Evaluation of short stature

Summary

Short stature is defined as a height that is 2 or more standard deviations (SD) below the mean for age and sex within a population (below the 2.5th percentile).

Growth deceleration is defined as a growth velocity that is below the 5th percentile for age and sex (e.g., <5 cm/year after the age of 5 years), or a height drop across 2 or more percentiles on the growth chart.

Epidemiology

In a US pediatric primary care population, 1.1% of all patients (2073 of 189,280 subjects; ages 0.5 to 20 years) had a height <-2.25 SD below the mean.[1] Short stature was associated with a history of prematurity, Medicaid insurance, and race/ethnicity. Males comprised the majority of growth hormone recipients for idiopathic short stature, despite no gender difference in prevalence of height (<-2.25 SD) being found.[1] Sex bias in referrals for poor growth evaluation has been reported previously.[2]

In England, approximately 2% of 4- to 5-year-olds are short for their age and sex; prevalence is highly associated with poverty.[3]

In a nationwide survey in China, short stature prevalence was 2.60% in developed, 3.72% in intermediately developed, and 4.69% in underdeveloped regions.[4] In resource-poor settings short stature is often a consequence of malnutrition.[5] [6]

Growth hormone deficiency (GHD) is a rare but important cause of short stature in children and adolescents. Pediatric GHD appears to vary widely; one systematic review of population-based epidemiologic studies reported a prevalence range of between 1/1107 and 1/8646.[7]

Normal growth

Factors determining normal growth depend on the child's age. An alteration in any of the factors can lead to growth failure.[8] [9] [10] [11]

Prenatal growth: the major determinants of fetal growth are uterine size, placental function, maternal nutrition, insulin, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs).
Postnatal growth: this is characterized by an initial rapid growth rate that declines progressively, reaching a plateau of about 5 to 7 cm/year between 3 years of age until puberty. Babies born large or small for their genetic potential will "channel" to their correct percentile in their first 2 years. Growth hormone, thyroid hormones, nutrition, and insulin play major roles at this time.
Pubertal growth: immediately prior to puberty, growth usually slows down ("prepubertal dip"), only to be followed by the pubertal growth spurt. Sex hormones exert important growth effects during puberty, in addition to other factors such as growth hormone, thyroid hormones, nutrition, and insulin. Girls have their growth spurt early in puberty. Boys experience their growth spurt toward the end of puberty and achieve greater height velocities than girls. This, combined with the fact that boys grow for approximately 2 years more than girls, explains the 13 cm (5 inches) difference in final heights between the sexes.

Library

The WHO and CDC growth charts
Familial short stature (TH target height)
Constitutional delay of growth and development (TH target height)
Severe growth hormone deficiency prior to treatment (TH target height)
Diagnostic algorithm of short stature
Craniopharyngioma: coronal postcontrast MRI

Citations

Key Articles

Wit JM, Kamp GA, Oostdijk W, et al. Towards a rational and efficient diagnostic approach in children referred for growth failure to the general paediatrician. Horm Res Paediatr. 2019;91(4):223-40.[Abstract][Full Text]
Cooke R, Goulet O, Huysentruyt K, et al. Catch-up growth in infants and young children with faltering growth: expert opinion to guide general clinicians. J Pediatr Gastroenterol Nutr. 2023 Jul 1;77(1):7-15.[Abstract][Full Text]
Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008 Nov;93(11):4210-7.[Abstract][Full Text]
Bryant J, Baxter L, Cave CB, et al. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004440.[Abstract][Full Text]

Other Online Resources

CDC: growth charts

Referenced Articles

1. Grimberg A, Huerta-Saenz L, Grundmeier R, et al. Gender bias in U.S. pediatric growth hormone treatment. Sci Rep. 2015 Jun 9;5:11099.[Abstract][Full Text]
2. Grimberg A, Kutikov J, Cucchiara A. Sex differences in patients referred for evaluation of poor growth. J Pediatr. 2005 Feb;146(2):212-6.[Abstract]
3. Orr J, Freer J, Morris JK, et al. Regional differences in short stature in England between 2006 and 2019: a cross-sectional analysis from the National Child Measurement Programme. PLoS Med. 2021 Sep 28;18(9):e1003760.[Abstract][Full Text]
4. Ma J, Pei T, Dong F, et al. Spatial and demographic disparities in short stature among school children aged 7-18 years: a nation-wide survey in China, 2014. BMJ Open. 2019 Jul 16;9(7):e026634.[Abstract][Full Text]
5. Yao WY, Yu YF, Li L, et al. Exposure to Chinese famine in early life and height across 2 generations: a longitudinal study based on the China Health and Nutrition Survey. Am J Clin Nutr. 2024 Feb;119(2):433-43.[Abstract]
6. Gao M, Wells JCK, Johnson W, et al. Socio-economic disparities in child-to-adolescent growth trajectories in China: findings from the China Health and Nutrition Survey 1991-2015. Lancet Reg Health West Pac. 2022 Feb 26;21:100399.[Abstract][Full Text]
7. Mameli C, Guadagni L, Orso M, et al. Epidemiology of growth hormone deficiency in children and adolescents: a systematic review. Endocrine. 2024 Mar 18.[Abstract][Full Text]
8. Lifshitz F (ed). Pediatric endocrinology. 5th ed. New York City, NY: Informa HealthCare; 2007.
9. Wit JM, Kamp GA, Oostdijk W, et al. Towards a rational and efficient diagnostic approach in children referred for growth failure to the general paediatrician. Horm Res Paediatr. 2019;91(4):223-40.[Abstract][Full Text]
10. Storr HL, Freer J, Child J, et al. Assessment of childhood short stature: a GP guide. Br J Gen Pract. 2023 Mar 30;73(729):184-6.[Full Text]
11. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins - Gynecology. ACOG practice bulletin no. 227: fetal growth restriction. Obstet Gynecol. 2021 Feb 1;137(2):e16-28.[Abstract]
12. Lifshitz F, Tarim O. Worrisome growth patterns in children. Int Pediatr. 1994;9:181-8.
13. Clayton PE, Cianfarani S, Czernichow P, et al. Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab. 2007 Mar;92(3):804-10.[Abstract][Full Text]
14. Hokken-Koelega ACS, van der Steen M, Boguszewski MCS, et al. International consensus guideline on small for gestational age: etiology and management from infancy to early adulthood. Endocr Rev. 2023 May 8;44(3):539-65.[Abstract][Full Text]
15. Lindsay R, Feldkamp M, Harris D, et al. Utah growth study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994 Jul;125(1):29-35.[Abstract]
16. Cooke R, Goulet O, Huysentruyt K, et al. Catch-up growth in infants and young children with faltering growth: expert opinion to guide general clinicians. J Pediatr Gastroenterol Nutr. 2023 Jul 1;77(1):7-15.[Abstract][Full Text]
17. Handa A, Nishimura G, Zhan MX, et al. A primer on skeletal dysplasias. Jpn J Radiol. 2022 Mar;40(3):245-61.[Abstract][Full Text]
18. Legare JM, Basel D. What the pediatric endocrinologist needs to know about skeletal dysplasia, a primer. Front Pediatr. 2023 Aug 22;11:1229666.[Abstract][Full Text]
19. Carpenter TO, Shaw NJ, Portale AA, et al. Rickets. Nat Rev Dis Primers. 2017 Dec 21;3:17101.[Abstract]
20. Chow EJ, Friedman DL, Yasui Y, et al. Decreased adult height in survivors of childhood acute lymphoblastic leukemia: a report from the childhood cancer survivor study. J Pediatr. 2007 Apr;150(4):370-5.[Abstract][Full Text]
21. Knijnenburg SL, Raemaekers S, van den Berg H, et al. Final height in survivors of childhood cancer compared with height standard deviation scores at diagnosis. Ann Oncol. 2013 Apr;24(4):1119-26.[Abstract][Full Text]
22. Xu W, Janss A, Moshang T. Adult height and adult sitting height in childhood medulloblastoma survivors. J Clin Endocrinol Metab. 2003 Oct;88(10):4677-81.[Abstract][Full Text]
23. Spohr HL, Steinhausen HC. Fetal alcohol spectrum disorders and their persisting sequelae in adult life. Dtsch Arztebl Int. 2008 Oct;105(41):693-8.[Abstract][Full Text]
24. Poulton A. Growth on stimulant medication; clarifying the confusion: a review. Arch Dis Child. 2005 Aug;90(8):801-6.[Abstract][Full Text]
25. Biederman J, Faraone SV, Monuteaux MC, et al. Growth deficits and attention-deficit/hyperactivity disorder revisited: impact of gender, development, and treatment. Pediatrics. 2003 May;111(5 Pt 1):1010-6.[Abstract]
26. Carucci S, Balia C, Gagliano A, et al. Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis. Neurosci Biobehav Rev. 2020 Oct 17 [Epub ahead of print].[Abstract]
27. Bondy CA; Turner Syndrome Consensus Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007 Jan;92(1):10-25.[Abstract][Full Text]
28. Giovenale D, Meazza C, Cardinale GM, et al. The prevalence of growth hormone deficiency and celiac disease in short children. Clin Med Res. 2006 Sep;4(3):180-3.[Abstract][Full Text]
29. Karavitaki N, Cudlip S, Adams CB, et al. Craniopharyngiomas. Endocr Rev. 2006 Jun;27(4):371-97.[Abstract]
30. Sklar CA, Antal Z, Chemaitilly W, et al. Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2761-84.[Abstract][Full Text]
31. Bravo-Valenzuela NJ, Passarelli ML, Coates MV. Growth charts in children with Down syndrome: a systematic review [in Portuguese]. Rev Paul Pediatr. 2011 Jun;29(2):261-9.[Full Text]
32. Grummer-Strawn LM, Reinold C, Krebs NF; Centers for Disease Control and Prevention (CDC). Use of World Health Organization and CDC growth charts for children aged 0-59 months in the United States. MMWR Recomm Rep. 2010 Sep 10;59(RR-9):1-15.[Abstract][Full Text]
33. Scherdel P, Reynaud R, Pietrement C, et al. Priority target conditions for algorithms for monitoring children's growth: interdisciplinary consensus. PLoS One. 2017 Apr 27;12(4):e0176464.[Abstract][Full Text]
34. Tanner JM, Goldstein H, Whitehouse RH. Standards for children's height at ages 2-9 years allowing for heights of parents. Arch Dis Child. 1970 Dec;45(244):755-62.[Abstract]
35. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and the wrist. Stanford, CA: Stanford University Press; 1950.
36. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pylehand standard. J Pediatr. 1952 Apr;40(4):423-41.[Abstract]
37. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008 Nov;93(11):4210-7.[Abstract][Full Text]
38. Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-97.[Abstract][Full Text]
39. Rogol AD, Hayden GF. Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J Pediatr. 2014 May;164(5 suppl):S1-14.e6.[Abstract][Full Text]
40. Bryant J, Baxter L, Cave CB, et al. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004440.[Abstract][Full Text]
41. Hilczer M, Smyczynska J, Lewinski A. Limitations of clinical utility of growth hormone stimulating tests in diagnosing children with short stature. Endocr Regul. 2006 Sep;40(3):69-75.[Abstract]
42. Canaris GJ, Steiner JF, Ridgway EC. Do traditional symptoms of hypothyroidism correlate with biochemical disease? J Gen Intern Med. 1997 Sep;12(9):544-50.[Abstract][Full Text]
43. Nwosu BJ, Coco M, Jones J. Short stature with normal growth hormone stimulation testing: lack of evidence for partial growth hormone deficiency or insensitivity. Horm Res. 2004;62(2):97-102.[Abstract]
44. Gravholt CH, Andersen NH, Conway GS, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017 Sep;177(3):G1-G70.[Abstract][Full Text]
45. Duis J, van Wattum PJ, Scheimann A, et al. A multidisciplinary approach to the clinical management of Prader-Willi syndrome. Mol Genet Genomic Med. 2019 Mar;7(3):e514.[Abstract][Full Text]
46. International Prader-Willi Syndrome Organisation. Overview and evaluation for adults with Prader-Willi syndrome. Jan 2018 [internet publication].[Full Text]
47. Doganci T, Bozkurt S. Celiac disease with various presentations. Pediatr Int. 2004 Dec;46(6):693-6.[Abstract]
48. Buller HA. Problems in diagnosis of IBD in children. Neth J Med. 1997 Feb;50(2):S8-11.[Abstract]
49. Gaillard EA, Kuehni CE, Turner S, et al. European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years. Eur Respir J. 2021 Nov 4;58(5):2004173.[Abstract][Full Text]
50. Green WH, Campbell M, David R. Psychosocial dwarfism: a critical review of the evidence. J Am Acad Child Psychiatry. 1984 Jan;23(1):39-48.[Abstract]

Diseases