SARS-CoV-2 infection by trimester of pregnancy and adverse perinatal outcomes: a Mexican retrospective cohort study.

OBJECTIVE: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection. DESIGN AND SETTING: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021. PARTICIPANTS: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy. OUTCOME MEASURES: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies. RESULTS: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations. CONCLUSIONS: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period.

Estimating the effect of realistic improvements of metformin adherence on COVID-19 mortality using targeted machine learning.

Background: Type 2 diabetes elevates the risk of severe outcomes in COVID-19 patients, with multiple studies reporting higher case fatality rates. Metformin is a widely used medication for glycemic management. We hypothesize that improved adherence to metformin may lower COVID-19 post-infection mortality risk in this group. Utilizing data from the Mexican Social Security Institute (IMSS), we investigate the relationship between metformin adherence and mortality following COVID-19 infection in patients with chronic metformin prescriptions. Methods: This is a retrospective cohort study consisting of 61,180 IMSS beneficiaries who received a positive polymerase chain reaction (PCR) or rapid test for SARS-CoV-2 and had at least two consecutive months of metformin prescriptions prior to the positive test. The hypothetical intervention is improved adherence to metformin, measured by proportion of days covered (PDC), with the comparison being the observed metformin adherence values. The primary outcome is all-cause mortality following COVID-19 infection. We defined the causal parameter using shift intervention, an example of modified treatment policies. We used the targeted learning framework for estimation of the target estimand. Findings: Among COVID-19 positive patients with chronic metformin prescriptions, we found that a 5% and 10% absolute increase in metformin adherence is associated with a respective 0.26% (95% CI: -0.28%, 0.79%) and 1.26% (95% CI: 0.72%, 1.80%) absolute decrease in mortality risk. Interpretation: Subject to the limitations of a real-world data study, our results indicate a causal association between improved metformin adherence and reduced COVID-19 post-infection mortality risk.

Ambient and household PM2.5 pollution and adverse perinatal outcomes: A meta-regression and analysis of attributable global burden for 204 countries and territories.

BACKGROUND: Particulate matter <2.5 micrometer (PM2.5) is associated with adverse perinatal outcomes, but the impact on disease burden mediated by this pathway has not previously been included in the Global Burden of Disease (GBD), Mortality, Injuries, and Risk Factors studies. We estimated the global burden of low birth weight (LBW) and preterm birth (PTB) and impacts on reduced birth weight and gestational age (GA), attributable to ambient and household PM2.5 pollution in 2019. METHODS AND FINDINGS: We searched PubMed, Embase, and Web of Science for peer-reviewed articles in English. Study quality was assessed using 2 tools: (1) Agency for Healthcare Research and Quality checklist; and (2) National Institute of Environmental Health Sciences (NIEHS) risk of bias questions. We conducted a meta-regression (MR) to quantify the risk of PM2.5 on birth weight and GA. The MR, based on a systematic review (SR) of articles published through April 4, 2021, and resulting uncertainty intervals (UIs) accounted for unexplained between-study heterogeneity. Separate nonlinear relationships relating exposure to risk were generated for each outcome and applied in the burden estimation. The MR included 44, 40, and 40 birth weight, LBW, and PTB studies, respectively. Majority of the studies were of retrospective cohort design and primarily from North America, Europe, and Australia. A few recent studies were from China, India, sub-Saharan Africa, and South America. Pooled estimates indicated 22 grams (95% UI: 12, 32) lower birth weight, 11% greater risk of LBW (1.11, 95% UI: 1.07, 1.16), and 12% greater risk of PTB (1.12, 95% UI: 1.06, 1.19), per 10 µg/m3 increment in ambient PM2.5. We estimated a global population-weighted mean lowering of 89 grams (95% UI: 88, 89) of birth weight and 3.4 weeks (95% UI: 3.4, 3.4) of GA in 2019, attributable to total PM2.5. Globally, an estimated 15.6% (95% UI: 15.6, 15.7) of all LBW and 35.7% (95% UI: 35.6, 35.9) of all PTB infants were attributable to total PM2.5, equivalent to 2,761,720 (95% UI: 2,746,713 to 2,776,722) and 5,870,103 (95% UI: 5,848,046 to 5,892,166) infants in 2019, respectively. About one-third of the total PM2.5 burden for LBW and PTB could be attributable to ambient exposure, with household air pollution (HAP) dominating in low-income countries. The findings should be viewed in light of some limitations such as heterogeneity between studies including size, exposure levels, exposure assessment method, and adjustment for confounding. Furthermore, studies did not separate the direct effect of PM2.5 on birth weight from that mediated through GA. As a consequence, the pooled risk estimates in the MR and likewise the global burden may have been underestimated. CONCLUSIONS: Ambient and household PM2.5 were associated with reduced birth weight and GA, which are, in turn, associated with neonatal and infant mortality, particularly in low- and middle-income countries.

Costs of coronary heart disease and mortality associated with near-roadway air pollution.

BACKGROUND: Emerging evidence indicates that the near-roadway air pollution (NRAP) mixture contributes to CHD, yet few studies have evaluated the associated costs. OBJECTIVE: We integrated an assessment of NRAP-attributable CHD in Southern California with new methods to value the associated mortality and hospitalizations. METHODS: Based on population-weighted residential exposure to NRAP (traffic density, proximity to a major roadway and elemental carbon), we estimated the inflation-adjusted value of NRAP-attributable mortality and costs of hospitalizations that occurred in 2008. We also estimated anticipated costs in 2035 based on projected changes in population and in NRAP exposure associated with California's plans to reduce greenhouse gas emissions. For comparison, we estimated the value of CHD mortality attributable to PM less than 2.5µm in diameter (PM2.5) in both 2008 and 2035. RESULTS: The value of CHD mortality attributable to NRAP in 2008 was between $3.8 and $11.5 billion, 23% (major roadway proximity) to 68% (traffic density) of the $16.8 billion attributable to regulated regional PM2.5. NRAP-attributable costs were projected to increase to $10.6 to $22 billion in 2035, depending on the NRAP metric. Cost of NRAP-attributable hospitalizations for CHD in 2008 was $48.6 million and was projected to increase to $51.4 million in 2035. CONCLUSIONS: We developed an economic framework that can be used to estimate the benefits of regulations to improve air quality. CHD attributable to NRAP has a large economic impact that is expected to increase by 2035, largely due to an aging population. PM2.5-attributable costs may underestimate total value of air pollution-attributable CHD.

Assessment of organochlorine pesticide residues in Indian flue-cured tobacco with gas chromatography-single quadrupole mass spectrometer.

Presence of pesticide residues in tobacco increases health risk of both active and passive smokers, apart from the imminent potential health problems associated with it. Thus, monitoring of pesticide residue is an important issue in terms of formulating stringent policies, enabling global trade and safeguarding the consumer's safety. In this study, a gas chromatography-single quadrupole mass spectrometry (GC-MS) method based upon quantifier-qualifier ions (m/z) ratio was employed for detecting and assessing ten organochlorine pesticide residues (α-HCH, ß-HCH, γ-HCH, δ-HCH, 2,4-DDT, 4,4-DDT, endrin, α-endosulfan, ß-endosulfan and endosulfan sulphate) in 152 flue-cured (FC) tobacco leave samples from two major tobacco growing states, Karnataka and Andhra Pradesh, of India. In the majority of samples, pesticide residue levels were below the limit of quantification (LOQ). In few samples, pesticide residues were detected and they found to comply with the guidance residue levels (GRL) specifications of the Cooperation Center for Scientific Research Relative to Tobacco (CORESTA). Detection of the phase out pesticides like DDT/HCH might be due to transfer of persistent residues from the environmental components to the plant. This is the first report on these ten organochlorine pesticide residues in Indian FC tobacco.

No improvement in socioeconomic inequalities in birthweight and preterm birth over four decades: a population-based cohort study.

BACKGROUND: Birthweight and gestational age are associated with socioeconomic deprivation, but the evidence in relation to temporal changes in these associations is sparse. We investigated changes in the associations between socioeconomic status (SES) and birthweight and gestational age in Newcastle upon Tyne, North of England, during 1961-2000. METHODS: We used population-based data from hospital neonatal records on all singleton births to mothers resident in Newcastle (births with complete covariate information n = 113,182). We used linear regression to analyse the associations between neighbourhood SES and birthweight over the entire 40-year period and by decade, and logistic regression for associations with low birthweight (LBW) and preterm birth, adjusting for potential confounders. RESULTS: There was a significant interaction between SES and decade of birth for birthweight (p = 0.028) and preterm birth (p < 0.001). Socioeconomic gradients were similar in each decade for birthweight outcomes, but for preterm birth, socioeconomic disparities were more evident in the later decades [for 1961-70, odds ratio (OR) was 1.1, 95% CI 0.9, 1.3, for the most deprived versus the least deprived quartile, while for 1991-2000, the corresponding OR was 1.5, 95% CI 1.3, 1.7]. In each decade, there was a significant decrease in birthweight adjusted for gestational age for the most deprived compared to the least deprived SES group [1961-1970: -113.4 g (95% CI-133.0, -93.8); 1991-2000: -97.5 g (95% CI-113.0, -82.0)], while there was a significant increase in birthweight in each SES group over time. CONCLUSIONS: Socioeconomic inequalities did not narrow over the four decades for birthweight and widened for preterm birth. Mean birthweight adjusted for gestational age increased in all socioeconomic groups, suggesting an overall increase in fetal growth.