Eficacy and Safety of Restricted Fluid Therapy in Transient Tachypnea of the Newborn: A Randomized Controlled Study

Transient tachypnea of the new-born (TTN) is the most common cause of respiratory distress, in term and late preterm infants. The pathophysiological basis of the disease is the inadequate resorption of fetal alveolar fluid (FAF) during the perinatal period. Normally, 10-20 mL/kg of FAF that fills in the alveoli during the fetal period plays a critical role in the development of lungs and maintaining airway patency. An increase in catecholamine and glucocorticoid levels with the onset of birth activates amiloride-sensitive sodium channels and thus facilitates the clearing of FAF through sodium and water absorption. In cesarean sections performed before the onset of labor, insufficient elevation of stress hormones delays the clearance of FAF. This leads to the accumulation of fluid in the interstitial space, alveolar air trapping, and ultimately impaired gas exchange, resulting in the development of TTN symptoms.

TTN presents with tachypnea, grunting, nasal flaring, increase in anterior-posterior chest diameter, and mild hypoxia that start in the first hours following birth. The diagnosis is based on clinical findings and is supported by chest radiography findings. Most cases resolve within a few days with supportive treatment which includes intravenous fluid support, oxygen therapy, and/or non-invasive ventilation (NIV) support. However, some cases may be complicated by persistent pulmonary hypertension or air leakage (pneumothorax, pneumomediastinum) and which may require invasive ventilation support.

Although diuretics, dopamine, nebulized epinephrine and beta-2 agonists have been investigated in the treatment of TTN, current meta-analyses have not demonstrated strong evidence supporting the efficacy of these agents. Recent studies have demonstrated evidence of increased fluid overload in infants with TTN, such as elevated serum NT-proBNP levels and reduced left atrial reservoir strain. Based on this pathophysiological basis, a limited number of studies have evaluated the efficacy of restricted fluid (RF) therapy in TTN. These studies have reported that RF therapy is safe and may shorten the duration of NIV. However, due to very low certainty about the current evidence, RF therapy is not included in the literature as standard approach and the need for further randomized studies is emphasized. Therefore, in the present study, the investigators aimed to evaluate the efficacy and safety of RF therapy, which is a low-risk and feasible approach that may influence the clinical course of TTN.