Hypertensive disorders of pregnancy (HDP) are the most common cardiometabolic complications of pregnancy, affecting nearly 10% of US pregnancies and contributing substantially to maternal and infant morbidity and mortality. In the US, women of African American race are at increased risk for HDP. Early biomarkers that reliably identify women at risk for HDP remain elusive, yet are essential for the early identification and targeting of interventions to improve maternal and infant outcomes. We employed high-resolution metabolomics (HRM) to identify metabolites and metabolic pathways that were altered in early (8-14 weeks) gestation serum samples of pregnant African American women who developed HDP after 20 weeks' gestation (n=20) - either preeclampsia (PE; n=11) or gestational hypertension (gHTN; n=9) - compared to those who delivered full term without complications (n=80). We found four metabolic pathways that were significantly (p<0.05) altered in women who developed PE and five pathways that were significantly (p<0.05) altered in women who developed gHTN compared to women who delivered full term without complications. We also found that four specific metabolites (p<0.05) were distinctly upregulated (retinoate, kynurenine) or downregulated (SN-glycero-3-phosphocholine, 2′4′-dihydroxyacetophenone) in women who developed PE compared to gHTN. These findings support that there are systemic metabolic disruptions that are detectable in early pregnancy (8-14 weeks of gestation) among pregnant African American women who develop PE and gHTN. Furthermore, the early pregnancy metabolic disruptions associated with PE and gHTN are distinct, implying they are unique entities rather than conditions along a spectrum of the same disease process despite the common clinical feature of high blood pressure.

Infection has been hypothesized to be one of the factors associated with spontaneous preterm birth (PTB) and with the racial disparity in rates of PTB between African American and Caucasian women. However, recent findings refute the generalizability of the role of infection and inflammation. African Americans have an increased incidence of PTB in the setting of intraamniotic infection, periodontal disease, and bacterial vaginosis compared to Caucasians. Herein we report variability in infection- and inflammation-related factors based on race/ethnicity. For African American women, an imbalance in the host proinflammatory response seems to contribute to infection-associated PTB, as evidenced by a greater presence of inflammatory mediators with limited or reduced presence of immune balancing factors. This may be attributed to differences in the genetic variants associated with PTB between African Americans and Caucasians. We argue that infection may not be a cause of racial disparity but in association with other risk factors such as stress, nutritional deficiency, and differences in genetic variations in PTB, pathways and their complex interactions may produce differential inflammatory responses that may contribute to racial disparity. © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Objective. To give an overview of the literature for evidence of nutrient deficiencies as contributors to the disparity in preterm birth (PTB) between African-American and Caucasian women. Design. Structured literature survey. Methods. We searched MEDLINE to identify observational and experimental studies that evaluated the relation between nutrient intake and/or supplementation and PTB. For nutrients for which studies supported an association, we searched MEDLINE for studies of the prevalence of deficiency in the USA by race. Main Outcome Measures. Summarized findings on nutrients for which there is both evidence of a role in PTB and variability in t he prevalence of deficiency by race. Results. Nutrient deficiencies for which there are varying levels of evidence for an association with PTB and a greater burden among African-American compared with Caucasian women include deficiencies of iron, folic acid, zinc, vitamin D, calcium and magnesium, and imbalance of ω-3 and ω-6 polyunsaturated fatty acids. There are inadequate high-quality studies that investigate the role of nutrient deficiencies in PTB, their potential interaction with other risks, the proportion of excess risk for which they account, and whether supplementation can reduce the risk of, and racial disparities in, PTB in US populations. Conclusion. Deficiencies of several nutrients have varying levels of evidence of association with PTB and are of greater burden among African-American compared with Caucasian women. Although further research is needed, strategies that improve the nutritional status of African-American women may be a means of addressing a portion of the racial disparity in PTB. © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Objective. We reviewed the evidence for three theories of how preconceptional psychosocial stress could act as a contributing determinant of excess preterm birth risk among African American women: early life developmental plasticity and epigenetic programming of adult neuroendocrine systems; blunting, weathering, or dysfunction of neuroendocrine and immune function in response to chronic stress activation through the life course; individuals' adoption of risky behaviors such as smoking as a response to stressful stimuli. Methods. Basic science, clinical, and epidemiologic studies indexed in MEDLINE and Web of Science databases on preconceptional psychosocial stress, preterm birth and race were reviewed. Results. Mixed evidence leans towards modest associations between preconceptional chronic stress and preterm birth (for example common odds ratios of 1.2-1.4), particularly in African American women, but it is unclear whether this association is causal or explains a substantial portion of the Black-White racial disparity in preterm birth. The stress-preterm birth association may be mediated by hypothalamic-pituitary-adrenal axis dysfunction and susceptibility to bacterial vaginosis, although these mechanisms are incompletely understood. Evidence for the role of epigenetic or early life programming as a determinant of racial disparities in preterm birth risk is more circumstantial. Conclusions. Preconceptional stress, directly or in interaction with host genetic susceptibility or infection, remains an important hypothesized risk factor for understanding and reducing racial disparities in preterm birth. Future studies that integrate adequately sized epidemiologic samples with measures of stress, infection, and gene expression, will advance our knowledge and allow development of targeted interventions. © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Objective. To investigate associations among serum 25-hydroxy-vitamin D (25-OH-D), folate, omega-6/omega-3 fatty acid ratio and bacterial vaginosis (BV) during pregnancy. Methods. Biospecimens and data were derived from a random sample (N = 160) of women from the Nashville Birth Cohort. We compared mean plasma nutrient concentrations for women with and without BV during pregnancy (based on Nugent score ≥7) and assessed the odds of BV for those with 25-OH-D <12 ng/mL, folate <5 ug/L, and omega-6/omega-3 ratio >15. Results. The mean plasma 25-OH-D was significantly lower among women with BV during pregnancy (18.00±8.14 ng/mL versus 24.34±11.97 ng/mL, P = 0.044). The adjusted odds of BV were significantly increased among pregnant women with 25-OH-D <12 ng/mL (aOR 5.11, 95% CI: 1.19–21.97) and folate <5 ug/L (aOR 7.06, 95% CI: 1.07–54.05). Conclusion. Vitamin D and folate deficiencies were strongly associated with BV (Nugent score ≥7) during pregnancy.

Objective. We seek to expand on a biopsychosocial framework underlying the etiology of excess preterm birth experienced by African-American women by exploring short inter-pregnancy intervals as a partial explanatory factor. Design. We conducted a qualitative analyses of published studies that met specified criteria for assessing the association of inter-pregnancy interval and preterm birth. Methods. We determine whether inter-pregnancy interval is associated with preterm birth, what the underlying causal mechanism may be, whether African-American women are more likely than Caucasian women to have short intervals, and whether achieving an optimal interval will result in reduced African-American-Caucasian gap in preterm births. Main Outcome Measures. Crude and adjusted odds ratios for preterm birth, with the referent group being the interval closest to the 'ideal' of 18-23 months and the exposed group having intervals < 12 months or some subset of that inter-pregnancy interval. Results. Inter-pregnancy interval less than six months increases preterm birth by about 40%. The mechanism may be through failure to replenish maternal nutritional stores. While there may not be an interaction between race and short inter-pregnancy interval, short intervals can explain about 4% of the African-American-Caucasian gap in preterm birth because African-American women are approximately 1.8 times as likely to have inter-pregnancy intervals of less than six months. Limited studies indicate that optimal intervals can be achieved through appropriate counseling and health care. Conclusions. Excess risk for preterm birth may be reduced by up to 8% among African-Americans and up to 4% among Caucasians through increasing inter-pregnancy intervals to the optimal length of 18-23 months.

This study sought to investigate associations between serum total and free 25(OH)D and bacterial vaginosis (BV) in early and later pregnancy among US black women to provide insight into the most clinically relevant measure of vitamin D status among pregnant black women with respect to risk for BV as well as insights into critical time points for measuring and/or addressing vitamin D status in pregnancy. Methods. Data and biospecimens were derived from a subsample (N = 137) of women from the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Cohort, for whom data related to vitamin D status (serum assays for total and free 25(OH)D) and Nugent score of Gram stained vaginal specimens in early (8-14 weeks) and later (24-30 weeks) were available. We compared total and free 25(OH)D concentrations for women according to Nugent score category (normal flora, intermediate flora, and BV) and assessed the odds of BV according to measures of vitamin D status. Results. Thirty-seven (27%) women had adequate vitamin D status at baseline, whereas 70 (51%) had insufficient vitamin D and 30 (22%) were vitamin D deficient; there were not significant differences in the proportion of women with adequate, insufficient, or deficient vitamin D according to Nugent score category. However, the odds of BV later in pregnancy were significantly higher for women who experienced a smaller rise in total 25(OH)D and free 25(OH)D from 8-14 through 24-30 weeks gestation. Conclusion. The change in measures of vitamin D status from early to later pregnancy is associated with the occurrence of BV in pregnancy. Further research is needed to examine the association between the change in vitamin D status over pregnancy and the occurrence of BV and other measures of vaginal microbial composition as well as to identify factors that influence change in vitamin D status over pregnancy.

Purpose This study systematically examines the impact of inclusion of HIPAA authorization on the willingness of African Americans of diverse sociodemographic characteristics to participate in a clinical research study and explores reasons for non-participation. Methods For a purposive sample of 384 African American outpatients at 4 metropolitan primary care clinics from August 2005 through May 2006, willingness to participate in a hypothetical clinical research study of an antihypertensive medication under one of two experimental conditions was compared. Interviewees were randomly assigned to undergo informed consent alone (control group) or informed consent with HIPAA authorization (HIPAA group). They were asked whether they would participate and reasons for their decision. Results A smaller proportion of interviewees in the HIPAA group were willing to enroll in the study (27% vs. 39%; p=.02), with an adjusted odds ratio = 0.56 (95% confidence interval: 0.36 – 0.91). Those in the HIPAA group were more likely to give reasons related to privacy (p<.001), poor understanding of the form (p=.01), and mistrust or fear of research (p=0.04) for non-participation. Conclusions The inclusion of HIPAA authorization within the informed consent process may adversely affect the willingness of African Americans to participate in clinical research and may raise concerns about privacy, understanding the forms, and mistrust or fear of research.

Objectives Very-low-birthweight (VLBW) delivery accounts for the majority of neonatal mortality and the black-white disparity in infant mortality. The risk of recurrent VLBW is highest for African-Americans of lower socioeconomic status. This study explores whether the provision of primary health care and social support following a VLBW delivery improves subsequent child spacing and pregnancy outcomes for low-income, African-American women. Methods This pilot study of mixed prospective-retrospective cohort design enrolled African-American women who qualified for indigent care and delivered a VLBW infant at a public hospital in Atlanta from November 2003 through March 2004 into the intervention cohort (n1 = 29). The intervention consisted of coordinated primary health care and social support for 24 months following the VLBW delivery. A retrospective cohort was assembled from consecutive women meeting the same eligibility criteria who delivered a VLBW infant during July 2001 through June 2002 (n2 = 58). The number of pregnancies conceived within 18 months of the index VLBW delivery and the number of adverse pregnancy outcomes for each cohort was compared with Poisson regression. Results Women in the control cohort had, on average, 2.6 (95% CI: 1.1 – 5.8) times as many pregnancies within 18 months of the index VLBW delivery and 3.5 (95% CI: 1.0 – 11.7) times as many adverse pregnancy outcomes as women in the intervention cohort. Conclusions This small, pilot study suggests that primary health care and social support for low-income, African-American women following a VLBW delivery may enhance achievement of a subsequent 18-month interpregnancy interval and reduce adverse pregnancy outcomes.

During pregnancy, women experience numerous physiological changes but, to date, there is limited published data that characterize accompanying changes in gene expression over pregnancy. This study sought to characterize the complexity of the transcriptome over the course of pregnancy among women with healthy pregnancies. Subjects provided a venous blood sample during early (6-15 weeks) and late (22-33 weeks) pregnancy, which was used to isolate peripheral blood mononuclear cells prior to RNA extraction. Gene expression was examined for 63 women with uncomplicated, term deliveries. We evaluated the association between weeks gestation at sample collection and expression of each transcript. Of the 16,311 transcripts evaluated, 439 changed over pregnancy after a Bonferroni correction to account for multiple comparisons. Genes whose expression increased over pregnancy were associated with oxygen transport, the immune system, and host response to bacteria. Characterization of changes in the transcriptome over the course of healthy term pregnancies may enable the identification of genes whose expression predicts complications or adverse outcomes of pregnancy.