Cytosine methylation profiling in small and large for gestational age newborns

In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA), small for gestational age (SGA) and adequate for gestational age/Control (AGA/Ctl) newborns. We found several differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) between LGA, SGA and AGA groups. A system biology approach identified several biological processes significantly enriched with genes in association with DMCs including Regulation of transcription, Regulation of epinephrine secretion, Norepinephrine biosynthesis, Receptor transactivation, Forebrain regionalization and several terms related with kidney and cardiovascular development. Gene ontology analysis of the genes in association with the DMRs identified several significantly enriched biological processes related with kidney development including Mesonephric duct development and Nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched at gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys and metabolism. Our study identified several DMCs/DMRs in association with fetal growth patterns. The use of cord blood as material for the identification of DNA methylation biomarkers gives us the possibility to perform follow up studies on the same patients as they enter childhood and puberty. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness. Overall design: A total of 36 newborns were included in the study: 13 were classified as SGA, 11 as LGA and 12 as AGA (Ctl). LGA: newborns = 34 weeks of gestational age, whose weight and / or length were >+ 2 SDS (Z-score) according to sex-specific birth weight and birth length gestational age reference charts. SGA: newborns = 34 weeks of gestational age, whose weight and / or length were <- 2 SDS according to sex-specific birth weight and birth length gestational age reference charts. AGA (Ctl): newborns = 34 weeks of gestational age, whose weight and length were between – 2 and + 2SDS according to sex-specific birth weight and birth length gestational age reference charts. Umbilical cord blood was collected and genomic DNA was immediately extracted from whole umbilical cord blood using an automated DNA extractor (BioRobot EZ1, QIAGEN, Hilden, Germany).