Comparison of the Isotonic and Hypotonic Intravenous Maintenance Fluids In Term Newborns: Neofluid Study (NEOFLUID)

Comparison of the Effects of Isotonic and Hypotonic Intravenous Maintenance Fluids on Term Neonatal Babies Undergoing Intravenous Fluid Therapy: Multicenter Observational Neofluid Study

Considering the physiological changes in fluid and electrolyte balance and providing proper support are one of the important aspects of neonatal intensive care. Maintenance intravenous fluids are designed to maintain homeostasis when a patient is unable to uptake required water, electrolytes, and energy. Hypotonic fluids are still the most commonly prescribed IV fluids for pediatric hospitalized patients. However, previous studies, including children older than one month of age revealed that traditionally used hypotonic fluids may lead to hyponatremia.

Because of the absence of evidence-based data, there is currently no clear consensus on the optimal composition of maintenance intravenous fluid therapy in newborns, leading to wide practice variation.

The National Clinical Guideline Center (NICE) 2015 recommends the use of isotonic fluids in term newborn infants and some newborn centers has begun to use isotonic fluids since guidelines recommendations. Since the publication of the NICE guideline, no studies have addressed this topic.

In this prospective, observational , multicentric study, conventional hypotonic fluids containing sodium chloride (NaCl) < 130 mmol/L compared with isotonic fluids (containing NaCl between 131-154 mmol/L) in terms of the risk of hyponatremia, hypernatremia, plasma sodium (pNa) level change, treatment morbidities, hospitalization duration and mortality.

Study Overview

• Status: Completed
• Conditions: Fluid Therapy; Newborn Complication; Isotonic Dehydration; Hyponatremia of Newborn; Hypernatremia of Newborn; Sodium Chloride
• Intervention / Treatment: Drug: Intravenous isotonic fluid - NaCl 131-154 mmol/L in 5% dextrose; Drug: Intravenous Hypotonic fluid- Sodium Chloride < 130 mmol/L

• Study Type: Observational
• Enrollment (Actual): 420

Contacts and Locations

Study Locations

• Turkey
  • İzmir, Turkey, 35340
    • Dokuz Eylül University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 month (Child)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Hospitalized term newborns (>37 weeks) , requiring iv fluid treatment after 24 hour postnatal age

Description

Inclusion Criteria are:

• Term newborns (>37 + 0/7 weeks) aged 24 hours to 30 days with a normal baseline serum sodium level between 135-145 mmol/L,with a treatment plan to include IV fluids at > 50% of maintenance
• Infants not received parenteral fluids in the last 24 hours before participation
• Infants receiving IV fluid administration at 50% to 100% of maintenance

Exclusion Criteria:

• Newborns with diagnoses that required specific fluid tonicity and volumes such as:

  • Severe dehydration presenting with shock
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
  • Renal insufficiency
  • Adrenal insufficiency
  • Diabetes mellitus and diabetes insipidus
  • Hypoxic ischemic encephalopathy
  • Major congenital anomaly
  • Patients receiving diuretic therapy
  • Patients with obvious edema
  • Heart or liver failure, portal hypertension with acid
  • Pre-post operative patients
  • Infants receiving total parenteral nutritional therapy
  • Other: all conditions that require non-standard liquid content and quantities

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Isotonic fluid; Group, received isotonic maintenance fluid containing NaCl between 131 to 154 mmol/L such as: Dextrose 5% in 0.9% NaCl,; Intravenous fluid containing NaCl between 131 to 154 mmol/L	Drug: Intravenous isotonic fluid - NaCl 131-154 mmol/L in 5% dextrose; Isotonic group will be given fluids containing 131-154 mmol/L Sodium Chloride; Other Names: B05BB02, 0.9% NaCl/Dextrose 5%
Hypotonic fluid; Group, received hypotonic maintenance fluid containing NaCl < 130 mmol/L such as: Dextrose 5 % in 0.02 % NaCl,; Dextrose 5% in 0.033 % NaCl; Dextrose 5% in 0.045 % NaCl; Intravenous fluid containing NaCl < 130 mmol/L	Drug: Intravenous Hypotonic fluid- Sodium Chloride < 130 mmol/L; Hypotonic group will be given fluids containing lower than 130 mmol/L : Dextrose 5% in 0.2% Sodium Chloride, or Dextrose 5% in 0.33 % Sodium Chloride,or Dextrose 5% in %0.45 Sodium Chloride, or Intravenous fluid containing Sodium Chloride < 130 mmol/L; Other Names: B05BB02, 0.45% NaCl/5% dextrose; B05BB02, 0.33 % NaCl/5% dextrose; B05BB02, 0.20 % NaCl/5% dextrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean plasma Na	Change in mean plasma sodium levels per hour (∆pNa mmol/L/hour)	24 hours after the intervention
Rate of development of hyponatremia	Plasma sodium (pNa) level <135 mmol/L	during the intervention
Rate of development of hypernatremia	Plasma sodium (pNa) level >145 mmol/L	during the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight in kilograms	weight gain	during the intervention
length of stay	hospitalisation day	during the intervention
mortality	mortality due to complications of administered fluid	during the intervention

Collaborators and Investigators

• Sponsor: Dokuz Eylul University
• Collaborators: Cukurova University; Kanuni Sultan Suleyman Training and Research Hospital; Baskent University; Istanbul University; Ankara Yildirim Beyazıt University; Selcuk University; Izmir Katip Celebi University; Inonu University; Mersin University; Necmettin Erbakan University; Istanbul Medeniyet University; Medipol University; Zekai Tahir Burak Women's Health Research and Education Hospital; Eskisehir Osmangazi University; Aydin Adnan Menderes University; Suleyman Demirel University; Uşak University; Cumhuriyet University; Gulhane School of Medicine; Umraniye Education and Research Hospital; Kecioren Education and Training Hospital; Cigli Regional Training Hospital; Istanbul University - Cerrahpasa (IUC); Yuksek Ihtisas University; Dr. Behcet Uz Children's Hospital; Mersin Training and Research Hospital; Dr. Lutfi Kirdar Kartal Training and Research Hospital; NCR International Hospital; Ministry of Health University, Bursa Yüksek İhtisas Training and Research Hospital; Ministry of Health University, Kayseri Regional Hospital; Konya Private Medova Hospital; Aydın Maternity and Children Hospital
• Investigators: Principal Investigator: Hasan Ozkan, Prof., Dokuz Eylül University- Faculty of Medicine

Publications and helpful links

General Publications

• Balasubramanian K, Kumar P, Saini SS, Attri SV, Dutta S. Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial. Acta Paediatr. 2012 Mar;101(3):236-41. doi: 10.1111/j.1651-2227.2011.02508.x. Epub 2011 Nov 19.
• McNab S, Ware RS, Neville KA, Choong K, Coulthard MG, Duke T, Davidson A, Dorofaeff T. Isotonic versus hypotonic solutions for maintenance intravenous fluid administration in children. Cochrane Database Syst Rev. 2014 Dec 18;(12):CD009457. doi: 10.1002/14651858.CD009457.pub2.
• National Clinical Guideline Centre. IV Fluids in Children: Intravenous Fluid Therapy in Children and Young People in Hospital. London: National Institute for Health and Care Excellence (UK); 2015 Dec. Available from http://www.ncbi.nlm.nih.gov/books/NBK338141/
• Tuzun F, Akcura Y, Duman N, Ozkan H. Comparison of isotonic and hypotonic intravenous fluids in term newborns: is it time to quit hypotonic fluids. J Matern Fetal Neonatal Med. 2022 Jan;35(2):356-361. doi: 10.1080/14767058.2020.1718094. Epub 2020 Mar 29.

Helpful Links

• Turkish Neonatology Society, Diagnosis and Treatment Guidelines, 2015

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Newborn, fluid therapy, isotonic, hypotonic,NaCl
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Water-Electrolyte Imbalance; Hyponatremia; Dehydration; Hypernatremia
• Other Study ID Numbers: 363-SBKAEK

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