Restricted Fluid Therapy for Newborn Breathing Problems

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

Evidence suggests that increased intravascular and interstitial fluid load in neonates with transient tachypnea of the newborn (TTN) may delay the clearance of fetal alveolar fluid (FAF). Restricted fluid (RF) therapy may accelerated FAF clearance and improve outcomes in these infants.

Term and late preterm infants with TTN requiring nasal intermittent positive pressure ventilation (NIPPV) were randomized within first 2 hours after birth to receive either RF or standard fluid (SF) therapy. Primary outcomes were the duration of NIPPV and the day of discharge. Secondary outcomes included changes in weight, urine output, biochemical parameters, and monitoring of potential adverse effects.

Study Overview

• Status: Completed
• Conditions: Fluid Therapy; Transient Tachypnea of the Newborn
• Intervention / Treatment: Procedure: restricted fluid regimen; Procedure: Standart fluid

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Çorum
    • Çorum, Çorum, Turkey (Türkiye), 19100
      • Hitit University Erol Olcok Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Neonates born at our hospital with a gestational age of ≥34⁰/⁷ weeks who were diagnosed with TTN were included in the study.

Exclusion Criteria:

• Infants with severe congenital anomalies, those who required intubation in the delivery room or upon admission to the NICU, infants born through meconium-stained amniotic fluid, perinatally asphyxiated infants, infants with suspected sepsis based on risk factors or clinical findings, and infants diagnosed with TTN who did not require NIV were not included from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Restricted Fluid; The total fluid volume administered on the first day was initiated at 50 mL/kg/day in the RF group for infants with a gestational age of 34⁰/₇-36⁶/₇ weeks. The total fluid volume administered on the first day was initiated at 40 mL/kg/day in the RF group for infants with agestational age of ≥37 weeks	Procedure: restricted fluid regimen; The total fluid volume administered on the first day was initiated at 50 mL/kg/day in the RF group for infants with a gestational age of 34⁰/₇-36⁶/₇ weeks. 40 mL/kg/day in gestational age of ≥37 weeks
Active Comparator: Standart Fluid; The total fluid volume administered on the first day was initiated at 70 mL/kg/day in the RF group for infants with a gestational age of 34⁰/₇-36⁶/₇ weeks. 60 mL/kg/day in gestational age of ≥37 weeks	Procedure: Standart fluid; 70 mL/kg/day in the standart fluid group for infants with a gestational age of 34⁰/₇-36⁶/₇ weeks, whereas it was initiated at 60 mL/kg/day in thestandart fluid group for infants with a gestational age of ≥37 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
primary outcome	Primary outcomes included duration of NIPPV	"From enrollment to the end of treatment at 3 mounts"
Primary Outcome	Discharge day,	From enrollment to the end of treatment at 3 mounts

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
secondary outcome	Changes in body weight in the following days	"From enrollment to the end of treatment at 8 weeks"
Secondary Outcome	Daily urine output (ml/kg/day) in the following days	from the time of recording to 7 days postnatal
Secondary outcome	Hypoglycemia monitoring (<50 mg/dL)	From enrollment to the end of treatment at 1 weeks"

Collaborators and Investigators

• Sponsor: Hitit University
• Investigators: Principal Investigator: İsmail K Gökçe, Assoc.prof, Hitit University

Publications and helpful links

General Publications

• Stroustrup A, Trasande L, Holzman IR. Randomized controlled trial of restrictive fluid management in transient tachypnea of the newborn. J Pediatr. 2012 Jan;160(1):38-43.e1. doi: 10.1016/j.jpeds.2011.06.027. Epub 2011 Aug 11.
• Gupta N, Bruschettini M, Chawla D. Fluid restriction in the management of transient tachypnea of the newborn. Cochrane Database Syst Rev. 2021 Feb 18;2(2):CD011466. doi: 10.1002/14651858.CD011466.pub2.
• Sardar S, Pal S, Mishra R. A randomized controlled trial of restricted versus standard fluid management in late preterm and term infants with transient tachypnea of the newborn. J Neonatal Perinatal Med. 2020;13(4):477-487. doi: 10.3233/NPM-190400.
• Dehdashtian M, Aramesh MR, Melekian A, Aletayeb MH, Ghaemmaghami A. Restricted versus Standard Maintenance Fluid Volume in Management of Transient Tachypnea of Newborn: A Clinical Trial. Iran J Pediatr. 2014 Oct;24(5):575-80. Epub 2014 Oct 1.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Noninvasive Ventilation; transient tachypnea of the newborn; restricted fluid therapy,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Signs and Symptoms, Respiratory; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Tachypnea; Transient Tachypnea of the Newborn
• Other Study ID Numbers: Elif1453!

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No