cosyntropin and Birth-Weight

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.. 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.. 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.. 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.

Topics: Adult; Anthropometry; Birth Weight; Blood Glucose; Body Weight; Cohort Studies; Cosyntropin; Dexamethasone; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Linear Models; Male; Middle Aged; Pituitary-Adrenal System; Pregnancy; Prenatal Exposure Delayed Effects; Starvation; Stimulation, Chemical

The aims of this study were to ascertain 1) whether fetal maturation could be induced precociously by maternal administration with adrenocorticotrophic hormone (ACTH) and 2) whether maturation could be achieved without significant risk to mare or fetus. Twenty-two mares received either 1 mg (low dose, LD, n = 6) or 4 or 5 mg (higher dose, HD, n = 16) synthetic Depot ACTH(1-24) at 300, 301 and 302 days gestation. Because, during the course of the study, ACTH appeared to have a greater influence on mares mated during the later part of the breeding season, the HD group were divided retrospectively into those mated before (HDE, n = 6), or after (HDL, n = 10), 1st July. All LD mares were mated before 1st July. Control injections were not performed but gestational data were compared retrospectively with 64 untreated, spontaneously foaling pony mares mated between May and October. Plasma progestagen and cortisol concentrations increased significantly (P<0.05) following ACTH administration in all groups, but progestagens were higher and cortisol elevated for longer in HD mares. ACTH stimulated mammary development and milk electrolyte changes in HD mares. Mean +/- s.e. gestation period (days) was significantly (P<0.01) shorter in HDL mares (318 +/- 1.8) compared with LD (335 +/- 3.7), HDE (340 +/- 4.3) and untreated mares mated after 1st July (327 +/- 1.3). All foals were mature except 2 HDL foals which were stillborn. HDL foals had a higher MCV and lower mean bodyweight, indicating they were delivered before full term. In conclusion, maternal ACTH administration appears to accelerate fetal maturation and delivery in pony mares given high doses and mated late in the breeding season. Further work is required to establish the optimal gestational age and dosage for maternal ACTH administration before clinical recommendations can be given for this therapy.

Topics: Animals; Birth Weight; Cosyntropin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Female; Horses; Hydrocortisone; Labor, Obstetric; Male; Mammary Glands, Animal; Pregnancy; Pregnancy, Animal; Progesterone