Glyphosate exposure in early pregnancy and reduced fetal growth: a prospective observational study of high-risk pregnancies.

BACKGROUND: Prenatal glyphosate (GLY) exposure is associated with adverse reproductive outcomes in animal studies. Little is known about the effects of GLY exposure during pregnancy in the human population. This study aims to establish baseline urine GLY levels in a high-risk and racially diverse pregnancy cohort and to assess the relationship between prenatal GLY exposure and fetal development and birth outcomes. METHODS: Random first trimester urine specimens were collected from high risk pregnant women between 2013 and 2016 as part of the Indiana Pregnancy Environmental Exposures Study (PEES). Demographic and clinical data were abstracted from mother and infant medical records. Urine glyphosate levels were measured as a proxy for GLY exposure and quantified using liquid chromatography-tandem mass spectrometry. Primary outcome variables included gestation-adjusted birth weight percentile (BWT%ile) and neonatal intensive care unit (NICU) admission. Relationships between primary outcome variables and GLY exposure were assessed using univariate and multivariate linear and logistic regression models. RESULTS: Urine GLY levels above the limit of detection (0.1 ng/mL) were found in 186 of 187 (99%) pregnant women. Further analyses were limited to 155 pregnant women with singleton live births. The mean age of participants was 29 years, and the majority were non-Hispanic white (70%) or non-Hispanic Black (21%). The mean (± SD) urine GLY level was 3.33 ± 1.67 ng/mL. Newborn BWT%iles were negatively related to GLY (adjusted slope ± SE = -0.032 + 0.014, p = 0.023). Infants born to women living outside of Indiana's large central metropolitan area were more likely to have a lower BWT%ile associated with mother's first trimester GLY levels (slope ± SE = -0.064 ± 0.024, p = 0.007). The adjusted odds ratio for NICU admission and maternal GLY levels was 1.16 (95% CI: 0.90, 1.67, p = 0.233). CONCLUSION: GLY was found in 99% of pregnant women in this Midwestern cohort. Higher maternal GLY levels in the first trimester were associated with lower BWT%iles and higher NICU admission risk. The results warrant further investigation on the effects of GLY exposure in human pregnancies in larger population studies.

Association between increasing agricultural use of 2,4-D and population biomarkers of exposure: findings from the National Health and Nutrition Examination Survey, 2001-2014.

BACKGROUND: 2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most extensively used herbicides in the United States. In 2012, 2,4-D was the most widely used herbicide in non-agricultural settings and the fifth most heavily applied pesticide in the US agricultural sector. The objective of this study was to examine trends in 2,4-D urinary biomarker concentrations to determine whether increases in 2,4-D application in agriculture are associated with increases in biomonitoring levels of urine 2,4-D. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) with available urine 2,4-D biomarker measurements from survey cycles between 2001 and 2014 were utilized. Urine 2,4-D values were dichotomized using the highest limit of detection (LOD) across all cycles (0.40 µg/L or 0.4 ppb). Agricultural use of 2,4-D was estimated by compiling publicly available federal and private pesticide application data. Logistic regression models adjusted for confounders were fitted to evaluate the association between agricultural use of 2,4-D and urine 2,4-D level above the dichotomization threshold. RESULTS: Of the 14,395 participants included in the study, 4681 (32.5%) had urine 2,4-D levels above the dichotomization threshold. The frequency of participants with high 2,4-D levels increased significantly (p < .0001), from a low of 17.1% in 2001-2002 to a high of 39.6% in 2011-2012. The adjusted odds of high urinary 2,4-D concentrations associated with 2,4-D agricultural use (per ten million pounds applied) was 2.268 (95% CI: 1.709, 3.009). Children ages 6-11 years (n = 2288) had 2.1 times higher odds of having high 2,4-D urinary concentrations compared to participants aged 20-59 years. Women of childbearing age (age 20-44 years) (n = 2172) had 1.85 times higher odds than men of the same age. CONCLUSIONS: Agricultural use of 2,4-D has increased substantially from a low point in 2002 and it is predicted to increase further in the coming decade. Because increasing use is likely to increase population level exposures, the associations seen here between 2,4-D crop application and biomonitoring levels require focused biomonitoring and epidemiological evaluation to determine the extent to which rising use and exposures cause adverse health outcomes among vulnerable populations (particularly children and women of childbearing age) and highly exposed individuals (farmers, other herbicide applicators, and their families).

Environmental pesticides increase the risk of developing hypertrophic pyloric stenosis.

BACKGROUND: Hypertrophic pyloric stenosis (HPS) is a condition noted within the first several weeks of life that results in hypertrophy of the pyloric muscle between the stomach and duodenum. The etiology has not been elucidated but genetic and environmental influences are suspected. We hypothesized that agricultural pesticides would be associated with an increased incidence of pyloric stenosis. STUDY DESIGN: Data from infants with HPS were obtained from the Indiana Birth Defects Registry (IBDR) for all counties in Indiana from 2005 to 2009. Data from all live births were obtained from the Indiana State Health Department (ISHD). Maternal demographics and clinical characteristics of infants were abstracted. The US Geological Survey (USGS) provided estimated use of agricultural pesticides (EPEST), and these values were correlated with HPS incidence. Univariate and multivariate logistical regression models were used to assess the association between HPS risk and pesticide use. RESULTS: A total of 442,329 newborns were studied with 1313 HPS cases recorded. The incidence of HPS was 30/10,000 live births. HPS incidence was correlated with total county pesticide use, as well as subcategories of pesticides (fungicides, fumigants, insecticides, herbicides). Indiana counties were then divided into low, moderate and high pesticide use (mean±standard deviation: 127,722±73,374, 308,401±36,915, and 482,008±97,260pounds of pesticides). Incidence of HPS was 26, 29, and 36 cases per 10,000 in low, moderate and high pesticide-use counties respectively. Subset analysis showed that the positive association between HPS and county pesticide use was more likely for male infants from mothers who were white, aged 20-35 years, had education at high school or lower, and smoked (p<0.05). CONCLUSION: Pesticide use correlated significantly with incidence of HPS. Positive correlations between HPS risk and pesticide use were found for most risk factors. Further studies will be needed to verify our findings and further delineate the nature of this correlation.

Agrichemicals in surface water and birth defects in the United States.

OBJECTIVES: To investigate if live births conceived in months when surface water agrichemicals are highest are at greater risk for birth defects. METHODS: Monthly concentrations during 1996-2002 of nitrates, atrazine and other pesticides were calculated using United States Geological Survey's National Water Quality Assessment data. Monthly United States birth defect rates were calculated for live births from 1996 to 2002 using United States Centers for Disease Control and Prevention natality data sets. Birth defect rates by month of last menstrual period (LMP) were then compared to pesticide/nitrate means using logistical regression models. RESULTS: Mean concentrations of agrichemicals were highest in April-July. Total birth defects, and eleven of 22 birth defect subcategories, were more likely to occur in live births with LMPs between April and July. A significant association was found between the season of elevated agrichemicals and birth defects. CONCLUSION: Elevated concentrations of agrichemicals in surface water in April-July coincided with higher risk of birth defects in live births with LMPs April-July. While a causal link between agrichemicals and birth defects cannot be proven from this study an association might provide clues to common factors shared by both variables.

Incidence of abdominal wall defects is related to surface water atrazine and nitrate levels.

BACKGROUND: Gastroschisis and omphalocele are congenital abdominal wall defects (AWD). Atrazine and nitrates are common agricultural fertilizers. METHODS: The Centers for Disease Control and Prevention natality data set was used to collect data for patients with AWD born between January 1990 and December 2002. Similar data were obtained from the Indiana State Department of Health. An estimated date of conception was calculated by birth date and gestational age. Surface water nitrate and atrazine levels for Indiana were collected from US Geological Survey data. Midwest was defined as Indiana, Illinois, Iowa, Ohio, and Nebraska. Statistical analysis was performed by chi2 test and Pearson correlation for P < or = .05. RESULTS: The Centers for Disease Control and Prevention identified 9871 children with AWD in 1990 and in 1995-2001 of 35,876,519 live births (rate 2.75/10(5)). In Indiana, 358 children from 1990-2001 had AWD of 1,013,286 live births (rate 3.53/10(5)). The AWD rate in Indiana was significantly higher than the national rate in 1996 (P = .0377), 1998 (P = .0005), and 2001 (P = .0365) and significantly higher than the Midwest rate in 1998 (P = .0104). Monthly comparison demonstrated a positive correlation of AWD rate and mean atrazine levels (P = .0125). CONCLUSION: Indiana has significantly higher rates of AWD compared with national rates. Increased atrazine levels correlate with increased incidence of AWD.