Metabolic Pathways Associated With Term Labor Induction Course in African American Women.
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ABSTRACT:
SUBMITTER: Carlson NS
PROVIDER: S-EPMC7273804 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Glucocorticoid resistance (GR) is associated with exposure to chronic stress and an increased risk of metabolic and inflammatory disorders in both animal and human populations. Studies on ethnic disparities highlight the African-American (AA) population as having a high propensity to both GR and chronic stress exposure. Glucocorticoids and inflammation play a very important role in pregnancy outcome and fetal development. To date, however, the metabolites and metabolic pathways associated with GR during pregnancy have not been identified, obscuring the mechanisms by which adverse health consequences arise, and thus impeding targeted therapeutic intervention. The objective of this study was to perform untargeted high-resolution metabolomics (HRM) profiling on 273 pregnant AA women, to identify metabolites and metabolic pathways associated with GR during the first trimester of pregnancy and to evaluate their cross-sectional association with birth outcomes and psychosocial variables related to chronic stress exposure. For this study, GR was determined by the concentration of dexamethasone required for 50% inhibition (Dex IC50) of the cytokine tumor-necrosis factor alpha (TNF-alpha) release in vitro in response to a standard dose of lipopolysaccharide. The results for Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for serum metabolic associations with Dex IC50, showed energy (nicotinamide and TCA cycle), amino acid, and glycosphingolipid metabolism as top altered pathways. Bioinformatic analysis showed that GR, as indicated by elevated Dex IC50 in the pregnant women, was associated with increased inflammatory metabolites, oxidative stress related metabolites, increased demand for functional amino acids to support growth and development, and disruption in energy-related metabolites. If confirmed in future studies, targeting these physiologically significant metabolites and metabolic pathways may lead to future assessment and intervention strategies to prevent inflammatory and metabolic complications observed in pregnant populations.
| S-EPMC7943062 | biostudies-literature
Project description:ObjectiveThe aim of the study is to evaluate the association between amniotomy at various time points during labor induction and maternal and neonatal outcomes among term, nulliparous women.Study designSecondary analysis of a randomized trial of term labor induction versus expectant management in low-risk, nulliparous women (2014-2017) was conducted. Women met inclusion criteria if they underwent induction ≥38 weeks' gestation using oxytocin with documented time and type of membrane rupture. Women with antepartum stillbirth or fetal anomaly were excluded. The primary outcome was cesarean delivery. Secondary outcomes included maternal and neonatal complications. Maternal and neonatal outcomes were compared among women with amniotomy versus women with intact membranes and no amniotomy at six 2-hour time intervals: before oxytocin initiation, 0 to <2 hours after oxytocin, 2 to <4 hours after, 4 to <6 hours after, 6 to <8 hours after, and 8 to <10 hours after. Multivariable logistic regression adjusted for maternal age, body mass index, race/ethnicity, modified Bishop score on admission, treatment group, and hospital (as a random effect).ResultsOf 6,106 women in the parent trial, 2,854 (46.7%) women met inclusion criteria. Of these 2,340 (82.0%) underwent amniotomy, and majority of the women had amniotomy performed between 2 and <6 hours after oxytocin. Cesarean delivery was less frequent among women with amniotomy 6 to <8 hours after oxytocin compared with women without amniotomy (21.9 vs. 29.7%; adjusted odds ratio 0.61, 95% confidence interval 0.42-0.89). Amniotomy at time intervals ≥4 hours after oxytocin was associated with lower odds of labor duration >24 hours. Amniotomy at time intervals ≥2 hours and <8 hours after oxytocin was associated with lower odds of maternal hospitalization >3 days. Amniotomy was not associated with postpartum or neonatal complications.ConclusionAmong a contemporary cohort of nulliparous women undergoing term labor induction, amniotomy was associated with either lower or similar odds of cesarean delivery and other adverse outcomes, compared with no amniotomy.
| S-EPMC7572589 | biostudies-literature
Project description:Comparing miRNAs expression levels in chorioamniotic membranes from women at term in labor (TL), women at term not in labor (TNL) and women who deliverd preterm (PTLC). The goal was to see if miRNA levels are indicators of preterm delivery or spontaneous labor at term. A two-channel technology was used in this experiment in which a pooled reference RNA was used for competitive hybridization. The pooled reference was generated at Exiqon in Denmark from a mixture of several human tissues (placenta, thyroid, brain, adipose, spleen, liver, colon, skeletal muscle, ovary, kidney, heart, cervix, testes, esophagus, small intestine, prostate, trachea, thymus, bladder, lung).
2008-10-01 | E-TABM-469 | biostudies-arrayexpress
Project description:Studying positive outliers, individuals who have achieved success with long-term (> 6-month) physical activity (PA) engagement, may be an important approach for understanding strategies for improving leisure-time PA maintenance among African American (AA) women. This cross-sectional, mixed-methods study (1) examined the personal characteristics, PA patterns, and behavioral practices of positive outliers among AA women and (2) compared characteristics of those who maintain PA at recommended levels (HIGH, ≥ 150 min/week > 6 months) with those who maintain low PA volumes (LOW, < 150 min/week > 6 months). A large sample of positive outliers completed this study (n = 290), and most became physically active on their own (76.2%). These AA women were committed to maintaining an active lifestyle, accumulated 249.7 ± 105.8 min of PA/week, and engaged in a variety of activities. Their behavioral practices included scheduling PA during the week (85.9%), goal-setting (82.4%), engaging in PA with others (55.9%), self-monitoring (78.3%), and having a backup plan for missed sessions (54.8%). HIGH maintainers (84.9%) made up most of the sample, and these women were characteristically similar to LOW maintainers with few differences. HIGH maintainers have been active longer, achieved higher commitment scores, and engaged in PA at a higher frequency, duration, and intensity, resulting in higher weekly PA volume compared to LOW maintainers (273.8 ± 96.1 vs. 114.4 ± 24.3 min per week, p ≤ 0.001). Our findings identify factors that may be important for successful PA maintenance among AA women and may help to inform the development of effective behavioral interventions to promote sustained, long-term PA engagement in this population.
| S-EPMC6500467 | biostudies-literature
Project description:OBJECTIVE:To evaluate whether elective induction of labor between 39 through 41 weeks of gestation, as compared with expectant management, is associated with reduced cesarean delivery and other adverse outcomes among obese women and their offspring. METHODS:We conducted a retrospective cohort study using the 2007-2011 California Linked Patient Discharge Data-Birth Cohort File of 165,975 singleton, cephalic, nonanomalous deliveries to obese women. For each gestational week (39-41), we used multivariable logistic regression models, stratified by parity, to assess whether elective induction of labor or expectant management was associated with lower odds of cesarean delivery and other adverse outcomes. RESULTS:At 39 and 40 weeks of gestation, cesarean delivery was less common in obese nulliparous women who were electively induced compared with those who were expectantly managed (at 39 weeks of gestation, frequencies were 35.9% vs 41.0%, respectively [P<.05]; adjusted odds ratio [OR] 0.82, 95% CI 0.77-0.88). Severe maternal morbidity was less frequent among electively induced obese nulliparous patients (at 39 weeks of gestation, 5.6% vs 7.6% [P<.05]; adjusted OR 0.75, 95% CI 0.65-0.87). Neonatal intensive care unit admission was less common among electively induced obese nulliparous women (at 39 weeks of gestation, 7.9% vs 10.1% [P<.05]; adjusted OR 0.79, 95% CI 0.70-0.89). Patterns were similar among obese parous women at 39 weeks of gestation (crude frequencies and adjusted ORs [95% CIs] were as follows: for cesarean delivery, 7.0% vs 8.7% [P<.05] and 0.79 [0.73-0.86]; for severe maternal morbidity, 3.3% vs 4.0% [P<.05] and 0.83 [0.74-0.94]; for neonatal intensive care unit admission: 5.3% vs 7.4% [P<.05] and 0.75 [0.68-0.82]). Similarly, elective induction at 40 weeks of gestation was associated with reduced odds of cesarean delivery, maternal morbidity, and neonatal intensive care unit admission among both obese nulliparous and parous patients. CONCLUSION:Elective labor induction after 39 weeks of gestation was associated with reduced maternal and neonatal morbidity among obese women. Further prospective investigation is necessary.
| S-EPMC5833989 | biostudies-literature
Project description:Obesity-driven Type 2 diabetes (T2D) is a systemic inflammatory condition associated with cardiovascular disease. However, plasma cytokines and tissue inflammation that discriminate T2D risk in African American women with obese phenotypes are not well understood. We analyzed 64 circulating cytokines and chemokines in plasma of 120 African American women enrolled in the Black Women's Health Study. We used regression analysis to identify cytokines and chemokines associated with obesity, co-morbid T2D and hypertension, and compared results to obese women without these co-morbidities, as well as to lean women without the co-morbidities. We then used hierarchical clustering to generate inflammation signatures by combining the effects of identified cytokines and chemokines and summarized the signatures using an inflammation score. The analyses revealed six distinct signatures of sixteen cytokines/chemokines (P = 0.05) that differed significantly by prevalence of T2D (P = 0.004), obesity (P = 0.0231) and overall inflammation score (P < E-12). Signatures were validated in two independent cohorts of African American women with obesity: thirty nine subjects with no metabolic complications or with T2D and hypertension; and thirteen breast reduction surgical patients. The signatures in the validation cohorts closely resembled the distributions in the discovery cohort. We find that blood-based cytokine profiles usefully associate inflammation with T2D risks in vulnerable subjects, and should be combined with metabolism and obesity counselling for personalized risk assessment.
| S-EPMC5940209 | biostudies-literature
Project description:BackgroundPreterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery.ObjectiveThe objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women.Study designThis is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term.ResultsOf the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term.ConclusionWe identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.
| S-EPMC4967390 | biostudies-literature
Project description:We sought to investigate genetic variation in hormone pathways in relation to risk of overall and subtype-specific breast cancer in women of African ancestry (AA). Genotyping and imputation yielded data on 143,934 SNPs in 308 hormone-related genes for 3663 breast cancer cases (1098 ER-, 1983 ER+, 582 ER unknown) and 4687 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. AMBER includes data from four large studies of AA women: the Carolina Breast Cancer Study, the Women's Circle of Health Study, the Black Women's Health Study, and the Multiethnic Cohort Study. Pathway- and gene-based analyses were conducted, and single-SNP tests were run for the top genes. There were no strong associations at the pathway level. The most significantly associated genes were GHRH, CALM2, CETP, and AKR1C1 for overall breast cancer (gene-based nominal p ≤ 0.01); NR0B1, IGF2R, CALM2, CYP1B1, and GRB2 for ER+ breast cancer (p ≤ 0.02); and PGR, MAPK3, MAP3K1, and LHCGR for ER- disease (p ≤ 0.02). Single-SNP tests for SNPs with pairwise linkage disequilibrium r (2) < 0.8 in the top genes identified 12 common SNPs (in CALM2, CETP, NR0B1, IGF2R, CYP1B1, PGR, MAPK3, and MAP3K1) associated with overall or subtype-specific breast cancer after gene-level correction for multiple testing. Rs11571215 in PGR (progesterone receptor) was the SNP most strongly associated with ER- disease. We identified eight genes in hormone pathways that contain common variants associated with breast cancer in AA women after gene-level correction for multiple testing.
| S-EPMC5082744 | biostudies-literature
Project description:BACKGROUND:African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those of other patient groups. Using a metabolomics approach, this study investigated how AA BLCA may differ molecularly from European Americans (EAs) BLCA, and it examined serum samples from patients with BLCA with the aim of identifying druggable metabolic pathways in AA patients. METHODS:Targeted metabolomics was applied to measure more than 300 metabolites in serum samples from 2 independent cohorts of EA and AA patients with BLCA and healthy EA and AA controls via liquid chromatography-mass spectrometry, and this was followed by the identification of altered metabolic pathways with a focus on AA BLCA. A subset of the differential metabolites was validated via absolute quantification with the Biocrates AbsoluteIDQ p180 kit. The clinical significance of the findings was further examined in The Cancer Genomic Atlas BLCA data set. RESULTS:Fifty-three metabolites, mainly related to amino acid, lipid, and nucleotide metabolism, were identified that showed significant differences in abundance between AA and EA BLCA. For example, the levels of taurine, glutamine, glutamate, aspartate, and serine were elevated in serum samples from AA patients versus EA patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as malic enzyme 3, prolyl 3-hydroxylase 2, and lysine demethylase 2A that predicted patient survival exclusively in AA patients with BLCA. CONCLUSIONS:This metabolic profile of serum samples might be used to assess risk progression in AA BLCA. These first-in-field findings describe metabolic alterations in AA BLCA and emphasize a potential biological basis for BLCA health disparities.
| S-EPMC6402983 | biostudies-literature
Project description:We assessed the relationship of lactation to long-term maternal weight gain among African-American women, who have a lower prevalence of lactation and a higher prevalence of obesity than other US women. A pregnancy cohort of 3,147 African-American women from the Black Women's Health Study who gave birth for the first time between 1995 and 2003 was followed for 8 years postpartum. Participants provided data on weight, lactation, gestational weight gain, education, diet, and exercise. Mean differences in weight gain were estimated in multivariable models. Overall, lactation was not associated with mean weight gain. However, the association was modified by prepregnancy body mass index (BMI; weight (kg)/height (m)2) (P for interaction=0.03): Among women with BMI<30 prior to the pregnancy, mean weight gain decreased with increasing months of lactation (P for trend<0.01), whereas among obese women (BMI≥30), mean weight gain increased with increasing duration of lactation (P for trend=0.04). Adjusted mean differences for ≥12 months of lactation relative to no lactation were -1.56 kg (95% confidence interval: -2.50, -0.61) among nonobese women and 2.33 kg (95% confidence interval: -0.35, 5.01) among obese women. The differences in postpartum mean weight gain persisted over the 8-year study period. Residual confounding by factors more common in women who breastfeed longer may have influenced the results.
| S-EPMC4462338 | biostudies-literature