The insufficient nutrient content may be compensated by an appropriate fortification of human milk (HM). Optimization of HM fortification relies on the use of high quality standard fortification completed by an individualized fortification. Evaluation of optimal standard fortification relies on the evaluation the safety and efficacy. Individualized fortification is either “targeted” or “adjustable”. The first one requires the analysis of HM and then a fortification adapted to reach the targeted nutrients’ intake. The definition of the target nutrient’s content relies on an assumption about nutrient’s requirement. Adaptation of fortification is performed by using protein (Polberger 1989) and /or energy: lipids (De Halleux 2007 ) and/ or carbohydrates (Rochow 2013). The second one relies on periodic determinations of serum urea assessment as a marker of the individual metabolic response to standardized fortification.