0148-6071/90/1401-0053$02.00/0
JOURNAL O F PARENTERAL AND ENTERAL NUTRITION Copyright 0 1990 by the American Society for Parenteral and Enteral Nutrition
Vol. 14,No. 1
Printed in U.S.A.
Reliability of the Twenty-Four-Hour Nitrogen Balance in Parenterally Fed Newborn Infants MARJOLAIN PINEAULT, B. PHARM., URS MAAG,PH.D.,
AND
PHILLIPPE CHESSEX,M.D.
From the Service de Neonatologie, Centre de Recherche, H6pital Sainte-Justine, Department de Pediatrie, Department D'Informatique et de Recherche Operationnelle & Faculte de Pharmacie, Universite de Montreal, Montreal, Canada
ABSTRACT. The reliability of shorter nitrogen balance determinations was evaluated in order to facilitate the nutritional assessment of parenterally fed infants. The intraindividual dayto-day variations of nitrogen intake, excretion, and retention were analyzed in 23 parenterally fed newborn infants (birth weight: 785-2630 g). Nitrogen retentions measured over 3 con-
secutive days were highly correlated ( r = 0.90-0.96), and the reliability for a single 24-hr collection was estimated by rl = 0.93. Nitrogen balance data obtained over a 24-hr period are reliable for the purpose of clinical investigations, provided the nutrient intake is constant. (Journal of Parenteral and Enteral Nutrition 1453-55, 1990)
In clinical nutrition, the nitrogen balance is used as an index of protein metabolism. For a given population, there is a great variability in nitrogen retention data. The factors known to influence the apparent nitrogen accretion are: the level' and source' of amino acids intake, the level of energy intake,lV2 the clinical3 and nutritional4 conditions, g r o ~ t h and , ~ sampling procedures.6The relative importance of the nutritional factors has recently been r e p ~ r t e d . ~ However, ' the sampling technique is thought to be one of the most critical components of this variability.6 Three-day urine collections have been performed in a number of balance studies of orally and intravenously fed infants, in order to minimize day-to-day variability in nitrogen retention. But, the longer the balance study, the higher the rate of failure and drop-outs will be. To facilitate the nutritional assessment of parenterally fed infants, we evaluated the reliability of shorter balances. The aim of this retrospective analysis was to verify if nitrogen balance data obtained over a 24-hr period would be as reliable as a 72-hr balance.
Total parenteral nutrition was delivered through a peripheral line at a constant rate. For a given infant the nutrient intakes (amino acids, 2.5-3 g/kg/day; glucose, 5-17 g/kg/day; fat emulsion, 1-3 g/kg/day) were constant and determined from the measured volume of infusion received (precision: 3%). The nitrogen intake was calculated using 0.167 g of nitrogen for each infused gram of amino acids in Travasol 10% (Baxter, Canada). The nitrogen balance was determined by subtracting output (urine estimated cutaneous 10sses)~from intake. No fecal nitrogen was measured as the parenterally fed infants had no stools. A 3-day-timed urinary output was planned from day 4 through 6. Using a leak-proof adaptor and tubing,' urine was collected on ice, separately for every 24-hr balance and immediately frozen until analysis. The nitrogen content of the samples was measured by the Kjeldahl method. A statistical analysis of the intraindividual day-to-day variations of the nitrogen balance data was performed. In order to estimate the reliabilityg an ANOVA (repeated measures) was performed on the nitrogen retention variable.
'
+
METHODS
The nitrogen balance data of two previously published s t u d i e ~on ~ parenteral '~ nutrition were reviewed. Twentythree patients were selected on the basis that they completed a 3-day nitrogen balance, during a 6-day constant intravenous nutrient infusion. They were all appropriatefor-gestational-age newborn infants; the mean f. SD birth weight was 1514 f. 572 g (range: 785-2630 g) and gestational age was 32 k 3 week (range: 27-38 week). At the initiation of the nitrogen balance the weight was 1496 +- 610 g (range: 720-2695 g ) and postnatal age was 14 f. 5 days (range: 6-22 days).
RESULTS
Table I summarizes the 3-day nitrogen balance data for intake, urinary excretion, and retention. Results are presented for each day separately, as well as for the entire 3-day period. The means of these variables do not differ over the 3 days. Table I1 shows the individual results of 24-hr nitrogen retentions determined over 3 consecutive days. The standard deviations give a measure of the interindividual variations for each day of the study. The intraindividual analysis shows a high correlation between values of nitrogen retention obtained on days 1 and 2 ( r = 0.96), days 1 and 3 ( r = 0.90) and on days 2 and 3 ( r = 0.93). Although the mean of the differences in nitrogen retention between any two days (1us 2, 2 us 3, 1 us 3) is close to 0, individual absolute values of the
Received for publication, December 12, 1988. Accepted for publication, February 13, 1989. Reprint requests: Phillippe Chessex, MD, Centre de Recherche, H6pital Sainte-Justine, 3175 C6te Sainte-Catherine, Montr6al H3T IC5. Canada. 53
Downloaded from pen.sagepub.com at UNIV TORONTO on July 18, 2015
54
Vol. 14, No. 1
PINEAULT AND CHESSEX
TABLE I Nitrogen balance data from 23 parenterally fed low-birth weight infants receiving a constant nutrient intake Consecutive 24-hr periods
Intake (mg/kg/day) Urinary excretion (mg/kg/day) Balance (mg/kg/day) Retention (%)
1
2
3
3 Days combined
442 f 32 147 73 295 f 77 66.6 f 16.3
435 f 51 143 f 70 292 f 69 67.4 f 14.7
435 f 37 146 72 289 71 66.7 f 15.9
437 f 33 145 f 70 292 f 66 66.9 f 15.3
*
*
+
(xf SD, n = 23). TABLE I1 Twenty-four-hrnitrogen retention (%) data, collected over 3 consecutive days in 23 parenterally fed low-birth weight infants receiving a constant nutrient intake Days
1 2 3 4 5 6 7
a 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
x * SD
1
2
3
73.5 64.2 73.4 64.6 60.3 44.2 51.8 56.6 29.3 53.0 70.5 87.2 81.6 89.5 78.8 73.0 70.4 93.3 50.9 81.4 72.0 73.1 40.2 66.6 f 16.3
73.9 61.2 68.1 66.9 58.1 50.2 51.7 65.5 30.9 52.1 73.7 83.3 76.9 89.3 86.7 75.1 73.3 82.9 54.5 87.4 70.2 70.4 48.5 67.4 f 14.7
72.4 57.2 65.7 63.2 50.5 51.5 57.0 67.1 23.9 54.5 81.3 90.4 76.5 79.8 89.9 77.4 74.1 83.6 48.2 72.2 71.0 76.9 49.3 66.7 f 15.9
differences were below ll%, except in patient 20 (Table 11) in whom the largest difference reached 15.2%. The measure of reliability for a single observation is estimated by rl = 0.93; the reliability for the mean of the three observations is estimated by r3 = 0.97.
no detectable leaks during three consecutive 24-hr periods were used for this retrospective analysis. The first 3 days of the protocol were considered an adaptation phase to the regimen. It was felt that this period was required to attain an equilibrium before starting the nitrogen balance. The data from total body protein turnover studies in parenterally fed preterm infants demonstrate indeed that the plateau of urinary15 N urea enrichment was reached within 72 hr.2 The results of nitrogen excretions and retentions (Table I) do confirm that a steady state was reached, as no systematic differences were found between individual days of the balance. From the high correlations between the daily values of nitrogen retention, it follows that a measure obtained in a single 24-hr period is almost as reliable as the mean over three such periods. Indeed the reliability coefficient for a 24-hr balance remains almost as high as the one established for a 3-day period. Nitrogen balance data obtained over a 24-hr period are reliable under the conditions of clinical, nutritional, and environmental steady state. However, for the purpose of clinical investigations, shorter balance periods’’ might lack in precision because of diurnal variations in urea excretion.12 ACKNOWLEDGMENTS
This work was supported by the Medical Research Council of Canada (MA 8664) and by a grant-in-aid from Baxter Canada, Inc., of Mississauga, Ontario.
REFERENCES 1. Zlotkin SH, Bryan MH, Anderson GH: Intravenous nitrogen and
DISCUSSION
2.
The nitrogen balance of parenterally fed newborn infants as opposed to adults, has to be strongly positive to sustain an adequate growth rate? The nitrogen balance (290 mg/kg/day) reported in these infants is similar to the accepted goal represented by the third trimester fetal nitrogen accretion rate.’ The precision of urine output collections performed in newborn infants has been questioned when leakages are estimated by measuring the absorption of urine on preweighted diapers.” However, in the present balance studies7v8any evidence of a leak resulted in the rejection of that 24-hr sample. Therefore, only the collections with
3. 4. 5.
6.
energy intakes required to duplicate in utero nitrogen accretion in prematurely born human infants. J Pediatr 99:115-120, 1981 Duffy B, Gunn T, Collinge J, et al: The effect of varying protein quality and energy intake on the nitrogen metabolism of parenterally fed very low birth weight ( 4 6 0 0 g) infants. Pediatr Res 15:1040-1044,1981 O’Keefe SJD, Senoer PM, James WDT: “Catabolic” loss of body nitrogen in response to surgery. Lancet 21035-1039, 1974 Elwyn DH, Gump FE, Munro HN, et al: Changes in nitrogen balance of depleted patients with increasing infusions of glucose. Am J Clin Nutr 32:1597-1611, 1979 Pencharz PB, Steffee WP, Cochran W, et al: Protein metabolism in human neonates: Nitrogen-balance studies, estimated obligatory losses of nitrogen and whole-body turnover of nitrogen. Clin Sci 52:485-498,1977 Fomon SJ, Owen GM: Comment on metabolic balance studies as a method of estimating body composition of infants. With special consideration of nitrogen balance studies. Pediatrics 29:495-498,
Downloaded from pen.sagepub.com at UNIV TORONTO on July 18, 2015
JanuarylFebruary 1990
RELIABILITY OF NITROGEN BALANCE
1962 7. Chessex P, Zebiche H, Pineault M, et al: Effect of amino acid composition of parenteral solutions on nitrogen retention and metabolic response in very-low-birth-weight infants. J Pediatr 106111-117, 1985 8. Pineault M, Chessex P, Bisaillon S, et al: Total parenteral nutrition in the newborn: 1. Impact of the quality of infused energy on nitrogen metabolism. Am J Clin Nutr 47:298-304, 1988 9. Winer BJ: Statistical Principles in Experimental Design, 2nd ed.
55
Mc Craw-Hill, New York, 1971, pp 283-296 10. Cooke RJ,Werkman S, Watson D: Urine output measurement in premature infants. Pediatrics 83:116-118, 1989 11. Lopez AM, Wolfsdorf J , Raszynski A, et al:Estimation of nitrogen balance based on a 6-hour urine collection in infants. JPEN 10:517518,1986 12. Sorkness MS: The estimation of 24-hour urine urea nitrogen excretion from urine collections of shorter duration in continuously alimented patients. JPEN 8:300-301, 1984
Downloaded from pen.sagepub.com at UNIV TORONTO on July 18, 2015
JOURNAL O F PARENTERAL AND ENTERAL NUTRITION Copyright 0 1990 by the American Society for Parenteral and Enteral Nutrition
Vol. 14,No. 1
Printed in U.S.A.
Reliability of the Twenty-Four-Hour Nitrogen Balance in Parenterally Fed Newborn Infants MARJOLAIN PINEAULT, B. PHARM., URS MAAG,PH.D.,
AND
PHILLIPPE CHESSEX,M.D.
From the Service de Neonatologie, Centre de Recherche, H6pital Sainte-Justine, Department de Pediatrie, Department D'Informatique et de Recherche Operationnelle & Faculte de Pharmacie, Universite de Montreal, Montreal, Canada
ABSTRACT. The reliability of shorter nitrogen balance determinations was evaluated in order to facilitate the nutritional assessment of parenterally fed infants. The intraindividual dayto-day variations of nitrogen intake, excretion, and retention were analyzed in 23 parenterally fed newborn infants (birth weight: 785-2630 g). Nitrogen retentions measured over 3 con-
secutive days were highly correlated ( r = 0.90-0.96), and the reliability for a single 24-hr collection was estimated by rl = 0.93. Nitrogen balance data obtained over a 24-hr period are reliable for the purpose of clinical investigations, provided the nutrient intake is constant. (Journal of Parenteral and Enteral Nutrition 1453-55, 1990)
In clinical nutrition, the nitrogen balance is used as an index of protein metabolism. For a given population, there is a great variability in nitrogen retention data. The factors known to influence the apparent nitrogen accretion are: the level' and source' of amino acids intake, the level of energy intake,lV2 the clinical3 and nutritional4 conditions, g r o ~ t h and , ~ sampling procedures.6The relative importance of the nutritional factors has recently been r e p ~ r t e d . ~ However, ' the sampling technique is thought to be one of the most critical components of this variability.6 Three-day urine collections have been performed in a number of balance studies of orally and intravenously fed infants, in order to minimize day-to-day variability in nitrogen retention. But, the longer the balance study, the higher the rate of failure and drop-outs will be. To facilitate the nutritional assessment of parenterally fed infants, we evaluated the reliability of shorter balances. The aim of this retrospective analysis was to verify if nitrogen balance data obtained over a 24-hr period would be as reliable as a 72-hr balance.
Total parenteral nutrition was delivered through a peripheral line at a constant rate. For a given infant the nutrient intakes (amino acids, 2.5-3 g/kg/day; glucose, 5-17 g/kg/day; fat emulsion, 1-3 g/kg/day) were constant and determined from the measured volume of infusion received (precision: 3%). The nitrogen intake was calculated using 0.167 g of nitrogen for each infused gram of amino acids in Travasol 10% (Baxter, Canada). The nitrogen balance was determined by subtracting output (urine estimated cutaneous 10sses)~from intake. No fecal nitrogen was measured as the parenterally fed infants had no stools. A 3-day-timed urinary output was planned from day 4 through 6. Using a leak-proof adaptor and tubing,' urine was collected on ice, separately for every 24-hr balance and immediately frozen until analysis. The nitrogen content of the samples was measured by the Kjeldahl method. A statistical analysis of the intraindividual day-to-day variations of the nitrogen balance data was performed. In order to estimate the reliabilityg an ANOVA (repeated measures) was performed on the nitrogen retention variable.
'
+
METHODS
The nitrogen balance data of two previously published s t u d i e ~on ~ parenteral '~ nutrition were reviewed. Twentythree patients were selected on the basis that they completed a 3-day nitrogen balance, during a 6-day constant intravenous nutrient infusion. They were all appropriatefor-gestational-age newborn infants; the mean f. SD birth weight was 1514 f. 572 g (range: 785-2630 g) and gestational age was 32 k 3 week (range: 27-38 week). At the initiation of the nitrogen balance the weight was 1496 +- 610 g (range: 720-2695 g ) and postnatal age was 14 f. 5 days (range: 6-22 days).
RESULTS
Table I summarizes the 3-day nitrogen balance data for intake, urinary excretion, and retention. Results are presented for each day separately, as well as for the entire 3-day period. The means of these variables do not differ over the 3 days. Table I1 shows the individual results of 24-hr nitrogen retentions determined over 3 consecutive days. The standard deviations give a measure of the interindividual variations for each day of the study. The intraindividual analysis shows a high correlation between values of nitrogen retention obtained on days 1 and 2 ( r = 0.96), days 1 and 3 ( r = 0.90) and on days 2 and 3 ( r = 0.93). Although the mean of the differences in nitrogen retention between any two days (1us 2, 2 us 3, 1 us 3) is close to 0, individual absolute values of the
Received for publication, December 12, 1988. Accepted for publication, February 13, 1989. Reprint requests: Phillippe Chessex, MD, Centre de Recherche, H6pital Sainte-Justine, 3175 C6te Sainte-Catherine, Montr6al H3T IC5. Canada. 53
Downloaded from pen.sagepub.com at UNIV TORONTO on July 18, 2015
54
Vol. 14, No. 1
PINEAULT AND CHESSEX
TABLE I Nitrogen balance data from 23 parenterally fed low-birth weight infants receiving a constant nutrient intake Consecutive 24-hr periods
Intake (mg/kg/day) Urinary excretion (mg/kg/day) Balance (mg/kg/day) Retention (%)
1
2
3
3 Days combined
442 f 32 147 73 295 f 77 66.6 f 16.3
435 f 51 143 f 70 292 f 69 67.4 f 14.7
435 f 37 146 72 289 71 66.7 f 15.9
437 f 33 145 f 70 292 f 66 66.9 f 15.3
*
*
+
(xf SD, n = 23). TABLE I1 Twenty-four-hrnitrogen retention (%) data, collected over 3 consecutive days in 23 parenterally fed low-birth weight infants receiving a constant nutrient intake Days
1 2 3 4 5 6 7
a 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
x * SD
1
2
3
73.5 64.2 73.4 64.6 60.3 44.2 51.8 56.6 29.3 53.0 70.5 87.2 81.6 89.5 78.8 73.0 70.4 93.3 50.9 81.4 72.0 73.1 40.2 66.6 f 16.3
73.9 61.2 68.1 66.9 58.1 50.2 51.7 65.5 30.9 52.1 73.7 83.3 76.9 89.3 86.7 75.1 73.3 82.9 54.5 87.4 70.2 70.4 48.5 67.4 f 14.7
72.4 57.2 65.7 63.2 50.5 51.5 57.0 67.1 23.9 54.5 81.3 90.4 76.5 79.8 89.9 77.4 74.1 83.6 48.2 72.2 71.0 76.9 49.3 66.7 f 15.9
differences were below ll%, except in patient 20 (Table 11) in whom the largest difference reached 15.2%. The measure of reliability for a single observation is estimated by rl = 0.93; the reliability for the mean of the three observations is estimated by r3 = 0.97.
no detectable leaks during three consecutive 24-hr periods were used for this retrospective analysis. The first 3 days of the protocol were considered an adaptation phase to the regimen. It was felt that this period was required to attain an equilibrium before starting the nitrogen balance. The data from total body protein turnover studies in parenterally fed preterm infants demonstrate indeed that the plateau of urinary15 N urea enrichment was reached within 72 hr.2 The results of nitrogen excretions and retentions (Table I) do confirm that a steady state was reached, as no systematic differences were found between individual days of the balance. From the high correlations between the daily values of nitrogen retention, it follows that a measure obtained in a single 24-hr period is almost as reliable as the mean over three such periods. Indeed the reliability coefficient for a 24-hr balance remains almost as high as the one established for a 3-day period. Nitrogen balance data obtained over a 24-hr period are reliable under the conditions of clinical, nutritional, and environmental steady state. However, for the purpose of clinical investigations, shorter balance periods’’ might lack in precision because of diurnal variations in urea excretion.12 ACKNOWLEDGMENTS
This work was supported by the Medical Research Council of Canada (MA 8664) and by a grant-in-aid from Baxter Canada, Inc., of Mississauga, Ontario.
REFERENCES 1. Zlotkin SH, Bryan MH, Anderson GH: Intravenous nitrogen and
DISCUSSION
2.
The nitrogen balance of parenterally fed newborn infants as opposed to adults, has to be strongly positive to sustain an adequate growth rate? The nitrogen balance (290 mg/kg/day) reported in these infants is similar to the accepted goal represented by the third trimester fetal nitrogen accretion rate.’ The precision of urine output collections performed in newborn infants has been questioned when leakages are estimated by measuring the absorption of urine on preweighted diapers.” However, in the present balance studies7v8any evidence of a leak resulted in the rejection of that 24-hr sample. Therefore, only the collections with
3. 4. 5.
6.
energy intakes required to duplicate in utero nitrogen accretion in prematurely born human infants. J Pediatr 99:115-120, 1981 Duffy B, Gunn T, Collinge J, et al: The effect of varying protein quality and energy intake on the nitrogen metabolism of parenterally fed very low birth weight ( 4 6 0 0 g) infants. Pediatr Res 15:1040-1044,1981 O’Keefe SJD, Senoer PM, James WDT: “Catabolic” loss of body nitrogen in response to surgery. Lancet 21035-1039, 1974 Elwyn DH, Gump FE, Munro HN, et al: Changes in nitrogen balance of depleted patients with increasing infusions of glucose. Am J Clin Nutr 32:1597-1611, 1979 Pencharz PB, Steffee WP, Cochran W, et al: Protein metabolism in human neonates: Nitrogen-balance studies, estimated obligatory losses of nitrogen and whole-body turnover of nitrogen. Clin Sci 52:485-498,1977 Fomon SJ, Owen GM: Comment on metabolic balance studies as a method of estimating body composition of infants. With special consideration of nitrogen balance studies. Pediatrics 29:495-498,
Downloaded from pen.sagepub.com at UNIV TORONTO on July 18, 2015
JanuarylFebruary 1990
RELIABILITY OF NITROGEN BALANCE
1962 7. Chessex P, Zebiche H, Pineault M, et al: Effect of amino acid composition of parenteral solutions on nitrogen retention and metabolic response in very-low-birth-weight infants. J Pediatr 106111-117, 1985 8. Pineault M, Chessex P, Bisaillon S, et al: Total parenteral nutrition in the newborn: 1. Impact of the quality of infused energy on nitrogen metabolism. Am J Clin Nutr 47:298-304, 1988 9. Winer BJ: Statistical Principles in Experimental Design, 2nd ed.
55
Mc Craw-Hill, New York, 1971, pp 283-296 10. Cooke RJ,Werkman S, Watson D: Urine output measurement in premature infants. Pediatrics 83:116-118, 1989 11. Lopez AM, Wolfsdorf J , Raszynski A, et al:Estimation of nitrogen balance based on a 6-hour urine collection in infants. JPEN 10:517518,1986 12. Sorkness MS: The estimation of 24-hour urine urea nitrogen excretion from urine collections of shorter duration in continuously alimented patients. JPEN 8:300-301, 1984
Downloaded from pen.sagepub.com at UNIV TORONTO on July 18, 2015
