Brain metabolite changes in neonates of mothers with SARS-CoV-2 infection during pregnancy: a case-control study

Exposure to SARS-CoV-2 during pregnancy may influence the intrauterine environment, with potential implications for fetal neurodevelopment.  OBJECTIVE: The objective of this study was to test our hypothesis that prenatal exposure to maternal SARS-CoV-2 influenced neonatal brain metabolites.

Neonates of mothers with SARS-CoV-2 infection during pregnancy (cases) and contemporary neonates of unexposed mothers (controls) were recruited prospectively. Baseline characteristics were extracted from mothers and neonates. ¹H-MRS data was acquired from the bilateral basal ganglia, bilateral frontal lobe, and cerebellum in newborns. Case and control groups were sex- and postmenstrual age-matched at scan. Metabolites were quantified using Osprey. MRS data with signal-to-noise ratio less than 6 and linewidth larger than 12.5 Hz were excluded to maintain data quality. Water-referenced metabolite measurements and ratios were compared between the two groups of neonates using independent sample t-tests and subgroup analyses for the neonates of mother infected during early and late trimesters were performed using ANCOVA.

MRS data was successfully obtained from 38 controls and 38 cases (postmenstrual age at scan 44.0±2.5 weeks and 44.1±2.8 weeks respectively); 52% were female and approximately 60% of the cases were exposed during the third trimester. No significant differences were observed in baseline characteristics including maternal age, maternal psychological distress measures, gestational age at delivery, infant weight, length, or head circumference. Levels of glutamate were significantly increased (P<0.01) and taurine were significantly decreased (P<0.02) in the cerebellum of neonates with prenatal exposures. For subgroup analysis, levels of glutamate and Glx were significantly higher in the cerebellum of neonates exposed to infection during early trimesters compared to controls. No significant differences were reported in the other two brain regions of interest.

Cerebellar glutamate and taurine levels were altered in neonates with prenatal maternal SARS-CoV-2 exposure compared to controls. The shift of their concentrations in opposite directions (i.e., increased glutamate and decreased taurine) may suggest attempts to regulate the excitatory/inhibitory balance in neonates with prenatal maternal SARS-CoV-2 exposure.