Fetal Effects of COVID-19 Infection: Targeted Metabolomic profiling of cord blood

ABSTRACT

Objective: The impact of maternal COVID-19 infection on fetal health remains to be determined. Using targeted metabolomic analysis of newborn umbilical cord blood, we aimed to evaluate the biological consequences of maternal infection on the fetus and develop metabolite biomarkers for the identification of newborn intrauterine exposure. Study Design: Cord blood serum samples from 23 COVID-19 cases (mother infected/ newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and direct injection liquid chromatography mass spectrometry-mass spectrometry. Logistic regression models were developed using metabolites to predict intrauterine exposure with Area under the Receiver Operating Characteristics curve [AUC (95% CI)], sensitivity, and specificity. Metabolite set enrichment analysis was used to evaluate altered biochemical pathways to highlight biological mechanisms of COVID-19 intrauterine exposure. Results: There were no significant differences in gestational age at delivery between groups (p >0.05). All neonates tested negative for COVID-19 infection. Significant concentration differences (p-value < 0.05 or -log10=1.301) were observed in 19 metabolites between groups. The top metabolite model [cortisol and Ceramide (d181/200)] achieved an AUC (95% CI) = 0.839 (0.722 - 0.956) with a sensitivity of 91% and specificity of 69% (Table 1). Enrichment analysis revealed significantly (p< 0.05) altered metabolic pathway of steroidogenesis and gluconeogenesis (Figure 1). Cortisol is the stress hormone that increases glucose production through gluconeogenesis resulting in higher oxidative metabolism and energy generation. Ceramides are known to have anti-inflammatory properties. Elevated hypoxanthine has also been correlated with tissue hypoxia and inflammation. Conclusion: We found evidence of intrauterine stress, altered energy metabolism and inflammation in fetal life in cases of maternal COVID-19 infection but ultimately negative newborn culture. Elucidation of long-term consequences is imperative considering the large number of exposures in the population. [Formula presented] [Formula presented]