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

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. Few studies have examined the association between DBM and LOH. We evaluated the association between feeding type and LOH beyond the second week of life in preterm infants. Methods: This was a single-center retrospective cohort study that included preterm neonates born at a gestational age < 32 weeks or birth weight < 1500 g 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) had LOH. Multivariable regression analysis suggested that each 10% increase in DBM intake was associated with higher odds of LOH (adjusted OR 1.08, 95% CI 1.01-1.16; p = 0.022). Lower gestational age, chlorothiazide use, and mild-to-moderate bronchopulmonary dysplasia (BPD) were also associated with higher odds of LOH. The use of furosemide, formula, and hemodynamically significant patent ductus arteriosus were not associated with LOH. Conclusions: Higher DBM intake, lower gestational age, chlorothiazide use, and mild-to-moderate BPD were associated with LOH in the primary multivariable analysis. However, the DBM association was attenuated and not statistically significant after excluding infants who had received prior sodium supplementation. Preterm infants receiving predominantly DBM, particularly those treated with chlorothiazide, may benefit from close serum sodium monitoring.