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3. Epigenetic associations with neonatal age in infants born very preterm, particularly among genes involved in neurodevelopment

Author

Hodge, Kenyaita M., Burt, Amber A., Camerota, Marie, Carter, Brian S., Check, Jennifer, Conneely, Karen N., Helderman, Jennifer, Hofheimer, Julie A., Hüls, Anke, McGowan, Elisabeth C., Neal, Charles R., Pastyrnak, Steven L., Smith, Lynne M., DellaGrotta, Sheri A., Dansereau, Lynne M., O’Shea, T. Michael, Marsit, Carmen J., Lester, Barry M., and Everson, Todd M.

Published
2024
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6. Developing a National-Scale Exposure Index for Combined Environmental Hazards and Social Stressors and Applications to the Environmental Influences on Child Health Outcomes (ECHO) Cohort

Author

Martenies, Sheena E, Zhang, Mingyu, Corrigan, Anne E, Kvit, Anton, Shields, Timothy, Wheaton, William, Him, Deana Around, Aschner, Judy, Talavera-Barber, Maria M, Barrett, Emily S, Bastain, Theresa M, Bendixsen, Casper, Breton, Carrie V, Bush, Nicole R, Cacho, Ferdinand, Camargo, Carlos A, Carroll, Kecia N, Carter, Brian S, Cassidy-Bushrow, Andrea E, Cowell, Whitney, Croen, Lisa A, Dabelea, Dana, Duarte, Cristiane S, Dunlop, Anne L, Everson, Todd M, Habre, Rima, Hartert, Tina V, Helderman, Jennifer B, Hipwell, Alison E, Karagas, Margaret R, Lester, Barry M, LeWinn, Kaja Z, Magzamen, Sheryl, Morello-Frosch, Rachel, O’Connor, Thomas G, Padula, Amy M, Petriello, Michael, Sathyanarayana, Sheela, Stanford, Joseph B, Woodruff, Tracey J, Wright, Rosalind J, and Kress, Amii M

Subjects
Epidemiology, Public Health, Health Sciences, Human Society, Prevention, Basic Behavioral and Social Science, Pediatric Research Initiative, Behavioral and Social Science, Perinatal Period - Conditions Originating in Perinatal Period, Climate-Related Exposures and Conditions, Pediatric, Patient Safety, Clinical Research, 2.2 Factors relating to the physical environment, Aetiology, Generic health relevance, Good Health and Well Being, Female, Humans, Pregnancy, Air Pollutants, Cohort Studies, Environmental Exposure, Environmental Health, Hispanic or Latino, Outcome Assessment, Health Care, White, Black or African American, Program Collaborators for Environmental Influences on Child Health Outcomes, environmental hazards, health disparities, neighborhoods, social stressors, Toxicology
Abstract

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a "high" exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.

Published
2023

7. Associations between combined exposure to environmental hazards and social stressors at the neighborhood level and individual perinatal outcomes in the ECHO-wide cohort

Author

Martenies, Sheena E, Zhang, Mingyu, Corrigan, Anne E, Kvit, Anton, Shields, Timothy, Wheaton, William, Bastain, Theresa M, Breton, Carrie V, Dabelea, Dana, Habre, Rima, Magzamen, Sheryl, Padula, Amy M, Him, Deana Around, Camargo, Carlos A, Cowell, Whitney, Croen, Lisa A, Deoni, Sean, Everson, Todd M, Hartert, Tina V, Hipwell, Alison E, McEvoy, Cindy T, Morello-Frosch, Rachel, O'Connor, Thomas G, Petriello, Michael, Sathyanarayana, Sheela, Stanford, Joseph B, Woodruff, Tracey J, Wright, Rosalind J, Kress, Amii M, and Outcomes, on behalf of program collaborators for Environmental influences on Child Health

Subjects
Human Geography, Health Sciences, Human Society, Women's Health, Pediatric, Behavioral and Social Science, Prevention, Preterm, Low Birth Weight and Health of the Newborn, Conditions Affecting the Embryonic and Fetal Periods, Clinical Research, Maternal Health, Minority Health, Health Disparities, Perinatal Period - Conditions Originating in Perinatal Period, Pregnancy, 2.3 Psychological, social and economic factors, Generic health relevance, Reproductive health and childbirth, Good Health and Well Being, Birth Weight, Cohort Studies, Female, Gestational Age, Humans, Infant, Infant, Newborn, Premature Birth, Neighborhoods, Environmental hazards, Social stressors, Prenatal, Perinatal health, program collaborators for Environmental influences on Child Health Outcomes, Public Health and Health Services, Public Health, Health sciences, Human society
Abstract

Limited studies examine how prenatal environmental and social exposures jointly impact perinatal health. Here we investigated relationships between a neighborhood-level combined exposure (CE) index assessed during pregnancy and perinatal outcomes, including birthweight, gestational age, and preterm birth. Across all participants, higher CE index scores were associated with small decreases in birthweight and gestational age. We also observed effect modification by race; infants born to Black pregnant people had a greater risk of preterm birth for higher CE values compared to White infants. Overall, our results suggest that neighborhood social and environmental exposures have a small but measurable joint effect on neonatal indicators of health.

Published
2022

8. Evaluation of pediatric epigenetic clocks across multiple tissues

Author

Fang, Fang, Zhou, Linran, Perng, Wei, Marsit, Carmen J., Knight, Anna K., Cardenas, Andres, Aung, Max T., Hivert, Marie-France, Aris, Izzuddin M., Goodrich, Jaclyn M., Smith, Alicia K., Gaylord, Abigail, Fry, Rebecca C., Oken, Emily, O’Connor, George, Ruden, Douglas M., Trasande, Leonardo, Herbstman, Julie B., Camargo, Jr., Carlos A., Bush, Nicole R., Dunlop, Anne L., Dabelea, Dana M., Karagas, Margaret R., Breton, Carrie V., Ober, Carole, Everson, Todd M., Page, Grier P., and Ladd-Acosta, Christine

Published
2023
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10. Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program

Author

Camerota, Marie, McGowan, Elisabeth C., Aschner, Judy, Stroustrup, Annemarie, Karagas, Margaret R., Conradt, Elisabeth, Crowell, Sheila E., Brennan, Patricia A., Carter, Brian S., Check, Jennifer, Dansereau, Lynne M., DellaGrotta, Sheri A., Everson, Todd M., Helderman, Jennifer B., Hofheimer, Julie A., Kuiper, Jordan R., Loncar, Cynthia M., Marsit, Carmen J., Neal, Charles R., O’Shea, Thomas Michael, Pastyrnak, Steven L., Sheinkopf, Stephen J., Smith, Lynne M., Zhang, Xueying, and Lester, Barry M.

Published
2023
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12. A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Author

Fernandez-Jimenez, Nora, Fore, Ruby, Cilleros-Portet, Ariadna, Lepeule, Johanna, Perron, Patrice, Kvist, Tuomas, Tian, Fu-Ying, Lesseur, Corina, Binder, Alexandra M, Lozano, Manuel, Martorell-Marugán, Jordi, Loke, Yuk J, Bakulski, Kelly M, Zhu, Yihui, Forhan, Anne, Sammallahti, Sara, Everson, Todd M, Chen, Jia, Michels, Karin B, Belmonte, Thalia, Carmona-Sáez, Pedro, Halliday, Jane, Daniele Fallin, M, LaSalle, Janine M, Tost, Jorg, Czamara, Darina, Fernández, Mariana F, Gómez-Martín, Antonio, Craig, Jeffrey M, Gonzalez-Alzaga, Beatriz, Schmidt, Rebecca J, Dou, John F, Muggli, Evelyne, Lacasaña, Marina, Vrijheid, Martine, Marsit, Carmen J, Karagas, Margaret R, Räikkönen, Katri, Bouchard, Luigi, Heude, Barbara, Santa-Marina, Loreto, Bustamante, Mariona, Hivert, Marie-France, and Bilbao, Jose Ramon

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Genetics, Pediatric, Prevention, Obesity, Childhood Obesity, Clinical Research, Nutrition, Conditions Affecting the Embryonic and Fetal Periods, Perinatal Period - Conditions Originating in Perinatal Period, Human Genome, Pregnancy, Maternal Health, Women's Health, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Infant, Newborn, Child, Humans, Female, Body Mass Index, DNA Methylation, Placenta, Mothers, Child Health, Biological sciences, Biomedical and clinical sciences
Abstract

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

Published
2022

13. Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth.

Author

Everson, Todd M, Vives-Usano, Marta, Seyve, Emie, Cardenas, Andres, Lacasaña, Marina, Craig, Jeffrey M, Lesseur, Corina, Baker, Emily R, Fernandez-Jimenez, Nora, Heude, Barbara, Perron, Patrice, Gónzalez-Alzaga, Beatriz, Halliday, Jane, Deyssenroth, Maya A, Karagas, Margaret R, Íñiguez, Carmen, Bouchard, Luigi, Carmona-Sáez, Pedro, Loke, Yuk J, Hao, Ke, Belmonte, Thalia, Charles, Marie A, Martorell-Marugán, Jordi, Muggli, Evelyne, Chen, Jia, Fernández, Mariana F, Tost, Jorg, Gómez-Martín, Antonio, London, Stephanie J, Sunyer, Jordi, Marsit, Carmen J, Lepeule, Johanna, Hivert, Marie-France, and Bustamante, Mariona

Subjects
Placenta, Humans, Tobacco, Smoking, DNA Methylation, Epigenesis, Genetic, Fetal Development, Pregnancy, Genetic Heterogeneity, Female, Nucleotide Motifs
Abstract

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

Published
2021

16. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Author

Küpers, Leanne K, Monnereau, Claire, Sharp, Gemma C, Yousefi, Paul, Salas, Lucas A, Ghantous, Akram, Page, Christian M, Reese, Sarah E, Wilcox, Allen J, Czamara, Darina, Starling, Anne P, Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie V, Allard, Catherine, Just, Allan C, Bakulski, Kelly M, Holloway, John W, Everson, Todd M, Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A, Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine AS, Richardson, Tom G, Magnus, Maria C, Nohr, Ellen A, Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L, Solomon, Olivia, Heimovaara, Joosje H, Jima, Dereje D, Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O, Hertz-Picciotto, Irva, Zhang, Hongmei, Karagas, Margaret R, Gehring, Ulrike, Marsit, Carmen J, Beilin, Lawrence J, Vonk, Judith M, Jarvelin, Marjo-Riitta, Bergström, Anna, Örtqvist, Anne K, Ewart, Susan, Villa, Pia M, Moore, Sophie E, Willemsen, Gonneke, Standaert, Arnout RL, Håberg, Siri E, Sørensen, Thorkild IA, Taylor, Jack A, Räikkönen, Katri, Yang, Ivana V, Kechris, Katerina, Nawrot, Tim S, Silver, Matt J, Gong, Yun Yun, Richiardi, Lorenzo, Kogevinas, Manolis, Litonjua, Augusto A, Eskenazi, Brenda, Huen, Karen, Mbarek, Hamdi, Maguire, Rachel L, Dwyer, Terence, Vrijheid, Martine, Bouchard, Luigi, Baccarelli, Andrea A, Croen, Lisa A, Karmaus, Wilfried, Anderson, Denise, de Vries, Maaike, Sebert, Sylvain, Kere, Juha, Karlsson, Robert, Arshad, Syed Hasan, Hämäläinen, Esa, Routledge, Michael N, Boomsma, Dorret I, Feinberg, Andrew P, Newschaffer, Craig J, Govarts, Eva, Moisse, Matthieu, Fallin, M Daniele, Melén, Erik, and Prentice, Andrew M

Subjects
Fetus, Humans, Prenatal Exposure Delayed Effects, Birth Weight, Folic Acid, DNA, Body Mass Index, Smoking, DNA Methylation, Epigenesis, Genetic, CpG Islands, Fetal Development, Pregnancy, Genome, Human, Adolescent, Adult, Child, Infant, Newborn, Female, Male, Genome-Wide Association Study, Epigenesis, Genetic, Genome, Human, Infant, Newborn
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 (PBonferroni

Published
2019

17. Associations between combined exposure to environmental hazards and social stressors at the neighborhood level and individual perinatal outcomes in the ECHO-wide cohort

Author

Martenies, Sheena E., Zhang, Mingyu, Corrigan, Anne E., Kvit, Anton, Shields, Timothy, Wheaton, William, Bastain, Theresa M., Breton, Carrie V., Dabelea, Dana, Habre, Rima, Magzamen, Sheryl, Padula, Amy M., Him, Deana Around, Camargo, Carlos A., Jr., Cowell, Whitney, Croen, Lisa A., Deoni, Sean, Everson, Todd M., Hartert, Tina V., Hipwell, Alison E., McEvoy, Cindy T., Morello-Frosch, Rachel, O'Connor, Thomas G., Petriello, Michael, Sathyanarayana, Sheela, Stanford, Joseph B., Woodruff, Tracey J., Wright, Rosalind J., and Kress, Amii M.

Published
2022
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19. Epigenetic age acceleration in follicular fluid and markers of ovarian response among women undergoing IVF.

Author

Hood, Robert B, Everson, Todd M, Ford, Jennifer B, Hauser, Russ, Knight, Anna, Smith, Alicia K, and Gaskins, Audrey J

Subjects
*GRANULOSA cells, *HUMAN in vitro fertilization, *AGE, *INDUCED ovulation, *OOCYTE retrieval, *OVARIAN reserve
Abstract

STUDY QUESTION Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation? SUMMARY ANSWER Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes. WHAT IS KNOWN ALREADY In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes. STUDY DESIGN, SIZE, DURATION Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006–2016). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol. MAIN RESULTS AND ROLE OF CHANCE Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (−819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: −1265.7, −373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: −21.8%; 95% CI: −37.1%, −2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: −23.8%; 95% CI: −39.9%, −3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response. LIMITATIONS, REASONS FOR CAUTION Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types. WIDER IMPLICATIONS OF THE FINDINGS Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870). TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, Janine F, Joubert, Bonnie R, Baccarelli, Andrea A, Sharp, Gemma C, Almqvist, Catarina, Annesi-Maesano, Isabella, Arshad, Hasan, Baïz, Nour, Bakermans-Kranenburg, Marian J, Bakulski, Kelly M, Binder, Elisabeth B, Bouchard, Luigi, Breton, Carrie V, Brunekreef, Bert, Brunst, Kelly J, Burchard, Esteban G, Bustamante, Mariona, Chatzi, Leda, Munthe-Kaas, Monica Cheng, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Smith, George Davey, De Boever, Patrick, Duijts, Liesbeth, Dwyer, Terence, Eng, Celeste, Eskenazi, Brenda, Everson, Todd M, Falahi, Fahimeh, Fallin, M Daniele, Farchi, Sara, Fernandez, Mariana F, Gao, Lu, Gaunt, Tom R, Ghantous, Akram, Gillman, Matthew W, Gonseth, Semira, Grote, Veit, Gruzieva, Olena, Håberg, Siri E, Herceg, Zdenko, Hivert, Marie-France, Holland, Nina, Holloway, John W, Hoyo, Cathrine, Hu, Donglei, Huang, Rae-Chi, Huen, Karen, Järvelin, Marjo-Riitta, Jima, Dereje D, Just, Allan C, Karagas, Margaret R, Karlsson, Robert, Karmaus, Wilfried, Kechris, Katerina J, Kere, Juha, Kogevinas, Manolis, Koletzko, Berthold, Koppelman, Gerard H, Küpers, Leanne K, Ladd-Acosta, Christine, Lahti, Jari, Lambrechts, Nathalie, Langie, Sabine AS, Lie, Rolv T, Liu, Andrew H, Magnus, Maria C, Magnus, Per, Maguire, Rachel L, Marsit, Carmen J, McArdle, Wendy, Melén, Erik, Melton, Phillip, Murphy, Susan K, Nawrot, Tim S, Nisticò, Lorenza, Nohr, Ellen A, Nordlund, Björn, Nystad, Wenche, Oh, Sam S, Oken, Emily, Page, Christian M, Perron, Patrice, Pershagen, Göran, Pizzi, Costanza, Plusquin, Michelle, Raikkonen, Katri, Reese, Sarah E, Reischl, Eva, Richiardi, Lorenzo, Ring, Susan, Roy, Ritu P, Rzehak, Peter, Schoeters, Greet, Schwartz, David A, Sebert, Sylvain, Snieder, Harold, Sørensen, Thorkild IA, and Starling, Anne P

Subjects
Epidemiology, Public Health, Health Sciences, Statistics, Mathematical Sciences, Child Health, Cohort Studies, DNA Methylation, Environmental Pollution, Epigenesis, Genetic, Female, Folic Acid, Humans, Infant, Newborn, Maternal Exposure, Maternal Health, Pregnancy, Prenatal Exposure Delayed Effects, Public Health and Health Services, Public health
Published
2018

23. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

Author

Sharp, Gemma C, Salas, Lucas A, Monnereau, Claire, Allard, Catherine, Yousefi, Paul, Everson, Todd M, Bohlin, Jon, Xu, Zongli, Huang, Rae-Chi, Reese, Sarah E, Xu, Cheng-Jian, Baïz, Nour, Hoyo, Cathrine, Agha, Golareh, Roy, Ritu, Holloway, John W, Ghantous, Akram, Merid, Simon K, Bakulski, Kelly M, Küpers, Leanne K, Zhang, Hongmei, Richmond, Rebecca C, Page, Christian M, Duijts, Liesbeth, Lie, Rolv T, Melton, Phillip E, Vonk, Judith M, Nohr, Ellen A, Williams-DeVane, ClarLynda, Huen, Karen, Rifas-Shiman, Sheryl L, Ruiz-Arenas, Carlos, Gonseth, Semira, Rezwan, Faisal I, Herceg, Zdenko, Ekström, Sandra, Croen, Lisa, Falahi, Fahimeh, Perron, Patrice, Karagas, Margaret R, Quraishi, Bilal M, Suderman, Matthew, Magnus, Maria C, Jaddoe, Vincent WV, Taylor, Jack A, Anderson, Denise, Zhao, Shanshan, Smit, Henriette A, Josey, Michele J, Bradman, Asa, Baccarelli, Andrea A, Bustamante, Mariona, Håberg, Siri E, Pershagen, Göran, Hertz-Picciotto, Irva, Newschaffer, Craig, Corpeleijn, Eva, Bouchard, Luigi, Lawlor, Debbie A, Maguire, Rachel L, Barcellos, Lisa F, Smith, George Davey, Eskenazi, Brenda, Karmaus, Wilfried, Marsit, Carmen J, Hivert, Marie-France, Snieder, Harold, Fallin, M Daniele, Melén, Erik, Munthe-Kaas, Monica C, Arshad, Hasan, Wiemels, Joseph L, Annesi-Maesano, Isabella, Vrijheid, Martine, Oken, Emily, Holland, Nina, Murphy, Susan K, Sørensen, Thorkild IA, Koppelman, Gerard H, Newnham, John P, Wilcox, Allen J, Nystad, Wenche, London, Stephanie J, Felix, Janine F, and Relton, Caroline L

Subjects
Biological Sciences, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Contraception/Reproduction, Pediatric, Human Genome, Obesity, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Adult, Body Mass Index, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Humans, Infant, Newborn, Male, Maternal Inheritance, Mothers, Pregnancy, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Medical and Health Sciences, Genetics & Heredity
Abstract

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (

Published
2017

24. Epigenome-wide analysis identifies genes and pathways linked to acoustic cry variation in preterm infants

Author

Aghagoli, Ghazal, Sheinkopf, Stephen J., Everson, Todd M., Marsit, Carmen J., Lee, Hannah, Burt, Amber A., Carter, Brian S., Helderman, Jennifer B., Hofheimer, Julie A., McGowan, Elisabeth C., Neal, Charles R., O’Shea, T. Michael, Pastyrnak, Steven L., Smith, Lynne M., Soliman, Antoine, Dansereau, Lynne M., DellaGrotta, Sheri A., Padbury, James F., and Lester, Barry M.

Published
2021
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25. Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Author

Camerota, Marie, primary, Lester, Barry M., additional, McGowan, Elisabeth C., additional, Carter, Brian S., additional, Check, Jennifer, additional, Dansereau, Lynne M., additional, DellaGrotta, Sheri A., additional, Helderman, Jennifer B., additional, Hofheimer, Julie A., additional, Loncar, Cynthia M., additional, Neal, Charles R., additional, O'Shea, T. Michael, additional, Pastyrnak, Steven L., additional, Smith, Lynne M., additional, Abrishamcar, Sarina, additional, Hüls, Anke, additional, Marsit, Carmen J., additional, and Everson, Todd M., additional

Published
2024
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26. Agreement Between Two Behavioral Rating Scales in Preschoolers Born Very Preterm

Author

Camerota, Marie, primary, Bagley, Jessica, additional, McGowan, Elisabeth C., additional, Carter, Brian S., additional, Check, Jennifer, additional, Dansereau, Lynne M., additional, DellaGrotta, Sheri A., additional, Helderman, Jennifer B., additional, Hofheimer, Julie A., additional, Loncar, Cynthia M., additional, Neal, Charles R., additional, O'Shea, T. Michael, additional, Pastyrnak, Steven L., additional, Smith, Lynne M., additional, Everson, Todd M., additional, and Lester, Barry M., additional

Published
2023
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29. Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm

Author

Paniagua, Uriel, primary, Lester, Barry M., additional, Marsit, Carmen J., additional, Camerota, Marie, additional, Carter, Brian S., additional, Check, Jennifer F., additional, Helderman, Jennifer, additional, Hofheimer, Julie A., additional, McGowan, Elisabeth C., additional, Neal, Charles R., additional, Pastyrnak, Steven L., additional, Smith, Lynne M., additional, DellaGrotta, Sheri A., additional, Dansereau, Lynne M., additional, O’Shea, T. Michael, additional, and Everson, Todd M., additional

Published
2023
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32. Contributors

Author

Aiello, Allison, primary, Alexis, Neil E., additional, Bulka, Catherine M., additional, Cavalieri, Vincenzo, additional, Clark, Jeliyah, additional, Dhingra, Radhika, additional, Eaves, Lauren A., additional, Emmanuel, Crisma Jazmin, additional, Everson, Todd M., additional, Fry, Rebecca C., additional, Gardner, Amaree J., additional, Ghantous, Akram, additional, Herceg, Zdenko, additional, Jessen, Nicolette, additional, Joss-Moore, Lisa, additional, King, Blythe, additional, Manuck, Tracy A., additional, Marsit, Carmen J., additional, Novoloaca, Alexei, additional, Nwanaji-Enwerem, Jamaji C., additional, O’Shea, T. Michael, additional, Palakodety, Niharika, additional, Pinder, Margaret, additional, Rager, Julia E., additional, Santos, Hudson P., additional, Sentilles, Francie, additional, Sexton-Oates, Alexandra, additional, Venkatratnam, Abhishek, additional, and Ward-Caviness, Cavin, additional

Published
2020
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39. Sex-based differences in placental DNA methylation profiles related to gestational age: an NIH ECHO meta-analysis

Author

Bulka, Catherine M., primary, Everson, Todd M., additional, Burt, Amber A., additional, Marsit, Carmen J., additional, Karagas, Margaret R., additional, Boyle, Kristen E., additional, Niemiec, Sierra, additional, Kechris, Katerina, additional, Davidson, Elizabeth J., additional, Yang, Ivana V., additional, Feinberg, Jason I., additional, Volk, Heather E., additional, Ladd-Acosta, Christine, additional, Breton, Carrie V., additional, O’Shea, T. Michael, additional, and Fry, Rebecca C., additional

Published
2023
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40. Acoustic Cry Characteristics in Preterm Infants and Developmental and Behavioral Outcomes at 2 Years of Age

Author

Manigault, Andrew W., primary, Sheinkopf, Stephen J., additional, Carter, Brian S., additional, Check, Jennifer, additional, Helderman, Jennifer, additional, Hofheimer, Julie A., additional, McGowan, Elisabeth C., additional, Neal, Charles R., additional, O’Shea, Michael, additional, Pastyrnak, Steven, additional, Smith, Lynne M., additional, Everson, Todd M., additional, Marsit, Carmen J., additional, Dansereau, Lynne M., additional, DellaGrotta, Sheri A., additional, and Lester, Barry M., additional

Published
2023
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41. Additional file 1 of Traffic-related air pollution and supplemental folic acid intake in relation to DNA methylation in granulosa cells

Author

Gaskins, Audrey J., Hood, Robert B., Ford, Jennifer B., Hauser, Russ, Knight, Anna K., Smith, Alicia K., and Everson, Todd M.

Abstract

Additional file 1. Supplemental Figure 1. Scatterplots depicting the association between chronological age and predicted epigenetic age of the granulosa cells according to the Horvath Pan-tissue, Grim Age, and Granulosa Cell clocks. Supplemental Figure 2. QQ plots of EWAS results from the analysis of NO2 (A) and supplemental folate (B), where models were adjusted for age and for three surrogate variables. Supplemental Figure 3. Volcano Plots of EWAS results from the analysis of NO2 (A) and supplemental folate (B), where models were adjusted for age and for three surrogate variables; CpGs that yielded FDR q-values < 0.1 are highlighted with red outlines. Supplemental Table 1. Differentially methylated CpGs associated with high versus low NO2 exposure that yielded FDR q-values < 0.10. Supplemental Table 2. Differentially methylated CpGs associated with high versus low supplemental folate intake that yielded FDR q-values < 0.10.

Published
2023
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45. A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Author

Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Fernández Jiménez, Nora, Fore, Ruby, Cilleros Portet, Ariadna, Lepeule, Johanna, Perron, Patrice, Kvist, Tuomas, Tian, Fu-Ying, Lesseur, Corina, Binder, Alexandra M., Lozano, Manuel, Martorell Marugán, Jordi, Loke, Yuk J., Bakulski, Kelly M., Zhu, Yihui, Forhan, Anne, Sammallahti, Sara, Everson, Todd M., Chen, Jia, Michels, Karin B., Belmonte, Thalia, Carmona Sáez, Pedro, Halliday, Jane, Fallin, M. Daniele, LaSalle, Janine M., Tost, Jorg, Czamara, Darina, Fernández, Mariana F., Gómez Martín, Antonio, Craig, Jeffrey M., González Alzaga, Beatriz, Schmidt, Rebecca J., Dou, John F., Muggli, Evelyne, Lacasaña, Marina, Vrijheid, Martine, Marsit, Carmen J., Karagas, Margaret R., Raikkonen, Katri, Bouchard, Luigi, Heude, Barbara, Santa Marina Rodríguez, Loreto, Bustamante, Mariona, Hivert, Marie France, Bilbao Catalá, José Ramón, Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Fernández Jiménez, Nora, Fore, Ruby, Cilleros Portet, Ariadna, Lepeule, Johanna, Perron, Patrice, Kvist, Tuomas, Tian, Fu-Ying, Lesseur, Corina, Binder, Alexandra M., Lozano, Manuel, Martorell Marugán, Jordi, Loke, Yuk J., Bakulski, Kelly M., Zhu, Yihui, Forhan, Anne, Sammallahti, Sara, Everson, Todd M., Chen, Jia, Michels, Karin B., Belmonte, Thalia, Carmona Sáez, Pedro, Halliday, Jane, Fallin, M. Daniele, LaSalle, Janine M., Tost, Jorg, Czamara, Darina, Fernández, Mariana F., Gómez Martín, Antonio, Craig, Jeffrey M., González Alzaga, Beatriz, Schmidt, Rebecca J., Dou, John F., Muggli, Evelyne, Lacasaña, Marina, Vrijheid, Martine, Marsit, Carmen J., Karagas, Margaret R., Raikkonen, Katri, Bouchard, Luigi, Heude, Barbara, Santa Marina Rodríguez, Loreto, Bustamante, Mariona, Hivert, Marie France, and Bilbao Catalá, José Ramón

Abstract

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

Published
2022

47. Placental Expression of Imprinted Genes, Overall and in Sex-Specific Patterns, Associated with Placental Cadmium Concentrations and Birth Size

Author

Everson, Todd M., Marable, Carmen, Deyssenroth, Maya A., Punshon, Tracy, Jackson, Brian P., Lambertini, Luca, Karagas, Margaret R., Chen, Jia, and Marsit, Carmen J.

Subjects
Protein binding -- Genetic aspects -- Analysis, Genetic research -- Genetic aspects -- Analysis, Cadmium -- Analysis, Genes -- Genetic aspects -- Analysis, Fetal development -- Genetic aspects -- Analysis, Pregnant women -- Analysis, Gene expression -- Genetic aspects -- Analysis, Biochemistry, Toxicity, Integrins, Child health, Children, Environmental issues, Health, Dartmouth College
Abstract

Background: Prenatal cadmium (Cd) exposure has been recognized to restrict growth, and male and female fetuses may have differential susceptibility to the developmental toxicity of Cd. Imprinted genes, which exhibit monoallelic expression based on parent of origin, are highly expressed in placental tissues. The function of these genes is particularly critical to fetal growth and development, and some are expressed in sex-specific patterns. Objectives: We aimed to examine whether prenatal Cd associates with the expression of imprinted placental genes, overall or in fetal sex-specific patterns, across two independent epidemiologic studies. Methods: We tested for Cd-sex interactions in association with gene expression, then regressed the placental expression levels of 74 putative imprinted genes on placental log-Cd concentrations while adjusting for maternal age, sex, smoking history, and educational attainment. These models were performed within study- and sex-specific strata in the New Hampshire Birth Cohort Study (NHBCS; n = 326) and the Rhode Island Child Health Study (RICHS; n = 211). We then used fixed-effects models to estimate the sex-specific and overall associations across strata and then examine heterogeneity in the associations by fetal sex. Results: We observed that higher Cd concentrations were associated with higher expression of distal-less homeobox 5 (DLX5) (p = 0.000025), and lower expression of h19 imprinted maternally expressed transcript (H19) (p = 0.00027) and necdin, MAGE family member (NDN) (p = 0.00064) across study and sex-specific strata, while three other genes [carboxypeptidase A4 (CPA4), growth factor receptor bound protein 10 (GRB10), and integrin-linked kinase (ILK)] were significantly associated with Cd concentrations, but only among female placenta ([p.sub.interaction] < 0.05). Additionally, the expression of DLX5, H19, and NDN, the most statistically significant Cd-associated genes, were also associated with standardized birth weight z-scores. Discussion: The differential regulation of a set of imprinted genes, particularly DLX5, H19 and NDN, in association with prenatal Cd exposure may be involved in overall developmental toxicity, and some imprinted genes may respond to Cd exposure in a manner that is specific to infant gender., Introduction Cadmium (Cd) is an ubiquitous environmental contaminant that bioaccumulates in plants grown in contaminated soils, resulting in human exposure when those plants are consumed (Khan et al. 2017). Though [...]

Published
2019
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49. Variation in placental microRNA expression associates with maternal family history of cardiovascular disease.

Author

Tehrani, Jesse M., Kennedy, Elizabeth M., Tian, Fu-Ying, Everson, Todd M., Deyssenroth, Maya, Burt, Amber, Hermetz, Karen, Hao, Ke, Chen, Jia, Koestler, Devin C., and Marsit, Carmen J.

Subjects
GENE expression, FAMILY history (Medicine), MICRORNA, NON-coding RNA, PLACENTA
Abstract

In the United States, cardiovascular disease is the leading cause of death and the rate of maternal mortality remains among the highest of any industrialized nation. Maternal cardiometabolic health throughout gestation and postpartum is representative of placental health and physiology. Both proper placental functionality and placental microRNA expression are essential to successful pregnancy outcomes, and both are highly sensitive to genetic and environmental sources of variation. Placental pathologies, such as preeclampsia, are associated with maternal cardiovascular health but may also contribute to the developmental programming of chronic disease in offspring. However, the role of more subtle alterations to placental function and microRNA expression in this developmental programming remains poorly understood. We performed small RNA sequencing to investigate microRNA in placentae from the Rhode Island Child Health Study (n = 230). MicroRNA counts were modeled on maternal family history of cardiovascular disease using negative binomial generalized linear models. MicroRNAs were considered to be differentially expressed at a false discovery rate (FDR) less than 0.10. Parallel mRNA sequencing data and bioinformatic target prediction software were then used to identify potential mRNA targets of differentially expressed microRNAs. Nine differentially expressed microRNAs were identified (FDR < 0.1). Bioinformatic target prediction revealed 66 potential mRNA targets of these microRNAs, many of which are implicated in TGFβ signaling pathway but also in pathways involving cellular metabolism and immunomodulation. A robust association exists between familial cardiovascular disease and placental microRNA expression which may be implicated in both placental insufficiencies and the developmental programming of chronic disease. [ABSTRACT FROM AUTHOR]

Published
2023
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50. Selenium-associated differentially expressed microRNAs and their targeted mRNAs across the placental genome in two U.S. birth cohorts

Author

Tian, Fu-Ying, primary, Kennedy, Elizabeth M., additional, Hermetz, Karen, additional, Burt, Amber, additional, Everson, Todd M., additional, Punshon, Tracy, additional, Jackson, Brian P., additional, Hao, Ke, additional, Chen, Jia, additional, Karagas, Margaret R., additional, Koestler, Devin C., additional, and Marsit, Carmen, additional

Published
2021
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