Diabetes during pregnancy among Métis people in Alberta: a retrospective cohort study.

BACKGROUND: Diabetes in pregnancy is an important public health concern for Indigenous populations. We sought to evaluate the prevalence and outcomes of pre-existing and gestational diabetes among Métis pregnancies compared with other pregnancies in Alberta, Canada. METHODS: We conducted a retrospective cohort study using administrative health data from 2006 to 2016 and the Métis Nation of Alberta Identification Registry to compare the prevalence of pre-existing and gestational diabetes among all singleton Métis births with non-Métis births. We compared 10 maternal and neonatal outcomes using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in multivariable analyses. RESULTS: The study population included 7902 Métis and 471 886 non-Métis births. The age-standardized prevalence of pre-existing diabetes was 1.7% (95% CI 1.4%-2.1%) for Métis and 1.1% (95% CI 1.1%-1.2%) for non-Métis pregnancies. For gestational diabetes, the age-standardized prevalence was 6.3% (95% CI 5.6%-6.9%) for Métis and 5.4% (95% CI 5.3%-5.4%) for non-Métis pregnancies. After adjusting for parity, maternal weight, age, smoking during pregnancy and material and social deprivation, Métis pregnancies had 1.72 times higher prevalence of preexisting diabetes (adjusted OR 1.72, 95% CI 1.15-2.56) and 1.30 times higher prevalence of gestational diabetes (adjusted OR 1.30, 95% CI 1.08-1.57) than non-Métis pregnancies. Métis pregnancies with pre-existing diabetes had nearly 3 times the odds of developing preeclampsia (adjusted OR 2.96, 95% CI 1.27-6.90), while those with gestational diabetes had 48% higher odds of large-for-gestational-age infants (adjusted OR 1.48, 95% CI 1.00-2.19). INTERPRETATION: Métis pregnancies have an increased prevalence of pre-existing and gestational diabetes than non-Métis pregnancies and an elevated risk of some perinatal outcomes. Interventions to tackle these health inequities should address both physiologic and cultural dimensions of health, informed by Métis perspectives.

Perinatal and early life factors and asthma control among preschoolers: a population-based retrospective cohort study.

BACKGROUND: Preventing poor childhood asthma control is crucial for short-term and long-term respiratory health. This study evaluated associations between perinatal and early-life factors and early childhood asthma control. METHODS: This retrospective study used administrative health data from mothers and children born 2010-2012 with a diagnosis of asthma before age 5 years, in Alberta, Canada. The outcome was asthma control within 2 years after diagnosis. Associations between perinatal and early-life factors and risk of partly and uncontrolled asthma were evaluated by multinomial logistic regression. RESULTS: Of 7206 preschoolers with asthma, 52% had controlled, 37% partly controlled and 12% uncontrolled asthma 2 years after diagnosis. Compared with controlled asthma, prenatal antibiotics (adjusted risk ratio (aRR): 1.19; 95% CI 1.06 to 1.33) and smoking (aRR: 1.18; 95% CI 1.02 to 1.37), C-section delivery (aRR: 1.11; 95% CI 1.00 to 1.25), summer birth (aRR: 1.16; 95% CI 1.00 to 1.34) and early-life hospitalisation for respiratory illness (aRR: 2.24; 95% CI 1.81 to 2.76) increased the risk of partly controlled asthma. Gestational diabetes (aRR: 1.41; 95% CI 1.06 to 1.87), C-section delivery (aRR: 1.18; 95% CI 1.00 to 1.39), antibiotics (aRR: 1.32; 95% CI 1.08 to 1.61) and hospitalisation for early-life respiratory illness (aRR: 1.65; 95% CI 1.19 to 2.27) were associated with uncontrolled asthma. CONCLUSION: Maternal perinatal and early-life factors including antibiotics in pregnancy and childhood, gestational diabetes, prenatal smoking, C-section and summertime birth, and hospitalisations for respiratory illness are associated with partly or uncontrolled childhood asthma. These results underline the significance of perinatal health and the lasting effects of early-life experiences on lung development and disease programming.

Intraurban Geographic and Socioeconomic Inequalities of Mortality in Four Cities in Colombia.

Mortality inequalities have been described across Latin American countries, but less is known about inequalities within cities, where most populations live. We aimed to identify geographic and socioeconomic inequalities in mortality within the urban areas of four main cities in Colombia. We analyzed mortality due to non-violent causes of diseases in adults between 2015 and 2019 using census sectors as unit of analysis in Barranquilla, Bogotá, Cali, and Medellín. We calculated smoothed Bayesian mortality rates as main health outcomes and used concentration indexes (CInd) for assessing inequalities using the multidimensional poverty index (MPI) as the socioeconomic measure. Moran eigenvector spatial filters were calculated to capture the spatial patterns of mortality and then used in multivariable models of the association between mortality rates and quintiles of MPI. Social inequalities were evident but not consistent across cities. The most disadvantaged groups showed the highest mortality rates in Cali. Geographic inequalities in mortality rates, regardless of the adults and poverty distribution, were identified in each city, suggesting that other social, environmental, or individual conditions are impacting the spatial distribution of mortality rates within the four cities.

Right Ventricular Remodeling in Hypoplastic Left Heart Syndrome is Minimally Impacted by Cardiopulmonary Bypass: A Comparison of Norwood vs. Hybrid.

Right ventricular (RV) remodeling in hypoplastic left heart syndrome (HLHS) begins prenatally and continues through staged palliations. However, it is unclear if the most marked observed remodeling post-Norwood is secondary to cardiopulmonary bypass (CPB) exposure or if it is an adaptation intrinsic to the systemic RV. This study aims to determine the impact of CPB on RV remodeling in HLHS. Echocardiograms of HLHS survivors undergoing stage 1 Norwood (n = 26) or Hybrid (n = 20) were analyzed at pre- and post-stage 1, pre- and post-bidirectional cavo-pulmonary anastomosis (BCPA), and pre-Fontan. RV fractional area change (FAC), vector velocity imaging for longitudinal & derived circumferential deformation (global radial shortening (GRS) = peak radial displacement/end-diastolic diameter), and deformation ratio (longitudinal/ circumferential) were assessed. Both groups had similar age, clinical status and functional parameters pre-stage 1. No difference in RV size and sphericity at any stage between groups. RVFAC was normal (> 35%) throughout for both groups. Both Norwood and Hybrid patients had increased GRS (p = 0.0001) post-stage 1 and corresponding unchanged longitudinal strain, resulting in decreased deformation ratio (greater relative RV circumferential contraction), p = 0.0001. Deformation ratio remained decreased in both groups in subsequent stages. Irrespective of timing of the first CPB exposure, both Norwood and Hybrid patients underwent similar RV remodeling, with relative increase in circumferential to longitudinal contraction soon after stage 1 palliation. The observed RV remodeling in HLHS survivors were minimally impacted by CPB.

Clinical predictors of a positive test result in patients undergoing genetic evaluation for a hereditary kidney cancer syndrome.

INTRODUCTION: Guidelines are available to assist providers in identifying patients with renal cell carcinoma (RCC) that may benefit from genetic counselling, however, the evidence for these recommendations lacks support from the literature and controversy remains as to who should be referred. We aimed to delineate risk factors associated with a positive genetic test in a real-life cohort of patients with RCC referred to a regional medical genetics unit for evaluation of a hereditary kidney cancer syndrome. METHODS: Patients with a diagnosis of RCC referred to Maritime Medical Genetics Service (Nova Scotia, Canada) from 2006-2017 were reviewed using retrospective data. The primary outcome was identification of clinical features that were associated with a positive test result. Logistic regression models were used for analysis. RESULTS: A total of 135 patients were referred to medical genetics for evaluation; 102 patients were evaluated, 75 underwent testing, and 74 were included in the final analysis. Five patients tested positive: three Birt-Hogg-Dubé, one Cowden syndrome, and one Von Hippel-Lindau. Presence of dermatological lesions (specifically fibrofolliculomas) and more than two high-risk features were the only predictors of a positive test result. CONCLUSIONS: The presence of dermatological lesions and more than two high-risk features are the only predictors of a positive test result in patients with a suspected hereditary kidney cancer syndrome. These findings are not reflected in current guidelines, and the clinical implementation of our results may improve the identification of high-risk patients for genetic counselling.

Socioeconomic gradients of adverse birth outcomes and related maternal factors in rural and urban Alberta, Canada: a concentration index approach.

OBJECTIVE: Using a summary measure of health inequalities, this study evaluated the distribution of adverse birth outcomes (ABO) and related maternal risk factors across area-level socioeconomic status (SES) gradients in urban and rural Alberta, Canada. DESIGN: Cross-sectional study using a validated perinatal clinical registry and an area-level SES. SETTING: The study was conducted in Alberta, Canada. Data about ABO and related maternal risk factors were obtained from the Alberta Perinatal Health Program between 2006 and 2012. An area-level SES index derived from census data (2006) was linked to the postal code at delivery. PARTICIPANTS: Women (n=3 30 957) having singleton live births with gestational age ≥22 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated concentration indexes to assess inequalities across SES gradients in both rural and urban areas (CIdxR and CIdxU, respectively) for spontaneous preterm birth (PTB), small for gestational age (SGA), large for gestational age (LGA), gestational hypertension, gestational diabetes, smoking and substance use during pregnancy and pre-pregnancy weight >91 kg. RESULTS: The highest health inequalities disfavouring low SES groups were identified for substance abuse and smoking in rural areas (CIdxR-0.38 and -0.23, respectively). Medium inequalities were identified for LGA (CIdxR-0.08), pre-pregnancy weight >91 kg (CIdxR-0.07), substance use (CIdxU-0.15), smoking (CIdxU-0.14), gestational diabetes (CIdxU-0.10) and SGA (CIdxU-0.07). Low inequalities were identified for PTB (CIdxR-0.05; CIdxU-0.05) and gestational diabetes (CIdxR-0.04). Inequalities disfavouring high SES groups were identified for gestational hypertension (CIdxR+0.04), SGA (CIdxR+0.03) and LGA (CIdxU+0.03). CONCLUSIONS: ABO and related maternal risk factors were unequally distributed across the socioeconomic gradient in urban-rural settings, with the greatest concentrations in lower SES groups of rural areas. Future research is needed on underlying mechanisms driving SES gradients in perinatal health across the rural-urban spectrum.

Latent Cytomegalovirus Infection in Female Mice Increases Breast Cancer Metastasis.

Cytomegalovirus (CMV) infects 40⁻70% of women, but infection has been reported in >95% of breast cancer patients. We investigated the consequences of these observations by infecting mice with mCMV or a negative control medium for 4 days, 11 days or 10 weeks to establish active, intermediate or latent infections, respectively. Syngeneic 4T1 or E0771 breast cancer cells were then injected into a mammary fat pad of BALB/c or C57BL/6 mice, respectively. Infection did not affect tumor growth in these conditions, but latently infected BALB/c mice developed more lung metastases. The latent mCMV infection of MMTV-PyVT mice, which develop spontaneous breast tumors, also did not affect the number or sizes of breast tumors. However, there were more tumors that were multilobed with greater blood content, which had enhanced vasculature and decreased collagen content. Most significantly, mCMV infection also increased the number and size of lung metastases, which showed a higher cell proliferation. Viral DNA was detected in breast tumors and lung nodules although viral mRNA was not. These novel results have important clinical implications since an increased metastasis is prognostic of decreased survival. This work provides evidence that treating or preventing HCMV infections may increase the life expectancy of breast cancer patients by decreasing metastasis.

Reduced Right Ventricular Fractional Area Change, Strain, and Strain Rate before Bidirectional Cavopulmonary Anastomosis is Associated with Medium-Term Mortality for Children with Hypoplastic Left Heart Syndrome.

BACKGROUND: Ventricular dysfunction is associated with increased morbidity and mortality in children with hypoplastic left heart syndrome. The aim of this study was to assess the diagnostic performance of conventional and speckle-tracking echocardiographic measures of right ventricular (RV) function before bidirectional cavopulmonary anastomosis palliation in predicting death or need for heart transplantation (HTx). METHODS: RV fractional area change (RVFAC) and longitudinal and circumferential strain and strain rate (SR) were measured in 64 prospectively recruited patients with hypoplastic left heart syndrome from echocardiograms obtained before bidirectional cavopulmonary anastomosis surgery. The composite end point of death or HTx was examined. Receiver operating characteristic analysis was performed, and cutoff values optimizing sensitivity and specificity were derived. RESULTS: At a median follow-up of 5.0 years (interquartile range, 2.8-6.4 years), 13 patients meeting the composite end point had lower longitudinal strain and SR, circumferential SR, and RVFAC compared with survivors (n = 51). The conventional cutoff of RVFAC < 35% was specific for death or HTx (86%) but had poor sensitivity (46%), with an area under the curve of 0.73. Speckle-tracking echocardiographic variables showed similar areas under the curve (range, 0.69-0.79), with negative predictive values >90%. Addition of speckle-tracking echocardiographic variables to RVFAC < 35% showed no added benefit. However, in a subpopulation of patients with RVFAC ≥ 35% (n = 44), those meeting the composite end point (n = 7) had lower longitudinal SR (median, -1.0 1/sec [interquartile range, -0.8 to -1.1 1/sec] vs -1.21/sec [interquartile range, -1.0 to -1.3 1/sec], P = .03). Interobserver reproducibility was superior for longitudinal strain and SR (intraclass correlation coefficient > 0.92) compared with RVFAC (intraclass correlation coefficient = 0.75). CONCLUSIONS: Children with hypoplastic left heart syndrome with normal RVFAC and ventricular deformation before bidirectional cavopulmonary anastomosis have a low likelihood of death or HTx in the medium term. In the presence of reduced RVFAC, speckle-tracking echocardiography does not provide additional prognostic value. However, in patients with "normal" RVFAC, it may have a role in improving outcome prediction and warrants further investigation.

TNFα and IL-6 Responses to Particulate Matter in Vitro: Variation According to PM Size, Season, and Polycyclic Aromatic Hydrocarbon and Soil Content.

BACKGROUND: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions. OBJECTIVES: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples. METHODS: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores. RESULTS: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size. CONCLUSIONS: Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies. CITATION: Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406-412; http://dx.doi.org/10.1289/ehp.1409287.