BACKGROUND
Growing evidence implicates prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common endocrine-disrupting plasticizer, in the development of autism and attention-deficit/hyperactivity disorder (ADHD). Yet underlying mechanisms remain unclear.
METHODS
Here, we examined whether cord blood DNA methylation, a key epigenetic marker, mediates the association between prenatal DEHP exposure and autism and ADHD symptoms in 847 children from the Barwon Infant Study. Autism and ADHD are complex phenotypes driven by alterations in higher-level gene networks and neuronal circuits, where diverse genetic and environmental risk factors converge. Accordingly, rather than a gene-by-gene approach, we employed a data-driven strategy to elucidate broader functional epigenetic signatures of autism and ADHD elicited by DEHP exposure. This included (1) a methylation profile score for DEHP exposure (MPSDEHP), and (2) a targeted analysis of DEHP-associated co-methylated gene networks.
FINDINGS
Causal mediation analysis showed that both MPSDEHP and a network of 531 co-methylated genes mediated the effect of DEHP on increased autism and ADHD symptoms at ages 2 and 4 years (proportion mediated: 0.21-0.80). The co-methylation network was enriched for neural cell-type markers, autism and ADHD risk genes (including FOXP1, SHANK2, and PLXNB1), and targets of endocrine receptors previously linked to DEHP (including estrogen and glucocorticoid receptors), providing biological plausibility. We validated key results in independent blood (n = 66) and postmortem-brain (n = 40) DNA methylation datasets.
CONCLUSION
These findings provide mechanistic evidence linking DEHP to adverse neurodevelopment and reinforce mounting concerns regarding the risks of prenatal exposure.
FUNDING
Funding was obtained from the NHMRC, the Minderoo Foundation, and additional sources (detailed in acknowledgments).
S. Tanner, Alex Eisner, Boris Novakovic et al.· i Medicina· 0 citations
Background: Maternal depressive symptoms have been associated with adverse child and family outcomes, including child behavioural problems, suboptimal parenting quality, and increased child screen time. However, the developmental pathways linking these factors remain poorly understood. The first model of this study examined whether children’s behavioural problems mediated associations between maternal depressive symptoms and later parenting quality (i.e., nurturant, hostile, consistent). The second model then investigated whether these pathways extended to preschool children’s screen time during the pre-bedtime period. Methods: Longitudinal data from the APrON Study (N = 373 dyads) were analyzed. A mean score for maternal depressive symptoms (EPDS) was derived using data collected across pregnancy and 3, 6, and 12 months postpartum. At age 3 years, child behaviour was assessed using the Child Behavior Checklist. At 5 years, parenting quality was measured using the Parenting Scale, and children’s screen time (frequency of use before bedtime) was assessed using a single maternal-reported item developed by the APrON team. Parallel and parallel serial mediation models were estimated using structural equation modeling. Findings: Maternal depressive symptoms were indirectly associated with more hostile parenting through children’s externalizing problems (p < 0.01, 95% CI [0.02, 0.11]) and directly associated with less nurturant parenting (p = 0.02, 95% CI [−0.19, −0.02]). Results from the parallel serial mediation model indicated that maternal depressive symptoms were indirectly associated with greater child screen time via children’s externalizing problems (p = 0.02, 95% CI [0.01, 0.06]). Significance: These findings suggest that children’s externalizing problems may represent a plausible pathway linking maternal depressive symptoms with later maternal hostile parenting and preschool children’s screen time.
S. Kurbatfinski, Rahul Gandhi, D. Dewey et al.· Children· 0 citations
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