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Serum Dehydroepiandrosterone Sulfate Levels and Pubarche in Short Children Born Small for Gestational Age before and during Growth Hormone Treatment

Department of Pediatrics, Division of Endocrinology (V.H.B., A.C.S.H.-K.), Sophia Children’s Hospital; and Departments of Epidemiology and Biostatistics (P.G.H.M.) and Internal Medicine (F.H.d.J.), Erasmus University Medical Centre, 3000 CB Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Venje H. Boonstra, M.D., Sophia Children’s Hospital/Erasmus University Medical Centre, Department of Paediatrics, Division of Endocrinology, Postbus 2060, 3000 CB Rotterdam, The Netherlands. E-mail: v.h.boonstra{at}erasmusmc.nl.

It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and will be affected by intrauterine growth retardation. As a result, children born small for gestational age (SGA) might have several hormonal disturbances. In later life, one of the questions that might arise is: Do short children born SGA have higher serum dehydroepiandrosterone sulfate (DHEAS) levels than their peers? Therefore, we compared serum DHEAS levels of 181 short prepubertal children aged 3–9 yr born SGA [birth length (SD score) below -2 for gestational age] with a control group of 170 prepubertal age-matched, normal-statured children born appropriate for gestational age (birth length between -2 and +2 SD score). Because relatively high serum DHEAS levels at a young age might result in a premature pubarche, we investigated the incidence of premature pubarche. We also investigated the association between serum DHEAS levels and bone maturation. In addition, we analyzed whether 1 yr of GH treatment with 1 and 2 mg/m²·d (0.035 and 0.070 mg/kg·d, respectively) had an effect on serum DHEAS levels of prepubertal short SGA children.

Serum DHEAS levels of the SGA group were comparable with those of age-matched appropriate for gestational age controls. The incidence of premature pubarche was comparable with that of the normal population. There was a weak negative correlation between serum DHEAS levels and bone maturation after the age of 7 yr. After 1 yr of GH treatment, the increase of serum DHEAS levels was the same for both GH dosage groups and the untreated group.

In conclusion, this study shows that small size at birth, which might be a feature of fetal growth restriction, has no effect on serum DHEAS levels before the age of 9 yr. The incidence of premature pubarche is comparable with the normal population. Finally, 1 yr of GH treatment has no effect on serum DHEAS levels.

This work was supported by Novo Nordisk A/S (Bagsvaerd, Denmark) and Novo Nordisk Farma (Alphen a/d Rijn, The Netherlands).

Abbreviations: AGA, Appropriate for gestational age; BA, bone age; BMI, body mass index; CA, chronological age; DHEA, dehydroepiandrosterone; DHEAS, DHEA sulfate; SDS, SD score; SGA, small for gestational age.

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