Prenatal pyrethroid exposure, placental gene network modules, and neonatal neurobehavior.

Prenatal pesticide exposure may adversely affect child neurodevelopment which may partly arise from impairing the placenta's vital role in fetal development. In a cohort of pregnant farmworkers from Thailand (N = 248), we examined the links between urinary metabolites of pyrethroid pesticides during pregnancy, placental gene expression networks derived from transcriptome sequencing, and newborn neurobehavior assessed using the NICU Network Neurobehavioral Scales (NNNS) at 5 weeks of age. Focusing on the 21 gene network modules in the placenta identified by Weighted Gene Co-expression Network Analysis, our analysis revealed significant associations between metabolites and nine distinct modules, and between thirteen modules and NNNS, with eight modules showing overlap.

Single-Cell Multiome Impact of Prenatal Heavy Metal Exposure on Early Airway Development.

Prenatal exposure to cadmium (Cd) and arsenic (As) can severely impair fetal lung development, leading to lifelong adverse effects. As two of the most common and toxic heavy metals, Cd and As pose risks to many communities through food and water consumption. We have shown that prenatal co-exposure to Cd and As at levels relevant to human intake inhibits branching morphogenesis, yet cell-type-specific mechanisms remain elusive.

Prenatal Stress and Socioeconomic Status as Predictors of Placental Methylation in Pregnant People.

Despite growing interest in placental epigenetics, the combined impact of prenatal stress and socioeconomic status (SES) on placental methylation is still largely understudied. We conducted a study to examine the associations of prenatal stress and socioeconomic factors (household income, Hollingshead socioeconomic index) with placental methylation. Pregnant people ( = 143; = 25.

The Associations of Air Pollution Mixture Exposure with Plasma Proteins in an Elderly U.S. Panel.

The impact of air pollution exposure on circulating proteins remains underexplored, particularly in vulnerable elderly populations. This study investigated the individual and joint effects of air pollutants on circulating proteins in 208 elderly participants from the Cancer Prevention Study-II Nutrition Cohort. Prediagnostic plasma samples were collected (1998-2001), and 484 proteins were measured using the Olink platform.

Impact of placental and peripheral blood DNA methylation on celiac disease susceptibility.

Objectives: Several studies suggest that the first immunogenic insult in celiac disease (CeD) could occur during fetal development. The placenta is a key organ that could link the environment with the genome and future outcomes, including CeD. Our objective is to determine the involvement of placental DNA methylation (DNAm) as potential mediator of the genetic susceptibility to CeD.

Adverse Birth Outcomes Associated with Heat Stress and Wildfire Smoke Exposure During Preconception and Pregnancy.

We investigated associations between preconception and prenatal heat stress and wildfire (WF) smoke exposures on adverse birth outcomes and whether neighborhood climate vulnerability is an effect modifier in the Maternal And Developmental Risks from Environmental and Social stressors cohort ( = 713). Generalized linear models were fit to test the association between exposures and small-for-gestational-age (SGA), low birthweight (LBW), and Fenton growth -score outcomes, adjusting for confounders. Living in a high climate vulnerability index neighborhood was tested as an effect modifier.

Blood Pressure and Late Pregnancy Circulating miRNAs in the MADRES Study.

Background: Circulating extracellular and vesicle particle (EVP) miRNAs have been associated with cardiovascular risk and adverse birth outcomes. Hypertensive disorders of pregnancy (HDP) increase risk for adverse birth outcomes and future cardiovascular outcomes in mothers and children and have been associated with altered maternal circulating EVP miRNA levels during pregnancy. Whether these relationships exist for elevated blood pressure (BP) in the subclinical range is unknown.

Associations of placental lncRNA expression with maternal pre-pregnancy BMI and infant birthweight in two birth cohorts.

Pre-pregnancy obesity (ppOB) is linked to pregnancy complications and abnormal fetal growth through placental mechanisms, and long non-coding RNAs (lncRNAs) may play an epigenetic role in these processes. We investigated overall and sex-specific associations of pre-pregnancy body mass index (ppBMI), ppOB, and birthweight with placental lncRNA transcripts in two birth cohorts. Study participants were mother-child dyads recruited to the CANDLE (Memphis, TN)( = 725) and GAPPS (Seattle and Yakima, WA)( = 159) cohorts.

Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases.

Sex differences in physiological and disease traits are pervasive and begin during early development, but the genetic architecture of these differences is largely unknown. Here, we leverage the human placenta, a transient organ during pregnancy critical to fetal development, to investigate the impact of sex in the regulatory landscape of placental autosomal methylome and transcriptome, and its relevance to health and disease. We find that placental methylation and its genetic regulation are extensively impacted by fetal sex, whereas sex differences in placental gene expression and its genetic regulation are limited.

Isolating the effects of HIV infection and HIV exposure on epigenetic profiles in infants using historical data from the Mothers and Infants Cohort Study.

Background: Epigenetics offers insight into the mechanisms by which early life HIV infection and HIV exposure in utero affects offspring health. However, due to the widespread use of antiretroviral therapy (ART) during pregnancy/infancy, contemporary studies are unable to disentangle effects of HIV from ART exposure on epigenetic profiles.

Methods: Using historical specimens collected before widespread use of ART (1985-1991), we compared DNA methylation (DNAm) profiles among infants with perinatally-acquired HIV (PHIV), HIV-exposed but uninfected (HEU), and HIV-unexposed uninfected (HUU).

Attention problems in children born very preterm: evidence from a performance-based measure.

Background: Children born very preterm (VPT) are at high risk for attention problems. This study's purpose was to describe the Conners Kiddie Continuous Performance Test (K-CPT) assessment in children born VPT, including rates of clinically elevated scores, change over time, and associations between K-CPT scores and parent reported attention problems.

Methods: We studied 305 children from a multi-site study of children born VPT who completed at least one K-CPT assessment at age 5, 6, and/or 7 years.

Child Opportunity Index at birth and asthma with recurrent exacerbations in the US ECHO program.

Background: Environmental exposures and social determinants likely influence specific childhood asthma phenotypes.

Objective: We hypothesized that the Child Opportunity Index (COI) at birth, measuring multiple neighborhood opportunities, influences incidence rates (IRs) for asthma with recurrent exacerbations (ARE).

Methods: We tested for COI associations with ARE IRs in 15,877 children born between 1990 and 2018 in the ECHO (Environmental Influences on Child Health Outcomes) program.

Prenatal exposure to pesticide mixtures and the placental transcriptome: Insights from trimester-specific, sex-specific and metabolite-scaled analyses in the SAWASDEE cohort.

We investigated the effect of exposure to pesticide mixtures during pregnancy on the placental transcriptome, to link these exposures and placental functions. The Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) enrolled pregnant farmworkers from Thailand (n = 248), who were primarily exposed to organophosphate (OP) and pyrethroid pesticides. We measured maternal urinary levels of six non-specific OP metabolites expressed as three summary measures (dimethylalkylphosphates (DMAP), diethylalkylphosphates (DEAP), and dialkylphosphates (DAP) and three pyrethroid metabolites (3-phenoxybenzoic acid (3-PBA), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA, trans-DCCA) during early, middle, and late pregnancy, and adjusted for urine dilution using creatinine.

A Prospective Analysis of Per- and Polyfluoroalkyl Substances from Early Pregnancy to Delivery in the Atlanta African American Maternal-Child Cohort.

Background: Longitudinal trends in per- and polyfluoroalkyl substances (PFAS) serum concentrations across pregnancy have not been thoroughly examined, despite evidence linking prenatal PFAS exposures with adverse birth outcomes.

Objectives: We sought to characterize longitudinal PFAS concentrations across pregnancy and to examine the maternal-fetal transfer ratio among participants in a study of risk and protective factors for adverse birth outcomes among African Americans.

Methods: In the Atlanta African American Maternal-Child cohort (2014-2020), we quantified serum concentrations of four PFAS in 376 participants and an additional eight PFAS in a subset of 301 participants during early (8-14 weeks gestation) and late pregnancy (24-30 weeks gestation).

Relationships of mitochondrial DNA mutations and select clinical diagnoses in perinatally HIV- and ART-exposed uninfected children.

The prevalence of pathogenic mutations within mitochondrial (mt) DNA of youth who were perinatally exposed to HIV and ART but remained uninfected (YHEU) were assessed relative to phenotypic clinical indicators of mitochondrial dysfunction (MtD). This was a cross-sectional, nested case-control study. A total of 144 cases met at least one clinical MtD definition and were matched with up to two controls each (n = 287).

Association of per- and polyfluoroalkyl substances with the antioxidant bilirubin across pregnancy.

Background: In mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy.

Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs).

Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria.

Differential impact of prenatal PTSD symptoms and preconception trauma exposure on placental and methylation.

Perinatal stress is associated with altered placental methylation, which plays a critical role in fetal development and infant outcomes. This proof-of-concept pilot study investigated the impact of lifetime trauma exposure and perinatal PTSD symptoms on epigenetic regulation of placenta glucocorticoid signaling genes ( and Lifetime trauma exposure and PTSD symptoms during pregnancy were assessed in a racially/ethnically diverse sample of pregnant women ( = 198). Participants were categorized into three groups: (1) No Trauma (-T); (2) Trauma, No Symptoms (T - S); and (3) Trauma and Symptoms (T + S).

Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs).

Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria.

Examining the Biological Impacts of Parent-Child Relationship Dynamics on Preschool-Aged Children who have Experienced Adversity.

Parent-child relationship dynamics have been shown to predict socioemotional and behavioral outcomes for children, but little is known about how they may affect biological development. The aim of this study was to test if observational assessments of parent-child relationship dynamics (cohesion, enmeshment, and disengagement) were associated with three biological indices of early life adversity and downstream health risk: (1) methylation of the glucocorticoid receptor gene (), (2) telomere attrition, and (3) mitochondrial biogenesis, indexed by mitochondrial DNA copy number (mtDNAcn), all of which were measured in children's saliva. We tested hypotheses using a sample of 254 preschool-aged children ( age = 51.