Ambient air pollution and hypertensive disorders of pregnancy in Rome.

BACKGROUND: Ambient air pollution has been associated with hypertensive disorders of pregnancy (HDP), but few studies rely on assessment of fine-scale variation in air quality, specific subtypes and multi-pollutant exposures. AIM: To study the impact of long-term exposure to individual and mixture of air pollutants on all and specific subtypes of HDP. METHODS: We obtained data from 130,470 liveborn singleton pregnacies in Rome during 2014-2019. Spatiotemporal land-use random-forest models at 1 km spatial resolution assigned to the maternal residential addresses were used to estimate the exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3). RESULTS: For PM2.5, PM10 and NO2, there was suggestive evidence of increased risk of preeclampsia (PE, n = 442), but no evidence of increased risk for all subtypes of HDP (n = 2297) and gestational hypertension (GH, n = 1901). For instance, an interquartile range of 7.0 µg/m3 increase in PM2.5 exposure during the first trimester of pregnancy was associated with an odds ratio (OR) of 1.06 (95% confidence interval: 0.81, 1.39) and 1.04 (0.92, 1.17) after adjustment for NO2 and the corresponding results for a 15.7 µg/m3 increase in NO2 after adjustment for PM2.5 were 1.11 (0.92, 1.34) for PE and 0.83 (0.76, 0.90) for HDP. Increased risks for HDP and GH were suggested for O3 in single-pollutant models and for PM after adjustment for NO2, but all other associations were stable or attenuated in two-pollutant models. CONCLUSIONS: The results of our study suggest that PM2.5, PM10 and NO2 increases the risk of PE and that these effects are robust to adjustment for O3 while the increased risks for GH and HDP suggested for O3 attenuated after adjustment for PM or NO2. Additional studies are needed to evaluate the effects of source-specific component of PM on subtypes as well as all types of HDP which would help to target preventive actions.

Shift work and incidence of dementia: A Danish Nurse Cohort study.

INTRODUCTION: A few studies suggest that working night and rotating shifts increase the risk of dementia. We examined the association between shift work and the incidence of dementia in a cohort of female Danish nurses. METHODS: We linked Danish Nurse Cohort participants, who reported work schedules (day, evening, night, rotating shifts) in 1993 and/or 1999 and their duration in 2009, to Danish registers to obtain information on dementia hospitalizations and prescription medication until November 2018. RESULTS: Among 6048 nurses who reported work schedules in 1993 and 1999, nurses working night shifts ≥6 years had higher dementia incidence (hazard ratio: 2.43, 95% confidence interval: 1.39 to 4.23) than those working day shifts ≥6 years. Among 8059 nurses who reported shift work duration, nurses working night shifts ≥6 years had higher dementia incidence than those working night shifts <1 year (1.47, 1.06 to 2.06). DISCUSSION: Persistent night shift work may increase the risk of dementia.

Nitrosatable drug exposure during pregnancy and risk of stillbirth.

PURPOSE: Nitrosatable drugs can react with nitrite in the stomach and form N-nitroso compounds. Exposure to nitrosatable drugs has been associated with congenital malformations and preterm birth, but use during pregnancy as a cause of fetal death is not well-known. We examined if prenatally nitrosatable drug use is associated with risk of stillbirth. METHODS: A nationwide cohort was conducted using 554 844 women with singleton and first recorded pregnancies regardless of previous pregnancy history from the Danish Medical Birth Register from 1996 to 2015. Exposure was recorded by use of the Danish National Prescription Register and defined as women who had redeemed a prescribed nitrosatable drug in the first 22 weeks of pregnancy. The reference group was women with no redeemed prescribed nitrosatable drug in this time period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for stillbirth. RESULTS: Among the 84 720 exposed women, 348 had a stillbirth compared with 1690 stillbirths among the 470 124 unexposed women. Women who used any prescribed nitrosatable drug were more likely to have a stillbirth compared with unexposed women (aHRs 1.24; 95% CI, 1.03-1.49). CONCLUSION: Nitrosatable drug use during the first 22 weeks of pregnancy might increase risk of stillbirth. The findings should be interpreted cautiously because of important unmeasured factors that might influence the observed association, including maternal vitamin C intake, dietary, and other sources of nitrate/nitrite intake.

Coffee Drinking and the Risk of Endometrial Cancer: An Updated Meta-Analysis of Observational Studies.

BACKGROUND: Several compounds contained in coffee have been found to suppress carcinogenesis in experimental studies. We conducted a dose-response meta-analysis to assess the impact of coffee consumption on the risk of endometrial cancer. MATERIALS AND METHODS: We searched MEDLINE and EMBASE databases for studies published up to August 2016. Using random effects models, we estimated summary relative risks (RR) for cohort studies and odds ratios (OR) for case-control studies with 95% confidence intervals (CI). Dose-response analyses were conducted by using generalized least square trend estimation. RESULTS: We identified 12 cohort studies and 8 case-control studies eligible for inclusion, contributing with 11,663 and 2,746 endometrial cancer cases, respectively. The summary RR for highest compared with lowest coffee intake was 0.74 (95% CI: 0.68-0.81; pheterogeneity = 0.09, I2 = 32%). The corresponding summary RR among cohort studies was 0.78 (95% CI: 0.71-0.85; pheterogeneity = 0.14, I2 = 31.9%) and 0.63 (95% CI: 0.53-0.76; pheterogeneity = 0.57, I2 = 0%) for case-control studies. One-cup increment per day was associated with 3% risk reduction (95% CI: 2-4%) in cohort studies and 12% (95% CI: 5-18%) in case-control studies. After pooling the results from 5 cohort studies, the association remained significant only in women with body mass index over 30 (RR = 0.71, 95% CI: 0.61-0.81). CONCLUSION: The results from our meta-analysis strengthen the evidence of a protective effect of coffee consumption on the risk of EC and further suggest that increased coffee intake might be particularly beneficial for women with obesity.

Atrazine and nitrate in drinking water and the risk of preterm delivery and low birth weight in four Midwestern states.

BACKGROUND: Atrazine and nitrate are common contaminants in water, and there is limited evidence that they are associated with adverse birth outcomes. The objective of this study was to examine whether atrazine and nitrate in water are associated with an increased risk of preterm delivery (PTD) and term low birth weight (LBW). METHODS: The study included a total of 134,258 singletons births born between January 1, 2004 and December 31, 2008 from 46 counties in four Midwestern states with public water systems that were included in the U.S. Environmental Protection Agency (EPA)'s atrazine monitoring program (AMP). Counties with a population of >300,000 were eliminated from the analyses in order to avoid confounding by urbanicity. Monthly child's sex, race and Hispanic ethnicity specific data were obtained from the states for estimating rates of PTD (<37 weeks) and very preterm (VPTD, <32 weeks), term LBW (<2.5kg among infants born at term) and very low birth weight (VLBW, <1.5kg). The rates were linked with county specific monthly estimates of the concentration of atrazine and nitrate in finished water. Multivariable negative binomial models were fitted to examine the association between the exposures and the adverse birth outcomes. Models were fitted with varying restrictions on the percentage of private well usage in the counties in order to limit the degree of exposure misclassification. RESULTS: Estimated water concentrations of atrazine (mean=0.42 ppb) and nitrate (mean=0.95ppm) were generally low. Neither contaminant was associated with an increased risk of term LBW. Atrazine exposure was associated with a significant increased rate of PTD when well use was restricted to 10% and the exposure was averaged over 4-6 months prior to birth (Rate Ratio for 1ppm increase [RR1ppm]=1.08, 95%CI=1.05,1.11) or over 9 months prior to birth (RR1ppm=1.10, 95%CI=1.01,1.20). Atrazine exposure was also associated with an increased rate of VPTD when when well use was restricted to 10% and the exposure was averaged over 7-9 months prior to birth (RR1ppm=1.19, 95%CI=1.04,1.36). Exposure to nitrate was significantly associated with an increased rate of VPTD (RR1ppm=1.08, 95%CI=1.02,1.15) and VLBW (RR1ppm=1.17, 95%CI=1.08,1.25) when well use was restricted to 20% and the exposure was averaged over 9 months prior to birth. CONCLUSION: The positive and negative findings from our study need to be interpreted cautiously given its ecologic design, and limitations in the data for the exposures and other risk factors. Nonetheless, our findings do raise concerns about the potential adverse effects of these common water contaminants on human development and health, and the adequacy of current regulatory standards. Further studies of these issues are needed with individual level outcome data and more refined estimates of exposure.

Maternal use of nitrosatable drugs during pregnancy and adult male reproductive health: A population-based cohort study.

BACKGROUND: Prenatal exposures to xenobiotics during the masculinization programming window are suggested to impact male fecundity later in life. Frequently used nitrosatable drugs, such as penicillins and beta2-agonists, contain amines or amides that may form teratogenic compounds in reaction with nitrite. OBJECTIVES: We explored whether maternal nitrosatable drug use during gestation was associated with biomarkers of male fecundity in adulthood; moreover, the potential modifiable effect of nitrate and vitamin intake was investigated. METHOD: We performed a cohort study in the Fetal Programming of Semen Quality cohort that includes semen characteristics, reproductive hormone concentrations, and measures of testis size on 1058 young adult sons in the Danish National Birth Cohort. Information on maternal use of nitrosatable drugs was obtained from questionnaires and interviews around gestational weeks 11 and 16. A multivariable negative binomial regression model was used to obtain relative differences in biomarkers of male fecundity for those whose mothers used nitrosatable drugs compared to those without such maternal use. In sub-analyses, the exposure was categorized according to nitrosatable drug type: secondary amine, tertiary amine, or amide. We investigated dose dependency by examining the number of weeks with intake and explored potential effect modification by low versus high maternal nitrate and vitamin intake from diet and nitrate concentration in drinking water. We added selection weights and imputed values of missing covariates to limit the risk of selection bias. RESULTS: In total, 19.6% of the study population were born of mothers with an intake of nitrosatable drugs at least once during early pregnancy. Relative differences in biomarkers related to male fecundity between exposed and unexposed participants were negligible. Imputation of missing covariates did not fundamentally alter the results. Furthermore, no sensitive subpopulations were detected. CONCLUSIONS: The results suggest that maternal use of nitrosatable drugs does not have a harmful influence on the male fecundity of the offspring.

Prenatal Exposure to Nitrate in Drinking Water and Adverse Health Outcomes in the Offspring: a Review of Current Epidemiological Research.

PURPOSE OF REVIEW: Recently, several epidemiological studies have investigated whether prenatal exposure to nitrate from drinking water may be harmful to the fetus, even at nitrate levels below the current World Health Organization drinking water standard. The purpose of this review was to give an overview of the newest knowledge on potential health effects of prenatal exposure to nitrate. RECENT FINDINGS: We included 13 epidemiological studies conducted since 2017. Nine studies investigated outcomes appearing around birth, and four studies investigated health outcomes appearing in childhood and young adulthood. The reviewed studies showed some indications of higher risk of preterm delivery, lower birth weight, birth defects, and childhood cancer related to prenatal exposure to nitrate. However, the numbers of studies for each outcome were sparse, and some of the results were conflicting. We suggest that there is a need for additional studies and particularly for studies that include information on water consumption patterns, intake of nitrate from diet, and intake of nitrosatable drugs.

Prenatal exposure to nitrosatable drugs and timing of puberty in sons and daughters: A nationwide cohort study.

BACKGROUND: N-nitroso compounds (NOCs) can be formed by endogenous reactions between nitrosatable drugs and nitrite. Animal studies have found that several NOCs are teratogenic, and epidemiological studies report associations between prenatal exposure to nitrosatable drugs and adverse birth outcomes. It is unknown whether prenatal exposure to nitrosatable drugs is harmful to the child's reproductive health, including pubertal development. OBJECTIVES: We investigated whether prenatal exposure to nitrosatable drugs was associated with timing of puberty and whether nitrate, nitrite and antioxidant intake modified any association. METHODS: The population-based Danish National Birth Cohort (DNBC) Puberty Cohort, which includes 15,819 children, was used to investigate the association between prenatal exposure to nitrosatable drugs and timing of puberty. Around gestational week 11 and gestational week 18, mothers provided information about drug use during pregnancy. The children's self-reported information on onset of pubertal milestones was collected every six months from 11 years of age and throughout puberty. To investigate potential effect modification by nitrite, nitrate and antioxidant intake, information on these factors was obtained from a food frequency questionnaire completed by the mothers in gestational week 25, and information on nitrate concentration in maternal drinking water at her residential address was obtained from monitoring data from public waterworks. Data were analysed using a multivariable regression model for interval-censored data estimating difference in months in timing of puberty between exposure groups. RESULTS: A total of 2,715 children were prenatally exposed to nitrosatable drugs. We did not find an association between prenatal exposure to nitrosatable drugs and timing of puberty. This finding was supported by null-findings in the following sub-analyses investigating: 1. subtypes of nitrosatable drugs (secondary and tertiary amines and amides), 2. dose-dependency (duration of drug intake), 3. effect modification by maternal intake of nitrate, nitrite, and antioxidants. 4. confounding by indication. CONCLUSIONS: Prenatal exposure to nitrosatable drugs was not associated with timing of puberty. Nitrosatable drugs are commonly used drugs in pregnancy, and further research is needed to allow firm conclusions on the potential effect of prenatal exposure to nitrosatable drugs on the child's reproductive health.

Nitrate in drinking water and risk of birth defects: Findings from a cohort study of over one million births in Denmark.

BACKGROUND: A few studies have reported an increased risk of birth defects (BD) with maternal exposure to nitrate in drinking water. We examined this association in a large cohort study with well-characterized exposure. METHODS: Danish singletons liveborn to Danish-born parents from 1991-2013 were identified using civil and patient registries (n=1,018,914). Exposure to nitrate was estimated using a spatial model based on national data linked with individual addresses. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. FINDINGS: In total, 33,182 cases of BD were identified. Nitrate concentrations were generally well below US and EU standards. We observed an exposure-response relationship (p=0·004) between nitrate during pregnancy and eye BD, and increased risk in the highest exposure group (≥25 mg/L nitrate) (OR: 1·29; 95% CI: 1·00, 1·66). An interaction was observed between maternal age and continuous nitrate exposure for nervous system BD (p<0·001) indicating an increased risk among mothers <25 years-of-age (OR for 10 mg/L (OR10): 1·20; 95% CI: 1·06, 1·35). An interaction (p<0.01) with maternal age and continuous nitrate exposure was also observed for ear, face, and neck BD indicating an increased risk among babies born to mothers <25 years-of-age (OR10: 1·35; 95% CI: 1·11, 1·66). There was evidence of an inverse exposure-response relationship for any, digestive system, female genital, and urinary BD. INTERPRETATION: Our study is the first to report an association between nitrate and eye BD and BD of the ear, face, and neck. It also provides support to prior reports of increased risk of nervous system BD. FUNDING: This study was supported by a grant from the United States National Institute of Environmental Health Sciences (R01 ES027823-01A1).

Shift work and incidence of psychiatric disorders: The Danish Nurse Cohort study.

BACKGROUND: Research on health effects of shift work has especially focused on somatic diseases, such as breast cancer and cardiometabolic disease, while less attention has been given to the association between shift work and mental health. METHODS: We used information on 19 964 female nurses (≥44 years) from the Danish Nurse Cohort, who reported current work schedule (day, evening, night, or rotating) at recruitment (1993/1999). In 5102 nurses who participated in both cohort waves, we defined persistent night shift work as working night shift in 1993 and 1999. We used Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for relevant confounders. Through linkage of cohort participants to national registers, we defined incidence of mood and neurotic disorders as first hospital contact or redeemed prescription until November 2018. RESULTS: We found association between night shift work with mood disorders (HR = 1.31; 95%CI = 1.17-1.47) and neurotic disorders (1.29; 1.17-1.42), compared to day work. Associations were enhanced in nurses with persistent night shift work (1.85; 1.43-2.39 and 1.62; 1.26-2.09 for mood and neurotic disorders, respectively) and in nurses with specialist confirmed mood (1.69; 1.24-2.29) and neurotic (1.72; 1.22-2.44) disorders. Nurses with preexisting psychiatric disorders and full-time work seemed most susceptible. CONCLUSIONS: Night shift work is associated with increased risk of major psychiatric disorders. The novel suggestive findings of vulnerable groups, including nurses with a history of psychiatric disorders and full-time workers, are based on a limited number of cases, and further research is needed to confirm the results.

Occupational mercury exposure in association with prevalence of multiple sclerosis and tremor among US dentists.

BACKGROUND: The effects of chronic occupational exposure to elemental mercury (Hg(0)) are largely unknown. The objective was to evaluate the association of occupational Hg(0) exposure with multiple sclerosis (MS) and tremor. METHODS: The study included 13,906 dentists who attended the American Dental Association's annual meeting over 24 years (1986-2007 and 2011-2012). Participants reported MS and tremor and provided urine specimens for Hg(0) analysis. The authors estimated mean Hg(0) exposures over time and used logistic regression to estimate the associations of 3 Hg(0) exposure measures with MS or tremor. RESULTS: Among participants, 0.18% reported MS and 1.24% reported tremor. Hg(0) exposure was not associated with MS (odds ratio [OR] per 191 micrograms per liter in cumulative Hg(0) exposure, 0.85; 95% confidence interval [CI], 0.39-1.85). Increased prevalent risk of tremor was found with exposure to both urinary Hg(0) exposure (OR, 1.10 [95% CI, 1.00-1.22]) and cumulative Hg(0) exposure among younger dentists (< 51 years; OR, 1.13 [95% CI, 1.05-1.22]). CONCLUSIONS: Occupational Hg(0) exposure in US dentists decreased over time and now is approaching that of the general population. Our results suggest a positive association between Hg(0) exposure and tremor. PRACTICAL IMPLICATIONS: Studies with more sophisticated outcome and exposure measures, and including more retired dentists, would provide critical information toward understanding the relation of Hg(0) exposures to MS and tremor risk.

Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes.

BACKGROUND: Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk. OBJECTIVE: We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes. METHODS: MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother-child cohort in Crete, Greece, in 2007-2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression. RESULTS: BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 µg/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 µg/L=1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 µg/L=1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 µg/week=3.14; 95% CI: 1.16, 8.50). CONCLUSIONS: These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes.