Abstract
Background
The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental
structure and function have been associated with adverse neurodevelopmental outcomes
later in life. Placental CpG methylation represents an epigenetic modification with
the potential to impact placental function, fetal development and child health later in life.
Study design
Genome-wide placental CpG methylation levels were compared between spontaneous versus
indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association
between the identified differentially methylated CpG sites and neurocognitive outcome at
ten years of age was then evaluated.
Results
Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG
sites (217 unique genes) with the majority displaying hypermethylation. The identified genes
are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix
transcription factor binding sites. The placental CpG methylation levels for 17 of these sites
predicted cognitive function at ten years of age.
Conclusion
A hypermethylation signature is present in DNA from placentas in infants with spontaneous
EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted...