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Medical Research Council Environmental Epidemiology Unit (A.M.V.W., H.E.S., D.I.W.P.) and Regional Endocrine Laboratory (P.J.W.), Southampton General Hospital, Southampton, SO16 6YD, United Kingdom; and Pediatric and Reproductive Endocrinology Branch (G.P.C.), National Institute of Child Health and Human Development, Bethesda, Maryland 20892
Address all correspondence and requests for reprints to: Prof. David I. W. Phillips, Medical Research Council Environmental Epidemiology Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an intermediary in the association between reduced fetal growth and adult cardiovascular and metabolic diseases. Previous studies have shown that small size at birth is associated with increased fasting plasma cortisol and adrenal responsiveness to ACTH stimulation. We have extended these studies by evaluating the salivary cortisol response to awakening and plasma ACTH and cortisol responses to CRH stimulation and a dexamethasone-suppressed CRH (DEX/CRH) test in a group of low birth weight [LBW; <3.18 kg (7 lb), n = 58] and high birth weight [>3.86 kg (8.5 lb), n = 65] men aged 60–69 yr. Despite no difference in basal pituitary-adrenal activity or in their ACTH and cortisol responses to CRH, LBW men had significantly lower pituitary-adrenal responses in the DEX/CRH test. Although these findings do not explain the HPA abnormalities associated with LBW in previous studies, they provide further evidence of dysregulation of the HPA axis in people who were small at birth.
Supported in part by National Institutes of Health Grant 1 R01 HD41107-01 (to D.I.W.P.).
Abbreviations: AUC, Area under the curve; CV, coefficient of variation; DEX/CRH, dexamethasone-suppressed CRH; DST, dexamethasone suppression test; HAD, Hospital Anxiety and Depression; HBW, high birth weight; HPA, hypothalamic-pituitary-adrenal; iAUC, incremental AUC; LBW, low birth weight.
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