Evaluating treatment effectiveness in small for gestational age children by optimizing growth hormone dose

Main Article Content

O.V. Bolshova
N.M. Muz

Abstract

Background. According to world statistics, about 5–10 % of newborns are small for gestational age (SGA). They can have inadequate rates of postnatal growth during first two years of life. This growth deficiency is observed throughout childhood and adolescence, which ultimately leads to short stature in adulthood. The purpose was to analyze the efficacy of different doses of recombinant growth hormone (rGH) therapy in order to correct growth in pre-pubertal children born small for gestational age. Materials and methods. Fifty children born small for gestational age (16 girls and 34 boys with mean age of 6.82 ± 0.36 years) with growth failure were examined. According to the results of clonidine and insulin tests, SGA patients were divided into two groups: group A — children without grown hormone deficiency (n = 34; 68 %), group B — patients with growth hormone deficiency (n = 16; 32 %). The control group included 34 persons (13 girls and 21 boys with mean age of 6.58 ± 0.38 years) with growth hormone deficiency. All patients received rGH treatment starting with a dose of 0.03 mg/kg/day according to the pituitary hormone deficiency protocol, and in case of slow growth rate, the dose was gradually increased to 0.05 mg/kg/day in group B patients. Results. A significant slowdown in growth acceleration in the first 6 months of rGH treatment at dose of 0.033 mg/kg/day was found in SGA patients without grown hormone deficiency (p < 0.05). The rGH treatment at a dose of 0.05 mg/kg/day for the next 6 months showed a statistically significant increase in growth standard deviation score (SDS) of SGA patients without growth hormone deficiency (–2.00 ± 0.14 SDS vs. –2.58 ± 0.15 SDS in the first 6 months with rGH dose of 0.033 mg/kg/day) (p < 0.05). Conclusions. The optimal dose of rGH treatment in small for gestational age children with growth hormone deficiency is 0.033 mg/kg/day, and in SGA patients without growth hormone deficiency — 0.05 mg/kg/day.

Article Details

How to Cite
Bolshova, O., and N. Muz. “Evaluating Treatment Effectiveness in Small for Gestational Age Children by Optimizing Growth Hormone Dose”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 15, no. 5, Oct. 2019, pp. 381-5, doi:10.22141/2224-0721.15.5.2019.180041.
Section
Original Researches

References

Albertsson-Wikland K, Boguszewski M, Karlberg J. Children born small-for-gestational: postnatal growth and hormonal status. Horm Res. 1998;49 Suppl 2:7-13. doi: 10.1159/000053080.

Clayton PE, Cianfarani S, Czernichow P, Johannsson G, Rapaport R, Rogol A. Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Paediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab. 2007 Mar;92(3):804-10. doi: 10.1210/jc.2006-2017.

Peleg D, Kennedy CM, Hunter SK. Intrauterine Growth Restriction: Identification and Management. Am Fam Physician. 1998 Aug;58(2):453-60, 466-7.

Krishnamurthy MB, Popiel A, Malhotra A. Screening investigations in small-for-gestational-age near-term and term infants. Eur J Pediatr. 2017 Dec;176(12):1707-1712. doi: 10.1007/s00431-017-3031-8.

De Zegher F. Endocrinology of small-for gestation-age children: recent advances. Horm Res 2004;62(suppl 3):141-142. doi: 10.1159/000080516.

Rosilio M, Carel JC, Ecosse E, Chaussainon JL. Adult height of prepubertal short children born small for gestational age treated with GH. Eur J Endocrinol. 2005 Jun;152(6):835-43. doi: 10.1530/eje.1.01916.

Bolshova O, Sprynchuk N, Muz N, Vyshnevska O, Kulchitska N. Clinical features and hormonal status of children born small for gestational age. Pediatriia. Vostochnaia Evropa. 2015;(9):79-87. (in Russian).

Van der Steen M, Hokken-Koelega A. Growth and metabolism in children born small for gestational age. Endocrinol Metab Clin North Am. 2016 Jun;45(2):283-94. doi: 10.1016/j.ecl.2016.01.008.

Grunt JA, Enriquez AR, Daughaday WH. Acute and long-term responses to hGH in children with idiopathic small-of-dates dwarfism. J Clin Endocrinol Metab. 1972 Jul;35(1):157-68. doi: 10.1210/jcem-35-1-157.

Tanner J, Whitehouse RH, Hughes PC, Vince FP. Effect of human growth hormone treatment for 1 to 7 years on the growth of 100 children with growth hormone deficiency, low birth weight, inherited smallness, Turner’s syndrome, and other complaints. Arch Dis Child. 1971 Dec;46(250):745-82. doi: 10.1136/adc.46.250.745.

Ranke MB. Growth hormone deficiency: diagnostic principles and practice. In: Ranke MB, Mullis PE, editors. Diagnostics of endocrine function in children and adolescents. 4th ed. Basel: Karger; 2011. 102-137 pp. doi: 10.1159/000327405.

Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for north American children. J Pediatr. 1985 Sep;107(3):317-29. doi: 10.1016/s0022-3476(85)80501-1.

Ministry of Нealth of Ukraine. Order on April 24, 2006 № 254. On Adoption of Protocols for the Provision of Medical Care to Children in Children's Endocrinology. Available from: https://zakon.rada.gov.ua/rada/show/v0254282-06?lang=uk. Accessed: April 24, 2006. (in Ukrainian).

Labarta JI, Ruiz JA, Molina I, De Arriba A, Mayayo E, Longás AF. Growth and growth hormone treatment in short stature children born small for gestational age. Pediatr Endocrinol Rev. 2009 Feb;6 Suppl 3:350-7.

Bang P, Ahmed SF, Argente J, et al. Identification and management of poor response to growth-promoting therapy in children with short stature. Clin Endocrinol (Oxf). 2012 Aug;77(2):169-81. doi: 10.1111/j.1365-2265.2012.04420.x.

Karlberg J, Fryer JG, Engström I, Karlberg P. Analysis of linear growth using a mathematical model. II. From 3 to 21 years of age. Acta Paediatr Scand Suppl. 1987;337:12-29.

Van Dijk M, Mulder P, Houdijk M, et al. High serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) during high-dose GH treatment in short children born small for gestational age. J Clin Endocrinol Metab. 2006 Apr;91(4):1390-6. doi: 10.1210/jc.2005-1663.

Rapaport R, Lee P, Ross J, Saenger P, Ostrow V, Piccoli G. Growth hormone therapy in children born small for gestational age: results from the ANSWER program. Endocr Connect. 2018 Aug 23. pii: EC-18-0286. doi: 10.1530/EC-18-0286.

Cutfield WS, Lindberg A, Rapaport R, Wajnrajch MP, Saenger P. Safety of growth hormone treatment in children born small for gestational age: the US trial and KIGS analysis. Horm Res. 2006;65 Suppl 3:153-9. doi: 10.1159/000091719.

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