(Submitted Sept. 13, 1983: accepted for publication February 3, 1964.)
Supported by research grant (AM-01351) from the National Institutes of Health, Public Health
Serv-ice, Bethesda, Maryland.
ADDRESS: Department of Pediatrics, University Hospital, Columbia, Missouri.
PEDIATRICS, June 1964
SERUM
MAGNESIUM
LEVELS
1N THE
NEWBORN
969
Constantine S. Anast, M.D.
Department of Pedkitrics, University of Missouri School of Medicine, Columbia, Mlssouri
K
NOWLEDGE of magnesium has laggedbehind that of other electrolytes
largely due to difficulties in methodology. However, interest in magnesium metabolism
is indicated by the increasing number of
articles on the subject that have appeared
in the recent literature. Low serum
mag-nesium levels have been observed in states of malnutrition with loss of body fluids such as may be found in postoperative patients
with nasogastric suction who are being
maintained on magnesium-free parenteral
fluids. Low serum magnesium levels have
also been found in patients with hyper- and
hypoparathvroidism, alcoholism with
de-lirium tremens, hyperaldosteronism, and
diabetic acidosis. In renal disease the serum
magnesium levels may either be elevated or
depressed, hypermagnesemia being found
in the presence of significantly depressed glomerular filtration rates. In some patients
low levels of magnesium have been
associ-ated with tetany, generalized convulsions,
athetoid motion of the extremities, and
marked reaction to mechanical and auditory stimulation. The mental status varies from complete lucidity to semi-coma. Increased neuromuscular irritability with convulsions is known to occur in the
magnesium-dc-ficient animal.
Similarities exist between calcium and
magnesium metabolism. Both are divalent
ions and a decrease in the serum level of
either is associated with an increase in
neuromuscular irritability. Phosphate
infu-sion in dogs results in decreased serum
levels of calcium and magnesium.1 Both are
incompletely absorbed from the
gastroin-testinal tract and bone is the chief reservoir
for each in the body. Although there are
several reported studies of serum calcium
levels in the newborn infant, there are very limited data concerning serum magnesium
concentrations in this age group. The
pur-pose of the present study was to carry out
serial determinations of serum magnesium levels in the newborn period in an effort to:
(
1) establish the normal values in this age group; (2) compare the values found innew-born infants with those of older children
and adults; and
(
3) compare the values inbreast-fed and artificially fed newborn
in-fants.
CASE MATERIAL
A study was made of 72 normal, full-term infants who were the products of
uncompli-cated pregnancies and deliveries.
Thirty-four of the infants were breast fed and 38
received evaporated milk
(
13 oz ofevapo-rated milk with 400 U. Vit. D, 24 oz of
water, and 3 tablespoons of Karo syrup).
Milk feedings were started after 24 hours of
age and no supplemental vitamins were
offered. Birth weights of the infants ranged from 2,500 gm to 4,250 gm.
Sixty-six older children, ages 2 months to
16 years, and 47 adults were also studied.
The adults were all normal hospital
per-sonnel. The children were either normal or
admitted to the hospital for elective surgical
procedures. In no instance was there any
history or evidence of metabolic disease,
fluid and electrolyte problems, or convulsive disorders.
METHOD OF STUDY
Samples of blood were collected from the heel of the infants during the first 5 days of life and from the finger tips of the older
children and adults in Hinton capillary
970
TABLE I
SERUM MAGNESIUM LEVELS
Newborn Infants Determi-. nations (no.) Mean+S.D. (mg/100 ml) Range Day I Day 2 DayS Day4 Day 5 Total5days Cordblood
Adults and older children 56 56 55 49 22 238 41 111
1 .94 ± .26
1 .87 ± .27
1.95±.24
1.91±27
2 .01 ± .28
1.92±27 1.89±26 1.96±24 1.40-2.90 1.36-2.90 1.41-2.59 1.36-2.62 1 .49-2.73 1.36-2.90 1.43-2.45 1.20-2.58
the morning midway between feedings and
the serum samples were stored in a freezer. In most cases, a minimum of three samples
from each infant was analyzed, for a total
of 238 determinations. In 41 cases, cord
blood was also examined.
Magnesium determinations were done by
a modification of the Titan yellow method
of Orange and Rhine.2 The reaction
con-sists of the combining of magnesium
hy-droxide with the dye Titan yellow in the
presence of the dispersing agent polyvinyl alcohol. The magnesium hydroxide-Titan
yellow lake results in a pink color, the
in-tensity of which is measured
spectrophoto-metrically. The method was modified to
de-termine magnesium concentrations in 0.2
ml of serum.
The precision of the method was tested
by making a total of 20 analyses of samples
of the same serum on five different days.
The values found ranged from 1.60 to 1.88
mg/100 ml with a mean of 1.70 and an aver-age deviation of plus or minus 0.07 mg/100 ml.
The validity of the method was further
tested by carrying out recovery studies.
Dc-terminations were performed on 0.2 ml of
sera to which varying quantities of
mag-nesium ranging from 50 to 300 micrograms
were added. The average recovery in 10
analyses was 100.64 ± 3.4% showing that
recovery is complete.
One limitation of the Titan yellow method
is the variation that may be found when the
same sample is analyzed on different days.
Therefore, in order to compare serial
sam-ples more accurately all of the sera from a
given infant were analyzed on the same day
in the same run. Included with each run
were one or two samples obtained from
older children and adults. This allowed for
more accurate comparison of the newborn
sera with that of the control group.
In a previous study we found strikingly
false low serum magnesium levels in
new-born infants receiving intravenous calcium gluconate. In no case in the present study were any of the subjects receiving calcium gluconate or any other medication.
RESULTS
The mean value of 238 determinations of
serum magnesium levels during the first 5
days of life was 1.92 mg/100 ml with a
range of 1.36 to 2.90 mg/100 ml. The mean
value, the standard deviation, and the range
for this group as well as for 41 cord bloods
and for 111 older children and adults are
listed in Table I. No statistically significant
difference was found among the mean
values of the three groups. Neither was any
significant difference found when the
con-trol group was broken down by age to
groups of less than one year, 1 to 16 years
and 16 to 35 years.
The values determined for each of the
first 5 days of life also are listed in Table I.
Differences in mean values between any of
the days were not statistically significant nor were any significant differences found when the values of each day were compared
with the mean value of older children and
adults or the mean value of the cord bloods.
No differences were found that could be
related to the birth weight, sex, or race of the infant.
In Table II the magnesium levels have
been tabulated according to the type of
feeding (breast or evaporated milk) and the
age of the infant in days. In addition the
5-day mean for each feeding schedule is
Day 1 Day 2 Day 3 Day 4 Day 5 Total
Evaporated milk
Mean±S.D 1.96±26 1.87±2.5 1.88±25 1.85±24 1.95±23 1.89±25
Range 1.62-2.90 1.36-2.32 1.41-2.51 1.36-2.32 1.49-2.27 1.36-2.90
Number (27) (32) (29) (30) (13) (131)
Breast milk
Mean±S.D. 1.92±26 1.88±31 2.03±21 2.01±27 2.11±34 1.97±.28
Range 1.40-2.59 1.44-2.90 1.67-2.59 1.56-2.62 1.72-2.73 1.40-2.90
Number (29) (24) (26) (19) (9) (107)
pvalue <0.60 <0.90 <0.02 <0.05 <0.20 <0.02
2 3 4 I 2 3 4
DAYS OF LIFE DAYS OF LIFE
Fic. 1. Serum magnesium levels on each of the
first 4 days of life in 8 breast-fed and 10
evapo-rated-milk-fed infants. TABLE II
SERUM MAGNESIUM LEVELS (mg/100 ml) ACCORDING TO TYPE OF FEEDING
of the evaporated-milk-fed infants were
found to be lower than those of the breast-fed infants on days 3, 4, and 5. The differ-ences on days 3 and 4 are significant at the 98 and 95% confidence limits respectively. The lack of statistical significance on day 5
may reflect the smaller number of determi-nations for this day. The smaller number of
determinations on day 5 is a result of the
routine discharge of many healthy infants from our nursery before this day.
Eight of the breast-fed infants and 10 of the evaporated-milk-fed infants had serum
magnesium levels measured on each of the
first 4 days of life. Plotting these results
(
Fig. 1) allows a comparison of values for the same infants on each of the first 4 days.A tendency for increasing values for the
breast-fed infants and decreasing values for the evaporated-milk-fed infants after day 2
is graphically demonstrated. This group
in-eludes the last 12 babies studied in which there were 6 breast-fed and 6
evaporated-milk-fed infants. Each breast-fed infant
was paired with an evaporated-milk-fed
in-fant who was born at approximately the
same time (within a week). All of the sera
collected from each pair were analyzed on
the same day in the same run. In addition a
reference standard of magnesium was
anal-yzed in each of the 6 paired runs. The
results for the standard reference samples varied from 1 .90 to 2.04 mg/100 ml during
the study of the 6 pairs. Increasing serum
magnesium levels on days 3 and 4 as
com-pared to day 1 were found in 5 of these 6
breast-fed infants while decreasing levels were found in 5 of the 6 corresponding
evaporated-milk-fed infants. The serum
magnesium levels of the 2 groups on day 1
were comparable. In 2 pairs the level was
higher in the breast-fed infant, in 2 pairs it was higher in the infants fed evaporated
milk, and in 2 pairs there was no
appreci-able difference in the initial serum
mag-nesium concentration.
Further analysis of serum magnesium
levels as related to type of feeding is found
in Table III. The number of infants in
which there was a rise or fall in serum
mag-nesium concentrations of at least 0.1 mg/
100 ml on day 3 and on day 4 (day 5 not
included because of small number of
de-terminations) when compared to day 1 in
2.6 2.5
\ 2.2
2I
2.0
‘.9
TABLE III
INCREASE OR DECREASE IN SERUM MAGNESIUM ON DAYS 3 AND 4 AS COMPARED TO LEVEL ON DAY 1 IN
THE SAME INFANT ACCORDING TO TYPE OF FEEDING
TABLE IV
SIncluded infants up to 24 months of age. Feeding Increase Decrease
No Change (<0.1 mgI 100 ml) Breast Evaporated milk Breast Evaporated milk Day 3 11 3 S 9 X2=7.82 p=O.O2 Day 4 8 2 S 9 X2=6.6 p<O.O5 7 9 5 6
the same infant is listed according to the
type of feeding. Also listed are the number of intervals during which the difference
from day 1 was less than 0.1 mg/100 ml.
The tendency for increasing values in the
breast-fed infants and decreasing values in
evaporated-milk-fed infants is again
demon-strated.
COMMENT
We believe that the major contribution of the present study is that it presents nor-mal values for serum magnesium concentra-lions during the first 5 days of life. The
re-suits represent analysis of 238 serum
sam-pies from this age group. The tendency for
increasing levels in breast-fed infants and decreasing levels in evaporated-milk-fed in-fants in this study is of interest. In some
in-fants the changes were small. Because of
this and because of the limitations of the
Titan yellow method it is probably best to
view the differences in formula and breast-fed infants with some reservation until they are confirmed.
Previously reported studies of serum
mag-nesium levels in the newborn period are
summarized in Table IV. When available,
SUMMARY OF THE LITERATURE OF SERUM MAGNESIUM LEVELS IN TILE NEWBORN PERIOD
(
The mean in mg/i#{174} ml, the range, and the number of determinations are listed for each group)Autker Method 3Iater,at Cord First Week 1-12 Jfo Older Children Adults
Bogert&Plass’ PhosphatePpt. 2.0 1.4-3.2 (23) 2.1 1.4-3.4 (23) 2.3 1.9-2.7 (8)
Salmi’ 2.68 Art. 2.76 2.98 1 .88
1.7-3.5 (32) 1.5-4.0 (8) Yen. 2.74 2.3-4.0 (14) 1.3-2.3 (20) 1.7-2.9 (10) 1.5-4.1 (37)
Orange & Rhine2 Titan yellow i.18
1.6-2.3
(12)
2.16 1.9-2.4
(12)
2.27 1.9-2.5
(45)
Breton eld.6 Titan yellow 3.26
2.16-4.0
2. 57’
1.8-3.2
2.57
2.0-3.6
Mays&Keele’ EDTA 1.68
(23) I.3 (18) 1.63 (193) 1.64 (15)
Marioni at al. Phosphate Ppt. I.80 1.84
1.20-2.20
(30)
1.25-2.35
(31)
Present series Titan yellow 1.89
1.28-2.45
(41)
1.92
1.36-2.90
(238)
2.04
1.80-2.40
(1 1)
i.94
1.51-2.58
(52)
.98
1.36-2.36
973
the values determined by the authors for
older children and adults also are listed. It can be seen that our values are of the same general magnitude as those found by Bogert and Plass,4 Orange and Rhine,2 and Marioni
et al.s Differences from results found by
other authors5’ ‘ may be due in large part
to methodology and indicate the importance of each laboratory establishing its own nor-ma! values.
Of prime interest is the comparison of
values for different age groups within each author’s series. No significant difference was
found between cord blood and maternal
serum magnesium concentrations in the
three studies where both were
deter-45 8 J addition, Salmi did not find
any difference in magnesium levels in blood
obtained from the umbilical artery as
com-pared to the umbilical vein. Both Salmi and
Breton et al. found cord blood levels to
be higher than those of older children and
adults. The number of determinations in
Breton’s study is not listed and therefore
the significance of his findings is difficult to evaluate. The studies of Bogart and Piass4
and of Mays and Kcele are in agreement
with ours in that no significant difference
was found between magnesium levels in
cord blood and in the blood of older
chil-dren and adults.
It can be seen from Table IV that only a
relatively few determinations have
previ-ously been performed in infants during the
first week of life. In neither of the two
stud-ies was the type of infant
feed-ing published. Of interest is Salmi’s study in
which the serum magnesium levels found
during the first week of life tended to be
higher than the level of the cord blood of
the same infant. This tendency of rising
levels during the first week is in keeping with our findings in breast-fed infants.
If the differences reported here in mag-nesium levels of the breast-fed and formula-fed infants are confirmed by additional data
they may be explainable by differences in
the ratios of dietary phosphorus and
mag-nesium. The magnesium concentration of
cow’s milk is .013% as compared to .004%
for human milk.9 However, the ratio of
phosphorus to magnesium in human milk
is 4 to 1 and in cow’s milk 7.6 to 1. Gardner
et al.b0 demonstrated a rise in serum
in-organic phosphate and a fall in serum
cal-cium and magnesium in a newborn infant
receiving a cow’s milk formula. When
cal-cium was added to the formula they
ob-served a diminution in the serum inorganic
phosphorus level with the return of the
ionized calcium and total magnesium to
normal levels.
Bruck and Weintraub,11 Graham et al.,12 and Gittleman and Pincusl3 have all demon-strated that the intake of cow’s milk is
fre-quently associated with a rise in serum
phosphorus concentration in the newborn
infant, while in breast-fed infants the level
tends usually not to vary or to decrease
somewhat. The serum phosphorus
concen-tration in a number of evaporated-milk-fed infants was seen to approximate the values
for breast-fed infants by the second week of
life.12 In the study of Gittleman and Pincus, infants fed evaporated milk showed a
tend-ency to hypocalcemia while the calcium
level in the breast-fed infants did not
de-crease. Neither Bruck and Weintraub nor
Graham et al. were able to demonstrate any
definite correlation between serum calcium and phosphorus levels in individual infants.
However, Bruck and Weintraub studying
premature and full-term infants found that
a falling calcium level was usually
associ-ated with a rising phosphorus level.
Bak-win14 observed a fall in serum calcium
fol-lowing the oral loading of phosphate to
newborn infants. Sulvesen, Hastings, and
Mclntoshl fed neutral phosphate to dogs
by stomach tube in daily amounts such that
the phosphate intake closely approximated the intake of formula-fed infants when cal-culated on the basis of surface area. With
the ingestion of phosphate the dogs showed an elevation of serum inorganic phosphorus
and a reduction in serum magnesium and
calcium.
differences in serum magnesium levels in
breast-fed and evaporated-milk-fed infants is related to the phosphate content of cow’s
milk as compared to human milk. The rising
serum phosphorus level in infants fed cow’s
milk may account for the tendency
demon-strated in the study for lower serum
mag-nesium levels in this group as compared to
breast-fed infants during the third, fourth, and fifth day of life.
Consideration must also be given to the
serum proteins. Approximately 35% of the
serum magnesium is bound to protein. It is
possible that variations in protein levels in
the two groups may account for the
ob-served differences in serum magnesium
levels. This study will be extended to
de-termine serum magnesium, phosphate, and
protein levels simultaneously in the
new-born period.
SUMMARY
Two hundred and thirty-eight
determina-tions of serum magnesium levels during the
first 4 days of life were carried out on 78 infants. No statistically significant
differ-ences were found when these values were
compared to those determined in 111 older
children and adults. Differences in mean
values between any of the first 5 days were
not statistically significant nor were any
significant differences found when the
values of each day were compared with
the mean value of older children and adults
or the mean value of the cord bloods. The
mean values on days 3, 4, and 5 were higher
in breast-fed infants than in infants fed
evaporated milk. Higher values in
breast-fed infants and lower values in evaporated-milk-fed infants on days 3 and 4 when com.
pared to day 1 in the same infant were
found in a significant number of cases. The possibility that the observed differences in these two groups of infants may be related to the difference in phosphate to magnesium
ratio in cow’s milk as compared to human
milk is discussed. Further investigation of
this problem is needed before definite con-clusions can be drawn.
Acknowledgment
The technical assistance of Mrs. Joanne Bunge and Mrs. Marsha Schweiss is gratefully acknowl-edged.
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J. Biol. Chem., 60:311, 1924.
2. Orange, M., and Rhine, H. C. :
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Chem., 56:297, 1951.
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1963.
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