Abstract
BackgroundPreterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children.MethodsWe performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung.ResultsWe identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P < 1.06 × 10− 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels.ConclusionsWe identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
Highlights
Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life
This model was selected as the main model because associations of DNA methylation with gestational age related to pregnancy complications or potentially influenced by obstetric interventions may be less reflective of normal developmental processes than newborns with spontaneous uncomplicated delivery
We show that DNA methylation at numerous CpG sites and Differentially methylated regions (DMRs) across the genome is associated with gestational age at birth
Summary
Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. DNA methylation patterns have been associated with environmental factors relevant to preterm birth, including smoking, air pollution exposure, microbial and maternal nutritional factors [18,19,20,21,22]. Such exposure-related epigenetic patterns potentially influence gene expression profiles and/or susceptibility to chronic disease during the lifecourse [23, 24]. It is possible that DNA methylation changes at birth may contribute to the myriad immediate and late health outcomes that have been associated with gestational age
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
