Medications That Increase Osmolality and Compromise the Safety of Enteral Feeding in Preterm Infants

Abstract

Background: Medications added to preterm milk feeds have the potential to raise osmolality, causing feed intolerance and necrotizing enterocolitis. Objective: The aim of this study was to evaluate changes in the osmolality of milk feeds and water with 14 medications and the diluent amounts required to keep the osmolality below the safety threshold of ≤450 mOsm/kg. Changes in the osmolality of milk with medications while on continuous infusion over 2 and 4 h were determined. Methods: This study was designed to measure the osmolality of 14 commonly used medications in preterm infants both neat and when supplemented with expressed breast milk (EBM), EBM with fortifier (EBMF), preterm formula (PTF), and water. Dose-effect curves were plotted, and the volume of each diluent was calculated to keep the osmolality ≤450 mOsm/kg. Time-effect curves were plotted at 2 and 4 h for each medication for both EBM and EBMF. Results: Neat osmolality of all except 5 medications were above 2,000 mOsm/kg. The osmolality rose with decreasing proportions of diluents used, depicting an indirect curvilinear relationship between the increasing dilution and osmolality for all except 2 medications. As a diluent, EBM was required in lower dilutions than EBMF. Dilutions needed for additives with PTF were very similar to those of EBM. The change in osmolality over time with additives was statistically significant for EBMF. Conclusions: EBM and PTF were found to be safer diluents than EBMF for enteral additives. The practice of keeping milk feeds with medications for continuous feeding is safe for a period of 4 h in EBM.

Feeding Formula Eliminates the Necessity of Bacterial Dysbiosis and Induces Inflammation and Injury in the Paneth Cell Disruption Murine NEC Model in an Osmolality-Dependent Manner

“…While the osmolality of acceptable NICU feeds is below the levels that induced injury in our model, the formula and standard fortifiers commonly used do not take into consideration other substances that are often used with feeds in the NICU. A recent paper by Chandran et al examined fourteen common medications utilized in the NICU [63]. Of these medications, nine had osmolalities too high to measure and the five additional medications were all above 450 mOsm/kg H 2 O.…”

“…This list included iron, multi-vitamins, NaCl, NaPO 4 , and KPO 4 , which are all common additives to feeds. To keep the osmolality below 450 mOsm/kg H 2 O, the medications required significant dilutions of up to 1:40 when mixing the medication in preterm formulas and 1:250 when mixing with fortified expressed breast milk [63].…”

The Effect of Additives for Reflux or Dysphagia Management on Osmolality in Ready‐to‐Feed Preterm Formula: Practice Implications

“…Currently, although there are no osmolality limits for preterm infants, care should be taken not to exceed the AAP threshold. Additives, such as thickeners or supplements, to small volumes of milk may significantly increase osmolality and should be avoided if possible …”

“…Based on human milk norms and historical consensus in 1976, the American Academy of Pediatrics (AAP) Committee on Nutrition cautioned against infant feeds >400 mOsm/L (450 mOsm/kg) without a warning statement on the label until more evidence was obtained, because of hyperosmolality and safety reasons. 1,5,6 Currently, although there are no osmolality limits for preterm infants, care should be taken not to exceed the AAP threshold. Additives, such as thickeners or supplements, to small volumes of milk may significantly increase osmolality and should be avoided if possible.…”

“…Additives, such as thickeners or supplements, to small volumes of milk may significantly increase osmolality and should be avoided if possible. 1,5,6 In the convalescing preterm infant population, providers frequently supplement and modify the nutrient composition of feedings with additives to enhance caloric density and ensure proper growth and nutrition. [7][8][9][10][11] In addition, modifications to the feeding thickness are frequently used to treat premature infants with gastroesophageal reflux disease (GERD) or dysphagia (immature sucking ability, sucking-swallowing-breathing incoordination, aspiration, feeding intolerance).…”