Endocrinology Department, Pediatric Research Institute Hospital Sant Joan de Déu, University of Barcelona, 08950, Esplugues, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029, Madrid, Spain.
Pediatr Res. 2022 Sep;92(3):829-837. doi: 10.1038/s41390-021-01845-4. Epub 2021 Nov 19.
Children with low birth weight (LBW) have a higher risk of developing endocrine-metabolic disorders later in life. Deregulation of specific microRNAs (miRNAs) could underscore the programming of adult pathologies. We analyzed the miRNA expression pattern in both umbilical cord serum samples from LBW and appropriate-for-gestational-age (AGA) newborns and maternal serum samples in the 3rd trimester of gestation, and delineated the relationships with fetal growth, body composition, and markers of metabolic risk.
Serum samples of 12 selected mother-newborn pairs, including 6 LBW and 6 AGA newborns, were used for assessing miRNA profile by RNA-sequencing. The miRNAs with differential expression were validated in a larger cohort [49 maternal samples and 49 umbilical cord samples (24 LBW, 25 AGA)] by RT-qPCR. Anthropometric, endocrine-metabolic markers and body composition (by DXA) in infants were determined longitudinally over 12 months.
LBW newborns presented reduced circulating concentrations of miR-191-3p (P = 0.015). miR-191-3p levels reliably differentiated LBW from AGA individuals (ROC AUC = 0.76) and were positively associated with anthropometric and body composition measures at birth and weight Z-score at 12 months (P < 0.05).
miR-191-3p was reliably different in LBW individuals, and could be a new player in the epigenetic mechanisms linking LBW and future endocrine-metabolic adverse outcomes.
Children with low birth weight (LBW) have a higher risk of developing endocrine-metabolic disorders. Deregulation of specific microRNAs (miRNAs) could underscore the programming of those pathologies. miR-191-3p is downregulated in serum of LBW newborns, and its concentrations associate positively with neonatal anthropometric measures, with lean mass and bone accretion at age 15 days and with weight Z-score at age 12 months. miR-191-3p was reliably different in individuals with LBW, and could be a new player in the epigenetic mechanisms connecting LBW and future endocrine-metabolic adverse outcomes.
低出生体重(LBW)儿童在以后的生活中患内分泌代谢疾病的风险更高。特定 microRNA(miRNA)的失调可能突出了成年后发病机制的编程。我们分析了 LBW 和适合胎龄(AGA)新生儿的脐带血清样本以及妊娠第 3 个月的母体血清样本中的 miRNA 表达模式,并阐明了与胎儿生长、身体成分和代谢风险标志物的关系。
使用 RNA 测序评估 12 对选定的母婴样本(包括 6 对 LBW 和 6 对 AGA 新生儿)的 miRNA 图谱。通过 RT-qPCR 在更大的队列[49 个母体样本和 49 个脐带样本(24 个 LBW,25 个 AGA)]中验证差异表达的 miRNA。通过纵向研究在 12 个月内确定婴儿的人体测量、内分泌代谢标志物和身体成分(通过 DXA)。
LBW 新生儿的循环 miR-191-3p 浓度降低(P=0.015)。miR-191-3p 水平可靠地区分 LBW 与 AGA 个体(ROC AUC=0.76),并与出生时的人体测量和身体成分指标以及 12 个月时的体重 Z 分数呈正相关(P < 0.05)。
miR-191-3p 在 LBW 个体中可靠地不同,可能是将 LBW 与未来内分泌代谢不良结局联系起来的表观遗传机制中的新参与者。
低出生体重(LBW)儿童发生内分泌代谢疾病的风险较高。特定 microRNA(miRNA)的失调可能突出了这些疾病的编程。LBW 新生儿的血清 miR-191-3p 下调,其浓度与新生儿人体测量指标呈正相关,15 天时与瘦体重和骨量增加相关,12 个月时与体重 Z 分数相关。miR-191-3p 在 LBW 个体中存在显著差异,可能是将 LBW 与未来内分泌代谢不良结局联系起来的表观遗传机制中的新参与者。