Dynamics of DNA methylation at IGF2 in preterm and term infants during the first year of life: an observational study. (26th February 2015)

• Record Type: Journal Article
• Authors: Piyasena, Chinthika; Cartier, Jessy; Khulan, Batbayar; French, Karen; Menon, Gopi; Seckl, Jonathan R; Reynolds, Rebecca M; Drake, Amanda J
• Is Part Of: Lancet. Volume 385(2015)Supplement 1
• Page Start: S81
• Publication Date: 2015-02-26
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Medicine; Electronic journals; Periodicals; 610.5
• DOI: 10.1016/S0140-6736(15)60396-8
• Languages: English
• ISSNs: 0140-6736

Abstract

Abstract: Background: Preterm infants are at increased risk of cardiometabolic disease in later life. Extrauterine growth restriction, catch-up growth, altered adiposity, and abnormal hypothalamic–pituitary–adrenal axis activity could be predisposing factors. Altered DNA methylation (5-methylcytosine, 5mC) might be one underlying mechanism. We hypothesised that preterm infants have altered 5mC at the linked differentially methylated region 2 ( DMR2 ) of IGF2 and the H19 imprinting control region ( H19 ICR ) compared with term infants over the first year of life. Methods: We recruited 46 preterm (range 25 weeks + 2 days' gestation to 31 + 5, mean 28 + 6) and 40 term infants (38 + 3 to 42 + 2 weeks' gestation, mean 40 + 2). Anthropometric variables including body composition were measured at term age and 3 months corrected age with air displacement plethysmography and at 1-year-corrected age with skin-fold thickness. Salivary cortisol was measured at 3 months corrected age after the physical examination. Percentage methylation (%5mC) was analysed with pyrosequencing on buccal DNA. Statistical analysis used Student's t test and multivariate linear regression. Findings: Preterm infants demonstrated growth deficit early in postnatal life but had greater percentage body fat at term age (β=5·73, p<0·001), but not at 3 months (β=–0·28, p=0·82). Compared with term infants, preterm infants had a blunted cortisol response to physical examination (mean difference 0·38 μg/dL, p=0·024). At birth, preterm infants had a significant decrease in %5mC at DMR2 compared with term infants at birth (β=–11·48, p<0·001) and compared with preterm infants at term-corrected age ( t =3·13, p=0·01). By term-corrected age, preterm infants had decreased %5mC at both DMR2 (β=–2·84, p=0·013) and the H19 ICR (β=–2·31, p=0·048) compared with term infants at birth, although this difference disappeared at 1 year. Social deprivation was independently associated with decreased %5mC at DMR2 at birth (β=–1·73, p=0·006) and term-corrected age (β=–0·86, p=0·016) but not at 1 year (β=–0·89, p=0·07). Interpretation: Our results show that decreased %5mC accompanies the early growth deficit in preterm infants. The marked reduction in %5mC at IGF2 DMR2 in preterm infants at birth compared with term-age supports existing evidence that imprinting at secondary regions is established after fertilisation, whereas imprinting is established during gametogenesis at primary regions ( H19 ICR ). Both regions might be susceptible to early life stressors such as preterm birth and social deprivation. Funding: Chief Scientist Office of the Scottish Government.