Racial discrimination and adverse pregnancy outcomes: a systematic review and meta-analysis.

INTRODUCTION: Racial discrimination has been consistently linked to various health outcomes and health disparities, including studies associating racial discrimination with patterns of racial disparities in adverse pregnancy outcomes. To expand our knowledge, this systematic review and meta-analysis assesses all available evidence on the association between self-reported racial discrimination and adverse pregnancy outcomes. METHODS: Eight electronic databases were searched without language or time restrictions, through January 2022. Data were extracted using a pre-piloted extraction tool. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS), and across all included studies using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random effects meta-analyses were performed on preterm birth and small for gestational age. Heterogenicity was assessed using Cochran's χ2 test and I2 statistic. RESULTS: Of 13 597 retrieved records, 24 articles were included. Studies included cohort, case-control and cross-sectional designs and were predominantly conducted in the USA (n=20). Across all outcomes, significant positive associations (between experiencing racial discrimination and an adverse pregnancy event) and non-significant associations (trending towards positive) were reported, with no studies reporting significant negative associations. The overall pooled odds ratio (OR) for preterm birth was 1.40 (95% CI 1.17 to 1.68; 13 studies) and for small for gestational age it was 1.23 (95% CI 0.76 to 1.99; 3 studies). When excluding low-quality studies, the preterm birth OR attenuated to 1.31 (95% CI 1.08 to 1.59; 10 studies). Similar results were obtained across sensitivity and subgroup analyses, indicating a significant positive association. CONCLUSION: These results suggest that racial discrimination has adverse impacts on pregnancy outcomes. This is supported by the broader literature on racial discrimination as a risk factor for adverse health outcomes. To further explore this association and underlying mechanisms, including mediating and moderating factors, higher quality evidence from large ethnographically diverse cohorts is needed.

Epigenetic modifying enzyme expression in asthmatic airway epithelial cells and fibroblasts.

BACKGROUND: Recognition of the airway epithelium as a central mediator in the pathogenesis of asthma has necessitated greater understanding of the aberrant cellular mechanisms of the epithelium in asthma. The architecture of chromatin is integral to the regulation of gene expression and is determined by modifications to the surrounding histones and DNA. The acetylation, methylation, phosphorylation, and ubiquitination of histone tail residues has the potential to greatly alter the accessibility of DNA to the cells transcriptional machinery. DNA methylation can also interrupt binding of transcription factors and recruit chromatin remodelers resulting in general gene silencing. Although previous studies have found numerous irregularities in the expression of genes involved in asthma, the contribution of epigenetic regulation of these genes is less well known. We propose that the gene expression of epigenetic modifying enzymes is cell-specific and influenced by asthma status in tissues derived from the airways. METHODS: Airway epithelial cells (AECs) isolated by pronase digestion or endobronchial brushings and airway fibroblasts obtained by outgrowth technique from healthy and asthmatic donors were maintained in monolayer culture. RNA was analyzed for the expression of 82 epigenetic enzymes across 5 families of epigenetic modifying enzymes. Western blot and immunohistochemistry were also used to examine expression of 3 genes. RESULTS: Between AECs and airway fibroblasts, we identified cell-specific gene expression in each of the families of epigenetic modifying enzymes; specifically 24 of the 82 genes analyzed showed differential expression. We found that 6 histone modifiers in AECs and one in fibroblasts were differentially expressed in cells from asthmatic compared to healthy donors however, not all passed correction. In addition, we identified a corresponding increase in Aurora Kinase A (AURKA) protein expression in epithelial cells from asthmatics compared to those from non-asthmatics. CONCLUSIONS: In summary, we have identified cell-specific variation in gene expression in each of the families of epigenetic modifying enzymes in airway epithelial cells and airway fibroblasts. These data provide insight into the cell-specific variation in epigenetic regulation which may be relevant to cell fate and function, and disease susceptibility.