Winchester, Paul, Reiter, Jill L., Proctor, Cathy, Gerona, Roy R., Avery, Kayleigh D., Bromm, Jennifer R., Elsahy, Deena A, Hadley, Emily A., McGraw, Sara N., & Jones, Dana D., “Glyphosate in 1st Trimester of Pregnancy: Herbicides in the Womb,” 2019, Presented at the Pediatric Academic Societies (PAS) Meeting 2019, 4/24-5/1/2019, Baltimore, MD.
BACKGROUND: Our previous study demonstrated that >90% of pregnant Midwest women had detectable glyphosate (GLY) in their urine. Most glyphosate exposure occurs through food & certain beverages but not through drinking water. Shorter pregnancies, rural address and caffeinated beverages were associated with higher GLY levels. The cohort was small and predominantly Caucasian. The current study was needed to confirm high rates of GLY detection in a racially more diverse high risk population.
OBJECTIVE: Will GLY be detected in a majority of pregnancies regardless of race/ethnicity? Are GLY levels associated with adverse pregnancy outcomes? Do GLY levels vary by season of collection in pregnancy?
DESIGN/METHODS: Prospective observation study. Discarded urine from 1st trimester pregnancies were collected prospectively from a high risk University obstetrical clinic. All pregnancy outcomes and neonatal outcomes were abstracted. Urines were frozen, shipped to analytical lab (USCF, RG) for analysis. Urine GLY (Glyphosate (N(phosphomethyl) glycine) was analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), limit of quantification of 0.1 ng/mL. GLY measured as independent variable was compared to multiple variables using bivariate analysis.
RESULTS: GLY was detected in 99% (186 of 187) pregnancies. Levels varied from 1.004 to 10.31ng/mL with geometric mean 3.264ng/mL. Mean maternal age was 30, with 69% white, 4.2% Hispanic, 12% Black, 3.7% Asian and one “other”. GLY levels did not differ significantly by racial/ethnic group. GLY levels were not significantly difference between preterm and term outcomes, multiple/singleton or between fetal loss and live births. GLY levels were higher with increasing gestation at enrollment with 4-8 weeks GLY 2.73 vs 9-13 weeks 3.51(p=.0098). Significantly higher GLY levels were found in April-July pregnancies vs other months(3.64 vs 3.07 p=.03). NICU admission rates were 85% for preterm and 35% for term. Birth defect rate was12% and 37% had intrauterine drug exposure or NAS. Preterm birth rate was 31%. CONCLUSIONS: Glyphosate was found in virtually all of these high risk pregnancies in the first trimester regardless of race/ethnicity, plurality, fetal loss or gestation at birth. GLY levels rose with increasing gestation in the first trimester suggesting that gestation at measurement impacts GLY levels. Dietary sources contribute to GLY but we did find April-July are associated with higher GLY levels than other months. The fetal epigenetic consequences of 1st trimester GLY exposure remains unknown. FULL TEXT
Mattix KD, Winchester PD, Scherer LR, “Incidence of abdominal wall defects is related to surface water atrazine and nitrate levels,” Journal of Pediatric Surgery, 2007, 42:6, DOI: 10.1016/j.jpedsurg.2007.01.027
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.
Margaux McBirney, Stephanie E. King, Michelle Pappalardo, Elizabeth Houser, Margaret Unkefer, Eric Nilsson, Ingrid Sadler-Riggleman, Daniel Beck, Paul Winchester, Michael K. Skinner, “Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation pathology biomarkers,” PLOS One, 2017, 12:9, DOI: 10.1371/journal.pone.0184306
Ancestral environmental exposures to a variety of environmental toxicants and other factors have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The current study examined the potential transgenerational actions of the herbicide atrazine. Atrazine is one of the most commonly used herbicides in the agricultural industry, in particular with corn and soy crops. Outbred gestating female rats were transiently exposed to a vehicle control or atrazine. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation. The F1, F2 and F3 generation control and atrazine lineage rats were aged and various pathologies investigated. The male sperm were collected to investigate DNA methylation differences between the control and atrazine lineage sperm. The F1 generation offspring (directly exposed as a fetus) did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease and mammary tumors in males and females, early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations (motor hyperactivity) and a lean phenotype in males and females. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The transgenerational transmission of disease requires germline (egg or sperm) epigenetic alterations. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified in the F1, F2 and F3 generations. Gene associations with the DMRs were identified. For the transgenerational F3 generation sperm, unique sets of DMRs (epimutations) were found to be associated with the lean phenotype or testis disease. These DMRs provide potential biomarkers for transgenerational disease. The etiology of disease appears to be in part due to environmentally induced epigenetic transgenerational inheritance, and epigenetic biomarkers may facilitate the diagnosis of the ancestral exposure and disease susceptibility. Observations indicate that although atrazine does not promote disease in the directly exposed F1 generation, it does have the capacity to promote the epigenetic transgenerational inheritance of disease. FULL TEXT
S. Parvez, R. R. Gerona, C. Proctor, M. Friesen, J. L. Ashby, J. L. Reiter, Z. Lui, and P. D. Winchester, “Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study,” Environmental Health, 17:23, March 9, 2018, DOI: 10.1186/s12940-018-0367-0.
BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length.
METHOD: Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. GLY measurements were performed using liquid chromatography-tandem mass spectrometry. Demographic and survey information relating to food and water consumption, stress, and residence were obtained by questionnaire. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length.
RESULTS: The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5–7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths (r = − 0.28, p = 0.02).
CONCLUSIONS: This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized. FULL TEXT
“Tennessee Dept. of Agriculture issues new measures for Dicamba,” July 12, 2017, Winchester Herald Chronicle.
The Tennessee Department of Agriculture responded to increased farmer-to-farmer complaints of damage from dicamba drift by enacting new rules on dicamba use in the state. The rules include requiring special licensing and record keeping for applicators, banning the use of older formulations for the rest of the season, and limiting the timing that it can be applied, and will be effective through October 1, 2017. FULL TEXT
Markel TA, Proctor C, Ying J, Winchester PD, “Environmental pesticides increase the risk of developing hypertrophic pyloric stenosis,” Journal of Pediatric Surgery, 2015, 50:8, DOI: 10.1016/J.JPEDSURG.2014.12.009.
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.
Winchester PD, Huskins J, Ying J, “Agrichemicals in surface water and birth defects in the United States,” Acta Paediatrica, 2009, 98:4, DOI: 10.1111/j.1651-2227.2008.01207.
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. FULL TEXT
Winchester P, Proctor C, Ying J, “County-level pesticide use and risk of shortened gestation and preterm birth,” Acta Paediatrica, 2016, 105:3, DOI: 10.1111/apa.13288.
AIM: This study assesses the association between pesticide exposure in pregnancy, preterm birth (PTB) and shortened gestation.
METHODS: Pregnancy information was abstracted from the Centers for Disease Control (CDC) Non-Public Use Natality Datasets 1990-2005. Pesticide use in maternal county of residence was calculated using California Pesticide Use Reporting (PUR) data 1990-2005. Counties were ranked by pesticide use, and birth months were sorted by peak (May-June) or nonpeak (other months) pesticide use. Multivariate logistical regression models were used.
RESULTS: Counties with higher pesticide use were associated with higher PTB (low 8.59 ± 0.11%, moderate 9.25 ± 0.07%, high 10.0 ± 0.06%, p’s < 0.001) and shorter gestations (low 39.197 ± 0.014 weeks, moderate 39.126 ± 0.011 weeks, high 39.049 ± 0.011 weeks, p’s < 0.001). Peak pesticide months were associated with higher PTB (10.01 ± 0.05% vs. 9.36 ± 0.05%, p < 0.001) and shorter gestations (39.069 ± 0.007 weeks vs. 39.122 ± 0.007 weeks, p < 0.001). The pesticide effect on shortened gestation and higher PTB was found in all racial groups. Pesticide use was highest for fungicides > insecticides > fumigants > herbicides > others. Each pesticide type was found to be associated with higher PTB and shorter gestation.
CONCLUSION: PTB and shortened gestation were significantly associated with pesticide use in maternal county of residence regardless of race, gestation at birth, and in most risk categories. FULL TEXT
Winchester PD, Parvez S, Proctor C, Ying J, Gerona RR, “Fetal Exposure to Glyphosate,” Presentation, Pediatric Academic Societies, May 6-7, 2017, San Francisco, California.
Measured glyphosate in pregnant women to estimate fetal exposure and monitor potential adverse effects on pregnancy outcomes. Glyphosate was present in 91% of the urine samples and higher glyphosate levels were correlated with shorter pregnancies and lower birth weights. FULL TEXT