ABSTRACT
Objective: SARS-CoV-2 infection triggers a significant maternal inflammatory response. There is a dearth of data regarding whether maternal SARS-CoV-2 infection or SARS-CoV-2 vaccination triggers an inflammatory response in the fetus. Fetal Inflammatory Response Syndrome (FIRS) has been described in other clinical conditions such as intraamniotic infection and has been defined as a cord blood Interleukin-6 (IL-6) level > 11 pg/ml. The objective of the study is to evaluate Il-6 levels in the cord blood of three delivering women: SARS-CoV-2 infection group, SARS-CoV-2 vaccinated group, and a control group. Study Design: A prospective case control study of a total of 61 pregnant women who presented for delivery at William Beaumont Hospital, Royal Oak, MI. All patients were tested for SARS-CoV-2 infection by polymerase chain reaction test (PCR). Three groups were evaluated: 22 pregnant women with positive SARS-CoV-2 PCR test (case group), 23 Pregnant women with negative SARS-CoV-2 PCR test (control group), and 16 pregnant women who had recent SAR-CoV-2 vaccination and a negative SARS-CoV-2 PCR test. At delivery, cord blood was collected for IL-6 levels. Results: IL-6 level (mean +/- SEM) was for the case group: 8.99 +/- 3.33 pg/ml, control group: 5.19 +/- 0.76 pg/ml, and vaccine group: 7.11 +/- 2.47 pg/ml. There was no statistical difference between the three groups with ANOVA p-value 0.51. Pairwise comparison also revealed no statistical difference with p-values for case versus control, case versus vaccine, and control versus vaccine being 0.52, 0.85, and 0.84 respectively. Conclusion: IL-6, the most sensitive measure of inflammation in obstetric practice, did not identify increased inflammation in PCR negative newborns of vaccinated or SARS-CoV-2 infected mothers. Evaluation using other markers of possible intrauterine inflammation is warranted.
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 (d18:1/20:0)] 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]