Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. METHODS: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. RESULTS: The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively. CONCLUSIONS: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate.

Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study.

OBJECTIVE: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort. METHODS: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV1) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories. RESULTS: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV1 and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV1 and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV1 trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth. CONCLUSION: We found three parallel-running and one catch-up zFEV1 and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV1 but not zFVC catch-up growth.

Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. METHODS AND FINDINGS: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. CONCLUSIONS: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

Correction: Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.

[This corrects the article DOI: 10.1371/journal.pmed.1004036.].

Susceptible windows of exposure to fine particulate matter and fetal growth trajectories in the Spanish INMA (INfancia y Medio Ambiente) birth cohort.

While prior studies report associations between fine particulate matter (PM2.5) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure. We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid- (12-20 weeks), and late (20-34 weeks) pregnancy were calculated. A spatio-temporal random forest model with back-extrapolation provided weekly PM2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [ßcum, 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 µg/m3 in PM2.5, adjusted for covariates. Weeks 1-6 [ßcum = -0.77%, 95%CrI (-1.07%, -0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [ßcum = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM2.5 and EFW or AC trajectories in late pregnancy were not observed. PM2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such associations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth.

Coarse Particulate Air Pollution and Daily Mortality: A Global Study in 205 Cities.

Rationale: The associations between ambient coarse particulate matter (PM2.5-10) and daily mortality are not fully understood on a global scale. Objectives: To evaluate the short-term associations between PM2.5-10 and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide. Methods: We collected daily mortality (total, cardiovascular, and respiratory) and air pollution data from 205 cities in 20 countries/regions. Concentrations of PM2.5-10 were computed as the difference between inhalable and fine PM. A two-stage time-series analytic approach was applied, with overdispersed generalized linear models and multilevel meta-analysis. We fitted two-pollutant models to test the independent effect of PM2.5-10 from copollutants (fine PM, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide). Exposure-response relationship curves were pooled, and regional analyses were conducted. Measurements and Main Results: A 10 µg/m3 increase in PM2.5-10 concentration on lag 0-1 day was associated with increments of 0.51% (95% confidence interval [CI], 0.18%-0.84%), 0.43% (95% CI, 0.15%-0.71%), and 0.41% (95% CI, 0.06%-0.77%) in total, cardiovascular, and respiratory mortality, respectively. The associations varied by country and region. These associations were robust to adjustment by all copollutants in two-pollutant models, especially for PM2.5. The exposure-response curves for total, cardiovascular, and respiratory mortality were positive, with steeper slopes at lower exposure ranges and without discernible thresholds. Conclusions: This study provides novel global evidence on the robust and independent associations between short-term exposure to ambient PM2.5-10 and total, cardiovascular, and respiratory mortality, suggesting the need to establish a unique guideline or regulatory limit for daily concentrations of PM2.5-10.

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.

BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 µg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).

Identifying Sensitive Windows of Exposure to NO2 and Fetal Growth Trajectories in a Spanish Birth Cohort.

BACKGROUND: We previously identified associations between trimester-specific NO2 exposures and reduced fetal growth in the Spanish INfancia y Medio Ambiente (INMA) project. Here, we use temporally refined exposure estimates to explore the impact of narrow (weekly) windows of exposure on fetal growth. METHODS: We included 1,685 women from INMA with serial ultrasounds at 12, 20, and 34 gestational weeks. We measured biparietal diameter (BPD), femur length, and abdominal circumference (AC) and from them calculated estimated fetal weight (EFW). We calculated z-scores describing trajectories of each parameter during early (0-12 weeks), mid (12-20 weeks), and late (20-34 weeks) pregnancy, based on longitudinal growth curves from mixed-effects models. We estimated weekly NO2 exposures at each woman's residence using land-use regression models. We applied distributed lag nonlinear models to identify sensitive windows of exposure. We present effect estimates as the percentage change in fetal growth per 10 µg/m3 increase in NO2 exposure, and we calculated cumulative effect estimates by aggregating estimates across adjacent lags. RESULTS: We identified weeks 5-12 as a sensitive window for NO2 exposure on late EFW (cumulative ß = -3.0%; 95% CI = -4.1%, -1.9%). We identified weeks 6-19 as a sensitive window for late growth in BPD (cumulative ß = -2.0%; 95% CI = -2.7%, -1.4%) and weeks 8-13 for AC (cumulative ß = -0.68%; 95% CI = -0.97%, -0.40%). We found suggestive evidence that third trimester NO2 exposure is associated with increased AC, BPD, and EFW growth in late pregnancy. CONCLUSIONS: Our findings are consistent with the hypothesis that NO2 exposure is associated with alterations in growth of EFW, BPD, and AC dependent on the specific timing of exposure during gestation.

Differential Mortality Risks Associated With PM2.5 Components: A Multi-Country, Multi-City Study.

BACKGROUND: The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality. METHODS: We applied a 2-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators. RESULTS: We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95% confidence interval [95% CI] = 1.0030, 1.0097) to 1.0102 (95% CI = 1.0070, 1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95% CI = 1.0067, 1.0133) to 1.0037 (95% CI = 0.9998, 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk. CONCLUSIONS: These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.

Maternal occupational exposure to chemicals and child cognitive function.

BACKGROUND: Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs). METHODS: We included 1058 mother-child pairs from the INfancia y Medio Ambiente (INMA) project (2003-2008). Using a job-exposure matrix, exposure probability scores for ten EDC groups were assigned to each mother based on her longest held job during pregnancy. At the child's 5-year visit, the McCarthy Scales of Children's Abilities was administered, yielding the general cognitive index and scales for specific cognitive domains. We analyzed region-specific associations between EDC exposures and each outcome separately using adjusted linear regression and combined region-specific effect estimates using random-effects meta-analyses. RESULTS: Approximately 24% of women were exposed to at least one EDC group, but exposure to most individual EDC groups was low (<5%). Maternal organic solvent exposure was associated with lower quantitative scores among children (-5.8 points, 95% confidence interval: -11.0, -0.5). Though statistically non-significant, exposures to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds, and miscellaneous chemicals were associated with poorer offspring performance for most or all cognitive domains. CONCLUSIONS: This study found limited evidence for a role of maternal occupational EDC exposures on child cognition. Further research is needed to better characterize exposures among pregnant workers. IMPACT: Using data from a prospective birth cohort, we help fill an important research gap regarding the potential consequences of work-related exposure to endocrine-disrupting chemicals (EDCs) among pregnant women on child neurodevelopment. We expand on existing literature-largely limited to pesticide and organic solvent exposures-by using a job-exposure matrix to estimate exposure to several EDC groups. We found limited evidence of an association between maternal occupational EDC exposure and children's overall cognition. We did observe specific associations between exposure to organic solvents and lower quantitative reasoning scores.

Maternal Perfluoroalkyl Substances, Thyroid Hormones, and DIO Genes: A Spanish Cross-sectional Study.

Results of studies on perfluoroalkyl substances (PFASs) and thyroid hormones (THs) are heterogeneous, and the mechanisms underlying the action of PFASs to target THs have not been fully characterized. We examined the relation between first-trimester maternal PFAS and TH levels and the role played by polymorphisms in the iodothyronine deiodinase 1 (DIO1) and 2 (DIO2) genes in this association. Our sample comprised 919 pregnant Spanish women (recruitment = 2003-2008) with measurements of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4), and we genotyped for single-nucleotide polymorphisms in the DIO1 (rs2235544) and DIO2 (rs12885300) genes. We performed multivariate regression analyses between PFASs and THs and included the interaction term PFAS-genotypes in the models. PFHxS was associated with an increase in TSH (% change in outcome [95% CI] per 2-fold PFAS increase = 6.09 [-0.71, 13.4]), and PFOA and PFNA were associated with a decrease in TT3 (-7.17 [-13.5, -0.39] and -6.28 [-12.3, 0.12], respectively). We found stronger associations between PFOA, PFNA, and TT3 for DIO1-CC and DIO2-CT genotypes, although interaction p-values were not significant. In conclusion, this study found evidence of an inverse association between PFOA and TT3 levels. No clear effect modification by DIO enzyme genes was observed.

Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts.

The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4-12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07-1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07-1.36) compared to non-exposed children. Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.

Contrasting patterns of temperature related mortality and hospitalization by cardiovascular and respiratory diseases in 52 Spanish cities.

BACKGROUND: Climate change is a severe public health challenge. Understanding to what extent fatal and non-fatal consequences of specific diseases are associated with temperature may help to improve the effectiveness of preventive public health efforts. This study examines the effects of temperature on deaths and hospital admissions by cardiovascular and respiratory diseases, empathizing the difference between mortality and morbidity. METHODS: Daily counts for mortality and hospital admissions by cardiovascular and respiratory diseases were collected for the 52 provincial capital cities in Spain, between 1990 and 2014. The association with temperature in each city was investigated by means of distributed lag non-linear models using quasi-Poisson regression. City-specific exposure-response curves were pooled by multivariate random-effects meta-analysis to obtain countrywide risk estimates of mortality and hospitalizations due to heat and cold, and attributable fractions were computed. RESULTS: Heat and cold exposure were identified to be associated with increased risk of cardiovascular and respiratory mortality. Heat was not found to have an impact on hospital admissions. The estimated fraction of mortality attributable to cold was of greater magnitude in hospitalizations (17.5% for cardiovascular and 12.5% for respiratory diseases) compared to deaths (9% and 2.7%, respectively). CONCLUSIONS: There were noteworthy differences between temperature-related mortality and hospital admissions regarding cardiovascular and respiratory diseases, hence reinforcing the convenience of cause-specific measures to prevent temperature-related deaths.

Temperature-related effects on respiratory medical prescriptions in Spain.

BACKGROUND: The increased risk of mortality during periods of high and low temperatures has been well established. However, most of the studies used daily counts of deaths or hospitalisations as health outcomes, although they are the ones at the top of the health impact pyramid reflecting only a limited proportion of patients with the most severe cases. OBJECTIVES: This study evaluates the relationship between short-term exposure to the daily mean temperature and medication prescribed for the respiratory system in five Spanish cities. METHODS: We fitted time series regression models to cause-specific medical prescriptions, including different respiratory subgroups and age groups. We included a distributed lag non-linear model with lags up to 14 days for daily mean temperature. City-specific associations were summarised as overall-cumulative exposure-response curves. RESULTS: We found a positive association between cause-specific medical prescriptions and daily mean temperature with a non-linear inverted J- or V-shaped relationship in most cities. Between 0.3% and 0.6% of all respiratory prescriptions were attributed to cold for Madrid, Zaragoza and Pamplona, while in cities with only cold effects the attributable fractions were estimated as 19.2% for Murcia and 13.5% for Santander. Heat effects in Madrid, Zaragoza and Pamplona showed higher fractions between 8.7% and 17.2%. The estimated costs are in general higher for heat effects, showing annual values ranging between €191,905 and €311,076 for heat per 100,000 persons. CONCLUSIONS: This study provides novel evidence of the effects of the thermal environment on the prescription of medication for respiratory disorders in Spain, showing that low and high temperatures lead to an increase in the number of such prescriptions. The consumption of medication can reflect exposure to the environment with a lesser degree of severity in terms of morbidity.

Evaluation of the ERA5 reanalysis-based Universal Thermal Climate Index on mortality data in Europe.

Air temperature has been the most commonly used exposure metric in assessing relationships between thermal stress and mortality. Lack of the high-quality meteorological station data necessary to adequately characterize the thermal environment has been one of the main limitations for the use of more complex thermal indices. Global climate reanalyses may provide an ideal platform to overcome this limitation and define complex heat and cold stress conditions anywhere in the world. In this study, we explored the potential of the Universal Thermal Climate Index (UTCI) based on ERA5 - the latest global climate reanalysis from the European Centre for Medium-Range Weather Forecasts (ECMWF) - as a health-related tool. Employing a novel ERA5-based thermal comfort dataset ERA5-HEAT, we investigated the relationships between the UTCI and daily mortality data in 21 cities across 9 European countries. We used distributed lag nonlinear models to assess exposure-response relationships between mortality and thermal conditions in individual cities. We then employed meta-regression models to pool the results for each city into four groups according to climate zone. To evaluate the performance of ERA5-based UTCI, we compared its effects on mortality with those for the station-based UTCI data. In order to assess the additional effect of the UTCI, the performance of ERA5-and station-based air temperature (T) was evaluated. Whilst generally similar heat- and cold-effects were observed for the ERA5-and station-based data in most locations, the important role of wind in the UTCI appeared in the results. The largest difference between any two datasets was found in the Southern European group of cities, where the relative risk of mortality at the 1st percentile of daily mean temperature distribution (1.29 and 1.30 according to the ERA5 vs station data, respectively) considerably exceeded the one for the daily mean UTCI (1.19 vs 1.22). These differences were mainly due to the effect of wind in the cold tail of the UTCI distribution. The comparison of exposure-response relationships between ERA5-and station-based data shows that ERA5-based UTCI may be a useful tool for definition of life-threatening thermal conditions in locations where high-quality station data are not available.

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

High adherence to a mediterranean diet at age 4 reduces overweight, obesity and abdominal obesity incidence in children at the age of 8.

BACKGROUND/OBJECTIVES: A higher adherence to a Mediterranean diet has been shown to be protective against obesity in adults, but the evidence is still inconclusive in children at early ages. Our objective was to explore the association between adherence to Mediterranean Diet at the age of 4 and the prevalence of overweight, obesity, and abdominal obesity at 4 years of age, and incidence at the age of 8. SUBJECTS/METHODS: We analyzed data from children of the INMA cohort study who attended follow-up visits at age 4 and 8 years (n = 1801 and n = 1527, respectively). Diet was assessed at the age of 4 using a validated food frequency questionnaire. The adherence to MD was evaluated by the relative Mediterranean diet (rMED) score, and categorized as low (0-6), medium (7-10), and high (11-16). Overweight and obesity were defined according to the age-sex specific BMI cutoffs proposed by the International Obesity Task Force, and abdominal obesity as waist circumference >90th percentile. We used Poisson regression models to estimate prevalence ratios at 4 years of age, and Cox regression analysis to estimate hazard ratios (HR) from 4-8 years of age. RESULTS: In cross-sectional analyses at the age of 4 no association was observed between adherence to MD and overweight, obesity, or abdominal obesity. In longitudinal analyses, a high adherence to MD at age 4 was associated with lower incidence of overweight (HR = 0.38; 95% CI: 0.21-0.67; p = 0.001), obesity (HR = 0.16; 95% CI: 0.05-0.53; p = 0.002), and abdominal obesity (HR = 0.30; 95% CI: 0.12-0.73; p = 0.008) at the age of 8. CONCLUSION: This study shows that a high adherence to MD at the age of 4 is associated with a lower risk of developing overweight, obesity, and abdominal obesity at age 8. If these results are confirmed by other studies, MD may be recommended to reduce the incidence of obesity at early ages.

Air Conditioning and Heat-related Mortality: A Multi-country Longitudinal Study.

BACKGROUND: Air conditioning has been proposed as one of the key factors explaining reductions of heat-related mortality risks observed in the last decades. However, direct evidence is still limited. METHODS: We used a multi-country, multi-city, longitudinal design to quantify the independent role of air conditioning in reported attenuation in risk. We collected daily time series of mortality, mean temperature, and yearly air conditioning prevalence for 311 locations in Canada, Japan, Spain, and the USA between 1972 and 2009. For each city and sub-period, we fitted a quasi-Poisson regression combined with distributed lag non-linear models to estimate summer-only temperature-mortality associations. At the second stage, we used a novel multilevel, multivariate spatio-temporal meta-regression model to evaluate effect modification of air conditioning on heat-mortality associations. We computed relative risks and fractions of heat-attributable excess deaths under observed and fixed air conditioning prevalences. RESULTS: Results show an independent association between increased air conditioning prevalence and lower heat-related mortality risk. Excess deaths due to heat decreased during the study periods from 1.40% to 0.80% in Canada, 3.57% to 1.10% in Japan, 3.54% to 2.78% in Spain, and 1.70% to 0.53% in the USA. However, increased air conditioning explains only part of the observed attenuation, corresponding to 16.7% in Canada, 20.0% in Japan, 14.3% in Spain, and 16.7% in the USA. CONCLUSIONS: Our findings are consistent with the hypothesis that air conditioning represents an effective heat adaptation strategy, but suggests that other factors have played an equal or more important role in increasing the resilience of populations.

Postnatal exposure to mercury and neuropsychological development among preschooler children.

The objective of this study was to describe the postnatal exposure to Hg and to evaluate its association with neuropsychological development among preschool children. The study population are 4-5 years old children (n = 1252) participant in the Spanish INMA Project. Total Hg was measured in cord blood and in hair samples taken at 4 years of age (2008-2012). Neuropsychological development was assessed using the McCarthy Scales of Children's Abilities (MSCA). Information on covariates and possible confounders was obtained by questionnaires during pregnancy and childhood. Generalized additive and linear regression models were built in order to assess the relationship between MSCA scores and Hg exposure. We also evaluated the magnitude of the possible bias generated from measurement error in seafood intake estimate from questionnaire and Hg determination. The geometric mean of hair Hg was 0.98 µg/g [95% confidence interval (CI) 0.94, 1.03]. In the regression analysis, the association between Hg and the MSCA scores was positive for all the scales and statistically significant for the verbal (ß = 0.89; 95%CI 0.38, 1.39), memory (ß = 0.42; 95%CI 0.09, 0.76) and general cognitive scales (ß = 1.35; 95%CI 0.45, 2.25). However, these associations were clearly attenuated when we adjusted by the children's fish intake variables or when took into account theoretical scenarios of low precision in fish intake and Hg measurements. Hg levels in this Spanish population were high in comparison with other European countries; however, we did not observe adverse effects on child neuropsychological development associated with this postnatal exposure to Hg.