Multimorbidity is the co-occurrence of multiple chronic health problems, associated with aging, frailty, and poor functioning. Children born preterm experience more multimorbid conditions in early life compared to term-born peers. Though neonatal multimorbidity is linked to poor health-related quality of life, functional outcomes, and peer group participation, gaps in our theoretical understanding and conceptualization remain.
View Article and Find Full Text PDFStudy Question: Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation?
Summary Answer: Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes.
What Is Known Already: In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes.
Study Design, Size, Duration: Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006-2016).
The placenta is crucial for fetal development, is affected by PFAS toxicity, and evidence is accumulating that gestational PFAS perturb the epigenetic activity of the placenta. Gestational PFAS exposure is can adversely affect offspring, yet individual and cumulative impacts of PFAS on the placental epigenome remain underexplored. Here, we conducted an epigenome-wide association study (EWAS) to examine the relationships between placental PFAS levels and DNA methylation in a cohort of mother-infant dyads in Arkansas.
View Article and Find Full Text PDFPrevious research has found that living in a disadvantaged neighborhood is associated with poor health outcomes. Living in disadvantaged neighborhoods may alter inflammation and immune response in the body, which could be reflected in epigenetic mechanisms such as DNA methylation (DNAm). We used robust linear regression models to conduct an epigenome-wide association study examining the association between neighborhood deprivation (Area Deprivation Index; ADI), and DNAm in brain tissue from 159 donors enrolled in the Emory Goizueta Alzheimer's Disease Research Center (Georgia, USA).
View Article and Find Full Text PDFThe current work was designed to demonstrate the application of the exposome framework in examining associations between exposures and children's long-term neurodevelopmental and behavioral outcomes. Longitudinal data were collected from birth through age 6 from 402 preterm infants. Three statistical methods were utilized to demonstrate the exposome framework: exposome-wide association study, cumulative exposure and machine learning models, with and without epigenetic data.
View Article and Find Full Text PDFSmoking exposure during adulthood can disrupt oocyte development in women, contributing to infertility and possibly adverse birth outcomes. Some of these effects may be reflected in epigenome profiles in granulosa cells (GCs) in human follicular fluid. We compared the epigenetic modifications throughout the genome in GCs from women who were former (N = 15) versus never smokers (N = 44) undergoing assisted reproductive technologies (ART).
View Article and Find Full Text PDFPrior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age.
View Article and Find Full Text PDFChildren born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability.
View Article and Find Full Text PDFObjective: Broadband parent rating scales are commonly used to assess behavioral problems in children. Multiple rating scales are available, yet agreement between them is not well-understood. The objective of this study was to evaluate agreement between the Behavior Assessment System for Children, Third Edition (BASC-3), and Child Behavior Checklist 1.
View Article and Find Full Text PDFEpigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (<30 weeks gestation) infants to characterize whether infants with early morbidities or different neurobehavioral characteristics had accelerated or decelerated epigenetic ageing.
View Article and Find Full Text PDFPrenatal exposure to single chemicals belonging to the per- and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in the mother, fetus, and placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed to multiple PFAS, the potential joint effects of PFAS on the metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics to identify metabolites and metabolic pathways perturbed by exposure to a PFAS mixture during pregnancy.
View Article and Find Full Text PDFBackground: Epigenetic clocks are promising tools for assessing biological age. We assessed the accuracy of pediatric epigenetic clocks in gestational and chronological age determination.
Results: Our study used data from seven tissue types on three DNA methylation profiling microarrays and found that the Knight and Bohlin clocks performed similarly for blood cells, while the Lee clock was superior for placental samples.
Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes.
View Article and Find Full Text PDFBackground: Higher exposure to traffic-related air pollution (TRAP) is related to lower fertility, with specific adverse effects on the ovary. Folic acid may attenuate these effects. Our goal was to explore the relation of TRAP exposure and supplemental folic acid intake with epigenetic aging and CpG-specific DNA methylation (DNAm) in granulosa cells (GC).
View Article and Find Full Text PDFRecent efforts have focused on developing methylation risk scores (MRS), a weighted sum of the individual's DNA methylation (DNAm) values of pre-selected CpG sites. Most of the current MRS approaches that utilize Epigenome-wide association studies (EWAS) summary statistics only include genome-wide significant CpG sites and do not consider co-methylation. New methods that relax the p-value threshold to include more CpG sites and account for the inter-correlation of DNAm might improve the predictive performance of MRS.
View Article and Find Full Text PDFBackground: Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures.
Methods: We studied 1112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium.
The fate of environmental chemicals in maternal and fetal tissues might be affected by pregnancy-related hemodynamic changes that occur across gestation. Specifically, hemodilution and renal function are hypothesized to confound associations between per- and polyfluoroalkyl substances (PFAS) exposure measures in late pregnancy with gestational length and fetal growth. We sought to analyze two pregnancy-related hemodynamic biomarkers, creatinine and estimated glomerular filtration rate (eGFR), as confounders of the trimester-specific relationships between maternal serum PFAS concentrations and adverse birth outcomes.
View Article and Find Full Text PDFImportance: Acoustic cry characteristics have been associated with severe medical problems in newborns. However, little is known about the utility of neonatal acoustic cry characteristics in the prediction of long-term outcomes of very preterm infants.
Objectives: To evaluate whether acoustic characteristics of infant cry at neonatal intensive care unit (NICU) discharge are associated with behavioral and developmental outcomes at age 2 years in infants born very preterm.
During infancy, the interplay between the developing immune system and the microbiome is critical. We examined whether blood immune cell composition at birth in the umbilical cord (inferred by DNA methylation profiling) related to the early infant gut microbiome (assessed by 16S rRNA gene sequencing) among 73 infants in the New Hampshire Birth Cohort Study. We used generalized estimating equations and controlled for false discovery rate to select microbial taxa associated with immune cells.
View Article and Find Full Text PDFBackground: Survivors of child abuse experience high rates of adverse physical and mental health outcomes. Epigenetic alterations in the stress response system, the FKBP5 gene specifically, have been implicated as one mechanism that may link abuse to lifelong health issues. Prior studies primarily included older individuals with a remote history of maltreatment; our objective was to test for differential methylation of FKBP5 in children with abusive vs accidental injuries at the time of diagnosis.
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