Endocrine Abstracts (2002) 3 P269

Size at birth, gestational age and cortisol secretion in adult life: Do multiple mechanisms underlie fetal programming of the hypothalamic-pituitary-adrenal axis?

E Kajantie1,3, DIW Phillips2, L Dunkel1, S Andersson1, DJP Barker2, T Forsen3, C Osmond2, PJ Wood2, J Tuominen4 & J Eriksson3

1Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland; 2MRC Environmental Epidemiology Department, Southampton General Hospital, Southampton, UK; 3Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland; 4Department of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland.

Objective. Recent studies suggest that in utero programming of the hypothalamo-pituitary-adrenal axis is important in explaining the link between small size at birth and adult cardiovascular disease. We therefore examined the relationship between adult cortisol concentration and measurements at birth.

Subjects. 420 men and women (mean age 69.5, range 65.0-75.8 yrs) born and living in Helsinki, Finland, with detailed birth records.

Methods. Fasting total cortisol and cortisol-binding globulin (CBG) measured, free cortisol calculated as cortisol / CBG ratio. All correlations adjusted for gender, current age and body mass index.

Results. Fasting total (mean ± SE 384 ± 7 nmol/L) and free cortisol (8.63 ± 0.14 nmol/mg) showed a correlation with ponderal index at birth (r = 0.14; p = 0.003 and r = 0.13; p = 0.01, respectively) but not with birth weight, length or gestational age. However, there were interactions between effects of gestational age and birth weight and length on total and free cortisol (all p<=0.01). Data were thus analysed in subgroups below and above median (40.0 weeks) gestational age. In the below median gestational age subgroup, birth length showed a negative correlation with total (r = -0.18; p = 0.01) and free (r = -0.16; p = 0.03) cortisol. By contrast, in the above median gestational age subgroup, positive correlations were observed between birth weight and total (r = 0.13; p = 0.06) and free (r = 0.20; p = 0.002) cortisol as well as between ponderal index and total (r = 0.21; p = 0.003) and free (r = 0.20; p = 0.003) cortisol. No interaction with gender was observed.

Conclusions. Adulthood cortisol concentration is related to size at birth, this relationship being dependent on gestational age at birth. Gestational age may thus facilitate distinction between different mechanisms of hypothalamo-pituitary-adrenal axis programming operative in the same population.

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