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Browsing by Author "Winchester, Paul"
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Item 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, PaulBackground: 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.Item Preterm birth buccal cell epigenetic biomarkers to facilitate preventative medicine(Springer Nature, 2022-03-01) Winchester, Paul; Nilsson, Eric; Beck, Daniel; Skinner, Michael K.; Pediatrics, School of MedicinePreterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. The current study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). An epigenome-wide association study (EWAS) was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p < 1e-04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes. Observations identify a potential paternal germline contribution for preterm birth and identify the potential epigenetic inheritance of preterm birth susceptibility for the female child later in life. Although expanded clinical trials and preconception trials are required to optimize the potential epigenetic biomarkers, such epigenetic biomarkers may allow preventative medicine strategies to reduce the incidence of preterm birth.Item 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 MedicineAbnormal 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.