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.
Anzeige
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]
HM Fortification Method | Characteristics | Advantages/Disadvantages |
|---|---|---|
1. Adjustable (ADJ) HM Fortification | BUN is monitorized twice weekly, cut-off levels of BUN are 10–16 mg/dl. If the level is less than 10 mg/dl extra protein is added to the standard fortification. | Practical, not labor intensive Monitors protein status of each infant Safeguards also against excessive protein intake Does not need expensive devices Proven to be effective in optimizing growth and protein intake with a RCT. A real individualization method taking into consideration each infant’s protein requirement |
2. Targeted HM Fortification | Macronutrient concentrations in HM are analyzed and based on the results milk is supplemented with extra protein and/or fat. | Both protein and energy can be supplemented Bedside analyzers are available but are expensive May be labor intensive More importantly the method supplements the milk according to the general recommendations, does not take into consideration that each individual infant’s requirement may be different |
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
Anzeige
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 Mathes10, Christoph Maas10, Christine Bleeker10, Julia Vek10, Wolfgang Bernhard10, Andreas Peter12, 13, 14, Christian F. Poets10 and Axel R. Franz11
(10)
Department of Neonatology University Children’s Hospital, Tübingen, University Hospital, Tübingen, Germany
(11)
Centre for Pediatric Clinical Studies, University Children’s Hospital, Tübingen University Hospital, Tübingen, Germany
(12)
Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry and Pathobiochemistry, University of Tuebingen, Tübingen, Germany
(13)
Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tuebingen, Tübingen, Germany
(14)
German Center for Diabetes Research (DZD), Muenchen-Neuherberg, Tübingen, Germany
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.
Acknowledgements
Not applicable.
Funding
Not applicable.
Availability of data and materials
Not applicable.
Authors’ contributions
All authors participated to the discussion and the preparation of the manuscript. SA, CK, and JCP revised and finalized the manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Anzeige
Consent for publication
Not applicable.
Ethics approval and consent to participate
Not applicable.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.