Prenatal risk factors and neonatal DNA methylation in very preterm infants

Abstract

Background Prenatal risk factors are related to poor health and developmental outcomes for infants, potentially via epigenetic mechanisms. We tested associations between person-centered prenatal risk profiles, cumulative prenatal risk models, and epigenome-wide DNA methylation (DNAm) in very preterm neonates. Methods We studied 542 infants from a multi-center study of infants born < 30 weeks postmenstrual age. We assessed 24 prenatal risk factors via maternal report and medical record review. Latent class analysis was used to define prenatal risk profiles. DNAm was quantified from neonatal buccal cells using the Illumina MethylationEPIC Beadarray. Results We identified three latent profiles of women: a group with few risk factors (61%) and groups with elevated physical (26%) and psychological (13%) risk factors. Neonates born to women in higher risk subgroups had differential DNAm at 2 CpG sites. Higher cumulative prenatal risk was associated with methylation at 15 CpG sites, 12 of which were located in genes previously linked to physical and mental health and neurodevelopment. Conclusion We observed associations between prenatal risk factors and DNAm in very preterm infants using both person-centered and cumulative risk approaches. Epigenetics offers a potential biological indicator of prenatal risk exposure.

Elevated epigenetic age in wild compared to lab-raised house mice

“…Moreover, as we observed heightened epigenetic age in wild compared to lab mice even during the first ∼2 weeks of life, we suggest that peri- and early postnatal effects on offspring DNA methylation may vary between laboratory and wild mice and contribute to their different epigenetic age profiles. Various human, mouse, and other animal studies have demonstrated the association between prenatal maternal experience (such as food shortage, diet, infection, substance exposure, and stress) and offspring DNA methylation patterns, with differences from the prenatal (foetal) phase still detectable in later life (Tobi et al, 2009; Heijmans et al, 2008; Lan et al, 2013; Richetto et al, 2017; Camerota et al, 2021; Joubert et al, 2016; Kertes et al, 2016; Vangeel et al, 2017).…”

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

“…Preterm birth has been shown to leave an epigenetic signature that persists into adolescence and adulthood (Cruickshank et al, 2013; Tan et al, 2018). Prenatal risk, measured cumulatively and as distinct phenotypes, has been shown to predict DNA methylation at birth at multiple specific CpG sites across the epigenome in children born < 30 weeks (Camerota et al, 2021). In this study, prenatal risk was primarily associated with lower DNA methylation, and many of the identified CpGs were located in genes previously shown to be associated with physical and mental health outcomes as well as neurodevelopmental markers (Camerota et al, 2021).…”

“…Prenatal risk, measured cumulatively and as distinct phenotypes, has been shown to predict DNA methylation at birth at multiple specific CpG sites across the epigenome in children born < 30 weeks (Camerota et al, 2021). In this study, prenatal risk was primarily associated with lower DNA methylation, and many of the identified CpGs were located in genes previously shown to be associated with physical and mental health outcomes as well as neurodevelopmental markers (Camerota et al, 2021). Further candidate gene and epigenome-wide findings in preterm children show associations between DNA methylation and bacterial sepsis (Tendl et al, 2013), pain-related stress (Chau et al, 2014; Provenzi et al, 2015), medical morbidities (Everson et al, 2020), and neonatal neurobehavior (Everson et al, 2019; Lester et al, 2015).…”

Innate Immune Memory in Macrophages

“…23,240 Most work has been done in diseases of adulthood, but these data could provide useful insights into the susceptibility and pathogenesis of many neonatal conditions. [241][242][243]…”