Fluid and electrolyte therapy in newborns

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 in resource-abundant settings".)

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 neonate 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.

GA can be derived from a calculator (calculator 1). BW by percentile for the appropriate GA have been established (table 2 and figure 1).

These 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) neonates, 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 the term neonate, 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 neonates 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 neonates in the first day of life [2]. The postnatal diuresis is approximately 1 to 3 mL/kg per hour in term neonates and is greater in preterm neonates. Since fluid administration among ill or preterm neonates is entirely regulated by parents/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) neonates (BW ≤1500 g) and extremely low birth weight (ELBW) neonates (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 newborn 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 newborn, 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 neonate, 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 infant 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. The risk of volume depletion is increased in neonates because of the inability to maximally concentrate urine and as a result of increased insensible fluid losses 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 neonates 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 infant.

•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 infant, 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 newborn 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 neonates (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 neonates <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 neonates and 16 to 20 mmol/L in preterm neonates, 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 neonates. (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 neonates with GAs below 35 weeks is lower. For example, a full-term neonate has a GFR of approximately 26 mL/min per 1.73 m², whereas a preterm neonate at 27 weeks gestation will have a GFR of 13.4 mL/min per 1.73 m², (or approximately 50 percent the GFR of a term neonate). Lower GFR may result in higher potassium levels and sodium and water retention. (See "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Normal neonatal kidney function' and "Neonatal acute kidney injury: Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Presentation due to other laboratory abnormalities'.)

GFR increases at birth in all neonates due to recruitment of superficial nephrons and a substantial increase in kidney blood flow (RBF). This results from a decrease in renal vascular resistance and the physiologic increases in systemic blood pressure. However, the velocity of change is greater in term neonates compared with preterm neonates, especially VPT neonates. Thus, for term neonates, 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.

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 pregnant parent (usually less than 1 mg/dL [88 micromol/L]), and normally falls over time. For term neonates, 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 neonates, 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: Clinical manifestations, evaluation, and diagnosis", section on 'Staging'.)

In preterm neonates, 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 newborn infants. These may be excessive in extremely low birth weight (ELBW; BW <1000 g) or extremely preterm (EPT, GA <28 weeks) neonates with very thin skin (increased skin permeability). In addition, the surface area-to-volume (related to body weight) ratio increases with decreasing GA, which results in increased 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 neonates born after 28 weeks GA. For EPT neonates, these losses become less important one week after birth. As an example, insensible water loss in a neonate 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 neonate. 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 neonates 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 neonates are caused by water loss through the respiratory system [27,28]. Respiratory loss increases with increasing respiratory rate and decreases for neonates 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 neonates, skin water loss is greater than respiratory loss.

Effect of antenatal glucocorticoids — Antenatal administration of glucocorticoids to promote lung maturation in preterm neonates 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 neonates exposed and not exposed to antenatal glucocorticoids [29]. Exposed neonates 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 neonates [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.

EVALUATION AND MONITORING

Overview — Fluid and electrolyte management in the newborn infant 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 newborn infants. Evaluation and monitoring of the neonate's fluid and electrolyte status include serial physical examinations including measurements of body weight, monitoring intake and output, and frequent serial measurements 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 influence fluid losses and should 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 (eg, extremely small neonates with very immature skin or other factors that might lead to excess losses of water). Body weight changes 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.)

When weight measurements are available, changes are dependent on adequate nutrition as well as hydration status:

●Excess body water – This is suggested by weight gain often in conjunction with a low serum sodium concentration. In neonates 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) – This is manifested by excessive weight loss, a high sodium concentration, tachycardia, and poor capillary refill. The early signs of hypovolemia may be subtle, but 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 – This 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'.)

There is an expected physiologic weight loss in the first several days of life of 5 to 10 percent in term neonates [2] and as high as 15 percent in preterm neonates [33]. Nomograms illustrating the normal range of weight loss over the first several days have been developed for healthy term neonates 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 or ill term neonates, although there is some information available regarding weight loss among selected premature neonates [34].

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 healthy neonates 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) neonates (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.

Intake and output — For preterm or acutely ill term neonates during the first few days after birth, fluid intake and output of urine and stool should be measured and the net difference recorded. Input should exceed output. On subsequent days the volume is adjusted based on weight change and assessment of fluid balance as the postdiuresis phase begins.

Net difference in intake and output is determined by estimating the insensible fluid needs of the neonate 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), and subtracting the estimated normal fluid loss due to diuresis following delivery. The estimated insensible fluid loss is adjusted based on changes in body weight 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.

Specific considerations include:

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

●Smaller or less mature neonates – Fluid needs are increased for smaller or less mature neonates as follows:

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

•More mature neonates born at 28 to 30 weeks GA will lose 50 to 70 mL/kg/day through insensible loss. Thus, the required fluid intake for the first day of life is approximately 80 mL/kg/day for these neonates.

It is important to consider changes in serum sodium. For example, in an EPT neonate, an initial estimation that the insensible loss will be 100 mL/kg may 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 increased intake, which is reflected by a corresponding increase in the net difference between intake and output.

Serum sodium — Serial serum or plasma sodium measurements are essential for monitoring the fluid and electrolyte balance of ill neonates or neonates receiving parenteral fluids, especially in EPT neonates. When body weights are used in conjunction with serum sodium levels, 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 the neonate has adequate sodium intake and normal urine sodium losses. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Disorders of sodium balance'.)  

Sodium levels indicate fluid status as follows:

●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 serum sodium measurements should be increased when the risk of abnormalities increases. However, the frequency and timing of these measurements depend upon gestational and postnatal age and the neonate's clinical condition. In general, EPT neonates 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 neonates may be adequately monitored with daily measurements during those initial days [35]. The frequency of measurements should be reduced once a normal serum sodium is established, body weight is stable, and the rate or type of fluid administration is not changing significantly.

FLUID AND ELECTROLYTE MANAGEMENT

Initial therapy — 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 neonates born at gestational age (GA) less than 30 to 32 weeks, initial fluids are administered as parenteral fluids, ideally as parenteral nutrition. More mature neonates are likely to receive enteral fluids. It is important to note that newborn infants are typically given fluids with 10 percent glucose concentration to provide normal glucose requirements (4 to 7 mg/kg/min). However, extremely preterm neonates may be relatively glucose intolerant and should receive fluids with 5 percent glucose concentration or the addition of insulin therapy with high dextrose concentrations 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 neonates 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. During the first few days, physiologic fluid loss should be anticipated (approximating 2 to 3 percent of body weight per day in term neonates and 3 to 5 percent in preterm neonates) (see 'Intake and output' above):

•Extremely preterm (EPT) neonates (GA <28 weeks) – For EPT neonates who are cared for in a humidified environment, 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.

•More mature neonates (GA 28 to 34 weeks) – For more mature neonates who are cared for in a humidified environment or who are receiving respiratory support using humidified gas, the estimated fluid requirement for the first two days is approximately 80 mL/kg/day.

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

●Electrolytes – For neonates 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, we begin with the following electrolyte composition and adjust based on subsequent serum estimates of electrolyte measurements [36]:

•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 'Monitoring and replacing fluid losses'.)

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

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

Increased losses may be due to increased or excessive urine output (discussed below) or unaccounted insensible losses (eg, radiant heater or EPT neonates with increased skin loss compared with more mature neonates). 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 status – This is indicated by any weight gain during the first days after delivery and a decrease in serum sodium.

Neonates 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] neonates), fluid overload is associated with greater need for mechanical ventilation and higher mortality [37]. 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 neonates: Management", section on 'Fluid management'.)

●Markedly increased urine output – This may occur 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 and 'Evaluation and monitoring' above.)

Subsequent therapy — All fluid requirements are increased at three days of life after physiologic diuresis has occurred (table 5). For neonates receiving parenteral fluid, electrolytes are administered at a required maintenance level of 3 mEq/kg/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 neonates 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 neonates who have excessive increase in body weight, low serum sodium (suggesting hypervolemia), and/or intake that is more than the output plus the calculated insensible water loss.

●Serum sodium abnormalities are typically related to water balance issues. This is discussed in more detail elsewhere. (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. This is discussed in more detail elsewhere. (See 'Electrolyte disorders' 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) neonates (gestational age <28 weeks) [38]. Thus, 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. In contrast, potassium disorders are due to kidney dysfunction or inappropriate potassium supplementation.

Hyponatremia

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 [39]. (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. (See 'Evaluation and monitoring' above and 'Fluid and electrolyte management' above.)

Later newborn period — After the first four to five days of life, hyponatremia is usually caused by negative body sodium balance [40]. It is most commonly seen as a result of inadequate replacement of large renal sodium losses in EPT neonates due to immature tubular function or in neonates who receive diuretic therapy [40]. 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 newborn infants. 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 manifestations of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children: Treatment", section on 'Management in neonates ≤1 month'.)

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 equivalent to the total body water (TBW) because of the rapid osmotic equilibration between the extracellular and intracellular fluid. Although the TBW is 75 percent in healthy term neonates and increases further with immaturity, most clinicians use an estimated volume of distribution of 60 percent to minimize the likelihood of overly rapid correction. Sodium intake should also include maintenance sodium based on the patient's ongoing needs. The key to management is to calculate repletion needs and estimate the expected change over a several hour period. The sodium level should then be remeasured and replacement adjusted if needed. (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 (eg, skin and respiratory loss) and urine (due to inability to achieve maximal urinary concentration). In full-term neonates, this is most frequently caused by inadequate breastfeeding resulting in insufficient water replacement [41]. Affected neonates 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'.)

Diabetes insipidus is an unusual cause of hypernatremia in newborn infants, which is sometimes associated with hypoxic-ischemic encephalopathy or central nervous system malformations. Affected patients typically present with 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 [42]. Adequacy of therapy is determined by 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 neonates despite their normally high urinary loss [40,43].

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 (table 3) because of their reduced urinary potassium excretion caused by their relatively increased aldosterone insensitivity, perhaps due to low expression of mineralocorticoid receptors [44] and decreased glomerular filtration rate (GFR). Both of these factors are accentuated in preterm neonates, resulting in physiologically higher serum potassium levels than their term counterparts. Of note, hyperkalemia does occur frequently in EPT neonates [45-47]. The mechanism may be an exaggerated shift from intracellular to extracellular potassium after birth [45]. As discussed above, antenatal glucocorticoids may be protective [32]. (See 'Effect of antenatal glucocorticoids' above.)

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.

●Tissue destruction (eg, intraventricular hemorrhage, cephalohematoma, hemolysis, bowel infarction).

●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 neonates with oliguria or anuria.

Factitious hyperkalemia — Factitious hyperkalemia is common in newborn infants, as samples obtained by heel prick are prone to hemolysis, resulting in artificial 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

●Factors affecting electrolyte therapy – Water and electrolyte homeostasis in newborn neonates 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.

•Weight loss – After birth, there is a physiologic diuresis of extracellular fluid (ECF) resulting in 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 – Kidney function is affected by both GA and postnatal age.

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

-Tubular function – 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.)

•Insensible fluid loss – 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 – Monitoring to maintain the correct balance of fluid and electrolytes in the neonate consists of the following:

•Serial physical examination and body weight measurements – Physical examination to assess the neonate'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 and 'Body weight' above.)

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

•Measurement of serum sodium – Serial measurement of serum sodium, particularly for ill neonates or neonates receiving parenteral fluids. 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 neonate's clinical condition and GA. (See 'Serum sodium' above.)

●Calculating requirements – Calculation of fluid and electrolyte requirements must account for correction of fluid abnormalities (deficit or excess water) and ongoing maintenance requirements. (See 'Fluid and electrolyte management' above.)

•Fluid replacement – Initial and 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, birth weight (BW), environmental factors, kidney function, and ventilator dependence. For neonates receiving parenteral fluids (eg, preterm neonates born at 30 to 32 weeks gestation), the initial volume of fluid is based on gestational age. Excessive loss of other fluids, such as ileostomy or gastric drainage, must also be measured and replaced.

•Electrolyte replacement – Maintenance requirements for sodium, potassium, and chloride are approximately 2 to 3 mEq/kg per day. For neonates receiving intravenous fluids, these electrolytes are not given during the first 48 hours after birth. Additional electrolyte losses beyond maintenance requirements should be replaced.  

●Common electrolyte disorders – In the newborn, particularly preterm neonates, electrolyte disorders are common and include:

•Hyponatremia (see 'Hyponatremia' above)

•Hypernatremia (see 'Hypernatremia' above)

•Hypokalemia (see 'Hypokalemia' above)

•Hyperkalemia (see 'Hyperkalemia' above and 'Factitious hyperkalemia' above)

ACKNOWLEDGMENT — 

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