Placental omics and neuropsychiatric outcomes: A systematic review of longitudinal human studies

The placenta is increasingly recognized as a key mediator between the prenatal environment and long-term neurodevelopment. Emerging omics studies suggest that placental molecular profiles may predict neuropsychiatric outcomes, yet evidence has remained fragmented and rarely synthesized in a longitudinal framework. Here we present the first systematic review of longitudinal placental omics studies with direct placenta-child linkage, encompassing epigenomic, transcriptomic, and metabolomic approaches. A systematic search of PubMed, Scopus, and PsycINFO identified twelve eligible studies (total n = 1752 placentas), all of which followed children from birth to neurodevelopmental assessment in early or middle childhood. Across studies, specific loci and metabolites varied, but convergent signals consistently implicated three biological domains: immune signaling, oxidative stress, and metabolic regulation. Representative findings included replicated epigenetic alterations at DLL1, nutrient- and genotype-sensitive variation at CYP2E1 and IRS2, novel clusters at NHIP, transcriptomic integration involving LRRFIP1, environmentally responsive modules including GALC, AUTS2, and CSMD1, and metabolic shifts in fumarate, cystine, and 3-hydroxybutyrate. Notably, all longitudinal evidence to date centers on childhood outcomes, with the most robust associations reported for autism spectrum disorder, while links to schizophrenia and other adult psychiatric disorders remain speculative and are inferred indirectly from genetic or cross-sectional placental datasets. Together, these findings establish the placenta as a dynamic molecular interface where genetic background and environmental exposures converge to influence neurodevelopmental trajectories. By highlighting reproducible domains across omic layers, this review positions placental biology as a promising window into early biomarkers and mechanistic pathways of neuropsychiatric risk.