Vitamin D content in children with short stature due to intrauterine growth restriction against normosomatotropinemia




intrauterine growth restriction, prepubertal children, growth hormone, normosomatotropinemia, vitamin D, insulin-like growth factor-1


Background. There are no data about the status of vitamin D and its effect on the growth hormone/growth factors axis in prepubertal children with intrauterine growth restriction (IGR). Of particular interest is a group of patients who remain significantly short on the background of a decrease in insulin-like growth factor 1 (IGF-1) levels and normal stimulated release of growth hormone (GH). The purpose of our study was to determine the levels of 25-hydroxycalciferol in the blood plasma of prepubertal children with short stature due to IGR on the background of normosomatotropinemia. Materials and methods. We examined 34 prepubertal children (14 girls and 20 boys) with short stature (average age — 6.95 ± 0.46 years) who had signs of IGR at birth. A symmetrical type of IGR was found in 15 (44.2 %) patients, an asymmetrical type — in 19 (55.8 %). According to the results of functional tests all patients had a normal GH peak release (> 10 ng/ml). Thyroid-stimulating hormone, free thyroxine levels in the blood plasma were determined by the immunoradiometric assay with standard Immunotech® kit (Czech Republic). At the time of examination, all patients were euthyroid. GH, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3) levels were determined by enzyme-linked immunosorbent assay using Immulite 2000 Xi kits (Siemens, USA). 25-hydroxycalciferol level was determined by the immunochemiluminescent method (Abbott, USA). The results were evaluated according to the guidelines of the International Society of Endocrinology (2011). Results. It was found that in prepubertal children with IGR signs at birth, the average height standard deviation score (SDS) at the time of the examination was –2.83 ± 0.12. There were no significant differences between the height and body weight in patients with a symmetrical and an asymmetrical types of IGR at the time of examination (p > 0.05). Vitamin D content in the blood plasma of children with IGR signs was 49.70 ± 2.17 nmol/l in the whole group. Vitamin D insufficiency below 75 nmol/l was found in 16 (47 %) patients, and vitamin D deficiency below 50 nmol/l — in 18 (53 %). No significant differences were found between vitamin D values in girls and boys with signs of IGR (51.79 ± 3.38 nmol/l and 48.36 ± 2.86 nmol/l, respectively, p > 0.05). Height SDS in the group of patients with an asymmetrical type of IGR weakly correlates (r = 0.38) with vitamin D content. Vitamin D level significantly differed depending on IGR type (in a symmetrical type — 44.1 ± 3.2 nmol/l, in an asymmetrical type — 54.20 ± 2.56 nmol/l, p < 0.05). IGF-1 SDS in the group of patients with an asymmetrical type of IGR weakly correlated (r = 0.36) with vitamin D level. On the background of a significant decrease in IGFBP-3 content in children with an asymmetrical type of IGR compared to those with a symmetrical type (–1.32 ± 0.07 SDS and –1.00 ± 0.14 SDS, p < 0.05), there was a reduction in IGF-1 levels (–1.62 ± 0.10 SDS and –1.34 ± 0.14 SDS, p = 0.05). Conclusions. Patients born with signs of IGR, even against normosomatotropinemia, may still have significant growth deficit, a sharp decrease in IGF-1 and IGFBP-3 for a long time after birth. The results obtained indicate the presence of hypovitaminosis D in all prepubertal patients who were born with the signs of intrauterine growth restriction. No correlation was found between vitamin D level and the maximum peak of stimulated growth hormone release. However, patients with an asymmetrical type of IGR have a weak correlation (r = 0.36) between IGF-1 SDS and vitamin D content, a significant decrease in the content of IGF-1, IGFBP-3, as well as vitamin D compared to its level in a symmetrical type of IGR. It is recommended to include the determination of vitamin D level in the blood plasma irrespective of the type of disease and the state of somatotropic function in the list of studies for the examination of children with short stature who were born with signs of intrauterine growth restriction.


Download data is not yet available.


González-Leal R, Martínez-Villanueva J, Argente J, Martos-Moreno GÁ. Influence of neonatal anthropometry on the comorbidities of the obese patient. An Pediatr (Barc). 2019;90(6):362–369. doi:10.1016/j.anpedi.2018.05.017. (in Spanish).

Renes JS, van Doorn J, Hokken-Koelega ACS. Current Insights into the Role of the Growth Hormone-Insulin-Like Growth Factor System in Short Children Born Small for Gestational Age. Horm Res Paediatr. 2019;92(1):15–27. doi:10.1159/000502739.

Finken MJJ, van der Steen M, Smeets CCJ, et al. Children Born Small for Gestational Age: Differential Diagnosis, Molecular Genetic Evaluation, and Implications [published correction appears in Endocr Rev. 2019 Feb 1;40(1):96]. Endocr Rev. 2018;39(6):851–894. doi:10.1210/er.2018-00083.

Wang H, Xiao Y, Zhang L, Gao Q. Maternal early pregnancy vitamin D status in relation to low birth weight and small-for-gestational-age offspring. J Steroid Biochem Mol Biol. 2018;175:146–150. doi:10.1016/j.jsbmb.2017.09.010.

Hu Z, Tang L, Xu HL. Maternal Vitamin D Deficiency and the Risk of Small for Gestational Age: A Meta-analysis. Iran J Public Health. 2018;47(12):1785–1795.

Chen Y, Zhu B, Wu X, Li S, Tao F. Association between maternal vitamin D deficiency and small for gestational age: evidence from a meta-analysis of prospective cohort studies. BMJ Open. 2017;7(8):e016404. doi:10.1136/bmjopen-2017-016404.

Bi WG, Nuyt AM, Weiler H, Leduc L, Santamaria C, Wei SQ. Association Between Vitamin D Supplementation During Pregnancy and Offspring Growth, Morbidity, and Mortality: A Systematic Review and Meta-analysis. JAMA Pediatr. 2018;172(7):635–645. doi:10.1001/jamapediatrics.2018.0302.

Leffelaar ER, Vrijkotte TG, van Eijsden M. Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Children and their Development cohort. Br J Nutr. 2010;104(1):108–117. doi:10.1017/S000711451000022X.

Santamaria C, Bi WG, Leduc L, et al. Prenatal vitamin D status and offspring's growth, adiposity and metabolic health: a systematic review and meta-analysis. Br J Nutr. 2018;119(3):310–319. doi:10.1017/S0007114517003646.

Bogazzi F, Rossi G, Lombardi M, et al. Vitamin D status may contribute to serum insulin-like growth factor I concentrations in healthy subjects. J Endocrinol Invest. 2011;34(8):e200–e203. doi:10.3275/7228.

Ciresi A, Giordano C. Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess. Growth Horm IGF Res. 2017;33:35–42. doi:10.1016/j.ghir.2017.02.002.

Esposito S, Leonardi A, Lanciotti L, Cofini M, Muzi G, Penta L. Vitamin D and growth hormone in children: a review of the current scientific knowledge. J Transl Med. 2019;17(1):87. doi:10.1186/s12967-019-1840-4.

Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. USA: Pyle Stanford University Press; 1959. 272p.

Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American children. J Pediatr. 1985;107(3):317–329. doi:10.1016/s0022-3476(85)80501-1.

Ranke MB. Diagnosis of growth hormone deficiency and growth hormone stimulation tests. Diagnostics of endocrine function in Children and Adolescents. Basel, Karger; 2011. 4th ed. 102–137pp.

de Waal WJ, Hokken-Koelega AC, Stijnen T, de Muinck Keizer-Schrama SM, Drop SL. Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF-I and IGF-II levels in prepubertal children with short stature after intrauterine growth retardation. The Dutch Working Group on Growth Hormone. Clin Endocrinol (Oxf). 1994;41(5):621–630. doi:10.1111/j.1365-2265.1994.tb01828.x.

Lo TH, Wu TY, Li PC, Ding DC. Effect of Vitamin D supplementation during pregnancy on maternal and perinatal outcomes. Ci Ji Yi Xue Za Zhi. 2019;31(4):201–206. doi:10.4103/tcmj.tcmj_32_19.

Tao RX, Meng DH, Li JJ, et al. Current Recommended Vitamin D Prenatal Supplementation and Fetal Growth: Results From the China-Anhui Birth Cohort Study. J Clin Endocrinol Metab. 2018;103(1):244–252. doi:10.1210/jc.2017-00850.

Esmeraldo CUP, Martins MEP, Maia ER, et al. Vitamin D in Term Newborns: Relation with Maternal Concentrations and Birth Weight. Ann Nutr Metab. 2019;75(1):39–46. doi:10.1159/000502044.

Delecroix C, Brauner R, Souberbielle JC. Vitamin D in children with growth hormone deficiency due to pituitary stalk interruption syndrome. BMC Pediatr. 2018;18(1):11. doi:10.1186/s12887-018-0992-3.

Ciresi A, Giordano C. Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess. Growth Horm IGF Res. 2017;33:35–42. doi:10.1016/j.ghir.2017.02.002.

Chowdhury R, Taneja S, Kvestad I, Hysing M, Bhandari N, Strand TA. Vitamin D status in early childhood is not associated with cognitive development and linear growth at 6-9 years of age in North Indian children: a cohort study. Nutr J. 2020;19(1):14. doi:10.1186/s12937-020-00530-2.

Ameri P, Giusti A, Boschetti M, et al. Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency. Eur J Endocrinol. 2013;169(6):767–772. doi:10.1530/EJE-13-0510.



How to Cite

Bolshova, O., Muz, N., Kvacheniuk, D., & Ryznychuk, M. (2021). Vitamin D content in children with short stature due to intrauterine growth restriction against normosomatotropinemia. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 16(2), 104–110.



Original Researches

Most read articles by the same author(s)

1 2 > >>