Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life

• Published in: PloS one Vol. 13; no. 3; p. e0193271
• Main Authors: Tilley, Sloane K, Martin, Elizabeth M, Smeester, Lisa, Joseph, Robert M, Kuban, Karl C K, Heeren, Tim C, Dammann, Olaf U, O'Shea, T Michael, Fry, Rebecca C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.03.2018; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Biology and life sciences; Child; Cognition - physiology; Cognitive Dysfunction - genetics; Cognitive Dysfunction - metabolism; Cohort Studies; CpG Islands; Cytosine; Developmental disabilities; DNA Methylation; Female; Genetic aspects; Genome-Wide Association Study; Health aspects; Humans; Infant, Extremely Premature - metabolism; Infant, Extremely Premature - psychology; Male; Maternal Age; Medicine and Health Sciences; Methylation; Middle Aged; Neuropsychological Tests; People and Places; Physiological aspects; Placenta; Placenta - metabolism; Post-translational modifications; Pregnancy; Premature infants; Prognosis; Risk factors; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193271

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. 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. 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. 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 later life cognitive function, supporting the developmental origins of health and disease hypothesis (DOHaD).