: growth charts on paper, web-based applications and software, others?
What is your preferred method of presenting growth deviations (SDS, percentiles)?
What is the minimal period for monitoring of growth velocity at your Centre?
Which conditional curves are you using at your Centre?
Which method for bone age assessment are you using?
Which tests are mandatory at your Centre before you proceed with GH stimulation tests – hormonal, non-hormonal, others?
Which stimulation test is your first choice in diagnosing GHD?
Which stimulation test is your second choice in diagnosing GHD?
Which stimulation test is your third choice in diagnosing GHD?
What is the GH cut-off value in stimulation tests adopted by your Centre to differentiate GHD from normal response?
What laboratory method for GH testing are you using at your Centre?
What laboratory method for IGF-1 testing are you using at your Centre?
Are you testing for IGFBP-3 and, if so, what laboratory method are you using for the purpose?
Are you administering sex steroids as a priming before GH stimulation tests?
If you perform priming, are you considering the calendar age or the bone age of the patient in doing so and what is the age threshold for each gender at your Centre?
What medications and in what doses/regimen are you administering as GH tests priming for boys and girls, respectively?
What is the cut-off value set by your Centre in testing spontaneous GH secretion in newborns suspected for GHD?
What other diagnostic procedures are you routinely using in your practice with children with suspected GHD before commencing treatment with rhGH?
What is the initial dose of rhGH preferred by your Centre for treatment of children diagnosed with GHD?
What dose of rhGH are you administering to children with GHD during active puberty?
How do you regulate the rhGH dose in the course of the treatment?
How do you monitor the treatment with rhGH of children suffering from GHD during each visit? At what intervals?
What tests for assessment of cortisol secretion do you offer?
When is treatment with rhGH discontinued?
Are you administering medications to slow down pubertal development during treatment with rhGH? If yes, please list the medications you use.
How do you induce puberty in boys and girls suffering from hypogonadotropic hypogonadism: according to the calendar age or to the bone age?
Do you start treatment with rhGH in idiopathic short stature and when?
What is the period between the end of treatment of craniopharyngioma or other, including malignant, tumors and the beginning of treatment with rhGH in cases of organic hypopituitarism?
Have you observed any side effects of the treatment with rhGH?
What is your approach in newly diagnosed patient with GHD (referrals, treatment, follow up)?
At the 18 month after the start of the Programme’s implementation
In which year was your Centre (practice) for diagnostics and treatment of children suffering from growth hormone deficiency (GHD) and related conditions established?
How many children needing treatment with recombinant human growth hormone (rhGH) did you diagnose from 1 June 2019 to 30 November 2020?
How many children began treatment with GHD (isolated and combined) at your Centre from 1 June 2019 to 30 November 2020?
How many children, girls and boys, respectively, with GHD (isolated and combined) are you currently treating? What is their age range?
How many children, girls and boys, respectively, with Prader-Willi syndrome are you currently treating? What is their age range?
How many girls with Turner syndrome and boys with karyotype 45Х/46ХУ are you currently treating? What is their age range?
How many children, girls and boys, respectively, born small for gestational age (SGA), with or without syndromes, are you currently treating? What is their age range?
What technical anthropometric equipment are you using to examine your patients? Do you take height measurements of both parents?
What auxological methods for assessment of your patients are you using: growth charts on paper, web-based applications and software, others?
What is your preferred method of presenting growth deviations (SDS, percentiles)?
What is the minimal period for monitoring of growth velocity at your Centre?
Which conditional curves are you using at your Centre?
Which method for bone age assessment are you using?
When do you start testing to confirm diagnosis growth hormone deficiency?
Right after the diagnosis if there are written data about previous growth;
After 6 months follow-up of growth velocity;
After 12 months follow-up of growth velocity.
Which tests are mandatory at your Centre before you precede with GH stimulation tests – hormonal, non-hormonal, others?
Which stimulation test is your first choice in diagnosing GHD?
Which stimulation test is your second choice in diagnosing GHD?
Which stimulation test is your third choice in diagnosing GHD?
What is the GH cut-off value in stimulation tests adopted by your Centre to differentiate GHD from normal response?
What laboratory method for GH testing are you using at your Centre?
What laboratory method for IGF-1 testing are you using at your Centre?
Are you testing for IGFBP-3 and, if so, what laboratory method are you using for the purpose?
Are you administering sex steroids as a priming before GH stimulation tests?
If you perform priming, are you considering the calendar age or the bone age in doing so and what is the age threshold for each gender at your Centre?
What medications and in what doses/regimen are you administering as GH tests priming for boys and girls, respectively?
What is the cut-off value set by your Centre in testing spontaneous GH secretion in newborns suspected for GHD?
What other diagnostic procedures are you routinely using in your practice with children with suspected GHD before commencing treatment with rhGH?
What is the initial dose of rhGH preferred by your Centre for treatment of children diagnosed with GHD?
What is the initial dose of rhGH preferred by your Centre for treatment of children diagnosed with PWS?
What is the initial dose of rhGH preferred by your Centre for treatment of children diagnosed with TS?
What is the initial dose of rhGH preferred by your Centre for treatment of SGA children without postnatal catch-up?
What dose of rhGH are you administering to children with GHD during active puberty?
How do you regulate the rhGH dose in the course of the treatment?
How do you monitor the treatment with rhGH of GHD children during each visit? At what intervals?
What tests for assessment of cortisol secretion do you offer?
When is treatment with rhGH discontinued?
Are you administering medications to slow down pubertal development during treatment with rhGH?
If yes, please list the medications you use.
How do you induce puberty in boys and girls suffering from hypogonadotropic hypogonadism: according to the calendar age or to the bone age?
What is the period between the end of treatment of craniopharyngioma and other, including malignant, tumors and the beginning of treatment with rhGH in cases of organic hypopituitarism?
Have you observed any side effects of the treatment with rhGH?
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