ABSTRACT

Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene (NR3C1) and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 _F region of the NR3C1 gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 _F. Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 _F region of the NR3C1 gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.

摘要

围产期的不良经历与人类糖皮质激素受体基因 ( NR3C1 ) 的甲基化和长期疾病有关。我们对围产期逆境与NR3C1 1 _F区DNA 甲基化之间的关联进行了系统评价 新生儿基因。我们探索了 MEDLINE、Web of Science、Scopus、Scielo 和 Lilacs 数据库，没有时间或语言限制。两名独立的审稿人进行了文章的选择和数据的提取。三分之一参加了所有阶段的方法学质量评估和共识会议。最后，选择了十项研究。方法学质量在 6 人中被认为中等，在 4 人中被认为低。_{在外显子 1 F}的 47 个 CpG 位点中的 41 个报告了甲基化变化 . 六项研究针对妊娠期间的母体状况：两项报告在相同位点（CpG 10、13、20、21 和 47）发生甲基化变化，四项在 CpG 35 至 39 的一个或多个位点报告。四项研究针对新生儿参数和发病率：在两个相同的位点 4、8、10、16、25 和 35 的甲基化变化被报道。与压力条件相关的高甲基化盛行。低甲基化更常与保护性条件相关（怀孕期间的母胎附着、母乳摄入、较高的出生体重或阿普加）。总之，  NR3C1 1 _F区几个位点的甲基化变化新生儿和非常年幼婴儿的基因与围产期压力有关，但需要更可靠和可比较的结果来证实特定部位的关联。