The article “Increased osmolality of breast milk with therapeutic additives” by Srinivasan et al1 reports the osmolality of supplements, drugs, and fortifiers in breast milk for preterm infants based on the assumption that laboratory measured osmolality presents an increased risk of necrotising enterocolitis (NEC) for the preterm infant. When the association between hyperosmolar feeds and NEC is considered, there may be an important differentiation of osmolar substances into two groups: some substances create an osmotic gradient in vivo whereas others do not.2 There is a difference between the osmolality that is measured in a laboratory and the effective osmolality in vivo.3 Molecules that cross semipermeable membranes, such as alcohol, do not present an osmotic load in vivo, but do contribute to osmolality measured by an osmometer.3 Molecules that do not set up an osmotic gradient are not likely to increase the risk of NEC by their osmolality.
Drugs as well as vitamin supplements often contain carrier molecules that can diffuse across membranes.2 On the other hand, nutrients in feeds, such as sugars, amino acids, salts, minerals, and the constituents of breast milk fortifiers do not readily diffuse across membranes. Therefore hyperosmolar feeds are more likely to pose an osmolar risk when the source of the hyperosmolality is nutrients, but may not pose an osmolar risk when the source of the hyperosmolality is drugs and supplements.
The association between NEC and osmolality in preterm infants has been studied, inadvertently, in only one randomised clinical trial.4 The remainder of the evidence that associates NEC with high osmolality feeds is from one quasi‐experimental trial,5 three case reports,6,7,8 and some animal studies.9,10,11,12,13,14 In all of these studies, the source of hyperosmolality associated with damage to the intestine was substances that presented an osmolar load to the intestine.
The only substances that need to be considered risky in terms of osmolality for potential inducement of NEC are those that create an osmotic gradient across the intestinal membrane in vivo. Some of the measured osmolality from drugs and vitamin supplements is not likely to present a risk from their osmolar load.
Footnotes
Competing interests: none declared
References
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