In this study, CRP and EBV antibody levels, two markers reflective of chronic stress, were not associated with maternal demographic factors, including maternal race or indicators of relative socioeconomic status (e.g., employment status, income). There was discernable evidence, however, that EBV antibody levels were associated with some measures of stress, and in particular perceived stress and discrimination. Though the highest CRP levels were found in women with the fewest buffers against stressful events, this relationship did not reach statistical significance.
Elevated CRP levels have been associated with self-reported stress.36–37
Similarly, elevated CRP levels have been associated with preterm birth.31, 34–35
Yet, there have been no prospective studies that have linked stress, CRP levels, and preterm birth, and the relevance of CRP as a biomarker of stress relevant to reproductive-age women and to adverse obstetric outcomes has not been established. Indeed, in this prospective study, CRP levels were not strongly associated with multiple domains of an individual’s experience of stress.
However, EBV antibody levels were significantly associated with measures of stress. This relationship is of particular interest, given that the relationship of EBV antibodies with chronic stress has not been well studied in reproductive-age or pregnant women. EBV antibodies, however, have been widely studied among other populations and shown to be associated with negative life events, academic stress, strained social relationships, and emotional distress.8, 13, 32–33, 41–44
Indeed, in one meta-analysis, EBV antibodies were identified as one of the most consistent and strongest measures of stress.9
In this study of low-income, predominantly African-American women, we found elevated EBV antibody levels to be most strongly associated with elevated perceived stress and experiences of discrimination. Measures of perceived stress and discrimination have been associated with increased rates of low birth weight infants and preterm birth in African-American women. For example, Collins et al. reported that African-American mothers’ perceptions of increased stress were significantly associated with increased odds of having a very-low birth weight (VLBW) child. Additionally, it was noted that African-American women who reported higher exposure to racism had significantly increased odds for very low birth weight (VLBW) infants even when controlling for demographic, biomedical, and behavioral variables.45
The association of racial discrimination with adverse pregnancy outcomes, as well as with higher levels of EBV antibodies, is of particular relevance given the known racial disparity in preterm birth, the lack of an accepted etiology of the disparity, and the inability of traditional socioeconomic variables (e.g. economic differences) to fully account for this disparity.
This study also provides evidence that blood specimens, obtained in a community setting with a high degree of subject acceptance, can allow analysis of potentially relevant stress biomarkers. It has previously been shown that community-based research may more effectively overcome issues of trust, ease of access, and follow-up than hospital-based specimen collection, particularly in low-income populations.46–48
Community-based data collection may achieve higher rates of participation and retention and therefore diminish selection bias that may be associated with hospital-based data collection.
Limitations of our study should be noted. The size of the study population may have limited the ability to elucidate associations between biomarkers and survey measures of stress. Also, the detection of an association depends upon the ability to discern the stress that an individual is experiencing, and the best method or instrument to assess chronic stress remains uncertain. It may be that stress is best defined not by measurement from single instruments, but by a more elaborate combination of measures f rom different domains and instruments. Not all measures of stress used in surveys may be equally valid or reliable for different populations. For example, stressors experienced by low-income women living in an urban setting may need to be assessed differently than for women who have other socioeconomic or racial backgrounds. Nevertheless, the measures used in this study are well established and assess different domains of stress. Finally, women in the study all had a significant degree of economic deprivation which reduced any potential confounding by economic status. This population was chosen because chronic stress was likely to be more prevalent and greater in magnitude. Yet, it is also possible that the choice of this population limited the possibility of finding an association, as the overall levels of the stress biomarkers were higher and the distribution of these biomarkers was narrower than in a random sample of the entire population. In this case, a “ceiling effect” could have impaired the ability to discern associations between chronic stress and the biomarkers under study.
This study adds to the growing body of literature focused on the ramifications of stress in reproductive age women. Additional research needs to determine which biomarkers and which psychometric assessments best capture the stress that an individual experiences, as well as the exact relationship between self-reported stress, stress biomarkers and reproductive health outcomes such as preterm birth. In addition, prospective cohort studies may elucidate the importance of the gene-environment interaction with respect to stress and adverse pregnancy outcomes.