Resilience as a potential modifier of racial inequities in preterm birth.

PURPOSE: In the US, preterm birth (PTB) is 55% more common among Black compared to White individuals and psychosocial stressors may contribute. Resilience is associated with improved health outcomes; whether it modifies PTB inequity is unknown. We hypothesized high resilience would reduce inequities in PTB risk. METHODS: This study analyzes data from 535 pregnancies among Black (n = 101, 19%) and White (n = 434, 81%) participants from a prospective cohort. Participants completed the Connor-Davidson Resilience Scale. We calculated risk ratios (RR) stratified by resilience tertiles to test for effect measure modification. RESULTS: Among those in the lowest resilience tertile, there were six (20.7%) PTBs among Black and seven (4.9%) among White participants (RR: 4.26; 95% confidence interval (CI): 1.53, 11.81). Among those in the highest resilience tertile, there were 8 (18.2%) PTBs among Black and 14 (9.5%) among White participants (RR: 1.92; 95% CI: 0.87, 4.24. The adjusted Black:White RR was 2.00 (95% CI 0.47, 8.64) in the lowest and 3.49 (95% CI 1.52, 8.01) in the highest tertile. CONCLUSIONS: Black-White PTB inequity did not differ among resilience strata and remained significant in the highest tertile. Our findings suggest that high resilience is inadequate to overcome Black:White racial inequity in PTB.

Cervical microRNA expression and spontaneous preterm birth.

BACKGROUND: Preterm birth remains a major public health issue affecting 10% of all pregnancies and increases risks of neonatal morbidity and mortality. Approximately 50% to 60% of preterm births are spontaneous, resulting from preterm premature rupture of membranes or preterm labor. The pathogenesis of spontaneous preterm birth is incompletely understood, and prediction of preterm birth remains elusive. Accurate prediction of preterm birth would reduce infant morbidity and mortality through targeted patient referral to hospitals equipped to care for preterm infants. Two previous studies have analyzed cervical microRNAs in association with spontaneous preterm birth and the length of gestation, but the extent to which microRNAs serve as predictive biomarkers remains unknown. OBJECTIVE: This study aimed to examine associations between cervical microRNA expression and spontaneous preterm birth, with the specific goal of identifying a subset of microRNAs that predict spontaneous preterm birth. STUDY DESIGN: We performed a prospective, nested, case-control study of 25 cases with spontaneous preterm birth and 49 term controls. Controls were matched to cases in a 2:1 ratio on the basis of age, parity, and self-identified race. Cervical swabs were collected at a mean gestational age of 17.1 (4.8) weeks of gestation, and microRNAs were analyzed using a quantitative polymerase chain reaction array. Normalized microRNA expression was compared between cases and controls, and a false discovery rate of 0.2 was applied to account for multiple comparisons. Histopathologic analysis of slides of cervical swab samples was performed to quantify leukocyte burden for adjustment in conditional regression models. We explored the use of Relief-based unsupervised identification of top microRNAs and support vector machines to predict spontaneous preterm birth. We performed microRNA enrichment analysis to explore potential biologic targets and pathways in which up-regulated microRNAs might be involved. RESULTS: Of the 754 microRNAs on the polymerase chain reaction array, 346 were detected in ≥75% of participants' cervical swabs. Average cervical microRNA expression was significantly higher in cases of spontaneous preterm birth than in controls (P=.01). There were 95 significantly up-regulated individual microRNAs (>2-fold change) in cases of subsequent spontaneous preterm birth compared with term controls (P<.05; q<0.2). Notably, miR-143, miR-30e-3p, and miR-199b were all significantly up-regulated, which is consistent with the 1 previous study of cervical microRNA and spontaneous preterm birth. A Relief-based, novel variable (feature) selection machine learning approach had low-to-moderate prediction accuracy, with an area under the receiver operating curve of 0.71. Enrichment analysis revealed that identified microRNAs may modulate inflammatory cell signaling. CONCLUSION: In this prospective nested case-control study of cervical microRNA expression and spontaneous preterm birth, we identified a global increase in microRNA expression and up-regulation of 95 distinct microRNAs in association with subsequent spontaneous preterm birth. Larger and more diverse studies are required to determine the ability of microRNAs to accurately predict spontaneous preterm birth, and mechanistic work to facilitate development of novel therapeutic interventions to prevent spontaneous preterm birth is warranted.

Maternal anxiety and depression in pregnancy and DNA methylation of the NR3C1 glucocorticoid receptor gene.

Aim: To quantify associations of anxiety and depression during pregnancy with differential cord blood DNA methylation of the glucorticoid receptor (NR3C1). Materials & methods: Pregnancy anxiety, trait anxiety and depressive symptoms were collected using the Pregnancy Related Anxiety Scale, State-Trait Anxiety Index and Edinburgh Postnatal Depression Scale, respectively. NR3C1 methylation was determined at four methylation sites. Results: DNA methylation of CpG1 in the NR3C1 CpG island shore was higher in infants born to women with high pregnancy anxiety (ß 2.54, 95% CI: 0.49-4.58) and trait anxiety (ß 1.68, 95% CI: 0.14-3.22). No significant association was found between depressive symptoms and NR3C1 methylation. Conclusion: We found that maternal anxiety was associated with increased NR3C1 CpG island shore methylation.

Hemorrhagic morbidity in placenta accreta spectrum with and without placenta previa.

PURPOSE: The incidence of placenta accreta spectrum (PAS; pathologic diagnosis of placenta accreta, increta or percreta) continues to rise in the USA. The purpose of this study is to compare the hemorrhagic morbidity associated with PAS with and without a placenta previa. METHODS: This was a retrospective cohort study of 105 deliveries from 1997 to 2017 with histologically confirmed PAS comparing outcomes in women with and without a coexisting placenta previa. We used the Wilcoxon rank sum test to compare continuous data and Chi-square or Fisher's exact test for categorical data. We also performed log-binomial regression to calculate risk ratios adjusted for depth of invasion (aRR) and 95% confidence intervals (CI). RESULTS: We identified 105 pregnancies with PAS. Antenatal diagnosis of PAS was higher in women with coexisting placenta previa (72.3%) than those without (6.9%, p < 0.001). Women with coexisting placenta previa had greater median estimated blood loss and more units of packed red blood cells transfused (both p ≤ 0.03). Women with placenta previa were more likely to undergo a hysterectomy (RR 2.7; 95% CI 1.8-3.8) and be admitted to the intensive care unit (aRR 3.3; 95% CI 1.1-9.6). CONCLUSIONS: Among women with PAS, those with a coexisting placenta previa experienced greater hemorrhagic morbidity compared to those without. In addition, PAS without placenta previa typically was not diagnosed prior to delivery. This study further supports the recommendation for multi-disciplinary planning and assurance of resources for pregnancies complicated by PAS. In addition, our results highlight the need for mobilization of resources for those pregnancies where PAS is not diagnosed until delivery.