INFANT Research Centre, Ireland; Department of Paediatrics and Child Health, University College Cork, Cork, Ireland; National Children's Research Centre, Crumlin, Dublin, Ireland.
INFANT Research Centre, Ireland; Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
J Pediatr. 2021 Jan;228:74-81.e2. doi: 10.1016/j.jpeds.2020.08.051. Epub 2020 Aug 20.
To evaluate umbilical cord messenger RNA (mRNA) expression as biomarkers for the grade of hypoxic-ischemic encephalopathy (HIE) and long-term neurodevelopment outcome.
Infants were recruited from the BiHiVE1 study, Ireland (2009-2011), and the BiHiVE2 study, Ireland, and Sweden (2013-2015). Infants with HIE were assigned modified Sarnat scores at 24 hours and followed at 18-36 months. mRNA expression from cord blood was measured using quantitative real-time polymerase chain reaction.
We studied 124 infants (controls, n = 37; perinatal asphyxia, n = 43; and HIE, n = 44). Fzd4 mRNA increased in severe HIE (median relative quantification, 2.98; IQR, 2.23-3.68) vs mild HIE (0.88; IQR, 0.46-1.37; P = .004), and in severe HIE vs moderate HIE (1.06; IQR, 0.81-1.20; P = .003). Fzd4 mRNA also increased in infants eligible for therapeutic hypothermia (1.20; IQR, 0.92-2.37) vs those who were ineligible for therapeutic hypothermia group (0.81; IQR, 0.46-1.53; P = .017). Neurodevelopmental outcome was analyzed for 56 infants. Nfat5 mRNA increased in infants with severely abnormal (1.26; IQR, 1.17-1.39) vs normal outcomes (0.97; IQR, 0.83-1.24; P = .036), and also in infants with severely abnormal vs mildly abnormal outcomes (0.96; IQR, 0.80-1.06; P = .013). Fzd4 mRNA increased in infants with severely abnormal (2.51; IQR, 1.60-3.56) vs normal outcomes (0.74; IQR, 0.48-1.49; P = .004) and in infants with severely abnormal vs mildly abnormal outcomes (0.97; IQR, 0.75-1.34; P = .026).
Increased Fzd4 mRNA expression was observed in cord blood of infants with severe HIE; Nfat5 mRNA and Fzd4 mRNA expression were increased in infants with severely abnormal long-term outcomes. These mRNA may augment current measures as early objective markers of HIE severity at delivery.
评估脐带信使 RNA（mRNA）表达作为评估缺氧缺血性脑病（HIE）严重程度和长期神经发育结局的生物标志物。
本研究纳入了来自爱尔兰（2009-2011 年）和爱尔兰、瑞典（2013-2015 年）BiHiVE1 研究和 BiHiVE2 研究的婴儿。在 24 小时内，根据改良的 Sarnat 评分对 HIE 婴儿进行分组，并在 18-36 个月时进行随访。使用实时定量聚合酶链反应（PCR）测量脐带血中的 mRNA 表达。
本研究纳入了 124 名婴儿（对照组 n=37；围产期窒息 n=43；HIE n=44）。严重 HIE 患儿的 Fzd4 mRNA 表达增加（中位数相对定量，2.98；IQR，2.23-3.68），中度 HIE 患儿的 Fzd4 mRNA 表达也增加（中位数相对定量，1.06；IQR，0.81-1.20；P=0.003）。Fzd4 mRNA 还在适合接受治疗性低温的婴儿中增加（1.20；IQR，0.92-2.37），而在不适合接受治疗性低温的婴儿中则减少（0.81；IQR，0.46-1.53；P=0.017）。对 56 名婴儿的神经发育结局进行了分析。严重异常结局（1.26；IQR，1.17-1.39）患儿的 Nfat5 mRNA 表达增加，而正常结局患儿的 Nfat5 mRNA 表达降低（0.97；IQR，0.83-1.24；P=0.036），且严重异常结局患儿的 Nfat5 mRNA 表达也高于轻度异常结局患儿（0.96；IQR，0.80-1.06；P=0.013）。严重异常结局患儿的 Fzd4 mRNA 表达增加（2.51；IQR，1.60-3.56），而正常结局患儿的 Fzd4 mRNA 表达降低（0.74；IQR，0.48-1.49；P=0.004），且严重异常结局患儿的 Fzd4 mRNA 表达也高于轻度异常结局患儿（0.97；IQR，0.75-1.34；P=0.026）。
严重 HIE 婴儿脐带血中 Fzd4 mRNA 表达增加；Nfat5 mRNA 和 Fzd4 mRNA 表达在长期结局严重异常的婴儿中增加。这些 mRNA 可能会作为目前分娩时评估 HIE 严重程度的指标的补充，作为 HIE 严重程度的早期客观标志物。
