Quality Improvement in Perinatal Medicine and Translation of Preterm Birth Research Findings into Clinical Care

Billions of dollars are spent yearly in perinatal medicine on studies designed to improve outcomes for mothers and their neonates. However, implementing research findings is challenging and imperfect. Strategies for implementation must be multifaceted and comprehensive. These implementation challenges extend to, and are often greater in, translational and basic science research. The purpose of this review is to discuss current challenges in the provision of quality perinatal and neonatal medical care, particularly those related to preterm birth, and provide examples of prematurity-related perinatal quality collaborative initiatives. Finally, the authors review considerations in implementing both clinical and translational/basic science prematurity research

Sonographic and genetic findings in a case of asymptomatic spontaneous uterine rupture

An asymptomatic 25-year-old G4P0120 with history significant for cervical insufficiency and classical cesarean delivery 12.5 months prior to conception underwent routine transabdominal ultrasound at 36w4d; umbilical cord was found to be protruding into a fluid-filled pouch extruding from the lower uterine segment. During emergent cesarean delivery, a full-thickness uterine rupture was confirmed; the fetal cranium and umbilical cord were extrauterine. Maternal genotype revealed greater than expected minor allele frequencies for several collagen genes. Maternal gene expression (mRNA) and corresponding microRNA expression of these collagen genes differed several-fold between her G3 (cervical insufficiency, classical cesarean delivery) and G4 (uterine rupture) pregnancies. This case highlights that (1) cervical insufficiency, poor myometrial wound healing, and uterine rupture may co-occur and pathophysiology may be related to collagen abnormalities and (2) asymptomatic uterine rupture can be detected sonographically, even in late pregnancy. Clinicians should remain vigilant for the possibility of uterine rupture, particularly among high-risk patients

Culture change in a professional sports team: Shaping environmental contexts and regulating power

Although high performing cultures are crucial for the enduring success of professional sport performance teams, theoretical and practical understanding of how they are established and sustained is lacking. To develop knowledge in this area, a case study was undertaken to examine the key mechanisms and processes of a successful culture change programme at English Rugby Union’s Leeds Carnegie. Exploring the change process from a 360 degree perspective, semi-structured interviews were conducted with team management, one specialist coach, six players, and the CEO. Analysed and explained through decentred theory, results revealed that culture change was effectively facilitated by team management: a) subtly and covertly shaping the physical, structural, and psychosocial context in which support staff and players made performance-impacting choices, and b) regulating the ‘to and fro’ of power which characterises professional sport performance teams. Decentred theory is also supported as an effective framework for culture change study

Relationships among Inorganic Arsenic, Nutritional Status CpG Methylation and microRNAs: A Review of the Literature

Inorganic arsenic is a naturally occurring toxicant that poses a significant and persistent challenge to public health. The World Health Organization has identified many geographical regions where inorganic arsenic levels exceed safe limits in drinking water. Numerous epidemiological studies have associated exposure to inorganic arsenic with increased risk of adverse health outcomes. Randomized clinical trials have shown that nutritional supplementation can mitigate or reduce exacerbation of exposure-related effects. Although a growing body of evidence suggests that epigenetic status influences toxicity, the relationships among environmental exposure to arsenic, nutrition, and the epigenome are not well detailed. This review provides a comprehensive summary of findings from human, rodent, and in vitro studies highlighting these interactive relationships

Measurement of mitochondrial DNA copy number in dried blood spots: A pilot study

Background: We evaluated the feasibility of mitochondrial DNA (mtDNA) copy number measurement in dried blood spots (DBS), its comparability with measurement in whole blood samples, and stability of mtDNA copy number from DBS over time. Methods: Women in this pilot study were participants in the Sister Study, a large prospective cohort. Sister Study participants provided a whole blood sample and DBS at enrollment. A second DBS sample was collected 5–10 years later from a subcohort of women with and without an incident breast cancer diagnosis between collections. Among 54 women (27 with breast cancer, 27 without) we measured mtDNA copy number from whole blood at enrollment and from DBS at both time points. Results: The average age at enrollment was 58.7 years (range:50–69). Values of mtDNA copy number measured in whole blood samples and DBS from enrollment were moderately correlated (Spearman R = 0.45; p = 0.005). Stability of mtDNA copy number in DBS from the two time points was moderate overall (ICC = 0.50) and similar between women with (ICC = 0.50) and without (ICC = 0.51) a breast cancer diagnosis between the two collections. Conclusions: Our results suggest that measurement of mtDNA copy number in DBS is feasible and may be a valid alternative to measurement in whole blood samples

Identifying Risk Factors for Levels of Per- And Polyfluoroalkyl Substances (PFAS) in the Placenta in a High-Risk Pregnancy Cohort in North Carolina

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS), a ubiquitous class of chemicals, is associated with adverse outcomes such as pre-eclampsia, low infant birth weight, and later-life adiposity. The objectives of this study were to examine PFAS levels in the placenta and identify sociodemographic risk factors in a high-risk pregnancy cohort (n = 122) in Chapel Hill, North Carolina. Of concern, PFOS, PFHxS, PFHpS, and PFUnA were detected above the reporting limit in 99, 75, 55, and 49% of placentas, respectively. Maternal race/ethnicity was associated with significant differences in PFUnA levels. While the data from this high-risk cohort did not provide evidence for an association with hypertensive disorders of pregnancy, fetal growth, or gestational age, the prevalence of detectable PFAS in the placenta suggests a need to biomonitor for exposure to PFAS during pregnancy. Future research should investigate factors underlying the differences in PFAS levels in association with a mother's race/ethnicity, as well as potential effects on pregnancy and child health

Epigenetic Regulation of the Nitric Oxide Pathway, 17-α Hydroxyprogesterone Caproate, and Recurrent Preterm Birth

Objective We sought to evaluate nitric oxide pathway placental gene expression and the epigenome (CpG methylation) among women receiving 17-α hydroxyprogesterone caproate (17-OHPC) with and without recurrent preterm birth (PTB). Study Design This was a case-control study. We prospectively recruited women with ≥ 1 prior singleton spontaneous PTB <34 weeks receiving 17-OHPC. DNA and RNA were isolated from placentas. RNA abundance (gene expression) and the methylome were analyzed for 84 genes in nitric oxide pathways. Women with recurrent PTB <34 weeks (cases) were compared with those delivering at term (controls). Statistical analysis included multivariable models with Bonferroni's corrected p -values. Results In this study, 17 women met inclusion criteria; 7 preterm cases (delivered at 22.6 ± 2.9 weeks) and 10 term controls (delivered at 38.5 ± 0.8 weeks). Groups had similar PTB history, race/ethnicity, and socioeconomic risk factors for PTB. Twenty-seven nitric oxide genes displayed differential expression (p < 0.05 and q < 0.10) when comparing placentas from preterm cases and term controls; all were downregulated in preterm cases. Eight hundred sixty corresponding CpG sites were differentially methylated between the preterm cases and term controls (Bonferroni's p -value <0.05). Conclusion CpG methylation and gene expression patterns in nitric oxide pathway genes differ among placentas from recurrent PTB compared with term birth following 17-OHPC exposure

Organic nitrate and secondary organic aerosol yield from NO3 oxidation of ß-pinene evaluated using a gas-phase kinetics/aerosol partitioning model

The yields of organic nitrates and of secondary organic aerosol (SOA) particle formation were measured for the reaction NO3+beta-pinene under dry and humid conditions in the atmosphere simulation chamber SAPHIR at Research Center Julich. These experiments were conducted at low concentrations of NO3 (NO3+N2O5 < 10 ppb) and beta-pinene (peak similar to 15 ppb), with no seed aerosol. SOA formation was observed to be prompt and substantial (similar to 50% mass yield under both dry conditions and at 60% RH), and highly correlated with organic nitrate formation. The observed gas/aerosol partitioning of organic nitrates can be simulated using an absorptive partitioning model to derive an estimated vapor pressure of the condensing nitrate species of p(vap) similar to 5x10(-6) Torr (6.67x10(-4) Pa), which constrains speculation about the oxidation mechanism and chemical identity of the organic nitrate. Once formed the SOA in this system continues to evolve, resulting in measurable aerosol volume decrease with time. The observations of high aerosol yield from NOx-dependent oxidation of monoterpenes provide an example of a significant anthropogenic source of SOA from biogenic hydrocarbon precursors. Estimates of the NO3+beta-pinene SOA source strength for California and the globe indicate that NO3 reactions with monoterpenes are likely an important source (0.5-8% of the global total) of organic aerosol on regional and global scales

Understanding the relationship between environmental arsenic and prostate cancer aggressiveness among African-American and European-American men in North Carolina

High-level exposure to arsenic, a known carcinogen and endocrine disruptor, is associated with prostate cancer (PCa) mortality. Whether low-level exposure is associated with PCa aggressiveness remains unknown. We examined the association between urinary arsenic and PCa aggressiveness among men in North Carolina. This cross-sectional study included 463 African-American and 491 European-American men with newly diagnosed, histologically confirmed prostate adenocarcinoma. PCa aggressiveness was defined as low aggressive (Gleason score &lt; 7, stage = cT1–cT2, and PSA &lt; 10 ng/mL) versus intermediate/high aggressive (all other cases). Total arsenic and arsenical species (inorganic arsenic (iAsIII + iAsV), arsenobetaine, monomethyl arsenic, and dimethyl arsenic)) and specific gravity were measured in spot urine samples obtained an average of 23.7 weeks after diagnosis. Multivariable logistic regression was used to estimate the covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for PCa aggressiveness in association with arsenic tertiles/quantiles overall and by race. The highest (vs. lowest) tertile of total arsenic was associated with PCa aggressiveness ORs of 1.77 (95% CI = 1.05–2.98) among European-American men, and 0.94 (95% CI = 0.57–1.56) among African-American men (PInteraction = 0.04). In contrast, total arsenic and arsenical species were not associated with PCa aggressiveness in unstratified models. Low-level arsenic exposure may be associated with PCa aggressiveness among European-Americans, but not among African-Americans