Blunted Stress Response in Small for Gestational Age Neonates

Abstract

There is evidence that adverse conditions during intrauterine development affect future health of the offspring. Hypothalamus-pituitary-adrenal (HPA) axis dysregulation is assumed to play an important role in the association of small for gestational age (SGA) and the pathogenesis of hypertension and the metabolic syndrome. Stress response patterns in SGA neonates may identify a link with intrauterine-induced permanent maladaptation of the HPA axis. Salivary cortisol and cortisone levels were therefore analyzed during resting conditions and in response to a pain-induced stress event in SGA (Ͻ5th percentile) and appropriate for gestational age (AGA) neonates born Ն34 wk of gestation. In AGA neonates, salivary cortisol and cortisone levels significantly increased after the stress event (p Ͻ 0.05). In contrast, SGA infants exhibited a blunted steroid release after stress induction (p ϭ 0.76, p ϭ 0.65, respectively). No influence of mode of delivery (p ϭ 0.93), gender (p ϭ 0.21), and gestational age (p ϭ 0.57) on stress response patterns was observed in a multiple stepwise regression. SGA neonates show a blunted physiologic activation of the HPA axis in response to a stress stimulus. Thus, intrauterine-induced alteration of HPA axis regulation seems to persist into the postnatal period and represents a prerequisite for the hypothesis of HPA axis involvement in the fetal origin of adult diseases. (Pediatr Res 65: 231-235, 2009) S ubstantial evidence from epidemiologic data and experimental animal models indicate that stressful conditions during intrauterine fetal life affect behavioral development and future health of the offspring. Maladaptation of the fetal autonomic regulation has been suggested as a putative predisposing factor in the pathogenesis of cardiovascular, metabolic, and psychiatric diseases in low birth weight (LBW) infants (1-3). This has been reinforced by the discovery of an early programming of the stress response-mediating neuroendocrine system, namely the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (4,5). As such, LBW, a surrogate for fetal malnutrition has been linked with increased adrenocortical hormone activity and activation of the sympathetic nervous system (6 -9) in childhood and adult life in independent populations.A pathophysiologic explanation of this phenomenon described by Barker's group as "fetal programming" (10) has been derived from animal models revealing long-term changes in the molecular expression of steroid receptors within the limbic system (11).Increases in glucocorticoids, such as cortisol and cortisone, are generally considered as adaptive mechanisms to mobilize energy for survival in response to a stressful event or to danger (12). Prolonged intrauterine exposure to stress, however, may lead to an alteration of the set point of the stress regulatory system resulting in increased levels of cortisol that can negatively effect the functioning of several biologic systems (13,14) and ultimately result in arterial hypertension and diabe...

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