Browsing by Author "Winchester, Paul D."

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    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
    (BMC, 2022-02-10) Freisthler, Marlaina S.; Robbins, C. Rebecca; Benbrook, Charles M.; Young, Heather A.; Haas, David M.; Winchester, Paul D.; Perry, Melissa J.; Obstetrics and Gynecology, School of Medicine
    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).
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    FETAL AND NEONATAL FACTORS INFLUENCING FREE CARNITINE
    (Office of the Vice Chancellor for Research, 2012-04-13) Winchester, Paul D.; Proctor, Cathy; Pandya, Janit; Ying, Jun
    Background: Free Carnitine (FC) is now measured routinely in new-borns in Indiana. Studies with small numbers have suggested that FC may be dependent on fetal and neonatal factors. Objective: Our objective was to compare FC levels with various fetal and neonatal factors. Our goal was to establish normative data by gestation in a very large cohort (Indiana State) and to use these carnitine values to develop hypotheses about FC in fetal life and disease. Design/Methods: Indiana State Health Department FC values (tandem mass spec) and demographic variables were obtained for the years 2005-2010. Gender, race, birth weight, gestation, NICU admission, age at collec-tion information was also evaluated. Multivariate fixed effect models were used to compare carnitine values with independent variables. Results: The number of newborns analyzed was 459,932. FC levels were lowest in babies with gestational age 37-40 weeks and higher in both preterm and post-term babies (Table 1). Table 1. Free Carnitine vs. Gestation Gestation FC mean SE mean Gestation FC mean SE mean 23 40.88 1.00 33 39.81 0.28 24 39.86 0.73 34 38.28 0.22 25 42.61 0.69 35 37.14 0.19 26 42.77 0.64 36 36.37 0.17 27 42.65 0.63 37 35.76 0.20 28 42.47 0.57 38 35.11 0.22 29 43.51 0.53 39 35.04 0.19 30 40.4 0.46 40 35.36 0.07 31 41.96 0.41 41 38.58 0.48 32 40.65 0.34 42 40.96 1.52 FC levels were lowest in babies with birth weights between 3150-4050g (34.390.07) and higher in groups with both lower (<2500g;39.540.08**, 2500-2850g;35.82 0.08**, 2850-3150g;34.890.08) and higher weights (>4500g;35.660.1**). FC levels were lowest when collected be-tween 24-48 hours (34.290.05) and higher either before (36.930.1**) or after that time (2-3,3-4,4-5,>5days;34.960.06**,36.210.11**,37.320.15**,36.80.14**). Female, white, non singleton and non NICU babies had significantly lower FC levels (Table 2). Table 2. Free Carnitine vs. Demographics Category FC mean SE mean Male 39.40 0.08 Female 36.60 0.08** White 37.16 0.06 Black 37.34 0.08* Asian 39.12 0.18** Other 38.39 0.1** Singleton 38.30 0.06 Multiple 37.70 0.11** NICU 40.46 0.09 Non-NICU 35.55 0.07** *&** are p<0.05 & <0.01 vs. comp group Conclusions: FC values are significantly influenced by gestation, gender, race, time of collection, NICU admission, multiple birth and birth weight. Generally, factors which increased mortality and morbidity (immaturity, post maturity, low birth weight, male gender, black race) were associated with higher FC values. These data will be used to construct normative curves and may be useful in predicting neonatal outcomes (Figure 1). 1Biostatistics, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267
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    Glyphosate exposure in early pregnancy and reduced fetal growth: a prospective observational study of high-risk pregnancies
    (BMC, 2022-10-11) Gerona, Roy R.; Reiter, Jill L.; Zakharevich, Igor; Proctor, Cathy; Ying, Jun; Mesnage, Robin; Antoniou, Michael; Winchester, Paul D.; Medical and Molecular Genetics, School of Medicine
    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.
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    Maternal IQ Predicts Child's Birth Weight
    (Office of the Vice Chancellor for Research, 2011-04-08) Winchester, Paul D.; Scales, William; Proctor, Cathy; Ying, Jun
    Background: Prior studies correlated birth weight with child IQ. Maternal IQ correlates with IQ in her offspring. Birth weight predicted IQ in monozygotic twins dicordant for birth weight. IUGR alters global DNA methylation. IQ in mother may be a biological marker for her child's rate of intrauterine growth (birth weight). Objective: Does maternal IQ predict her child's intrauterine growth rate (birth weight)? Design/Methods: Births from 1970-2004 using NLSY '79 database were studied Primary variables were children's IQ score from most recent Peabody Picture Vocabulary Revised Form L test and birth weight in grams. Maternal IQ was estimated from AirForce Qualifying test (AFQT)and categorized as 75, 50-74, 25-49 and <25%ile resp. Race, economic status, singleton, gestation, use of tobacco, alcohol and other drugs were used as covariates. Multivariate models were used to assess associations of Children's IQ and birth weight with maternal IQ levels controlling for other covariates. Results: 9,125 children were analyzed. 98.3% singleton, 12.3% preterm, and 51.2% male. Means Std's of birth weight and IQ score were 3,307 597 grams and 38 30.4 respectively.Of the total 4,121 mothers, 25.7% were blacks, 18.3% were Hispanics and 54.0% were non Hispanic non blacks(nHnB). The mean std of the AFQT was 36.9 28.1. Proportions of IQs were 13.6%, 17.2%, 27.2% and 42% from low to high IQs respectively among mothers. Multivariate models showed children's IQ scores were related to their mother's IQ ,birth weight, race/ethnicity, and economic status. In particular, the mean children's IQ scores were 28.1, 37.1, 46.8, and 55 at mother's IQ levels from low to high respectively (p-values<0.001). Children's IQs was increased by 0.14 0.06 (slope) for every 100 gram increase in birth weight (p=0.013). Children's birth weights were positively associated with their mothers' IQ. Means birth weight increased from 3,334 grams to 3,465 grams as mothers' IQ rose from low to high (p<0.001). When sub-populations stratified by race/ethnicity were analyzed, positive relationships between childs IQ and mother's IQ were found in all Hispanic, black and nHnB groups (p's<0.001); while the positive relationship between birth weight and mother's IQ levels was found significant only in the nHnB (white) group (p<0.001). The findings held even after preterm and non singleton births were excluded from analysis. Conclusions: Child's IQ correlates with birth weight and maternal IQ. Maternal IQ may also predict birth weight of offspring.