Browsing by Author "Proctor, Cathy"

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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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    Is the Day of Last Menstrual Period a Predictor of Preterm Birth?
    (Office of the Vice Chancellor for Research, 2016-04-08) Singhal, Ahaan; Proctor, Cathy; Ying, Jun; Winchester, Paul
    Background: Preterm birth is the leading cause of infant death and disability in the US. Previous studies have demonstrated that preterm birth rates (PTBR) are seasonal and linked to month of last menstrual period (LMP). We wondered whether LMP day (LMPD) might correlate with PTBR. Objective: Is preterm birth risk positively correlated with LMPD? Design/Methods: CDC natality data from 1990-2008 were analyzed. Included were continental US residents, 22-43 weeks. Excluded were pregnancies with no prenatal care, non-US residence and LMP unknown. PTBR was calculated for each LMPD across all LMP months and years. Maternal age, race, parity, education, tobacco, alcohol, diabetes, hypertension, induction, delivery route, meconium, plurality, gestation, assisted ventilation were abstracted. PTBR was aggregated by year, month and LMPD after adjusting for month and year. Analysis was repeated in subpopulations stratified by abstracted risk factors. Random effects were used to account for within unit correlation caused by repeated measurements over months and years. Results: 64,872,927 records were reviewed. PTBR was positively correlated with LMPD(slope±SE0.08±0.01(p‹0.001). PTBR rose by 0.08% for each LMP day from 1-31. This relationship remained significant in each year from 1990-2008 and in all months except October. Subgroup analysis showed that the correlation remained significant for every demographic and pregnancy outcome variable tested. That is, regardless of race or maternal demographics, PTBR can be predicted by LMPD with lower to higher risk associated with lower to higher PTBR. LMPD represents a covariate in predicting preterm birth rates. Conclusions: PTBR increases with increasing LMPD. The correlation was remarkably strong and persisted throughout all risk categories. Despite its biological implausibility we were unable to find an explanation for this correlation within the usual risk categories. LMPD was removed from the birth certificate in 2008. These data suggest that LMPD may be more important than was previously thought.
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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.
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    Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
    (Springer Nature, 2023-01-11) Kaefer, Martin; Rink, Richard; Misseri, Rosalia; Winchester, Paul; Proctor, Cathy; Ben Maamar, Millissia; Beck, Daniel; Nilsson, Eric; Skinner, Michael K.; Pediatrics, School of Medicine
    Abnormal penile foreskin development in hypospadias is the most frequent genital malformation in male children, which has increased dramatically in recent decades. A number of environmental factors have been shown to be associated with hypospadias development. The current study investigated the role of epigenetics in the etiology of hypospadias and compared mild (distal), moderate (mid shaft), and severe (proximal) hypospadias. Penile foreskin samples were collected from hypospadias and non-hypospadias individuals to identify alterations in DNA methylation associated with hypospadias. Dramatic numbers of differential DNA methylation regions (DMRs) were observed in the mild hypospadias, with reduced numbers in moderate and low numbers in severe hypospadias. Atresia (cell loss) of the principal foreskin fibroblast is suspected to be a component of the disease etiology. A genome-wide (> 95%) epigenetic analysis was used and the genomic features of the DMRs identified. The DMR associated genes identified a number of novel hypospadias associated genes and pathways, as well as genes and networks known to be involved in hypospadias etiology. Observations demonstrate altered DNA methylation sites in penile foreskin is a component of hypospadias etiology. In addition, a potential role of environmental epigenetics and epigenetic inheritance in hypospadias disease etiology is suggested.