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Background: Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. Methods: A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. Results: At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. Conclusions: Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. Impact: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines. [ABSTRACT FROM AUTHOR]

Background: Police-reported crime data (hereafter "crime") is routinely used as a psychosocial stressor in public health research, yet few studies have jointly examined (a) differences in crime exposure based on participant race and ethnicity, (b) differences in measures of crime exposure, and (c) considerations for how exposure to police is captured in police-recorded crime data. We estimate neighborhood exposure to crime and discuss the implications of structural differences in exposure to crime and police based on race and ethnicity.Methods: Using GPS coordinates from 1188 participants in the Newborn Epigenetics Study, we estimated gestational exposure to crime provided by the Durham, North Carolina, Police Department within (a) 800 m and (b) the Census block group of residence. We controlled for non-overlapping spatial boundaries in crime, Census, residential, and police data to report crime spatial (crime per km2) and population (crime per 1000 people per km2) density.Results: We demonstrate dramatic disparities in exposure to crime based on participant race and ethnicity and highlight variability in these disparities based on the type of crime and crime measurement method chosen.Conclusions: Public health researchers should give thoughtful consideration when using police-reported crime data to measure and model exposure to crime in the United States, as police-reported data encompasses joint exposure to police and crime in the neighborhood setting. [ABSTRACT FROM AUTHOR]

Background and Objectives: Breastfeeding during infancy is associated with healthier beverage consumption later in childhood, but little is known about this relation during infancy. This was a longitudinal study of breastfeeding and less healthy beverage consumption during the first year of life, in a birth cohort study conducted 2013–2018 in the Southeastern United States (n = 666). Methods: We estimated monthly rates of 100% juice and sugar‐sweetened beverage (SSB) consumption comparing infants who were exclusively or partially breastfed, versus those who were not, in multivariable adjusted models. Results: Mothers had a median age of 26.5 years, 71% identified as Black/African‐American, and 61% reported household incomes <$20 000/year. The prevalence of any breastfeeding during the first month was 78.2% and 18.7% at month 12. By age 12 months, infants consumed juice a mean (SD) 9.1 (10.1) times per week and SSBs 3.6 (9.5) times per week. Breastfed infants had a 38% lower incidence rate of weekly juice consumption (95% CI 52%, 15%, p = 0.003) and a 57% lower incidence rate of weekly SSB consumption (95% CI 76%, 22%, p = 0.006), compared with infants who were not breastfed. Conclusions: Research on early‐life correlates of dietary health should focus on the earliest beverages, given evidence that consumption of obesogenic beverages may begin prior to age 1 year. [ABSTRACT FROM AUTHOR]

Epigenetic processes, such as changes in DNA methylation, likely mediate the link between environmental exposures in utero and altered gene expression. Differentially methylated regions (DMRs) that regulate imprinted genes may be especially vulnerable to environmental exposures since imprinting is established and maintained largely through DNA methylation, resulting in expression from only one parental chromosome. We used the human embryonic kidney cell line, HEK-293, to investigate the effects of exposure to physiologically relevant doses of lead acetate (Pb) on the methylation status of nine imprinted gene DMRs. We assessed mean methylation after seventy-two hours of Pb exposure (0–25 μg/dL) using bisulfite pyrosequencing. The PEG1 / MEST and IGF2 DMRs had maximum methylation decreases of 9.6% (20 μg/dL; p < 0.005) and 3.8% (25 μg/dL; p < 0.005), respectively. Changes at the MEG3 DMRs had a maximum decrease in methylation of 2.9% ( MEG3) and 1.8% ( MEG3-IG) at 5 μg/dL Pb, but were not statistically significant. The H19, NNAT, PEG3 , PLAGL1, and SGCE / PEG10 DMRs showed a less than 0.5% change in methylation, across the dose range used, and were deemed non-responsive to Pb in our model. Pb exposure below reportable/actionable levels increased expression of PEG1 / MEST concomitant with decreased methylation. These results suggest that Pb exposure can stably alter the regulatory capacity of multiple imprinted DMRs. [ABSTRACT FROM AUTHOR]

Background: Despite many efforts, preterm birth (PTB) is poorly understood and remains a major public health problem in the United States. Toxicological work suggests gestational parent (GP) diet may modify the effect of ambient pollutants on birth outcomes. We assessed risk of PTB in humans in relation to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) and variation by diet. Methods: 684 GP-singleton infant pairs in the Newborn Epigenetics Study prospective birth cohort were attributed ambient air pollutant exposures for each trimester based on residence. Total energy intake, percent of energy intake from saturated fat, and percent of energy intake from total fat were dichotomized at the 75th percentile. >We used log binomial regressions to estimate risk ratios (RR (95%CI)) for PTB by pollutant interquartile ranges, adjusting for GP age, pre-pregnancy body mass index, GP race/ethnicity, GP education, season of conception, household income, and each diet factor. We assessed departure from additivity using interaction contrast ratios (ICRs). We addressed missing covariate data with multiple imputation. Results: Point estimates suggest that O3 may be inversely associated with PTB when exposure occurs in trimester 2 (min RR: 0.77, 95% CI: 0.39, 1.49), but may be harmful when exposure occurs in trimester 3 (max RR: 1.51, 95% CI: 0.62, 3.64). Additionally, PM2.5 may be inversely associated with PTB when considered with total fat and saturated fat in trimester 2. Imprecise ICRs suggest departure from additivity (evidence of modification) with some pollutant-diet combinations. Conclusions: While confidence intervals are wide, we observed potential modification of pollutant associations by dietary factors. It is imperative that large cohorts collect the required data to examine this topic, as more power is necessary to investigate the nuances suggested by this work. [ABSTRACT FROM AUTHOR]

Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle-related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non-coding RNAs are viable mechanistic candidates for a non-genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health-related effects in future generations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Polymorphisms in the vitamin D receptor (VDR) gene have been shown in some studies to be associated with the risk of epithelial ovarian cancer (EOC) in Caucasian women. There are no published reports among African Americans. Methods: Case–control data from the North Carolina Ovarian Cancer Study were analyzed using logistic regression to determine the association between seven VDR polymorphisms and EOC in both Caucasians (513 cases, 532 controls) and African Americans (74 cases, 79 controls). In a larger sample of African–Americans (125 cases, 155 controls), we assessed associations between six SNPs in proximity of rs7975232. Results: African American women who carried at least one minor allele of rs7975232 were at higher risk for invasive EOC controlling for age and admixture with an odds ratio (OR) for association under the log-additive model of 2.08 (95% confidence interval (CI)=1.19, 3.63, p=0.010). No association was observed between any of the VDR variants and EOC among Caucasians. A larger sample of African Americans revealed a nearly two-fold increased risk of invasive EOC associated with rs7305032, a SNP in proximity to rs7975232 (R2 =0.369) with a log-additive OR of 1.87 (95% CI=1.20, 2.93, p=0.006). Conclusions: This is the first report showing VDR variants associated with ovarian cancer risk in African American women. A larger study of African American women is needed to confirm these findings. These results imply that vitamin D exposure is a possible modifiable risk factor of ovarian cancer among African Americans. [Copyright &y& Elsevier]

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008–2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2–2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7–48.6) and ICC (OR = 29.5, 95% CI 6.3–38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress. [ABSTRACT FROM AUTHOR]

Background Previous studies suggest an association between obesity and oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However, these studies have been limited in their ability to assess whether the effects of obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD) symptoms.Methods Individual participant data from 12 epidemiological studies (8 North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA cases and 11 159 control subjects were pooled. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between body mass index (BMI, kg/m2) and the risk of OA and OGJA. Random-effects meta-analysis was used to combine these ORs. We also investigated effect modification and synergistic interaction of BMI with GERD symptoms and gender.Results The association of OA and OGJA increased directly with increasing BMI (P for trend <0.001). Compared with individuals with a BMI <25, BMI &geq;40 was associated with both OA (OR 4.76, 95% CI 2.96–7.66) and OGJA (OR 3.07, 95% CI 1.89–4.99). These associations were similar when stratified by gender and GERD symptoms. There was evidence for synergistic interaction between BMI and GERD symptoms in relation to OA/OGJA risk.Conclusions These data indicate that BMI is directly associated with OA and OGJA risk in both men and women and in those with and without GERD symptoms. Disentangling the relationship between BMI and GERD will be important for understanding preventive efforts for OA and OGJA. [ABSTRACT FROM PUBLISHER]

The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9-5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2. [ABSTRACT FROM AUTHOR]

Background: Folate and iron deficiency during pregnancy are risk factors for anaemia, preterm delivery, and low birth weight, and may contribute to poor neonatal health and increased maternal mortality. The World Health Organization recommends supplementation of folic acid (FA) and iron for all pregnant women at risk of malnutrition to prevent anaemia. We assessed the use of prenatal folic acid and iron supplementation among women in a geographical area with a high prevalence of anaemia, in relation to socio-demographic, morbidity and health services utilization factors. Methods: We analysed a cohort of 21,889 women who delivered at Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania, between 1999 and 2008. Logistic regression models were used to describe patterns of reported intake of prenatal FA and iron supplements. Results: Prenatal intake of FA and iron supplements was reported by 17.2% and 22.3% of pregnant women, respectively. Sixteen percent of women reported intake of both FA and iron. Factors positively associated with FA supplementation were advanced maternal age (OR = 1.17, 1.02-1.34), unknown HIV status (OR = 1.54, 1.42-1.67), a diagnosis of anaemia during pregnancy (OR = 12.03, 9.66-14.98) and indicators of lower socioeconomic status. Women were less likely to take these supplements if they reported having had a malaria episode before (OR = 0.57, 0.53-0.62) or during pregnancy (OR = 0.45, 0.41-0.51), reported having contracted other infectious diseases (OR = 0.45, 0.42-0.49), were multiparous (OR = 0.73, 0.66-0.80), had preeclampsia/eclampsia (OR = 0.48, 0.38-0.61), or other diseases (OR = 0.55, 0.44-0.69) during pregnancy. Similar patterns of association emerged when iron supplementation alone and supplementation with both iron and FA were evaluated. Conclusions: FA and iron supplementation are low among pregnant women in Northern Tanzania, in particular among women with co-morbidities before or during pregnancy. Attempts should be made to increase supplementation both in general and among women with pregnancy complications. [ABSTRACT FROM AUTHOR]

Background: Folic acid (FA) added to foods during fortification is 70-85% bioavailable compared to 50% of folate occurring naturally in foods. Thus, if FA supplements also are taken during pregnancy, both mother and fetus can be exposed to FA exceeding the Institute of Medicine's recommended tolerable upper limit (TUL) of 1,000 micrograms per day (μg/d) for adult pregnant women. The primary objective is to estimate the proportion of women taking folic acid (FA) doses exceeding the TUL before and during pregnancy, and to identify correlates of high FA use. Methods: During 2005-2008, pre-pregnancy and pregnancy-related data on dietary supplementation were obtained by interviewing 539 pregnant women enrolled at two obstetrics-care facilities in Durham County, North Carolina. Results: Before pregnancy, 51% of women reported FA supplementation and 66% reported this supplementation during pregnancy. Before pregnancy, 11.9% (95% CI = 9.2%-14.6%) of women reported supplementation with FA doses above the TUL of 1,000 μg/day, and a similar proportion reported this intake prenatally. Before pregnancy, Caucasian women were more likely to take FA doses above the TUL (OR = 2.99; 95% = 1.28-7.00), compared to African American women, while women with chronic conditions were less likely to take FA doses above the TUL (OR = 0.48; 95%CI = 0.21-0.97). Compared to African American women, Caucasian women were also more likely to report FA intake in doses exceeding the TUL during pregnancy (OR = 5.09; 95%CI = 2.07-12.49). Conclusions: Fifty-one percent of women reported some FA intake before and 66% during pregnancy, respectively, and more than one in ten women took FA supplements in doses that exceeded the TUL. Caucasian women were more likely to report high FA intake. A study is ongoing to identify possible genetic and nongenotoxic effects of these high doses. [ABSTRACT FROM AUTHOR]

Abstract: Background : Middle-aged African American women have the highest incidence and mortality of invasive cervical cancer in the United States and the lowest adherence to pap smear screening. Methods : In 2001, we identified factors associated with non-adherence to screening recommendations using three focus group interviews and subsequently developed a questionnaire administered to 144 African American women aged 45 to 65 years. Results : The perception that the Pap test was painful was associated with non-adherence to screening recommendations (OR = 4.78; 95%CI: 1.67–13.7). Difficulty to pay for the office visit coupled with perceived pain was associated with a nearly sixfold increase in risk of non-adherence (OR = 5.8; 95%CI: 2.8–15.5). Previously identified barriers to screening including lower education and socioeconomic status, poor access to care, knowledge of and exposure to known risk factors of invasive cervical cancer, cancer fatalism, and perceived racism were not independently associated with non-adherence. Conclusions : These data suggest that, among middle-aged African American women, future interventions addressing pain during a Pap test will likely increase acceptability of and adherence to cervical cancer screening. Pain could be addressed either by providing information during the pap test and/or using smaller lubricated speculums. [Copyright &y& Elsevier]

To estimate the prevalence of lower urinary tract symptoms (LUTS) by severity (using the International Prostate Symptom Score, IPSS) in a population-based study of men aged ≥ 20 years, and to assess the association between putative risk factors and the presence of moderate to severe LUTS. Between 1995 and 1997, LUTS data were collected from 21 694 male residents aged ≥ 20 years in Nord Trøndelag County in Norway, using the IPSS; from the IPSS (score 0–35) LUTS was defined as a score of ≥ 8, indicating moderate to severe symptoms. We estimated the prevalence of LUTS and used logistic regression analysis to study lifestyle and anthropometric factors, and comorbidity related to LUTS. The overall prevalence of moderate to severe LUTS was 15.8% (13.2% moderate and 2.6% severe). The prevalence of LUTS increased strongly with age, from ≈ 5% among men aged < 40 years to > 30% when aged ≥ 70 years. Factors positively associated with an increased risk of moderate and severe LUTS were anthropometric (body mass index and waist hip ratio) and lifestyle factors (alcohol consumption and smoking), as well as comorbid conditions, including diabetes, history of stroke, muscle complaints and osteoarthritis. The findings from this population-based study suggest that the prevalence of LUTS among men aged ≥ 20 years may be lower than previously estimated. Although LUTS may be viewed as an inevitable consequence of ageing, it appears to be exacerbated by lifestyle factors and comorbid conditions. [ABSTRACT FROM AUTHOR]

Objectives/goal: Most resource-poor settings rely on syndromic criteria to diagnose genital ulcer disease (GUD). However, the etiologic pathogens of GUD vary temporally and geographically, and current criteria may not reflect changes in the prevalence of specific pathogens.Study: In 1999, we estimated the prevalence of Treponema pallidum (Tp), herpes simplex virus (HSV), and Haemophilus ducreyi (Hd) in Malawi. We then used regression coefficients of independent correlates of HSV and Hd to develop weighted diagnostic algorithms, in which weights were beta-coefficients corresponding to each factor.Results: Overall, a decrease in the proportion of sexually transmitted disease attributable to GUD was noted in 7 years. Thirty-five percent were attributable to HSV, 30% to H. ducreyi, and 4% to T. pallidum. Areas under the receiver operating characteristic curves for weighted and unweighted HSV diagnostic algorithms were 67.6% and 66.5%, respectively. There was no significant difference in the explanatory performance of the weighted and unweighted algorithms.Conclusions: Unweighted algorithms can therefore be used to improve diagnostic accuracy of GUD. [ABSTRACT FROM AUTHOR]

Tobacco retail outlet (TRO) density has been associated with increased cotinine levels in pregnant persons and their children. As such, the higher densities of TROs may represent higher levels of active smoking during pregnancy. The purpose of this study is to simulate the reduction in cotinine (a biomarker of smoke exposure) and health care utilization that could occur in pregnant persons under enactment of several candidate TRO reduction policy recommendations. Using existing retail outlet data from the state of North Carolina and from the Newborn Epigenetic Study (NEST), the present study created hypothetical policy-informed datasets of TROs that a) limited the number of TROs to the same density as the 2014 San Francisco (SF) policy (Policy 1), b) set the minimum distance to 500 feet between TROs from a school and from other TROs (Policy 2), c) restricted the types of TROs to exclude pharmacies (Policy 3), and d) a combination of Policies 1–3 (Policy 4). We estimated the effects of each policy individually and in a separate model with their combined effects in terms of the reduction on cotinine levels and health care utilization, as measured by number of visits to the emergency department (ED). We found that the hypothetical policies were likely to be effective in reducing maternal cotinine and ED visits, with the majority of the mothers in the dataset demonstrating reductions in these outcomes after implementation of the policies. We found that Policy 1 led to moderate reductions in TRO exposure for the majority of the sample as well as stratified by race/ethnicity. Additionally, Policy 4 had slightly larger estimated effects than Policy 1, but could be more onerous to implement in practice. Overall, we identified evidence supporting the efficacy of TRO reduction strategies that could impact smoke exposure during pregnancy in our diverse sample in North Carolina. [ABSTRACT FROM AUTHOR]

Introduction Identifying healthcare utilization and costs associated with active and passive smoking during pregnancy could help improve health management strategies. Aims and Methods Data are from the Newborn Epigenetics STudy (NEST), a birth cohort enrolled from 2005 to 2011 in Durham and adjacent counties in North Carolina, United States. Participants included those for whom prenatal serum samples were assayed and for whom administrative data were obtainable (N  = 1045). Zero-inflated poisson regression models were used to assess associations between cotinine, adjusted for covariates (eg, race and ethnicity, age at delivery, cohabitation status, and education), and health care utilization outcomes. Generalized linear regression models were used to estimate average total charges. Simulation models were conducted to determine the economic benefits of reducing secondhand smoke and smoking during pregnancy. Results Increasing levels of cotinine were positively associated with parent's number of emergency department (ED) visits (coefficient[b] = 0.0012, standard error [SE] = 0.0002; p  < .001), the number of ICU hours (b = 0.0079, SE = 0.0025; p  = .002), time spent in the ICU (b = 0.0238, SE = 0.0020, p  < .001), and the number of OP visits (b = 0.0003, SE = 0.0001; p  < .001). For infants, higher cotinine levels were associated with higher number of ED (b = 0.0012, SE = 0.0004; p  = .005), ICU (b = 0.0050, SE = 0.001; p  < .001), and OP (b = 0.0006, SE = 0.0002; p  < .001) visits and longer time spent in the ED (b = 0.0025, SE = 0.0003; p  < .001), ICU (b = 0.0005, SE = 0.0001; p  < .001), and IP (b = 0.0020, SE = 0.0002; p  < .001). Simulation results showed that a 5% reduction in smoking would correspond to a potential median cost savings of $150 533 from ED visits of parents and infants. Conclusions Our findings highlight the importance of smoke exposure cessation during pregnancy to reduce health care utilization and costs for both parents and infants. Implications This study reinforces the importance of reducing smoking and secondhand smoke exposure during pregnancy. Focusing on expanding cessation services to this group could help reduce morbidities observed within this population. Furthermore, there is the potential for healthcare cost savings to healthcare systems, especially for those with high delivery numbers. These cost savings are represented by potential reductions in ED, OP, and ICU hours and visits. [ABSTRACT FROM AUTHOR]

Low food security during pregnancy can negatively affect women's physical and mental health. Although many women make a greater effort to eat a healthy diet during pregnancy, the influence of low food security during pregnancy on maternal diet is not well understood. This study aimed to assess the association between adult food security and maternal diet during pregnancy in a sample from North Carolina. This was a cross-sectional, secondary data analysis of food security (marginal, low, and very low vs high) and maternal diet during pregnancy. This study included 468 predominantly Black/African American women during pregnancy from the Nurture cohort, enrolled through prenatal clinics in central North Carolina between 2013 and 2016. Diet quality was assessed using the Alternate Healthy Eating Index-Pregnancy and the Mediterranean Diet Score. Dietary intake from seven food groups included in the Alternate Healthy Eating Index-Pregnancy and/or Mediterranean Diet Score was assessed as well. Multiple linear regression models were used to examine the association between food security and diet quality and dietary intake during pregnancy, adjusting for race/ethnicity; participation in the Special Supplemental Nutrition Program for Women, Infants, and Children; education; prepregnancy body mass index; age; parity; and mean daily energy intake. In this study, there was no association between maternal food security status and diet quality during pregnancy. However, researchers observed an association between low and marginal food security and greater intake of red and processed meats (marginal: β = 2.20 [ P = 0.03]; low: β = 2.28 [ P = 0.04]), as well as an association between very low food security and decreased vegetable consumption (β = –.43; P = 0.03). Very low food security was associated with reduced vegetable intake. In addition, low and marginal food security were associated with greater red and processed meat intake. Future research should focus on nationally representative populations and include longitudinal assessments to allow for the study of the influence of food security on health during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Differentially methylated imprint control regions (ICRs) regulate the monoallelic expression of imprinted genes. Their epigenetic dysregulation by environmental exposures throughout life results in the formation of common chronic diseases. Unfortunately, existing Infinium methylation arrays lack the ability to profile these regions adequately. Whole genome bisulfite sequencing (WGBS) is the unique method able to profile the ICRs. However, it is very expensive and it requires not only a high coverage, but it is also computationally intensive to assess these regions. Findings: To address this deficiency, we developed a custom methylation array containing 22,819 probes. Among them, 10,438 are CG probes targeting unique CpG sites, with 9,757 probes successfully mapping to 1,088 out of the 1,488 candidate ICRs recently described. To assess the performance of the array, we created matched samples processed with the Human Imprintome array and WGBS, which is the current standard method for assessing the methylation of the Human Imprintome. We compared the methylation levels from the shared CpG sites, and obtained a mean R2 = 0.569. We also created matched samples processed with the Human Imprintome array and the Infinium Methylation EPIC v2 array, and obtained a mean R2 = 0.796. Furthermore, replication experiments demonstrated high reliability (ICC: 0.799–0.945). Conclusions: Our custom array will be useful for replicable and accurate assessment, mechanistic insight, and targeted investigation of ICRs. This tool should accelerate the discovery of ICRs associated with a wide range of diseases and exposures, and advance our understanding of genomic imprinting and its relevance in development and disease formation throughout the life course. [ABSTRACT FROM AUTHOR]

Given growing specialization in medical care, optimal care may require regionalization, which may create access barriers. We tested this within a large prostate cancer (PC) screening program in Brazil. In 2004–2007, Barretos Cancer Hospital prospectively screened men for PC throughout rural Brazil. Men with abnormal screen were referred for follow-up and possible biopsy. We tested the link between distance from screening site to Barretos Cancer Hospital and risk of noncompliance with showing up for biopsy, PC on biopsy and, among those with PC, PC grade using crude and multivariable logistic regression analysis. Among 10,467 men undergoing initial screen, median distance was 257 km (IQR: 135–718 km). On crude and multivariable analyses, farther distance was significantly linked with biopsy noncompliance (OR/100 km: 0.83, P < 0.001). Among men who lived within 150 km of Barretos Cancer Hospital, distance was unrelated to compliance (OR/100 km: 1.09, P = 0.87). There was no association between distance and PC risk or PC grade (all P > 0.25). In Brazil, where distances to referral centers can be large, greater distance was related to reduced biopsy compliance in a PC screening cohort. Among men who lived within 150 km, distance was unrelated to compliance. Care regionalization may reduce access when distances are large. [ABSTRACT FROM AUTHOR]

Background: Early introduction of complementary foods has been associated with various immune disorders, oxidative stress, and obesity in childhood. The gut microbiota and the short chain fatty acids (SCFAs) they produce are postulated to be on the causal pathway. The objective of this study was to determine if early complementary feeding (i.e. consumption of solids or non-water/formula liquids at or before 3 months) is prospectively associated with infant gut microbiota composition, diversity and SCFAs at 3 and 12 months of age in the Nurture birth cohort. Results: Mother-infant dyads in the early complementary feeding group (n = 18) had similar baseline characteristics to those in the later feeding group (n = 49). We assessed differential abundance of microbial taxa (measured by 16S rRNA gene sequencing of the V4 region) by timing of complementary feeding using beta-binomial regression models (considering a two-sided FDR corrected p-value of < 0.05 as significant), and we fittted linear regression models to assess the association between early complementary feeding and SCFA concentrations (quantified using gas chromatography). After multivariable adjustment for breastfeeding, delivery method, birth weight, and gestational age, there were 13 differentially abundant microbial amplicon sequence variants (ASVs) by timing of introduction to complementary foods at 3 months and 20 ASVs at 12 months. Infants introduced to complementary foods early (vs. later) had higher concentrations of the SCFA butyric acid (mean difference = 0.65, 95% CI: 0.27, 1.04, p < 0.01) and total SCFAs (mean difference = 38.8, 95% CI: 7.83, 69.7) at 12 months. Bilophila wadsworthia and Lachnospiraceae Roseburia were associated with early (vs. later) complementary feeding and with higher butyric acid concentrations at 3 and 12 months, respectively. Conclusions: Our findings are consistent with the hypothesis that early (vs. later) introduction to complementary foods is associated with altered gut microbiota composition and butyric acid concentrations measured in stool until at least 1 year of age. Further research is needed to determine if these changes mediate future development of metabolic and immune conditions. [ABSTRACT FROM AUTHOR]

The authors explores the foundation investigating the role of genetic and environmental factors in the aetiology of neurological disorders and complex diseases. They highlight the use of genotypes in the assessment of genetic factors. According to the authors, genetic risk factors promise to result in epidemiological studies focusing on the development of chronic complex disease on individuals.

Investigate residential segregation and prenatal depression in a non-Hispanic (NH) Black and Hispanic North Carolina pregnancy cohort. Demographics, prenatal depression (Center for Epidemiological Studies Depression scale ≥ 16), and residence from the 2006–2009 Newborn Epigenetic Survey were linked to Census-tract levels of racial and economic segregation (Index of Concentration at the Extremes) from the American Community Survey 2005–2009 5-year estimates. Adjusted prevalence ratios (aPR) for prenatal depression compared living in Index of Concentration at the Extremes tertiles 1 and 2 (higher proportion NH Black or Hispanic and/or low income) to 3 (higher proportion NH white and/or high-income), accounting for neighborhood clustering, age, education, employment, parity, and marital status. Among the 773 survey participants (482 NH Black and 291 Hispanic), 35.7% and 27.2% of NH Black and Hispanic participants had prenatal depression, respectively. For NH Black participants, depression prevalence was 17% lower for tertile 1 versus 3 for the NH Black/white (aPR=0.83; 95% CI=0.62–1.10), low/high income (aPR=0.83; 95% CI=0.62–1.11), and low-income NH Black/high-income NH white (aPR=0.82; 95% CI=0.61–1.09) measures. For Hispanic participants, estimates were weaker in the opposite direction for the Hispanic/NH white (aPR=1.02; 95% CI=0.71–1.47), low/high income (aPr=1.14; (95% CI=0.76–1.69), and low-income Hispanic/high-income NH white (aPR=1.12; 95% CI=0.78–1.60) measures. Residential segregation's impact on prenatal depression may differ by race/ethnicity and level of segregation, but findings are imprecise due to small sample sizes. Longitudinal research spanning greater geographic areas is needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]). Methods: Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy. Results: There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 – -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 – -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02–0.08). Conclusions: Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress. [ABSTRACT FROM AUTHOR]

Background: To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]). Methods: Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy. Results: There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 – -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 – -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02–0.08). Conclusions: Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress. [ABSTRACT FROM AUTHOR]

Background: To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]). Methods: Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy. Results: There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 – -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 – -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02–0.08). Conclusions: Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress. [ABSTRACT FROM AUTHOR]

Background: To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]). Methods: Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy. Results: There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 – -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 – -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02–0.08). Conclusions: Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress. [ABSTRACT FROM AUTHOR]

Introduction: Smoking and smoke exposure among pregnant women remain persistent public health issues. Recent estimates suggest that approximately one out of four nonsmokers have measurable levels of cotinine, a marker indicating regular exposure to secondhand smoke. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy. However, most of these studies have relied upon self-reported measures of smoking.Aims and Methods: To more accurately assess smoke exposure resulting from both smoking and secondhand exposure in mothers during pregnancy, we used Bayesian regression models to estimate the association of cotinine levels with tobacco retail outlet (TRO) exposure and a neighborhood deprivation index (NDI) in six counties in North Carolina centered on Durham County.Results: Results showed a significant positive association between TRO exposure (β = 0.008, 95% credible interval (CI) = [0.003, 0.013]) and log cotinine after adjusting for individual covariates (eg, age, race/ethnicity, education, marital status). TRO exposure was not significant after including the NDI, which was significantly associated with log cotinine (β = 0.143, 95% CI = [0.030, 0.267]). However, in a low cotinine stratum (indicating secondhand smoke exposure), TRO exposure was significantly associated with log cotinine (β = 0.005, 95% CI = [0.001, 0.009]), while in a high cotinine stratum (indicating active smoking), the NDI was significantly associated with log cotinine (β = 0.176, 95% CI = [0.005, 0.372]).Conclusions: In summary, our findings add to the evidence that contextual factors are important for active smoking during pregnancy.Implications: In this study, we found several significant associations that suggest a more nuanced understanding of the potential influence of environmental- and individual-level factors for levels of prenatal smoke exposure. Results suggested a significant positive association between TRO exposure and cotinine levels, after adjusting for the individual factors such as race, education, and marital status. Individually, NDI was similarly positively associated with cotinine levels as well. However, when combining TRO exposure alongside NDI in the same model, TROs were no longer significantly associated with overall cotinine levels. [ABSTRACT FROM AUTHOR]

Background: Psychosocial and physiologic stressors, such as depression and obesity, during pregnancy can have negative consequences, such as increased systemic inflammation, contributing to chronic disease for both mothers and their unborn children. These conditions disproportionately affect racial/ethnic minorities. The effects of recommended dietary patterns in mitigating the effects of these stressors remain understudied. Objectives: We aimed to evaluate the relations between maternal Mediterranean diet adherence (MDA) and maternal and offspring outcomes during the first decade of life in African Americans, Hispanics, and Whites. Methods: This study included 929 mother–child dyads from the NEST (Newborn Epigenetics STudy), a prospective cohort study. FFQs were used to estimate MDA in pregnant women. Weight and height were measured in children between birth and age 8 y. Multivariable linear regression models were used to examine associations between maternal MDA, inflammatory cytokines, and pregnancy and postnatal outcomes. Results: More than 55% of White women reported high MDA during the periconceptional period compared with 22% of Hispanic and 18% of African American women (P < 0.05). Higher MDA was associated with lower likelihood of depressive mood (β = −0.45; 95% CI: −0.90, −0.18; P = 0.02) and prepregnancy obesity (β = −0.29; 95% CI: −0.57, −0.0002; P = 0.05). Higher MDA was also associated with lower body size at birth, which was maintained to ages 3–5 and 6–8 y—this association was most apparent in White children (3–5 y: β = −2.9, P = 0.02; 6–8 y: β = −3.99, P = 0.01). Conclusions: If replicated in larger studies, our data suggest that MDA provides a potent avenue by which effects of prenatal stressors on maternal and fetal outcomes can be mitigated to reduce ethnic disparities in childhood obesity. [ABSTRACT FROM AUTHOR]

Despite years of advisories against the behavior, smoking among pregnant women remains a persistent public health issue in the USA. Recent estimates suggest that 9.4% of women smoke before pregnancy and 7.1% during pregnancy in the USA. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy, including educational attainment, employment status, housing conditions, poverty, and racial demographics. However, most of these studies have relied upon self-reported measures of smoking, which are subject to reporting bias. To more accurately and objectively assess smoke exposure in mothers during pregnancy, we used Bayesian index models to estimate a neighborhood deprivation index (NDI) for block groups in Durham County, North Carolina, and its association with cotinine, a marker of smoke exposure, in pregnant mothers (n = 887 enrolled 2005–2011). Results showed a significant positive association between NDI and log cotinine (beta = 0.20, 95% credible interval = [0.11, 0.29]) after adjusting for individual covariates (e.g., race/ethnicity and education). The two most important variables in the NDI according to the estimated index weights were percent females without a high school degree and percent Black population. At the individual level, Hispanic and other race/ethnicity were associated with lowered cotinine compared with non-Hispanic Whites. Higher education levels were also associated with lowered cotinine. In summary, our findings provide stronger evidence that the socio-geographic variables of educational attainment and neighborhood racial composition are important factors for smoking and secondhand smoke exposure during pregnancy and can be used to target intervention efforts. [ABSTRACT FROM AUTHOR]

Children conceived with assisted reproductive technology (ART) have an increased risk of adverse outcomes, including congenital malformations and imprinted gene disorders. In a retrospective North Carolina-based-birth-cohort, we examined the effect of ovulation drugs and ART on CpG methylation in differentially methylated CpGs in known imprint control regions (ICRs). Nine ICRs containing 48 CpGs were assessed for methylation status by pyrosequencing in mixed leukocytes from cord blood. After restricting to non-smoking, college-educated participants who agreed to follow-up, ART-exposed (n = 27), clomifene-only-exposed (n = 22), and non-exposed (n = 516) groups were defined. Associations of clomifene and ART with ICR CpG methylation were assessed with linear regression and stratifying by offspring sex. In males, ART was associated with hypomethylation of the PEG3 ICR [β(95% CI) = −1.46 (−2.81, −0.12)] and hypermethylation of the MEG3 ICR [3.71 (0.01, 7.40)]; clomifene-only was associated with hypomethylation of the NNAT ICR [−5.25 (−10.12, −0.38)]. In female offspring, ART was associated with hypomethylation of the IGF2 ICR [−3.67 (−6.79, −0.55)]. Aberrant methylation of these ICRs has been associated with cardiovascular disease and metabolic and behavioral outcomes in children. The results suggest that the increased risk of adverse outcomes in offspring conceived through ART may be due in part to altered methylation of ICRs. Larger studies utilizing epigenome-wide interrogation are warranted. [ABSTRACT FROM AUTHOR]

Background Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood. Methods We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010-2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences. Results Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education. Conclusions Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers. [ABSTRACT FROM AUTHOR]

Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation profiles. This theoretical 50% level of methylation provides a baseline from which endogenously- or exogenously-induced deviations in methylation can be detected. We quantified DNA methylation at imprinted gene DMRs in a large panel of human conceptal tissues, in matched buccal cell specimens collected at birth and at one year of age, and in the major cell fractions of umbilical cord blood to assess the stability of methylation at these regions. DNA methylation was measured using validated pyrosequencing assays at seven DMRs regulating the IGF2/H19, DLK1/MEG3, MEST, NNAT and SGCE/PEG10 imprinted domains. DMR methylation did not significantly differ for the H19, MEST and SGCE/PEG10 DMRs across all conceptal tissues analyzed (ANOVA p.0.10). Methylation differences at several DMRs were observed in tissues from brain (IGF2 and MEG3-IG DMRs), liver (IGF2 and MEG3 DMRs) and placenta (both DLK1/MEG3 DMRs and NNAT DMR). In most infants, methylation profiles in buccal cells at birth and at one year of age were comparable, as was methylation in the major cell fractions of umbilical cord blood. Several infants showed temporal deviations in methylation at multiple DMRs. Similarity of inter-individual and intra-individual methylation at some, but not all of the DMRs analyzed supports the possibility that methylation of these regions can serve as useful biosensors of exposure. [ABSTRACT FROM AUTHOR]

Abstract: Experimental studies suggest omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA promote prostate tumor carcinogenesis. Epidemiologic evidence remains inconclusive. The objectives of this study were to examine the association between n-3 and n-6 PUFA and prostate cancer risk and determine if these associations differ by race or disease aggressiveness. We hypothesize that high intakes of n-3 and n-6 PUFA will be associated with lower and higher prostate cancer risk, respectively. A case-control study comprising 79 prostate cancer cases and 187 controls was conducted at the Durham VA Medical Center. Diet was assessed using a food frequency questionnaire. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations between n-3 and n-6 PUFA intakes, the dietary ratio of n-6/n-3 fatty acids, and prostate cancer risk. Our results showed no significant associations between specific n-3 or n-6 PUFA intakes and prostate cancer risk. The highest dietary ratio of n-6/n-3 was significantly associated with elevated risk of high-grade (OR, 3.55; 95% CI, 1.18-10.69; P trend = 0.03), but not low-grade prostate cancer (OR, 0.95; 95% CI, 0.43-2.17). In race-specific analyses, an increasing dietary ratio of n-6/n-3 fatty acids correlated with higher prostate cancer risk among white men (P trend = 0.05), but not black men. In conclusion, our findings suggest that a high dietary ratio of n-6/n-3 fatty acids may increase the risk of overall prostate cancer among white men and possibly increase the risk of high-grade prostate cancer among all men. [Copyright &y& Elsevier]

Summary: Background: Although maternal systemic inflammation is hypothesized to link maternal pre‐pregnancy obesity to offspring metabolic dysfunction, patient empirical data are limited. Objectives: In this study, we hypothesized that pre‐pregnancy obesity alters systemic chemo/cytokines concentrations in pregnancy, and this alteration contributes to obesity in children. Methods: In a multi‐ethnic cohort of 361 mother‐child pairs, we measured prenatal concentrations of plasma TNF‐α, IL‐6, IL‐8, IL‐1β, IL‐4, IFN‐γ, IL‐12 p70 subunit, and IL‐17A using a multiplex ELISA and examined associations of pre‐pregnancy obesity on maternal chemo/cytokine levels, and associations of these cytokine levels with offspring body mass index z score (BMI‐z) at age 2–6 years using linear regression. Results: After adjusting for maternal smoking, ethnicity, age, and education, pre‐pregnancy obesity was associated with increased concentrations of TNF‐α (P =.026) and IFN‐γ (P =.06). While we found no evidence for associations between TNF‐α concentrations and offspring BMI‐z, increased IFN‐γ concentrations were associated with decreased BMI‐z (P =.0002), primarily in Whites (P =.0011). In addition, increased maternal IL‐17A concentrations were associated with increased BMI‐z in offspring (P =.0005) with stronger associations in African Americans (P =.0042) than Whites (P =.24). Conclusions: Data from this study are consistent with maternal obesity‐related inflammation during pregnancy, increasing the risk of childhood obesity in an ethnic‐specific manner. [ABSTRACT FROM AUTHOR]

Introduction: Many children suffer from secondhand smoke exposure (SHSe), which leads to a variety of negative health consequences. However, there is no consensus on how clinicians can best query parents for possible SHSe among children. We employed a data-driven approach to create an efficient screening tool for clinicians to quickly and correctly identify children at risk for SHSe.Methods: Survey data from mothers and biospecimens from children were ascertained from the Neurodevelopment and Improving Children's Health following Environmental Tobacco Smoke Exposure (NICHES) study. Included were mothers and their children whose saliva were assayed for cotinine (n = 351 pairs, mean child age = 5.6 years). Elastic net regression predicting SHSe, as indicated from cotinine concentration, was conducted on available smoking-related questions and cross-validated with 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to select the most predictive items of SHSe among children (n = 1670, mean child age = 8.4 years).Results: Answering positively to at least one of the two final items ("During the past 30 days, did you smoke cigarettes at all?" and "Has anyone, including yourself, smoked tobacco in your home in the past 7 days?") showed area under the curve = .82, and good specificity (.88) and sensitivity (.74). These results were validated with similar items in the nationally representative NHANES sample, area under the curve = .82, specificity = .78, and sensitivity = .77.Conclusions: Our data-driven approach identified and validated two items that may be useful as a screening tool for a speedy and accurate assessment of SHSe among children.Implications: The current study used a rigorous data-driven approach to identify questions that could reliably predict SHSe among children. Using saliva cotinine concentration levels as a gold standard for determining SHSe, our analysis employing elastic net regression identified two questions that served as good classifier for distinguishing children who might be at risk for SHSe. The two items that we validated in the current study can be readily used by clinicians, such as pediatricians, as part of screening procedures to quickly identify whether children might be at risk for SHSe. [ABSTRACT FROM AUTHOR]

Background: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. Methods: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race. Results: Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03–2.36). Conclusions: While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases. [ABSTRACT FROM AUTHOR]

Objectives. This study assessed the impact on HIV test-seeking of North Carolina's restriction of anonymous testing to 18 of its 100 counties as of September 1, 1991. Methods. Trends from 4 months prerestriction to the 16-month restriction period in counties retaining vs counties eliminating anonymous testing were compared. Results. HIV testing increased throughout the state, but more rapidly where anonymous testing was retained than elsewhere: 64% vs 44%. These differences held for all sociodemographic subgroups and were most pronounced among adolescents and African Americans and other non-Whites. Conclusions. The data are consistent with a detrimental effect of elimination of anonymous testing, although confounding from differences in AIDS awareness or in repeat tests is possible. [ABSTRACT FROM AUTHOR]

Background: Attention‐deficit/hyperactivity disorder (ADHD) symptoms have been linked with eating behaviors and obesity adolescence and young adulthood. Yet, little is known about whether these associations occur during early childhood and few studies have examined these associations prospectively. Objectives: To assess magnitude and direction of associations between childhood ADHD symptoms and eating behaviors. Methods: Participants were from the Newborn Epigenetics Study (N = 470, M age = 4 years). Multivariable linear regression models were used to examine cross‐sectional associations between ADHD symptoms and eating behaviors. Latent Change Score (LCS) modeling was performed to examine prospective association among a subset of children with available follow‐up data. (N = 100, M age = 7 years). Results: The cross‐sectional results showed that attention problem (AP) and hyperactivity (HY) were positively associated with food responsiveness, emotional overeating, desire to drink, and slowness in eating. AP, but not HY, was inversely associated with enjoyment of food. Results of the LCS models revealed AP and HY were both positively associated with prospective changes in emotional overeating and satiety responsiveness. AP was further positively associated with prospective changes in food responsiveness. The reverse relationship predicting changes in ADHD symptoms from earlier assessments of eating behaviors was not significant. Conclusion: Results suggest a link between ADHD symptoms and obesity‐related eating behaviors in early childhood, highlighting the need to address self‐regulation and healthy eating behaviors in the prevention of childhood obesity. [ABSTRACT FROM AUTHOR]

Objectives: Childhood asthma is a common chronic illness that has been associated with mode of delivery. However, the effect of cesarean delivery alone does not fully account for the increased prevalence of childhood asthma. We tested the hypothesis that neuraxial anesthesia used for labor analgesia and cesarean delivery alters the risk of developing childhood asthma.Methods: Within the Newborn Epigenetics Study birth cohort, 196 mother and child pairs with entries in the electronic anesthesia records were included. From these records, data on maternal anesthesia type, duration of exposure, and drugs administered peripartum were abstracted and combined with questionnaire-derived prenatal risk factors and medical records and questionnaire-derived asthma diagnosis data in children. Logistic regression models were used to evaluate associations between type of anesthesia, duration of anesthesia, and the development of asthma in males and females.Results: We found that longer duration of epidural anesthesia was associated with a lower risk of asthma in male children (OR = 0.80; 95% CI = 0.66-0.95) for each hour of epidural exposure. Additionally, a unit increase in the composite dose of local anesthetics and opioid analgesics administered via the spinal route was associated with a lower risk of asthma in both male (OR = 0.59, 95% CI = 0.36-0.96) and female children (OR 0.26, 95% CI 0.09-0.82).Conclusion: Our data suggest that peripartum exposure to neuraxial anesthesia may reduce the risk of childhood asthma primarily in males. Larger human studies and model systems with longer follow-up are required to elucidate these findings. [ABSTRACT FROM AUTHOR]

Introduction: Both prenatal smoke exposure and depression have been linked to lower birth weight, a risk factor for morbidity and mortality. Few studies have looked at the interaction between these risk factors and none have used a biomarker to objectively measure prenatal smoke exposure. The current study sought to examine independent and interactive effects of cotinine and depression on birth weight. The effect of race was also explored.Method: Data were drawn from a prospective study of pregnant women (N = 568) in the southeastern United States. Maternal demographic, health information, depressive symptoms, and birth data were collected via self-report and medical record abstraction. Prenatal blood samples were assayed for cotinine.Results: Controlling for covariates, multiple regression analyses indicated that both cotinine and depressive symptoms independently predicted lower birth weight and a significant interaction was also observed. Upon probing the interaction, a negative association between cotinine levels and birth weight was found in the context of higher depression but not lower depression scores. Similarly, logistic regression analyses revealed a significant interaction between cotinine and depression, such that cotinine predicted having a baby less than 2500 g among women who fell above the indicated cutoff score. African American women had the highest levels of cotinine and lowest weight babies; however, race was not a significant moderator.Conclusions: Results suggest prenatal smoke exposure has a greater negative effect on birth weight for women endorsing co-occurring depressive symptoms. Findings can inform targeted interventions and assist medical providers with identifying women at increased risk for poor perinatal outcomes.Implications: Despite the common occurrence of smoking during pregnancy and prenatal depression, the interaction between these risk factors on birth weight has rarely been examined. Further, the extant results have been mixed, likely due in part to difficulties in measurement. The current study was the first to use prenatal cotinine to assess bias-free, continuous levels of prenatal smoke exposure. Results indicate that prenatal cotinine was a significant predictor of birth weight only in the context of maternal depressive symptoms. These findings have important implications for mitigating negative perinatal outcomes for pregnant women and their children. [ABSTRACT FROM AUTHOR]

The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4–5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors. [ABSTRACT FROM AUTHOR]

Background: Approximately 17% of children in the U.S. are obese. Children that are overweight or obese are also more likely to be obese as adults and suffer from various chronic diseases and premature death. Maternal obesity can affect the weight status of her offspring through intrauterine mechanisms like excessive gestational weight gain (GWG). Current literature shows a positive association between maternal weight status and GWG on child obesity, yet the direct and indirect effects have not been decomposed or quantified. The purpose of this study was to estimate the effect of maternal obesity on child obesity, mediated by GWG, which is a modifiable risk factor.Methods: The study participants were a birth cohort of offspring from women who received prenatal care in the Duke/Durham Regional health care system in Durham, NC between 2005 and 2009. Anthropomorphic data was collected via electronic medical records (EMRs) during each voluntary visit to a health care facility. The exposure of interest was maternal obesity, measured by pre-pregnancy body mass index, the mediator was GWG, dichotomized into excessive and not excessive based on maternal prenatal BMI, and the outcome was child obesity at age 4, measured as BMI z-scores from the last recorded height and weight. A counterfactual theory-based product method analysis estimated the mediated effects of GWG, adjusted for maternal race, socioeconomic status, and smoking status.Results: Of the 766 children, 25% were overweight or obese, and among all mothers, 25 and 31% were overweight and obese, respectively. Maternal BMI was associated with an overall increase of 0.04 in offspring z-score. The proportion of the effect of maternal obesity on child age 4 obesity mediated by GWG was 8.1%.Conclusion: GWG, in part, mediated the relationship between maternal BMI and childhood adiposity. Even when the mediator is fixed, children are at an increased risk of a higher BMI if the mother is obese. These findings highlight an important public health education opportunity to stress the impact of a pre-pregnancy weight and excessive GWG on the risk of child obesity for all mothers. [ABSTRACT FROM AUTHOR]

Background: Many pregnant women in the United States have suboptimal vitamin D, but the impact on infant development is unclear. Moreover, no pregnancy-specific vitamin D recommendations have been widely accepted.Aims: Given the ubiquitous expression of vitamin D receptors in the brain, we investigated the association between early prenatal plasma 25-hydroxyvitamin D (25(OH)D) concentrations and children's social and emotional development in the Newborn Epigenetic Study, a prospective study of pregnancies from 2009 to 2011 in Durham, North Carolina.Methods: We measured 25(OH)D concentrations in first or second trimester plasma samples and categorized 25(OH)D concentrations into quartiles. Covariates were derived from maternal questionnaires. Mothers completed the Infant Toddler Social-Emotional Development Assessment when children were 12-24 months of age. We used multivariable linear regression to evaluate associations between 25(OH)D and specific behavior scores, adjusted for season of blood draw, maternal age, education, parity, smoking, marital status, prepregnancy BMI, and infant gender. We investigated effect-measure modification by race/ethnicity.Results: Of the 218 mother-infant pairs with complete data, Black mothers had much lower 25(OH)D concentrations as compared to White and Hispanic mothers. After adjustment, lower prenatal 25(OH)D was associated with slightly higher (less favorable) Internalizing scores among White children, but lower (more favorable) Internalizing scores among Black and Hispanic children. Lower prenatal 25(OH)D also appears to be associated with higher (less favorable) dysregulation scores, though only among White and Hispanic children.Conclusions: Though imprecise, preliminary results warrant further investigation regarding a role for prenatal vitamin D on children's early social and emotional development. [ABSTRACT FROM AUTHOR]

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom‐designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high‐grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 1.2 × 10−6, BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6‐3.4, P = 1.6 × 10−5, BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2‐1.7, P = 2.3 × 10−5, BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC. [ABSTRACT FROM AUTHOR]