Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva.
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ABSTRACT:
SUBMITTER: Laubach ZM
PROVIDER: S-EPMC6802709 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva.
Laubach Zachary M ZM Perng Wei W Cardenas Andres A Rifas-Shiman Sheryl L SL Oken Emily E DeMeo Dawn D Litonjua Augusto A AA Duca Radu-Corneliu RC Godderis Lode L Baccarelli Andrea A Hivert Marie-France MF
Epigenomics 20190911 12
<b>Aim:</b> We investigated associations of prenatal socioeconomic status (SES) with DNA methylation at birth, and to explore persistence of associations into early (∼3 years) and mid-childhood (∼7 years) among 609 mother-child pairs in a Boston-area prebirth cohort. <b>Materials & methods:</b> First, we created a prenatal SES index comprising individual- and neighborhood-level metrics and examined associations of low (lowest 10%) versus high (upper 90%) SES with genome-wide DNA methylation in c ...[more]
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Project description:ObjectiveOur objective was to use longitudinal data from a US birth cohort to test whether the probability of overweight or obesity during the first 6 years of life varied according to socioeconomic status.Design and methodsUsing six waves of longitudinal data from full-term children in the Early Childhood Longitudinal Study-Birth Cohort (2001-2007; n?4,950), we examined the prevalence of overweight or obesity (Body Mass Index (BMI)>2 standard deviations above age- and sex- specific WHO Childhood Growth Standard reference mean; henceforth, "overweight/obesity") according to age, socioeconomic status, and race/ethnicity using generalized estimating equation models.ResultsThe association between socioeconomic status and overweight/obesity varied significantly by race/ethnicity, but not by sex. Overweight/obesity was significantly associated with socioeconomic status among whites, Hispanics and Asians; the adjusted odds of overweight/obesity began to diverge according to SES after the first 9 months of life. By approximately 4 years, children with the highest SES had a significantly lower odds of overweight/obesity. SES was not significantly related to overweight/obesity among African Americans and American Indians during early childhood.ConclusionsFew studies have assessed the associations between SES and overweight/obesity within racial/ethnic groups in the US. We find that in contemporary, US-born children, SES was inversely associated with overweight/obesity among more racial/ethnic groups (whites, Hispanics, and Asians) than previously reported.
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Project description:BackgroundEpigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health.ObjectiveWe sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes.MethodsWe estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression [[Formula: see text]]. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y ([Formula: see text]). We ran the same analyses in the Generation R Study for replication ([Formula: see text]). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression.ResultsLiving closer to major roadways at birth was associated with higher cord blood (and-more weakly-midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88% at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%, 0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study.ConclusionsOur discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2-a gene known to be linked to axonal development-in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7-11 y in the same children. https://doi.org/10.1289/EHP2034.
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Project description:BACKGROUND:Corticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood. METHODS:We investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n?=?239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn. RESULTS:Maternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P?<?0.05, ??=?0.64, SE?=?0.30). CONCLUSION:In our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood.
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Project description:BACKGROUND:Lead is an established neurotoxicant and early life exposure to lead is associated with detrimental impacts on IQ and several neurobehavioral domains. Less is known, however, about effects of prenatal lead exposure below 5??g/dL on executive function and on social, emotional and self-regulatory behaviors in childhood. OBJECTIVES:To examine the association between prenatal lead exposure and childhood executive function and social, emotional and self-regulatory behaviors. METHODS:We included 1006 mother-child pairs from the Project Viva prospective pre-birth cohort. We measured prenatal maternal lead in second-trimester erythrocytes. In mid-childhood (median 7.7?years), parents and teachers rated executive function related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ). We used multivariable linear regression models adjusted for maternal, paternal, and child characteristics and metal co-exposures. RESULTS:Mean maternal erythrocyte lead concentration was 1.2??g/dL (interquartile range [IQR] 0.8-1.5??g /dL), equivalent to approximately 0.4??g/dL in whole blood. In adjusted models, associations with parent and teacher-rated scales were largely null, although effect estimates were consistently positive, suggesting worse scores with increasing lead levels. For an IQR increase in lead, BRIEF Global Executive Composite (GEC) was 0.73 (95% CI: -0.06, 1.52) points higher for parent-rated scores and 0.42 (95% CI: -0.39, 1.23) points higher for teacher-rated scores. Associations were strongest for parent-rated BRIEF plan/organize (??=?0.85; 95% CI: 0.12, 1.59) and shift (??=?0.88; 95% CI: 0.01, 1.75) subscales, as well as the SDQ emotional problems subscale (??=?0.18; 95% CI: 0.03, 0.33). DISCUSSION:In this cohort with lead levels commonly experienced by U.S. women, there were few statistically significant associations with childhood executive function and behavior. However, there was a trend of worse neurobehavioral scores with increasing prenatal lead concentrations, in particular for childhood emotional problems and capacity to plan/organize and shift. Our results highlight the importance of continuing efforts to eliminate lead exposure in the general population.
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Project description:Study questionIs cesarean delivery associated with earlier offspring pubertal development?Summary answerWe identified that boys born by cesarean delivery developed puberty earlier, evidenced by an earlier age at peak height velocity and earlier attainment of puberty score > 1, than boys born by vaginal delivery.What is known alreadyCesarean delivery is posited to have long-term effects on health outcomes. However, few studies have examined whether mode of delivery is related to pubertal development.Study design, size, durationProspective pre-birth cohort study consisting of 1485 mother-child pairs enrolled during pregnancy from obstetric practices and followed up until early adolescence (median age 12.9 years). Participant inclusion required data on mode of delivery and at least one measure of pubertal development.Participants/materials, setting, methodsParticipants are children from the Project Viva study. We abstracted information on delivery mode from electronic medical records from children followed since birth (1999-2002) and examined the following markers of pubertal development: age at peak height velocity (APHV); age at menarche (girls only); parent-reported pubertal development score; and child-reported pictograph Tanner pubic hair staging. We used multivariable regression models to examine associations of delivery mode with these four pubertal indices, adjusting for the following confounders: demographic and socioeconomic factors; maternal height, pre-pregnancy BMI, total gestational weight gain, pregnancy conditions, parity, and maternal age at menarche; paternal height and BMI; gestational age at delivery and birthweight-for-gestational-age z-score.Main results and the role of chanceIn this study, 23.2% of children were born by cesarean delivery. Girls had an earlier APHV, had a higher pubertal score throughout childhood and in early adolescence, and were more likely to attain puberty score >1 and Tanner pubic hair Stage >1 earlier compared to boys. Mean (SD) age at menarche in girls was 12.4 (1.0) years. Boys born by cesarean delivery had significantly earlier APHV (β -0.23 years; 95% CI -0.40, -0.05) and higher risk of earlier attainment of puberty score > 1 (hazard ratio 1.09; 95% CI 1.01, 1.19) than boys born by vaginal delivery, after adjusting for confounders. These associations were not mediated by pre-pubertal BMI and were similar for planned (no labor) and unplanned (labor) cesarean delivery. No associations were observed between delivery mode and time to attain Tanner pubic hair Stage > 1 in boys. In girls, mode of delivery was not associated with any of the measured pubertal development markers.Limitations, reasons for cautionThis study used, as secondary outcomes, parent- and child-reported measures of pubertal development, which may be more prone to error and misclassification than information collected by trained observers or physicians during clinical examinations. The findings may also not be generalizable to populations from different settings, because all participants lived in one geographic area, were well educated, and had health care.Wider implications of the findingsOur findings provide support for cesarean delivery as a potential indicator of identifying children who are likely to experience earlier pubertal development; however, more studies are needed to confirm or refute these observations.Study funding/competing interest(s)The project was funded by grants from the National Institutes of Health. The authors have no financial relationships or competing interests to disclose.Trial registration numberN/A.
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