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.

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 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.

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.

Firefighting and Cancer: A Meta-analysis of Cohort Studies in the Context of Cancer Hazard Identification.

Objective: We performed a meta-analysis of epidemiological results for the association between occupational exposure as a firefighter and cancer as part of the broader evidence synthesis work of the IARCMonographs program. Methods: A systematic literature search was conducted to identify cohort studies of firefighters followed for cancer incidence and mortality. Studies were evaluated for the influence of key biases on results. Random-effects meta-analysis models were used to estimate the association between ever-employment and duration of employment as a firefighter and risk of 12 selected cancers. The impact of bias was explored in sensitivity analyses. Results: Among the 16 included cancer incidence studies, the estimated meta-rate ratio, 95% confidence interval (CI), and heterogeneity statistic (I2) for ever-employment as a career firefighter compared mostly to general populations were 1.58 (1.14-2.20, 8%) for mesothelioma, 1.16 (1.08-1.26, 0%) for bladder cancer, 1.21 (1.12-1.32, 81%) for prostate cancer, 1.37 (1.03-1.82, 56%) for testicular cancer, 1.19 (1.07-1.32, 37%) for colon cancer, 1.36 (1.15-1.62, 83%) for melanoma, 1.12 (1.01-1.25, 0%) for non-Hodgkin lymphoma, 1.28 (1.02-1.61, 40%) for thyroid cancer, and 1.09 (0.92-1.29, 55%) for kidney cancer. Ever-employment as a firefighter was not positively associated with lung, nervous system, or stomach cancer. Results for mesothelioma and bladder cancer exhibited low heterogeneity and were largely robust across sensitivity analyses. Conclusions: There is epidemiological evidence to support a causal relationship between occupational exposure as a firefighter and certain cancers. Challenges persist in the body of evidence related to the quality of exposure assessment, confounding, and medical surveillance bias.

Early-Life Exposure to Ambient Air Pollution from Multiple Sources and Asthma Incidence in Children: A Nationwide Birth Cohort Study from Denmark.

BACKGROUND: Ambient air pollution exposure has been associated with childhood asthma, but previous studies have primarily focused on prevalence of asthma and asthma-related outcomes and urban traffic-related exposures. OBJECTIVE: We examined nationwide associations between pre- and postnatal exposure to ambient air pollution components and asthma incidence in children age 0-19 y. METHODS: Asthma incidence was identified from hospital admission, emergency room, and outpatient contacts among all live-born singletons born in Denmark between 1998 and 2016. We linked registry data with monthly mean concentrations of particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5) and PM with aerodynamic diameter ≤10µm (PM10), nitrogen dioxide (NO2), nitrogen oxides, elemental carbon, and organic carbon (OC), sulfur dioxide, ozone, sulfate, nitrate, ammonium, secondary organic aerosols, and sea salt. Associations were estimated with Cox proportional hazard models using fixed prenatal exposure means and time-varying postnatal exposures. RESULTS: Of the 1,060,154 children included, 6.1% had asthma during the mean follow-up period of 8.8 y. The risk of asthma increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. We also observed increased risk after restriction to asthma after age 4 y, after additional adjustment for area-specific socioeconomic status, and for postnatal exposure to most pollutants. The hazard ratio (HR) associated with an interquartile range increase of 2.4 and 8.7 µg/m3 in prenatal exposure was 1.06 [95% confidence interval (CI): 1.04, 1.08] for PM2.5 and 1.04 (95% CI: 1.02, 1.05) for NO2, respectively. This association with PM2.5 was stable after adjustment for NO2, whereas it attenuated for NO2 to 1.01 (95% CI: 0.99, 1.03) after adjustment for PM2.5. For a 0.5-µg/m3 increase in prenatal OC exposure, for which biomass is an important source, the HR was 1.08 (95% CI: 1.06, 1.10), irrespective of adjustment for PM2.5. DISCUSSION: These findings suggest that early-life exposure to ambient air pollution from multiple sources contributes to asthma development. https://doi.org/10.1289/EHP11539.

Prenatal exposure to tap water containing nitrate and the risk of small-for-gestational-age: A nationwide register-based study of Danish births, 1991-2015.

BACKGROUND: Prenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. METHODS: We linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991-2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. RESULTS: In the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2-5 mg/L) (OR = 1.04, 95% CI: 1.03-1.06) and third category (>5-25 mg/L) (OR = 1.02, 95% CI: 1.00-1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01-1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). CONCLUSIONS: Our findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA.

Prenatal exposure to nitrate from drinking water and the risk of preterm birth: A Danish nationwide cohort study.

Evidence is emerging that preterm birth (PTB, birth before 37 completed weeks of gestation), a risk factor for neonatal mortality and future morbidity, may be induced by maternal nitrate ( N O 3 - ) exposure from drinking water. The objective of this study is to assess the association between maternal exposure to nitrate and the risk of PTB in a nationwide study of liveborn singletons. Methods: We estimated maternal nitrate exposure from household tap water for 1,055,584 births in Denmark to Danish-born parents during 1991-2015 by linkage of individual home address(es) with nitrate concentrations from a national monitoring database. Nitrate exposure during pregnancy was modeled using four categories and continuously. Logistic models adjusted for sex, birth year, birth order, urbanicity, and maternal age, smoking, education, income, and employment, with generalized estimating equations were used to account for sibling clusters. Results: A total of 1,009,189 births were included, comprising 51,747 PTB. An increase in the risk of PTB was seen across categories of exposure (P < 0.001) with an odds ratio (OR) in the uppermost category (>25 mg/L nitrate) of 1.05 (95% confidence interval [CI] = 1.00, 1.10). Evidence of an exposure-response relationship was observed in models using continuous nitrate (OR = 1.01 [95% CI = 1.00, 1.03] per 10 mg/L nitrate). In sensitivity analyses, results were robust to the addition of variables for short inter-pregnancy interval (<1 year between births), maternal pre-pregnancy body mass index, paternal socioeconomic status and age, season of birth, and inclusion of post-term births. Results were virtually unchanged when the analysis was restricted to women exposed to less than the current European Union standard of 50 mg/L. Conclusion: We observed an increasing risk of PTB with increases in nitrate in household tap water. These findings add to a growing body of evidence of adverse effects from nitrate in drinking water at levels below current regulatory levels.

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).

Prenatal nitrate exposure from diet and drinking water and timing of puberty in sons and daughters: A nationwide cohort study.

BACKGROUND: In Western countries, age at pubertal development has declined during the last century in girls, and probably also in boys. No studies have investigated whether nitrate, a widespread environmental exposure with teratogenic and hormone disrupting properties, might affect timing of puberty. OBJECTIVES: We investigated if prenatal exposure to nitrate from drinking water and diet was associated with timing of puberty. METHODS: This cohort study included 15,819 children born from 2000 to 2003 within the Danish National Birth Cohort. Self-reported information on current status of various pubertal milestones was provided every six months by a questionnaire from 11 years of age until 18 years or full maturity, whichever came first. Maternal nitrate intake from diet (mg/day) was derived from a mid-pregnancy food frequency questionnaire and individual level nitrate exposure from drinking water (mg/L) was derived using measurements from Danish public waterworks. Adjusted average differences in months in age at attaining several pubertal milestones as well as the average age difference in age at attaining all the milestones were estimated separately for diet and water using a regression model for interval-censored data. C- and E-vitamin, red meat and processed meat intake were explored as potential effect modifiers in sub-analyses. RESULTS: No strong associations were observed between prenatal exposure to nitrate and timing of puberty in children. However, sons born of mothers with a nitrate concentration in drinking water at their residential address of > 25 mg/L (half of the World Health Organisation (WHO) guideline value) compared with ≤ 1 mg/L showed a tendency towards earlier age at pubertal development with an average age difference of -1.2 months (95 % confidence interval,-3.0;0.6) for all the pubertal milestones combined. DISCUSSION: Studies including more highly exposed children are needed before the current WHO drinking water guideline value for nitrate can be considered safe concerning pubertal development.

Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997-2017.

BACKGROUND: Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth. METHODS: We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L. RESULTS: Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15-2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08-8.94)]. CONCLUSIONS: The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.

Exposure to nitrate from drinking water and the risk of childhood cancer in Denmark.

BACKGROUND: There is limited evidence that nitrate, a common contaminant in drinking water, increases the risk of childhood cancers. Our objective was to examine this association in Denmark. METHODS: We conducted a nationwide case-control study based on all singletons liveborn to Danish-born parents from 1991 to 2015 (N = 1,219,140) that included 596 leukemias, 180 lymphomas, and 310 central nervous system cancers (CNC) who were ≤15 years of age at diagnosis and were identified from the Danish Cancer Registry. Approximately 100 controls were randomly selected and matched to each case on date of birth and sex. Nitrate measurements in public water systems were linked with an address registry to estimate individual average nitrate concentrations during preconception, prenatal, and postnatal periods. Odd ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression controlling for the matching variables, and birth order, birthweight, urbanicity, maternal education, employment, income and smoking, and parental age. RESULTS: There was no evidence of an association of nitrate with leukemia or lymphoma. An association between CNC and the highest category of nitrate exposure (>25 mg/L nitrate) was observed for preconception (OR = 1.82, 95%CI:1.09 to 3.04), prenatal (OR = 1.65, 95%CI:0.97 to 2.81), and postnatal exposure (OR = 1.48, 95%CI:0.82 to 2.68) in fully adjusted models. There was also some evidence of an exposure-response in models of continuous nitrate exposure and CNC. CONCLUSIONS: Our findings provide some evidence that exposure to nitrate from drinking water may increase the risk of childhood CNC cancer, but not leukemia or lymphoma.

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.

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children.

BACKGROUND: High levels of nitrate (NO3-) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent. OBJECTIVES: We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term (≥37 wk gestation) live-born singletons. METHODS: We estimated maternal nitrate exposure for 898,206 births in Denmark during 1991-2011 by linkage of individual home address(es) with nitrate data from the national monitoring database. Maternal address during pregnancy, infant size at birth [i.e., birth weight, low birth weight (LBW), body length, and birth head circumference] and covariates were compiled from the Danish Civil Registration System, the Danish Medical Birth Register, and The Integrated Database for Longitudinal Labor Market Research. Linear and logistic models with generalized estimating equations were used to account for multiple births to an individual. Nitrate exposure was modeled using five categories and as a log-transformed continuous variable. RESULTS: There was evidence of a decreasing trend in models for term birth weight using categorical or continuous measures of exposure. Modeling exposure continuously, a difference of -9.71 g (95% confidence interval: -14.60, -4.81) was predicted at 25 mg/L (half the value of the European Union drinking water standard) compared with 0 mg/L NO3-. Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO3- and head circumference or LBW. DISCUSSION: Although the estimated effects were small, our findings for live singleton births to Danish-born parents suggest that maternal intake of nitrate from drinking water may reduce term birth weight and length, which are markers of intrauterine growth. However, there was little evidence for an association between nitrate and head circumference or LBW. Future studies in other populations and with data on dietary sources of nitrate are encouraged to confirm or refute these findings. https://doi.org/10.1289/EHP7331.

Night work and incidence of Parkinson's disease in the Danish Nurse Cohort.

OBJECTIVES: Evidence on the association between night work and Parkinson's disease (PD) is sparse and conflicting, calling for more definitive studies. METHODS: We included 20 138 female nurses from the Danish Nurse Cohort without PD who at baseline in 1993 and/or 1999 reported their most common current work schedule (day, evening, night, and rotating (a combination of at least two of these)), including information on lifetime cumulative duration (years) of each shift in a 2009 follow-up survey. We obtained information on PD hospital contacts and PD medication until November 2018 via linkage to the Danish National Patient (inpatient from 1977 and outpatient contacts from 1995 onwards) and Prescription Registers starting in 1995. We defined the incidence of PD as the first-ever hospital contact due to PD, or the first-ever redeemed levodopa prescription, whichever came first. We used Cox regression models to calculate HRs and 95% CIs, adjusting for age, smoking status, coffee consumption and use of hormone replacement therapy. RESULTS: We found no significant difference in PD risk among nurses who reported working evening (HR=0.86; 95% CI=0.55 to 1.34), night (HR=1.26; 95% CI=0.79 to 2.02) or rotating shifts (HR=0.83; 95% CI=0.56 to 1.21) at cohort baseline in 1993 or 1999, when compared with permanent day workers. Similarly, persistency of shift work (working the same work schedule for 6+ years) or duration of shift work was not associated with PD risk. CONCLUSIONS: Overall, there was little evidence for an association between various shift work schedules including night work and PD in this cohort of middle-aged female nurses.

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.

Residential proximity to agriculture and risk of childhood leukemia and central nervous system tumors in the Danish national birth cohort.

BACKGROUND: Living in an agricultural area or on farms has been associated with increased risk of childhood cancer but few studies have evaluated specific agricultural exposures. We prospectively examined residential proximity to crops and animals during pregnancy and risk of childhood leukemia and central nervous system (CNS) tumors in Denmark. METHODS: The Danish National Birth Cohort (DNBC) consists of 91,769 pregnant women (96,841 live-born children) enrolled in 1996-2003. For 61 childhood leukemias and 59 CNS tumors <15 years of age that were diagnosed through 2014 and a ~10% random sample of the live births (N = 9394) with geocoded addresses, we linked pregnancy addresses to crop fields and animal farm locations and estimated the crop area (hectares [ha]) and number of animals (standardized by their nitrogen emissions) by type within 250 meters (m), 500 m, 1000 m, and 2000 m of the home. We also estimated pesticide applications (grams, active ingredient) based on annual sales data for nine herbicides and one fungicide that were estimated to have been applied to >30% of the area of one or more crop. We used Cox proportional hazard models (weighted to the full cohort) to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of childhood leukemia and CNS tumors with crop area, animals, and pesticide applications adjusted for gender and maternal age. RESULTS: Sixty-three percent of mothers had crops within 500 m of their homes during pregnancy; winter and spring cereals were the major crop types. Compared to mothers with no crops <500 m, we found increasing risk of childhood leukemia among offspring of mothers with increasing crop area near their home (highest tertile >24 ha HR: 2.0, CI:1.02-3.8), which was stronger after adjustment for animals (within 1000 m) (HR: 2.6, CI:1.02-6.8). We also observed increased risk for grass/clover (highest tertile >1.1 ha HR: 3.1, CI:1.2-7.7), peas (>0 HR: 2.4, CI: 1.02-5.4), and maize (>0 HR: 2.8, CI: 1.1-6.9) in animal-adjusted models. We found no association between number of animals near homes and leukemia risk. Crops, total number of animals, and hogs within 500 m of the home were not associated with CNS tumors but we observed an increased risk with >median cattle compared with no animals in crop-adjusted models (HR = 2.2, CI: 1.02-4.9). In models adjusted for total animals, the highest tertiles of use of three herbicides and one fungicide were associated with elevated risk of leukemia but no associations were statistically significant; there were no associations with CNS tumors. CONCLUSIONS: Risk of childhood leukemia was associated with higher crop area near mothers' homes during pregnancy; CNS tumors were associated with higher cattle density. Quantitative estimates of crop pesticides and other agricultural exposures are needed to clarify possible reasons for these increased risks.