Birthsize, gestational age and adrenal function in adult life: studies of dexamethasone suppression and ACTH1-24 stimulation.
OBJECTIVE
Several studies show that low birthweight is associated with long-term alterations in the function of the hypothalamic-pituitary-adrenal axis (HPAA). We recently reported that the relationship between birthweight and fasting serum cortisol concentrations differed according to the gestational age of the babies, suggesting that both hypercortisolism and hypocortisolism could be a consequence of impaired fetal growth. We have now extended these findings by examining the relationship between birthweight, gestational age and tests of adrenal suppression and stimulation.


METHODS
Prospective birth cohort study.


METHODS
We studied 165 women (mean age 71.3 Years) born at term in Helsinki, Finland, between 1924 and 1933, whose body size and gestational age at birth were recorded. These women underwent an overnight 0.25 mg dexamethasone suppression test followed by a 1 microg ACTH(1-24) stimulation test.


RESULTS
In all women combined, low birthweight was associated with lower total (P=0.03) and free (P=0.02) cortisol concentrations following dexamethasone. However, these relationships were dependent on gestational age at birth, interactions between the effects of birth size and gestational age on dexamethasone responsiveness being statistically significant. To demonstrate these interactions, we divided the study population into two groups according to gestational age. In subjects born at 40 weeks of gestation or more, low birthweight was strongly associated with enhanced dexamethasone suppression (P=0.003 for total and P=0.0004 for free cortisol), while in subjects born before 40 weeks of gestation there was no association. There was, however, no correlation between birth size and the adrenal response to ACTH(1-24).


CONCLUSIONS
These findings reinforce our suggestions that events during prenatal life may lead to both up-regulation and down-regulation of the HPAA.
Kajantie
Eero
E
National Public Health Institute, 00300 Helsinki, Finland. eero.kajanti@helsinki.fi
Eriksson
Johan
J
Barker
David J P
DJ
Forsén
Tom
T
Osmond
Clive
C
Wood
Peter J
PJ
Andersson
Sture
S
Dunkel
Leo
L
Phillips
David I W
DI
D000302:Adrenal Cortex / Q000502:physiology*; D000304:Adrenal Cortex Function Tests; D000324:Adrenocorticotropic Hormone; D000368:Aged; D001724:Birth Weight; D015992:Body Mass Index; D015331:Cohort Studies; D003907:Dexamethasone; D005260:Female; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008875:Middle Aged; D010446:Peptide Fragments; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011446:Prospective Studies; D012307:Risk Factors
D010446:Peptide Fragments; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone