Serial blood sugar determinations in normal newborn infants

S E R I A L BLOOD SUGAR D E T E R M I N A T I O N S IN NORMAL NEWBORN INFANTS JOHN

B. MCKITTaIC~,

M.D.

BOSTON, MASS. t t E inadequacy of existing information concerning the blood sugar

T values of normal newborn infants and the recent interest expressed in their carbohydrate metabolism 1-9 furnish the rationale of this report. The statistics are based on 1,586 blood sugar determinations made upon seventy-three normal newborn infants and upon one infant of a diabetic mother. P L A N OF S T U D Y

It was purposed to obtain data illustrating tile normal t r e n d of tile blood sugar during tile first two weeks of life. Clinic inpatients of the Boston Lying-in Hospital were used in this study. During the time that any infant was included in tile study, its blood sugar was determined at intervals of eight hollrs. Each blood sample was eollected at least three and one-half hours postprandial. The babies were studied in two groups. The first group dealt with thirty-four infants, each followed for a period of about seven days starting at birth. The second group was concerned with older infants, followed usually to the termination of the hospital stay of two weeks. Newborn infants were first fed at the regular feeding period whieh most nearly coincided with the end of their first 24-hour period. A f t e r this, they were gradually put onto a regular four-hour schedule. Only babies exhibiting a normal course during their hospital stay are included in the statistics. A temperature elevation which did not respond immediately to sterile water by mouth excluded the infant from the normal group. TECHNICAL

PROCEDURE

The micromethod of Folin, 9 as described in his last paper on this subject, was used. The method was modified ~ to simplify the preparation of the necessary solutions. From the Departments of Pediatrics and Obstetrics, Harvard Medical School, the Boston Lying-in Hospital. *I am indebted to Miss Hazel Hunt, Director of the Clinical Laboratory of the New England ]Deaconess Hospital, for the following suggestions as to technical procedure. l~,eagent number 1 (sulfate-tungstate solution) and reagent number 2 (sulpkuric acid) of the ~Ve*o l~ngZct~d Jour~a~ of Medicine ~~ method of Folin are combined into one solution: Dilute tungstic acid solution. This is freshly made each day as follows: In a 250 c.c. volumetric flask place approximately 100 c.c. of distilled water. Add 5 c.c. of I0 per cent sodium tungstate and 5 c.c. of ~ N sulphurie acid. Dilute t o volume with distilled water and mix, In the determination I0 c.c. of this ,dilute tungstic acid solution are used in place of 4 c,c. of reagent number 1 plus 1 e.c. of reagent number 2. In keeping with this, 4 c.c. of the clear supernatant fluid are used for each determination in place of 2 c.c. as described in Folin's paper. This procedure is the one followed at the ~krew England Deaconess Hospital in the clinic of Dr. Elliott P. Joslin. and

151

152

THE JOURNAL OF PEDIATRICS

T h e v a l u e o b t a i n e d is t h e " t o t a l r e d u c i n g s u b s t a n c e " of the blood a n d n o t t h e " t r u e b lo o d sugar."~~ 14 T h e s t a n d a r d glucose s o l u t i o n was checked at i n t e r v a l s by t h e c l i n i c a l l a b o r a t o r i e s of t h e N e w E n g l a n d Deaconess H o s p i t a l a n d t h e C h i l d r e n ' s a n d I n f a n t s ' H o s p i t a l of Bo st o n . A l l samples w e r e co l l ect ed a n d c a l c u l a t e d by t h e w r i t e r . C a l c u l a t i o n was done imm e d i a t e l y to m i n i m i z e e r r o r d u e to glycolysis. PRESENTATION

OF DATA

Charts 1 and 2 give the trend of the blood sugar values found during the first two weeks of life in the seventy-four normal infants studied. Tables I and II give the figures from which Charts 1 and 2 were constructed. The middle line on each chart shows the average figure; the upper line is the highest individual value obtained, and the lower line indicates the lowest value found for each 24-hour period. The average trend during the first three 24-hour periods is downward. From the third 24-hour period to the eighth 24-hour period the trend is gradually upward. During the second week of life the average is seen to remain between 80 rag. per cent and 90 rag. per cent. The low extreme values are seen to ascend gradually from birth and during the last six 2 4 - h o u r p e r i o d s lie above 60 mg. p e r cent. Th e h i g h e x t r e m e v a l u e s show a less c l e a r - c u t a l t e r a t i o n , b u t d u r i n g t h e last w e e k all f a l l below 120 rag. TABLE I DATA FOR FEMALES (CHART 1)

Maximum Average Minimum Number of determinations Number of infants

1 160 82 55 65 16

2 109 77 59 46

24-Hou~ PERIODS 3 4 5 6 7 8 9 10 11 12 13 14 99 99 111 120 105 114 110 100 118 105 114 100 73 78 79 79 81 85 86 85 85 89 85 84 54 52 54 43 54 67 62 65 58 63 62 70 46 52 63 81 93 56 58 42 43 35 34 15

16 16

18

23

29

33

22

26

17

21

13

19

9

1 2 3 4 5 6 7 8 9 10 11 12 13 113 102 93 109 109 111 110 109 113 109 105 109 103 76 72 67 74 77 81 83 83 87 87 85 86 86 45 45 45 43 53 56 54 55 66 67 59 69 68 71 55 54 57 76 92 104 66 68 54 g0 43 42

14 99 91 83 13

TABLE I I DATA FORM~LES (C~A~T 2)

24-~o~ PERIODS Maximum Average Minimum Number of determinations Number of infants

18

18 18

22

27

34

36 25

29

19

24 1 6

22

7

p e r cent. D u r i n g t h e first f o u r 2 4 - h o u r periods, v a l u e s f o r the, m a l e inf a n t s in t h i s g r o u p ( C h a r t 2) a r e a p p r e c i a b l y l o w e r t h a n c o r r e s p o n d i n g values for the female infants. C h a r t s 3, 4, 5, a n d 6 a r e e x a m p l e s of t h e v a r i o u s t y p e s of i n d i v i d u a l charts obtained.

M0 KITTRICK:

SERIAL BLOOD SUGAR DETERMINATIONS

153

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SERIAL BLOOD SUGAR DETER1VIIi'qATIONS

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156

THE JOURNAL OF PEDIATRICS TABLE I I I ~UMERIOAL DISTI~IBUTIO~ OF ~LOOD ~UGAR VALUES FO~ FEMALES DAYS

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1

2

3

40-44.9 ---45-49.9 50-54.9 1 1 55-59.9 3 2 60-64.9 4 7 65-69.9 8 7 70-74.9 9 8 75-79.9 18 11 80-84.9 8 3 85-89.9 5 4 90-94.9 2 1 95-99.9 2 1 100-104.9 __ 1 105-109.9 3 110-114.9 115-119.9 120-124.9 125-129.9 1 Totals *65 46 *Single value of 160

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58 46 52 63 81 9 3 56 Mg. per cent not included in table.

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TABLE I V ~N-UMEI~ICAL

DISTRIBUTION

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VALUES

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M~LES

DAYS •

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40-44.9 45-49.9

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50-54.9 55-59.9

60-64.9 65-69.9 70-74.9 75-79.9 80-84.9 85-89.9 90-94.9 95-99.9 ]00-104.9 105-109.9 110-114.9 115-119.9 Totals

5 6 15 12 6 17 1 1 2 2 2 1 71

Dr. Frederick

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C. I r v i n g o f t h e D e p a r t m e n t

vard Medical SehooI has granted

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of O b s t e t r i c s of the H a r -

permission to report

the serial blood

sugar values obtained from the infant of a mild diabetic mother delivered by him.

T h e s e v M u e s a r e s h o w n o n C h a r t 7.

This infant was first fed

twenty-four hours after birth, having received no oral or parenteral feedings before that time.

Feedings

were at four-hour

intervals, and the

blood samples were taken just before the succeeding feeding. Were e x t r a a d d i t i o n s m a d e t o t h e c a r b o h y d r a t e

intake.

At no time

T h e course fol-

l o w e d b y t h i s i n f a n t is n o t d i s s i m i l a r f r o m t h a t o f t h e n o r m a l studied.

infants

The mother's diabetes was fi~t detected during pregnancy

was well under control throughout

gestation.

and

MC KITTRIGK:

157

SERIAL BLOOD SUGAR DETERMINAT?ONS

Table V gives comparative maternal and fetal blood sugar values obtained at birth. Determinations were made upon sixteen male infants and fifteen mothers (one pair of twins) and upon thirteen female infants and mothers. All maternal vahles were collected within twenty minutes of birth, the great majority within ten minutes of delivery. Most of the mothers received small amounts of ether during the second stage of labor. TABLE V AVEr~E

M A T E ~ N A ~ AND FE~-L CAI'IImA~u BLO09 SU~Ag V a l u e s •

I

FETAL 72 rag. % 92 rag. %

Males Females

Bm~:I~

MATERNAL 105 mg. % 109 rag. %

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Chart 7.

The percentage difference between the average m a t e r n a l a n d the average fetal values is 31.2 rag. per cent in the male infant group a n d 15.6 rag. per cent in the female i n f a n t group. This m a r k e d difference is due to the lower average value obtained in the real e i n f a n t group since the maternai average in each instance is essentially similar. REVIEW OF LITERATURE A complete review of the literature on blood sugar Values in normal infants will not be made. I t was known that the blood s u g a r values of infants m a y be expected to be lower than those of o l d e r children or

]58

THE JOURNAL OF PEDIATRICS

adults.4, 7, s, 11, 12 I t was also known that thet'e is a gradual rise in the premature i n f a n t ' s and the normal i n f a n t ' s blood sugar during the first few weeks of life. ~ Our findings are in agreement with these statements. Von Creveld ~ studied premature infants and f o u n d low values for blood sugar early in life. He reports some values below 30 rag. per cent without abnormal phenomena being' observed. He used the mieromethod of I I a g e d o r n and Jensen la which determines " t o t a l reducing substance" of the blood. Of interest is a paper by K5hler 9 who made 479 "double determinat i o n s " on f o r t y normal newborn children. She used the IIerold modification of the B a n g method of determining the blood sugar. This method determines " t o t a l reducing substances." Samples were never collected less than five and one-half hours after the preceding meal, and most of them were taken seven hours postprandial. One blood sugar value was obtained from each infant each day. She f o u n d the. blood sugar lowest on the t h i r d day, with values going as low as 20 rag. per cent. A t no time were symptoms observed to accompany these extremely low blood sugars. KShler quotes M. Aldo as finding' the low average blood sugar on the second day. K5hler feels that the weight curve is intimately associated with the blood sugar curve in that the weight drop is paralleled by the blood sugar drop. She divides normal infants into several groups on the basis of the rapidity with which the weight and blood sugar fall. Blood sugar is said to begin usually to rise two days before the weight. The heavier children presented the more rapid fail in weight and blood sugar. The more, premature the infant, the less the fall in blood sugar and weight. KShler finds 60 rag. per cent the average blood sugar value for the first d a y of life with variations from 92 mg. per cent to 34 rag. per cent. On the second and third day values as low as 20 rag. per t e n , were obtained. STABILITY OF THE NEWBORN I N ~ A N T ' S BLOOD SUGAR

Examination of the charts as a group reveals that there is considerable instability of the blood sugar in these infants. I n the course of a few hours values m a y be found to v a r y greatly. This observation is very imp o r t a n t for two reasons: One, it suggests an unstable blood sugar regulating apparatus in the newborn; and, two, a single determination of the blood sugar is apt to be misleading. I n evaluating the examples of hypoglycemia, this tendency of the normal newborn i n f a n t ' s blood sugar level to v a r y greatly over a period of a few hours must not be overlooked. I n the cases as reported, ~' 2, 3, ,, 6 frequent serial blood sugar determinations were not made. I n the event that a given value is found to be low, there is no assurance that a sample taken a few hours hence m a y not be several points higher, even in the absence of intervening feedings. B y the same reasoning, a value f o u n d high now m a y in a few hours be low. Therefore, in order to discover more accurately what a given i n f a n t ' s

MC KITTRICK:

SERIAL BLOOD SUGAR DETEtgMINATIONS

159

blood sugar may be, it is necessary to make a series of determinations rather than just a single determination. Examination of Charts 1 and 2 would seem to indicate progressive increase in stability of the blood sugar during the first two weeks of life. I n this short time, the blood sugar is seen to reach a more stable level as shown by the diminution in the degree of spread of values d u r i n g the second, as opposed to the first, week. SUMMARY AND CONCLUSIONS

In summary it may be said that, during the first week of life, low blood sugar values may be expected and that the lowest point is reached by the average baby on the t h i r d day. On the basis of our figures, values above 40 rag. per cent blood sugar may be regarded as normal in the first week of life. During the second week the range is from 60 rag. per cent to 120 mg. per cent, with the average, between 80 rag. per cent and 90 mg. per cent. The male infants studied were observed to r u n slightly lower values than the female infants in the first six 24-hour periods. During the first two weeks of life, there is a gradual elevation of the blood sugar values with a decrease in the sp~:ead of the maximum and minimum extremes. The blood sugar regulating mechanism of the ne,wborn i n f a n t is unstable and undergoes an alteration toward greater stability during the first two weeks of life. Attention is called to the inaccuracy of conclusions based upon single determinations of the blood sugar in newborn infants and to the caution which should be employed in ascribinr symptoms or death to hypoglycemia during the first week of life. s should llke to acknowledge the helpful interest shown me by Dr. Clement Smith Medical School in organizing this work. of the Department of Pediatrics of the Harvard

REFERENCES 1. Randall, L. M., and lgynearson, E. H. : Proc. Staff Meet., Mayo Clin. 10: 705, 1935: 2. t~andall, L. ~ . , and 1%ynearson, E . H . : J. A, M. A. 107: 919, 1936. 3. }Iiggons, 1%. A.: Am. J. Dis. Child. 50: 162, 1935. 4. Greenwald, I-[. M., and ~ennell, S.: Am. J. Dis. Child. 39: 281, 1930. ,5. Neff, F . C . : J. Kansas 3/[. Soe. 37: 95, 1936. 6. Gordon, W. ~ . : J. Michigan IVI. Soe. 34: 167, 1935. 7. Von Creveld, S.: Am. J. Dis. Child. 38: 912, 1929. 8. Kilhler, A. : Arch. f. Gyn~k. 149: 421, 1932. 9. Folin, O. : New England J. l~Ied. 206: 727, 1932. 10. Somogyi, M.: J. Biol. Chem. 75: 33~ 1927; J. BioL Chem. 78: 117, 1928; Proc. Soc. Exper. Biol. & 1Vied. 26: 353, 1929. 11. Lueas, W. P., ]:)earing, B. F., Hoobler, I{. 1%., Cos, A., Jones, M. 1%., and Smyth~ F.S.: Am. J. Dis. Child. 22: 525, 1921. 12. Brown, IV[. J . : Quart. J. Med. 18: 175, 1924-5. 13. Hagedorn, I-I. C., and Jensen, B. N. : Biochem. Ztschr. 135: 46, 1923; t~iochem. Ztschr. 137: 92, 1923. 14. West, E. S., Scharles, F. H., and Peterson, V. L.: J. Biol. Chem. 82: 137, 1929.