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Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

BACKGROUND: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. METHODS: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. RESULTS: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values

BACKGROUND: Methods of sustaining the deimplementation of overused medical practices (i.e., practices not supported by evidence) are understudied. In pediatric hospital medicine, continuous pulse oximetry monitoring of children with the common viral respiratory illness bronchiolitis is recommended only under specific circumstances. Three national guidelines discourage its use for children who are not receiving supplemental oxygen, but guideline-discordant practice (i.e., overuse) remains prevalent. A 6-hospital pilot of educational outreach with audit and feedback resulted in immediate reductions in overuse; however, the best strategies to optimize sustainment of deimplementation success are unknown. METHODS: The Eliminating Monitor Overuse (EMO) trial will compare two deimplementation strategies in a hybrid type III effectiveness-deimplementation trial. This longitudinal cluster-randomized design will be conducted in Pediatric Research in Inpatient Settings (PRIS) Network hospitals and will include baseline measurement, active deimplementation, and sustainment phases. After a baseline measurement period, 16-19 hospitals will be randomized to a deimplementation strategy that targets unlearning (educational outreach with audit and feedback), and the other 16-19 will be randomized to a strategy that targets unlearning and substitution (adding an EHR-integrated clinical pathway decision support tool). The primary outcome is the sustainment of deimplementation in bronchiolitis patients who are not receiving any supplemental oxygen, analyzed as a longitudinal difference-in-differences comparison of overuse rates across study arms. Secondary outcomes include equity of deimplementation and the fidelity to, and cost of, each deimplementation strategy. To understand how the deimplementation strategies work, we will test hypothesized mechanisms of routinization (clinicians developing new routines supporting practice change) and institutionalization (embedding of practice change into existing organizational systems). DISCUSSION: The EMO trial will advance the science of deimplementation by providing new insights into the processes, mechanisms, costs, and likelihood of sustained practice change using rigorously designed deimplementation strategies. The trial will also advance care for a high-incidence, costly pediatric lung disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05132322 . Registered on November 10, 2021.

Study questionIs sperm epigenetic aging (SEA) associated with probability of pregnancy among couples in the general population?Summary answerWe observed a 17% lower cumulative probability at 12 months for couples with male partners in the older compared to the younger SEA categories.What is known alreadyThe strong relation between chronological age and DNA methylation profiles has enabled the estimation of biological age as epigenetic 'clock' metrics in most somatic tissue. Such clocks in male germ cells are less developed and lack clinical relevance in terms of their utility to predict reproductive outcomes.Study design, size, durationThis was a population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 and followed for up to 12 months.Participants/materials, setting, methodsSperm DNA methylation from 379 semen samples was assessed via a beadchip array. A state-of-the-art ensemble machine learning algorithm was employed to predict age from the sperm DNA methylation data. SEA was estimated from clocks derived from individual CpGs (SEACpG) and differentially methylated regions (SEADMR). Probability of pregnancy within 1 year was compared by SEA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates.Main results and the role of chanceOur SEACpG clock had the highest predictive performance with correlation between chronological and predicted age (r = 0.91). In adjusted discrete Cox models, SEACpG was negatively associated with TTP (fecundability odds ratios (FORs)=0.83; 95% CI: 0.76, 0.90; P = 1.2×10-5), indicating a longer TTP with advanced SEACpG. For subsequent birth outcomes, advanced SEACpG was associated with shorter gestational age (n = 192; -2.13 days; 95% CI: -3.67, -0.59; P = 0.007). Current smokers also displayed advanced SEACpG (P

Background: Phthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation-reduction reaction stress and endocrine disruption, evidence for the impact of women's phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive. Objectives: We aimed to determine the relationship of preconception phthalate metabolite exposure with a) fecundability and pregnancy loss and b) markers of potential biological mechanisms, including reproductive hormones, inflammation, and oxidative stress. Methods: Data were collected from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a preconception study following 1,228 women who were attempting pregnancy, for up to six menstrual cycles and throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured in a consecutive 3-d pooled urine sample at enrollment. Pregnancy was determined through urinary human chorionic gonadotropin (hCG) at the expected date of menses during each cycle and pregnancy loss as an observed loss following positive hCG. Highly sensitive C-reactive protein (hsCRP) and isoprostanes were measured at enrollment, and reproductive hormones were measured during the follicular phase, ovulation, and luteal phase. Discrete-time Cox proportional hazards models evaluated the relationship of phthalate metabolites with fecundability and weighted Poisson models with robust variance evaluated the risk of pregnancy loss. Results: An interquartile range (IQR) higher mono-(2-ethylhexyl) phthalate [fecundability odds ratio (FOR) =0.88; 95% confidence interval (CI): 0.78, 1.00], mono-butyl phthalate (FOR = 0.82; 95% CI: 0.70, 0.96), and mono-benzyl phthalate (FOR = 0.85; 95% CI: 0.74, 0.98) was associated with lower fecundability. No consistent associations were observed with pregnancy loss. Preconception phthalates were consistently associated with higher hsCRP and isoprostanes, as well as lower estradiol and higher follicle-stimulating hormone across the menstrual cycle. Discussion: Women's preconception exposure to phthalates was associated with lower fecundability, changes in reproductive hormones, and increased inflammation and oxidative stress. The pre- and periconception periods may represent sensitive windows for intervening to limit the reproductive toxicity of phthalate exposure. https://doi.org/10.1289/EHP12287, Introduction Phthalates are esters of 1,2-benzene dicarboxylic acid commonly used as plasticizers in polyvinyl chloride and as stabilizers in many personal care products. Common sources of phthalate exposure include inhalation [...]

Using web-based survey data collected June - August 2018 from the Society for Epidemiologic Research (SER) members, we characterized numerous dimensions of social identity and lived experience, and assessed relationships between these characteristics and perceptions of inclusion and society participation. We quantified associations between characteristics, feeling very welcomed, high (top 25th percentile) self-initiated participation, and any (top 10th percentile) society-initiated participation. Racial/ethnic and religious minority categories were blinded to preserve anonymity and we accounted for missing data. Most 2018 SER members (n = 1631) were white (62%) or female (66%). Females with racial/ethnic non-response were least likely, while white males were most likely to report feeling very welcomed. Members who did not report race, identified with a specific racial/ethnic minority, or were politically conservative/right-leaning were less likely than white or liberal/left-leaning members to have high self-initiated participation. Women and individuals of a specific racial/ethnic minority or minority religious affiliations were less likely to participate in events initiated by the society. These data represent a baseline for assessing trends and the impact of future initiatives aimed at improving diversity, inclusion, representation and participation within SER.

Using web-based survey data collected June - August 2018 from the Society for Epidemiologic Research (SER) members, we characterized numerous dimensions of social identity and lived experience, and assessed relationships between these characteristics and perceptions of inclusion and society participation. We quantified associations between characteristics, feeling very welcomed, high (top 25th percentile) self-initiated participation, and any (top 10th percentile) society-initiated participation. Racial/ethnic and religious minority categories were blinded to preserve anonymity and we accounted for missing data. Most 2018 SER members (n = 1631) were white (62%) or female (66%). Females with racial/ethnic non-response were least likely, while white males were most likely to report feeling very welcomed. Members who did not report race, identified with a specific racial/ethnic minority, or were politically conservative/right-leaning were less likely than white or liberal/left-leaning members to have high self-initiated participation. Women and individuals of a specific racial/ethnic minority or minority religious affiliations were less likely to participate in events initiated by the society. These data represent a baseline for assessing trends and the impact of future initiatives aimed at improving diversity, inclusion, representation and participation within SER.

Residential clusters of non-communicable diseases are a source of enduring public concern, and at times, controversy. Many clusters reported to public health agencies by concerned citizens are accompanied by expectations that investigations will uncover a cause of disease. While goals, methods and conclusions of cluster studies are debated in the scientific literature and popular press, investigations of reported residential clusters rarely provide definitive answers about disease etiology. Further, it is inherently difficult to study a cluster for diseases with complex etiology and long latency (e.g., most cancers). Regardless, cluster investigations remain an important function of local, state and federal public health agencies. Challenges limiting the ability of cluster investigations to uncover causes for disease include the need to consider long latency, low statistical power of most analyses, uncertain definitions of cluster boundaries and population of interest, and in- and out-migration. A multi-disciplinary Workshop was held to discuss innovative and/or under-explored approaches to investigate cancer clusters. Several potentially fruitful paths forward are described, including modern methods of reconstructing residential history, improved approaches to analyzing spatial data, improved utilization of electronic data sources, advances using biomarkers of carcinogenesis, novel concepts for grouping cases, investigations of infectious etiology of cancer, and "omics" approaches.

Background: Multifetal gestation could be associated with higher long‐term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. Objectives: We examined whether spontaneously conceived multifetal versus singleton gestation was associated with long‐term maternal mortality in a racially diverse U.S. cohort. Methods: We ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959–1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all‐cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all‐cause and cause‐specific mortality over the study period and until age 50, 60, and 70 years (premature mortality). Results: Of eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all‐cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all‐cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all‐cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96). Conclusions: In a cohort with over 50 years of follow‐up, history of multifetal gestation was not associated with all‐cause mortality, but may be associated with a lower risk of premature mortality. [ABSTRACT FROM AUTHOR]