The Association of Late-Onset Hyponatremia with Feeding Type in Preterm Infants: A Retrospective Study

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Background/Objectives: Late-onset hyponatremia (LOH), often develops after the second week of life in preterm infants and has been associated with poor growth and adverse neurodevelopmental outcomes. Human milk, including pasteurized donor breast milk (DBM), has less sodium content than preterm infants require. There is paucity of studies examining the association between DBM and LOH. We evaluated the association between feeding type and LOH beyond the second week of life. Methods: This was a single-center retrospective cohort study that included preterm neonates born at gestational age < 32 weeks or birth weight < 1500 grams, between January 2017 and October 2022. Eligible infants had serum sodium levels measured after 14 days of life and after achieving full enteral feeds. Hyponatremia was defined as serum sodium < 135 mEq/L. Results: Of 373 infants, 43% (n=159) developed LOH. Using multivariable regression analysis, increased DBM intake, lower gestational age, use of chlorothiazide, and mild-moderate bronchopulmonary dysplasia were independently associated with higher odds of developing LOH. The use of furosemide, formula, and patent ductus arteriosus were not associated with LOH. Conclusion: A higher proportion of DBM intake, lower gestational age, chlorothiazide use, and mild-to-moderate BPD were independently associated with LOH. Preterm infants receiving DBM and long-acting diuretics like chlorothiazide are at increased risk for LOH and should be monitored closely.

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