Data_Sheet_1_Metabolomics Applied to Cord Serum in Preeclampsia Newborns: Implications for Neonatal Outcomes.xlsx

Preeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality. However, it is still uncertain how PE affects neonate metabolism. We conducted an untargeted metabolomics analysis of cord blood to explore the metabolic changes in PE neonates. Umbilical cord serum samples from neonates with preeclampsia (n = 29) and non-preeclampsia (non-PE) (n = 32) pregnancies were analyzed using the UHPLC-QE-MS metabolomic platform. Different metabolites were screened, and pathway analysis was conducted. A subgroup analysis was performed among PE neonates to compare the metabolome between appropriate-for-gestational-age infants (n = 21) and small-for-gestational-age (SGA) infants (n = 8). A total of 159 different metabolites were detected in PE and non-PE neonates. Creatinine, N4-acetylcytidine, sphingomyelin (D18:1/16:0), pseudouridine, uric acid, and indolelactic acid were the most significant differential metabolites in the cord serum of PE neonates. Differential metabolite levels were elevated in PE neonates and were involved in the following metabolic pathways: glycine, serine, and threonine metabolism; sphingolipid, glyoxylate, and dicarboxylate metabolism; and arginine biosynthesis. In PE neonates, SGA neonates showed increased levels of hexacosanoyl carnitine and decreased abundance of 3-hydroxybutyric acid and 3-sulfinoalanine. Taurine-related metabolism and ketone body-related pathways were mainly affected. Based on the UHPLC-QE-MS metabolomics analysis, we identified the metabolic profiles of PE and SGA neonates. The abundance of metabolites related to certain amino acid, sphingolipid, and energy metabolism increased in the umbilical cord serum of PE neonates.

子痫前期（preeclampsia, PE）是引发孕产妇及围产儿发病与死亡的主要诱因之一，但目前学界尚未明确子痫前期对新生儿代谢的具体影响机制。本研究通过脐带血非靶向代谢组学（untargeted metabolomics）分析，探究子痫前期新生儿的代谢变化特征。研究采用超高效液相色谱-四极杆-静电场轨道阱质谱（UHPLC-QE-MS）代谢组学平台，对29例子痫前期新生儿与32例非子痫前期（non-PE）新生儿的脐带血清样本进行检测；随后筛选差异代谢物并开展代谢通路富集分析。此外，本研究对子痫前期新生儿亚群进行分析，比较适于胎龄儿（appropriate-for-gestational-age, n=21）与小于胎龄儿（small-for-gestational-age, SGA, n=8）的代谢组差异。本研究在子痫前期与非子痫前期新生儿中共检测到159种差异代谢物，其中肌酐、N4-乙酰胞苷、鞘磷脂（D18:1/16:0）、假尿苷、尿酸及吲哚乳酸为子痫前期新生儿脐带血清中最显著的差异代谢物。子痫前期新生儿的差异代谢物水平显著升高，且这些代谢物富集于以下代谢通路：甘氨酸、丝氨酸与苏氨酸代谢；鞘脂、乙醛酸与二羧酸代谢；以及精氨酸生物合成。在子痫前期新生儿亚群中，小于胎龄儿的二十六酰基肉碱水平升高，而3-羟基丁酸与3-磺基丙氨酸的丰度降低，其主要受影响的代谢通路为牛磺酸相关代谢与酮体相关通路。基于UHPLC-QE-MS代谢组学分析结果，本研究明确了子痫前期新生儿与小于胎龄儿的代谢谱特征；子痫前期新生儿的脐带血清中，与特定氨基酸、鞘脂及能量代谢相关的代谢物丰度均显著升高。