Maternal exposure to ambient air temperature and adverse birth outcomes: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Multiple systematic reviews on prenatal ambient temperature and adverse birth outcomes exist, but the overall epidemiological evidence and the appropriate metric for thermal stress remain unclear. An umbrella review was performed to summarise and appraise the evidence with recommendations. METHODS: Systematic reviews and meta-analyses on the associations between ambient temperature and adverse birth outcomes (preterm birth, stillbirth, birth weight, low birth weight, and small for gestational age) up to December 20, 2023, were synthesised according to a published protocol. Databases PubMed, CINAHL, Scopus, MEDLINE/Ovid, EMBASE/Ovid, Web of Science Core Collection, systematic reviews repositories, electronic grey literature, and references were searched. Risk of bias was assessed using Joanna Briggs Institute's critical appraisal tool. RESULTS: Eleven systematic reviews, including two meta-analyses, were included. This comprised 90 distinct observational studies that employed multiple temperature assessment metrics with a very high overlap of primary studies. Primary studies were mostly from the United States while both Africa and South Asia contributed only three studies. A majority (7 out of 11) of the systematic reviews were rated as moderate risk of bias. All systematic reviews indicated that maternal exposures to both extremely high and low temperatures, particularly during late gestation are associated with increased risks of preterm birth, stillbirth, and reduced fetal growth. However, due to great differences in the exposure assessments, high heterogeneity, imprecision, and methodological limitations of the included systematic reviews, the overall epidemiological evidence was classified as probable evidence of causation. No study assessed biothermal metrics for thermal stress. CONCLUSIONS: Despite the notable methodological differences, prenatal exposure to extreme ambient temperatures, particularly during late pregnancy, was associated with adverse birth outcomes. Adhering to the appropriate systematic review guidelines for environmental health research, incorporating biothermal metrics into exposure assessment, evidence from broader geodemographic settings, and interventions are recommended in future studies.

Critical Windows of Maternal Exposure to Biothermal Stress and Birth Weight for Gestational Age in Western Australia.

BACKGROUND: There is limited and inconsistent evidence on the risk of ambient temperature on small for gestational age (SGA) and there are no known related studies for large for gestational age (LGA). In addition, previous studies used temperature rather than a biothermal metric. OBJECTIVES: Our aim was to examine the associations and critical susceptible windows of maternal exposure to a biothermal metric [Universal Thermal Climate Index (UTCI)] and the hazards of SGA and LGA. METHODS: We linked 385,337 singleton term births between 1 January 2000 and 31 December 2015 in Western Australia to daily spatiotemporal UTCI. Distributed lag nonlinear models with Cox regression and multiple models were used to investigate maternal exposure to UTCI from 12 weeks preconception to birth and the adjusted hazard ratios (HRs) of SGA and LGA. RESULTS: Relative to the median exposure, weekly and monthly specific exposures showed potential critical windows of susceptibility for SGA and LGA at extreme exposures, especially during late gestational periods. Monthly exposure showed strong positive associations from the 6th to the 10th gestational months with the highest hazard of 13% for SGA (HR=1.13; 95% CI: 1.10, 1.14) and 7% for LGA (HR=1.07; 95% CI: 1.03, 1.11) at the 10th month for the 1st UTCI centile. Entire pregnancy exposures showed the strongest hazards of 11% for SGA (HR=1.11; 95% CI: 1.04, 1.18) and 3% for LGA (HR=1.03; 95% CI: 0.95, 1.11) at the 99th UTCI centile. By trimesters, the highest hazards were found during the second and first trimesters for SGA and LGA, respectively, at the 99th UTCI centile. Based on estimated interaction effects, male births, mothers who were non-Caucasian, smokers, ≥35 years of age, and rural residents were most vulnerable. CONCLUSIONS: Both weekly and monthly specific extreme biothermal stress exposures showed potential critical susceptible windows of SGA and LGA during late gestational periods with disproportionate sociodemographic vulnerabilities. https://doi.org/10.1289/EHP12660.

Fluoride-induced apoptosis in non-skeletal tissues of experimental animals: A systematic review and meta-analysis.

Different studies have suggested that fluoride can induce apoptosis in non-skeletal tissues, however, evidence from these experimental studies is still controversial. This meta-analysis aims to clarify the mechanism of fluoride-induced apoptosis in non-skeletal tissues of experimental animals. Primary studies which measured apoptosis were identified through exhaustive database searching in PubMed, Embase, Web of Science Core Collection, Scopus, and references of included studies. A random effects model with standardized mean difference (SMD) was used for meta-analyses. The heterogeneity of the studies was evaluated using Higgin's I2 statistics. The risk of bias and publication bias were assessed using the SYRCLE's risk of bias tool and Egger's test, respectively. There was an increase in total apoptotic cells, and the expression of Bax, Bax/Bcl-2 ratio, caspase-3, caspase-8, caspase-9, Cyt c, and p53, and a decrease in the expression of Bcl-2 in the fluoride-treated groups as compared to the control groups. However, there was no evidence of a difference in the expression of APAF-1 in the two groups. The subgroup analysis highlighted the role of the intervention period in modification of the apoptotic effect of fluoride and that the susceptibility and tolerance of different animal species and tissues vary. Meta-regression analysis indicated that the studies' effect size for total apoptotic cells was influenced by animal species and that of Bax by the sample source. The results of this meta-analysis revealed that fluoride causes apoptosis by up-regulating caspase-3, -8, and -9, Cyt c, p53, Bax, and down-regulating Bcl-2 with a concomitant up-regulation of the Bax/Bcl-2 ratio.

Bullying Victimization and Suicidal Behavior among adolescents in 28 Countries and Territories: A Moderated Mediation Model.

BACKGROUND: Previous studies have increasingly shown the adverse effects of being bullied on suicidal behavior among young people, but the mechanisms underlying this association remain unclear. We examined the association between bullying and suicidal behavior among in-school adolescents. We further tested whether loneliness mediated the link between bullying and suicidal behavior and explored the moderated role of parental involvement in this association. METHODS: We used cross-sectional school-based data from the Global School-based Student Health Survey among 28 countries and territories. Adjusted, modified Poisson regressions with robust variance relative risks and moderation analyses were used to examine associations among bullying, suicidal behavior, and parental involvement. The mediating effect of loneliness on the bullying-suicidal behavior link was assessed using the generalized decomposition method. RESULTS: A total of 78,558 school-going adolescents participated in this study. Bullying was associated with a 44% increased risk of suicidal behavior after adjusting for potential confounders (relative risk = 1.44; 95% confidence interval = 1.39-1.48). Loneliness partially mediated the association between bullying and suicidal behavior, and parental involvement moderated the association. DISCUSSION: The findings suggest the need to recognize the dual burden of bullying and loneliness when addressing suicidal behavior and the importance of parental support in adolescents' mental health and well-being.

Prenatal exposure to long-term heat stress and stillbirth in Ghana: A within-space time-series analysis.

INTRODUCTION: Few studies examined the association between prenatal long-term ambient temperature exposure and stillbirth and fewer still from developing countries. Rather than ambient temperature, we used a human thermophysiological index, Universal Thermal Climate Index (UTCI) to investigate the role of long-term heat stress exposure on stillbirth in Ghana. METHODS: District-level monthly UTCI was linked with 90,532 stillbirths of 5,961,328 births across all 260 local districts between 1st January 2012 and 31st December 2020. A within-space time-series design was applied with distributed lag nonlinear models and conditional quasi-Poisson regression. RESULTS: The mean (28.5 ± 2.1 °C) and median UTCI (28.8 °C) indicated moderate heat stress. The Relative Risks (RRs) and 95% Confidence Intervals (CIs) for exposure to lower-moderate heat (1st to 25th percentiles of UTCI) and strong heat (99th percentile) stresses showed lower risks, relative to the median UTCI. The higher-moderate heat stress exposures (75th and 90th percentiles) showed greater risks which increased with the duration of heat stress exposures and were stronger in the 90th percentile. The risk ranged from 2% (RR = 1.02, 95% CI 0.99, 1.05) to 18% (RR = 1.18, 95% CI 1.02, 1.36) for the 90th percentile, relative to the median UTCI. Assuming causality, 19 (95% CI 3, 37) and 27 (95% CI 3, 54) excess stillbirths per 10,000 births were attributable to long-term exposure to the 90th percentile relative to median UTCI for the past six and nine months, respectively. Districts with low population density, low gross domestic product, and low air pollution which collectively defined rural districts were at higher risk as compared to those in the high level (urban districts). DISCUSSION: Maternal exposure to long-term heat stress was associated with a greater risk of stillbirth. Climate change-resilient interventional measures to reduce maternal exposure to heat stress, particularly in rural areas may help lower the risk of stillbirth.

Prenatal acute thermophysiological stress and spontaneous preterm birth in Western Australia, 2000-2015: A space-time-stratified case-crossover analysis.

Epidemiologic evidence on acute heat and cold stress and preterm birth (PTB) is inconsistent and based on ambient temperature rather than a thermophysiological index. The aim of this study was to use a spatiotemporal thermophysiological index (Universal Thermal Climate Index, UTCI) to investigate prenatal acute heat and cold stress exposures and spontaneous PTB. We conducted a space-time-stratified case-crossover analysis of 15,576 singleton live births with spontaneous PTB between January 1, 2000 and December 31, 2015 in Western Australia. The association between UTCI and spontaneous PTB was examined with distributed lag nonlinear models and conditional quasi-Poisson regression. Relative to the median UTCI, there was negligible evidence for associations at the lower range of exposures (1st to 25th percentiles). We found positive associations in the 95th and 99th percentiles, which increased with increasing days of heat stress in the first week of delivery. The relative risk (RR) and 95% confidence interval (CI) for the immediate (delivery day) and cumulative short-term (up to six preceding days) exposures to heat stress (99th percentile, 31.2 °C) relative to no thermal stress (median UTCI, 13.8 °C) were 1.01 (95% CI: 1.01, 1.02) and 1.05 (95% CI: 1.04, 1.06), respectively. Elevated effect estimates for heat stress were observed for the transition season, the year 2005-2009, male infants, women who smoked, unmarried, ≤ 19 years old, non-Caucasians, and high socioeconomic status. Effect estimates for cold stress (1st percentile, 0.7 °C) were highest in the transition season, during 2005-2009, and for married, non-Caucasian, and high socioeconomic status women. Acute heat stress was associated with an elevated risk of spontaneous PTB with sociodemographic vulnerability. Cold stress was associated with risk in a few vulnerable subgroups. Awareness and mitigation strategies such as hydration, reducing outdoor activities, affordable heating and cooling systems, and climate change governance may be beneficial. Further studies with the UTCI are required.

Prenatal exposure to ambient air pollution and adverse birth outcomes: An umbrella review of 36 systematic reviews and meta-analyses.

Multiple systematic reviews and meta-analyses linked prenatal exposure to ambient air pollutants to adverse birth outcomes with mixed findings, including results indicating positive, negative, and null associations across the pregnancy periods. The objective of this study was to systematically summarise systematic reviews and meta-analyses on air pollutants and birth outcomes to assess the overall epidemiological evidence. Systematic reviews with/without meta-analyses on the association between air pollutants (NO2, CO, O3, SO2, PM2.5, and PM10) and birth outcomes (preterm birth; stillbirth; spontaneous abortion; birth weight; low birth weight, LBW; small-for-gestational-age) up to March 30, 2022 were included. We searched PubMed, CINAHL, Scopus, Medline, Embase, and the Web of Science Core Collection, systematic reviews repositories, grey literature databases, internet search engines, and references of included studies. The consistency in the directions of the effect estimates was classified as more consistent positive or negative, less consistent positive or negative, unclear, and consistently null. Next, the confidence in the direction was rated as either convincing, probable, limited-suggestive, or limited non-conclusive evidence. Final synthesis included 36 systematic reviews (21 with and 15 without meta-analyses) that contained 295 distinct primary studies. PM2.5 showed more consistent positive associations than other pollutants. The positive exposure-outcome associations based on the entire pregnancy period were more consistent than trimester-specific exposure averages. For whole pregnancy exposure, a more consistent positive association was found for PM2.5 and birth weight reductions, particulate matter and spontaneous abortion, and SO2 and LBW. Other exposure-outcome associations mostly showed less consistent positive associations and few unclear directions of associations. Almost all associations showed probable evidence. The available evidence indicates plausible causal effects of criteria air pollutants on birth outcomes. To strengthen the evidence, more high-quality studies are required, particularly from understudied settings, such as low-and-middle-income countries. However, the current evidence may warrant the adoption of the precautionary principle.

Maternal acute thermophysiological stress and stillbirth in Western Australia, 2000-2015: A space-time-stratified case-crossover analysis.

BACKGROUND: The extreme thermal environment driven by climate change disrupts thermoregulation in pregnant women and may threaten the survival of the developing fetus. OBJECTIVES: To investigate the acute effect of maternal exposure to thermophysiological stress (measured with Universal Thermal Climate Index, UTCI) on the risk of stillbirth and modification of this effect by sociodemographic disparities. METHODS: We conducted a space-time-stratified case-crossover analysis of daily UTCI and 2835 singleton stillbirths between 1st January 2000 and 31st December 2015 across multiple small areas in Western Australia. Distributed lag non-linear models were combined with conditional quasi-Poisson regression to investigate the effects of the UTCI exposure from the preceding 6 days to the day of stillbirth. We also explored effect modification by fetal and maternal sociodemographic factors. RESULTS: The median UTCI was 13.9 °C (representing no thermal stress) while the 1st and 99th percentiles were 0.7 °C (slight cold stress) and 31.7 °C (moderate heat stress), respectively. Relative to median UTCI, we found positive associations between acute maternal cold and heat stresses and higher risks of stillbirth, increasing with the intensity and duration of the thermal stress episodes. The cumulative risk from the preceding 6 days to the day of stillbirth was stronger in the 99th percentile (RR = 1.19, 95% CI: 1.17, 1.21) than the 1st percentile (RR = 1.14, 95% CI: 1.12, 1.15), relative to the median UTCI. The risks were disproportionately higher in term and male stillborn fetuses, smoking, unmarried, ≤19 years old, non-Caucasian, and low socioeconomic status mothers. DISCUSSION: Acute maternal exposure to both cold and heat stresses may contribute to the risk of stillbirth and be exacerbated by sociodemographic disparities. The findings suggest public health attention, especially for the identified higher-risk groups. Future studies should consider the use of a human thermophysiological index, rather than surrogates such as ambient temperature.

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Prenatal Tobacco Exposure and the Risk of Tobacco Smoking and Dependence in Offspring: a Systematic Review and Meta-Analysis.

BACKGROUND: There is some compelling, though not comprehensive, epidemiological evidence which suggests an association between prenatal tobacco exposure and tobacco smoking/dependence in offspring. We conducted a systematic review and meta-analysis to identify the magnitude and consistency of associations reported between prenatal tobacco exposure and subsequent tobacco smoking/dependence in offspring. METHODS: Using the PRISMA guideline, we systematically searched PubMed, SCOPUS, EMBASE and Psych-INFO to identify relevant studies. The methodological quality of all identified studies was checked by the Newcastle-Ottawa Scale. Inverse variance weighted random effects meta-analysis was used to estimate pooled risk ratio (RR) and 95 % confidence intervals (CI). We stratified outcomes by tobacco smoking initiation, lifetime tobacco smoking, current tobacco smoking and tobacco dependence. We further performed subgroup and leave-one-out sensitivity analyses. The protocol of this review was registered in the PROSPERO. RESULTS: Twenty-six cohort and one case-control study were included in the final meta-analysis. We found elevated pooled risks of tobacco smoking initiation [RR = 2.08, (95 % CI: 1.18-3.68)], ever tobacco smoking [RR = 1.21, (95 % CI: 1.05-1.38)], current tobacco smoking [RR = 1.70, (95 % CI: 1.48-1.95)] and tobacco dependence [RR = 1.50, (95 % CI: 1.31-1.73)] in offspring exposed to maternal prenatal tobacco use compared to non-exposed. We also noted higher risk estimate of current tobacco smoking in offspring exposed to heavy prenatal tobacco smoking [RR = 1.68, (95 % CI: 1.26-2.23)] when compared to prenatal exposure to lighter tobacco use [RR = 1.39, (95 % CI: 1.09-1.78)]. There was no association observed between paternal smoking during pregnancy and tobacco smoking in offspring. CONCLUSION: Offspring exposed to maternal prenatal tobacco smoking are at an increased risk of tobacco smoking/dependence, indicating that tobacco smoking cessation during gestation may be imperative to reduce these risks in offspring.

Ambient Air Pollution, Extreme Temperatures and Birth Outcomes: A Protocol for an Umbrella Review, Systematic Review and Meta-Analysis.

Prenatal exposure to ambient air pollution and extreme temperatures are among the major risk factors of adverse birth outcomes and with potential long-term effects during the life course. Although low- and middle-income countries (LMICs) are most vulnerable, there is limited synthesis of evidence in such settings. This document describes a protocol for both an umbrella review (Systematic Review 1) and a focused systematic review and meta-analysis of studies from LMICs (Systematic Review 2). We will search from start date of each database to present, six major academic databases (PubMed, CINAHL, Scopus, MEDLINE/Ovid, EMBASE/Ovid and Web of Science Core Collection), systematic reviews repositories and references of eligible studies. Additional searches in grey literature will also be conducted. Eligibility criteria include studies of pregnant women exposed to ambient air pollutants and/or extreme temperatures during pregnancy with and without adverse birth outcomes. The umbrella review (Systematic Review 1) will include only previous systematic reviews while Systematic Review 2 will include quantitative observational studies in LMICs. Searches will be restricted to English language using comprehensive search terms to consecutively screen the titles, abstracts and full-texts to select eligible studies. Two independent authors will conduct the study screening and selection, risk of bias assessment and data extraction using JBI SUMARI web-based software. Narrative and semi-quantitative syntheses will be employed for the Systematic Review 1. For Systematic Review 2, we will perform meta-analysis with two alternative meta-analytical methods (quality effect and inverse variance heterogeneity) as well as the classic random effect model. If meta-analysis is infeasible, narrative synthesis will be presented. Confidence in cumulative evidence and the strength of the evidence will be assessed. This protocol is registered with PROSPERO (CRD42020200387).

Geo-visual integration of health outcomes and risk factors using excess risk and conditioned choropleth maps: a case study of malaria incidence and sociodemographic determinants in Ghana.

BACKGROUND: Recently, exploratory spatial data analysis is for problem solving, hypothesis generation and knowledge construction. Unless geographically weighted regression, sophisticated spatial regression models best control spatial heterogeneity in outcomes and the associated risk factors but cannot visually display and identify areas of the significant associations. The under-utilised excess risk maps (ERMs) and conditioned choropleth maps (CCMs) are useful to address this issue and simplify epidemiological information to public health stakeholders without much statistical backgrounds. Using malaria and sociodemographic determinants in Ghana as case study, this paper applied ERM and CCM techniques for identification of areas at elevated risk of disease-risk factor co-location. METHOD: We computed and smoothed mean district-specific malaria incidences for the period 2010 to 2014 as a function of sociodemographic determinants. The spatial distribution of malaria was investigated through global and local spatial autocorrelations, and the association with sociodemographic risk factors evaluated with bivariate correlations. ERMs and CCMs were produced for the statistically significant risk factors. RESULTS: The incidence of malaria increased over time with cluster locations detected, predominantly at the northern parts but later few spread to the middle parts of the country. Our results suggested that with respect to sociodemographic determinants, district variations in malaria rates might be explained by inequalities in seven sociodemographics, including an unexpected significant negative association with non-religious affiliation. The sociodemographics had positive spatial autocorrelations, exhibited statistically significant interactions and the strongest was observed in urbanisation-basic education correlation (p< 0.01, r = +0.969). The ERMs and CCMs specifically identified locations with lower or higher than expected rates with respect to particular risk factor(s) where improving risk factor(s) such as employment-to-population ratio in rural areas, basic education could have cascade effects to reduce the expected malaria incidence in endemic areas. CONCLUSION: Ghana remains malaria hyperendemic region with district-level spatial heterogeneity. Significant association between malaria and sociodemographics was detected and the ERMs and CCMs geo-visually pinpointed locations of these significant associations. To complement sophisticated spatial regression models, the easily interpretable ERMs and CCMs could be used to specify where disease-risk factor associations are significant, simplifying complex spatial epidemiological information for efficient public health administration.

Spatial and temporal heterogeneities of district-level typhoid morbidities in Ghana: A requisite insight for informed public health response.

Typhoid fever is estimated to cause between 9.9-24.2 million cases and 75,000-208,000 deaths per year globally. Low-income and middle-income countries report the majority of cases, especially those in sub-Saharan Africa. The epidemiology of typhoid fever is poorly understood, particularly in Ghana where there has been no study of the within-country variation. Our objective was to explore and analyze the spatial and temporal patterns of typhoid fever morbidities in Ghana. We used the global and local Moran's indices to uncover the existence of global and local spatial patterns, respectively. Generalized linear autoregressive moving average (glarma) models were developed to explore the overall and regional level temporal patterns of morbidities. The overall index of spatial association was 0.19 (p < 0.001). The global Moran's monthly indices of clustering ranged from ≈ 0 - 0.28, with few non-significant (p > 0.05) estimates. The yearly estimates were all significant (p < 0.001) and ranged from 0.1-0.19, suggesting spatial clustering of typhoid. The local Moran's maps indicated isolated high contributions of clustering within the Upper West and Western regions. The overall and regional level glarma models indicated significant first and second-order serial correlation as well as quarterly trends. These findings can provide relevant epidemiological insight into the spatial and temporal patterns of typhoid epidemiology and useful to complement the development of control strategies by public health managers.