Analysis of Heat Exposure During Pregnancy and Severe Maternal Morbidity.

Importance: The rate of severe maternal morbidity (SMM) is continuously increasing in the US. Evidence regarding the associations of climate-related exposure, such as environmental heat, with SMM is lacking. Objective: To examine associations between long- and short-term maternal heat exposure and SMM. Design, Setting, and Participants: This retrospective population-based epidemiological cohort study took place at a large integrated health care organization, Kaiser Permanente Southern California, between January 1, 2008, and December 31, 2018. Data were analyzed from February to April 2023. Singleton pregnancies with data on SMM diagnosis status were included. Exposures: Moderate, high, and extreme heat days, defined as daily maximum temperatures exceeding the 75th, 90th, and 95th percentiles of the time series data from May through September 2007 to 2018 in Southern California, respectively. Long-term exposures were measured by the proportions of different heat days during pregnancy and by trimester. Short-term exposures were represented by binary variables of heatwaves with 9 different definitions (combining percentile thresholds with 3 durations; ie, ≥2, ≥3, and ≥4 consecutive days) during the last gestational week. Main Outcomes and Measures: The primary outcome was SMM during delivery hospitalization, measured by 20 subconditions excluding blood transfusion. Discrete-time logistic regression was used to estimate associations with long- and short-term heat exposure. Effect modification by maternal characteristics and green space exposure was examined using interaction terms. Results: There were 3446 SMM cases (0.9%) among 403 602 pregnancies (mean [SD] age, 30.3 [5.7] years). Significant associations were observed with long-term heat exposure during pregnancy and during the third trimester. High exposure (≥80th percentile of the proportions) to extreme heat days during pregnancy and during the third trimester were associated with a 27% (95% CI, 17%-37%; P < .001) and 28% (95% CI, 17%-41%; P < .001) increase in risk of SMM, respectively. Elevated SMM risks were significantly associated with short-term heatwave exposure under all heatwave definitions. The magnitude of associations generally increased from the least severe (HWD1: daily maximum temperature >75th percentile lasting for ≥2 days; odds ratio [OR], 1.32; 95% CI, 1.17-1.48; P < .001) to the most severe heatwave exposure (HWD9: daily maximum temperature >95th percentile lasting for ≥4 days; OR, 2.39; 95% CI, 1.62-3.54; P < .001). Greater associations were observed among mothers with lower educational attainment (OR for high exposure to extreme heat days during pregnancy, 1.43; 95% CI, 1.26-1.63; P < .001) or whose pregnancies started in the cold season (November through April; OR, 1.37; 95% CI, 1.24-1.53; P < .001). Conclusions and Relevance: In this retrospective cohort study, long- and short-term heat exposure during pregnancy was associated with higher risk of SMM. These results might have important implications for SMM prevention, particularly in a changing climate.

Neighborhood disadvantage is associated with KRAS-mutated non-small cell lung cancer risk.

PURPOSE: It remains unclear why individuals living in disadvantaged neighborhoods have shorter non-small cell lung cancer (NSCLC) survival. It is possible that living in these deprived areas is linked with increased risk of developing aggressive NSCLC biology. Here, we explored the association of somatic KRAS mutations, which are associated with shorter survival in NSCLC patients, and 11 definitions of neighborhood disadvantage spanning socioeconomic and structural environmental elements. METHODS: We analyzed data from 429 NSCLC patients treated at a Comprehensive Cancer Center from 2015 to 2018. Data were abstracted from medical records and each patient's home address was used to assign publicly available indices of neighborhood disadvantage. Prevalence Ratios (PRs) for the presence of somatic KRAS mutations were estimated using modified Poisson regression models adjusted for age, sex, smoking status, race/ethnicity, educational attainment, cancer stage, and histology. RESULTS: In the NSCLC cohort, 29% had KRAS mutation-positive tumors. We found that five deprivation indices of socioeconomic disadvantage were associated with KRAS mutation. A one decile increase in several of these socioeconomic disadvantage indices was associated with a 1.06 to 1.14 increased risk of KRAS mutation. Measures of built structural environment were not associated with KRAS mutation status. CONCLUSION: Socioeconomic disadvantage at the neighborhood level is associated with higher risk of KRAS mutation while disadvantage related to built environmental structural measures was inversely associated. Our results indicate not only that neighborhood disadvantage may contribute to aggressive NSCLC biology, but the pathways linking biology to disadvantage are likely operating through socioeconomic-related stress.

The Role of Neighborhood Air Pollution Exposure on Somatic Non-Small Cell Lung Cancer Mutations in the Los Angeles Basin (2013-2018).

Limited previous work has identified a relationship between exposure to ambient air pollution and aggressive somatic lung tumor mutations. More work is needed to confirm this relationship, especially using spatially resolved air pollution. We aimed to quantify the association between different air pollution metrics and aggressive tumor biology. Among patients treated at City of Hope Comprehensive Cancer Center in Duarte, CA (2013-2018), three non-small cell lung cancer somatic tumor mutations, TP53, KRAS, and KRAS G12C/V, were documented. PM2.5 exposure was assessed using state-of-the art ensemble models five and ten years before lung cancer diagnosis. We also explored the role of NO2 using inverse-distance-weighting approaches. We fitted logistic regression models to estimate odds ratio (OR) and their 95% confidence intervals (CIs). Among 435 participants (median age: 67, female: 51%), an IQR increase in NO2 exposure (3.5 µg/m3) five years before cancer diagnosis was associated with an increased risk in TP53 mutation (OR, 95% CI: 1.30, 0.99-1.71). We found an association between highly-exposed participants to PM2.5 (>12 µg/m3) five and ten years before cancer diagnosis and TP53 mutation (OR, 95% CI: 1.61, 0.95-2.73; 1.57, 0.93-2.64, respectively). Future studies are needed to confirm this association and better understand how air pollution impacts somatic profiles and the molecular mechanisms through which they operate.

Association between blood metals mixtures concentrations and cognitive performance, and effect modification by diet in older US adults.

BACKGROUND: Chronic exposure to heavy metals has been associated with adverse neurological outcomes in older adults. Inflammatory processes are suspected as an underlying pathway by which metals exert their neurotoxicity. In parallel, a diet rich in antioxidant and anti-inflammatory components may protect against chronic inflammation. OBJECTIVES: We examined the associations of blood concentrations of lead, cadmium, and manganese as a mixture with cognitive performance in older US adults and potential modification of these associations by diet as measured by the Healthy Eating Index 2015 (HEI-2015) and the Adapted Dietary Inflammatory Index (ADII). METHODS: We used data on 1,777 adults ≥60 years old from the US National Health and Nutrition Examination Survey (NHANES; 2011-2014). We derived the ADII and the HEI-2015 from two nonconsecutive 24-hour diet recalls. Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, the animal fluency test, and the Digit Symbol Substitution Test (DSST). We also constructed a composite z-score reflecting overall cognitive performance. We used quantile g-computation to evaluate the joint associations of a mixture of metals with cognitive performance test scores. We also evaluated effect modification by sex and diet quality indices using Cochran Q tests. RESULTS: The median (interquartile range) of blood metals were 0.38 µg/L (0.35), 14.70 µg/L (11.70), and 8.74 µg/L (4.06) for cadmium, lead, and manganese, respectively. Increasing blood concentrations of all metals by one quartile was associated with a decrease in overall cognitive performance (-0.04; 95% confidence interval [CI] = -0.09, 0.02), CERAD (-0.04; 95% CI = -0.12, 0.03), animal fluency (-0.02; 95% CI, -0.11, 0.06), and DSST (-0.05; 95% CI = -0.11, 0.02) test scores. These associations were more pronounced in adults with high pro-inflammatory or low-diet quality and null or positive though imprecise associations in participants with a high anti-inflammatory. These associations also varied by sex with inverse associations in men and positive associations in women. CONCLUSIONS: Our findings suggest that adherence to an antioxidant and anti-inflammatory diet may prevent blood metals adverse cognitive effects among older adults. If confirmed, strategies based on diet could provide a potential complementary and efficient approach to counteract effects of environmental pollutants.