Fluid and Electrolyte Requirements in the Newborn Infant

Symposium on The Newborn

Fluid and Electrolyte Requirements in the Newborn Infant Moises Dreszer, M.D. *

The management of water and electrolytes in high risk premature infants is a difficult task in neonatal intensive care units. Some of the characteristics of water composition and distribution, metabolic rate variation, use of heat warmers, phototherapy, and different disease states make this task more difficult. The purpose of this article is to review water and electrolyte balance in intrauterine and extrauterine life, including mechanisms of water loss, the endocrine control of fluids, and the clinical assessment of hydration in the sick neonate.

Role of the Fetus in Water Exchange of Amniotic Fluid The fetus in utero participates in a net circulation of water involving mother, fetus, and amniotic fluid. It is estimated that 3500 ml of water are exchanged hourly between the mother and fetus, with a net flux in maternal-fetus direction. There is some exchange of water between fetus and amniotic fluid. Fetal swallowing and micturition contribute one tenth or less of the hourly exchange. 32 • 33 The fetus swallows 20 ml per hour at term. After birth, the water supply to the fetus is abolished, and there is increased evaporation of water from the skin and respiration. At that time, there is compensatory conservation of water by the kidneys. It is important to understand fetal physiology of the urogenital system. 36 Campbell measured antenatal urine production with a compound B-scan ultrasonogram and studied the filling and emptying cycle of the bladder.s In the 33 cases studied, the length of complete filling and emptying cycles of the bladder in term infants varied from 50 to 155 minutes with a mean cycle time of 110.3 minutes. In this study, the hourly fetal urine production rate was 19.6 ml in the morning and 20 ml in the afternoonY Thus, no diurnal variation in urine production was apparent. In infants 32 weeks of gestation, the average hourly' urine production rate was 12.2 ml, with a gradual increase to 28.2 ml at 40 weeks of gestation. "Director of Newborn Services, St. Joseph's Hospital, Louisville; Clinical Instructor, Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky

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Changes in Body Water Distribution There is a marked instability in the premature infant's control of total body water. 9 ,16 McClaren and Cheek10 ,26 demonstrated that the major fluid shift between intravascular and intracellular compartments occurs during the first three to four hours of life. Under normal circumstances, passive osmotic shifts of water, with alterations of intracellular water, equalize the total solute concentration of intracellular and extracellular fluids. Extracellular fluid volume is controlled by at least two mechanisms. First, there are direct volume receptors. Second, the release of antidiuretic hormone regulates water read sorption by the renal tubules and is dependent upon extracellular solute concentrations. The renal function of the newborn kidney, when compared with the adult, is characterized by a decreased glomerular filtration rate,2, 18 decreased solid excretion, and diminished maximal concentrating power. Therefore, this insufficiency of the kidney results in an increased extracellular solute concentration and decreased intracellular volume. l l In normal infants, there is a rise in hemoglobin concentration and red cell volume after birth. This increase is secondary to a shift of plasma from the intravascular to the extravascular compartments. It has been hypothesized that this shift may be secondary to the opening of the pulmonary circulation system. 1O In the premature infant, the hemoglobin concentration increases by approximately 9 per cent during the first four hours of life. The mean cord hemoglobin level is 17.9 gm per 100 ml and finally reaches a peak level of 19.4 gm per 100 ml by eight hours of life. Apparently there is no significant change in plasma protein concentration following birth. The mean plasma protein concentration of cord blood in infants is 5.3 gm per 100 ml, and the mean level at eight hours following birth is 5.2 gm per 100 ml.

Glomerulotubular Function Nephrogenesis is complete by 35 weeks of gestationP The glomerular basement membrane at this time is thin, and the glomerular structure is small. The ratio of glomerular surface area to proximal tubule volume is high. The loops of Henle are short, with a few loops located in the renal cortex. 27 ,28 The glomerular filtration rate is low at birth and gradually increases thereafter.!' 21 An adult kidney is twice as effective in concentrating urine osmolality as is a newborn kidney. Therefore, a high protein load will increase the solute load, and increase the risk of infants developing dehydration. 7 There is frequently a small amount of urea excreted by the newborn. If fed more protein, more urea is excreted, and there is an increase in water requirements. 49 Some studies demonstrated little difference between the ability of newborn and adult kidneys to excrete an acid or ammonia load. 41 The bicarbonate threshold of the adult kidney is 24 to 26 mEq per liter, and of the infant kidney is 22 mEq per liter. In the newborn, the length of the proximal tubule is short relative to the glomerulus. This short tubular length permits the excretion of amino acids in the normal infant.

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The relationship between glomerular and tubular function can be ascertained by calculating the filtration fraction as a percentage of the total renal plasma flow that is filtrated. 44 In infants, only 64 per cent of a dosage of parahippuric acid is excreted, compared with an 85 to 90 per cent excretion in adults. 44 This indicates that there is a decrease of organic acid by the proximal tubule. Since the kidney develops in a centrifugal pattern, the deeper nephrons are more effectively vascularized by the vasa recta system than are the more newly developing superficial nephronsP· 44 It is known that under normal hydration conditions, newborns and infants are unable to concentrate their urine as efficiently as adults. The maximal limit of urine osmolality in infants during the first week of life is about 800 mOsm per liter,44 compared with normal adult values of 1600 to 1900 mOsm per liter. The difference may be due to immaturity of the hypothalamic neurohypophyseal system, or an insensitivity of the distal portion of the nephron system to antidiuretic hormone. 2 DEVELOPMENT OF ANTIDIURETIC ACTIVITY. Antidiuretic hormone activity is not detected in infants younger than 2112 months of age under normal hydration states,24 and is only rarely detected after a sodium chloride load. Between 2112 and 5 months of age, diuretic activity is still not detected in normal hydration but is regularly found during states of increased osmotic loads. 37 After the age of five months, however, diuretic activity can be consistently demonstrated during normal hydration states. This more mature regulation of water and electrolyte economy at this age is characterized by a decreased intake of fluids. There is, therefore, a decreased hydration of the body at this time and decreased urine flow. Renal Water Conservation In utero, large amounts of hypotonic urine are produced by the fetal kidney, simulating water diuresis. 8 During this period, the renal blood flow and glomerular filtration rates are low, but a high rate of urine flow is maintained by virtue of reduced tubular read sorption of water. 25 Gresham et al. 18 noted a marked reduction of fetal urine flow and an increase in fetal urine osmolality during natural labor and delivery. He speculated that the stress associated with birth is an important factor in triggering the transition between fetal and neonatal renal function. Following birth, when the kidney has become a major organ of excretion, the glomerular filtration rate rises steadily with advancing postnatal age. 19 Various renal tubular functions increase at this time as does reabsorption of water by the renal tubule.42 Insensible Water Loss in the Low Birth Weight Infant The relationship of insensible water loss and the metabolic rate was first noted by Benedict in 1907 and DuBois in 1917. The validity of their observations was confirmed by Lavine in 1930, and more recently by Hey and Katz.19 These authors found that infants between 2 and 10 days of age, weighing greater than 1500 gm, lose 33.6 gm of water per kilogram of body weight per day. If these infants are in a heat shield, however, loss of water is reduced to 26.6 gm per kg per day under standard conditions. There was a difference of up to 10.8 gm per kg between the weight loss of infants with or without the heat shield.

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Under standard experimental conditions, insensible water loss is directly proportional to the metabolic rate. 15 Approximately 0.58 calories are expended per gm of water metabolized. This relationship, however, appears to change with different environmental conditions in any number of disease states. The relative water loss in small immature infants is secondary to a combination of the increased metabolic rate and enhanced insensible loss via the lungs and skin.40 Factors that elevate the metabolic rate in the low birth weight infant include increased activity, specific dynamic action, and temperature on either side of the neutral thermal environment. It has been noted that insensible water loss is increased by a factor of 1. 7 by increased activity.50 Hey and Katz 20 noted that infants in a cool environment experience a 30 per cent increase in water loss during episodes of crying and increased activity. There is an increase in the metabolic rate of 25 per cent in infants immediately following a meal, but the average rate decreases to approximately a 10 per cent increase over a more prolonged period of time following eating. By oxygen consumption measurements, it has been demonstrated conclusively that the metabolic rate is elevated on either side of the neutral thermal zone. Insensible water loss accompanies the increased metabolic rate in the neutral thermal range. 15 . 50 However, with environmental changes, insensible water loss did not increase because the proportion of heat expenditure via insensible water loss diminishes. The response to cooling may, in part, be due to vasoconstriction and reduced evaporation. The amount of water vapor leaving the respiratory tract is related to the temperature and water content of the inspired air,39.40 together with the minute volume. Therefore, there is a potential for significant wat€)r loss via the lungs. This water loss may be minimized during periods of respiratory distress by increasing the ambient humidity to 40 per cent.40 Evaporation of water from the skin is affected by many factors, including humiditY,3s. 39 temperature, air currents, blood flow to the skin, character of the skin covering, and body water content. 43 . 4S The skin of the newborn differs considerably from that of the adult. The epidermal layers, especially transitional and cornified, are thinner. In premature infants, the outer layer of the skin is remarkably transparent with numerous blood vessels which can be observed with the naked eye. The blood supply is relatively greater than the infant's metabolic requirements and provides a convenient channel for the convective transfer of internal body heat to the surface of the skin. These alterations in the infant's skin may critically increase water loss by reducing the physical barrier to diffusion of water vapor. Large water losses from the skin may occur in association with sweating or with alterations in the physical properties in the skinY' 19 Sweating, which can cause a threefold increase in evaporative water loss, has been observed by Hey and Katz l9 . 2o in neonates with environmental temperatures of about 35° C. and rectal temperatures of 37.1 ° C. Infants under 2000 gm, however, have a significantly lesser ability to sweat. 17 The maturity of the infant appears to be a more important factor than birth weight in the conservation of insensible water loss. RADIANT HEAT WARMERS. Infants subjected to radiant heat warmers demonstrate an increase in insensible water 10ss.45 Wu et al. 4S

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demonstrated that infants under 1500 gm experienced an increase in insensible water loss of 50 to 100 per cent, and infants greater than 1500 gm an increase of 80 to 190 per cent. In term babies, there was an average of 100 per cent increase in insensible water loss while infants were under the warmers. PHOTOTHERAPY. Oh and KareckPo demonstrated that phototherapy increased insensible water loss from 1.7 to 2.4 ml per kg per hour. Other investigators demonstrated that infants over 1500 gm had greater losses of insensible water than those weighing less than 1500 gm.6. 30. 35. 36 Infants weighing greater than 1500 gm demonstrated a loss of 1.3 to 1.8 ml per kg per hour, and infants under 1500 gm a loss of 0.8 to 1.7 ml per kg per hour. They postulated that the mechanism of this enhanced loss is probably secondary to a 30 to 80 per cent increase in the superficial blood flow. 3o . 31 AMBIENT TEMPERATURE. Term infants exposed to increased environmental temperature demonstrated an increased evaporative water 10ss.17.20 In premature babies, this loss is negligible because of their inability to sweat. POSTNATAL AGE. Wu and Hodgman4B demonstrated a decreased insensible water loss in infants less than 1500 gm with advanced age. In infants weighing greater than 1500 gm, however, there was an increase in insensible water loss during the second week of life, and this loss finally stabilized between the third and fourth weeks of age. ACTIVITY AND SLEEP. In infants, there is a decrease in insensible water loss during sleep.50 With increased activity, there is a loss of approximately 1. 7 ml of water per kg per hour. Crying doubles the amount of insensible water loss, and in infants weighing greater than 2.3 kg, triples the insensible water loss. SWEATING. Infants less than 34 weeks of gestation sweat very little. 17 Infants under 30 weeks of gestation do not sweat. Thus, water loss in premature infants is generally not from sweating, but more likely from evaporation through urine and stools. HUMIDITY. Insensible water loss decreases with increased humidity.3B.39 Hey and Katz 19 demonstrated a 30 per cent decrease in basal evaporative water loss at high humidity with water vapor pressures of 24 to 26. The total water loss is one third the total evaporative water loss in the absence of sweating. Increased insensible water loss with low humidity is most marked in the respiratory tract. 29 HEAT SHIELD. Placement of a heat shield over a newborn infant causes an increase in the abdominal skin temperature which would be expected to cause cutaneous vasodilation and increased skin perfusion, which would favor increased evaporative water 10ss.2o.43 Investigators5o have observed a reduction in oxygen consumption of up to 25 per cent following the placement of a heat shield. Most investigators have found a 25 per cent decrease in insensible water loss in infants placed under the heat shield. METABOLIC RATE. Under basal conditions, the insensible water loss which utilizes 0.58 calories for each gram of evaporation correlates with the basal metabolic rate. 40 The basal metabolic rate accounts for 23 to 25 per cent of the energy expenditure. Sulyok et al. 42 • 43 demonstrated a minimal evaporative heat loss in term infants who comprised 18 per

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cent of the total heat production in an ambient temperature of 32° C. and a humidity of 50 per cent. Out of neutral thermal regulation, this loss varies from 15 to 25 per cent in an ambient temperature of 28 to 36°C.

Renal Control of Sodium and Fluid Balance During Intravenous Therapy The use of intravenous therapy in newborns has become a more common procedure during the past decade. New recommendations for saline content of these fluids have generally been based on empirical observations.42 It has been observed that the salt tolerance of the neonate is very low. This assumption has been supported by the fact that the sodium content of breast milk is low, and is further supported by newborn infants' suppressed response to high solute loads. It is generally noted, however, that when no extra or very low amounts of sodium are added to intravenous fluids, hyponatremia occurs frequently. With saline infusates containing 20 mEq of sodium per 1000 ml of fluids, there is an equal amount of urinary salt loss with no significant net change in the total body sodium. However, with 40 mEq of sodium per 1000 ml in the intravenous solution, the sodium balance becomes increasingly positive. In infants below 36 weeks of gestation, however, the sodium balance becomes negative with solutions containing large amounts of saline. 3 RENAL WATER REQUIREMENTS. Assessment of renal water requirements are to be individualized. Adjustments in fluid intake should be made according to the patient's clinical condition.14, 25, 46 The normal urine osmolality in the newborn is between 75 and 300 mOsm which generally correlates with a urine specific gravity of between 1.002 a~d 1.010. The normal urine output in the neonate is between 50 and 100 ml of fluid per kg per day. GASTROINTESTINAL LOSSES. Newborns who do not have diarrhea or jaundice lose approximately 7 ml of water per kg per day.22,36 Jaundiced babies under phototherapy with secondary diarrhea may lose up to 19 ml of water per kg per day.35 SOLUTE LOAD. The water requirements in infants on proprietary formulas depend on the amount of solute excreted by the kidneys as end products of protein metabolism and electrolytes. 7 • 49 Under normal circumstances in healthy newborns, the concentration of solute afforded the kidney does not place a demand on body water which results in dehydration. Feeding premature infants with increased protein, which is decomposed to urea and acts osmotically, requires more water for excretion. 12 The electrolytes which are not utilized produce an osmotic effect. It has been shown that the full term infant's kidney has a concentrating capacity of 700 mOsm per liter and is capable of excreting the renal solute from formulas with an average of 30 mOsm per literP It has been estimated that each gram of dietary protein yields 4 mOsm of renal solute load, and 1 mEq of sodium, potassium, and chloride each contributes 1 mOsm. A water imbalance should be suspected in infants on formulas when there is extrarenal water loss, high protein intake, and inability of the kidney to excrete the solute load to prevent dehydration.

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MODIFYING EFFECT ON GROWTH. Many substances, such as proteins, potassium, and phosphorus, which are normally excreted by the adult kidney, are withheld by the renal tubules of premature infants because of the requirement of these substances for tissue formation. It has been demonstrated that for each gram of body weight gained in infants, there was a decrease of 1 mOsm of urinary solute load excreted. Premature infants weighing approximately 1500 gm with a 200 calorie intake will typically excrete a urinary solute load of 20 mOsm per 100 calories. If, however, the patient is not growing, for each 100 calories of intake there will be 40 mOsm of urinary solute excreted. If the infant is ill and not gaining weight appropriately, there will be an excessive solute load present in the kidneys, and therefore an increased water requirement for excretion. WATER OF OXIDATION. Approximately 12 ml of water are produced per 100 calories expended from the oxidation of carbohydrates and fatty acids. This water from oxidation is derived from the caloric expenditure of about 45 to 130 cal per kg per day. REPLACEMENT OF INSENSIBLE WATER Loss. Renal water requirements change in every infant. Table 1 gives some of;' the guidelines for replacement and requirements in premature newborns. ADMINISTRATION OF WATER AND ELECTROLYTES. The ideal method to maintain caloric and fluid balance in the newborn is by early administration of water and calories. 4 • 5 • 46 Newborns normally excrete from 4 to 6 mg of glucose per kg which approximates the output of glucose by the liver. Hyperglucosemia has been reported in infants weighing less than 1250 gm when receiving greater than 6 mg per kg of glucose per minute.

Assessment of Hydration Status It is much more difficult to clinically assess the status of hydration in infants than in the older children. Daily or more frequent weighings are mandatory. Infants under phototherapy and those with diarrhea or edema should be weighed more often. Monitoring the hematocrit and hemoglobin is generally not an adequate indicator of hydration since infants have an increased incidence of hemolysis and blood loss through other routes. True dehydration implies an increase in the osmolality of the extracellular fluid space of which plasma provides a modified sample. In most circumstances, the plasma sodium level represents half of the plasma osmolality. Since the plasma osmolality depends on the total number of dissolved particles in the plasma, the relationship between the sodium level and osmolality is not always fixed. The relationship between these two parameters is especially inconsistent in the premature infant. In early life, the concentrating and diluting mechanisms which are essential for osmolality homeostasis are poorly developed. 14• 36 The immature glomeruli provide only limited sodium and urea clearance. Since the infant is in an anabolic stage of growth at this time of development, substances which would otherwise be presented to the kidney for excretion are incorporated into the developing body. The disturbance of plasma osmolality equilibrium is reduced to a minimum.

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Table 1. Water Requirements in Premature Infants* WATER REQUIRED (ML PER KG PER

<1500 Losses Basal insensible water loss Urinet Stool TOTAL

Increment for phototherapy

24

HR)

1500 to 2500

GM

30 to 60

GM

15 to 35 50 to 100 5 to 10

85 to 170 20

70 to 145

To these totals must be added increments for increased metabolic rate with cold stress, activity, or illness. The final totals are often in the following ranges: < 1000 gm "" 200 ml per kg per 24 hr 1000 to 1500 gm 175 to 200 ml per kg per 24 hr 1500 to 2500 gm 150 to 180 ml per kg per 24 hr "From Roy, R. N., and Sinclair, J. C.: Hydration of the low-birth weight infant. CHn. Perinatol., 2 :400, 1975, with-permission. t Urinary water loss is calculated from urine osmolality of 75 to 300 mOsm per kg of water.

Some investigators have demonstrated rapid weight gain in infants receiving formulas with high protein content. Much of this weight gain was not due, however, to an increase in body mass, but in fact was secondary to fluid retention. The most effective way of measuring the status of hydration is by measuring the total body water content with deuterium or antipyrine and measuring the extracellular fluid volume with bromide. However, these methods are used only for investigative purposes at this time. Summary Most of the studies of water and electrolyte balance have been performed on full term infants; few studies have been done on premature infants weighing less than 1250 gm. When balancing the hydration and electrolyte status of all infants, it is most important to relate the treat-

Table 2.

Rates of Fluid Administration" BIRTH WEIGHT

1000 1st day 2nd day 3rd day on

GM

100 to 120 140 to 160 180 to 200+

1000 to 1500 80 to 100 110 to 130 140 to 180

GM

1500 to 2500

GM

60 to 80 90 to 110 120 to 160

"From Roy, R. N., and Sinclair, J. C.: Hydration of the low-birth weight infant. Clin. Perinatol., 2 :407,1975, with permission. Volumes quoted (ml per kg per 24 hr) are total parenteral plus gastrointestinal. These fluids are suggested as a starting point and should be adjusted for different disease states.

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545

ment regimen to the infant's gestational age and weight, and to make appropriate adjustments for various environmental conditions which affect water and salt requirements, such as phototherapy, type of warmer, and humidity.

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28. Olbing, H., Blaufex, M. D., Aschinberg, L. C., et al.: Postnatal changes in renal glomerular blood flow distribution in puppies. J. Clin. Invest., 52:2885, 1973. 29. O'Brien, D., Hansen, J. D. L., and Smith, C. A.: Effect of supersaturated atmospheres on insensible water loss in the newborn infant. Pediatrics, 13: 126, 1954. 30. Oh, W., and Karecki, H.: Phototherapy and insensible water loss in the newborn infant. Am. J. Dis. Child., 124:230, 1972. 31. Oh, W., Yao, A. C., Hanson, J. S., et al.: Peripheral circulating response to phototherapy in newborn infants. Acta Paediat. Scand., 62:49, 1973. 32. Pritchard, J. A.: Deglutition by normal and anencephalic fetuses. Obstet. Gynecol. 25 :289, 1965. 33. Pynnonen, A. L., Kouvailanen, K., and Jaykka, S.: Time of the first urination in male and female newborns. Acta. Paediat. Scand., 61 :303, 1972. 34. Roy, R. N., and Sinclair, J. C.: Hydration of the low-birth weight infant. Clin. Perinatol., 2:407, 1975. 35. Rubaltelli, F. F., and Largajolli, G.: Effect of light exposure on gut transit time in jaundiced newborns. Acta Paediat. Scand., 62:146, 1973. 36. Sherry, S. N., and Kramer, I.: The time of passage of the first stool and first urine by the newborn infant. J. Pediat., 46:158,1955. 37. Siegel, S. R., Fisher, D. A., and Oh, W.: Serum aldosterone concentration related to sodium balance in the newborn infant. Pediatrics, 53:410, 1974. 38. Silverman, W. A., Agate, F. J., and Fertig, J. W.: A sequential trial of the nonthermal effect of atmospheric humidity on survival of newborn infants of low birth weight. Pediatrics, 31 :719, 1963. 39. Silverman, W. A., and Blanc, W. A.: The effect of humidity on survival of newly born premature infants. Pediatrics, 20:477, 1957. 40. Soderstrom, E., and Dubois, E.: Water elimination through skin and respiratory passages in health and disease. Arch. Intern. Med., 19:931, 1971. 41. Spitzer, A., and Brandis, M.: Functional and morphologic maturation of the superficial nephrons. Relationship to total kidney function. J. Clin. Invest., 53:279, 1974. 42. Sulyok, E.: The relationship between electrolytes and acid-base balance in the premature infant dUring early postnatal life. BioI. Neonate, 17:227, 1971. 43. Sulyok, E., Jequier, E., and Prod'hom, L. S.: Respiratory contributions on the thermal balance of the newborn infant under various ambient conditions. Pediatrics, 51 :641, 1973. 44. West, J. R., Smith, H. W., and Chasis, H.: Glomerular filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. J. Pediatr., 32:10,1948. 45. Williams, P. R., and Oh, W.: Effect of radiant warmer on insensible water loss in newbo.rn infants. Am. J. Dis. Child., 128:511, 1974. 46. Winters, R. W.: Maintenance fluid therapy. In Winters, R. W. (ed.): The Body Fluids in Pediatrics. Boston, Little, Brown and Co., 1973, p. 124. 47. Wladimiiroff, J. W., and Campbell, S.: Fetal urine production rates in normal and complicated pregnancy. Lancet, 1 :151,1974. 48. Wu, P. Y. K., and Hodgman, J. E.: Insensible water loss in preterm infants: Changes with postnatal development and nonionizing radiant energy. Pediatrics, 54:704, 1974. 49. Ziegler, E. E., and Femon, S. J.: Fluid intake, renal solute, load, and water balance in infancy. J. Pediat., 78:561, 1970. 50. Zeymuller, E., and Preining, 0.: The insensible water loss of the newborn infant. Acta Paediat. Scand. Suppl. 205, 1970. Department of Pediatrics University of Louisville School of Medicine Louisville, Kentucky 40201