Original Articles
Increased adrenocortical and adrenomedullary hormonal activity in 12-year-old children born small for gestational age,☆☆

https://doi.org/10.1067/mpd.2002.126923Get rights and content

Abstract

Objectives: To determine whether adrenal hormonal activity is altered in children born small for gestational age (SGA), and whether concentrations of adrenal hormones relate to those of serum lipids or to anthropometric measures. Study design: We studied 55 SGA children and 55 appropriate for gestational age (AGA) children at the age of 12 years in a case-control setting. The concentrations of fasting serum cortisol, dehydroepiandrosterone sulfate (DHEAS), plasma epinephrine (E), and norepinephrine (NE) were analyzed. Results: The SGA children had significantly higher mean concentrations of serum DHEAS (3.53 vs 2.89 μmol/L, P =.009) and plasma E (0.33 vs 0.25 nmol/L, P =.005) than their age- and sex-matched control subjects. The mean serum cortisol and plasma NE concentrations did not differ significantly between the groups. However, the SGA children in the highest quartile for serum cortisol had significantly higher concentrations of plasma E (0.50 vs 0.28 nmol/L, P <.001), serum LDL (3.21 vs 2.73 mmol/L, P =.025) and total cholesterol (5.06 vs 4.42 mmol/L, P =.021) than the SGA children in the lower cortisol quartiles. The factors associating with high levels of plasma E in the SGA children were high level of serum cortisol [odds ratio (OR) = 3.8, 95% confidence interval (95% CI) = 1.5-10], LDL cholesterol (OR = 3.9, 95% CI = 1.3-12), male sex (OR = 8.3, 95% CI = 1.0-68) and low birth weight (OR = 1.4, 95% CI = 1.0-1.8) in multiple logistic regression analysis. Conclusions: Twelve-year-old children born SGA had increased DHEAS and epinephrine levels in circulation. High serum cortisol concentrations are associated with high epinephrine, LDL, and total cholesterol levels. (J Pediatr 2002;141:477-82)

Section snippets

Definitions

SGA was defined as birth weight and/or length and/or ponderal index >2 SD scores below the respective mean for the gestational age.10 The ponderal index was calculated as (weight [g]/length3[cm]) × 100. AGA was defined as birth weight, birth length and ponderal index ≥−2 SD scores and ≤2 SD scores of the respective mean for the gestational age. Full-term applied to babies born at or after week 37 and before the 42nd week of gestation (calculated from the beginning of the last menstruation).

Serum cortisol concentrations and their relationship with plasma catecholamines, serum lipids, and anthropometric measures

The mean serum cortisol concentrations did not differ between the SGA and AGA children (292.5 vs 272.1 nmol/L, P =.624). The SGA boys had significantly higher mean concentrations of serum cortisol than the SGA girls (329.5 vs 271.3 nmol/L, P =.046). Serum cortisol had a positive correlation with plasma E and NE in the SGA group (Table II), whereas in the AGA group, its correlation with E was weaker (r = 0.297, P =.028) and with NE not significant.Serum cortisol levels correlated positively with

Discussion

We have shown an association between high levels of serum cortisol and elevated concentrations of plasma E, serum LDL, and total cholesterol in SGA children at 12 years of age. The SGA children had significantly higher concentrations of serum DHEAS and circulating plasma E when compared with their matched AGA control subjects. In multiple logistic regression analysis, high levels of serum cortisol and LDL cholesterol, and male sex were associated with elevated levels of plasma E in the SGA

References (24)

  • DJP Barker et al.

    Fetal nutrition and cardiovascular disease in adult life

    Lancet

    (1993)
  • WA Divers et al.

    Amniotic fluid catecholamines and metabolites in intrauterine growth retardation

    Am J Obstet Gynecol

    (1981)
  • I Francois et al.

    Adrenarche and fetal growth

    Pediatr Res

    (1997)
  • L Ibanez et al.

    Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age

    J Clin Endocrinol Metab

    (1999)
  • J Dahlgren et al.

    Adrenal steroid hormones in short children born small for gestational age

    Clin Endocrinol

    (1998)
  • P Ghirri et al.

    Adrenarche, pubertal development, age at menarche, and final height of full-term, born small for gestational age (SGA) girls

    Gynecol Endocrinol

    (2001)
  • PM Clark et al.

    Size at birth and adrenocortical function in childhood

    Clin Endocrinol

    (1996)
  • Y Dalmaz et al.

    Neonatal pattern of adrenergic metabolites in urine of small for gestational age and preterm infants

    J Neural Transm

    (1980)
  • S Tenhola et al.

    Serum lipid concentrations and growth characteristics in 12-year-old children born small for gestational age

    Pediatr Res

    (2000)
  • J Pihkala et al.

    New Finnish fetal growth charts (in Finnish)

    Duodecim

    (1989)
  • WA Marshall et al.

    Variations in pattern of pubertal changes in girls

    Arch Dis Child

    (1969)
  • WA Marshall et al.

    Variations in pattern of pubertal changes in boys

    Arch Dis Child

    (1970)
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    Supported by the Pediatric Research Foundation, Sigrid Jusélius Foundation, Kuopio University Hospital, Academy of Finland, and Emil Aaltonen Foundation.

    ☆☆

    Reprint requests: Raimo Voutilainen, MD, PhD, Department of Pediatrics, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland.

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