Managing Paediatric Growth Disorders: Integrating Technology Into a Personalised Approach

Long-term growth management can be challenging for patients, families and healthcare professionals (HCP). Personalised optimal responses to growth hormone (GH) therapy depend on the creation of a good working relationship between the patient and family and the HCPs responsible for care. Current unmet needs in growth management will be discussed, focusing on the likelihood of a poor growth response and its identification and management with emphasis on the importance of good adherence to GH therapy. Digital tools are now available to record injections and communicate accurate adherence data to the HCP and patient. Psychological barriers to good adherence will be covered, with techniques identified to change behaviour and improve outcome. Motivational interviewing is a valuable skill in this respect and should be taught to both medical and nursing HCPs to enhance the quality of the relationship with the patient and family. Key messages are, firstly, the importance of personalised care with the HCP using acquired psychological skills to prevent and manage poor adherence. Secondly, a human-eHealth partnership is necessary to maximise the benefit of new digital tools to aid in successful growth management.

Abnormal linear growth in paediatric adrenal diseases: Pathogenesis, prevalence and management.

Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.

Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants.

AIM: To analyze different methods to assess postnatal growth in a cohort of very premature infants (VPI) in a clinical setting and identify potential early markers of growth failure. METHODS: Study of growth determinants in VPI (≤32 weeks) during hospital stay. Nutritional intakes and clinical evolution were recorded. Growth velocity (GV: g/kg/day), extrauterine growth restriction (%) (EUGR: weight < 10th centile, z-score < -1.28) and postnatal growth failure (PGF: fall in z-score > 1.34) at 36 weeks postmenstrual age (PMA) were calculated. Associations between growth and clinical or nutritional variables were explored (linear and logistic regression). RESULTS: Sample: 197 VPI. GV in IUGR patients was higher than in non-IUGRs (28 days of life and discharge). At 36 weeks PMA 66.0% of VPIs, including all but one of the IUGR patients, were EUGR. Prevalence of PGF at the same time was 67.4% (IUGR patients: 48.1%; non-IUGRs: 70.5% (p = 0.022)). Variables related to PGF at 36 weeks PMA were initial weight loss (%), need for oxygen and lower parenteral lipids in the first week. CONCLUSIONS: The analysis of z-scores was better suited to identify postnatal growth faltering. PGF could be reduced by minimising initial weight loss and assuring adequate nutrition in patients at risk.

Impact of Universal Health Coverage on Child Growth and Nutrition in Argentina.

OBJECTIVES: To estimate trends of undernutrition (stunting and underweight) among children younger than 5 years covered by the universal health coverage programs Plan Nacer and Programa Sumar. METHODS: From 2005 to 2013, Plan Nacer and Programa Sumar collected high-quality information on birth and visit dates, age (in days), gender, weight (in kg), and height (in cm) for 1.4 million children in 6386 health centers (13 million records) with broad coverage of vulnerable populations in Argentina. RESULTS: The prevalence of stunting and underweight decreased 45.0% (from 20.6% to 11.3%) and 38.0% (from 4.0% to 2.5%), respectively, with differences between rural versus urban areas, gender, regions, age, and seasons. CONCLUSIONS: Undernutrition prevalence substantially decreased in 2 programs in Argentina as a result of universal health coverage.

Growth assessment and risk factors of malnutrition in children with cystic fibrosis.

OBJECTIVES: To evaluate the nutritional status, to screen for the presence of malnutrition, and to study the possible risk factors associated with malnutrition in patients with cystic fibrosis (CF). METHODS: A retrospective cross-sectional review of medical records of all diagnosed CF patients in the Pediatric Department, Salmaniya Medical Complex, Manama, Kingdom of Bahrain, between January 1984 and May 2015 was conducted. Demographic and anthropometric data were collected from records of last visit to CF clinic. Nutritional status and risk factors of malnutrition were assessed. RESULTS: All records of 109 CF patients were reviewed. Forty-seven pediatric patients were included in the study. All included patients were on pancreatic enzyme replacement and 42 (89%) received high-calorie supplementation. Growth failure was noted in 34 (72%) patients, 19 (56%) were wasted and stunted, 8 (23.5%) were wasted only, and 7 (20.5%) were stunted. Low birth weight (p=0.032), and the presence of gastroesophageal reflux disease (GERD) (p=0.039) were the significant risk factors for malnutrition. CONCLUSIONS: Most CF patients in Bahrain (72%) are malnourished. Low birth weight and the presence of GERD are risk factors.

Parental Concerns Influencing Decisions to Seek Medical Care for a Child's Short Stature.

AIMS: To examine parental concerns about child growth and factors that drive parents' decisions whether to intervene medically with their child's height. METHODS: Parents of 9- to 14-year-old pediatric primary care patients of various heights, oversampled for those with short stature, participated in exploratory focus groups and nominal group technique sessions. Growth concerns expressed by the groups were incorporated into a survey, completed by 1,820 parents, and rated for their degree of impact on medical decision-making. Ordinal logistic regression modeled concern scores against parent traits. Explanatory focus groups clarified the survey results. RESULTS: Research team consensus and factor analysis organized the 22 distinct concerns expressed by the parent groups into 7 categories. Categories rated as having the greatest influence on parental decision-making involved: treatment efficacy and side effects, child health and psychosocial function. Level of concern was highly associated with parental education and parenting style. CONCLUSION: Psychosocial issues are influential, but parental decision-making is most impacted by concerns about treatment and child health. By discussing the real risks and benefits of hormone treatment and addressing parents' perceptions of what is needed for physical and psychosocial health, clinicians can be highly effective educators to assure that treatment is used only as medically indicated.

Efectividad y seguridad de la somatropina para el tratamiento de la restricción del crecimiento en niñas con síndrome de Turner / Effectiveness and safety of somatropin for the treatment of growth restriction in girls with Turner syndrome

Introducción: la somatropina es una opción para el tratamiento de la restricción del crecimiento en niñas con síndrome de Turner. Esta evaluación tecnológica se desarrolló en el marco de la actualización integral del Plan Obligatorio de Salud para el año 2015. Objetivo: evaluar la efectividad y seguridad de la somatropina comparada con placebo o no tratamiento para la restricción del crecimiento en niñas con síndrome de Turner. Metodología: la evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS, sin restricciones de idioma y limitada a revisiones sistemáticas publicadas en los últimos cinco años. Las búsquedas en bases de datos fueron hechas entre octubre y diciembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por dos revisores de forma independiente y los desacuerdos fueron resueltos por consenso. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad. Se seleccionaron revisiones sistemáticas de ensayos clínicos, su calidad fue valorada con la herramienta AMSTAR. Las características de las revisiones fueron extraídas a partir de las publicaciones originales. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés a partir de los estudios de mejor calidad con AMSTAR. Resultados: se seleccionó una revisión sistemática que incluyó 28 ensayos clínicos (1830 pacientes), cinco de estos ensayos (496 pacientes) fueron relevantes para la pregunta abordada por la presente evaluación. La somatropina comparada con placebo se asoció con un aumento estadísticamente significativo de la velocidad de crecimiento y no presentó una diferencia estadísticamente significativa sobre el contenido mineral óseo total. En comparación con no tratamiento, la somatropina se asoció con un aumento estadísticamente significativo de la velocidad de crecimiento, desviación estándar de la velocidad de crecimiento, talla, desviación estándar de la talla, desviación estándar de la talla para adulto con Turner y desviación estándar de la talla ajustada por edad específica para síndrome de Turner. La velocidad de crecimiento fue significativamente más alta con bajas y altas dosis de somatropina en comparación con placebo. Se presentó una diferencia estadísticamente significativa en contra de la somatropina versus placebo sobre la frecuencia de otitis media (ocurrencia/empeoramiento). En comparación con no tratamiento, la somatropina se asoció con una disminución estadísticamente significativa en la aparición de bocio, y un aumento estadísticamente significativo en la ocurrencia de procedimientos quirúrgicos, otitis media, trastornos del oído, trastornos de la articulación, trastornos respiratorios y sinusitis. Conclusiones: el desempeño global de la somatropina para el tratamiento de la restricción del crecimiento en niñas con síndrome de Turner, muestra que la mayoría de los desenlaces de efectividad favorecen a la somatropina, mientras que la mayoría de los eventos adversos están en contra de esta tecnología. Estas conclusiones se basan en los hallazgos de una revisión sistemática de alta calidad.(AU)

Efectividad y seguridad de la somatropina para el tratamiento de niños con déficit de la hormona del crecimiento / Effectiveness and safety of somatropin for the treatment of children with growth hormone deficiency

Introducción: la somatropina es una opción para el tratamiento del déficit de la hormona del crecimiento en niños. Esta evaluación tecnológica se desarrolló en el marco de la actualización integral del Plan Obligatorio de Salud para el año 2015. Objetivo: evaluar la efectividad y seguridad de la somatropina comparada con placebo o no tratamiento para el déficit de la hormona del crecimiento en niños. Metodología: la evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS, sin restricciones de idioma y limitada a revisiones sistemáticas publicadas en los últimos cinco años. Las búsquedas en bases de datos fueron hechas entre octubre y diciembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por dos revisores de forma independiente y los desacuerdos fueron resueltos por consenso. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad. Se incluyeron revisiones sistemáticas de ensayos clínicos, su calidad fue valorada con la herramienta AMSTAR. Las características de las revisiones fueron extraídas a partir de las publicaciones originales. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés a partir de los estudios de mejor calidad con AMSTAR. Resultados: se seleccionó una revisión sistemática que incluyó 28 ensayos clínicos (1830 pacientes), uno de estos ensayos (19 pacientes) fue de interés para la presente evaluación. La somatropina comparada con no tratamiento se asoció con un aumento estadísticamente significativo de la velocidad de crecimiento, la desviación estándar de la talla y los niveles de IGF-1 (somatomedina C). Conclusiones: el desempeño global de la somatropina para el tratamiento de niños con déficit de la hormona del crecimiento, muestra que la totalidad de los desenlaces de efectividad favorecen a la somatropina, en cuanto a su seguridad comparativa existe incertidumbre. Estas conclusiones se basan en los hallazgos de una revisión sistemática de alta calidad.(AU)

Efectividad y seguridad de somatropina para el tratamiento del retardo de crecimiento en niños menores de 18 años con insuficiencia renal crónica / Effectiveness and safety of somatropin for the treatment of growth retardation in children under 18 years of age with chronic renal failure

Antecedentes: Descripción de la condición de salud de interés: La Insuficiencia Renal Crónica (IRC) es un síndrome clínico complejo, resultante de un deterioro progresivo e irreversible de la función renal, que se traduce en la incapacidad del riñón para remover los productos de desecho y mantener la homeostasis orgánica. Puede producirse por una variedad de condiciones, incluyendo trastornos congénitos, glomerulares o infecciones. Descripción de la tecnología: La HC es una hormona no sexual, producida en el lóbulo anterior de la glándula pituitaria o hipófisis, en respuesta fundamentalmente, al factor liberador de HC producido por el hipotálamo. La somatropina es la HC obtenida por tecnología de ADN recombinante; actúa como agente anabólico y anticatabólico, estimulando el crecimiento de los huesos largos e incrementando el número y tamaño de las células musculares en niños con deficiencia de HC, con lo cual se consigue un aumento de la talla final del paciente. Evaluación de efectividad y seguridad: Pregunta de evaluación: En niños menores de 18 años con insuficiencia renal crónica, ¿cuál es la efectividad y seguridad de la somatropina comparada con placebo o no intervención, para el tratamiento del retardo de crecimiento? La pregunta de investigación fue refinada y validada con base en: autorización de mercadeo de la tecnología para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de la tecnología en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (código ATC: Anatomical, Therapeutic, Chemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías, revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, etc), estudios de prevalencia/incidencia y carga de enfermedad, y consulta con un experto temático (especialista clínico) representante de la Asociación Colombiana de Endocrinología Pediátrica. Población: Niños menores de 18 años con insuficiencia renal crónica. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: -Efectividad: en niños menores de 18 años con insuficiencia renal crónica, somatropina comparada con placebo o no intervención, es más efectiva para el aumento de la talla (después de 1 año de tratamiento) y de la velocidad de crecimiento (después de 6 meses y 1 año de tratamiento). La calidad global de la evidencia es baja (metodología GRADE), -Seguridad: los eventos adversos reportados con somatropina son poco comunes y su frecuencia es generalmente similar al grupo control.

Internet informs parents about growth hormone.

BACKGROUND: Parents' knowledge influences decisions regarding medical care for their children. METHODS: Parents of pediatric primary care patients aged 9-14 years, irrespective of height, participated in open focus groups (OFGs). Moderators asked the question, 'How do people find out about growth hormone (GH)?' Because many parents cited the Internet, the top 10 results from the Google searches of 'growth hormone children' and 'parents of children who take growth hormone' were examined. Three investigators independently performed content analysis and then reached a consensus. The results were tabulated via summary statistics. RESULTS: Eighteen websites were reviewed, most with the purpose of education (56%) and many funded by commercial sources (44%). GH treatment information varied, with 33% of the sites containing content only about US FDA-approved indications. Fifty-six percent of the sites included information about psychosocial benefits from treatment, with 44% acknowledging them as controversial. Although important to OFG participants, risks and costs were each omitted from 39% of the websites. CONCLUSION: Parents often turn to the Internet for GH-related information for their children, although its content may be incomplete and/or biased. Clinicians may want to provide parents with tools for critically evaluating Internet-based information, a list of prereviewed websites, or their own educational materials.

The effect of a multidisciplinary care clinic on the outcomes in pediatric chronic kidney disease.

BACKGROUND: Current best evidence-based practice for children with chronic kidney disease (CKD) attempts to achieve good clinical outcomes through careful management of comorbidities and is likely best achieved with a multidisciplinary care (MDC) CKD clinic. METHODS: In this retrospective study of children with CKD in British Columbia, Canada, we analyzed clinical outcomes in a cohort of 73 CKD patients from 2003 under a standard care model and a second cohort of 125 CKD patients from 2009 under a MDC clinic model. RESULTS: Patient demographics were similar, but there was a decrease in the percentage of patients with CKD stage 3-5 in 2009 (59 vs. 75 %; p = 0.002), although the absolute number increased. After adjustment for severity of CKD, hemoglobin was significantly higher (13.0 g/dl vs. 12.2 g/dl, p < 0.03), calcium was significantly higher (9.6 mg/dl vs. 9.1 mg/dl, p < 0.001), and albumin was significantly higher (4.4 g/dl vs. 3.8 g/dl, p < 0.001) in the 2009 MDC cohort. The rate of disease progression, assessed by annualized estimated glomerular filtration rate (eGFR) slope, improved from -4.0 ml/min/1.73 m(2) in the 2003 cohort to 0.5 ml/min/1.73 m(2) in the 2009 cohort (p < 0.01). Blood pressure control was better in 2009 although not statistically significant. CONCLUSIONS: Multidisciplinary care improved the outcomes of children with CKD especially in anemia management, bone mineral metabolism, nutrition, and renal disease progression.

Pathophysiology, assessment and management of the child with growth hormone resistance.

Defects in the growth hormone (GH)-insulin-like growth factor (IGF)I axis may cause GH resistance characterized by IGFI deficiency and growth failure. The range of defects causing GH resistance is broad as are their biochemical and phenotypical characteristics. We propose that GH-IGFI axis defects form a continuum of clinical and biochemical effects ranging from GH deficiency to GH resistance. The pathophysiology of GH resistance is described followed by a scheme for investigation of the child with severe short stature and normal GH secretion. We critically discuss GH therapy for such patients and define acceptable growth responsiveness. Finally we discuss therapy with IGF-I within the limits of the USA Food and Drug Administration and European Medicines Agency labels for GH resistance.

Growth hormone and health policy.

GH treatment for short children is representative of many frontline issues in health care policy. In this paper, we highlight key policy issues exemplified by GH, focusing on pharmaceutical innovation, insurance coverage and pricing, and physician decisions, and we discuss their implications for endocrinology and GH use.

Undernutrition and obesity in indigenous children: epidemiology, prevention, and treatment.

Over the past 50 years there has been a shift in nutritional problems amongst Indigenous children in developed countries from under-nutrition and growth faltering to overweight and obesity; the major exception is small numbers of Indigenous children predominately living in remote areas of Northern Australia. Nutritional problems reflect social disadvantage and occur with disproportionately high incidence in all disadvantaged subgroups. There is limited evidence of benefit from any strategies to prevent or treat undernutrition and obesity; there are a limited number of individual studies with generalizable high grade evidence of benefit. Potential solutions require a whole of society approach.

Decreasing stunting, anemia, and vitamin A deficiency in Peru: results of the Good Start in Life Program.

BACKGROUND: The rates of stunting, iron-deficiency anemia, and vitamin A deficiency in Peru are among the highest in South America. There is little scaled-up experience on how to solve these problems countrywide. OBJECTIVE: To evaluate the Good Start in Life Program during the period from 2000 to 2004. METHODS: Data on weight, height, hemoglobin, serum retinol, urinary iodine, and age were obtained from children under 3 years of age during two transverse surveys in 2000 and 2004. RESULTS: In 2004, the program covered 75,000 children, 35,000 mothers, and 1 million inhabitants from 223 poor communities. The rate of stunting decreased from 54.1% to 36.9%, the rate of iron-deficiency anemia decreased from 76.0% to 52.3%, and the rate of vitamin A deficiency decreased from 30.4% to 5.3% (p < .01). The annual cost per child was US$116.50. CONCLUSIONS: Adaptations of this participative program could contribute to decreased stunting, iron-deficiency anemia, and vitamin A deficiency at the national scale in Peru and many other countries.

Growth hormone treatment of renal growth failure during infancy and early childhood.

Despite major progress in dialysis, nutrition and drug treatment in the past 20 years, growth of infants and toddlers with chronic kidney disease (CKD) remains a major challenge in paediatric nephrology. Our hypothesis is that early growth deficit is one of the most important factors for impaired final height in children with CKD, and we conclude that early implementation of recombinant human growth hormone (rhGH) therapy should be offered to infants with growth failure. Infants with delayed growth, adequate caloric intake and stable parameters of bone metabolism are candidates for rhGH therapy. One predictive factor for the selection of infants for rhGH treatment may be growth retardation at birth. Our conclusion from the limited published data is that the use of rhGH in young children with CKD is effective and safe. Compared with its use in older children, the early use of growth hormone requires lower absolute dosages of rhGH, which therefore reduce the annual treatment costs and allow earlier renal transplantation. Furthermore, an early start on rhGH improves the psychosocial situation later in childhood and may lead to a further improvement in adult height. A multi-centre randomised controlled study should be initiated to analyse the short-term and long-term effects of early rhGH therapy on infants with CKD.

Management of idiopathic short stature: psychological endpoints, assessment strategies and cognitive-behavioral intervention.

BACKGROUND: In 2007, a Conference on Idiopathic Short Stature (ISS) endorsed the definition of ISS as a statistical (auxologic) rather than a medical (pathologic) deviation from the norm. Consequently, the ultimate criteria for evaluation of treatment in ISS shift from medical to psychological endpoints. OBJECTIVE: This review synthesizes empirical evidence of psychological outcomes in treated and untreated subjects with ISS, recommendations from the recent ISS Consensus Conference, theoretical concepts from pediatric psychology and rationales used for various intervention strategies to better evaluate and manage psychological endpoints in ISS in accordance with the Consensus Conference definition. METHODS: Different measures of psychological outcome in ISS are reviewed to explain apparent heterogeneity among empirical study findings. Key issues include: (1) adaptation to major stressors associated with short stature (e.g., bullying, peer relations) and the correlation of adaptation failure with low socioeconomic status and impaired quality of life in adulthood; (2) development of valid and sensitive assessment tools; (3) clinical decision-making based on psychological assessment, ethical principles concerning informed consent and expectation of benefit from psychological treatment and (4) intervention approaches including counselling, cognitive-behavioral therapy, assertiveness training and growth hormone therapy. CONCLUSIONS: There are different but complementary strategies for medical and psychological enhancement of psychosocial outcome in subjects with ISS.

Cost-effectiveness of gastrostomy placement for children with neurodevelopmental disability.

INTRODUCTION: Malnutrition and growth deficiency are common in neurologically impaired children. Gastrostomy placement has been shown to result in significant catch-up growth, improved health of the child and reduction in family stress; its cost-effectiveness has not been investigated. AIMS: Costs related to gastrostomy placement are estimated here from a prospective controlled study of children referred to a tertiary paediatric centre in the UK. METHODS: Costs of inpatient stay, medication, tests, general practitioner consultations, community healthcare, equipment, and parents' indirect costs were estimated at baseline and follow-up. Costs of the different types of gastrostomy surgery are given. RESULTS: Results for both time periods were available for 54 of the 76 children recruited to the study. Five-day food diaries were kept at baseline and follow-up. Costs of food increased slightly but not significantly post surgery from pound sterling 33 to pound sterling 40 (Euro 44 to Euro 54, US$65 to US$78) per week. Variation in cost between cases was considerable but the mean net cost difference of pound sterling 20.80 (CI - pound sterling 43.79 to pound sterling 85.35) (Euro 28 (CI Euro-59 to Euro 115), US$41 (CI US$-86 to US$167)) per week per child including for food and surgery, was also not significant. Community service costs were significantly lower post surgery. Few parents reported personal costs at either time point, although many had reduced or stopped paid work to care for the child. CONCLUSION: As gastrostomy placement for these children resulted in significant clinical benefit at no significant extra cost, it is concluded that the procedure is cost-effective.