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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Restricted Fluid | Experimental | 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 |
|
| Standart Fluid | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| restricted fluid regimen | Procedure | 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 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| İsmail K Gökçe, Assoc.prof | Hitit University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hitit University Erol Olçok Training and Research Hospital | Çorum | Çorum | 19100 | Turkey (Türkiye) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33599990 | Background | 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. | |
| 32444567 | Background | 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. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 15, 2021 | Apr 13, 2026 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 15, 2021 | Apr 13, 2026 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D059245 | Transient Tachypnea of the Newborn |
| ID | Term |
|---|---|
| D012127 | Respiratory Distress Syndrome, Newborn |
| D012128 | Respiratory Distress Syndrome |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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Infants with TTN requiring NIPPV were randomized within the first two hours of life to either the RF group or the standard fluid (SF) group using the sealed opaque envelope method. To ensure homogeneous distribution of infants with similar gestational ages between the groups, infants born at 34⁰/₇-36⁶/₇ weeks and those born at ≥37 weeks of gestation were randomized separately using a stratified randomization approach. The total fluid volume administered on the first day was initiated at 50 mL/kg/day in the RF group and 70 mL/kg/day in the SF group for infants with a gestational age of 34⁰/₇-36⁶/₇ weeks, whereas it was initiated at 40 mL/kg/day in the RF group and 60 mL/kg/day in the SF group for infants with a gestational age of ≥37 weeks.
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| Standart fluid | Procedure | 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. |
|
| 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" |
| 25793064 | Background | 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. |
| 21839467 | Background | 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. |
| 42420914 | Derived | Gokce IK, Turgut H, Kaya H, Deveci MF, Alagoz M, Ozdemir R. Eficacy and safety of restricted fluid therapy in transient tachypnea of the newborn: a randomized controlled study. BMC Pediatr. 2026 Jul 8. doi: 10.1186/s12887-026-07303-6. Online ahead of print. |
| D012120 | Respiration Disorders |
| D059246 | Tachypnea |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |