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Most patients (94%) received at least one hyperosmolar medication. No significant risk of developing NEC could be found. The medications used in clinical practice can significantly exceed the limit set by the AAP. This study does not indicate an increased risk of developing NEC in extremely preterm infants following exposure to hyperosmolar medications. Further studies in larger cohorts are needed to determine the specific cut-off level of osmolality in relation to the pathogenesis of NEC. The medications used in clinical practice can sign