Low-Level Prenatal and Postnatal Blood Lead Exposure and Adrenocortical Responses to Acute Stress in Children

Article excerpt

BACKGROUND: A few recent studies have demonstrated heightened hypothalamic--pituitary--adrenal (HPA) axis reactivity to acute stress in animals exposed to heavy metal contaminants, particularly lead. However, Pb-induced dysregulation of the HPA axis has not yet been studied in humans.

OBJECTIVE: In this study, we examined children's cortisol response to acute stress (the glucocorticoid product of HPA activation) in relation to low-level prenatal and postnatal Pb exposure.

METHODS: Children's prenatal blood Pb levels were determined from cord blood specimens, and postnatal lead levels were abstracted from pediatrician and state records. Children's adrenocortical responses to an acute stressor were measured using assays of salivary cortisol before and after administration of a standard cold pressor task.

RESULTS: Pb exposure was not associated with initial salivary cortisol levels. After an acute stressor, however, increasing prenatal and postnatal blood Pb levels were independently associated with significantly heightened salivary cortisol responses.

CONCLUSIONS: Our results suggest that relatively low prenatal and postnatal blood lead levels--notably those below the 10 [micro]g/dL blood lead level identified by the Centers for Disease Control and Prevention for public health purposes--can alter children's adrenocortical responses to acute stress. The behavioral and health consequences of this Pb-induced HPA dysregulation in children have yet to be determined.

KEY WORDS: adrenocortical, children, cortisol, HPA axis, lead, metal pollution, Pb, stress. Environ Health Perspect 116:249-255 (2008). doi:10.1289/ehp.10391 available via http://dx.doi.org/[Online 17 November 2007]


Recent research has evaluated the effects of lead exposure on responses of the hypothalamic-pituitary-adrenal (HPA) axis to acute stress. These responses have been considered in animals, through assessment of glucocorticoid blood levels before and after the onset of an acute stressor. Several studies (Cory-Slechta et al. 2004; Virgolini et al. 1999, 2004) have demonstrated a significant positive association in rats between Pb exposure and baseline plasma corticosterone (the glucocorticoid equivalent of cortisol in humans). In addition, many studies have shown that greater Pb exposure is associated with heightened corticosterone reactivity to acute stress [Baos et al. 2006; Cory-Slechta et al. 2004; Virgolini et al. 2004 (in rats)]; however, in some cases, Pb exposure is associated with either a diminished glucocoticoid response to acute stress [Levesque et al. 2003 (in yellow perch); Virgolini et al. 2004 (in rats)] or no significant effect on acute stress reactivity (Virgolini et al. 2004). To our knowledge, the HPA response to acute stress as a function of Pb exposure has not been evaluated in humans. In the present study we consider salivary cortisol response to acute stress, in children with low-level Pb exposure.

Several studies have considered factors that affect children's adrenocortical responses to acute stress. Such research has generally focused either on intrinsic differences such as temperament (van Bakel and Riksen-Walraven 2004) and attachment (Gunnar et al. 1989) or social contextual factors such as parental maltreatment (Cicchetti and Rogosch 2001) and abuse (De Bellis et al. 1994). Although exposure to environmental toxicants may co-vary with these variables (e.g., Gump et al. 2007), the study of toxicant effects is relatively novel to developmental psychobiology. Similarly, the study of acute stress responses in children is novel in neurotoxicology. Notably, however, we recently reported a positive association between blood Pb and cardiovascular reactivity to acute stress in children (Gump et al. 2005). Here we consider the further association of blood Pb to adrenocortical reactivity to acute stress in these children.

Pb-induced increases in HPA reactivity in children are likely to have far-reaching consequences. …