van Dokkum Nienke H, Bachini Sofia, Verkaik-Schakel Rikst Nynke, Baptist Dyvonne H, Salavati Sahar, Kraft Karianne E, Scherjon Sicco A, Bos Arend F, Plösch Torsten
Department of Pediatrics, Division of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Front Pediatr. 2022 Jun 1;10:876803. doi: 10.3389/fped.2022.876803. eCollection 2022.
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.
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).
Twenty-four infants had atypical MOS-R, 19 infants had near-optimal MOS-R. We identified differences in average methylation of (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%), = 0.008 for atypical], and at three of the five individual CpG-sites. For and we found no differences between the groups.
Hypomethylation of 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.
了解早产后脑发育障碍的潜在机制可能会增加针对性干预的机会。我们旨在评估所选基因的胎盘DNA甲基化是否会影响早产儿的早期神经功能。
我们纳入了43例孕周<30周和/或出生体重<1000g的婴儿及其出生时的胎盘样本。我们根据基因与几种可能与不良神经发育结局相关的产前状况的关联来选择基因。我们使用焦磷酸测序法测定DNA甲基化，并在足月后3个月使用Prechtl的一般运动评估，包括修订后的运动最优性评分（MOS-R）来评估神经功能。
24例婴儿的MOS-R不典型，19例婴儿的MOS-R接近最优。我们发现（编码糖皮质激素受体）的平均甲基化存在差异[接近最优组为3.3%（95%置信区间：2.4%-3.9%），不典型组为2.3%（95%置信区间：1.7%-3.0%），P = 0.008]，并且在五个单个CpG位点中的三个位点上也存在差异。对于和，我们发现两组之间没有差异。
胎盘组织中的低甲基化与极早产儿足月后3个月时较差的神经功能有关。应进一步研究减轻孕期应激及其对早产儿及其神经发育结局的影响。
