Differential Placental DNA Methylation of NR3C1 in Extremely Preterm Infants With Poorer Neurological Functioning

Frontiers in Pediatrics

article

Nienke H. van Dokkum¹  Sofia Bachini¹  Rikst Nynke Verkaik-Schakel²  Dyvonne H. Baptist¹  Sahar Salavati¹  Karianne E. Kraft¹  Sicco A. Scherjon²  Arend F. Bos¹  Torsten Plösch² 

[1] Department of Pediatrics, Division of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen;Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen

关键词: placenta;    DNA methylation;    stress;    prematurity;    neurological functioning;   

DOI  :  10.3389/fped.2022.876803

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background Understanding underlying mechanisms of neurodevelopmental impairment following preterm birth may enhance opportunities for targeted interventions. We aimed to assess whether placental DNA methylation of selected genes affected early neurological functioning in preterm infants. Methods We included 43 infants, with gestational age <30 weeks and/or birth weight <1,000 g and placental samples at birth. We selected genes based on their associations with several prenatal conditions that may be related to poor neurodevelopmental outcomes. We determined DNA methylation using pyrosequencing, and neurological functioning at 3 months post-term using Prechtl's General Movement Assessment, including the Motor Optimality Score-Revised (MOS-R). Results Twenty-four infants had atypical MOS-R, 19 infants had near-optimal MOS-R. We identified differences in average methylation of NR3C1 (encoding for the glucocorticoid receptor) [3.3% (95%-CI: 2.4%−3.9%) for near-optimal vs. 2.3% (95%-CI: 1.7%−3.0%), p = 0.008 for atypical], and at three of the five individual CpG-sites. For EPO, SLC6A3, TLR4, VEGFA, LEP and HSD11B2 we found no differences between the groups. Conclusion Hypomethylation of NR3C1 in placental tissue is associated with poorer neurological functioning at 3 months post-term in extremely preterm infants. Alleviating stress during pregnancy and its impact on preterm infants and their neurodevelopmental outcomes should be further investigated.

【 授权许可】

CC BY