Background
Preterm birth rates are higher among individuals of lower socioeconomic status and non‐White race, which is possibly related to life‐course stressors. It is important to understand the ...underlying mechanisms of these health disparities, and inflammation is a possible pathway to explain the disparities in birth outcomes.
Objective
In this study, we aimed to determine whether patterns of inflammation differed by maternal race and socioeconomic status.
Study design
Seven hundred and forty‐four participants in a multi‐site, prospective study of pregnancy and birth outcomes provided biological and psychological data between 12′0‐20′6 weeks gestation. Participants with recent infection, fever, antibiotics or steroid treatment were excluded. Cytokines including INFɣ, IL‐10, IL‐13, IL‐6, IL‐8, and TNFα, and the acute phase protein CRP were measured in serum and values and were log‐transformed for normality when appropriate, and a non‐orthogonal rotation (Oblimid) was performed to allow the extracted factor to inter‐correlate. IFNγ, IL‐8, IL‐10, IL‐6, TNF‐a, and IL‐13 loaded onto Inflammatory Factor 1 (IF‐1), while CRP and IL‐6 loaded onto Inflammatory Factor 2 (IF‐2). Race and education were collected via self‐report during an in‐person study visit. Multivariable models were used to determine the association of race and SES with IF‐1 and IF‐2 during the second trimester, and a mediation model was used to examine if inflammation is on the causal pathway. Models were adjusted for study site, prenatal age, pre‐pregnancy BMI, smoking during pregnancy, and gestational age at the time of blood collection.
Results
Six hundred and five participants were included in our final analysis, with 61.2% of low or moderate SES, and 35.5% identifying as a person of color (POC). Identifying as a POC, being of low and moderate SES, and being both low‐SES and POC or moderate‐SES and POC were associated with higher odds of preterm birth and lower birth weight percentile infants. Low SES POC participants had significantly higher IF‐1 and IF‐2 scores when compared to high‐SES White participants. Additionally, higher IF‐1 and IF‐2 were associated with shorter gestation. In the mediation analysis, we observed a significant direct effect of race/SES on preterm birth; however, the results did not support an indirect pathway where IF‐1 or IF‐2 acted as mediators.
Conclusion
Maternal race and SES are significantly associated with inflammatory biomarkers during pregnancy, and when race and SES are considered in combination, they are stronger predictors of adverse pregnancy outcomes than when evaluated separately.
Objective
Inflammation as a risk factor for preterm birth is well‐established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of ...mid‐pregnancy inflammation are significantly associated with risk for adverse birth outcomes.
Study design
A multi‐site prospective study was conducted in a socio‐demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks’ gestation, low‐grade inflammation was measured via log‐transformed serum concentrations of the biomarkers IFN‐γ, IL‐10, IL‐13, IL‐6, IL‐8, TNF‐α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC).
Results
Principal component analysis analysis yielded a two‐factor solution, with the first factor (IF1) composed of IL‐8, IL‐10, IL‐13, IFN‐ɣ, and TNF‐α, and the second factor (IF2) containing IL‐6 and CRP. When adjusted for race, education, BMI, smoking status, gestational age at time of blood draw, and study site, a one standard deviation (SD) increase in IF1 remained significantly associated with a decrease in standardized gestational age (β = ‐.13, 95% CI: ‐.21, ‐.05) and an increase in odds of preterm delivery (OR = 1.46, 95% CI: 1.13, 1.88) (Table 3). A one SD increase in IF2 was similarly associated with a decrease in standardized gestational age at delivery (β = ‐.13, 95% CI: ‐.23, ‐.04) and an increase in odds of preterm delivery (OR: 1.46, 95% CI: 1.04, 2.05). Neither IF1 nor IF2 was associated with measures of fetal growth. AIC identified that IL‐6 was a slightly better fit for length of gestation compared to either composite measure, though all performed similarly.
Conclusion
Independent of known sociodemographic risk factors, an elevated mid‐pregnancy inflammatory profile was associated with a nearly 50% increase in odds of preterm delivery. The composite performed similarly to IL‐6. These results suggest that maternal low‐grade inflammation is a risk factor for preterm delivery, and that mid‐pregnancy inflammatory biomarkers may be useful in predicting risk for preterm delivery.
Problem
Current scientific guidelines recommend collecting placental specimens within two hours of delivery for gene expression analysis. However, collecting samples in a narrow time window is a ...challenge in the dynamic and unpredictable clinical setting, so delays in placental specimen collection are possible. The purpose of our analysis was to investigate temporal changes in placental gene expression by longitudinally sampling placentas over a 24 h period.
Method of Study
Eight placentas from individuals with uncomplicated, term pregnancies delivered by scheduled cesarean section were collected and sampled following the placental delivery and again at 1, 2, 4, 6, and 24 h post‐delivery. At each time point, biopsies of chorionic villous tissue were taken from 3 cotyledons to account for intra‐placental heterogeneity. The 3 biopsies from each time point were pooled prior to RNA extraction. Expression of 382 mRNA transcripts was quantified using the NanoString nCounter System. Fold change values were calculated for each time point relative to delivery, and a fold change threshold of 1.25 was used to determine a meaningful change from delivery.
Results
Based on a fold change threshold of 1.25, 84.3% of transcripts were stable for at least 1 h, 80.2% were stable for at least two hours, and 20.6% of transcripts were stable through the collection at 24 h.
Conclusion
Our results suggest that for some mRNA transcripts, expression changes as time to sample collection increases. We have developed a Web application to allow investigators to explore transcripts relevant to their research interests and to set appropriate thresholds to aid in determining whether placentas with delayed sample collection can be included in analyses (https://placentaexpression.foundationsofhealth.org/).
Exposure to traumatic events during pregnancy may influence pregnancy and birth outcomes. Growing evidence suggests that exposure to traumatic events well before pregnancy, such as childhood ...maltreatment (CM), also may influence the course of pregnancy and risk of adverse birth outcomes. We aimed to estimate associations between maternal CM exposure and small-for-gestational-age birth (SGA) and preterm birth (PTB) in a diverse US sample, and to examine whether common CM-associated health and behavioral sequelae either moderate or mediate these associations. The Measurement of Maternal Stress (MOMS) Study was a prospective cohort study that enrolled 744 healthy English-speaking participants ≥ 18 years with a singleton pregnancy, who were < 21 weeks at enrollment, between 2013 and 2015. CM was measured via the Childhood Trauma Questionnaire (CTQ) and participants above the moderate/severe cut-off for any of the five childhood abuse and neglect scales were assigned to the CM-exposed group. Common CM-associated health (obesity, depressive symptoms, hypertensive disorders) and behavioral (substance use) sequelae were obtained from standardized questionnaires and medical records. The main outcomes included PTB (gestational age < 37 weeks at birth) and SGA (birthweight < 10%ile for gestational age) abstracted from the medical record. Multivariable logisitic regression was used to test associations between CM, sequeale, and birth outcomes, and both moderation and mediation by CM-related sequelae were tested. Data were available for 657/744 participants. Any CM exposure was reported by 32% of participants. Risk for SGA birth was 61% higher among those in the CM group compared to the non-CM group (14.1% vs. 7.6%), and each subsequent form of CM that an individual was exposed to corresponded with a 27% increased risk for SGA (aOR 1.27, 95% CI 1.05, 1.53). There was no significant association between CM and PTB (9.3% vs. 13.0%, aOR 1.07, 95% CI 0.58, 1.97). Of these sequelae only hypertensive disorders were associated with both CM and SGA and hypertensive disorders of pregnancy did not mediate the association between CM and SGA. Our findings indicate that maternal CM exposure is associated with increased risk for SGA birth and highlight the importance of investigating the mechanisms whereby childhood adversity sets the trajectory for long-term and intergenerational health issues.
Intestinal malrotation is a congenitally acquired condition of abnormally rotated proximal small bowel in neonates and infants. Prompt recognition prevents lifethreatening complications. A structured ...approach to diagnosing malrotation at UGIS is required for accurate diagnosis.
Retrospective analysis of the images and radiological reports of UGIS, with the aim of identifying potential shortfalls in diagnosing malrotation. A secondary objective is to formulate a reporting template to improve overall quality of UGIS reports, specifically in cases of suspected malrotation.
Identification and retrospective review of UGIS studies which were subsequently re-read by a blinded consultant radiologist using the proposed reporting template adapted from the literature.
367 UGIS studies between 1 January 2016 and 31 December 2021 were included in the study cohort, which were then re-read. Using McNemar's chi-square test, we found discrepancy between the number of studies positive for malrotation on the original reports versus the re-read studies, highlighting shortfalls in our current practise.
A structured approach is paramount to the correct diagnosis of malrotation at UGIS. The position of the DJ-flexure (on frontal and lateral projections) proves most sensitive and specific in the diagnosis of malrotation at UGIS. Dedicated true lateral images were often found to be excluded in daily practise. We propose a structured inclusive reporting template.
Our proposed standardized reporting template aims to improve radiological, clinical, and surgical outcomes at UGIS, specifically in patients with suspected malrotation.
Problem
The immune system represents a leading pathway of interest in the pathophysiology of preterm birth. The majority of human clinical studies interrogating this pathway have utilized circulating ...immune biomarkers; however, these concentrations typically reflect only basal production but not key functional properties of the immune system, particularly variation in the pro‐inflammatory response to antigen challenge and the regulation of this response. Thus, in this study, we utilized an ex vivo stimulation protocol that quantifies these processes, and we examined their prospective association with the gestation length and risk of preterm birth.
Method of Study
Immune responsiveness and regulation were assessed in 128 pregnant women in mid‐gestation using an ex vivo stimulation protocol. Maternal pro‐inflammatory responsivity of leukocytes was quantified by assessing the release of the pro‐inflammatory cytokines IL‐6, TNF‐α, and IL‐1β in response to antigen stimulation, and regulation of the pro‐inflammatory response was quantified by assessing the suppression of stimulated cytokine response upon co‐incubation with increasing dexamethasone concentrations (ie, glucocorticoid receptor resistance; GRR).
Results
Higher maternal GRR, indicating impaired regulation of the pro‐inflammatory response, was significantly and independently associated with shorter gestational length (β = −0.42, p = .0091) and a 3.0‐fold increase in risk for preterm birth (OR = 3.01, 95% CI = 1.17–7.70, p = .0218). Basal circulating IL‐6 and TNF‐α were not associated with either outcome.
Conclusion
The association of maternal GRR with length of gestation and preterm birth risk suggests that the processes represented by this measure—maternal pro‐inflammatory propensity and immune regulation—may provide further mechanistic insight into the pathophysiology of preterm birth.
This study aims to examine whether maternal household income is associated with histological evidence of chronic placental inflammation.
A total of 152 participants completed surveys of household ...income and consented to placenta collection at delivery and postpartum chart review for birth outcomes. Placental inflammatory lesions were evaluated via histological examination of the membranes, basal plate, and villous parenchyma by a single, experienced pathologist. Associations between household income and the presence of inflammatory lesions were adjusted for known perinatal risk factors.
Overall, 45% of participants reporting household income below $30,000/y had chronic placental inflammation, compared with 25% of participants reporting income above $100,000 annually (odds ratio OR = 4.23, 95% confidence interval CI = 1.25, 14.28;
= 0.02). Middle-income groups showed intermediate rates of chronic inflammatory lesions, at 40% for those reporting $30,000 and 50,000 (OR = 3.60, 95% CI = 1.05, 12.53;
= 0.04) and 38% for those reporting $50,000 to 100,000 (OR = 1.57, 95% CI = 0.60, 4.14;
= 0.36). Results remained significant after adjustment for maternal age, race, and marital status.
Chronic placental inflammation is associated with maternal household income. Greater occurrence of placental lesions in low-income mothers may arise from a systemic inflammatory response to social and physical environmental factors.
To identify pathways between stress indicators and adverse pregnancy outcomes, we applied a nonparametric graph-learning algorithm, PC-KCI, to data from an observational prospective cohort study. The ...Measurement of Maternal Stress study (MOMS) followed 744 women with a singleton intrauterine pregnancy recruited between June 2013 and May 2015. Infant adverse pregnancy outcomes were prematurity (<37 weeks' gestation), infant days spent in hospital after birth, and being small for gestational age (percentile gestational weight at birth). Maternal adverse pregnancy outcomes were pre-eclampsia, gestational diabetes, and gestational hypertension. PC-KCI replicated well-established pathways, such as the relationship between gestational weeks and preterm premature rupture of membranes. PC-KCI also identified previously unobserved pathways to adverse pregnancy outcomes, including 1) a link between hair cortisol levels (at 12-21 weeks of pregnancy) and pre-eclampsia; 2) two pathways to preterm birth depending on race, with one linking Hispanic race, pre-gestational diabetes and gestational weeks, and a second pathway linking black race, hair cortisol, preeclampsia, and gestational weeks; and 3) a relationship between maternal childhood trauma, perceived social stress in adulthood, and low weight for gestational age. Our approach confirmed previous findings and identified previously unobserved pathways to adverse pregnancy outcomes. It presents a method for a global assessment of a clinical problem for further study of possible causal pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bacteriophages are the most abundant organisms in the biosphere and play major roles in the ecological balance of microbial life. The genomic sequences of ten newly isolated mycobacteriophages ...suggest that the bacteriophage population as a whole is amazingly diverse and may represent the largest unexplored reservoir of sequence information in the biosphere. Genomic comparison of these mycobacteriophages contributes to our understanding of the mechanisms of viral evolution and provides compelling evidence for the role of illegitimate recombination in horizontal genetic exchange. The promiscuity of these recombination events results in the inclusion of many unexpected genes including those implicated in mycobacterial latency, the cellular and immune responses to mycobacterial infections, and autoimmune diseases such as human lupus. While the role of phages as vehicles of toxin genes is well established, these observations suggest a much broader involvement of phages in bacterial virulence and the host response to bacterial infections.
The use of components in municipal solid waste (MSW) as feedstock for liquid transportation biofuels and chemicals can be a sustainable solution for energy needs while minimizing impacts of landfills ...on the environment. This study conducts a resource assessment for available MSW in Mexico and concludes that when the organic and polyolefin plastic components are converted to liquid hydrocarbon transportation biofuels through a pyrolysis-based pathway, up to 7% of Mexico’s transportation-fuel consumption needs could be met. A preliminary carbon footprint analysis (CFA) using stage-specific emission factors from the literature shows that liquid transportation biofuels from the organic portion of MSW (paper, packaging, wood, yard trimmings) sequesters 9.5 g CO2 eq per MJ biofuel, with significant pathway credits due to avoiding landfill CH4 emissions. The greenhouse gas (GHG) emissions from the conversion of the polyolefin plastic in the MSW are positive (88 g CO2 eq per MJ), though still lower than current fossil transportation fuels in Mexico (95.5 g CO2 eq per MJ). Based on these resource assessments and preliminary carbon footprint results, MSW in Mexico should be considered a promising feedstock for biofuel production through conversion research and updated carbon footprint analyses.
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