The Impact of Chloride Imbalance on BPD Development and Mortality in Preterm Infants

Chloride balance usually parallels that of sodium, and it is strictly correlated to the extracellular volume balance. In addition plasma chloride and bicarbonate concentrations are inversely regulated through the chloride-bicarbonate exchange pump in renal collecting ducts, independent of sodium. Consequently, plasma chloride levels are closely correlated with pH (hypochloremia/metabolic alkalosis, hyperchloremia/metabolic acidosis).

In adults, dyschloremia is associated with mortality, acute kidney injury, and prolonged hospital stay. Hyperchloremia is often associated with severe sepsis. It has been shown that resuscitation with high-chloride fluids (eg: saline solution) instead of balanced fluids (e.g., Ringer's lactate) increases the need for inotropes in critically ill adults. Similarly, hyperchloremia in septic pediatric patients is linked to acute renal injury requiring dialysis, increased inotropic support, and mortality. In 1979, infants fed with chloride-deficient formula were reported to develop impaired head growth and neurologic sequelae.

Although serum chloride is routinely measured in neonatal intensive care units, its clinical significance is often overlooked. For this reason unlike sodium, literature on chloride metabolism in preterm infants is exceedingly limited.

Advancements in perinatal care over the past 50 years have significantly improved survival rates in preterm infants. However, a large proportion of very preterm infants who survive the neonatal period develop bronchopulmonary dysplasia (BPD). BPD, a chronic lung disease, manifests clinically through persistent respiratory support and/or oxygen dependency. Despite efforts to optimize neonatal care -such as controlled oxygen usage, non-invasive ventilation, volume-guarantee techniques, high-frequency ventilation, and caffeine therapy- BPD remains the most common complication among preterm infants and is associated with increased morbidity and mortality.

It has been suggested that extracellular volume expansion (edema) plays a role in the pathophysiology of BPD. Perlman et al.'s 1986 study demonstrated that infants who died from BPD exhibited hypochloremia, metabolic alkalosis, and complications like inadequate head growth, more frequently than those who survived. These findings highlight the critical importance of chloride imbalance in neonates, similar to findings in adult and pediatric populations.