Dear Editor,

We read with great interest the paper from Mathes et al. [1] which underlines the importance of monitoring plasma and urinary urea to adapt enteral protein intake in preterm infants. The authors aimed to obtain a practical non-invasively measured metabolic marker reflecting the short term protein intake of preterm infants. They showed that higher-protein group infants had higher plasma and urinary urea concentrations compared to lower-protein group. It is noteworthy that the authors demonstrated a highly positive correlation between plasma urea concentrations and the urinary urea-creatinine-ratio, and between actual protein intakes and plasma urea concentrations and the urinary urea-creatinine-ratio. They concluded that urinary urea to creatinine ratio might help to estimate actual protein intake in these well thriving infants.

We appreciate the attempt of Mathes et al. [1] to search for a non-invasive metabolic marker on which individualization of human milk (HM) fortification could be based. Methods employed to individualize fortification of milk fed to preterm infants should continue and adjusting protein fortification on the basis of urinary urea-creatinine ratio warrants further investigation in relation with other outcomes such as growth.

On the other hand we would like to remind them that there is a type of individualized HM fortification method, namely “adjustable fortification,” proposed in 2006 and comprises twice weekly assessments of blood urea nitrogen (BUN) as a marker of protein intake [2]. This method has been shown to be effective in improving protein intake and postnatal growth (weight gain and head circumference) in VLBW infants in the original randomized controlled trial [2] and the results have been replicated by the following observational studies [3, 4].

We are also aware that there is some confusion regarding the terminology around individualized human milk fortification, as we noticed previously [5, 6]. Therefore we are taking the opportunity to clarify this. As clearly defined in 2010 [7], there are two types of individualized fortification (Table 1): 1) Adjustable Fortification-based on regular BUN assessments; 2) Targeted Fortification- based on the macronutrient analysis of human milk.

Table 1 Individualized Human Milk Fortification Methods [7]
Full size table

The nutrient and energy requirements stated in the international recommendations refer to the populations not individuals. We know that some infants will require more than the recommended intakes and some less. To find out how much protein an individual infant requires it is important to monitor the physiological response of each baby to the amount received and respond accordingly. In addition, protein and energy requirements may be particularly high in subgroups of infants for example those with bronchopulmonary dysplasia or extra-uterine growth restriction. Therefore fortification of HM should be adapted to specific nutrient needs of each individual infant. Adjustable human milk fortification in this sense is a good compromise

European Milk Bank Association (EMBA) Working Group on Human Milk Fortification

Authors’ Response to Letter-to-the-Editor (Clarifying some aspects and the terminology of individualized human milk fortification)

  • Michaela Mathes,
  • Christoph Maas,
  • Christine Bleeker,
  • Julia Vek,
  • Wolfgang Bernhard,
  • Andreas Peter,
  • Christian F. Poets &
  • Axel R. Franz 

  1. Department of Neonatology University Children’s Hospital, Tübingen, University Hospital, Tübingen, Germany

    Michaela Mathes, Christoph Maas, Christine Bleeker, Julia Vek, Wolfgang Bernhard & Christian F. Poets

  2. Centre for Pediatric Clinical Studies, University Children’s Hospital, Tübingen University Hospital, Tübingen, Germany

    Axel R. Franz

  3. Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry and Pathobiochemistry, University of Tuebingen, Tübingen, Germany

    Andreas Peter

  4. Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tuebingen, Tübingen, Germany

    Andreas Peter

  5. German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Tübingen, Germany

    Andreas Peter

We greatly appreciate the clarification by the colleagues from the European Milk Bank Association and we agree to their comments.

According to the data we were able to present in our original article (Ref [1]), it seems that instead of measuring BUN twice weekly, measuring urinary urea or urinary urea/creatinine ratio may prove similarly effective to guide adjustable fortification of human milk in very preterm infants.