Racial discrimination and leukocyte glucocorticoid sensitivity: Implications for birth timing

Abstract

Rationale. Psychological stress-induced cortisol elevations appear to contribute to preterm birth. Yet, some studies suggest that the biological ramifications of racial discrimination-associated stress are unique and may involve development of decreased glucocorticoid sensitivity despite normalized cortisol levels. Objective. In this study, we examined the effects of racial discrimination on maternal cortisol output, leukocyte glucocorticoid sensitivity, and the degree of correspondence between cortisol levels and birth timing in an African American cohort. Method. A generally healthy prospective cohort was enrolled at 28 to 32 weeks gestation (n=91). The Experiences of Discrimination scale was administered, whole blood collected, and plasma cortisol levels, cytokine levels, and leukocyte counts quantified for examination of patterns of endogenous feedback. Results. Racial discrimination in the mid-tertile was associated with greater maternal cortisol levels than the bottom tertile among women reporting internalizing responses (b*=0.68, p=0.001). Decreased leukocyte glucocorticoid sensitivity was witnessed at greater frequencies of experiences of racial discrimination, as evidenced by decreased correspondence between maternal cortisol levels and plasma IL-8 levels, monocyte counts, and lymphocyte counts (ps≤0.043). The association between maternal cortisol levels and birth timing differed by discrimination tertile (p values≤0.005), with greater cortisol levels predictive of earlier birth among women without (b*=−0.59, p<0.001) but not with racial discrimination (ps≥0.497). Conclusion. We provide novel evidence of decreased glucocorticoid sensitivity at increasing frequency of exposure to racial discrimination. Our findings suggest that the biology of preterm birth may depend upon racial discriminatory exposures, favoring pathways dependent upon glucocorticoid-induced increases in leukocyte tissue surveillance versus glucocorticoid resistance-associated inflammatory aberrations at increasing levels of exposure. Precision approaches to prenatal care are sorely needed to combat preterm birth, particularly among African American women, with efforts dependent upon further research examining the pathways contributing to the syndrome dependent upon the totality of an individual’s exposures.

Glucocorticoid receptor sensitivity in early pregnancy in an African American cohort

“…Across the 16 studies included, sample characteristics (including race/ethnicity and sex) varied, which may have obscured subpopulation‐specific findings. In a novel study on leukocyte glucocorticoid sensitivity and racial discrimination among 91 African American women, Gillespie and Anderson 1 found that decreased GC sensitivity was associated with a higher frequency of experiences with racial discrimination. Experiences of discrimination have also been linked to preterm birth among African American women 54 …”

“…Alterations in glucocorticoid (GC) sensitivity may occur as a result of chronic stress, including that due to racial discrimination, and thus may be implicated in the persistent adverse maternal and infant health outcomes of African Americans 1 . Despite the appeal of this mechanism, there are many gaps in the literature.…”

“…GC resistance is associated with loss of the normal negative association between GC concentration and indicators of inflammatory immune activation 4 . In obstetrical populations, few studies of GC sensitivity have focused on African American populations, who may experience and embody chronic exposure to racial discrimination uniquely 1,20‐23 . Moreover, there are only a few large‐scale studies in human pregnancy that have measured both cytokines and HPA axis hormones, and none of these directly measured glucocorticoid sensitivity at the cellular level 4,24,25 .…”

Promoting health protection worldwide: The International Labour Organisation and health systems financing, 1952–2012

“…In order to encourage the USA to ratify its constitution in 1946, and to avoid a repeat of the pre-war period, when it had refused to join the League of Nations, the WHO avoided direct engagement with the subject of healthcare financing, restricted to a 'study and report' role. 19 This left the ILO as the de facto UN agency with power to directly advise governments on health financing, albeit solely in relation to social security. From the outset, this led to some friction with the WHO, which had direct responsibility for international health.…”

“…This is evident from the WHO's hostile reaction to the report of the Commission on Organisation of Medical Care (COMC) in 1952. 48 Initiated in response to the ILO's draft social security convention, the COMC featured prominent interwar advocates of social medicine such as Henry Sigerist and Ren e Sand. The Commission advanced proposals, which were anathema to organised interests such as the American Medical Association, such as universal healthcare, salaried medical services and group practice.…”