Fetal effects of mild maternal COVID-19 infection: metabolomic profiling of cord blood.
INTRODUCTION: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized.
OBJECTIVES: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection.
METHODS: Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry. Metabolite set enrichment analysis (MSEA) was used to evaluate altered biochemical pathways due to COVID-19 intrauterine exposure. Logistic regression models were developed using metabolites to predict intrauterine exposure.
RESULTS: Significant concentration differences between groups (p-value < 0.05) were observed in 19 metabolites. Elevated levels of glucocorticoids, pyruvate, lactate, purine metabolites, phenylalanine, and branched-chain amino acids of valine and isoleucine were discovered in cases while ceramide subclasses were decreased. The top metabolite model including cortisol and ceramide (d18:1/23:0) achieved an Area under the Receiver Operating Characteristics curve (95% CI) = 0.841 (0.725-0.957) for detecting fetal exposure to maternal COVID-19 infection. MSEA highlighted steroidogenesis, pyruvate metabolism, gluconeogenesis, and the Warburg effect as the major perturbed metabolic pathways (p-value < 0.05). These changes indicate fetal increased oxidative metabolism, hyperinsulinemia, and inflammatory response.
CONCLUSION: We present fetal biochemical changes related to intrauterine inflammation and altered energy metabolism in cases of mild maternal COVID-19 infection despite the absence of viral infection. Elucidation of the long-term consequences of these findings is imperative considering the large number of exposures in the population.
Turkoglu O, Alhousseini A, Sajja S, Idler J, Stuart S, Ashrafi N, et al. [Yilmaz A, Wharton K, Graham SF, Bahado-Singh RO] Fetal effects of mild maternal COVID-19 infection: metabolomic profiling of cord blood. Metabolomics. 2023 Apr 15;19(4):41. doi: 10.1007/s11306-023-01988-x. PMID: 37060499.