The purpose of this study was to design the shortest suitable magnesium load test for infants up to six months of age. A 56-hour test was used to study cation and creatinine excretion before and after an intramuscular load of 0.49 mEq of magnesium/kg of body weight. No diurnal excretion pattern for magnesium was found, and most of the magnesium rejected by the kidney was excreted by neonates within 32 hours, and by infants from one to six months of age within 24 hours. The postload urinary magnesium value usually stabilized at a slightly higher level than the preload level. The mean plasma magnesium level increased about 0.65 mEq/liter one hour after the load, and at the end of the test was 0.25 mEq/liter higher than the initial value; abnormally low plasma values were normalized. Renal excretion of creatinine and potassium was not affected by the magnesium load, but the 24-hour postload excretion was higher than the 24-hour preload excretion of calcium for all patients, and of sodium for some full-term neonates. Because of slow excretion of magnesium and concomitant calcium loss, special precautions are required for testing and repletion of young infants to avoid magnesium overload and calcium depletion. A suitable test would have an eight-hour preload period, a load of 0.49 mEq of magnesium (0.12 ml of 50 per cent 2 .7H 4 MgSO O ) per kg of body weight, and a postload collection of 32 hours for neonates and 24 hours for infants from one to six months of age.
The
Magnesium
Load Test: I. A
Design for
Infants
NUMEROUS
recent reports of young infants associate a low serum magnesium value with a number of clinical findings, including low birth weight, peripheral edema, and neurological signs.1-5 Cockburn and associates2 have reported that an imbalance of serum calcium and magnesium accounts for convulsions in 0.7 per cent of infants in England. Because the symptoms of deficiency are often transient and the magnesium value often spontaneously reverts to normal within a few days,4 the true magnesium status of the infant is sometimes uncertain.
*
sity
Joan L. Caddell, M.D.*
a
Assistant Professor of Pediatrics, St. Louis UniverSchool of Medicine, St. Louis, Mo. 63104.
449
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TABLE L
Data from 56-Hour Parenteral Magnesium Load Tests: Six Premature Neonates (Each Collection Period Was Corrected to Eight Hours)
Several surveys of the plasma magnesium values in infants have been made,-9 but no other evaluation of they magnesium status was found. The serum magnesium value represents only 1 to 2 per cent of the magnesium in the- body and is not always a reliable guide to the magnesium status of the patient; it is helpful when low, but it may often be normal in a magnesium-depleted subject. The parenteral magnesium load test is a more accurate guide.5,1&dquo;,&dquo; A subject in magnesium balance will excrete a parenteral load of magnesium in the urine; a magnesium deficient subject will retain a high per cent of the load. The test has not been standardized. Harris and Wilkinson5 de-
signed
a
test
for young children, including a 24-hour pre-
neonates, which consisted of
load collection of urine, a parenteral load of 0.5 mEq of magnesium/kg of body weight, followed by a 24-hour postload collection. Caddell and associates,10 working with children about two years of age, found that a test foreshortened to an 8-hour preload and a 16-hour postload collection period was satisfactory. However, published data on renal excretion in the neonatal period&dquo; suggested that this test might not be applicable for very young infants. The purpose of this study was to design the shortest suitable magnesium load test for premature and full-term infants from the early neonatal period through the first six months of life. Studies were made of the diurnal pattern of excretion and the time required to excrete the parenteral mag-
TABLE 2. Data from 56-Hour Parenteral Magnesium Load ’Tesis: 11 Full-Terna Neonates (Each Collection Period Was C’orrected to Eight Hours)
450
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TABLE 3.
Data from 56-Hour Parenteral llfiagnesiurra Load Tests: (Each Collection Period
nesium load in premature and
fants.
mature
Five Premature Infants C3ver t?ne Month YYas Correeted to Eight Hours)
in-
;
Materials and Methods Parenteral magnesium load tests were conducted in 43 infants from birth to six months of age hospitalized for a variety of reasons,
including respiratory distress, jaun-
dice, neurological disturbances, and congenital defects. The patients were studied with the informed consent of a parent or guardian. Laboratory investigation. Preload plasma cations were determined in all patients, and plasma magnesium one to one and one-half hours after the load and at the end of the test in a representative group of patients. Blood was obtained by heel puncture and collected in heparinized capillary tubes. TABLE 4.
The 56-hour parenteral magnesium load test. Twenty-eight infants were studied for approximately 56 hours. Each test included seven urine collection periods of approximately eight hours, each one ending when the patient voided. Three were preload and four immediately followed the intramuscular load of magnesium, 0.12 ml of 50 per cent magnesium sulfate heptahydrate/kg, equal to 0.49 mEq of magnesium/kg of body weight. Collections of urine were made over ice, using urine collection bags. The seven collections were analyzed for magnesium, calcium, sodium, potassium, and creatinine. The percentage of the magnesium load retained was calculated from data from the preload period and the net excretion after the load. (Continued
l3ata frarrs 56-Hour Parenteral Magnesium Load (Each Collection Period
of are
on
Tests: Six Full-Term Infants Over One Month Was Corrected to Eight Hours)
page 457)
of Age
451
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Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
FIG. 1. Per cent retention of magnesium loads in 18 premature infants from birth to two weeks of age. The infants had a birth weight of mean 2.09 ±- to.12 (S.E.M.) kg and were studied at a mean of 6.5 ± I.41 (S.E.I~Z.) days of age. Data were grouped according to final retention values, i.e.: 0 to 40, 40 to 60, 60 to 85, and 85 to 100 per cent. Each point represents the mean and each vertical bar, the standard error of the mean for retention values calculated from collection periods corrected to exactly 8, 16, 24, and 32 hours. See text.
(Continued from page 451) Comparison was made between the preload and postload excretion of creatinine and of calcium, sodium, and potassium. The 40-hour parenteral magnesium load test. In this test, an eight-hour preload collection replaced the 24-hour preload collection. The test was otherwise as described above. Methods f’ar analysis. Plasma and urine were analyzed for cations on an atomic absorption
spectrophotometer, as previously described.&dquo; Creatinine determinations were made on a Technicon Autoanalyzer II, using the method described by the manufacturer. Results The results of the magnesium load tests are presented in Tables 1 through 4, which present data from 56-hour magnesium load tests in premature and mature infants from one to six months of age. Analysis of variance revealed no significant difference between the three eighthourly preload excretions of magnesium or
creatinine or in data obtained from the day (7 a.m.-7 p.m.) or night (7 p.m.-7 a.m.) collections. Most of the magnesium load was usually excreted during the first eight hours postload; in a few instances, neonates excreted more during the second postload period than during the first, which accounts for the irregularity noted in the plotted data from neonates in Figures 1 and 2. For these plots, excretion during each period was corrected to exactly eight hours to facilitate comparison of excretion at 8, 16, 24, and 32 hours, from which final retention values were calculated. Figure 3 reveals corresponding data for infants over one month of
age (Table 5). The slope of the lines in Figures 1 to 3 indicate that progressively longer collection times greatly influence patients who are actively excreting the load, but have little influence on the final values of patients who retain most of the load. Although renal clearance of magnesium was not complete at 32 hours in all patients, the rate of mag-
457
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FIG. 2. Per cent retention of magnesium loads in 19 full-term infants studied from birth to two weeks of age. The infants had a mean birth weight of 3.47 t 0.10 (S.E.M.) kg and were studied at a mean of6.5 ± 1.19(S.E.M.) days of age. See legend for
Figure 1.
nesium excretion was reasonably stable in neonates at 32 hours and in infants over one month of age at 24 hours. Approximate data could be obtained from shorter tests. Values for plasma magnesium, expressed as mean ± standard error of the mean (S.E.M.), increased from 1.57 ± 0.03 mEq/1 at the beginning of the test to 2.22 ~- 0.07 mEq/1 from one to one and one-half hours after the injection of magnesium in 15 infants. Values at 32 hours were determined in only seven infants; the plasma magnesium value at the end of the test was 1.75 ± 0.06 mEq/1, still significantly higher than the values at the beginning of the test in those infants, 1.55 -~ 0.03 mEq/1 (P < 0.025). Low initial values stabilized at a higher level and remained higher than the initial value. To learn whether or not the cations or ,
creatinine excreted during any single eighthour collection period was affected by the magnesium load, all values of these urinary components for the seven collection periods presented in Tables 1 to 4 were compared by t the analysis of variance. For both newborn and older prematurely born infants, the urinary calcium in any one collection was not significantly different from the calcium in any other collection; differences between the collections were, however, noted in full-term neonates (P < 0.01) and full-term infants over one month of age (P < 0.001), both of whom had significant increases immediately following the magnesium load. Next, comparison by Student’s t test was made between all grouped data in the 24 hours preload with the° data collected during the first 24 hours postload. The calcium excreted dur-
458
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
FIG. 3. Per cent retention of magnesium loads in 16 infants from one to six months of age. Seven were
prematurely born,
with a mean birth weight of 1.9 kg, and were studied at 9.2 ±2.09 (S.E.M.) weeks, and nine were full term, with a birth weight of 3.3’7 ± 0.20 (S.E.M.) kg, and were studied at 7.4 :!: 1.37 (S.E.M.) weeks. These data were combined because the individual plots were similar.
ing
the
postload periods
was
significantly
greater in the premature neonate (P < 0.05) and in the older premature infant (P
The
Magnesium
Load Test: I. A
Design for
Infants
NUMEROUS
recent reports of young infants associate a low serum magnesium value with a number of clinical findings, including low birth weight, peripheral edema, and neurological signs.1-5 Cockburn and associates2 have reported that an imbalance of serum calcium and magnesium accounts for convulsions in 0.7 per cent of infants in England. Because the symptoms of deficiency are often transient and the magnesium value often spontaneously reverts to normal within a few days,4 the true magnesium status of the infant is sometimes uncertain.
*
sity
Joan L. Caddell, M.D.*
a
Assistant Professor of Pediatrics, St. Louis UniverSchool of Medicine, St. Louis, Mo. 63104.
449
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
TABLE L
Data from 56-Hour Parenteral Magnesium Load Tests: Six Premature Neonates (Each Collection Period Was Corrected to Eight Hours)
Several surveys of the plasma magnesium values in infants have been made,-9 but no other evaluation of they magnesium status was found. The serum magnesium value represents only 1 to 2 per cent of the magnesium in the- body and is not always a reliable guide to the magnesium status of the patient; it is helpful when low, but it may often be normal in a magnesium-depleted subject. The parenteral magnesium load test is a more accurate guide.5,1&dquo;,&dquo; A subject in magnesium balance will excrete a parenteral load of magnesium in the urine; a magnesium deficient subject will retain a high per cent of the load. The test has not been standardized. Harris and Wilkinson5 de-
signed
a
test
for young children, including a 24-hour pre-
neonates, which consisted of
load collection of urine, a parenteral load of 0.5 mEq of magnesium/kg of body weight, followed by a 24-hour postload collection. Caddell and associates,10 working with children about two years of age, found that a test foreshortened to an 8-hour preload and a 16-hour postload collection period was satisfactory. However, published data on renal excretion in the neonatal period&dquo; suggested that this test might not be applicable for very young infants. The purpose of this study was to design the shortest suitable magnesium load test for premature and full-term infants from the early neonatal period through the first six months of life. Studies were made of the diurnal pattern of excretion and the time required to excrete the parenteral mag-
TABLE 2. Data from 56-Hour Parenteral Magnesium Load ’Tesis: 11 Full-Terna Neonates (Each Collection Period Was C’orrected to Eight Hours)
450
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
TABLE 3.
Data from 56-Hour Parenteral llfiagnesiurra Load Tests: (Each Collection Period
nesium load in premature and
fants.
mature
Five Premature Infants C3ver t?ne Month YYas Correeted to Eight Hours)
in-
;
Materials and Methods Parenteral magnesium load tests were conducted in 43 infants from birth to six months of age hospitalized for a variety of reasons,
including respiratory distress, jaun-
dice, neurological disturbances, and congenital defects. The patients were studied with the informed consent of a parent or guardian. Laboratory investigation. Preload plasma cations were determined in all patients, and plasma magnesium one to one and one-half hours after the load and at the end of the test in a representative group of patients. Blood was obtained by heel puncture and collected in heparinized capillary tubes. TABLE 4.
The 56-hour parenteral magnesium load test. Twenty-eight infants were studied for approximately 56 hours. Each test included seven urine collection periods of approximately eight hours, each one ending when the patient voided. Three were preload and four immediately followed the intramuscular load of magnesium, 0.12 ml of 50 per cent magnesium sulfate heptahydrate/kg, equal to 0.49 mEq of magnesium/kg of body weight. Collections of urine were made over ice, using urine collection bags. The seven collections were analyzed for magnesium, calcium, sodium, potassium, and creatinine. The percentage of the magnesium load retained was calculated from data from the preload period and the net excretion after the load. (Continued
l3ata frarrs 56-Hour Parenteral Magnesium Load (Each Collection Period
of are
on
Tests: Six Full-Term Infants Over One Month Was Corrected to Eight Hours)
page 457)
of Age
451
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
FIG. 1. Per cent retention of magnesium loads in 18 premature infants from birth to two weeks of age. The infants had a birth weight of mean 2.09 ±- to.12 (S.E.M.) kg and were studied at a mean of 6.5 ± I.41 (S.E.I~Z.) days of age. Data were grouped according to final retention values, i.e.: 0 to 40, 40 to 60, 60 to 85, and 85 to 100 per cent. Each point represents the mean and each vertical bar, the standard error of the mean for retention values calculated from collection periods corrected to exactly 8, 16, 24, and 32 hours. See text.
(Continued from page 451) Comparison was made between the preload and postload excretion of creatinine and of calcium, sodium, and potassium. The 40-hour parenteral magnesium load test. In this test, an eight-hour preload collection replaced the 24-hour preload collection. The test was otherwise as described above. Methods f’ar analysis. Plasma and urine were analyzed for cations on an atomic absorption
spectrophotometer, as previously described.&dquo; Creatinine determinations were made on a Technicon Autoanalyzer II, using the method described by the manufacturer. Results The results of the magnesium load tests are presented in Tables 1 through 4, which present data from 56-hour magnesium load tests in premature and mature infants from one to six months of age. Analysis of variance revealed no significant difference between the three eighthourly preload excretions of magnesium or
creatinine or in data obtained from the day (7 a.m.-7 p.m.) or night (7 p.m.-7 a.m.) collections. Most of the magnesium load was usually excreted during the first eight hours postload; in a few instances, neonates excreted more during the second postload period than during the first, which accounts for the irregularity noted in the plotted data from neonates in Figures 1 and 2. For these plots, excretion during each period was corrected to exactly eight hours to facilitate comparison of excretion at 8, 16, 24, and 32 hours, from which final retention values were calculated. Figure 3 reveals corresponding data for infants over one month of
age (Table 5). The slope of the lines in Figures 1 to 3 indicate that progressively longer collection times greatly influence patients who are actively excreting the load, but have little influence on the final values of patients who retain most of the load. Although renal clearance of magnesium was not complete at 32 hours in all patients, the rate of mag-
457
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
FIG. 2. Per cent retention of magnesium loads in 19 full-term infants studied from birth to two weeks of age. The infants had a mean birth weight of 3.47 t 0.10 (S.E.M.) kg and were studied at a mean of6.5 ± 1.19(S.E.M.) days of age. See legend for
Figure 1.
nesium excretion was reasonably stable in neonates at 32 hours and in infants over one month of age at 24 hours. Approximate data could be obtained from shorter tests. Values for plasma magnesium, expressed as mean ± standard error of the mean (S.E.M.), increased from 1.57 ± 0.03 mEq/1 at the beginning of the test to 2.22 ~- 0.07 mEq/1 from one to one and one-half hours after the injection of magnesium in 15 infants. Values at 32 hours were determined in only seven infants; the plasma magnesium value at the end of the test was 1.75 ± 0.06 mEq/1, still significantly higher than the values at the beginning of the test in those infants, 1.55 -~ 0.03 mEq/1 (P < 0.025). Low initial values stabilized at a higher level and remained higher than the initial value. To learn whether or not the cations or ,
creatinine excreted during any single eighthour collection period was affected by the magnesium load, all values of these urinary components for the seven collection periods presented in Tables 1 to 4 were compared by t the analysis of variance. For both newborn and older prematurely born infants, the urinary calcium in any one collection was not significantly different from the calcium in any other collection; differences between the collections were, however, noted in full-term neonates (P < 0.01) and full-term infants over one month of age (P < 0.001), both of whom had significant increases immediately following the magnesium load. Next, comparison by Student’s t test was made between all grouped data in the 24 hours preload with the° data collected during the first 24 hours postload. The calcium excreted dur-
458
Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on May 25, 2015
FIG. 3. Per cent retention of magnesium loads in 16 infants from one to six months of age. Seven were
prematurely born,
with a mean birth weight of 1.9 kg, and were studied at 9.2 ±2.09 (S.E.M.) weeks, and nine were full term, with a birth weight of 3.3’7 ± 0.20 (S.E.M.) kg, and were studied at 7.4 :!: 1.37 (S.E.M.) weeks. These data were combined because the individual plots were similar.
ing
the
postload periods
was
significantly
greater in the premature neonate (P < 0.05) and in the older premature infant (P
