Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study

Charmian A. Quigley, Christopher J. Child, Alan G. Zimmermann, Ronald (Ron) Rosenfeld, Leslie L. Robison, Werner F. Blum

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Context: Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood.

Objective: To assess mortality in children receiving GH.

Design: Prospective, multinational, observational study.

Setting: Eight hundred twenty-seven study sites in 30 countries.

Patients: Children with growth disorders.

Interventions: GH treatment during childhood.

Main Outcome Measure: Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population.

Results: Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non-GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65).

Conclusions: No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non-GH-deficient medical conditions.

Original languageEnglish (US)
Pages (from-to)3195-3205
Number of pages11
JournalThe Journal of clinical endocrinology and metabolism
Volume102
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Neuroendocrinology
Growth Disorders
Child Mortality
Growth Hormone
Confidence Intervals
Mortality
Therapeutics
Turner Syndrome
Hormones
Homeobox Genes
Pediatrics
Gestational Age
Neoplasms
Genetics
Genes
Observational Studies
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders : Data From the Genetics and Neuroendocrinology of Short Stature International Study. / Quigley, Charmian A.; Child, Christopher J.; Zimmermann, Alan G.; Rosenfeld, Ronald (Ron); Robison, Leslie L.; Blum, Werner F.

In: The Journal of clinical endocrinology and metabolism, Vol. 102, No. 9, 01.09.2017, p. 3195-3205.

Research output: Contribution to journalArticle

Quigley, Charmian A. ; Child, Christopher J. ; Zimmermann, Alan G. ; Rosenfeld, Ronald (Ron) ; Robison, Leslie L. ; Blum, Werner F. / Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders : Data From the Genetics and Neuroendocrinology of Short Stature International Study. In: The Journal of clinical endocrinology and metabolism. 2017 ; Vol. 102, No. 9. pp. 3195-3205.
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abstract = "Context: Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood.Objective: To assess mortality in children receiving GH.Design: Prospective, multinational, observational study.Setting: Eight hundred twenty-seven study sites in 30 countries.Patients: Children with growth disorders.Interventions: GH treatment during childhood.Main Outcome Measure: Standardized mortality ratios (SMRs) and 95{\%} confidence intervals (CIs) using age- and sex-specific rates from the general population.Results: Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95{\%} CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95{\%} CI, 3.81 to 11.69) and borderline elevated for those with other serious non-GH-deficient conditions (2.47; 95{\%} CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95{\%} CI, 0.17 to 5.20), idiopathic GHD (0.11; 95{\%} CI, 0.02 to 0.33), idiopathic short stature (0.20; 95{\%} CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95{\%} CI, 0.08 to 2.37), Turner syndrome (0.51; 95{\%} CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95{\%} CI, 0.02 to 4.65).Conclusions: No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non-GH-deficient medical conditions.",
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T1 - Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders

T2 - Data From the Genetics and Neuroendocrinology of Short Stature International Study

AU - Quigley, Charmian A.

AU - Child, Christopher J.

AU - Zimmermann, Alan G.

AU - Rosenfeld, Ronald (Ron)

AU - Robison, Leslie L.

AU - Blum, Werner F.

PY - 2017/9/1

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N2 - Context: Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood.Objective: To assess mortality in children receiving GH.Design: Prospective, multinational, observational study.Setting: Eight hundred twenty-seven study sites in 30 countries.Patients: Children with growth disorders.Interventions: GH treatment during childhood.Main Outcome Measure: Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population.Results: Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non-GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65).Conclusions: No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non-GH-deficient medical conditions.

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