@article{wang_tzeng_huang_maguire_hoyo_allen_2023, title={Duration of exposure to epidural anesthesia at delivery, DNA methylation in umbilical cord blood and their association with offspring asthma in Non-Hispanic Black women}, volume={9}, ISSN={["2058-5888"]}, DOI={10.1093/eep/dvac026}, abstractNote={Abstract Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother–child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother–child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76–1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.}, number={1}, journal={ENVIRONMENTAL EPIGENETICS}, author={Wang, Yaxu and Tzeng, Jung-Ying and Huang, Yueyang and Maguire, Rachel and Hoyo, Cathrine and Allen, Terrence K.}, year={2023}, month={Jan} }
 @article{moylan_mavis_jima_maguire_bashir_hyun_cabezas_parish_niedzwiecki_diehl_et al._2022, title={Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2022.2039850}, abstractNote={Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for identifying children at high risk for NAFLD and associated metabolic dysfunction. We investigated the association between differential DNAm and liver fat content (LFC) and liver injury in pre-adolescent children. Leveraging data from the Newborn Epigenetics Study (NEST), we enrolled 90 mother-child dyads and used linear regression to identify CpG sites and differentially methylated regions (DMRs) in peripheral blood associated with LFC and alanine aminotransferase (ALT) levels in 7-12yo children. DNAm was measured using Infinium HumanMethylationEPIC BeadChips (Illumina). LFC and fibrosis were quantified by magnetic resonance imaging proton density fat fraction and elastography. Median LFC was 1.4% (range, 0.3-13.4%) and MRE was 2.5 kPa (range, 1.5-3.6kPa). Three children had LFC ≥ 5%, while six (7.6%) met our definition of NAFLD (LFC ≥ 3.7%). All children with NAFLD were obese and five were Black. LFC was associated with 88 DMRs and 106 CpGs (FDR<5%). The top two CpGs, cg25474373 and cg07264203, mapped to or near RFTN2 and PRICKLE2 genes. These two CpG sites were also significantly associated with a NAFLD diagnosis. As higher LFC associates with an adverse cardiometabolic profile already in childhood, altered DNAm may identify these children early in disease course for targeted intervention. Larger, longitudinal studies are needed to validate these findings and determine mechanistic relevance.}, journal={EPIGENETICS}, author={Moylan, Cynthia A. and Mavis, Alisha M. and Jima, Dereje and Maguire, Rachel and Bashir, Mustafa and Hyun, Jeongeun and Cabezas, Melanie N. and Parish, Alice and Niedzwiecki, Donna and Diehl, Anna Mae and et al.}, year={2022}, month={Feb} }
 @article{lloyd_skinner_maguire_murphy_motsinger-reif_hoyo_house_2022, title={Clomifene and Assisted Reproductive Technology in Humans Are Associated with Sex-Specific Offspring Epigenetic Alterations in Imprinted Control Regions}, volume={23}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms231810450}, DOI={10.3390/ijms231810450}, abstractNote={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.}, number={18}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Lloyd, Dillon T. and Skinner, Harlyn G. and Maguire, Rachel and Murphy, Susan K. and Motsinger-Reif, Alison A. and Hoyo, Cathrine and House, John S.}, year={2022}, month={Sep} }
 @article{gonzalez-nahm_marchesoni_maity_maguire_house_tucker_atkinson_murphy_hoyo_2022, title={Maternal Mediterranean Diet Adherence and Its Associations with Maternal Prenatal Stressors and Child Growth}, volume={6}, ISSN={["2475-2991"]}, DOI={10.1093/cdn/nzac146}, abstractNote={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.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.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.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).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.}, number={11}, journal={CURRENT DEVELOPMENTS IN NUTRITION}, author={Gonzalez-Nahm, Sarah and Marchesoni, Joddy and Maity, Arnab and Maguire, Rachel L. and House, John S. and Tucker, Rachel and Atkinson, Tamara and Murphy, Susan K. and Hoyo, Cathrine}, year={2022}, month={Nov} }
 @misc{solomon_huen_yousefi_kupers_gonzalez_suderman_reese_page_gruzieva_rzehak_et al._2022, title={Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation}, volume={789}, ISSN={["1388-2139"]}, DOI={10.1016/j.mrrev.2022.108415}, abstractNote={Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.}, journal={MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH}, author={Solomon, Olivia and Huen, Karen and Yousefi, Paul and Kupers, Leanne K. and Gonzalez, Juan R. and Suderman, Matthew and Reese, Sarah E. and Page, Christian M. and Gruzieva, Olena and Rzehak, Peter and et al.}, year={2022} }
 @article{wheeler_boyle_barsell_maguire_dahman_murphy_hoyo_zhang_oliver_mcclernon_et al._2022, title={Neighborhood Deprivation is Associated with Increased Risk of Prenatal Smoke Exposure}, ISSN={["1573-6695"]}, DOI={10.1007/s11121-022-01355-7}, abstractNote={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.}, journal={PREVENTION SCIENCE}, author={Wheeler, David C. and Boyle, Joseph and Barsell, D. Jeremy and Maguire, Rachel L. and Dahman, Bassam and Murphy, Susan K. and Hoyo, Cathrine and Zhang, Jim and Oliver, Jason A. and McClernon, Joseph and et al.}, year={2022}, month={Feb} }
 @article{king_sparling_lloyd_satusky_martinez_grenier_bergemann_maguire_hoyo_meyer_et al._2022, title={Sex-specific DNA methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2022.2043591}, abstractNote={Sex-linked differences in mitochondrial ATP production, enzyme activities, and reactive oxygen species generation have been reported in multiple tissue and cell types. While the effects of reproductive hormones underlie many of these differences, regulation of sexually dimorphic mitochondrial function has not been fully characterized. We hypothesized that sex-specific DNA methylation contributes to sex-specific expression of nuclear genes that influence mitochondrial function. Herein, we analysed DNA methylation data specifically focused on nuclear-encoded mitochondrial genes in 191 males and 190 females. We found 596 differentially methylated sites (DMSs) (FDR p < 0.05), corresponding to 324 genes, with at least a 1% difference in methylation between sexes. To investigate the potential functional significance, we utilized gene expression microarray data. Of the 324 genes containing DMSs, 17 showed differences in gene expression by sex. Particularly striking was that ATP5G2, encoding subunit C of ATP synthase, contains seven DMSs and exhibits a sex difference in expression (p = 0.04). Finally, we also found that alterations in DNA methylation associated with in utero tobacco smoke exposure were sex-specific in these nuclear-encoded mitochondrial genes. Interestingly, the level of sex differences in DNA methylation at nuclear-encoded mitochondrial genes and the level of methylation changes associated with smoke exposure were less prominent than that of other genes. This suggests more conservative regulation of DNA methylation at these nuclear-encoded mitochondrial genes as compared to others. Overall, our findings suggest that sex-specific DNA methylation may help establish sex differences in expression and function and that sex-specific alterations in DNA methylation in response to exposures could contribute to sex-variable toxicological responses.}, journal={EPIGENETICS}, author={King, Dillon E. and Sparling, Anna Clare and Lloyd, Dillon and Satusky, Matthew Joseph and Martinez, Mackenzie and Grenier, Carole and Bergemann, Christina Michelle and Maguire, Rachel and Hoyo, Cathrine and Meyer, Joel Newman and et al.}, year={2022}, month={Mar} }
 @article{glasgow_adams_ksinan_barsell_lunsford-avery_chen_kollins_schechter_maguire_engelhard_et al._2022, title={Sleep onset, duration, or regularity: which matters most for child adiposity outcomes?}, ISSN={["1476-5497"]}, DOI={10.1038/s41366-022-01140-0}, abstractNote={Sleep measures, such as duration and onset timing, are associated with adiposity outcomes among children. Recent research among adults has considered variability in sleep and wake onset times, with the Sleep Regularity Index (SRI) as a comprehensive metric to measure shifts in sleep and wake onset times between days. However, little research has examined regularity and adiposity outcomes among children. This study examined the associations of three sleep measures (i.e., sleep duration, sleep onset time, and SRI) with three measures of adiposity (i.e., body mass index [BMI], waist circumference, and waist-to-height ratio [WHtR]) in a pediatric sample.Children (ages 4-13 years) who were part of the U.S. Newborn Epigenetic STudy (NEST) participated. Children (N = 144) wore an ActiGraph for 1 week. Sleep measures were estimated from actigraphy data. Weight, height, and waist circumference were measured by trained researchers. BMI and WHtR was calculated with the objectively measured waist and height values. Multiple linear regression models examined associations between child sleep and adiposity outcomes, controlling for race/ethnicity, child sex, age, mothers' BMI and sleep duration.When considering sleep onset timing and duration, along with demographic covariates, sleep onset timing was not significantly associated with any of the three adiposity measures, but a longer duration was significantly associated with a lower BMI Z-score (β = -0.29, p < 0.001), waist circumference (β = -0.31, p < 0.001), and WHtR (β = -0.38, p < 0.001). When considering SRI and duration, duration remained significantly associated with the adiposity measures. The SRI and adiposity associations were in the expected direction, but were non-significant, except the SRI and WHtR association (β = -0.16, p = 0.077) was marginally non-significant.Sleep duration was consistently associated with adiposity measures in children 4-13 years of age. Pediatric sleep interventions should focus first on elongating nighttime sleep duration, and examine if this improves child adiposity outcomes.}, journal={INTERNATIONAL JOURNAL OF OBESITY}, author={Glasgow, Trevin E. and Adams, Elizabeth L. and Ksinan, Albert and Barsell, D. Jeremy and Lunsford-Avery, Jessica and Chen, Shanshan and Kollins, Scott and Schechter, Julia C. and Maguire, Rachel and Engelhard, Matthew and et al.}, year={2022}, month={May} }
 @article{wheeler_boyle_barsell_maguire_zhang_oliver_jones_dahman_murphy_hoyo_et al._2022, title={Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/ntac164}, abstractNote={Abstract 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.}, journal={NICOTINE & TOBACCO RESEARCH}, author={Wheeler, David C. and Boyle, Joseph and Barsell, D. Jeremy and Maguire, Rachel L. and Zhang, Junfeng and Oliver, Jason A. and Jones, Shawn and Dahman, Bassam and Murphy, Susan K. and Hoyo, Cathrine and et al.}, year={2022}, month={Jul} }
 @article{maguire_house_lloyd_skinner_allen_raffi_skaar_park_mccullough_kollins_et al._2021, title={Associations between maternal obesity, gestational cytokine levels and child obesity in the NEST cohort}, volume={16}, ISSN={["2047-6302"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85098446153&partnerID=MN8TOARS}, DOI={10.1111/ijpo.12763}, abstractNote={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.}, number={7}, journal={PEDIATRIC OBESITY}, author={Maguire, Rachel L. and House, John S. and Lloyd, Dillon T. and Skinner, Harlyn G. and Allen, Terrence K. and Raffi, Asifa Mohamed and Skaar, David A. and Park, Sarah S. and McCullough, Lauren E. and Kollins, Scott H. and et al.}, year={2021}, month={Jul} }
 @article{fuemmeler_dozmorov_do_zhang_grenier_huang_maguire_kollins_hoyo_murphy_2021, title={DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study}, volume={129}, ISSN={["1552-9924"]}, DOI={10.1289/EHP8099}, abstractNote={Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown.This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip.Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure.Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=-1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=-0.16, SE=0.21, p=0.44).Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.}, number={5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Fuemmeler, Bernard F. and Dozmorov, Mikhail G. and Do, Elizabeth K. and Zhang, Junfeng and Grenier, Carole and Huang, Zhiqing and Maguire, Rachel L. and Kollins, Scott H. and Hoyo, Cathrine and Murphy, Susan K.}, year={2021}, month={May} }
 @article{ksinan_sheng_do_schechter_zhang_maguire_hoyo_murphy_kollins_rubin_et al._2021, title={Identifying the Best Questions for Rapid Screening of Secondhand Smoke Exposure Among Children}, volume={23}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/ntaa254}, abstractNote={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.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).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.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.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.}, number={7}, journal={NICOTINE & TOBACCO RESEARCH}, author={Ksinan, Albert J. and Sheng, Yaou and Do, Elizabeth K. and Schechter, Julia C. and Zhang, Junfeng and Maguire, Rachel L. and Hoyo, Cathrine and Murphy, Susan K. and Kollins, Scott H. and Rubin, Bruce and et al.}, year={2021}, month={Jul}, pages={1217–1223} }
 @article{white_schechter_neely_reyes_maguire_perrin_ksinan_kollins_fuemmeler_2021, title={Parenting Stress, Child Weight-Related Behaviors, and Child Weight Status}, ISSN={["2153-2176"]}, DOI={10.1089/chi.2021.0098}, abstractNote={Background: There has been limited examination of the association between parenting stress and child weight-related behaviors. We aimed to determine whether parenting stress is associated with child weight-related behaviors, including physical activity, screen time, diet, sedentary time, and eating in the absence of hunger (EAH). Secondarily, we assessed association between parenting stress and child weight status. Methods: Mother-child dyads (N = 291) enrolled in the Newborn Epigenetic STudy (NEST), a longitudinal cohort study, completed surveys to describe parenting stress, and child diet. Children participated in the EAH task and wore accelerometers to assess sedentary time and physical activity. Child weight status was assessed using measured height and weight. Outcomes and exposures were examined using generalized linear models and restricted cubic splines as appropriate based on linear lack-of-fit test. Results: Child sedentary time and vegetable consumption were inversely associated with parenting stress (Total Stress B = -0.78; 95% confidence interval [CI]: -1.35 to -0.20; p = 0.017; and Total Stress adjusted odds ratio [aOR] = 0.98; 95% CI: 0.99 to 1.00; p = 0.022, respectively). Child screen time was directly associated with parenting stress (Total Stress = aOR 1.01; 95% CI: 1.00-1.02; p = 0.032). Fast-food intake was nonlinearly associated with parenting stress. There was no evidence of association between parenting stress and child EAH, physical activity, or weight status. Associations between parenting stress and child weight-related behaviors were not moderated by race or family structure. Conclusions: Parenting stress was associated with important child weight-related behaviors but not weight status. Management of parenting stress may represent a reasonable adjunct to family-based behavioral interventions.}, journal={CHILDHOOD OBESITY}, author={White, Michelle J. and Schechter, Julia C. and Neely, Benjamin and Reyes, Camila and Maguire, Rachel L. and Perrin, Eliana M. and Ksinan, Albert J. and Kollins, Scott H. and Fuemmeler, Bernard F.}, year={2021}, month={Sep} }
 @article{fallavollita_do_schechter_kollins_zheng_qin_maguire_hoyo_murphy_fuemmeler_2021, title={Smoke-Free Home Rules and Association with Child Secondhand Smoke Exposure among Mother-Child Dyad Relationships}, volume={18}, ISSN={["1660-4601"]}, DOI={10.3390/ijerph18105256}, abstractNote={Smoke-free home rules restrict smoking in the home, but biomarkers of secondhand smoke exposure are needed to help understand the association between smoke-free homes and child secondhand smoke exposure. Participants (n = 346) were majority Black/African American mother–child dyads from a longitudinal study in North Carolina. Mothers completed questionnaires on household smoking behaviors and rules, and child saliva samples were assayed for secondhand smoke exposure. Regression models used smoke-free home rules to predict child risk for secondhand smoke exposure. Children in households with smoke-free home rules had less salivary cotinine and risk for secondhand smoke exposure. After controlling for smokers in the household, home smoking rules were not a significant predictor of secondhand smoke exposure. Compared to children in households with no smokers, children in households with at least one smoker but a non-smoking mother (OR 5.35, 95% CI: 2.22, 13.17) and households with at least one smoker including a smoking mother (OR 13.73, 95% CI: 6.06, 33.28) had greater risk for secondhand smoke exposure. Results suggest smoke-free home rules are not sufficient to fully protect children from secondhand smoke exposure, especially in homes with smokers. Future research should focus on how household members who smoke can facilitate the prevention of child secondhand smoke exposure.}, number={10}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Fallavollita, Westley L. and Do, Elizabeth K. and Schechter, Julia C. and Kollins, Scott H. and Zheng, Junfeng and Qin, Jian and Maguire, Rachel L. and Hoyo, Cathrine and Murphy, Susan K. and Fuemmeler, Bernard F.}, year={2021}, month={May} }
 @article{neumann_walton_alemany_cecil_gonzalez_jima_lahti_tuominen_barker_binder_et al._2020, title={Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis}, volume={10}, ISSN={["2158-3188"]}, DOI={10.1038/s41398-020-01058-z}, abstractNote={Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4-15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10-7), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10-7. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.}, number={1}, journal={TRANSLATIONAL PSYCHIATRY}, author={Neumann, Alexander and Walton, Esther and Alemany, Silvia and Cecil, Charlotte and Gonzalez, Juan Ramon and Jima, Dereje D. and Lahti, Jari and Tuominen, Samuli T. and Barker, Edward D. and Binder, Elisabeth and et al.}, year={2020}, month={Nov} }
 @article{fuemmeler_sheng_schechter_do_zucker_majors_maguire_murphy_hoyo_kollins_2020, title={Associations between attention deficit hyperactivity disorder symptoms and eating behaviors in early childhood}, volume={15}, ISSN={["2047-6302"]}, DOI={10.1111/ijpo.12631}, abstractNote={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.To assess magnitude and direction of associations between childhood ADHD symptoms and eating behaviors.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).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.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.}, number={7}, journal={PEDIATRIC OBESITY}, author={Fuemmeler, Bernard F. and Sheng, Yaou and Schechter, Julia C. and Do, Elizabeth and Zucker, Nancy and Majors, Alesha and Maguire, Rachel and Murphy, Susan K. and Hoyo, Cathrine and Kollins, Scott H.}, year={2020}, month={Jul} }
 @article{vehmeijer_kuepers_sharp_salas_lent_jima_tindula_reese_qi_gruzieva_et al._2020, title={DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies}, volume={12}, ISSN={["1756-994X"]}, DOI={10.1186/s13073-020-00810-w}, abstractNote={DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7).There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.}, number={1}, journal={GENOME MEDICINE}, author={Vehmeijer, Florianne O. L. and Kuepers, Leanne K. and Sharp, Gemma C. and Salas, Lucas A. and Lent, Samantha and Jima, Dereje D. and Tindula, Gwen and Reese, Sarah and Qi, Cancan and Gruzieva, Olena and et al.}, year={2020}, month={Dec} }
 @article{huang_tzeng_maguire_hoyo_allen_2020, title={The association between neuraxial anesthesia and the development of childhood asthma - a secondary analysis of the newborn epigenetics study cohort}, volume={36}, ISSN={["1473-4877"]}, DOI={10.1080/03007995.2020.1747417}, abstractNote={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.}, number={6}, journal={CURRENT MEDICAL RESEARCH AND OPINION}, author={Huang, Yueyang and Tzeng, Jung-Ying and Maguire, Rachel and Hoyo, Cathrine and Allen, Terrence}, year={2020}, month={Jun}, pages={1025–1032} }
 @article{do_zucker_huang_schechter_kollins_maguire_murphy_hoyo_fuemmeler_2019, title={Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children}, volume={14}, ISSN={["2047-6302"]}, DOI={10.1111/ijpo.12454}, abstractNote={Knowledge regarding genetic influences on eating behaviours is expanding; yet less is known regarding contributions of epigenetic variation to appetitive traits and body mass index (BMI) in children.The purpose of this study was to explore relationships between methylation at differentially methylated regions (DMRs) of imprinted genes (insulin-like growth factor 2/H19 and Delta-like, Drosophila, homolog 1/maternally expressed gene 3) using DNA extracted from umbilical cord blood leucocytes, two genetically influenced appetitive traits (food responsiveness and satiety responsiveness) and BMI.Data were obtained from participants (N = 317; mean age = 3.6 years; SD = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were implemented to investigate the associations between DMRs of imprinted genes and BMI, and test whether this association was mediated by appetitive traits and birthweight and moderated by sex.Appetitive traits and birthweight did not mediate the relationship between methylation at DMRs. Increased insulin-like growth factor 2 DMR methylation was associated with higher satiety responsiveness. Higher satiety responsiveness was associated with lower BMI. Associations between methylation at DMRs, appetitive traits and BMI differed by sex.This is one of the first studies to demonstrate associations between epigenetic variation established prior to birth with appetitive traits and BMI in children, providing support for the need to uncover genetic and epigenetic mechanisms for appetitive traits predisposing some individuals to obesity.}, number={2}, journal={PEDIATRIC OBESITY}, author={Do, E. K. and Zucker, N. L. and Huang, Z. Y. and Schechter, J. C. and Kollins, S. H. and Maguire, R. L. and Murphy, S. K. and Hoyo, C. and Fuemmeler, B. F.}, year={2019}, month={Feb} }
 @article{sorrow_maguire_murphy_belcher_hoyo_2019, title={Elevated metabolites of acetaminophen in cord blood of children with obesity}, volume={14}, ISSN={["2047-6302"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053785805&partnerID=MN8TOARS}, DOI={10.1111/ijpo.12465}, abstractNote={High-throughput metabolomics has been used cross-sectionally to evaluate differential metabolic profiles associated with human obesity.This study longitudinally assessed the cord blood metabolome to explore if metabolic signatures of obesity at age 3-5 are apparent at birth.In a nested case-control design, metabolomics analysis was performed on umbilical cord blood of 25 children who developed obesity by age 3-5 years, compared with 25 sex-matched non-obese children enrolled as part of an ongoing birth cohort. Logistic regression models were used to identify significant metabolites, adjusting for maternal pre-pregnancy obesity.Children who had obesity by age 3-5 years had elevated levels of medium and long chain fatty acids including stearate, oleate and palmitate at birth. Children with obesity were also more likely to have elevated levels of acetaminophen metabolites at birth, specifically: 3-(N-acetyl-L-cystein-S-yl) acetaminophen, 2-hydroxyacetaminophen sulfate, 2-methoxyacetaminophen glucuronide and p-acetamidophenyl glucuronide.Although the observed increases in lipids are consistent with previous metabolomic studies of obesity, this study is the first to report associations between acetaminophen metabolites and obesity in children; however, we lack mechanistic insights for this link. Larger human studies with longer follow-up and laboratory-controlled animal experiments are needed to clarify associations.}, number={1}, journal={PEDIATRIC OBESITY}, author={Sorrow, P. and Maguire, R. and Murphy, S. K. and Belcher, S. M. and Hoyo, C.}, year={2019}, month={Jan} }
 @article{reese_xu_dekker_lee_sikdar_ruiz-arenas_merid_rezwan_page_ullemar_et al._2019, title={Epigenome-wide meta-analysis of DNA methylation and childhood asthma}, volume={143}, ISSN={["1097-6825"]}, DOI={10.1016/j.jaci.2018.11.043}, abstractNote={Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.We sought to identify differential DNA methylation in newborns and children related to childhood asthma.Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions.In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2.Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.}, number={6}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={Reese, Sarah E. and Xu, Cheng-Jian and Dekker, Herman T. and Lee, Mi Kyeong and Sikdar, Sinjini and Ruiz-Arenas, Carlos and Merid, Simon K. and Rezwan, Faisal I and Page, Christian M. and Ullemar, Vilhelmina and et al.}, year={2019}, month={Jun}, pages={2062–2074} }
 @article{martin_jima_sharp_mccullough_park_gowdy_skaar_cowley_maguire_fuemmeler_et al._2019, title={Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study}, volume={14}, ISSN={["1559-2308"]}, url={https://doi.org/10.1080/15592294.2019.1581594}, DOI={10.1080/15592294.2019.1581594}, abstractNote={Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4-5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: -0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: -0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity.}, number={4}, journal={EPIGENETICS}, author={Martin, Chantel L. and Jima, Dereje and Sharp, Gemma C. and McCullough, Lauren E. and Park, Sarah S. and Gowdy, Kymberly M. and Skaar, David and Cowley, Michael and Maguire, Rachel L. and Fuemmeler, Bernard and et al.}, year={2019}, month={Apr}, pages={325–340} }
 @article{kupers_monnereau_sharp_yousefi_salas_ghantous_page_reese_wilcox_czamara_et al._2019, title={Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight}, volume={10}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-019-09671-3}, abstractNote={Abstract Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.}, journal={NATURE COMMUNICATIONS}, author={Kupers, Leanne K. and Monnereau, Claire and Sharp, Gemma C. and Yousefi, Paul and Salas, Lucas A. and Ghantous, Akram and Page, Christian M. and Reese, Sarah E. and Wilcox, Allen J. and Czamara, Darina and et al.}, year={2019}, month={Apr} }
 @article{fuemmeler_zucker_sheng_sanchez_maguire_murphy_kollins_hoyo_2019, title={Pre-Pregnancy Weight and Symptoms of Attention Deficit Hyperactivity Disorder and Executive Functioning Behaviors in Preschool Children}, volume={16}, ISSN={["1660-4601"]}, DOI={10.3390/ijerph16040667}, abstractNote={This study examines pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG) in relation to early childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and related executive self-regulation behaviors. The analyses sample (n = 331) included a subsample of participants from a birth cohort recruited from prenatal clinics and hospital facilities from April 2005 to June 2011 in Durham, North Carolina. Pre-pregnancy BMI was calculated from weight at the last menstrual period and height was extracted from medical records. Gestational weight gain was calculated from pre-pregnancy weight and weight measured at the time of delivery. ADHD symptoms and executive self-regulation behaviors were assessed by maternal report (mean age = 3 years). Multivariable regression methods with inverse probability weighting (IPW) were used to evaluate associations accounting for sample selection bias and confounding. Pre-pregnancy BMI at levels ≥35 was positively associated with higher ADHD symptoms and worse executive self-regulation behaviors (inhibitory control and attention). Compared to adequate GWG, less than adequate GWG was related to more ADHD hyperactive-impulsive symptoms, whereas greater than adequate GWG was related to more problematic behaviors related to working memory and planning. The findings support a link between maternal weight and child neurodevelopment. Continued research that help identify biological mechanisms are needed.}, number={4}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Fuemmeler, Bernard F. and Zucker, Nancy and Sheng, Yaou and Sanchez, Carmen E. and Maguire, Rachel and Murphy, Susan K. and Kollins, Scott H. and Hoyo, Cathrine}, year={2019}, month={Feb} }
 @article{xue_maguire_liu_kollins_murphy_hoyo_fuemmeler_2019, title={Snacking frequency and dietary intake in toddlers and preschool children}, volume={142}, ISSN={["1095-8304"]}, DOI={10.1016/j.appet.2019.104369}, abstractNote={Understanding the relationship between snacking and dietary intake in early life years is one key but understudied area. In this study, we examined snacking patterns in toddlers and preschool children and the associations between snacking frequency and daily energy intake. We analyzed data from children aged 12-72 months (N = 1186) in the Newborn Epigenetic STudy (NEST). We used Bonferroni multiple comparison methods to examine the differences in snacking patterns across subgroups. Linear and quantile regression models were fit to investigate the association between dietary intake and snacking frequency. Our estimates suggest that Non-Hispanic blacks had the highest total daily energy intake from snacks (334 kcal/day) compared to non-Hispanic whites (270 kcal/day) and Hispanics (274 kcal/day) in 12-to-24-month-olds. In 2-to-6-year-olds, mean energy intake from snacks was 296 kcal/day without a significant racial/ethnic difference. Carbohydrate, fat and protein from snacks contributed about 17%, 9% and 4% respectively of the total energy intake in 12-to-24-month-olds while they contributed about 15%, 7% and 2% respectively of the total energy intake in the other age group. Snacking frequency was positively and significantly associated with total daily energy intake in both 12-to-24-month-olds and 2-to-6-year-olds as indicated by regression coefficient estimates of snacking frequency (β = 31.3 kcal/day with P = 0.027 and β = 175.4 kcal/day with P < 0.0001, respectively, indicating a higher snacking frequency was associated with a greater total daily energy intake). In conclusion, snacking frequency was positively associated with daily energy intake. Carbohydrates and fats from snacks are significant energy contributors. Age differentiation was apparent regarding the relationship between snacking frequency and dietary intake. Differentiated interventions that are age-specific and focus on the dietary quality of snacks instead of quantity are needed.}, journal={APPETITE}, author={Xue, Hong and Maguire, Rachel L. and Liu, Jin and Kollins, Scott H. and Murphy, Susan K. and Hoyo, Cathrine and Fuemmeler, Bernard F.}, year={2019}, month={Nov} }
 @article{felix_joubert_baccarelli_sharp_almqvist_annesi-maesano_arshad_baiz_bakermans-kranenburg_bakulski_et al._2018, title={Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium}, volume={47}, number={1}, journal={International Journal of Epidemiology}, author={Felix, J. F. and Joubert, B. R. and Baccarelli, A. A. and Sharp, G. C. and Almqvist, C. and Annesi-Maesano, I. and Arshad, H. and Baiz, N. and Bakermans-Kranenburg, M. J. and Bakulski, K. M. and et al.}, year={2018}, pages={22-} }
 @article{gomih_smith_north_hudgens_brewster_huang_skaar_valea_bentley_vidal_et al._2018, title={DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions}, volume={143}, ISSN={["1097-0215"]}, DOI={10.1002/ijc.31350}, abstractNote={The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow-up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine-phosphate-guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non-regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time-point), adjusting for age, race, high-risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0-64.4 years), 39% were African-American, and 11% were current smokers. Most participants were hrHPV-positive at enrollment (80.5%). Over one-third of cases regressed (n = 53, 35.1%). Median time-to-regression was 12.6 months (range: 4.5-24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23-0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65-0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.}, number={3}, journal={INTERNATIONAL JOURNAL OF CANCER}, author={Gomih, Ayodele and Smith, Jennifer S. and North, Kari E. and Hudgens, Michael G. and Brewster, Wendy R. and Huang, Zhiqing and Skaar, David and Valea, Fidel and Bentley, Rex C. and Vidal, Adriana C. and et al.}, year={2018}, month={Aug}, pages={552–560} }
 @article{cowley_skaar_jima_maguire_hudson_park_sorrow_hoyo_2018, title={Effects of cadmium exposure on DNA methylation at imprinting control regions and genome-wide in mothers and newborn children}, volume={126}, number={3}, journal={Environmental Health Perspectives}, author={Cowley, M. and Skaar, D. A. and Jima, D. D. and Maguire, R. L. and Hudson, K. M. and Park, S. S. and Sorrow, P. and Hoyo, C.}, year={2018} }
 @article{house_mendez_maguire_gonzalez-nahm_huang_daniels_murphy_fuemmeler_wright_hoyo_2018, title={Periconceptional maternal mediterranean diet is associated with favorable offspring behaviors and altered CpG methylation of imprinted genes}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053720031&partnerID=MN8TOARS}, DOI={10.3389/fcell.2018.00107}, abstractNote={Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse. Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations. Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation. Results: Child depression was significantly associated with maternal MDA (Bonferroni-corrected p = 0.048). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors (OR (95%CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile)), for maladaptive behaviors (0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile) and for an index of autism spectrum disorder behaviors (0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile). Offspring of women with the highest MDA tertile were less likely to exhibit depressive (OR=0.28 (0.12, 0.64)) and anxiety (0.42 (0.18, 0.97)) behaviors and increased odds of social relatedness (2.31 (1.04, 5.19)) behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE (females: Beta (95%CI) = 1.66 (0.52, 2.80) - Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)), as well as both MEG3 and IGF2 in males (0.97 (0.00, 1.94)) and -0.92 (-1.65, -0.19) respectively. Conclusions: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.}, number={SEP}, journal={Frontiers in Cell and Developmental Biology}, author={House, John S. and Mendez, M. and Maguire, R.L. and Gonzalez-Nahm, S. and Huang, Z. and Daniels, J. and Murphy, S.K. and Fuemmeler, B.F. and Wright, F.A. and Hoyo, C.}, year={2018}, pages={107} }
 @article{maguire_vidal_murphy_hoyo_2017, title={Disparities in cervical cancer incidence and mortality: Can epigenetics contribute to eliminating disparities?}, volume={133}, journal={Cancer disparities}, author={Maguire, R. L. and Vidal, A. C. and Murphy, S. K. and Hoyo, C.}, year={2017}, pages={129–156} }
 @article{gao_millstein_siegmund_dubeau_maguire_gilliland_murphy_hoyo_breton_2017, title={Epigenetic regulation of AXL and risk of childhood asthma symptoms}, volume={9}, journal={Clinical Epigenetics}, author={Gao, L. and Millstein, J. and Siegmund, K. D. and Dubeau, L. and Maguire, R. and Gilliland, F. D. and Murphy, S. K. and Hoyo, C. and Breton, C. V.}, year={2017} }
 @article{sharp_salas_monnereau_allard_yousefi_everson_bohlin_xu_huang_reese_et al._2017, title={Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium}, volume={26}, number={20}, journal={Human Molecular Genetics}, author={Sharp, G. C. and Salas, L. A. and Monnereau, C. and Allard, C. and Yousefi, P. and Everson, T. M. and Bohlin, J. and Xu, Z. L. and Huang, R. C. and Reese, S. E. and et al.}, year={2017}, pages={4067–4085} }
 @article{luo_mccullough_tzeng_darrah_vengosh_maguire_maity_samuel-hodge_murphy_mendez_et al._2017, title={Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight}, volume={17}, journal={BMC Public Health}, author={Luo, Y. W. and McCullough, L. E. and Tzeng, J. Y. and Darrah, T. and Vengosh, A. and Maguire, R. L. and Maity, A. and Samuel-Hodge, C. and Murphy, S. K. and Mendez, M. A. and et al.}, year={2017} }
 @article{mccullough_miller_calderwood_shivappa_steck_forman_mendez_maguire_fuemmeler_kollins_et al._2017, title={Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?}, volume={12}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2017.1347241}, abstractNote={Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = −0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (Pinteraction = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m2 (Pinteraction = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.}, number={8}, journal={EPIGENETICS}, author={McCullough, Lauren E. and Miller, Erline E. and Calderwood, Laura E. and Shivappa, Nitin and Steck, Susan E. and Forman, Michele R. and Mendez, Michelle A. and Maguire, Rachel and Fuemmeler, Bernard F. and Kollins, Scott H. and et al.}, year={2017}, pages={688–697} }
 @article{fuemmeler_wang_iversen_maguire_murphy_hoyo_2016, title={Association between Prepregnancy Body Mass Index and Gestational Weight Gain with Size, Tempo, and Velocity of Infant Growth: Analysis of the Newborn Epigenetic Study Cohort}, volume={12}, ISSN={["2153-2176"]}, DOI={10.1089/chi.2015.0253}, abstractNote={The first 1000 days of life is a critical period of infant growth that has been linked to future adult health. Understanding prenatal factors that contribute to variation in growth during this period could inform successful prevention strategies.Prenatal and maternal characteristics, including prepregnancy obesity and gestational weight gain were evaluated in relation to weight growth trajectories during the first 24 months of life using the SuperImposition by Translation and Rotation (SITAR) method, which provides estimates of infant size, timing to peak velocity, and growth velocity. The study sample included 704 mother-infant dyads from a multiethnic prebirth cohort from the Southeastern United States. The total number of weight measures was 8670 (median number per child = 14).Several prenatal and maternal characteristics were linked with infant growth parameters. The primary findings show that compared to women with a prepregnancy BMI between 18 and 24.9, women with a prepregnancy BMI ≥40 had infants that were 8% larger during the first 24 months, a delayed tempo of around 9 days, and a slower velocity. Mothers who had greater than adequate gestational weight gain had infants that were 5% larger even after controlling for prepregnancy BMI and several other covariates.The findings contribute new data on the associations between gestational weight gain and aspects of early growth using the SITAR method, and support a growing consensus in the literature that both prepregnancy BMI and gestational weight gain relate independently to risk for greater postnatal weight growth.}, number={3}, journal={CHILDHOOD OBESITY}, author={Fuemmeler, Bernard F. and Wang, Lin and Iversen, Edwin S. and Maguire, Rachel and Murphy, Susan K. and Hoyo, Cathrine}, year={2016}, month={Jun}, pages={210–218} }
 @article{king_darrah_money_meentemeyer_maguire_nye_michener_murtha_jirtle_murphy_et al._2015, title={Geographic clustering of elevated blood heavy metal levels in pregnant women}, volume={15}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-015-2379-9}, abstractNote={Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) exposure is ubiquitous and has been associated with higher risk of growth restriction and cardiometabolic and neurodevelopmental disorders. However, cost-efficient strategies to identify at-risk populations and potential sources of exposure to inform mitigation efforts are limited. The objective of this study was to describe the spatial distribution and identify factors associated with Cd, Pb, Hg, and As concentrations in peripheral blood of pregnant women. Heavy metals were measured in whole peripheral blood of 310 pregnant women obtained at gestational age ~12 weeks. Prenatal residential addresses were geocoded and geospatial analysis (Getis-Ord Gi* statistics) was used to determine if elevated blood concentrations were geographically clustered. Logistic regression models were used to identify factors associated with elevated blood metal levels and cluster membership. Geospatial clusters for Cd and Pb were identified with high confidence (p-value for Gi* statistic <0.01). The Cd and Pb clusters comprised 10.5 and 9.2 % of Durham County residents, respectively. Medians and interquartile ranges of blood concentrations (μg/dL) for all participants were Cd 0.02 (0.01–0.04), Hg 0.03 (0.01–0.07), Pb 0.34 (0.16–0.83), and As 0.04 (0.04–0.05). In the Cd cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.06 (0.02–0.16), Hg 0.02 (0.00–0.05), Pb 0.54 (0.23–1.23), and As 0.05 (0.04–0.05). In the Pb cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.03 (0.02–0.15), Hg 0.01 (0.01–0.05), Pb 0.39 (0.24–0.74), and As 0.04 (0.04–0.05). Co-exposure with Pb and Cd was also clustered, the p-values for the Gi* statistic for Pb and Cd was <0.01. Cluster membership was associated with lower education levels and higher pre-pregnancy BMI. Our data support that elevated blood concentrations of Cd and Pb are spatially clustered in this urban environment compared to the surrounding areas. Spatial analysis of metals concentrations in peripheral blood or urine obtained routinely during prenatal care can be useful in surveillance of heavy metal exposure.}, number={1}, journal={BMC PUBLIC HEALTH}, publisher={Springer Science and Business Media LLC}, author={King, Katherine E. and Darrah, Thomas H. and Money, Eric and Meentemeyer, Ross and Maguire, Rachel L. and Nye, Monica D. and Michener, Lloyd and Murtha, Amy P. and Jirtle, Randy and Murphy, Susan K. and et al.}, year={2015}, month={Oct} }
 @article{vidal_skaar_maguire_dodor_musselwhite_bartlett_oneko_obure_mlay_murphy_et al._2015, title={IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes}, volume={10}, journal={Infectious Agents and Cancer}, author={Vidal, A. C. and Skaar, D. and Maguire, R. and Dodor, S. and Musselwhite, L. W. and Bartlett, J. A. and Oneko, O. and Obure, J. and Mlay, P. and Murphy, S. K. and et al.}, year={2015} }
 @article{vidal_semenova_darrah_vengosh_huang_king_nye_fry_skaar_maguire_et al._2015, title={Maternal cadmium, iron and zinc levels, DNA methylation and birth weight}, volume={16}, journal={BMC Pharmacology & Toxicology}, author={Vidal, A. C. and Semenova, V. and Darrah, T. and Vengosh, A. and Huang, Z. Q. and King, K. and Nye, M. D. and Fry, R. and Skaar, D. and Maguire, R. and et al.}, year={2015} }