Hypothalamic-pituitary-adrenal axis activity in adults who were prenatally exposed to the Dutch famine.
OBJECTIVE
The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis.


METHODS
We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1-24 -stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944-1945 Dutch famine.


RESULTS
Cortisol profiles after dexamethasone suppression and ACTH1-24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P = 0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference -2% (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47)) or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 to 12)) differed between exposed and unexposed participants.


CONCLUSIONS
Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.
de Rooij
Susanne R
SR
Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, 1100DD Amsterdam, The Netherlands. s.r.derooij@amc.uva.nl
Painter
Rebecca C
RC
Phillips
David I W
DI
Osmond
Clive
C
Michels
Robert P J
RP
Bossuyt
Patrick M M
PM
Bleker
Otto P
OP
Roseboom
Tessa J
TJ
D000328:Adult; D000886:Anthropometry; D001724:Birth Weight; D001786:Blood Glucose; D001835:Body Weight / Q000502:physiology; D015331:Cohort Studies; D003366:Cosyntropin; D003907:Dexamethasone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007328:Insulin / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013217:Starvation / Q000503:physiopathology*; D013268:Stimulation, Chemical
D001786:Blood Glucose; D007328:Insulin; D003366:Cosyntropin; D003907:Dexamethasone; D006854:Hydrocortisone