The early care environment and DNA methylome variation in childhood

Garg, Elika; Chen, Li; Nguyen, Thao T. T.; Pokhvisneva, Irina; Chen, Lawrence M.; Unternäehrer, Eva; MacIsaac, Julia L.; McEwen, Lisa M.; Mah, Sarah M; Gaudreau, Hélène; Levitan, Robert D.; Moss, Ellen; Sokolowski, Marla B.; Kennedy, James L.; Steiner, Meir; Meaney, Michael J.; Holbrook, Joanna D.; Silveira, Patrícia Pelufo; Karnani, Neerja; Kobor, Michæl S.; O’Donnell, Kieran J.; Team, Mavan Study

doi:10.1017/s0954579418000627

Cited by 78 publications

(47 citation statements)

References 84 publications

(112 reference statements)

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“…Eight studies analyzed how maternal behavior can be a predictor of a certain outcome . The remaining three assessed the role of maternal behavior in interaction with early adversities and/or epigenetic regulation .…”

Section: Resultsmentioning

confidence: 99%

“…A summary of each study timeline is reported in Figure . Five papers had a prospective study design while the other six had a retrospective study design. Adult studies were included only if they retrospectively investigated the link between adversity in infancy or childhood and epigenetic markers later in life.…”

Section: Resultsmentioning

confidence: 99%

“…Adult studies were included only if they retrospectively investigated the link between adversity in infancy or childhood and epigenetic markers later in life. Maternal caregiving was assessed either with self‐report tools or observational measures …”

Section: Resultsmentioning

confidence: 99%

“…Finally, in OXTR TS1 DNA methylation did not differ between maternal care groups and there were no effects for sex or age. Garg et al reported on the association between infant attachment at 36 months infants and DNA methylation at 7 years old. They found that infant attachment at 36 months was significantly predictive (11.9% of variance) of CpG‐specific increase in genome‐wide DNA methylation.…”

Section: Resultsmentioning

confidence: 99%

“…It has been long suggested the presence of developmental sensitive periods in which environmental factors have greater probabilities of affecting long‐term outcomes through epigenetic mechanisms . The studies reviewed here focused on different age periods during which protective caregiving took place: prenatal period, first months of life (5 weeks; 3 months; 4 months), toddlerhood (3 years), pre‐adolescence and a broader range of time up until adolescence (0‐16 years) and they all reported on short‐ and long‐term effects on a set of diverse developmental outcomes. On the one hand, these findings may be suggestive that maternal care variations have a significant effect on infants' DNA methylation independently from infant's age.…”

Section: Discussionmentioning

confidence: 99%

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Maternal caregiving and DNA methylation in human infants and children: Systematic review

Provenzi

Brambilla

Minico

et al. 2019

Genes Brain and Behavior

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The integration of behavioral epigenetics' principles (eg, DNA methylation) into the study of human infants' development has mainly focused on the effects of early adverse exposures, paying less attention to protective caregiving experiences. The present review focused on DNA methylation linked to variations in maternal behavior in human infants and children. Literature search occurred on three databases (PubMed, Scopus and Web of Science) and 11 records were selected. Key variables were abstracted from each article including: sample size and characteristics, time and type of maternal caregiving behavior exposure, time and locus of methylation biomarker, presence/absence, time and type of adverse exposure. Six out of eleven records documented the predictive effect of maternal caregiving on DNA methylation, whereas the remaining five reported on the role of maternal behavior as an influencing factor of the adversity‐to‐methylation link. Consistent with evidence from the animal model, the quality of maternal caregiving in humans (a) might be associated with variations in DNA methylation status of specific genes involved in socio‐emotional development and (b) might partially buffer the association between early adversities and epigenetic variations in infants and children. Current evidence suggests that the quality of maternal caregiving can contribute to behavioral development trajectories of human infants and children at least partially through epigenetic regulation. Open questions and methodological aspects are discussed to guide future human developmental research in behavioral epigenetics.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Maternal caregiving and DNA methylation in human infants and children: Systematic review

Provenzi

Brambilla

Minico

et al. 2019

Genes Brain and Behavior

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Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection

et al. 2022

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ImportanceVery preterm neonates (24-32 weeks’ gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population.ObjectivesTo characterize the pediatric buccal epigenetic (PedBE) clock—a recently developed tool to measure biological aging—among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age.Design, Setting, and ParticipantsThis prospective cohort study was conducted in 2 neonatal intensive care units of 2 hospitals in Toronto, Ontario, Canada. A total of 35 very preterm neonates (24-32 weeks’ gestation) were recruited in 2017 and 2018, and neuroimaging was performed and buccal swab samples were acquired at 2 time points: the first in early life (median postmenstrual age, 32.9 weeks [IQR, 32.0-35.0 weeks]) and the second at term-equivalent age (TEA) at a median postmenstrual age of 43.0 weeks (IQR, 41.0-46.0 weeks). Follow-ups for neurodevelopmental assessments were completed in 2019 and 2020. All neonates in this cohort had at least 1 infection because they were originally enrolled to assess the association of neonatal infection with neurodevelopment. Neonates with congenital malformations, genetic syndromes, or congenital TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes and other agents) infection were excluded.ExposuresThe extent of prematurity was measured by gestational age at birth and PedBE age difference. PedBE age was computed using DNA methylation obtained from 94 age-informative CpG (cytosine-phosphate-guanosine) sites. PedBE age difference (weeks) was calculated by subtracting PedBE age at each time point from the corresponding postmenstrual age.Main Outcomes and MeasuresTotal cerebral volumes and cerebral growth during the neonatal intensive care unit period were obtained from magnetic resonance imaging scans at 2 time points: approximately the first 2 weeks of life and at TEA. Bayley Scales of Infant and Toddler Development, Third Edition, were used to assess neurodevelopmental outcomes at 18 months.ResultsAmong 35 very preterm neonates (21 boys [60.0%]; median gestational age, 27.0 weeks [IQR, 25.9-29.9 weeks]; 23 [65.7%] born extremely preterm [&lt;28 weeks’ gestation]), extremely preterm neonates had an accelerated PedBE age compared with neonates born at a later gestational age (β = 9.0; 95% CI, 2.7-15.3; P = .01). An accelerated PedBE age was also associated with smaller cerebral volumes (β = –5356.8; 95% CI, −6899.3 to −2961.7; P = .01) and slower cerebral growth (β = –2651.5; 95% CI, −5301.2 to −1164.1; P = .04); these associations remained significant after adjusting for clinical neonatal factors. These findings were significant at TEA but not earlier in life. Similarly, an accelerated PedBE age at TEA was associated with lower cognitive (β = –0.4; 95% CI, −0.8 to −0.03; P = .04) and language (β = –0.6; 95% CI, −1.1 to −0.06; P = .02) scores at 18 months.Conclusions and RelevanceThis cohort study of very preterm neonates suggests that biological aging may be associated with impaired brain growth and neurodevelopmental outcomes. The associations between epigenetic aging and adverse neonatal brain health warrant further attention.

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Maternal–infant interaction quality is associated with child NR3C1 CpG site methylation at 7 years of age

Holdsworth

Schell

Appleton

2023

American J Hum Biol

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Objective Infancy is both a critical window for hypothalamic–pituitary–adrenal (HPA) axis development, and a sensitive period for social–emotional influences. We hypothesized that the social–emotional quality of maternal–infant interactions are associated with methylation of HPA‐axis gene NR3C1 later in childhood. Methods Using a subsample of 114 mother‐infant pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC), linear regression models were created to predict variance in methylation of seven selected CpG sites from NR3C1 in whole blood at age 7 years, including the main predictor variable of the first principal component score of observed maternal–infant interaction quality (derived from the Thorpe Interaction Measure at 12 months of age) and covariates of cell‐type proportion, maternal financial difficulties and marital status at 8 months postnatal, child birthweight, and sex. Results CpG site cg27122725 methylation was negatively associated with warmer, more positive maternal interaction with her infant (β = 0.19, p = .02, q = 0.13). In sensitivity analyses, the second highest quartile of maternal behavior (neutral, hesitant behavior) was positively associated with cg12466613 methylation. The other five CpG sites were not significantly associated with maternal–infant interaction quality. Conclusions Narrow individual variation of maternal interaction with her infant is associated with childhood methylation of two CpG sites on NR3C1 that may be particularly sensitive to environmental influences. Infancy may be a sensitive period for even small influences from the social–emotional environment on the epigenetic determinants of HPA‐axis function.

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The early care environment and DNA methylome variation in childhood

Cited by 78 publications

References 84 publications

Maternal caregiving and DNA methylation in human infants and children: Systematic review

Maternal caregiving and DNA methylation in human infants and children: Systematic review

Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection

Maternal–infant interaction quality is associated with child NR3C1 CpG site methylation at 7 years of age

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