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.

Assessing Residential Exposure to Microbes from Industrial Hog Operations in Rural North Carolina: Methods and Lessons Learned.

BACKGROUND: Recent advances in molecular source tracking make answering questions from residents regarding their exposure to microbial contaminants from industrial hog operations (IHOs) possible. Associations between residential distance to IHOs and exposure can be addressed by measuring livestock-associated (Staphylococcus aureus) and pig-specific bacteria in the air, on household surfaces, and in participants' nasal and saliva swabs. OBJECTIVES: Here we assess the mechanics, feasibility, capacity-building, and lessons learned during a pilot study employing this novel technology in community-based participatory research of bacterial exposure and human health. METHODS: Together, our team of academics and community members designed a field- and laboratory-based pilot study. Air samples, surface and human swabs, and questionnaires from households at varying distances from IHOs were collected. Data were assessed for completeness and quality by two independent reviewers. These metrics were defined as: missingness (completeness), incorrect data type (validity), out of range (validity), and outliers (accuracy). LESSONS LEARNED: While critical field equipment was obtained, and knowledge exchange occurred, leading to an increased capacity for future work, after review, 38 of 49 households were deemed eligible for inclusion in the study. Of eligible participants, 98% of required electronic survey questions were complete and 100% were valid; an improvement over prior work which employed paper surveys. While all human microbial and air samples were collected from eligible households (n = 231), (5%) of environmental swabs were reported missing. CONCLUSIONS: Using community-appropriate sampling protocols, a pilot study of residential exposure to bacteria from IHOs was completed. While high-quality data was collected from those eligible, we learned the necessity of early and continual data review.

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).

Personal protective equipment use during industrial hog operation work activities and acute lung function changes in a prospective worker cohort, North Carolina 2014-2015.

INTRODUCTION: Occupational activities related to industrial hog operation (IHO) worker lung function are not well defined. Therefore, we aimed to identify IHO work activities associated with diminished respiratory function and the effectiveness, if any, of personal protective equipment (PPE) use on IHOs. METHODS: From 2014 to 2015, 103 IHO workers were enrolled and followed for 16 weeks. At each biweekly visit, work activities and PPE use were self-reported via questionnaire and lung function measurements were collected via spirometry. Generalized linear and linear fixed-effects models were fitted to cross-sectional and longitudinal data. RESULTS: Increasing years worked on an IHO were associated with diminished lung function, but baseline and longitudinal work activities were largely inconsistent in direction and magnitude. Unexpectedly, a -0.3 L (95% confidence interval: -0.6, -0.04) difference in forced expiratory volume in the first second (FEV1 ) was estimated when workers wore PPE consistently (≥80% of the time at work) versus those weeks they did not. In post-hoc analyses, we found that coveralls and facemasks were worn less consistently when workers experienced worse barn conditions and had more contact with pigs, but coveralls were worn more consistently as cleaning activities increased. CONCLUSIONS: Similar to past studies, baseline estimates were likely obscured by healthy worker effect bias, but showed decrements in worker lung function as years of work increased. A challenge to disentangling the effect of work activities on lung function was the discovery that IHO workers used PPE differently according to the work task. These data suggest that interventions may be targeted toward improving barn conditions so that workers can consistently utilize IHO-provided PPE.

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.

Self-reported work activities, eye, nose, and throat symptoms, and respiratory health outcomes among an industrial hog operation worker cohort, North Carolina, USA.

INTRODUCTION: Respiratory disease among industrial hog operation (IHO) workers is well documented; however, it remains unclear whether specific work activities are more harmful and if personal protective equipment (PPE), as used by workers, can reduce adverse health outcomes. METHODS: IHO workers (n = 103) completed baseline and up to eight bi-weekly study visits. Workers reported typical (baseline) and transient (bi-weekly) work activities, PPE use, and physical health symptoms. Baseline and longitudinal associations were assessed using generalized logistic and fixed-effects logistic regression models, respectively. RESULTS: At baseline, reports of ever versus never drawing pig blood, applying pesticides, and increasing years worked at any IHO were positively associated with reports of eye, nose, and/or throat irritation. Over time, transient exposures, associated with dustiness in barns, cleaning of barns, and pig contact were associated with increased odds of sneezing, headache, and eye or nose irritation, particularly in the highest categories of exposure. When PPE was used, workers had lower odds of symptoms interfering with sleep (odds ratio [OR]: 0.1; 95% confidence interval [CI]: 0.01-0.8), and eye or nose irritation (OR: 0.1; 95% CI: 0.02-0.9). Similarly, when they washed their hands eight times or more per shift (median frequency) versus less frequently, the odds of any respiratory symptom were reduced (OR: 0.3; 95% CI: 0.1-0.8). CONCLUSIONS: In this healthy volunteer worker population, increasingly unfavorable IHO activities were associated with self-reported eye, nose, throat, and respiratory health symptoms. Strong protective associations were seen between PPE use and handwashing and the odds of symptoms, warranting further investigation.

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.

The use of personal protective equipment during common industrial hog operation work activities and acute lung function changes in a prospective worker cohort, North Carolina, USA.

INTRODUCTION: As occupational activities related to acute industrial hog operation (IHO) worker lung function are not well defined, we aimed to identify IHO work activities associated with diminished respiratory function and the effectiveness, if any, of personal protective equipment (PPE) on IHOs. METHODS: From 2014-2015, 103 IHO workers were enrolled and followed for 16 weeks. At each bi-weekly visit, lung function measurements were collected via spirometry and work activities and PPE use were self-reported via questionnaire. Generalized linear and linear fixed-effects models were fitted to cross-sectional and longitudinal data. RESULTS: At baseline, increasing years worked on an IHO were associated with diminished lung function, but other activities were less consistent in direction and magnitude. In longitudinal models, only reports of working in feeding/finisher barns, showed a consistent association. However, a -0.3 L (95% confidence interval: -0.6, -0.04) difference in FEV 1 was estimated when workers wore PPE consistently versus those weeks they did not. In post-hoc analyses, we found that coveralls and facemasks were worn less consistently when workers experienced worse barn conditions and had more contact with pigs, but coveralls were worn more consistently as cleaning activities increased. CONCLUSIONS: Similar to past studies, baseline estimates were likely obscured by healthy worker bias. Also making it challenging to disentangle the effect of work activities on lung function was the discovery that IHO workers used PPE differently according to work task. These data suggest that interventions may be targeted toward improving barn conditions so that workers can consistently utilize IHO-provided PPE. KEY MESSAGES: What is already known about this subject?: Working on industrial hog operations may be deleterious to long- and short-term respiratory health due to airborne bacteria, endotoxin, hazardous gases, dust, and dander in barns. In efficacy studies PPE has been shown to be protective, but studies have shown that PPE utilization among hog workers has historically been sub-optimal.What are the new findings?: As barn conditions worsened and contact with pigs increased, workers in this cohort reported wearing coveralls and face masks less often; however, they reported increased PPE use as they conducted more cleaning activities at work. During weeks when workers wore PPE their lung function declined, a possible cause being the improper use of the equipment leading to a false sense of protection or re-exposure to hazardous contaminants.How might this impact on policy or clinical practice in the foreseeable future?: Given COVID-19, the H1N1 "swine flu" pandemic, our knowledge of antimicrobial resistant pathogens, and increasing awareness about how food systems are linked to the spread of emerging infectious diseases, occupational health intervention research and workplace policies may focus on creating barn environments that are more conducive to PPE use which could help protect workers and consequently the community.