Return To The Previous Page
Buy a Package
Number Of Visible Items Remaining : 3 Item

Fluid and electrolyte therapy in newborns

Fluid and electrolyte therapy in newborns
Steven Ringer, MD, PhD
Section Editors:
Steven A Abrams, MD
Tej K Mattoo, MD, DCH, FRCP
Deputy Editor:
Laurie Wilkie, MD, MS
Literature review current through: Mar 2023. | This topic last updated: Jun 29, 2022.

Introduction — Management of neonatal fluid and electrolyte therapy is challenging, as several factors (eg, gestational age, physiological changes in kidney function, and total body water changes) and the clinical setting need to be accounted for while caring for neonates, especially preterm infants.

Fluid and electrolyte therapy in newborns, including the underlying principles of fluid and electrolyte homeostasis, determination of fluid and electrolyte requirements, influence of the care environment (eg, radiant warmers, humidity), and management of electrolyte and water abnormalities is discussed here. Maintenance fluid therapy and management of hypovolemia in older infants and children are discussed elsewhere. (See "Maintenance intravenous fluid therapy in children" and "Treatment of hypovolemia (dehydration) in children".)

Neonatal acute kidney injury is also discussed separately. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis" and "Neonatal acute kidney injury: Evaluation, management, and prognosis".)

Definitions — Different degrees of prematurity are defined by gestational age (GA) or birth weight (BW) (table 1). The use of BW to determine the degree of prematurity may be misleading when the infant is either small or large for GA. As a result, GA has become the standard used to indicate the degree of prematurity, as it is more reflective of organ maturation, including kidney function.

The classification based upon GA is as follows:

Late preterm birth – GA between 34 and less than 37 weeks

Moderate preterm birth – GA between 32 and <34 weeks

Very preterm (VPT) birth – GA between 28 and 31 6/7 weeks

Extremely preterm (EPT) birth – GA less than 28 weeks

Preterm infants are also classified by BW:

Low birth weight (LBW) – BW less than 2500 g

Very low birth weight (VLBW) – BW less than 1500 g

Extremely low birth weight (ELBW) – BW less than 1000 g

BW by percentile for the appropriate GA have been established (table 2). The above definitions are used throughout this review.

Water and electrolyte homeostasis — Water and electrolyte balance in a healthy individual is primarily dependent on kidney function and fluid intake versus losses. However, a newborn is more susceptible to derangements in water and electrolyte homeostasis because of the normal postnatal changes in body water components, functional immaturity of the neonatal kidney, increased insensible water losses compared with older individuals, and an inability to independently access water. In particular, the magnitude of postnatal diuresis, immaturity of kidney function, and insensible fluid loss is higher at lower gestational age (GA). Thus, it is important for the clinician caring for the neonate, especially very preterm (VPT) infants, to have an understanding of the basic physiologic mechanisms that regulate and maintain water and electrolyte balance.

Changes in total body water — Total body water (TBW) is composed of extracellular fluid (ECF), which includes intravascular and interstitial fluid, and intracellular fluid. The amount of TBW as a percentage of body weight and its distribution in various fluid compartments increase with decreasing GA [1]. In newborn term infant, the TBW is 75 percent of the body weight as compared with 80 to 90 percent in an infant born <27 weeks gestation; the ECF volumes are 45 and 70 percent, respectively.

After birth, there is a physiologic diuresis of ECF resulting in a weight loss during the first week of life. Fluid loss results primarily from an isotonic reduction in extracellular water, although the mechanism for this process is uncertain. The magnitude of diuresis and relative weight loss decreases with increasing GA. Normal weight loss varies between infants and may be as much as approximately 10 to 15 percent of birth weight in preterm and 4 to 7 percent of birth weight for term breastfed infants in the first day of life [2]. The postnatal diuresis is approximately 1 to 3 mL/kg per hour in term infants and is greater in preterm infants. Since fluid administration among ill or preterm infants is entirely regulated by caregivers, recognition of the normal physiologic fluid loss is a major determinant for fluid management. In addition, other concomitant fluid losses vary depending on the clinical setting. (See 'Sources of water loss' below.)

Prospective studies involving very low birth weight (VLBW) infants (BW ≤1500 g) and extremely low birth weight (ELBW) infants (BW ≤1000 g) demonstrated a consistent pattern of fluid and sodium balance despite varying intakes of sodium and water over the first five to seven days of life [3,4]. Results demonstrated that in preterm neonates there were three consistent phases of water and sodium changes based on day of life. In these studies, day 0 is the date of birth, and it will be of variable length depending on the hour of birth. Day 1 begins at 0001 on the calendar day that follows the birth date, and subsequent days follow accordingly. However, there is natural variation in the actual time that an individual infant moves between phases.

Pre-diuretic phase – Birth through day 1 of life is characterized by oliguria.

Diuretic and natriuretic phase – Days 2 to 3 of life are characterized by increases in both urine output and sodium losses. In this second phase, lung fluid is thought to be absorbed, resulting in increased extracellular volume. This leads to an increase in urine output.

Post-diuretic phase – Days 4 to 5 are characterized by varied urine output dependent upon changes in fluid intake compared with days 2 to 3.

As a result, monitoring of intake and output and body weight is important to ensure adequate fluid intake to maintain fluid balance. For the term infant, prior to discharge, parents are counseled on assessing intake and urinary output, and a follow-up appointment is scheduled within 48 to 72 hours after discharge to monitor weight loss and fluid intake. (See 'Intake and output' below and "Initiation of breastfeeding", section on 'Assessment of intake' and "Overview of the routine management of the healthy newborn infant", section on 'Follow-up visit'.)

Kidney function — Neonatal kidney function is varied due to the following factors (see "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Normal neonatal kidney function'):

Developmental immaturity – Kidney function improves with increasing GA.

Postnatal hemodynamic changes at birth that affect kidney function. The magnitude and rate of changes vary with GA.

Developmental immaturity, especially in the preterm infant, affects the following kidney functions, which can result in water and electrolyte imbalance:

Glomerular filtration

Ability to concentrate urine

Tubular reabsorption of sodium and bicarbonate and secretion of potassium and hydrogen

Urinary concentration and other tubular functions

Urinary concentration – Urine concentrating ability is limited in the newborn compared with older infants and children. The maximum urine concentration that can be achieved increases from 400 mosmol/kg in the first few days after birth to 1200 mosmol/kg at one year of age. As a result, the risk of volume depletion is increased in the newborn because of the inability to maximally concentrate urine and due to increased insensible fluid loss compared with older individuals. If fluid repletion is inadequate, this results in hypovolemia and hypernatremia. (See 'Sources of water loss' below.)

Limited concentrating ability in newborn infants is due to the following [5-7]:

Limited the medullary osmotic gradient – This is due in part to the short loop of Henle in newborns that restricts the countercurrent multiplication that forms the osmotic gradient from the corticomedullary junction to the inner medulla. In addition, tonicity within the medullary interstitium is limited by reduced availability of osmolar molecules (eg, urea) due to a low dietary intake of sodium and protein from human milk and formula and reduced urea synthesis due to the typical anabolic state of the newborn.

Diminished response to antidiuretic hormone (ADH, also referred to as arginine vasopressin) – ADH increases the water permeability of the collecting tubule by activation of its receptors. In the newborn, the collecting tubule is relatively unresponsive to changes in ADH, and the response diminishes with decreasing GA [8].

Concentrating ability matures after birth, but the pace of this maturation is lower in infants of lower GA.

Sodium – In the neonate, maximum reabsorption of sodium is limited due to tubular immaturity and tubuloglomerular imbalance, which improves with increasing GA. Limited sodium reabsorption is in part due to reduced responsiveness to aldosterone [9-11]. Sodium transport throughout the kidney also depends on the Na-K-ATPase pump located on the basolateral membrane of various sections of the tubule and membrane transporters. In the neonate, especially VPT infants (GA <32 weeks), the immature developmental expression and function of the Na-K-ATPase pump and membrane transporters result in decreased sodium reabsorption [12]. As a result, the fraction of the filtered sodium that is excreted (FENa) is as high as 5 percent in preterm infants less than 30 weeks gestation, compared with less than 2 percent in older infants and children.

Bicarbonate – Bicarbonate resorption in the proximal tubule is reduced due to decreased expression and activity of the NA-K-ATPase pump and carbonic anhydrase and sodium-hydrogen antiporter. This leads to a lower resorptive threshold for bicarbonate of 19 to 21 mmol/L in term infants and 16 to 20 mmol/L in preterm infants, which in turn leads to a lower serum bicarbonate level [13,14].

Potassium – Potassium excretion primarily occurs in the gastrointestinal tract, with only approximately 10 to 15 percent excreted in the urine. In the neonate, this excretion is dependent largely on the NA-K-ATPase pump. Low renal excretion is due to the decreased expression and activity of this pump, decreased responsiveness of the neonatal kidney to aldosterone, and lower GFR. This leads to higher normal values of potassium (table 3) and an increased risk of hyperkalemia, especially in ill preterm infants. (See "Causes, clinical manifestations, diagnosis, and evaluation of hyperkalemia in children".)

Glomerular filtration rate (GFR) — Embryogenesis is complete by approximately 35 weeks gestation, at which time there are between 0.6 and 1.2 million nephrons in each kidney. As a result, GFR in preterm infants with GAs below 35 weeks is lower. So, for example, a full term infant has a GFR of approximately 26 mL/min per 1.73 m2, whereas a preterm infant at 27 weeks gestation will have a GFR of 13.4 mL/min per 1.73 m2. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Normal neonatal kidney function'.)

GFR increases at birth in all infants due to recruitment of superficial nephrons and a substantial increase in kidney blood flow (RBF) due to a decrease in renal vascular resistance and increases in systemic blood pressure. However, the velocity of change is greater in term infants compared with preterm infants, especially VPT infants. So for term infants, GFR doubles by two weeks of age to 54 mL/min per 1.73 m2 compared with a GFR of 16.2 mL/min per 1.73 m2 for a neonate born at 27 weeks gestation.

Lower GFR may result in higher potassium levels and sodium and water retention.

GFR is measured clinically by serum creatinine (SCr) values. Similar to GFR, SCr normally varies with GA and postnatal age. At birth, SCr concentration is the same as the concentration in the mother (usually less than 1 mg/dL [88 micromol/L]), and normally falls over time. For term infants, the decline is rapid to nadir values (SCr 0.2 to 0.4 mg/dL [18 to 35 micromol/L]) by the first or second week of life. For preterm newborns, the decline is slower, and may take up to two months to reach normal baseline (table 4).The diagnosis of either acute kidney injury or chronic kidney disease (CKD) is suspected with an abnormally elevated SCr for GA and postnatal age or increasing SCr from a previous baseline. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Serum creatinine' and "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Diagnosis' and "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Children less than two years of age'.)

In preterm infants, blood urea nitrogen (BUN) is not a reliable marker for kidney function or protein intolerance, especially for infants who receive parenteral amino acid [15-17].

Sources of water loss — Water loss is divided into insensible losses through the skin and lungs, and sensible losses through the kidney (urine output). The absolute and relative amounts of water loss through these routes change with GA. Other fluid losses may include stool and gastric, ileostomy, or thoracostomy drainage.

Kidney – After birth, most neonates demonstrate low urinary volume <1 mL/kg per hour) in the first day of life [3,4]. After 24 hours of life, urine output (sensible losses) increases and is approximately 45 mL/kg per day, or 2 mL/kg per hour. As noted above, neonates have a limited ability to concentrate their urine. (See 'Urinary concentration and other tubular functions' above.)

Skin – Evaporation through the skin can result in large insensible water losses in newborns. These may be excessive in extremely low birth weight (ELBW; BW <1000 g) or extremely preterm (EPT, GA <28 weeks) infants with very thin skin (increased skin permeability). In addition, the surface area-to-volume (related to body weight) ratio increases with deceasing GA, which also increases fluid loss.

As the skin matures with increasing GA and postnatal age, the surface area-to-volume ratio decreases and evaporative loss is reduced. These factors are less significant for infants born after 28 weeks GA. For EPT infants, these losses become less important one week after birth. As an example, insensible water loss in an infant born at 24 weeks gestation may be as high as 200 mL/kg per day compared with a loss of 20 mL/kg per day for a term infant. Water loss also may be excessive in conditions in which skin integrity is compromised (eg, epidermolysis bullosa, abdominal wall defect) [18-20].

Other factors that may increase skin losses include:

Radiant warmers, which increase evaporative water loss by approximately 50 percent [21]. Use of humidification and plastic wrap may minimize this loss [22]. Newer incubators that provide humidification and easier access to infants have been developed, resulting in a decreased use of radiant warmers [23].

Heat-emitting phototherapy devices, which increase transepidermal water loss [24,25]. However, these devices are rapidly being replaced by newer ones using high-intensity gallium nitride light-emitting diode (LED) phototherapy, which have no effect on transepidermal water loss [26].

Respiratory – With the typical ambient humidity in the nursery, approximately one-half of insensible losses in term infants are caused by water loss through the respiratory system [27,28]. Respiratory loss increases with increasing respiratory rate and decreases for infants who receive warmed humidified air, including those who are intubated and mechanically ventilated. Although respiratory water loss increases with decreasing GA, transepidermal loss increases even more [28]. Thus, in preterm infants, skin water loss is greater than respiratory loss.

Effect of antenatal glucocorticoids — Antenatal administration of glucocorticoids to promote lung maturation in preterm infants also results in maturation of the skin and kidneys (see "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery").

In one report, water and sodium homeostasis during the first week after birth were compared in ELBW infants exposed and not exposed to antenatal glucocorticoids [29]. Exposed infants had lower insensible water loss, less hypernatremia, and an earlier diuresis and natriuresis than unexposed infants. These changes were thought to result from enhanced epithelial cell maturation that improved the barrier function of the skin. In experimental studies, glucocorticoid exposure resulted in maturation of ion channels in the proximal renal tubular epithelium [30,31].

In another report, exposure to antenatal glucocorticoids prevented nonoliguric hyperkalemia that frequently occurs in ELBW infants [32]. The mechanism is uncertain, but may be related to enhanced stabilization of cell membranes and upregulation of Na-K-ATPase activity, leading to a decrease in the movement of potassium from intracellular to extracellular compartments.

Monitoring tools

Overview — Fluid and electrolyte management in the newborn is challenging due to several factors that include gestational age (GA), homeostatic changes after delivery, and the clinical setting (environmental factors, severity of illness, and therapeutic intervention). Monitoring and consideration of the various concomitant and changing factors are essential to correcting and maintaining optimal balance of fluid and electrolytes in newborns. The monitoring tools used to evaluate the neonate's fluid and electrolyte status are serial physical examinations including measurements of body weight, monitoring intake and output, and frequent serial assessments of serum sodium.

Physical examination — Physical examination begins with a general assessment of the patient, including determining GA and postnatal age. These factors affect the degree of water loss (especially skin loss) (see 'Sources of water loss' above). Other factors that will influence fluid losses and need to be considered include loss of skin integrity and the use of humidified air or radiant heater. As care proceeds, serial examination should include daily weights, signs of cardiovascular stability (heart rate, blood pressure, capillary refill), state of hydration (skin turgor, mucus membrane status, fullness of the anterior fontanelle), and the presence or absence of edema.

Body weight — Body weight should be measured at least daily and in some cases more frequently. There is an expected physiologic weight loss in the first several days of life of 5 to 10 percent in term infants [2] and as high as 15 percent in preterm infants [33]. Nomograms illustrating the normal range of weight loss over the first several days have been developed for healthy term infants based on the route of delivery [2]. Where clinical concern exists, it may be helpful to consult these nomograms directly. However, similar data are not available for preterm infants or ill term infants.

With appropriate nutrition and fluid intake, weight typically reaches a nadir at approximately three to four days and rebounds to near birth weight (BW) by seven days, although a significant percentage of otherwise normal infants may not regain BW for 14 days or longer. The absence of this normal weight loss or weight gain over the first few days suggests excess fluid intake or abnormally low losses. When calculating fluid intake, it makes practical sense to employ a standard convention that avoids limiting fluids during the period of normal expected postnatal weight loss. Many neonatal care units use the BW for the first seven days, while others continue to use BW until the measured weight exceeds that value.

However, it is important to note that body weight measurements in extremely low birth weight (ELBW) infants (BW <1000 g) may be unreliable, or subject to technical errors or estimates of the added weight of items such as intravenous boards or other small equipment. Built-in electronic scales in modern beds minimize these errors, but clinicians should be vigilant about accepting measured weights that vary excessively from the accepted pattern.

When weight measurements are available, changes are obviously dependent on adequate nutrition as well as hydration status. Body weight changes often in conjunction with serum sodium concentration are the best measure of fluid status. The frequency of serial electrolyte measurements is increased when there is fluid and electrolyte imbalance. (See 'Serum sodium' below.)

Excess body water is suggested by weight gain often in conjunction with a low serum sodium concentration. In infants with diminished kidney function, volume overload may be identified by an increase in blood pressure and physical findings of generalized edema.

Inadequate fluid intake (hypovolemia) is manifested by excessive weight loss, a high sodium concentration, tachycardia, and poor capillary refill. In the most severe cases, hypotension may be observed as a prelude to neonatal shock. (See "Assessment and management of low blood pressure in extremely preterm infants" and "Neonatal shock: Etiology, clinical manifestations, and evaluation", section on 'Clinical manifestations'.)

Decrease in effective circulation can occur when third spacing takes place, such as with sepsis or ileus. In this case, body weight may be increased with evidence of edema or ascites and a diminished sodium concentration. (See "Neonatal shock: Etiology, clinical manifestations, and evaluation", section on 'Clinical manifestations'.)

Intake and output — For the first few days after birth, fluid intake and output of urine and stool should be measured and the net difference recorded for preterm or term infants with acute illness.

The input should exceed the output by the estimated insensible fluid needs of the infant based on the gestational age (GA), which varies due to skin permeability and surface area-to-volume ratio and clinical setting (eg, use of humidified air or radiant heater) minus the estimated normal fluid loss due to diuresis following delivery. The estimated insensible fluid loss is adjusted based on body weight changes outside of the normal range and abnormal sodium levels. The key to optimal management is to make reasonable estimates and then adjust intake based on the assessment of output, body weight, and serum sodium levels. (See 'Changes in total body water' above and 'Sources of water loss' above.)

Respiratory losses are minimized when respiratory support includes warmed humidified gases and are higher in infants who are breathing on their own and with an increased respiratory rate.

Fluid needs are increased for smaller or less mature infants:

Extremely preterm infants (<28 weeks GA) may lose as much as 100 to 125 mL/kg/d through insensible loss during the first few days of life. Since fluid management allows for the normal diuresis and weight loss, the required intake volumes for the first day of life are usually estimated at 100 to 120 mL/kg/d for extremely preterm (EPT) infant (GA <28 weeks).

For more mature infants born at 28 to 30 weeks GA will lose 50 to 70 mL/kg/d through insensible loss. The required fluid intake for the first day of life is approximately 80 mL/kg/d for these infants >28 weeks GA and greater.

For example, in an EPT infant, an initial estimation that the insensible loss will be 100 mL/kg may be shown to be inadequate if there is an excess weight loss and a concomitant increase in serum sodium. In this case, the estimated insensible fluid loss is increased, resulting in an increase in intake, which is reflected by a corresponding increase in the net difference between intake and output.

On subsequent days the volume is adjusted based on weight change and assessment of fluid balance as the post-diuresis phase begins.

Serum sodium — Serial serum or plasma sodium determinations are essential for monitoring the fluid and electrolyte balance of ill neonates, especially in EPT infants. When body weights are used in conjunction with serum sodium determinations, the etiology of any sodium derangement and plan for treatment can more readily be established by calculating total body sodium. During the first days of life, changes in sodium concentration reflect primarily changes in water intake and loss, and not changes in sodium balance assuming adequate sodium intake and normal urine sodium losses for the infant. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Disorders of sodium balance'.)

Hyponatremia suggests excess of free water (hypervolemia) (see "Hyponatremia in children: Etiology and clinical manifestations", section on 'Hypervolemia')

Hypernatremia suggests depletion of free water or dehydration (hypovolemia) (see "Hypernatremia in children", section on 'Excess water losses')

The frequency of monitoring serum sodium is increased when the risk of abnormalities increases. The specific monitoring schedule depends upon GA and postnatal age, as well as the infant's clinical condition. In general, EPT infants who have very high insensible water losses will require monitoring as frequently as every six to eight hours over the first two to three days after birth, while older preterm and term infants may be adequately monitored with daily determinations [34]. Once a normal serum sodium is established with stable body weights and the rate or type of fluid administration is not changing significantly, monitoring frequency can be reduced.

Fluid and electrolyte management

Initial prescription — Fluid and electrolyte requirements are those needed for neutral balance after accounting for obligatory losses (eg, urine and stool), insensible losses (eg, skin and lungs), and initial diuresis for the first few days of life (table 5). For most infants born at gestational age (GA) less than 30 to 32 weeks, initial fluids are administered as parenteral fluids, ideally as parenteral nutrition. More mature infants are likely to receive enteral fluids. Note that newborns are typically given 10 percent glucose concentration to provide normal glucose requirements (4 to 7 mg/kg/min). Extremely preterm infants may be relatively glucose intolerant and should receive 5 percent glucose concentration or the addition of insulin therapy with high dextrose concentration to prevent hyperglycemia. (See "Parenteral nutrition in premature infants" and "Neonatal hyperglycemia", section on 'Insulin therapy'.)

Fluid – Requirements are influenced by factors that include the GA, environmental temperature and humidity, kidney function, and ventilator dependence (which affects respiratory losses) (see 'Intake and output' above). Excessive loss of other fluids, such as ileostomy or gastric drainage, must also be measured and replaced.

For infants receiving parenteral fluids, the initial volume of fluid is based on gestational age. Intravenous pumps used in neonatal intensive care units can dispense fluid in increments as small as 0.1 mL/hr, so fluid rates should be rounded to one decimal place (see 'Intake and output' above):

For extremely preterm (EPT) infant (GA <28 weeks) who receive humidified air, estimated fluid requirement from birth through day 2 is between 90 to 120 mL/kg/day. The volume is increased by 15 to 25 percent if the infant is cared for in an open radiant warmer or if they are not receiving humidified gas/respiratory support.

For more mature infants born (GA 28 to 34 weeks) who are cared for in a humidified incubator or if receiving respiratory support using humidified gas, the estimated fluid requirement for the first two days is approximately 80 mL/kg/d.

For ill term or late preterm infants (GA >34 weeks) who are unable to receive enteral fluids, the estimated fluid requirement of the first two days is between 60 to 80 mL/kg/day.

During the first few days, physiologic fluid loss should be anticipated, approximating 2 to 3 percent of body weight per day in term infants and 3 to 5 percent in preterm infants.

Electrolytes – For infants receiving parenteral fluids, maintenance electrolytes generally are not given before 24 hours of life because of the relatively volume-expanded state and normal isotonic losses during the first days of life.

Electrolyte losses from gastric, ileostomy, or thoracostomy drainage should be replaced. Ideally, the actual concentrations of electrolytes in these fluids can be measured directly. If not, begin with the following electrolyte composition and adjust based on subsequent serum estimates of electrolyte measurements [35]:

Gastric output is composed of 20 to 80 mEq/L sodium, 5 to 20 mEq/L potassium, and 100 to 150 mEq/L chloride. The presence of bile, in which the electrolyte levels are similar to serum, may alter these estimates.

Small bowel output is composed of 100 to 140 mEq/L sodium, 5 to 15 mEq/L potassium, 90 to 130 mEq/L chloride, and 40 to 75 mEq/L bicarbonate.

Thoracostomy fluid mirrors serum in electrolyte composition. Depending on the etiology of the effusion, it may also contain a significant amount of protein. (See "Management of chronic pleural effusions in the neonate", section on 'Our approach'.)

Adjustment of initial therapy — Fluid and electrolyte management should be adjusted based on the ongoing monitoring of the neonate's clinical status, including serial measurements of body weights and serum sodium and net intake and output. Normal urine output is approximately 1 to 3 mL/kg/hr. (See 'Monitoring tools' above.)

Inadequate intake is indicated by excessive loss of body weight (>3 percent in preterm infants and >10 percent in term infants during the first two or three days of life) and an increase in serum sodium. Larger than normal losses should prompt an assessment for excess losses and/or inadequate intake.

Increased losses may be due to increased excessive urine output (discussed below) or unaccounted insensible losses (eg, radiant heater or EPT infant with increased skin loss compared with more mature infants). Fluid intake is increased until water balance is achieved and then maintained as determined by body weight and sodium concentration. (See 'Kidney function' above and 'Sources of water loss' above.)

Fluid deficits associated with cardiovascular changes indicative of poor peripheral perfusion (tachycardia and poor capillary refill) require prompt correction with a bolus infusion of normal saline (10 to 20 mL/kg); in severe cases, this may need to be repeated. Once hemodynamic stability has been restored, the remaining deficit may be more slowly corrected over one to two days. (See "Neonatal shock: Management", section on 'Fluid resuscitation'.)

Excessive fluid is indicated by any weight gain during the first days after delivery and a decrease in serum sodium.

Infants with excessive fluid coupled with decreased urine output should prompt evaluation for evidence of kidney dysfunction, congestive cardiac failure, and hypoalbuminemia. In this setting, fluid intake is decreased until water balance is achieved and then maintained based on clinical status, including body weight and serum sodium concentration. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Diagnosis'.)

In critically ill neonates (especially very preterm [VPT] and extremely preterm [EPT] infants), fluid overload is associated with greater need for mechanical ventilation and higher mortality [36]. Thus, fluid management in VPT and EPT neonates aims to maintain a neutral to slightly negative water balance, as discussed separately. (See "Respiratory distress syndrome (RDS) in preterm infants: Management", section on 'Fluid management'.)

Markedly increased urine output may be seen with or without excessive fluid intake. The increased urine output may be appropriate due to an excess intake or may be pathologic due to impaired renal concentrating ability secondary to an underlying congenital tubular defect or diabetes insipidus. It is also common during the diuretic phase of recovery from oliguric or anuric acute kidney injury. Fluid intake is adjusted based on the underlying etiology to achieve and maintain a balance as determined by monitoring the intake and output, body weight, and sodium concentration. (See 'Urinary concentration and other tubular functions' above.)

Subsequent therapy — All fluid requirements are increased at day 3 of life after the normal diuresis has occurred (table 5). For infants receiving parenteral fluid, electrolytes are administered at a required maintenance level of 3 mEq/kg per day for sodium and 2 mEq/kg/day for potassium. In addition, as noted above, electrolytes and fluid losses from gastric, ileostomy, or thoracic drainage should be replaced.

Readjustment of therapy is based on serial measurements of body weight and electrolytes and net fluid intake and output.

Fluid intake is increased for infants who have a loss or inadequate increase in body weight, high serum sodium (suggesting hypovolemia) and documented intake that is less than the combination of measured output and calculated insensible water loss.

Fluid intake is decreased for infants who have excessive increase in body weight, low serum sodium (suggesting hypervolemia), and/or intake that is less than the output plus the calculated insensible water loss.

Serum sodium abnormalities are typically related to water balance issues. (See 'Electrolyte disorders' below.)

Hypokalemia (low serum potassium) is often due to excessive kidney or intestinal losses that have not been adequately replaced, whereas hyperkalemia (high serum potassium) is caused by a variety of etiologies including kidney dysfunction and congenital adrenal hyperplasia. (See 'Hypokalemia' below.)

Electrolyte disorders — In the first week of life, disorders of sodium balance are primarily due to abnormalities of water balance especially in extremely preterm (EPT) infants (gestational age <28 weeks) [37]. So, when evaluating abnormal sodium values, it is more likely that there is a change in total body water rather than an excess or deficiency in total body sodium. Whereas potassium disorders are due to kidney dysfunction or inappropriate potassium supplementation.


Early newborn period — During the early newborn period (first four to five days of life), hyponatremia, defined as a serum sodium concentration of 128 mEq/L or less, most often reflects excess total body water (TBW) with normal total body sodium. This likely results from excessive fluid intake, or, infrequently, water retention due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH may accompany pneumonia or meningitis, pneumothorax, or severe intraventricular hemorrhage [38]. (See "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)" and "Hyponatremia in children: Etiology and clinical manifestations", section on 'Syndrome of inappropriate ADH secretion'.)

Hyponatremia due to these causes is treated by fluid restriction, which usually results in a slow return to normal levels. Adjustment of fluid intake is based on changes of body weight, sodium concentration, and net fluid intake.

Later newborn period — After the first four to five days of life, hyponatremia is usually caused by negative body sodium balance [39]. It is most commonly seen as a result of inadequate replacement of large renal sodium losses in EPT infants due to immature tubular function or infants who receive diuretic therapy [39]. Rarely, hyponatremia is caused by congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, which may present as hyponatremia, hyperkalemia, metabolic acidosis, and shock in the newborn. This disorder most commonly is diagnosed as part of the standard newborn screening. For these patients, management includes correction of hypovolemia with normal saline followed by repletion of the sodium deficit along with appropriate replacement steroids. (See "Genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Management in neonates'.)

In patients with hyponatremia due to excess sodium loss, correction of hyponatremia is based on the repletion of the sodium deficit. This is calculated as the product of the total body volume times the sodium deficit per liter (ie, 140 minus the serum sodium concentration). The volume of distribution of sodium is the TBW because of the rapid osmotic equilibration between the extracellular and intracellular fluid. Although the TBW is 75 percent in normal term infants and increases with immaturity, most clinicians use a volume of distribution of 60 percent to minimize the likelihood of overly rapid correction. Sodium intake also needs to provide maintenance sodium based on the patient's ongoing needs. (See "Hyponatremia in children: Evaluation and management", section on 'Treatment'.)

Factitious hyponatremia — Hyponatremia occasionally is factitious due to increased serum glucose level. Hyperglycemia causes an osmotic shift of fluid into the intravascular space, diluting the true sodium concentration. The measured level decreases by 1.6 mEq/L for every 100 mg/dL increase in glucose level. Erroneously low sodium level may also be caused by sample collection error (eg, drawing blood out of a central line that was not adequately cleared or upstream from an intravenous infusion).

Hypernatremia — Neonatal hypernatremia is serum sodium concentration ≥150 mEq/L. It is most often caused by inadequate fluid intake or excessive fluid loss and less commonly by excessive sodium intake.

Excessive fluid loss — Neonatal hypernatremia is most commonly due to excessive fluid loss and presents as abnormally large weight loss in the first few days after delivery. Hypovolemia and hypernatremia result from inadequate fluid replacement of fluid loss due to insensible water loss (skin and respiratory loss) and urine (inability for maximal urinary concentration). In full-term infants, this is most frequently caused by inadequate breastfeeding resulting in insufficient water replacement [40]. Affected infants often have >10 percent weight loss, which exceeds the weight loss normally observed due to diuresis after delivery. (See 'Changes in total body water' above and "Initiation of breastfeeding", section on 'Assessment of intake'.)

An unusual cause of hypernatremia in newborns is diabetes insipidus, which is sometimes associated with hypoxic-ischemic encephalopathy or central nervous system malformations. Affected patients typically manifest polyuria and hypernatremia due to inadequate water replacement.

For patients with hypernatremia due to excessive water loss, treatment consists of increasing free water administration. Rapid correction of the hypernatremia (generally defined as more than 0.5 mEq/L per hour) should be avoided since this may result in cerebral edema and seizures [41]. Adequacy of therapy is based on serial sodium measurements.

Excess sodium intake — Hypernatremia without significant weight loss or fluid deficit should prompt a search for inadvertent high sodium administration. Neonatal hypernatremia can be caused by excessive sodium delivered through parenteral fluids, medication, or blood products, and may occur even in preterm infants despite their normally high urinary loss [39,42].

If hypernatremia is caused by excessive sodium intake, sodium administration should be reduced and, if necessary, water intake increased.

Hypokalemia — Hypokalemia, defined as a serum potassium concentration <3 mEq/L, usually results from excessive losses of potassium. Contributing factors include chronic diuretic use, renal tubular defects, or significant loss due to output from a nasogastric tube or ileostomy.

Hypokalemia usually is asymptomatic. However, it can cause weakness and paralysis, ileus, urinary retention, and conduction defects detected on the electrocardiogram (ECG) (eg, ST segment depression, low voltage T waves, and U waves).

In most cases, treatment consists of increasing the daily potassium intake by 1 to 2 mEq/kg. In severe or symptomatic hypokalemia, potassium chloride (KCl) (0.5 to 1 mEq/kg) is infused intravenously (IV) over one hour with continuous ECG monitoring to detect arrhythmias. (See "Hypokalemia in children".)

Hyperkalemia — Hyperkalemia is defined as a serum potassium concentration >6 mEq/L. However, neonates have a higher normal range of potassium than older infants and children because of their reduced urinary potassium excretion caused by their relatively increased aldosterone insensitivity, perhaps due to low expression of mineralocorticoid receptors [43] and decreased glomerular filtration rate (GFR) (table 3). Both of these factors are accentuated in preterm infants, resulting in normally higher serum potassium levels than their term counterparts. Of note, hyperkalemia does occur frequently in EPT infants [44-46]. The mechanism may be an exaggerated shift from intracellular to extracellular potassium after birth [44]. As discussed above, antenatal glucocorticoids may be protective [32].

Pathologic hyperkalemia may result from multiple causes, including decreased potassium clearance (eg, kidney failure, certain forms of congenital adrenal hyperplasia), increased potassium release caused by bleeding or tissue destruction (eg, intraventricular hemorrhage, cephalohematoma, hemolysis, bowel infarction) and inadvertent excessive administration of potassium (eg, supplementation for hypokalemia associated with diuretic therapy).

Depending upon severity and the rate of onset, hyperkalemia can be asymptomatic or so severe as to constitute a medical emergency. Signs include arrhythmias and cardiovascular instability. ECG findings associated with hyperkalemia consist of peaked T waves, flattened P waves, increased PR interval, and widening of the QRS complex. Bradycardia, supraventricular or ventricular tachycardia, and ventricular fibrillation may occur. (See "Causes, clinical manifestations, diagnosis, and evaluation of hyperkalemia in children", section on 'Clinical manifestations'.)

When the diagnosis is made, administration of any fluid that contains potassium should be discontinued immediately. Treatment is aimed at three factors (algorithm 1) (see "Management of hyperkalemia in children"):

Reversal of the effect of hyperkalemia on the cell membrane by infusion of 10 percent calcium gluconate (0.5 mL/kg) or calcium chloride (dose of 20 mg/kg or 0.2 mL/kg) over five minutes.

Promotion of potassium movement from the extracellular fluid compartment into the cells by administering intravenous (IV) glucose and insulin (0.05 units/kg human regular insulin with 2 mL/kg 10 percent dextrose in water), followed by a continuous infusion of insulin (0.1 units/kg per hour with 4 mL/kg per hour of 10 percent dextrose in water [100 mL/kg per day]). Glucose levels must be monitored and the infusion rate of glucose adjusted as necessary.

Other treatment methods that promote intracellular movement of potassium that may also be used after administration of glucose and insulin include:

Administration of IV sodium bicarbonate (in a dose of 1 to 2 mEq/kg over 30 to 60 minutes).

Administration of beta agonists, such as albuterol, via nebulization.

Increasing urinary excretion with IV administration of furosemide (1 mg/kg per dose) in infants with adequate kidney function.

Dialysis can be considered in infants with oliguria or anuria.

Factitious hyperkalemia — Factitious hyperkalemia is common in newborns, as samples obtained by heel prick are prone to hemolysis, resulting in artifactual elevation of potassium levels.

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fluid and electrolyte disorders in children".)

Summary and recommendations — Water and electrolyte homeostasis in newborn infants is shaped by gestational and postnatal effects on the distribution of total body water (TBW), kidney function, and water loss. Fluid and electrolyte therapy must account for these factors when determining maintenance requirements and correction of any abnormalities:

After birth, there is a physiologic diuresis of extracellular fluid (ECF) resulting in a weight loss during the first week of life. The magnitude of diuresis and relative weight loss increases with decreasing gestational age (GA). Normal weight loss is approximately 5 percent for term infants and is approximately 10 to 15 percent in preterm infants. (See 'Changes in total body water' above and 'Body weight' above.)

Kidney function is affected by both GA and postnatal age.

Glomerular filtration rate (GFR) is low in neonates and decreases with lower GA. Although GFR increases in all infants after delivery, the rate of rise decreases with lower GA. (See 'Glomerular filtration rate (GFR)' above.)

Tubular function is immature in the neonate, resulting in limited ability to concentrate urine, reduced sodium and bicarbonate reabsorption (leading to increased kidney losses), and low kidney potassium excretion. (See 'Urinary concentration and other tubular functions' above.)

The neonate has a proportionally greater insensible fluid loss compared with older individuals. This is primarily due to increased evaporative losses through the skin, which increase with decreasing GA and with the use of radiant heaters. (See 'Sources of water loss' above.)

Monitoring to maintain the correct balance of fluid and electrolytes in the neonate consists of the following:

Physical examination to assess the infant's GA and other factors that contribute to fluid loss (eg, loss of skin integrity). Sequential physical examinations to assess fluid status that include evaluation of cardiovascular stability, daily weights, and the presence of edema. Normal weight loss over the first three to five days should be expected. Volume overload is suggested by inadequate weight loss in this time period or excessive weight gain, edema, and increased blood pressure. Inadequate fluid administration may be accompanied by excessive weight loss, tachycardia, poor capillary refill, and, in severe cases, hypotension. (See 'Physical examination' above.)

Monitoring fluid intake and output of urine and stool. (See 'Intake and output' above.)

For infants receiving parenteral fluids, serial measurement of serum sodium. During the first days of life, changes in sodium concentration primarily reflect changes in water intake with hyponatremia associated with excess water (hypervolemia) and hypernatremia with excessive water loss (hypovolemia). The frequency of monitoring is dependent on the infant's clinical condition and GA. (See 'Serum sodium' above.)

Calculation of fluid and electrolyte requirements must account for correction of fluid abnormalities (deficit or excess water) and ongoing maintenance requirements. Maintenance fluid requirements are those needed for neutral water balance after accounting for obligatory losses (eg, urine and stool) and insensible losses (eg, skin and lungs) (table 5) and are influenced by postnatal age and birth weight (BW), environmental factors, kidney function, and ventilator dependence. (See 'Fluid and electrolyte management' above.)

Maintenance requirements for sodium, potassium, and chloride are approximately 2 to 3 mEq/kg per day. For infants receiving intravenous fluids, these electrolytes are not given during the first 48 hours after birth. Additional electrolyte losses beyond maintenance requirements should be replaced. (See 'Initial prescription' above.)

In the newborn, particularly preterm infants, electrolyte disorders are common and include:

Hyponatremia (see 'Hyponatremia' above)

Hypernatremia (see 'Hypernatremia' above)

Hypokalemia (see 'Hypokalemia' above)

Hyperkalemia (see 'Hyperkalemia' above)

Acknowledgment — The UpToDate editorial staff acknowledges Jochen Profit, MD, MPH, who contributed to an earlier version of this topic review.

  1. Young A, Brown LK, Ennis S, et al. Total body water in full-term and preterm newborns: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2021; 106:542.
  2. Flaherman VJ, Schaefer EW, Kuzniewicz MW, et al. Early weight loss nomograms for exclusively breastfed newborns. Pediatrics 2015; 135:e16.
  3. 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; 101:423.
  4. Lorenz JM, Kleinman LI, Ahmed G, Markarian K. Phases of fluid and electrolyte homeostasis in the extremely low birth weight infant. Pediatrics 1995; 96:484.
  5. Joppich R, Scherer B, Weber PC. Renal prostaglandins: relationship to the development of blood pressure and concentrating capacity in pre-term and full term healthy infants. Eur J Pediatr 1979; 132:253.
  6. Yasui M, Marples D, Belusa R, et al. Development of urinary concentrating capacity: role of aquaporin-2. Am J Physiol 1996; 271:F461.
  7. CALCAGNO PL, RUBIN MI, WEINTRAUB DH. Studies on the renal concentrating and diluting mechanisms in the premature infant. J Clin Invest 1954; 33:91.
  8. Quigley R, Chakravarty S, Baum M. Antidiuretic hormone resistance in the neonatal cortical collecting tubule is mediated in part by elevated phosphodiesterase activity. Am J Physiol Renal Physiol 2004; 286:F317.
  9. Normal kidney development. In: Pediatric Kidney Disease, 2nd ed, Edelman CM Jr (Ed), Little, Brown and Company, Boston 1992. p.3.
  10. Arant BS. Neonatal adjustments to extrauterine life. In: Pediatric Kidney Disease, 2nd ed, Edelman CM (Ed), Little, Brown and Company, Boston 1992. p.1015.
  11. Bueva A, Guignard JP. Renal function in preterm neonates. Pediatr Res 1994; 36:572.
  12. Horster M. Embryonic epithelial membrane transporters. Am J Physiol Renal Physiol 2000; 279:F982.
  13. Rodríguez Soriano J. Renal tubular acidosis: the clinical entity. J Am Soc Nephrol 2002; 13:2160.
  14. Rodríguez-Soriano J. New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies. Pediatr Nephrol 2000; 14:1121.
  15. Balakrishnan M, Tucker R, Stephens BE, Bliss JM. Blood urea nitrogen and serum bicarbonate in extremely low birth weight infants receiving higher protein intake in the first week after birth. J Perinatol 2011; 31:535.
  16. Thureen PJ, Melara D, Fennessey PV, Hay WW Jr. Effect of low versus high intravenous amino acid intake on very low birth weight infants in the early neonatal period. Pediatr Res 2003; 53:24.
  17. Ridout E, Melara D, Rottinghaus S, Thureen PJ. Blood urea nitrogen concentration as a marker of amino-acid intolerance in neonates with birthweight less than 1250 g. J Perinatol 2005; 25:130.
  18. Kjartansson S, Arsan S, Hammarlund K, et al. Water loss from the skin of term and preterm infants nursed under a radiant heater. Pediatr Res 1995; 37:233.
  19. Agren J, Sjörs G, Sedin G. Transepidermal water loss in infants born at 24 and 25 weeks of gestation. Acta Paediatr 1998; 87:1185.
  20. Nonato LB, Lund CH, Kalia YN, Guy RH. Transepidermal water loss in 24 and 25 weeks gestational age infants. Acta Paediatr 2000; 89:747.
  21. Williams PR, Oh W. Effects of radiant warmer on insensible water loss in newborn infants. Am J Dis Child 1974; 128:511.
  22. Baumgart S. Reduction of oxygen consumption, insensible water loss, and radiant heat demand with use of a plastic blanket for low-birth-weight infants under radiant warmers. Pediatrics 1984; 74:1022.
  23. Kim SM, Lee EY, Chen J, Ringer SA. Improved care and growth outcomes by using hybrid humidified incubators in very preterm infants. Pediatrics 2010; 125:e137.
  24. Engle WD, Baumgart S, Schwartz JG, et al. Insensible water loss in the critically III neonate. Combined effect of radiant-warmer power and phototherapy. Am J Dis Child 1981; 135:516.
  25. Oh W, Karecki H. Phototherapy and insensible water loss in the newborn infant. Am J Dis Child 1972; 124:230.
  26. Bertini G, Perugi S, Elia S, et al. Transepidermal water loss and cerebral hemodynamics in preterm infants: conventional versus LED phototherapy. Eur J Pediatr 2008; 167:37.
  27. Riesenfeld T, Hammarlund K, Sedin G. Respiratory water loss in fullterm infants on their first day after birth. Acta Paediatr Scand 1987; 76:647.
  28. Riesenfeld T, Hammarlund K, Sedin G. Respiratory water loss in relation to gestational age in infants on their first day after birth. Acta Paediatr 1995; 84:1056.
  29. Omar SA, DeCristofaro JD, Agarwal BI, La Gamma EF. Effects of prenatal steroids on water and sodium homeostasis in extremely low birth weight neonates. Pediatrics 1999; 104:482.
  30. Ali R, Amlal H, Burnham CE, Soleimani M. Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules. Kidney Int 2000; 57:1063.
  31. Baum M, Amemiya M, Dwarakanath V, et al. Glucocorticoids regulate NHE-3 transcription in OKP cells. Am J Physiol 1996; 270:F164.
  32. Omar SA, DeCristofaro JD, Agarwal BI, LaGamma EF. Effect of prenatal steroids on potassium balance in extremely low birth weight neonates. Pediatrics 2000; 106:561.
  33. Paul IM, Schaefer EW, Miller JR, et al. Weight Change Nomograms for the First Month After Birth. Pediatrics 2016; 138.
  34. Baumgart S, Costarino AT. Water and electrolyte metabolism of the micropremie. Clin Perinatol 2000; 27:131.
  35. Nelson Textbook of Pediatrics, 18th ed, Kleigman RM, Berhman RE, Jenson HB, Stanton BF (Eds), WB Saunders, Philadelphia 2007.
  36. Matsushita FY, Krebs VLJ, de Carvalho WB. Association between fluid overload and mortality in newborns: a systematic review and meta-analysis. Pediatr Nephrol 2022; 37:983.
  37. Monnikendam CS, Mu TS, Aden JK, et al. Dysnatremia in extremely low birth weight infants is associated with multiple adverse outcomes. J Perinatol 2019; 39:842.
  38. Rees L, Brook CG, Shaw JC, Forsling ML. Hyponatraemia in the first week of life in preterm infants. Part I. Arginine vasopressin secretion. Arch Dis Child 1984; 59:414.
  39. Späth C, Sjöström ES, Ahlsson F, et al. Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants. Pediatr Res 2017; 81:455.
  40. Moritz ML, Manole MD, Bogen DL, Ayus JC. Breastfeeding-associated hypernatremia: are we missing the diagnosis? Pediatrics 2005; 116:e343.
  41. Blum D, Brasseur D, Kahn A, Brachet E. Safe oral rehydration of hypertonic dehydration. J Pediatr Gastroenterol Nutr 1986; 5:232.
  42. Eibensteiner F, Laml-Wallner G, Thanhaeuser M, et al. ELBW infants receive inadvertent sodium load above the recommended intake. Pediatr Res 2020; 88:412.
  43. Martinerie L, Viengchareun S, Delezoide AL, et al. Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates. Endocrinology 2009; 150:4414.
  44. Lorenz JM, Kleinman LI, Markarian K. Potassium metabolism in extremely low birth weight infants in the first week of life. J Pediatr 1997; 131:81.
  45. Mildenberger E, Versmold HT. Pathogenesis and therapy of non-oliguric hyperkalaemia of the premature infant. Eur J Pediatr 2002; 161:415.
  46. Shaffer SG, Kilbride HW, Hayen LK, et al. Hyperkalemia in very low birth weight infants. J Pediatr 1992; 121:275.
Topic 5065 Version 26.0


Do you want to add Medilib to your home screen?