Maternal infections and prenatal inflammation are recognized risk factors for neurodevelopmental diseases. Astrocytes are glial cells essential for synapse formation and refinement, but they also may react to inflammatory environment affecting neuronal network homeostasis. However, how an inflammatory episode occurring during fetal development influences astrocyte generation and phenotype remains largely unknown.In the brain, the innate immune molecule Pentraxin3 (PTX3) is produced by astrocytes and promotes the maturation of excitatory synapses. Its expression is induced by inflammatory stimuli both in mouse and in human iPSC-derived astrocytes.By using a mouse model of maternal immune activation (MIA) to mimic a viral or bacterial infection, with Poly(I:C) or LPS respectively, we demonstrated that astrocytes from MIA offspring retain a long-lasting molecular signature related to the type of immunogen used when analyzed three weeks after the maternal insult. When in co-cultures with wild-type neurons, MIA-derived astrocytes affect synapse formation and functional maturation. We demonstrated MIA affects PTX3 levels in the cerebral cortex, but not in the hippocampus, of the offspring, during the first and second postnatal weeks, a critical period for synapse development. Interestingly, also the number of astrocytes is altered exclusively in the cerebral cortex at this stage. These results underscore, for the first time, the contribution of astrocytes to the long-term alterations observed during brain development following prenatal inflammation.