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BACKGROUND: Postpartum depression (PPD) has been associated with biological, emotional, social, and environmental factors. However, evidence regarding the effect of temperature on PPD is extremely limited. OBJECTIVES: We aimed to examine the associations between postpartum temperature exposure and PPD. METHODS: We conducted a retrospective cohort study using data from Kaiser Permanente Southern California electronic health records from 1 January 2008 through 31 December 2018. PPD was first assessed using the Edinburgh Postnatal Depression Scale (score ≥10) during the first year of the postpartum period and further identified by using both diagnostic codes and prescription medications. Historical daily ambient temperatures were obtained from the 4-km resolution gridMET dataset (https://www.climatologylab.org/gridmet.html) and linked to participants residential addresses at delivery. Postpartum temperature exposures were measured by calculating various temperature metrics during the period from delivery to PPD diagnosis date. A time-to-event approach with a discrete-time logistic regression was applied to estimate the association between temperature exposure and time to PPD. Effect modification by maternal characteristics and other environmental factors was examined. RESULTS: There were 46,114 (10.73%) PPD cases among 429,839 pregnancies (mean±standard deviation age =30.22±5.75 y). Increased PPD risks were positively associated with exposure to higher mean temperature [adjusted odds ratio (aOR) per interquartile range increment: 1.07; 95% confidence interval (CI): 1.05, 1.09] and diurnal temperature range (aOR=1.08; 95% CI: 1.06, 1.10); the associations were stronger for maximum temperature compared with minimum temperature. The temperature-related PPD risks were greater among African American, Asian, and Hispanic mothers and among mothers ≥25 years of age compared with their counterparts. We also observed higher effects of temperature on PPD among mothers exposed to higher air pollution or lower green space levels and among mothers with lower air conditioning penetration rates. CONCLUSION: Maternal exposure to higher temperature and diurnal temperature variability during the postpartum period was associated with an increased risk of PPD. Effect modification by maternal age, race/ethnicity, air pollution, green space, and air conditioning penetration was identified. https://doi.org/10.1289/EHP14783.

1 Leishmaniasis is a heterogeneous group of diseases caused by protozoan parasites of the genus Leishmania, transmitted by the bite of phlebotomine sand flies (1). The 3 typical clinical presentations [...]

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 μm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 μg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochrans Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Gestational diabetes mellitus (GDM) is a major pregnancy complication affecting approximately 14.0% of pregnancies around the world. Air pollution exposure, particularly exposure to PM2.5, has become a major environmental issue affecting health, especially for vulnerable pregnant women. Associations between PM2.5 exposure and adverse birth outcomes are generally assumed to be the same throughout a large geographical area. However, the effects of air pollution on health can very spatially in subpopulations. Such spatially varying effects are likely due to a wide range of contextual neighborhood and individual factors that are spatially correlated, including SES, demographics, exposure to housing characteristics and due to different composition of particulate matter from different emission sources. This combination of elevated environmental hazards in conjunction with socioeconomic-based disparities forms what has been described as a double jeopardy for marginalized sub-populations. In this manuscript our analysis combines both an examination of spatially varying effects of a) unit-changes in exposure and examines effects of b) changes from current exposure levels down to a fixed compliance level, where compliance levels correspond to the Air Quality Standards (AQS) set by the U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality guideline values. Results suggest that exposure reduction policies should target certain hotspot areas where size and effects of potential reductions will reap the greatest rewards in terms of health benefits, such as areas of southeast Los Angeles County which experiences high levels of PM2.5 exposures and consist of individuals who may be particularly vulnerable to the effects of air pollution on the risk of GDM.

Few studies have assessed extreme temperatures' impact on gestational diabetes mellitus (GDM). We examined the relation between GDM risk with weekly exposure to extreme high and low temperatures during the first 24 weeks of gestation and assessed potential effect modification by microclimate indicators.MethodsWe utilized 2008-2018 data for pregnant women from Kaiser Permanente Southern California electronic health records. GDM screening occurred between 24 and 28 gestational weeks for most women using the Carpenter-Coustan criteria or the International Association of Diabetes and Pregnancy Study Groups criteria. Daily maximum, minimum, and mean temperature data were linked to participants' residential address. We utilized distributed lag models, which assessed the lag from the first to the corresponding week, with logistic regression models to examine the exposure-lag-response associations between the 12 weekly extreme temperature exposures and GDM risk. We used the relative risk due to interaction (RERI) to estimate the additive modification of microclimate indicators on the relation between extreme temperature and GDM risk.ResultsGDM risks increased with extreme low temperature during gestational weeks 20--24 and with extreme high temperature at weeks 11-16. Microclimate indicators modified the influence of extreme temperatures on GDM risk. For example, there were positive RERIs for high-temperature extremes and less greenness, and a negative RERI for low-temperature extremes and increased impervious surface percentage.DiscussionSusceptibility windows to extreme temperatures during pregnancy were observed. Modifiable microclimate indicators were identified that may attenuate temperature exposures during these windows, which could in turn reduce the health burden from GDM.

BackgroundLittle research exists regarding the relationships between green space and postpartum depression (PPD). We aimed to investigate the relationships between PPD and green space exposure, and the mediating role of physical activity (PA).MethodsClinical data were obtained from Kaiser Permanente Southern California electronic health records in 2008-2018. PPD ascertainment was based on both diagnostic codes and prescription medications. Maternal residential green space exposures were assessed using street view-based measures and vegetation types (i.e., street tree, low-lying vegetation, and grass), satellite-based measures [i.e., Normalized Difference Vegetation Index (NDVI), land-cover green space, and tree canopy cover], and proximity to the nearest park. Multilevel logistic regression was applied to estimate the association between green space and PPD. A causal mediation analysis was performed to estimate the proportion mediated by PA during pregnancy in the total effects of green space on PPD.FindingsIn total, we included 415,020 participants (30.2 ± 5.8 years) with 43,399 (10.5%) PPD cases. Hispanic mothers accounted for about half of the total population. A reduced risk for PPD was associated with total green space exposure based on street-view measure [500 m buffer, adjusted odds ratio (OR) per interquartile range: 0.98, 95% CI: 0.97-0.99], but not NDVI, land-cover greenness, or proximity to a park. Compared to other types of green space, tree coverage showed stronger protective effects (500 m buffer, OR = 0.98, 95% CI: 0.97-0.99). The proportions of mediation effects attributable to PA during pregnancy ranged from 2.7% to 7.2% across green space indicators.InterpretationStreet view-based green space and tree coverage were associated with a decreased risk of PPD. The observed association was primarily due to increased tree coverage, rather than low-lying vegetation or grass. Increased PA was a plausible pathway linking green space to lower risk for PPD.FundingNational Institute of Environmental Health Sciences (NIEHS; R01ES030353).

BACKGROUND: Significant mortality and morbidity in pregnant women and their offspring are linked to premature rupture of membranes (PROM). Epidemiological evidence for heat-related PROM risk is extremely limited. We investigated associations between acute heatwave exposure and spontaneous PROM. METHODS: We conducted this retrospective cohort study among mothers in Kaiser Permanente Southern California who experienced membrane ruptures during the warm season (May-September) from 2008 to 2018. Twelve definitions of heatwaves with different cut-off percentiles (75th, 90th, 95th, and 98th) and durations (≥ 2, 3, and 4 consecutive days) were developed using the daily maximum heat index, which incorporates both daily maximum temperature and minimum relative humidity in the last gestational week. Cox proportional hazards models were fitted separately for spontaneous PROM, term PROM (TPROM), and preterm PROM (PPROM) with zip codes as the random effect and gestational week as the temporal unit. Effect modification by air pollution (i.e., PM2.5 and NO2), climate adaptation measures (i.e., green space and air conditioning [AC] penetration), sociodemographic factors, and smoking behavior was examined. RESULTS: In total, we included 190,767 subjects with 16,490 (8.6%) spontaneous PROMs. We identified a 9-14% increase in PROM risks associated with less intense heatwaves. Similar patterns as PROM were found for TPROM and PPROM. The heat-related PROM risks were greater among mothers exposed to a higher level of PM2.5 during pregnancy, under 25 years old, with lower education and household income level, and who smoked. Even though climate adaptation factors were not statistically significant effect modifiers, mothers living with lower green space or lower AC penetration were at consistently higher heat-related PROM risks compared to their counterparts. CONCLUSION: Using a rich and high-quality clinical database, we detected harmful heat exposure for spontaneous PROM in preterm and term deliveries. Some subgroups with specific characteristics were more susceptible to heat-related PROM risk.

BackgroundEpidemiological findings are inconsistent regarding the associations between air pollution exposure during pregnancy and gestational diabetes mellitus (GDM). Several limitations exist in previous studies, including potential outcome and exposure misclassification, unassessed confounding, and lack of simultaneous consideration of air pollution mixtures and particulate matter (PM) constituents.ObjectivesTo assess the association between GDM and maternal residential exposure to air pollution, and the joint effect of the mixture of air pollutants and PM constituents.MethodsDetailed clinical data were obtained for 395,927 pregnancies in southern California (2008-2018) from Kaiser Permanente Southern California (KPSC) electronic health records. GDM diagnosis was based on KPSC laboratory tests. Monthly average concentrations of fine particulate matter

BACKGROUND: Recent studies have reported inconsistent associations between maternal residential green space and preterm birth (PTB, born

BackgroundRecent studies have reported inconsistent associations between maternal residential green space and preterm birth (PTB, born

Sandfly vectors transmit Leishmania through egestion of parasites into the host skin. The transmissible dose is shaped by Leishmania development in the sandfly gut, described as a sequential differentiation of promastigote morphotypes. Apart from isolated mammal-infective metacyclic promastigotes, little is known about the transcriptional programs and molecular markers for other stages coinhabiting the midgut in mature infections and cotransmitted by the sandfly bite. Here, we elucidate the single-cell transcriptomic complexity of Leishmania major colonizing its natural vector Phlebotomus duboscqi at early and late infection, providing markers for three transmissible stages. Contrary to prevailing models, our analyses indicate a nonlinear developmental progression, with bifurcation into either replicating early metacyclics or attached and detached haptomonads. We demonstrate that haptomonads constitute a key component of the transmitted inoculum and, along with nondividing late metacyclics, are infectious to and exacerbate the pathology in mice. Our single-cell analysis and validated markers will facilitate further studies on the Leishmania life cycle and its implications for vector-to-host transmission dynamics. [ABSTRACT FROM AUTHOR]

Objective Fetal fibronectin (fFN) testing and transvaginal ultrasound (TVUS) are diagnostic tools used to predict impending spontaneous preterm birth (sPTB) among women presenting with preterm labor (PTL). We evaluated the association between fFN testing or TVUS cervical length (CL) measurement in predicting sPTB, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, and sPTB-related costs. Study Design We conducted a retrospective cohort study using data from the Kaiser Permanente Southern California electronic health system (January 1, 2009–December 31, 2020) using diagnostic and procedure codes, along with a natural language processing algorithm to identify pregnancies with PTL evaluations. PTL evaluation was defined as having fFN and/or TVUS assessment. Outcomes were ascertained using diagnostic, procedural, and diagnosis-related group codes. Multivariable logistic regression assessed the association between fFN and/or TVUS results and perinatal outcomes. Results Compared with those without PTL evaluations, those with positive fFN tests had higher adjusted odds ratio (adj.OR) for sPTB (2.95, 95% confidence interval [CI]: 2.64, 3.29), RDS (2.34, 95% CI: 2.03, 2.69), and NICU admission (2.24, 95% CI: 2.01, 2.50). In contrast, those who tested negative had lower odds for sPTB (adj.OR: 0.75, 95% CI: 0.70, 0.79), RDS (adj.OR: 0.67, 95% CI: 0.61, 0.73), and NICU admission (adj.OR: 0.74, 95% CI: 0.70, 0.79). Among those with positive fFN results, the odds of sPTB was inversely associated with CL. Health care costs for mothers and neonates were lowest for those with fFN testing only. Conclusion This study demonstrates that positive fFN results were associated with an increased odds of sPTB, RDS, and NICU admission and the association with sPTB was inversely proportional to CL. Additionally, negative fFN results were associated with decreased odds of sPTB, RDS, and NICU admissions. fFN testing may predict these and other sPTB-related adverse outcomes hence its utility should be explored further. Moreover, fFN testing has some cost savings over TVUS. Key Points Patients with positive fFN tests had higher odds of sPTB, RDS, and NICU admission. Inverse relationship between sPTB and CL among those with positive fFN tests was observed. Health care costs for mothers and neonates were lowest for those with fFN testing only. [ABSTRACT FROM AUTHOR]

BACKGROUND: Postpartum depression (PPD) has been associated with biological, emotional, social, and environmental factors. However, evidence regarding the effect of temperature on PPD is extremely limited. OBJECTIVES: We aimed to examine the associations between postpartum temperature exposure and PPD. METHODS: We conducted a retrospective cohort study using data from Kaiser Permanente Southern California electronic health records from 1 January 2008 through 31 December 2018. PPD was first assessed using the Edinburgh Postnatal Depression Scale (score =10) during the first year of the postpartum period and further identified by using both diagnostic codes and prescription medications. Historical daily ambient temperatures were obtained from the 4-km resolution gridMET dataset (https://www.climatologylab.org/gridmet.html) and linked to participants’ residential addresses at delivery. Postpartum temperature exposures were measured by calculating various temperature metrics during the period from delivery to PPD diagnosis date. A time-to-event approach with a discrete-time logistic regression was applied to estimate the association between temperature exposure and time to PPD. Effect modification by maternal characteristics and other environmental factors was examined. RESULTS: There were 46,114 (10.73%) PPD cases among 429,839 pregnancies (mean±standard?deviation age =30.22±5.75 y). Increased PPD risks were positively associated with exposure to higher mean temperature [adjusted odds ratio (aOR) per interquartile range increment: 1.07; 95% confidence interval (CI): 1.05, 1.09] and diurnal temperature range (aOR=1.08; 95% CI: 1.06, 1.10); the associations were stronger for maximum temperature compared with minimum temperature. The temperature-related PPD risks were greater among African American, Asian, and Hispanic mothers and among mothers =25 years of age compared with their counterparts. We also observed higher effects of temperature on PPD among mothers exposed to higher air pollution or lower green space levels and among mothers with lower air conditioning penetration rates. CONCLUSION: Maternal exposure to higher temperature and diurnal temperature variability during the postpartum period was associated with an increased risk of PPD. Effect modification by maternal age, race/ethnicity, air pollution, green space, and air conditioning penetration was identified. [ABSTRACT FROM AUTHOR]

Objective Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. Study Design A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. Results During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. Conclusion The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. Key Points Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Estrogen receptor α (ER-α) is a nuclear hormone receptor that controls selected genes, thereby regulating proliferation and differentiation of target tissues, such as breast. Gene expression controlled by ER-α is modulated by Ca2+ via calmodulin (CaM). Here we present the NMR structure of Ca2+-CaM bound to two molecules of ER-α (residues 287-305). The two lobes of CaM bind to the same site on two separate ER-α molecules (residues 292, 296, 299, 302, and 303), which explains why CaM binds two molecules of ER-α in a 1:2 complex and stabilizes ER-α dimerization. Exposed glutamate residues in CaM (Glu-11, Glu-14, Glu-84, and Glu-87) form salt bridges with key lysine residues in ER-α (Lys-299, Lys-302, and Lys-303), which is likely to prevent ubiquitination at these sites and inhibit degradation of ER-α. Transfection of cells with full-length CaM slightly increased the ability of estrogen to enhance transcriptional activation by ER-α of endogenous estrogen-responsive genes. By contrast, expression of either the N- or C-lobe of CaM abrogated estrogen-stimulated transcription of the estrogen responsive genes pS2 and progesterone receptor. These data suggest that CaM-induced dimerization of ER-α is required for estrogen-stimulated transcriptional activation by the receptor. In light of the critical role of ER-α in breast carcinoma, our data suggest that small molecules that selectively disrupt the interaction of ER-α with CaM may be useful in the therapy of breast carcinoma.