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Introduction Valproic acid (VPA) is rarely used in neonatal period. In children under 2 years old, serious adverse effects are appear to be more frequent. Aim The aim of our study is to report the adverse effects observed in a population of full-term newborns treated with VPA. Method Full-term newborns, hospitalized at the Toulouse CHU, who presented with neonatal seizures and who received long-term treatment with VPA between 2004 and 2014 were included. Results For 5 of the 123 newborns treated with VPA, treatment had to be discontinued due to adverse effects. Three patients presented with disturbances in consciousness within 48 hours of treatment initiation, one case with a moderate overdose and two with hyperammoniemia (157 and 327 μmol/L) without any drug overdose or underlying liver or metabolic disease (VPA-induced hyperammonemic encephalopathy). Two patients presented with secondary hematological alterations. No patient presented with liver toxicity or exacerbation of an underlying metabolic disease. Conclusion While the serious adverse effects of VPA notedwere all reversiblewith the discontinuation of the treatment, the occurrence of encephalopathies with hyperammoniemia is a serious complication that is potentially lethal and calls for close clinicalmonitoring of newborns treated with valproate.We provide precautions for the implementation and follow-up of VPA in newborns. [ABSTRACT FROM AUTHOR]