Ambient air pollution is among the greatest environmental risks to human health. However, little is known about the health effects of nitrogen dioxide (NO2), a traffic-related air pollutant. Herein, ...we aimed to conduct a meta-analysis to investigate the long-term effects of NO2 on mortality.
We conducted a systematic search for studies that were published up to February 2020 and performed a meta-analysis of all available epidemiologic studies evaluating the associations between long-term exposure to NO2 with all-cause, cardiovascular, and respiratory mortality. Overall pooled effect estimates as well as subgroup-specific pooled estimates (e.g. location, exposure assessment method, exposure metric, study population, age at recruitment, and key confounder adjustment) and 95% confidence intervals were calculated using random-effects models. Risk of bias assessment was accessed by following WHO global air quality guidelines. Publication bias was accessed by visually inspecting funnel plot and Egger's liner regression was used to test of asymmetry.
Our search initially retrieved 1349 unique studies, of which 34 studies met the inclusion criteria. The pooled hazard ratio (HR) for all-cause mortality was 1.06 (95%CI: 1.04–1.08, n = 28 studies, I2 = 98.6%) per 10 ppb increase in annual NO2 concentrations. The pooled HRs for cardiovascular and respiratory mortality per 10 ppb increment were 1.11 (95%CI: 1.07–1.16, n = 20 studies, I2 = 99.2%) and 1.05 (95%CI: 1.02–1.08, n = 17 studies, I2 = 94.6%), respectively. The sensitivity analysis pooling estimates from multi-pollutant models suggest an independent effect of NO2 on mortality. Funnel plots indicate that there is no evidence for publication bias in our study.
We provide robust epidemiological evidence that long-term exposure to NO2, a proxy for traffic-sourced air pollutants, is associated with a higher risk of all-cause, cardiovascular, and respiratory mortality that might be independent of other common air pollutants.
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•A meta-analysis of long-term exposure to NO2 and all-cause, cardiovascular and respiratory mortality.•Our study creates the largest evidence base to date.•NO2 has an independent effect on mortality.
Maternal exposure to extreme ambient temperature during pregnancy has been proposed as a potential risk factor for birth defects. Comprehensive investigations on this association remain limited, ...particularly in low- and middle-income countries. This study aims to examine the association between ambient temperature exposure during pregnancy and the risk of birth defects in Brazil, contributing to the broader understanding of environmental influences on birth outcomes. Using a large dataset of over 11 million live birth records, we analyzed 12 categories of birth defects, encompassing a time frame from 2001 to 2018. Ambient temperature data were assigned at the municipality level. For the exposure assessment, we considered two biologically driven pregnancy stages by dividing the gestational period into two specific windows: the first trimester (from week 1 to week 12) and the second trimester (from week 13 to week 28). We employed a two-stage case-control design. In the first stage, we applied a conditional logistic regression model to estimate the odds ratio (OR) for specific birth defects and each of the five Brazilian regions (North, Northeast, Midwest, Southeast, and South). The model was adjusted for potential confounding variables, including PM2.5, relative humidity, and socioeconomic status. Temporal trends were addressed using time-stratified sampling. In the second stage, we used mixed-effects meta-analysis to pool region-specific estimates. Our analysis revealed a significant association between maternal exposure to higher ambient temperatures during the first trimester and an increased risk of specific birth defect categories, including those affecting the genital organs (OR = 1.08, 95% CI: 1.02; 1.14), digestive system (OR = 1.12, 95% CI: 1.06; 1.19); circulatory system (OR = 1.08, 95% CI: 1.01; 1.17); eyes, ears, face, and neck (OR = 1.08, 95% CI: 1.02; 1.15); benign neoplasms tumors (OR = 1.17, 95% CI: 1.03; 1.32), musculoskeletal system (OR = 1.03, 95% CI: 1.01; 1.05); and other congenital anomalies (OR = 1.22, 95% CI: 1.15; 1.29). The associations with respiratory system, nervous system, and chromosomal anomalies were null. These findings have significant implications for public health policies aimed at mitigating the impact of environmental factors on birth outcomes, both in Brazil and globally.Maternal exposure to extreme ambient temperature during pregnancy has been proposed as a potential risk factor for birth defects. Comprehensive investigations on this association remain limited, particularly in low- and middle-income countries. This study aims to examine the association between ambient temperature exposure during pregnancy and the risk of birth defects in Brazil, contributing to the broader understanding of environmental influences on birth outcomes. Using a large dataset of over 11 million live birth records, we analyzed 12 categories of birth defects, encompassing a time frame from 2001 to 2018. Ambient temperature data were assigned at the municipality level. For the exposure assessment, we considered two biologically driven pregnancy stages by dividing the gestational period into two specific windows: the first trimester (from week 1 to week 12) and the second trimester (from week 13 to week 28). We employed a two-stage case-control design. In the first stage, we applied a conditional logistic regression model to estimate the odds ratio (OR) for specific birth defects and each of the five Brazilian regions (North, Northeast, Midwest, Southeast, and South). The model was adjusted for potential confounding variables, including PM2.5, relative humidity, and socioeconomic status. Temporal trends were addressed using time-stratified sampling. In the second stage, we used mixed-effects meta-analysis to pool region-specific estimates. Our analysis revealed a significant association between maternal exposure to higher ambient temperatures during the first trimester and an increased risk of specific birth defect categories, including those affecting the genital organs (OR = 1.08, 95% CI: 1.02; 1.14), digestive system (OR = 1.12, 95% CI: 1.06; 1.19); circulatory system (OR = 1.08, 95% CI: 1.01; 1.17); eyes, ears, face, and neck (OR = 1.08, 95% CI: 1.02; 1.15); benign neoplasms tumors (OR = 1.17, 95% CI: 1.03; 1.32), musculoskeletal system (OR = 1.03, 95% CI: 1.01; 1.05); and other congenital anomalies (OR = 1.22, 95% CI: 1.15; 1.29). The associations with respiratory system, nervous system, and chromosomal anomalies were null. These findings have significant implications for public health policies aimed at mitigating the impact of environmental factors on birth outcomes, both in Brazil and globally.
Exposure to ambient temperature has been linked to adverse birth outcomes in several regions, including the USA, Australia, China, countries in the Middle East, and European countries. To date, no ...studies were performed in South America, a region with serious challenges related to climate change. Our investigation addresses this literature lack by examining the association between Low Birth Weight (LBW) and ambient temperature exposure in the largest county in South America, Brazil. We applied a nationwide case-control study design using a logistic regression model to estimate the odds ratio (OR) for LBW associated with ambient temperature during a specific trimester of pregnancy (1–3 trimester). Our sample size includes 5,790,713 birth records nationwide over 18 years (2001–2018), of which 264,967 infants were included in the model as cases of LBW, representing 4.6% of our total sample. We adjusted our model for several confounding variables, including weather factors, air pollution, seasonality, and SES variables at the individual level. Our findings indicate that North was the only region with positive and statistically significant associations in the primary analysis and most of the sensitivity analysis, which is the region where the Amazon is located. In this region, we estimated an increase of 5.16% (95%CI: 3.60; 6.74) in the odds of LBW per 1 °C increase in apparent temperature when the exposure occurred in the second trimester. Our results may be explained by the climate conditions in the Amazon region in the past years. A large body of literature indicates that the Amazon region has been facing serious climate challenges including issues related to policy, governance, and deforestation. Specifically, regarding deforestation, it is suggested that land use change and deforestation is projected to increase heat stress in the Amazon region, because of Amazon savannization, increasing the risk of heat stress exposure in Northern Brazil. Our study can assist public sectors and clinicians in mitigating the risk and vulnerability of the Amazonian population.
•We assessed more than 5 million birth records nationwide in Brazil.•North was the only region with positive and statistically significant associations.•In the North, we estimated an increase of 5% in the odds of LBW per 1 °C increase.
To systematically review and integrate data on the neurodevelopmental outcome of children after administration of a single course of antenatal corticosteroids for threatened preterm labor.
MEDLINE, ...Scopus, CENTRAL, and www.clinicaltrials.gov (inception to August 2014) using combinations of the terms "prenatal," "antenatal," "cortico*," "*steroid*," "betamethasone," "dexamethasone," "neurodevelopment*," "*development*," and "follow-up." We perused the references of the retrieved articles.
We included randomized and nonrandomized trials reporting on the neurodevelopmental outcomes of children whose mothers were administered a single course of betamethasone or dexamethasone antenatally for threatened preterm birth as opposed to placebo or no treatment.
Summary risk ratio (RR) was calculated for dichotomous data; standardized mean difference was calculated for trials that measured the same outcome but used different methods. Heterogeneity was assessed using the I statistic. Sensitivity and subgroup analyses were planned according to study design, specific steroid, and mean gestational age at birth. A single course of antenatal corticosteroids was associated with reduced risk for cerebral palsy (seven studies; treated: 390 of 5,199, untreated: 146 of 1,379; RR 0.678, 95% confidence interval CI 0.564-0.815), psychomotor development index less than 70 (two studies; treated: 783 of 3,049, untreated: 258 of 969; RR 0.829, 95% CI 0.737-0.933), and severe disability (five studies; treated: 1,567 of 4,840, untreated: 475 of 1,211; RR 0.787, 95% CI 0.729-0.850). Steroid treatment increased the rates of intact survival (six studies; treated: 1,082 of 2,013, untreated: 273 of 561; RR 1.186, 95% CI 1.056-1.332). Betamethasone was found to significantly decrease the risk for severe disability and increase the rate of intact survival. Dexamethasone increased the rate of intact survival; however, data for dexametasone and the other planned subgroup analyses were limited (fewer than 1,000 children at most). The major limitations involved inclusion of nonrandomized studies and scarcity of data on finer neurodevelopmental outcomes.
A single course of antenatal corticosteroids in women at high risk for preterm birth appears to improve most neurodevelopmental outcomes in offspring born before 34 weeks of gestation.
Ambient air pollution has been characterized as a leading cause of mortality worldwide and has been associated with cardiovascular and respiratory diseases. There is increasing evidence that ...short-term exposure to nitrogen dioxide (NO2), is related to adverse health effects and mortality.
We conducted a systematic review of short-term NO2 and daily mortality, which were indexed in PubMed and Embase up to June 2021. We calculated random-effects estimates by different continents and globally, and tested for heterogeneity and publication bias.
We included 87 articles in our quantitative analysis. NO2 and all-cause as well as cause-specific mortality were positively associated in the main analysis. For all-cause mortality, a 10 ppb increase in NO2 was associated with a 1.58% (95%CI 1.28%–1.88%, I2 = 96.3%, Eggers' test p < 0.01, N = 57) increase in the risk of death. For cause-specific mortality, a 10 ppb increase in NO2 was associated with a 1.72% (95%CI 1.41%–2.04%, I2 = 87.4%, Eggers' test p < 0.01, N = 42) increase in cardiovascular mortality and a 2.05% (95%CI 1.52%–2.59%, I2 = 78.5%, Eggers’ test p < 0.01, N = 38) increase in respiratory mortality. In the sensitivity analysis, the meta-estimates for all-cause mortality, cardiovascular and respiratory mortality were nearly identical. The heterogeneity would decline to varying degrees through regional and study-design stratification.
This study provides evidence of an association between short-term exposure to NO2, a proxy for traffic-sourced air pollutants, and all-cause, cardiovascular and respiratory mortality.
•A meta-analysis of short-term exposure to NO2 and all-cause, cardiovascular, and respiratory mortality.•Including the most studies up to date, stratified by region and study design.•NO2 has significant and independent impacts on mortality.
Racial/ethnic disparities in the association between short-term (e.g. days, weeks) ambient fine particulate matter (PM2.5) and temperature exposures and stillbirth in the US have been understudied. A ...time-stratified, case-crossover design using a distributed lag non-linear model (0 to 6-day lag) estimated stillbirth odds due to short-term increases in average daily PM2.5 and temperature exposures among 118,632 Medicaid recipients from 2000-2014. Disparities by maternal race/ethnicity (Black, White, Hispanic, Asian, American Indian) and zip-code level socioeconomic status (SES) were assessed. In the temperature-adjusted model, a 10 μg/m3 increase in PM2.5 concentration was marginally associated with increased stillbirth odds at lag 1 (0.68% 95%CI:-0.04,1.40) and lag 2 (0.52% 95%CI:-0.03,1.06), but not lag 0-6 (2.80% 95%CI:-0.81,6.45). An association between daily PM2.5 concentrations and stillbirth odds was found among Black individuals at the cumulative lag (0-6 days: 9.26% 95%CI:3.12,15.77), but not among other races/ethnicities. A stronger association between PM2.5 concentrations and stillbirth odds existed among Black individuals living in zip codes with the lowest median household income (lag0-6:14.13% 95%CI:4.64,25.79). Short-term temperature increases were not associated with stillbirth risk among any race/ethnicity. Black Medicaid enrollees, and especially those living in lower SES areas, may be more vulnerable to stillbirth due to short-term increases in PM2.5 exposure.
Background
Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm ...pregnancies accelerate lung maturation and reduce the incidence of respiratory complications.
Objectives
The objective of this review was to assess the effect of prophylactic corticosteroid administration before elective caesarean section at term, as compared to usual management without corticosteroids, in reducing neonatal respiratory morbidity and admission to special care with respiratory complications.
Search methods
We searched Cochrane Pregnancy and Childbirth's Trials Register (14 June 2017), and reference lists of retrieved studies.
Selection criteria
Randomised controlled trials comparing prophylactic antenatal corticosteroid administration (betamethasone or dexamethasone) with placebo or with no treatment, given before elective caesarean section at term (at or after 37 weeks of gestation).
Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.
Main results
We included four trials (3956 women and 3893 neonates) at a moderate risk of bias, comparing prophylactic administration of betamethasone or dexamethasone versus placebo or usual treatment without steroids in term elective caesarean section. Women randomised to treatment group received either two intramuscular doses of betamethasone in the 48 hours before delivery, or intramuscular dexamethasone (two or four doses) prior to delivery (at 37 weeks' gestation or 48 hours before delivery), and were compared to the control group who received a saline placebo or treatment as usual.
Prophylactic antenatal corticosteroid administration appeared to decrease the risk of respiratory distress syndrome (RDS) (risk ratio (RR) 0.48; 95% confidence interval (CI) 0.27 to 0.87; 4 studies; 3817 participants; low‐quality evidence), transient tachypnoea of the neonate (TTN) (RR 0.43; 95% CI 0.29 to 0.65; 4 studies; 3821 participants; low‐quality evidence), admission to the neonatal intensive care unit (NICU) for respiratory morbidity (RR 0.42; 95% CI 0.22 to 0.79; 3 studies; 3441 participants), and admission to neonatal special care (all levels) for respiratory complications (RR 0.45; 95% CI 0.22 to 0.90; 1 study; 942 participants; low‐quality evidence). Administration of antenatal corticosteroids also appeared to reduce admission to neonatal special care (RR 0.62; 95% CI 0.43 to 0.89; 2 studies; 2169 participants) and neonatal intensive care (RR 0.14; 95% CI 0.03 to 0.61; 1 study; 452 participants) for any indication, compared to placebo or usual care. Finally, prophylactic antenatal corticosteroids also appeared to reduce the length of stay in NICU by 2.70 days (mean difference (MD) ‐2.70; 95% CI ‐2.76 to ‐2.64; 2 studies; 32 participants).
No reduction was found in the need for mechanical ventilation (RR 0.67; 95% CI 0.27 to 1.68; 3 studies; 3441 participants; very‐low quality), perinatal death (RR 0.67; 95% CI 0.11 to 4.10; 4 studies; 3893 participants) or neonatal sepsis (RR 1.00; 95% CI 0.06 to 15.95; 2 studies; 2214 participants) .
There were no reported events of neonatal respiratory complications (other than RDS and tachypnoea of the newborn (TTN)), chronic lung disease, duration of mechanical ventilation or maternal postpartum infection, therefore results on these outcomes are non‐estimable. The studies did not provide data on other pre‐defined outcomes.
The quality of evidence, as assessed using GRADE was low for the outcomes of RDS, TTN and admission to NICU for respiratory morbidity, indicating that the true effect could potentially be substantially different from our estimate of effect.
Authors' conclusions
The results from the four trials are promising, but more high‐quality studies with larger sample sizes that are adequately powered to detect the effect of prophylactic antenatal corticosteroids on outcomes of respiratory morbidity are needed, given the potential of the current studies for bias. Consideration should be given to the balance between statistical significance and clinical significance, particularly in view of the low event rates of significant respiratory morbidity (RDS or admission to NICU for respiratory complications) in this population. In addition, further trials on the long‐term outcomes of these infants are needed to identify any potential harms and complications of antenatal corticosteroid administration at term.
The literature suggests an increased risk between anthropometrics including higher body mass index and lymphoma incidence; however, the association with physical activity remains unclear. A ...systematic review/meta-analysis was therefore performed to examine this association with physical activity (total, recreational or occupational).
PubMed, Web of Science and Embase were reviewed from inception to October 2019 identifying relevant observational studies. Non-Hodgkin lymphoma (NHL) including subtypes diffuse large B cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, and Hodgkin lymphoma (HL) were analyzed. Included studies reported activity, lymphoma cases, effect size and variability measures, and were restricted to human subjects of any age. Data was pooled generating summary relative risk (RR) estimates with 95% confidence intervals (CI) using random-effects models with primary outcome of histologically confirmed incident lymphoma.
One thousand four hundred studies were initially identified with 18 studies (nine cohort, nine case-control) included in final analysis. Comparing highest vs. lowest activity categories was protective for all lymphoma (RR 0.89, 95%CI 0.81-0.98). Sensitivity analysis demonstrated effect persistence within case-control studies (RR 0.82, 95% CI 0.71-0.96), but not cohort studies (RR 0.95, 95%CI 0.84-1.07). Borderline protective effect was seen for NHL (RR 0.92, 95%CI 0.84-1.00), but not HL (RR 0.72, 95%CI 0.50-1.04). Analysis by NHL subtype or gender showed no effect. Dose response analysis demonstrated a protective effect (p = 0.034) with a 1% risk reduction per 3 MET hours/week (RR 0.99, 95%CI 0.98-1.00).
Physical activity may have a protective effect against lymphoma development; further studies are required to generate recommendations regarding health policy.
This study was registered prospectively at PROSPERO: CRD42020156242 .
Abstract
Background
Numerous studies have assessed the association of gallstones or cholecystectomy (CE) with risk of colorectal cancer (CRC). However, the findings are mixed.
Objective
To ...systematically review and meta-analyse the association between the presence of gallstone disease (GD), or CE and the incidence of CRC. Secondary endpoints were the risk based on type of exposure, study design, tumour subsites and sex.
Methods
PubMed and EMBASE were searched from September 2020 to May 2021. The protocol was registered on the Open Science Foundation Platform. We identified and classified studies according to their design into prospective cohort, population-based case-control, hospital-based case-control and necropsy studies reporting CRC incidence among individuals with diagnosed GD or after CE (or both). Among 2157 retrieved studies, 65 (3%) met the inclusion criteria. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two independent reviewers. We evaluated the quality of the study according to the Newcastle-Ottawa Scale and only studies with a score of 6 and above were included in the final analyses. We pooled log-transformed odds ratios/risk ratios from the available adjusted models to estimate a summary relative risk (RR) and 95% confidence interval (CI) in a random-effects model. The primary outcome was overall CRC incidence. We also conducted secondary analyses according to sex and CRC subsites (proximal colon, distal colon and rectum). The outcome was measured by RRs with 95% CIs.
Results
The overall association of GD and/or CE with CRC was RR = 1.15 (1.08; 1.24), primarily driven by hospital-based case-control studies RR = 1.61 (1.29; 2.01), whereas a more modest association was found in population-based case-control and cohort studies RR = 1.10 (1.02; 1.19). Most hospital-based case-control and necropsy studies reported estimates that were adjusted for age and sex only, leaving room for residual confounding; therefore we restricted to population-based case-control and cohort studies for our subsequent analyses. Similar associations were found for women RR = 1.21 (1.05; 1.4) and men (RR = 1.24 (1.06; 1.44). When assessed by CRC subsites, GD and CE were primarily associated with higher risk of proximal colon cancer RR = 1.16 (1.07; 1.26) but not distal colon cancer RR = 0.99 (0.96; 1.03) or rectal cancer RR = 0.94 (0.89; 1.00).
Conclusions
Gallstones are associated with a modestly increased risk of colon cancer, primarily in the proximal colon.
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