Preconception COVID‐19 Vaccination Reprograms Fetal Metabolism to Accelerate Intrauterine Recovery and Suppress Persistent Metabolic Memory

This study aimed to investigate the impact of preconception maternal inactivated COVID-19 vaccination on fetal metabolic recovery following maternal SARS-CoV-2 infection during pregnancy. Umbilical cord blood samples were collected from neonates born to mothers with SARS-CoV-2 infection during pregnancy. Mothers were stratified into two groups: those fully vaccinated (inactivated COVID-19 vaccines) before conception (n = 81) and unvaccinated (n = 56). Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for metabolomic profiling. The vaccinated group exhibited markedly reduced amino acid/purine metabolism dysregulation and oxidative stress compared to unvaccinated counterparts. Crucially, within the critical IRT window of 5-6 months, vaccination effectively suppressed mTOR signaling-driven pathological metabolic remodeling. In contrast, the unvaccinated group demonstrated sustained metabolic disturbances (> 6 months from infection). In conclusion, preconception maternal inactivated COVID-19 vaccination reprograms fetal metabolism and accelerates intrauterine recovery from maternal SARS-CoV-2 infection, which may confer a beneficial impact on early-life growth. It prevents the establishment of a detrimental "metabolic memory" effect posing potential developmental risks. These findings reveal a novel non-immune, metabolome-mediated protective mechanism of maternal vaccination, which thus supports COVID-19 vaccination for women of childbearing age.