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Background: In the United States, Black women experience preterm birth (PTB; <37 weeks gestation) at more than 1.5 times the rate of non-Hispanic White women. Social determinants of health including the neighborhood environment have been recognized as contributing to the risk of PTB. Due to historical segregation, Black women are more likely to live in neighborhoods with higher levels of neighborhood disorder compared with White women. Perceived neighborhood disorder appears to be a risk factor for maternal psychological distress in Black women and psychological distress has mediated the association between neighborhood disorder and the risk for PTB. However, the biological pathways underpinning these associations are not clear. Objective: We examined the associations among neighborhood disorder; psychological distress; DNA methylation of six stress-related, glucocorticoid candidate genes (AVP, CRH, CRHBP, FKBP5, HSD11B2, NR3C1); and gestational age at birth among 44 Black pregnant women. Methods: Women who were 18–45 years old and 8–18 weeks gestation had blood drawn and completed questionnaires measuring perceived neighborhood disorder, neighborhood crime, and psychological distress. Results: Three CpG sites were associated with neighborhood disorder (cg03405789 [ CRH ], cg14939152 and cg15910486 [ NR3C1 ]). One CpG site, cg03098337 (FKBP5) was associated with psychological distress. Three of the identified CpG sites were located within gene CpG islands or shores—areas at which DNA methylation is known to affect gene transcription. Conclusion: These findings warrant further research to clarify intermediate biological pathways and potential biomarkers to identify women at risk for PTB. Identification of PTB risk early in pregnancy would allow for interventions to prevent PTB. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB; <37 weeks gestation) rates have increased for 5 of the last 6 consecutive years in the United States. These rates are particularly alarming for U.S. non-Hispanic Black women who give birth prematurely at 1.5 times the rate of non-Hispanic White women. Previous research suggests that psychological stress is associated with PTB in Black women. However, the biological pathways by which stress alters birth timing are not clear. We examined DNA methylation (DNAm) in peripheral blood leukocytes in 6 glucocorticoid, stress-related genes in 44 (22 PTB; 22 term birth) pregnant Black women. Four cytosine-phosphate-guanine (CpG) sites were identified as differentially methylated (p < 0.05) between women with PTB and women with term births. The ability to identify stress-related biological markers that are associated with PTB among Black women would provide a critical step toward decreasing the PTB disparity among these women. Future studies should include larger sample sizes and gene expression analyses of the stress-related biological pathways to PTB. [ABSTRACT FROM AUTHOR]

Objective: We compared blood-based DNA methylation levels of endoglin (ENG) and transforming growth factor beta receptor 2 (TGFβR2) gene promoter regions between women with clinically-overt preeclampsia and women with uncomplicated, normotensive pregnancies. Methods: We used EpiTect Methyl II PCR Assays to evaluate DNA methylation of CpG islands located in promoter regions of ENG (CpG Island 114642) and TGFβR2 (CpG Island 110111). Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. N = 21 nulliparous preeclampsia case participants were 1:1 frequency matched to N = 21 nulliparous normotensive control participants on gestational age at sample collection (±2 weeks), smoking status, and labor status at sample collection. Methylation values were compared between case and control participant groups [(ENG subset: n = 20 (9 cases, 11 controls); TGFβR2 subset: n = 28 (15 cases, 13 controls)]. Results: The majority of the preeclampsia cases delivered at ⩾34 weeks' gestation (83%). Average methylation levels for ENG ([M ± (SD)]; Case Participant Group = 6.54% ± 4.57 versus Control Participant group = 4.81% ± 5.08; P =.102) and TGFβR2 (Case Participant Group = 1.50% ± 1.37 vs Control Participant Group = 1.70% ± 1.40; P =.695) promoter CpG islands did not differ significantly between the participant groups. Removal of 2 extreme outliers in the ENG analytic subset revealed a trend between levels of ENG methylation and pregnancy outcome (Case Participant Group = 5.17% ± 2.16 vs Control Participant Group = 3.36% ± 1.73; P =.062). Conclusion: Additional epigenetic studies that include larger sample sizes, investigate preeclampsia subtypes, and capture methylation status of CpG island shores and shelves are needed to further inform us of the potential role that ENG and TGFβR2 DNA methylation plays in preeclampsia pathophysiology. [ABSTRACT FROM AUTHOR]

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 28–32 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 (p values ≤ 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 (p s ≥ 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. Highlights • Racial discrimination predicts lower maternal leukocyte glucocorticoid sensitivity. • Elevated cortisol levels predict earlier birth in women without past discrimination. • Findings suggest biology of preterm birth may be unique based on prior exposures. [ABSTRACT FROM AUTHOR]

Preeclampsia, one of four hypertensive disorders of pregnancy, has traditionally been characterized as new-onset hypertension and proteinuria developing after 20 weeks' gestation. It is, however, now understood to be a complex, progressive, multisystem disorder with a highly variable presentation and a number of potentially life-threatening complications. The American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy has refined preeclampsia diagnostic criteria accordingly, and as the disorder's pathogenesis has been more clearly defined, new targets for screening, diagnosis, prevention, and treatment have emerged. This clinical update provides a review of current practice related to preeclampsia risk assessment, prediction, and management. It discusses preeclampsia pathophysiology and points readers to valuable health care resources on the topic. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Background: Despite strong prevention efforts and advances in neonatal care in recent decades, low birth weight remains a serious public health problem in the United States, and survivors remain at increased risk for lifelong problems including cognitive deficits. Current regional and local strategies for referral often rely on variable thresholds for birth weight and gestational age that may be poor analogues to cognitive risk. Improving early referral criteria offers many benefits, including improved cognitive outcomes for children and improved cost-effectiveness and resource utilization in resource-limited communities. Objectives: We hypothesized that social determinants measurable at birth or at birth hospital discharge, when combined with birth weight and gestational age, would offer an improvement over birth weight and gestational age alone in predicting cognitive test scores in school-aged children with low birth weight. Methods: We conducted a secondary analysis using a birth cohort of children from the Fragile Families and Child Wellbeing Study. We created a panel of maternal, familial, and community-level social determinant indicators from the data and examined associations with cognitive measures assessed at age of 9 years. Results: The final social determinant model was statistically significant and explained 35% of the total variance in composite test scores. The "standard care" model (birth weight and gestational age) only explained 9% of the variance. Discussion: Assessment of social determinants may offer improvement over traditional referral criteria to identify children most at risk of cognitive deficits after low birth weight. [ABSTRACT FROM AUTHOR]