Clinical trial NCT04035564
Conditions: Hyponatremia Premature
Keywords: Preterm infant Sodium Hyponatremia
Sponsor: Hospital del Niño "Dr. Federico Gomez Santos"
Start date: 2018-03-30; Completion date: 2020-03-20
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Hyponatremia is a common complication among preterm infants, renal losses of sodium contribute to the development of hyponatremia in preterm newborns. Sodium imbalances impact in newborns outcome. There is controversy about the time of initiation and the requirements of sodium in premature infants. Hypothesis: early (24 hours of life) sodium supplementation (5mEq/kg/day) prevents the develop of hyponatremia in preterm infants.

Detailed description:
This study is a randomized controlled trial in infants less than 35 weeks gestation admitted to the Newborn Intensive Care Unit at Children Hospital in Saltillo Coahuila Mexico.

Infants receive at 24 hours of life; sodium (5mEq/kg/day) versus less than 1mEq/kg/day. Weight, serum and urine sodium, serum chloride, serum and urine creatinine, serum chloride, bicarbonate and glucose are monitored daily during the first 3 days of life. Patients are assessed for hyponatremia, hypernatremia, weight change, sepsis, necrotizing enterocolitis and intraventricular hemorrhage.

Arms: arm 1: Sodium administration enteral and/or parenteral less than 1mEq/kg/day started on day of life one arm 2: Sodium administration enteral and/or parenteral 5mEq/kg/day started on day of life one
Interventions: intervention 1: Sodium < 1mEq/kg/day intervention 2: Sodium 5mEq/kg/day
Intervention descriptions: intervention 1: Sodium administration enteral and/or parenteral less than 1mEq/kg/day started on day of life 1 intervention 2: Sodium administration enteral and/or parenteral 5mEq/kg/day started on day of life 1

Protocol documents:
Prot_SAP_000.pdf: 
 
 
“Early 
Sodium 
Intake 
in 
Preterm 
Newborns; Randomized Clinical Trial”  
 
 
NCT04035564 
 
January 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 


Introduction 
Hyponatremia is a common complication among preterm infants, renal losses of sodium contribute 
to the development of hyponatremia in preterm newborns. Sodium imbalances impact in newborns 
outcome. There is controversy about the time of initiation and the requirements of sodium in 
premature infants. Hypothesis: early (24 hours of life) sodium supplementation (5mEq/kg/day) 
prevents the develop of hyponatremia in preterm infants. 
This study is a randomized controlled trial in infants less than 35 weeks gestation admitted to the 
Newborn Intensive Care Unit at Children Hospital in Saltillo Coahuila Mexico. 
Infants receive at 24 hours of life; sodium (5mEq/kg/day) versus less than 1mEq/kg/day. Weight, 
serum and urine sodium, serum chloride, serum and urine creatinine, serum chloride, bicarbonate and 
glucose are monitored daily during the first 3 days of life. Patients are assessed for hyponatremia, 
hypernatremia, weight change, sepsis, necrotizing enterocolitis and intraventricular hemorrhage. 
 
 Objectives: 
1. Compare the risk of hyponatremia in the first 72hrs of life, in preterm newborns with early 
sodium intake and late sodium intake.  
2. Compare the risk of hypernatremia in the first 72hrs of life, in preterm newborns with early 
sodium intake and late sodium intake.  
3. Assess the change in serum sodium in preterm newborns with early sodium intake and late 
sodium intake. 
4. Assess the weight change in preterm newborns with early sodium intake and late sodium 
intake. 
5. Assess the development of complications (sepsis, necrotizing enterocolitis, intraventricular 
hemorrhage, mortality) in preterm newborns with early sodium intake and late sodium intake. 
 
 
Study design and statistical analysis 
 
This study is a randomized controlled trial. 
Eligibility criteria: 
Preterm infants <35 weeks of gestation. 
Less than 24 hours of life. 
 
Exclusion criteria: 
Urinary malformations 
Congenital abdominal wall defect 
Intestinal atresia / obstruction 
Congenital heart defect 
 
The eligible patients will be simple randomized in two groups: 
1. Comparation: Sodium administration, enteral and/or parenteral less than 1mEq/kg/day 
starting on day of life one. 
2. Intervention: Sodium administration, enteral and/or parenteral of 5mEq/kg/day starting on 
day of life one. 


 
At admission, gestational age and sex and birth weight will be recorded. Weight will be evaluated 
every 24 hours for 3 days. 
Blood samples will be taken every 24 hours for 3 days to assess serum sodium, creatinine, glucose, 
sodium bicarbonate and serum chloride levels. 
Urine samples will be taken every 24 hours for 3 days to assess urine sodium and urine creatinine 
levels. 
The incidence of hyponatremia, hypernatremia, change of serum sodium and weight change will be 
evaluated and compared between groups during this time frame (72hrs). 
The patients will be following through hospital stay to record the development of sepsis, necrotizing 
enterocolitis, intraventricular hemorrhage and mortality. 
The distribution of variables will be assessed with Shaphiro Wilk test, normally distributed data will 
be compared with t test or Chi squared test and those with abnormal distribution with Mann-Whitney 
U test or Fisher exact test. The risk of hyponatremia and hypernatremia will be expressed using 
relative risk. 
The change of serum sodium, creatinine, chloride, sodium bicarbonate, glucose levels and weight will 
be evaluated using repeated measures ANOVA or Kruskal-Wallis test depending on data distribution. 
Exploratory analysis will include sodium balance (according to sodium intake and urinary 
excretion), urine output and total fluid administration.  
IBM SPSS Statistics (IBM Corp. Released in 2013. IBM Statistics for Windows, Version 21.0. 
Armonk NY: IBM Corp.) will be used for statistical analysis. A p-value <0.05 will be considered 
statistically significant. 
 
Definitions: 
Hyponatremia: Serum sodium <130mEq/L 
Hypernatremia: Serum sodium >150mEq/L 
Change in serum sodium: The difference between serum sodium (at 48 and 72hrs) and initial serum 
sodium. 
Weight change: The difference between weight (at 24, 48 and 72hrs) and birth weight. 
Sepsis: Positive blood culture and/or 5 days of continuous antimicrobial therapy. 
Necrotizing enterocolitis: Necrotizing enterocolitis according to Bell staging (II or grater). 
Intraventricular hemorrhage: Bleeding into the brain´s ventricular system (intracranial ultrasound). 
Mortality: Death during hospitalization. 
 
  


References 
Wang J, Xu E, Xiao Y. Isotonic versus hypotonic maintenance IV fluids in hospitalized children: a meta-
analysis. Pediatrics. 2014 Jan;133(1):105-13. doi: 10.1542/peds.2013-2041. Epub 2013 Dec 30.  
Bhatia J. Fluid and electrolyte management in the very low birth weight neonate. J Perinatol. 2006 May;26 
Suppl 1:S19-21.  
Moritz ML, Ayus JC. Hyponatremia in preterm neonates: not a benign condition. Pediatrics. 2009 
Nov;124(5):e1014-6. 
doi: 
10.1542/peds.2009-1869. 
Epub 
2009 
Oct 
26. 
 
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 
 
Al-Dahhan J, Haycock GB, Nichol B, Chantler C, Stimmler L. Sodium homeostasis in term and preterm 
neonates. 
III. 
Effect 
of 
salt 
supplementation. 
Arch 
Dis 
Child. 
1984 
Oct;59(10):945-50. 
 
Gawlowski Z, Aladangady N, Coen PG. Hypernatraemia in preterm infants born at less than 27 weeks gestation. 
J 
Paediatr 
Child 
Health. 
2006 
Dec;42(12):771-4.  
 
Lönnqvist PA. III. Fluid management in association with neonatal surgery: even tiny guys need their salt. Br J 
Anaesth. 
2014 
Mar;112(3):404-6. 
doi: 
10.1093/bja/aet436. 
Epub 
2013 
Dec 
23. 
 
Oh W. Fluid and electrolyte management of very low birth weight infants. Pediatr Neonatol. 2012 
Dec;53(6):329-33. doi: 10.1016/j.pedneo.2012.08.010. Epub 2012 Oct 12. Review. 
 
Hartnoll G, Bétrémieux P, Modi N. Randomised controlled trial of postnatal sodium supplementation on oxygen 
dependency and body weight in 25-30 week gestational age infants. Arch Dis Child Fetal Neonatal Ed. 2000 
Jan;82(1):F19-23. 
 
Hartnoll G, Bétrémieux P, Modi N. Randomised controlled trial of postnatal sodium supplementation on body 
composition in 25 to 30 week gestational age infants. Arch Dis Child Fetal Neonatal Ed. 2000 Jan;82(1):F24-
8. 
 
Lorenz JM, Kleinman LI, Kotagal UR, Reller MD. Water balance in very low-birth-weight infants: relationship 
to 
water 
and 
sodium 
intake 
and 
effect 
on outcome. 
J 
Pediatr. 
1982 
Sep;101(3):423-32. 
 
Costarino AT Jr, Gruskay JA, Corcoran L, Polin RA, Baumgart S. Sodium restriction versus daily maintenance 
replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial. J Pediatr. 1992 
Jan;120(1):99-106. 
 
Koletzko B, Goulet O, Hunt J, Krohn K, Shamir R; Parenteral Nutrition Guidelines Working Group; European 
Society for Clinical Nutrition and Metabolism; European Society of Paediatric Gastroenterology, Hepatology 
and Nutrition (ESPGHAN); European Society of Paediatric Research (ESPR). 1. Guidelines on Paediatric 
Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition 
(ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), Supported by the 
European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr. 2005 Nov;41 Suppl 2:S1-87. 
 
Bolisetty S, Osborn D, Sinn J, Lui K; Australasian Neonatal Parenteral Nutrition Consensus Group. 
Standardised neonatal parenteral nutrition formulations - an Australasian group consensus 2012. BMC Pediatr. 
2014 Feb 18;14:48. doi: 10.1186/1471-2431-14-48.