Metabolomics Applied to Cord Serum in Preeclampsia Newborns: Implications for Neonatal Outcomes

Abstract

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.

Decreased Fatty Acid Oxidation Gene Expression in Pre-Eclampsia According to the Onset and Presence of Intrauterine Growth Restriction

“…Recent in vitro studies have linked increased CPT1A expression in the placenta to the development of pre-eclampsia by inhibition of trophoblast cell invasion and migration [ 45 ]. Consistent with this theory, maternal and umbilical cord serum carnitine and acyl-carnitine levels increase in pre-eclampsia [ 46 , 47 , 48 , 49 ]. In addition, a maternal high-fat diet in rats downregulated the mRNA and protein expressions of CPT2 in the placenta [ 50 ].…”

Biomarkers of cardiovascular disease risk in the neonatal population

“…These include molecules such as creatinine, uric acid, N4-acetylcytidine, pseudouridine, carnitine, and sphingolipid metabolism, respectively. 70 Offspring of GDM pregnancies display deviant triglyceride and lipoprotein constituents and a possible predisposition for obesity as well as increased cord VEGF levels indicative of altered development of the vascular system. 71,72 SGA infants of GDM pregnancies presented increased levels of LDL-C, growth hormone, and fibrinogen and decreased levels of HDL-C and ApoA suggesting diminished antioxidative particle properties and a proneness of developing IR in the future.…”