Browsing by Author "Everson, Todd M"

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    Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium.
    (Hum Mol Genet, 2017-10-15) 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; Davey Smith, George; 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; Relton, Caroline L
    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 (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.
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    Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program.
    (Pediatric research, 2023-02) 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; Lester, Barry M

    Background

    Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures.

    Methods

    We studied 1112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium. We used latent profile analysis to characterize infant neurobehavioral profiles and generalized estimating equations to determine predictors of NNNS profiles.

    Results

    Six distinct neonatal neurobehavioral profiles were identified, including two dysregulated profiles: a hypo-aroused profile (16%) characterized by lethargy, hypotonicity, and nonoptimal reflexes; and a hyper-aroused profile (6%) characterized by high arousal, excitability, and stress, with low regulation and poor movement quality. Infants in the hypo-aroused profile were more likely to be male, have younger mothers, and have mothers who were depressed prenatally. Infants in the hyper-aroused profile were more likely to be Hispanic/Latino and have mothers who were depressed or used tobacco prenatally.

    Conclusions

    We identified two dysregulated neurobehavioral profiles with distinct perinatal antecedents. Further understanding of their etiology could inform targeted interventions to promote positive developmental outcomes.

    Impact

    Prior research on predictors of neonatal neurobehavior have included single-cohort studies, which limits generalizability of findings. In a multi-cohort study of preterm and term-born infants, we found six distinct neonatal neurobehavioral profiles, with two profiles being identified as dysregulated. Hypo- and hyper-aroused neurobehavioral profiles had distinct perinatal antecedents. Understanding perinatal factors associated with dysregulated neurobehavior could help promote positive developmental outcomes.