Premature Adrenarche and Obesity in Children Born Premature or Small for Gestational Age: A Review of the Literature and Case Reports.
Main Article Content
Abstract
Premature adrenarche (PA) is a condition characterized by the early onset adrenal androgen production and clinical signs of androgen action before age 8 in girls and 9 in boys [1]. Children born premature or small for gestational age (SGA) are at increased risk for PA and obesity, which can lead to metabolic complications and long-term health consequences [2-4]. This article reviews the literature on the pathophysiology, clinical implications, and management of PA in children born premature or SGA and presents three case reports of premature girls with overweight or obese body mass index and signs of early adrenarche.
Keywords:
Premature adrenarche, Preterm birth, Small for gestational age, Childhood obesity, Androgen excess, Dehydroepiandrosterone sulfate, Metabolic risk, Cardiometabolic monitoring
Article Details
How to Cite
LITTLEJOHN, Elizabeth; KHURSHID, Farwa.
Premature Adrenarche and Obesity in Children Born Premature or Small for Gestational Age: A Review of the Literature and Case Reports..
Medical Research Archives, [S.l.], v. 13, n. 8, aug. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6782>. Date accessed: 07 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i8.6782.
Section
Case Series
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Rosenfield RL. Normal and premature adrenarche. Endocr Rev. 2021;42(6):783-814. doi:10.1210/endrev/bnab009.
2. Augsburger P, Liimatta J, Fluck CE. Update on adrenarche—still a mystery. J Clin Endocrinol Metab. 2024;109(6):1403-1422. doi:10.1210/clinem/dgae008.
3. Voutilainen R, Jaaskelainen J. Premature adrenarche: etiology, clinical findings, andconsequences. J Steroid Biochem Mol Biol. 2015;145:226-236. doi:10.1016/j.jsbmb.2014.06.004.
4. Utriainen P, Laakso S, Liimatta J, Jaaskelainen J, Voutilainen R. Premature adrenarche— a common condition with variable presentation. Horm Res Paediatr. 2015;83(4):221-231. doi:10.1159/000369458.
5. Rege J, Turcu AF, Kasa-Vubu JZ, et al. 11-Ketotestosterone is the dominant circulating bioactive androgen during normal and premature adrenarche. J Clin Endocrinol Metab. 2018;103(12):4589-4598. doi:10.1210/jc.2018-00736.
6. Jee YH, Jumani S, Mericq V. The association of accelerated early growth, timing of puberty, and metabolic consequences in children. J Clin Endocrinol Metab.2023;108(9):e663-e670. doi:10.1210/clinem/dgad202.
7. Idkowiak J, Lavery GG, Dhir V, et al. Premature adrenarche: novel lessons from early onset androgen excess. Eur J Endocrinol. 2011;165(2):189-207. doi:10.1530/EJE-11- 0223.
8. Williams RM, Ward CE, Hughes IA. Premature adrenarche. Arch Dis Child. 2012;97(3):250-254. doi:10.1136/archdischild-2011-300011.
9. Janner M, Sommer G, Groessl M, Fluck CE. Premature adrenarche in girls characterized by enhanced 17,20-lyase and 17β-hydroxysteroid dehydrogenase activities. J Clin Endocrinol Metab. 2020;105(12):dgaa598. doi:10.1210/clinem/dgaa598.
10. Oberfield SE, Sopher AB, Gerken AT. Approach to the girl with early onset of pubic hair. J Clin Endocrinol Metab. 2011;96(6):1610-1622. doi:10.1210/jc.2011-0225.
11. Ibanez L, Dimartino-Nardi J, Potau N, Saenger P. Premature adrenarche—normal variant or forerunner of adult disease? Endocr Rev. 2000;21(6):671-696. doi:10.1210/edrv.21.6.0416.
12. Witchel SF, Pinto B, Burghard AC, Oberfield SE. Update on adrenarche. Curr Opin Pediatr. 2020;32(4):574-581. doi:10.1097/MOP.0000000000000928.
13. Martin-Calvo N, Goni L, Tur JA, Martinez JA. Low birth weight and small for gestational age are associated with complications of childhood and adolescence obesity: systematic review and meta-analysis. Obes Rev. 2022;23(Suppl 1):e13380. doi:10.1111/obr.13380.
14. Prinz N, Putri RR, Reinehr T, et al. The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: a retrospective two-cohort study. PLoS Med. 2023;20(1):e1004165. doi:10.1371/journal.pmed.1004165.
15. Yoshida-Montezuma Y, Sivapathasundaram B, Brown HK, et al. Association of late preterm birth and size for gestational age with cardiometabolic risk in childhood. JAMA Netw Open. 2022;5(5):e2214379. doi:10.1001/jamanetworkopen.2022.14379.
16. Mericq V, Martinez-Aguayo A, Uauy R, et al. Long-term metabolic risk among children born premature or small for gestational age. Nat Rev Endocrinol. 2017;13(1):50-62. doi:10.1038/nrendo.2016.127.
17. Chiavaroli V, Marcovecchio ML, de Giorgis T, et al. Progression of cardio-metabolic risk factors in subjects born small and large for gestational age. PLoS One. 2014;9(8):e104278. doi:10.1371/journal.pone.0104278.
18. Cauzzo C, Chiavaroli V, Di Valerio S, Chiarelli F. Birth size, growth trajectory and later cardio-metabolic risk. Front Endocrinol (Lausanne). 2023;14:1187261. doi:10.3389/fendo.2023.1187261.
19. Chernausek SD. Update: consequences of abnormal fetal growth. J Clin Endocrinol Metab. 2012;97(3):689-695. doi:10.1210/jc.2011-2741.
20. Kim YJ, Shin SH, Lee ES, et al. Impact of size at birth and postnatal growth on metabolic and neurocognitive outcomes in prematurely born school-age children. Sci Rep. 2021;11(1):6836. doi:10.1038/s41598-021-86292-1.
21. de Jong M, Cranendonk A, van Weissenbruch MM. Components of the metabolic syndrome in early childhood in very-low-birth-weight infants and term small and appropriate for gestational age infants. Pediatr Res. 2015;78(4):457-461. doi:10.1038/pr.2015.118.
22. Maguolo A, Olivieri F, Zusi C, et al. The risk of metabolic derangements is higher in children and adolescents with overweight or obesity born small for gestational age. Nutr Metab Cardiovasc Dis. 2021;31(6):1903-1910. doi:10.1016/j.numecd.2021.02.025.
23. Roth CL, Sathyanarayana S. Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: potential implications in the child born small for gestational age (SGA). Rev Endocr Metab Disord. 2012;13(2):129-140. doi:10.1007/s11154
2. Augsburger P, Liimatta J, Fluck CE. Update on adrenarche—still a mystery. J Clin Endocrinol Metab. 2024;109(6):1403-1422. doi:10.1210/clinem/dgae008.
3. Voutilainen R, Jaaskelainen J. Premature adrenarche: etiology, clinical findings, andconsequences. J Steroid Biochem Mol Biol. 2015;145:226-236. doi:10.1016/j.jsbmb.2014.06.004.
4. Utriainen P, Laakso S, Liimatta J, Jaaskelainen J, Voutilainen R. Premature adrenarche— a common condition with variable presentation. Horm Res Paediatr. 2015;83(4):221-231. doi:10.1159/000369458.
5. Rege J, Turcu AF, Kasa-Vubu JZ, et al. 11-Ketotestosterone is the dominant circulating bioactive androgen during normal and premature adrenarche. J Clin Endocrinol Metab. 2018;103(12):4589-4598. doi:10.1210/jc.2018-00736.
6. Jee YH, Jumani S, Mericq V. The association of accelerated early growth, timing of puberty, and metabolic consequences in children. J Clin Endocrinol Metab.2023;108(9):e663-e670. doi:10.1210/clinem/dgad202.
7. Idkowiak J, Lavery GG, Dhir V, et al. Premature adrenarche: novel lessons from early onset androgen excess. Eur J Endocrinol. 2011;165(2):189-207. doi:10.1530/EJE-11- 0223.
8. Williams RM, Ward CE, Hughes IA. Premature adrenarche. Arch Dis Child. 2012;97(3):250-254. doi:10.1136/archdischild-2011-300011.
9. Janner M, Sommer G, Groessl M, Fluck CE. Premature adrenarche in girls characterized by enhanced 17,20-lyase and 17β-hydroxysteroid dehydrogenase activities. J Clin Endocrinol Metab. 2020;105(12):dgaa598. doi:10.1210/clinem/dgaa598.
10. Oberfield SE, Sopher AB, Gerken AT. Approach to the girl with early onset of pubic hair. J Clin Endocrinol Metab. 2011;96(6):1610-1622. doi:10.1210/jc.2011-0225.
11. Ibanez L, Dimartino-Nardi J, Potau N, Saenger P. Premature adrenarche—normal variant or forerunner of adult disease? Endocr Rev. 2000;21(6):671-696. doi:10.1210/edrv.21.6.0416.
12. Witchel SF, Pinto B, Burghard AC, Oberfield SE. Update on adrenarche. Curr Opin Pediatr. 2020;32(4):574-581. doi:10.1097/MOP.0000000000000928.
13. Martin-Calvo N, Goni L, Tur JA, Martinez JA. Low birth weight and small for gestational age are associated with complications of childhood and adolescence obesity: systematic review and meta-analysis. Obes Rev. 2022;23(Suppl 1):e13380. doi:10.1111/obr.13380.
14. Prinz N, Putri RR, Reinehr T, et al. The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: a retrospective two-cohort study. PLoS Med. 2023;20(1):e1004165. doi:10.1371/journal.pmed.1004165.
15. Yoshida-Montezuma Y, Sivapathasundaram B, Brown HK, et al. Association of late preterm birth and size for gestational age with cardiometabolic risk in childhood. JAMA Netw Open. 2022;5(5):e2214379. doi:10.1001/jamanetworkopen.2022.14379.
16. Mericq V, Martinez-Aguayo A, Uauy R, et al. Long-term metabolic risk among children born premature or small for gestational age. Nat Rev Endocrinol. 2017;13(1):50-62. doi:10.1038/nrendo.2016.127.
17. Chiavaroli V, Marcovecchio ML, de Giorgis T, et al. Progression of cardio-metabolic risk factors in subjects born small and large for gestational age. PLoS One. 2014;9(8):e104278. doi:10.1371/journal.pone.0104278.
18. Cauzzo C, Chiavaroli V, Di Valerio S, Chiarelli F. Birth size, growth trajectory and later cardio-metabolic risk. Front Endocrinol (Lausanne). 2023;14:1187261. doi:10.3389/fendo.2023.1187261.
19. Chernausek SD. Update: consequences of abnormal fetal growth. J Clin Endocrinol Metab. 2012;97(3):689-695. doi:10.1210/jc.2011-2741.
20. Kim YJ, Shin SH, Lee ES, et al. Impact of size at birth and postnatal growth on metabolic and neurocognitive outcomes in prematurely born school-age children. Sci Rep. 2021;11(1):6836. doi:10.1038/s41598-021-86292-1.
21. de Jong M, Cranendonk A, van Weissenbruch MM. Components of the metabolic syndrome in early childhood in very-low-birth-weight infants and term small and appropriate for gestational age infants. Pediatr Res. 2015;78(4):457-461. doi:10.1038/pr.2015.118.
22. Maguolo A, Olivieri F, Zusi C, et al. The risk of metabolic derangements is higher in children and adolescents with overweight or obesity born small for gestational age. Nutr Metab Cardiovasc Dis. 2021;31(6):1903-1910. doi:10.1016/j.numecd.2021.02.025.
23. Roth CL, Sathyanarayana S. Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: potential implications in the child born small for gestational age (SGA). Rev Endocr Metab Disord. 2012;13(2):129-140. doi:10.1007/s11154