NRLF B M 575 fl?7 x^- -ffir- THE PHYSIOLOGY OF THE NEW-BORN INFANT CHARACTER AND AMOUNT OF THE KATABOLISM BY FRANCIS G. BENEDICT AND FRITZ B. TALBOT ' * WASHINGTON, D. C. V PUBLISHED BY THE CARNEGIE INSTITUTION OF WASHINGTON 1915 M, 4,500 53 1 1 45 33.5-33.5 -37.4 .775 300 .808 6 19 20 }M. 3,600 54 f 1 30 \ 2 30 33.5-33.3 32.5-32.5 33.9-35.2 35.2-35.8 .605 .490 400 306 .921 .849 : No food; no bath; wide awake; quite contented; no crying. 2 Hungry and sleepy in last two- thirds of experiment ; frequently sleeping, constantly awakened; no crying. 3 No food; no bath; awake and contented. 4 Sleeping quietly during nearly the whole experiment. 6 No food; bath; good condition; considerable birth swelling; lively and contented; later hungry and somewhat sleepy. 'Stupid; fell asleep now and then, but awake most of the time; cried 1 minute; at the last lively. A well-nourished infant, born at full term, has a store of carbohydrate which it lives on either exclusively or largely in the first hours of its life; gradually this store (which consequently can not be especially large) is used up, and this leads to an increase in the oxidation of the other elements. In table 3 five experiments are given with 4 under-weight, prema- turely-born infants. The experiments indicate that such infants show signs of being very poorly nourished, in that their carbohydrate store is very quickly spent. But if the infant is experimented upon soon 22 PHYSIOLOGY OF THE NEW-BORN INFANT. enough after birth (as in experiments 10 and 11, in which the infant was placed in the respiration chamber immediately after tying the navel cord) we see clearly that here also we have to deal with the consump- tion of a store of carbohydrate, which causes the organism to burn other materials in addition. In experiment 6 the quotient, even within an hour after birth, is 0.766. Experiment 11 serves well for comparison. In this experiment an infant of the same length, but weighing 200 grams more, shows a quo- tient of 0.897 an hour after birth. If experiments 10 and 11 are com- pared, we find in the case of prematurely-born children, also, the same influence of condition of nutrition and of interval of time after birth upon the quotient as with those born at full term. TABLE 3. Carbon- dioxide Experi- ment No. Sex. Body- weight. Height. Age. Temperature of air in apparatus. Body-tempera- ture (rectal). Carbon dioxide in air of cham- elimina- tion per kilogram per hour Respir- atory quo- tiont ber. at C. ulClllr. and 760 mm. gm. cm. hr. m. C. C. p. ct. c.c. *6 M. 2,550 47 I .. 33.0-33.5 0.524 339 0.766 5 F. 1,825 44 2 .. 34.5-34.5 33.4-35.8 .392 273 .871 4 M. 2,700 50 1 30 -33 33.1-35.0 .729 464 .858 no 11 }M. 2,750 47 d' 5 35.3-35.2 35 . 2-35 . 1 36.5- -37.8 .561 .521 462 420 .912 .897 *No food; quietly sleeping or sucking during the whole experiment. *No food; bath; sleeping; respirations irregular, very few movements; artificial delivery; more than 1 month premature; died day following. No food; lively in first half of experiment, sleeping in last half; born less than 1 month prema- turely. 4 No food; no bath; born 3 weeks before time; crying about one-third of the time. 6 Quieter; crying about one-fourth of the time. The infant in experiment 5, although very poorly nourished, has a somewhat high quotient of 0.871, 2 hours after instrumental delivery. The fact that this child when 2 hours old still had a large quantity of carbohydrate to draw from is presumably due to the unusually low metabolism. This experiment is important; it is a case of premature interruption of pregnancy of more than a month before the end of the full term. The prematurely-born infant, therefore, shows the same respiratory quotient as the full-term child, indicating that it is con- suming the remainder of its carbohydrate supply. It is an obvious supposition that during the fetal life in mammals, with a physiological nourishment by the mother, there are always sufficient carbohydrates at hand, so that the respiratory exchange takes place normally with an exclu- sive metabolism of carbohydrates. This supposition of mine is well supported by literature. The fact that the fetal tissues contain large quantities of glycogen, which steadily dimmish during growth (always excepting the liver, in which more and OBSERVATIONS BY HASSELBALCH. 23 more glycogen is stored) , and the fact that the invertin 1 from the mucous membrane of the small intestine provides the fetus with a ferment for the eventual katabolism of this glycogen, are both arguments that point towards the important r61e of the carbohydrate in the economy of the fetus. Charrin and Guillemonat 2 find more glycogen in the liver of the pregnant guinea-pig than in the non-pregnant; and this is true both during inanition and during a rich carbohydrate feeding. In preg- nant guinea-pigs this signifies, then, either an increased impulse towards preparing glycogen from its food material or, in case of need, from its own body elements. Furthermore, as already mentioned, Bohr has definitely shown that the respiratory quotient of the guinea-pig's embryo is 1.0, without reference to the fact that the respiratory quo- tient of the mother may be lower.' It may have been noticed that in most of the previous experiments the percentage of carbon dioxide in the respiration chamber was quite high, most frequently between 0.5 and 1.0 per cent. This was done in order that the unavoidable errors in the analyses would have less effect upon the results. That it is not this fairly high percentage of carbon dioxide which has caused the difference between my results and those of Scherer and Babdk is evident from the fact that these scientists have worked with approximately the same percentage of carbon dioxide in the respiration chamber. In the double experiments in table 2 the metabolism, i. e., the carbon dioxide per kilogram and per hour, in the second half of the experiment is in every instance considerably less than in the first half of the experi- ment. This smaller metabolism, which was a result of the infant's sleepiness in the later period, has no modifying influence on the size of the quotient. The decreasing lung ventilation at the beginning of sleep could well be thought in the first minutes 3 to be followed by a slight drop in the quotient (if the relationship in this regard is the same as in adults, which is not proved), but in the course of the 23 minutes of the experiment in every case such an effect was soon compensated for. The experimental period is after all so long that we can judge of the nature of the oxidized material from the quotient without fearing to be misled by the influence of lung ventilation or work. If we wish to be convinced that the quotients quoted above are not affected systematically (and therefore are unaffected) by work done during the experiment (crying, kicking, etc.) we need only to compare experiments like 2 and 9 in table 1 on the one hand and 3 and 8 in table 1, and 5 in table 3, on the other. The comparison between 3 and 8 is especially convincing; in 3 there is twice as great a metabolism as in 8, due to the difference in muscular activity, but the same quotient is found with both. That the percentage of carbon dioxide in the atmosphere about the infant can not be considered to have an effect upon the quotient has already been quite definitely settled for adults by Speck's 4 experiments. In his experiments the same percentage of carbon dioxide as that used , Zeitschr. f. Biol., 1895, 32. 2 Charrin and Guillemonat, Compt. rend, de la HOC. de biol., 1900. 3 Speck, Physiologic des menschlichen Athmens, Leipsic, 1892, p. 16. 4 Speck, loc. cit., p. 133. 24 PHYSIOLOGY OF THE NEW-BORN INFANT. in these experiments is shown to bring about a decrease in the oxygen intake, and a consequent increase in the respiratory quotient, only when the oxygen percentage in the atmosphere is at the same time very low (i. e., 8 per cent against 20 per cent in my experiments). This fact is strikingly demonstrated by a comparison of 12 and 2 in table 1 (with the same percentage of carbon dioxide and extreme difference between quotients) and a comparison of 13 in table 2 and 5 in table 3 (with an extreme difference between the percentage of carbon dioxide and approximately the same quotient). As regards the amount of the metabolism in the above experiments it seems impossible for me to conclude anything else from the tables than that the activity of the infant is the chief determining factor, and that the influence of other conditions, such as the condition of nourishment, age, etc., is not demonstrated, at least by my method of experimenta- tion. The influence of activity is overwhelming and is observed regularly in the double experiments in table 2, and 10 and 11 in table 3, in which the child in the second experiment is always either drowsy or asleep. In the single experiments, also, we find a striking parallelism between the amount of the metabolism recorded and the intensity of the activity. It is naturally quite difficult to judge of and to express in words the degree of strength with which the infant has contracted its muscles in the course of 23 minutes. In the experimental pairs 17- 18 and 19-20 (table 2) I have repeatedly awakened the infants in the second experiment by rapping loudly on the cover of the respiration chamber. The purpose was to keep the activity and thereby the metabolism artificially at the same level as in the first experiment. Although the infants reacted to every rap with severe general contrac- tion of the muscles, the drowsiness throughout the entire period has been the determining factor; the metabolism in experiments 19 and 20 fell 25 per cent. Even though it is difficult to determine the work which the different children have done during the experiment and therefore difficult to arrive at a numerical expression for the effect of work on the amount of the metabolism, it is easy to convince one's self of the absolute absence of visible contractions. When such a condition has prevailed throughout the 23 minutes of the experiment we find a very low metabo- lism value from 270 to 300 c.c. carbon dioxide per kilogram and per hour. Such figures are found both for infants overweight (3,950 grams in experiment 8 of table 1, etc.) and for infants underweight (1,825 grams in experiment 5 of table 3, etc.). After due reflection this is not surprising. The heat regulation of a new-born infant 1 is very poorly developed. Even if it were not poorly developed, the temperature during the experiment is so regulated that the question of the feeble heat regula- tion of the child is eliminated as far as possible. Thus every experi- mental condition which would produce a smaller metabolism per unit of weight in the large infant with a relatively small surface than in the smaller infant with a relatively large surface is eliminated. But there is cause for reflection in the fact that a figure like 270 c.c. for the 'Babdk, Archiv f. d. ges. Physiol., 1902, 89, p. 154. OBSERVATIONS BY HASSELBALCH. 25 carbon dioxide per kilogram and per hour for a new-born infant is not essentially higher than the corresponding figure for a grown individual in absolute repose. There is reason to investigate whether the different temperatures of the children experimented upon have had an effect upon the difference in the amount of the metabolism. As previously mentioned, a fairly accurate value for the infant's temperature during the experiment is the last figure in the column headed " Body-temperature" in the tables. Recorded in this way, the infants' body-temperatures during the experi- ments do not show large differences, and these are in all instances plainly not parallel with the differences in the amount of the metabo- lism; I emphasize experiment 3, table 1 (temp. 35.2, metabolism 481), in comparison with experiment 8-, table 1 (36.0, 270) ; experiment 5, table 3 (35.8, 273) with experiment 4, table 3 (35.0, 464), etc. More- over, it is sufficiently well known that strong and continuous crying can raise an infant's temperature about 0.5. As crying is followed by a rise in metabolism, a certain degree of parallelism between the infant's temperature and the figure for the metabolism was expected. As regards the low temperatures after the birth-bath, they are for full-term and strong infants obviously considerably lower than is considered the rule. Vierordt 1 reports a temperature fall on account of birth and birth-bath at an average of 1 C; a fall of 1.7 C. " comes very rarely," but with delicate infants it may amount to even 4.7 C. In my experiments the normal children in experiments 3 and 2 in table 1 show in one-half hour and 2 hours after birth a temperature which is 4 C. or more below normal. When no bath after birth was given prior to the experiment, the cooling-off after birth has been fol- lowed by a fall in temperature of about 1 C. (experiments 17 and 13 in table 2 and experiment 10 in table 3). I would not dispute the fact that the tepid birth-bath is in all cases a very important means of reflexly starting the respirations, but I consider it very possible that the cooling off brought about by the bath can be carried too far, and if special arrangements have not been made for effectively warming the child after the bath, the cooling effect can be of too long duration. How is the respiratory metabolism of the new-born infant altered under the influence of food, as well with respect to the quotient as to the amount of the metabolism? When a hungry individual is put on a nearly exclusive carbohydrate diet, 2 his respiratory quotient reaches 1 about an hour after the first meal. In the course of an hour, therefore, the absorption and combustion of the carbohydrates in the different organs is in full operation. If we make an experiment similar to this with fat, the quotient shows that the time for the combustion of fat is considerably longer, i. e., about 3 hours after eating; something similar is true of proteids. Carbohydrates, therefore, are for grown individuals the food element most easily and most quickly consumed. This agrees very well with the fact that Mosso found with dogs an increase in temperature of about 1 C. an hour after taking 1 to 2 grams l Vierordt, Physiol. d. Kindesalters, 1877, pp. 152-154. 2 Speck, Physiologic des menschlichen Athmens, Leipsic, 1892, p. 35; Magnus-Levy, Archiv f. d. ges. Physiol., 1894, 55, p. 1. 26 PHYSIOLOGY OF THE NEW-BORN INFANT. of cane sugar per kilogram of the dog's body-weight. From the records of the body-temperature of the dog during and after a meal, consisting of cane sugar or of isodynamic quantities of bread, Mosso concludes that about an hour after taking the sugar is all absorbed, small quanti- ties being used entirely for the formation of heat and larger deposits being used in part for the same purpose and in part stored for future consumption. Bread is utilized in the same way, but more slowly, since it takes longer before the other food elements in the bread are oxidized. The bread as a whole, therefore, can not develop a heat influence so suddenly as can isodynamic quantities of sugar. TABLE 4. Carbon- dioxide Experi- ment No. Sex. Body- weight. Height. Age. Temperature of air in apparatus. Body-tempera- ture (rectal). Carbon dioxide in air of cham- elimina- tion per kilogram per hour Respir- atory quo- tipnt ber. at C. tieiiu. and 760 mm. Q7ft>* cm. d.hr. C. C. p.ct. c.c. 1 25 M. 3,600 5 .. 33.0-33.0 36.5-37.0 1.148 510 0.930 222 F. 4,100 54 5 .. 31 -31 36.0-36.8 1.133 487 .916 321 M. 3,250 52 2 . . 32.0-32.0 35.2-36.8 .851 478 .799 <24 M. 3,400 52 5 . . 32.3-32.7 35.4-36.6 .743 395 .807 6 15 16 }. 1,900 5 .. J33.5-33.8 \33.4-33.7 .260 .373 205 235 .770 .806 28 M. 3,000 50 .. 15 32.5-32.5 37.0-37.0 .707 482 .849 7 30 F. 2,950 1 . . 31.8-32.5 36.8-37.0 .894 642 .872 23 F. 2,550 . . 15 32.0-32.0 34.4-34.6 .449 283 .691 breast-fed 1 hour before experiment; cried somewhat for about 8 minutes; passage of urine and feces; during the last 5 minutes asleep. See experiment 27, table 5. 2 Breast-fed; same as subject in experiment 12, table 1; breast-fed 1 hour previously; awake and satisfied. Same as subject in 17 and 18 in table 2; slight jaundice; breast-fed 2 hours previous to experi- ment; cried 3 minutes; awake and lively, sucking its fingers. 4 Breast-fed 2 hours and again just before experiment; asleep or drowsy; only a few movements; no signs of hunger. Incubator infant; weighed at birth 1,950 grams; takes to the breast poorly; is put to the breast every 2 hours; last time just previous to experiment; fast asleep. This applies to experiment 16 as well. Bottle and breast; last meal 3 hours and again just previous to experiment; awake and lively. See experiment 29, table 5. 'Breast; last meal 3 hours and again just before experiment; violently crying more than two- thirds of the time; rest of the time in light sleep. See experiment 31, table 5. 8 Breast; born 2 to 3 weeks prematurely; breast-fed altogether 2 times, 5 hours before and again just before experiment; took to breast well; absolutely quiet, half and wholly asleep. An individual on a liberal mixed diet does not show variations in the respiratory quotient which would suggest a selective choice of the different foodstuffs. For instance, he does not have an hour after a meal a respiratory quotient of 1 , 2 hours after a quotient of 0.8, and 3 hours after 0.7, but would, at any time selected, have a quotient which varies but little from 0.88, for example. The reason for this is that the nourishment is plentiful, or, in other words, that there is in the circu- lation almost the same mixture of all three chief nutrients or their OBSERVATIONS BY HASSELBALCH. 27 intermediate metabolism products. Meals, which as a rule follow so quickly after each other that the fat and albumin absorption in the course of a day does not cease at all, can therefore not have any recog- nizable influence on the quotient. The evident conclusion is that if a meal (having constant composition) causes variations in the quotient of the above-mentioned character, it must mean that the nourishment is insufficient. I am not certain whether experiments favor this con- clusion, but I do not doubt that the supposition is true in the case of the adult. The meal affects the amount of the metabolism in such a way that the activity of the muscles and of the glands, caused by the ingestion of the food, increases the respiratory metabolism about 10 per cent. If we consider table 4, in which the experiments are arranged according to the time which has elapsed after the last meal, there seems to be little doubt concerning the effect of the meal on the respiratory quo- tient. In the two experiments (25 and 22) which began an hour after the meal, the middle of the experiment corresponding to 1 J hours after the meal (intervals which are important in carbohydrate metabolism), high quotients are found, namely, 0.930 and 0.916. These quotients point towards a predominant carbohydrate metabolism. In experi- ment 21 the meal was given 2 hours previous and the quotient is 0.799. Almost the same quotient was found in experiment 24 (0.807). Pre- vious to this experiment the child had not been fed for 2 hours, but was put to the breast just before the experiment began. The preceding meal may, therefore, be considered as having increased the metabolism but not as having changed the quotient, because at the end of the exper- iment only 38 minutes had elapsed since the meal (15 plus 23 minutes). The metabolism during the experiment was the metabolism of the ele- ments from the previous meal. The exact correspondence between the quotients in these two experiments also seems to indicate that the metabolism of the food given just before experiment 24 did not begin during the experimental period. Experiments 15 and 16, with a 5-day-old incubator child for subject, are interesting because they point towards the time when the metabo- lism of a meal begins; they were conducted at 1-hour intervals. The child received its last meal 2 hours before experiment 15, and therefore in this experiment has a quotient of 0.770 (approximately the same as the quotient in 21 and 24). With experiment 16, however, the child had its last meal an hour previous to the beginning of the experimental period; we therefore find an increased quotient, i. e., 0.806. In experiments 28 and 30, both with infants fed at the breast 3 hours previous to and again just before the experiment, quotients of 0.849 and 0.872 were obtained, which again show fair uniformity. These quotients are considerably lower than those obtained one-half hour after the meal, but higher than those obtained 2 to 2| hours after. This may be only accidental, but it is impossible to decide concerning this point. If we determine the metabolism 5 hours after the meal, as in experimejit 23, the quotient is found to be 0.691, indicating the katabolism of fat. 28 PHYSIOLOGY OF THE NEW-BORN INFANT. It is quite clear to me that in investigating these circumstances it would have been experimentally more correct to have used the same instead of different infants. The material for the investigations, how- ever, was collected for another purpose. Nevertheless the dependence of the respiratory quotient upon the interval of time elapsing after the last meal is shown in table 4, and in such a striking manner that there can hardly be any other interpretation. There is, however, no doubt about one point. Even though the composition of the food of the infant is much more constant than that of the adult, the respiratory quotient of the infant varies continually with the meals, so that it is highest about If hours afterwards (during this period the metabolism of lactose is chiefly going on) , and very low about 5 hours after, when the lactose from the last meal had been used up. I would not insist that this is definitely in favor of more frequent feeding than the ordinary 5 feedings during the course of the day, but it certainly deserves some consideration. On the other hand, it is possible that it might be harmful to the infant if the meals were so near together that the respiratory quotient remained constant throughout the day. In any case the problem is interesting and deserves a more thorough investigation, especially in the case of the same child throughout a rather long interval of time, with varying frequency of feeding with the same quantity of food and under constant control of the weight curve. Table 4 does not give any new information concerning the amount of the metabolism. The influence of activity is also quite apparent here. The premature incubator infant in experiments 15 and 16, which was practically motionless during the experiments, has a metabo- lism even lower than that found in the experiments with infants immediately after birth; it is interesting to note that the metabolism rises in the second experiment (both the carbon dioxide produced and the oxygen consumed), because this is supposedly to be interpreted in the same manner as the rise of the quotient in experiment 16. The work of digestion is greater hi experiment 16 than in experiment 15. At any rate, it was impossible to recognize a difference in the muscular activity of the infant in the two experiments, as the child was lying relaxed and asleep. The quotients for the infants spoken of as " lively and content" are somewhat higher than those of similar cases in tables 1, 2, and 3; but it is also striking how much more energy is displayed by the child a few days old than by the new-born infant, exhausted after birth. In experiment 30 we find an enormous metabolism, 642 c.c. of carbon dioxide per kilogram and per hour; but in this case we observe that the child was " violently crying more than two-thirds of the time." Evi- dently we can not overestimate the increased metabolism due to the incessant crying of feeble infants. Experiment 27 (not given in the tables) illustrates the effect of crying on the amount of the metabolism. By moderately lowering the tem- perature (which caused a drop in the body-temperature of 0.4 C.) we succeeded in making the child cry very violently for about 17 min- OBSERVATIONS BY HASSELBALCH. 29 utes. The experiment was made with the same male infant as experi- ment 25 in table 4, the weight of the child being 3,600 grams and the age 6 days. It was breast-fed. The temperature of the apparatus was 25 to 26 C.; the body-temperature of the infant was 37.0 to 36.6 C. The percentage of carbon dioxide in the air of the chamber was 1.534; the carbon-dioxide elimination per kilogram per hour, reduced to C. and 760 mm., was 764 c.c. and the respiratory quotient 0.897. The child was crying violently three-quarters of the experi- mental period and was evidently cold. In the middle of the experi- ment there was a quiet period with a little sobbing. It would be erroneous to consider the great increase in metabolism (compare experiment 25, table 4) in this experiment a result of the child's " chemical heat regulation" brought about by a cold reflex. 1 The infant would have reacted to any other equally powerful irritant with as severe crying and with equally high metabolism. Even if the previous experiments leave no doubt that the carbo- hydrates of the food play the same r61e in the infant's nutrition as in that of adults, namely, that of the most accessible food elements and consequently most quickly consumed for heat production, and even if the results in table 4 are most easily interpreted on the supposition that the absorption and metabolism of carbohydrates reach their climax 1 to If hours after the meal, further experimental evidence is still needed of the correctness of this hypothesis. With this purpose in mind three infants were put on a diet so arranged that meats were given between their regular feedings. These meals consisted of 4 to 5 grams of grape or milk sugar dissolved in a little water. In experiment 29 of table 5 the respiration experiment commences 3 hours after the milk meal and about If hours after the lactose meal. The quotient is 1.0. In experiment 26, in which the grape-sugar was given 4 hours and again one-half hour previous to the experiment (breast-feeding between the two feedings about 2 hours previous to the experiment), it is seen that the quotient 0.869 does not point towards an exclusive carbohydrate metabolism. In the course of the half hour the absorption of the administered grape-sugar has not taken place. Finally, in experiment 31, undertaken about 3f hours after the last milk meal and about 2f hours after the last grape-sugar feeding, the quotient is 0.845, an index that the metabolism of the 4 grams of grape- sugar has to a great extent taken place as quickly as 2\ hours after admin- istration. This result corresponds strikingly with those obtained by Speck and Magnus-Levy with adults (my discussion of the results in table 4 were based on the results obtained by these two authors), and with Mosso's demonstration of a temperature rise of 1 C. in the case of a starving dog, about an hour after the ingestion of an amount of sugar correspond- ing to that used in these experiments. It is thus clear that the custom of feeding sugar-water immediately after the birth-bath rests upon a (Archiv f. d. ges. PhysioL, 1902, 89, p. 166) interprets a rise in metabolism from 332 c.c. to 579 c.c. carbon dioxide as a sign of an "auffallige Thatigkeit der chemischen Regulation," without giving information about the child's behavior in the two cases. 30 PHYSIOLOGY OF THE NEW-BORN INFANT. very sound principle. Of all the elements of nutrition sugar is digested by the infant the most quickly and the most easily, and doubtless causes a rise in temperature very much to be desired, because of the cooling-off at birth and during the birth-bath. Experiment 1 of table 5 is an experiment which should illustrate this utilization of sugar, but there are some objections. In the first place, it was not wise to select a period 3 hours after birth for feeding with sugar; in the second place, it will always be difficult to demonstrate in respiration experiments the utilization of sugar at such a period, for even without sugar the quotient at this period is close to 1.0. But a direct demonstration of this point is unnecessary. The fact that the small intestine of the fetus contains invertin shows that it is equipped for the digestion of carbohydrates, and therefore favors the supposition that the new-born infant should be able to digest cane-sugar without difficulty immediately after birth. TABLE 5. Carbon- dioxide Experi- ment No. Sex. Body- weight. Height. Age. Temperature of air in apparatus. Body-tempera- ture (rectal). Carbon dioxide in air of cham- elimina- tion per kilogram per hour Respir- atory quo- 4 i ri i + ber. at C. nent. and 760 mm. QW:. cm. d. hr. C. C. p. ct. c.c. 1 2Q M. 2,950 50 2 .. 31.8-32.1 36.4-36.5 0.806 617 1.027 *26 F. 2,450 2 . . 31.8-32.1 36.0-35.7 .553 370 .869 '31 F. 2,950 2 .. 31.0-31.3 36.3-36.7 .511 343 .845 <1 F. 3,700 51 .. 3 33.5-35.0 34.2-35.4 1.291 500 .902 1 Bottle and breast; same as subject of experiment 28 in table 4; in last 24 hours between the meal- times fed with 5x4 grams milk-sugar, last time l hours before experiment. Crying violently for 4 minutes, afterwards half or wholly asleep. 2 Breast; same as subject of experiment 23 in table 4; in last 36 hours 5x5 grams grape-sugar, last 4 hours and hour before experiment; sleeping or dozing; now and then vigorous movements. Breast; same as subject of experiment 30 in table 4; in the last 24 hours 5x4 grams grape-sugar; last feeding 2\ hours before experiment; half or wholly asleep. 4 Sugar-water at birth; bath; crying about one-half of the time; otherwise restless, kicking, and perspiring. It would be unreasonable to dispute the fact that mother's milk is the ideal nourishment for the infant. It is well to note, however, that the infant must be born at full term and be healthy. With premature infants and infants with intestinal catarrh or other digestive ailments, which result in diarrhea and rapid loss of weight, it is quite a different matter. Recent investigators in this line tend more towards localizing the logical cause of digestive diseases in those organs in which the final katabolism of the food elements takes place, instead of in the mucous membrane of the digestive tract and the accessory digestive glands; indeed, there are many points which favor a pathological retarded development of the oxidative functions of the liver tissues. OBSERVATIONS BY HASSELBALCH. 31 Meinhard Pfaundler 1 has shown in an interesting paper that an infant, and especially an infant weakened from some illness, is unable to oxidize the fat and albumin in the nourishment as completely as the adult, and he has shown by experiments that this is due to some extent to the small oxidative power of the liver tissue. Carbohydrates receive a prominent place as that constituent in milk which is most easily and most completely oxidized under all conditions, and which is therefore an important element in the feeding of the infant, whose fat and albumin digestion is supposedly overworked. In such cases the mother's milk is not the ideal food, for its contents of fat and albumin (which can not be digested and whose products of decomposition may do harm in the intestine) are altogether too large and cause the child in reality to starve. In reviewing the extensive amount of literature on artificial feeding of atrophic infants, it is evident that the composition which has had the best results, Keller's malt soup (a modified Liebig soup), points towards feeding largely with easily digested carbohydrates (maltose). With this kind of feeding the formerly atonic and poorly-nourished infant thrives and the disease is, as a rule, cured at one stroke. If, therefore, it is demonstrated that mother's milk is not the most favor- able nourishment in all pathological cases, it is well, bearing the previ- ous results in mind, not to take it for granted that mother's milk is indicated in the case of the premature infant, but to consider whether feeding with relatively large amounts of carbohydrates would not be preferable. CONCLUSIONS. I. The well-nourished infant, born at full term, has a store of carbo- hydrates (glycogen) in its organs, which is spent in the course of a few hours. II. The metabolism of a poorly-nourished and premature infant depends chiefly on the oxidation of carbohydrates during the first hours of life. III. There is every reason to suppose that the metabolism of the normal, well-nourished human fetus consists of the oxidation of carbohydrates. IV. When the infant is fed with mother's milk, the respiratory metab- olism shows a mixed quotient, which varies with the meals in such a way as to indicate that milk sugar is the element most quickly burned, that is, about 1 hours after the meal. This fact is confirmed by experiments. V. The amount of the infant's metabolism is to a very large extent dependent upon muscular contractions. At 32 C. and with least possible work, the metabolism per kilogram is hardly greater than that of the adult at absolute rest. VI. The relative ease with which carbohydrates are digested favors their extensive use in cases where the ability to digest the other constituents of human milk is decreased. Meinhard Pfaundler, Jahrb. f. Kinderheilk., 1901, 54, p. 247. See also here a large amount of literature on the subject. 32 PHYSIOLOGY OF THE NEW-BORN INFANT. DISCUSSION OF HASSELBALCH'S RESEARCH. We consider it peculiarly unfortunate that in our two earlier publica- tions reference to Hasselbalch's research and to his striking conclusions was inadvertently omitted, and although at that time we were unable to comment intelligently upon the results or make a satisfactory abstract of them, since there were some difficulties in the translation, nevertheless it would have been desirable to call attention earlier to the existence of this wholly remarkable piece of research upon infant metabolism. Although the study was made 11 years ago, the same degree of care and nicety of technique which has characterized Hassel- balch's subsequent observations is apparent in this research. It is obvious that we have here for the first time quantitative measurements of the gaseous metabolism of infants by a study of the carbon-dioxide increment and oxygen deficit in the ventilating current of air. It is an interesting fact, which should certainly be pointed out, that the appa- ratus used by Hasselbalch for this study embodied the same principle as the Jaquet 1 apparatus, and, indeed, both forms of apparatus were described in the same year, thus proving independent simultaneous development. Of particular importance in studying the respiratory exchange is a special appreciation of the significance of the difficulties of determining the oxygen in any gaseous mixture, even in ordinary atmospheric air. Researches in the Nutrition Laboratory have shown that the external air is of absolutely constant composition, irrespective of seasons, wind direction, weather conditions, barometric pressure, and altitude. 2 Consequently it can be assumed that any gas-analysis apparatus which fails to give constant values for the oxygen content of the atmospheric air may be considered on this a priori evidence as being an inaccurate apparatus, or the technique is at fault. It is, furthermore, obvious that the greater the carbon-dioxide incre- ment and the greater the oxygen deficit in the ventilating current of air, the less the analytical errors will influence the calculation of the respira- tory quotient. It has been frequently pointed out that those using the Jaquet method are too often inclined so to adjust the ventilating air-current as to have a minimum carbon-dioxide increase and an equivalent oxygen deficit. When this carbon-dioxide increment is less than 0.5 per cent, analytical errors play a great r61e not only in the calculation of the respiratory quotient, but likewise to a certain extent in the calculation of the total metabolism. Since the analytical errors in the determination of the carbon dioxide are very much less than those in determining oxygen, this may not of necessity be a serious matter. On the other hand, the exact determination of oxygen necessitates the skill of the best trained analyst and an especially accurate gas-analysis apparatus with a carefully controlled technique. When the oxygen 1 Jaquet, Verhandl. d. Naturforsch. Gesellsch. in Basel, 1904, 15, p. 252. Benedict, Carnegie Inst. Wash. Pub. No. 166, 1912. EARLIER RESEARCHES WITH NEW-BORN INFANTS. 33 deficit is less than 0.7 per cent, analytical errors of plus or minus 0.03 per cent (which are not at all infrequent) will have a very considerable influence upon the computations of the respiratory quotient. The air analyses published by most users of the Jaquet apparatus have shown discrepancies in the oxygen content of external air which lead one to suspect analytical errors. We note with interest, however, Hasselbalch's statement regarding his own experience in analytical analysis, which indicates that he found very insignificant variations in the composition of the atmosphere. Thus we may properly infer an especially careful analytical procedure. But of more significance is the fact that Hasselbalch's published results show us that his carbon- dioxide increment was frequently 1 per cent or even 1.5 per cent. It is clear that Hasselbalch's analytical data are probably as accurate as any determinations thus far made of the carbon-dioxide increment and the oxygen deficit in an open-circuit respiration apparatus, and we may have an unusual degree of confidence in his values. The number of infants studied by Hasselbalch was too few to obtain definite physiological constants, and although he reports 31 experi- mental periods on 20 infants, and as a result of his accurate technique was able to make deductions from them, it is obvious that a problem so important as the metabolism during the first week of life demands not simply confirmation but further elaboration of data. We shall have occasion, in discussing our own results subsequently, to refer to the sharply drawn conclusions reported by Hasselbalch. OBSERVATIONS BY WEISS. In 1908 G. Weiss, 1 employing a type of respiration apparatus which was entirely different from those previously used for studying infant metabolism, made a most interesting series of observations on new-born infants, in which both the carbon-dioxide output and oxygen intake were studied. Twelve new-born infants were observed, ranging in age from 1 to 11 days. His apparatus consisted of a metal chamber supplied with a window and a thermometer, and having a capacity of 60 liters. The infant was hermetically sealed in this chamber and remained there for approximately an hour. The air in the chamber was then thoroughly mixed by an electric fan and a sample taken for analy- sis. This method of studying the gaseous exchange was employed by Chauveau and Kaufmann and used with especial success by Laulanie*. The carbon-dioxide increment in the chamber and the oxygen deficit could be readily computed from the results of the analysis and data obtained as to the total oxygen absorption and carbon-dioxide produc- tion of the infant. The author points out that with new-born infants the carbon-dioxide excretion is two, three, or sometimes four times greater per kilogram of body-weight than it is with the adult. He found, for example, that the carbon dioxide excreted varied from 1,064 c.c. to 337 c.c. per kilogram 1 G. Weiss, Bui. de 1'Acad. M6d., 1908, 60, 3d ser., p. 458. 34 PHYSIOLOGY OF THE NEW-BORN INFANT. per hour, while the values for the oxygen consumed varied from 1,248 to 404 c.c. per hour. He also states that he found the respiratory quotient to be generally much higher than the results obtained by Scherer. Basing his discussion upon the law of surface area, Weiss concludes that the metabolism is proportional to the cube root of the square of the weight. We give here his argument in full. His result* are given in tables 6 and 7. La consommation de divers sujets de m&ne espece, et les phe"nomenes qui Paccompagnent, en particulier _Pintensite des ^changes respiratoires, doit done etre proportionnelle a ^P 2 , et en rapportant cette consommation i Punite de poids, on obtient = = , que je designerai par a. Si done tous les sujets se trouvaient dans lesmemes conditions d'utilisation d'oxygene, ils devraient, par kilogramme, faire une consommation propor- tionnelle a a. En designant Poxygene absorbe* par kilogramme-heure par Q, serait constant, quelle que soit la taille du sujet. En suivant les variations a de , on a reellement Pindication d'une utilisation surabondante ou defec- a tueuse de Poxygene; c'est pourquoi ce rapport peut etre designe" par le nom d'indice d'oxygenation. Get indice d'oxyge*nation est en somme le rapport de ce qu'un sujet prend reellement d'oxygene a ce qu'il devrait prendre nor- malement pour sa taille. En appliquant cette formule a Padulte pendant le cycle de vingt-quatre heures, P etant exprime en kilos et Q en litres, on obtient un indice voisin de Pimite*; 0.99 a 1.03, pour Phomme variant de 60 a 70 kilogrammes. Voyons maintenant ce que Pon trouve chez le nourrisson. J'ai calcuie les indices correspondant a mes di verses determinations chez le nouveau-ne'; les r^sultats sont reported dans la Table II. On ne constate plus alors cet e*cart considerable entre le nourrisson et Padulte. Dans les premiers jours apr&s la naissance, Pindice d'oxyg^nation est un peu inferieur a la normale, mais il se releve ensuite et ne la de"passe guere; chez un seul sujet particulierement beau il s'est e*leye* a 1.5 et meme 1.8. Mes mesures ne comprennent pas les premieres heures, il y a la une lacune a combler. Mais si, chez les enfants que Pon peut qualifier de normaux, c'est-a-dire qui augmentent regulierement de poids, Pindice d'oxyg^nation prend une valeur un peu supe*rieure a Punite, chez les d^biles Sieve's a la couveuse il est franchement au-dessous, il est au voisinage de 0.5 et ne se releve pas; c'est la un point qui me parait important et qu'il y a lieu d'examiner de plus pr&s au moyen de nouvelles experiences. Peut-etre devrais-je ni'arr^ter ici et me contender des constatations que j'ai faites; mais il y a lieu de se demander a quoi tiennent les differences d'indice que j'ai relevees. Je ne voudrais pas sortir des limites de la physiologic normale et penetrer sur un terrain peu sur pour moi; cependant je tiens a faire une remarque qui peut orienter les recherches a entreprendre. Jusque dans ces derniers temps, et confonnement ^, la theorie de Lavoisier, la question de Pabsorption d'oxygene par les e*tres vivants etait, sans restric- tion aucune, intimement liee a la production de Penergie utilisee par les ani- maux. Dans cet ordre d'idees on aurait pu se demander si certains enfants ne s'oxygenent pas plus que d'autres parce que, etant plus robustes, ils s'agitent et depensent davantage. EARLIER RESEARCHES W fra NEW-BORN INFANTS. 35 Mais cette explication ne peut pas nous contenter; on a vu en effet plus haut que les robustes Femportent sur les debiles meme alors que les premiers dorment au repos complet et que les seconds s'agitent. En dehors de 1'influence de Fagi- tation, il faut chercher une autre cause a la variation de 1'indice d'oxyge*nation. Au cours de recherches que je poursuis depuis plusieurs anne"es, et dont j'ai public quelques resultats a la Societe de Biologic, j'ai montre que non seulement, comme on le savait, certains animaux pouvaient yivre un certain temps a Fabri de Pair, y produisant du travail avec elimination d'acide car- bonique, mais que cette production de travail ne se faisait pas aux de*pens de provisions d'oxygene tiroes anterieurement de F atmosphere. Le muscle peut travailler sans intervention de Foxygene de Fair. Celui-ci ne semble intervenir que pour eViter Fencombrement de Forganisme par des de*chets et produits toxiques. Autrement dit, Foxygene est un e"purateur. II se peut qu'il y ait lieu de rapprocher ce role epurateur de Foxygene des bonnes conditions de developpement des enfants robustes, tandis qu'il est insuffisant chez les debiles. TABLE 6. 1 Nos. Age. Poids. CO 2 2 R.Q. Remarques. I. 9 BON fiTAT. 1 2 3 4 5 6 7 5 e jour. 3.120 0.960 0.887 0.975 1.064 0.922 0.884 0.556 1.067 0.935 1.023 1.248 0.971 0.912 0.598 0.90 0.95 0.95 0.90 0.95 0.97 0.93 22. Vient de teter. Cris frequents. 22 . 5. Cris frequents. 23 . 5. Cris frequents. 24. Cris frequents. 21. Tete il y a 2 h. 30. Cris frequents. 21.5. Vient de teter. 21.5. Repos complet. 8e jour. 3.370 II. rf 1 BON &TAT. 8 9 10 11 12 13 14 15 16 17 2 e jour. 3.300 0.403 0.530 0.604 0.613 0.701 0.753 0.659 0.756 0.815 0.837 0.498 0.631 0.695 0.730 0.779 0.801 0.701 0.796 0.886 0.854 0.81 0.84 0.87 0.84 0.90 0.94 0.94 0.95 0.92 0.98 21. Aucune tetee encore. Sommeil. 21.5. Quelques cris. 21. Vient de teter. Sommeil. Sommeil. 22. Vient de teter. Repos et sommeil. 23. Sommeil. 23.5. Vient de teter. Sommeil. 26. Cris, puis sommeil. 24. Vient de teter. Cris. Demi-som- meil. 24 . 5. Demi-sommeil. 4e jour. 3 270 7 e jour. 3.420 9 e jour. 3.520 lie jour. 3.620 III. 9 BON fiTAT. 18 19 20 21 22 23 24 25 2 jour. 3.570 0.403 0.413 0.407 0.525 0.629 0.596 0.696 0.589 0.504 0.504 0.509 0.610 0.732 0.678 0.757 0.685 0.80 0.82 0.80 0.86 0.86 0.88 0.92 0.86 24. Vient de teter. Sommeil. 25. Sommeil. 23. Vient de teter. Sommeil. 25 . 5. Cris et sommeil. 24 . 5. Vient de teter. Cris et sommeil. 26. Cris et sommeil. 22. Pas tete ce matin. Sommeil. Re- veil. Cris. 22. Tetee. Sommeil. 4e jour. 3.600 6e jour. 3.710 9 e jour. 3.860 IV. $ BON fiTAT. 26 27 28 29 2e jour. 3.050 0.469 0.579 0.479 0.451 0.579 0.697 0.614 0.609 0.81 0.83 0.78 0.74 22 . 5. Aucune tetee encore. Sommeil. 24. Reveil et pleurs. 23. Vient de teter. Sommeil. 24. Sommeil. 4 e jour. 2.780 x Table I in the Weiss article. 36 PHYSIOLOGY OF THE NEW-BOKN INFANT. TABLE 6 1 Continued. Nos. Age. Poids. C0 2 2 R. Q. Remarques. 2 V. cf JUMEAU DfiBILE A LA COUVEUSE. 30 31 32 33 4e jour. 6e jour. 9e jour. 11 jour. 1.570 1.530 1.470 1.480 0.443 0.337 0.408 0.364 0.554 0.481 0.517 0.444 0.80 0.70 0.79 0.82 23 . 5. Legere agitation et sommeil. 24 . 5. Sommeil. 25. L6gere agitation et sommeil. 23 . 5. Sommeil leger avec frequents mouve- ments. VI. d* BON 6TAT. 34 35 2 jour. 5 e jour. 3.070 2.900 0.403 0.401 0.492 0.521 0.82 0.77 24 . 5. Pas tete ce matin. Sommeil. 26. Vient de teter. Sommeil. VII. d* BON fiTAT. 36 37 38 39 40 2e jour. 4 jour. 7 e jour. 9e jour. lie jour. 2.470 2.250 2.320 2.370 2.430 0.406 0.551 0.556 0.565 0.685 0.556 0.771 0.670 0.698 0.753 0.73 0.72 0.83 0.81 0.91 24 . 5. Aucune tetee encore. Sommeil leger . 25.5. Petite tetee le matin. Demi-som- meil. 23. Vient de teter. Sommeil. 23. Tete il y a trois heures. Quelques cris. Sommeil. 21. Quelques pleurs. Sommeil. VIII. 9 Nfi A 8 MOIS. DfiBILE. COUVEUSE. 41 42 43 4 jour. 6e jour. 8 e jour. 1.860 1.850 1.790 0.425 0.349 0.514 0.518 0.459 0.591 0.82 0.76 0.87 23 . 5. Cris la moitiS du temps. 25. Quelques pleurs. Sommeil. 23 . 5. Sommeil et cris. IX. 9 BON fiTAT. 44 45 46 47 ler jour. 3 jour. 5 e jour. 10 6 jour. 3.200 3.000 3.030 3.150 0.342 0.341 0.555 0.638 0.433 0.421 0.646 0.701 0.79 0.81 0.86 0.91 26. Sommeil continu. 27. Vient de teter. Sommeil continu. 27. Quelques cris. Sommeil. 23 . 5. Quelques cris. Sommeil. X. d" BON fiTAT. 48 49 50 51 l er jour. 4e jour. 6e jour. 8 e jour. 3.700 3.450 3.530 3.550 0.404 0.447 0.545 0.664 0.481 0.552 0.641 0.772 0.84 0.81 0.85 0.86 25.5. Aucune tetee encore. Sommeil un peu agite. 23. Vient de teter. Sommeil. 23 . 5. Vient de teter. Demi-sommeil. 23. Vient de teter. Cris frequents. XL ! CO CO uorjBA -jasqo jo SuiuutSeg CO CO CO O5 O -d 3 . w CO iQ I s - 00 I s * ^5 ^j ^ CO 00 * 00 l"^ g : COCO "0 b- S 00 CO I. O5 I I! o -S OS O *'< b- oo co c6 CO CO CO CO co b- CO CO CO b- rH CO : 2 _OQ I 6 I* y Tt rH A ei a s STATISTICS OF OBSERVATIONS. 47 d 1 1 1 1 1 . Colostrum. fColostrum; sterile water 4 min- \ utes before the observation. fColostrum ; breast-milk commenc- l ing. More breast-milk. Breast-milk. f Sterile water 2 minutes before the \ observation. f Partly colostrum; sterile water 1 \ hour before the observation. d 0) 'Si 1 c3 ^ O ! 1 l fColostrum; sterile water 5 min- \ utes before the observation. fColostrum; sterile water 9 min- \ utes before the observation. fBreast-milk; sterile water 2 min- \ utes before the observation. Breast-milk. The ages here given are at the beginning of the period of observation. For 3 Died subsequently of congenital syphilis and jaundice, infants over 2 days old, the age is given to the nearest half day. 4 Axillary temperature. Calculated from the weight of carbon dioxide produced during the period. 5 Results with this subject have been previously published. (See Benedict The preliminary periods for all days are omitted in computing the and Talbot, Am. Journ. Diseases of Children, 1914, 8, pp. 38-39.) minimum metabolism. See table 12, page 95. 6 Intracranial hemorrhage found at operation on April 12, 1914. " : g : rH rH ^ CO o CO rH CO CO o CO "^ t* t^ CO CO CO CO CO CO CO CO t> CO CO CO CO CO O OS rH CO / w CO * \ ^H 00 10 OS CO ^ CO o o . * , CO CO CO CO N, Jo_ l> CO I * , * < CO CO c3 ss lO GO b rH O O rH rH CO OS CO rH CO CO rH rH rH rH rH ^ O CO O CO O t> ^ O 00 tfD *fl |> CO b *H C^ *C II CO CO CO rH l>- 1> II 11 i-4 jgiiii * ; S3 951 -- ;-- ;sa 3 S9 S3 ss 00 O *t t Os t^ rH -^ CO Tj( IO ^ Tjl s; 38 05 T< CO CO SS :3 :gg i Si OS CO CO 00 CO CO CO CO CO rH O GO :g^ :g^ ^^ , , ^-^-< ^^ v_^_ ' ^ ^^^ ,___, , , ^_ , ,_^_^ S : g s CO * 00 00 s g i i : OS -CO co 00 t ) l l / _^_ _^ ( t ^_^_^ f _^_^ 38 S3 8 2^s O 00 OS CO GO 00 > ^^SScSS ^00*COCOrHOCO^ CO CO OS OS rH O CO CO CO rH CO CO rH rH COrHrHCOCOCqCOCOCO CO CO rH CO CO CO ^ CO CO CO CO CO CO CO - CO CO CO CO CO rH CO CO CO CO CO CO CO CO a CO CO s 5 CO CO !) 8 CO CO rH rH CO CO CO rH rH rH CO TH >O ^ rH CO rH CO CO Th * 1 : : : a CO >0 I j 8 li 1 1 co I s * oo w w w 1 1 1 m m i4 !J rH CO rH CO | CO < CO ^ 4 4 i XX ** 6 -- ^b *I 48 PHYSIOLOGY OF THE NEW-BORN INFANT. * i PQ 8-go ^ - o 1 i MIIM 8 -qo jo png CO CO CCCC COCO -aasqo jo I If i 8 o if -ra -be . tS r ure.i3 ^i e ? fH rH CO ^^ ^ 00 -O5CO T-I > i JS- t^ * I s * t^ OilNiO CO ^ O i-t -OOO5 -CNi-i -rt(Oi -COO -lOCO -CO 10 t^ U5 10 <* * CO I> O O rj< rJH rf T}< Tt* O OS CO O> rH GO rH CN 0} ?5 ?5 ' JH 12 COt-l -COIN iO-<* OOCO k o CO -IN Tf^cOtN 'SrH OrHr-tTf<(N Tt -~^ --v _, v__, v_^^ v_^_. * * v ^ , ^-^ - v_^ - o ^.S 43 -0 -C -g CO 00 b- CO D ^O CO 00 CO I s * ^* D l> . b- b- 00 b- 00 3 5 ^^ ft a rt Q) H ( ( ', ^ , j , ', ' 1, '_ -^ =s '^^ ' m ^ =S ' ' ' " * '. ' 1131 CNO-*O(NrHOOOlOrHO rHrHCOrHOOrHOrHCOCO 3 ^ n ^^ fa 2-2 A 8'OT 'J8TVBSSl r j) -OJt3[ 00 O t^ CO I s * 00 CO i-H 00 O O O 00 10 CO CO 0> 00 CO l> CO t IO COl> rt00 1 * -O5> oo OOrH 1>O l>l> COt> ! I O 00 rHCOCOOirHOOCOOCOrH lOCOOJCOCOrHCOOCOiO ci * iO O O5 OO CO CO CO CO t -^ co I> l^ t CO CO Co' - CO CO rH rH CO <* s s STATISTICS OF OBSERVATIONS. 51 1 ? 6 6 S P Q M 5 ^ of o o 1 1 1 O PQ PQ O dioxide produced during the period all days are omitted in computing 3ee table 12, page 95. O O CO CO CO rH rH rH rH rH CO H h | . si! CO CO CO CO OS CM CM O CM ^ CO CO CO CO CO CO CO CO o & ifcj t> t> CO b- O OS O O O CO 111 s era O -CO Tf- o -CO O CO O -CO S "S o d b *O 00 CO CO CO CO *O ^ O CMCMOOOOb-OOTjO II : : : >O CO * CM ^1 03 CM 2 ft b- 00 OS B? b c s s s rH CO b- CO OS rH C CM b- CO 00 O rH CM * CO b- CO CO CO CO (N O CO 00 05 !> CO I s * ^.s s in TrHOOOOCO rH rH 00 T OCOO rH O O O O5 00 iO *O CO OO CO ' CO CO CO 00 :g| i :8! igg :Si rH IO GO CO *O i-H ^ co H ^*3 1 b- O5 TH CO O TH ^f GO rH CO O5 rH O^ O5 CO * 00 ^H Oi I s * o^ io^o *^^ -^10 -10^0 ;-- ;--^ ;ss " :Srn^ :gS :8 :8 l>* CO * t^ t> 00 !> t^ GO O O :$ :i5 :S5 rt . ^ . ^_, ^_, ^_^ ^^ - , ^^ 1- 00 CM TH -CD b- -00 -00 -00 : 8 : 8 : : F: : f: 00 00 4 s * ' . > ' ( - / _^_^ % / _^^ > i l . r _^^ ^ s O5COTflCOI>COrHOCMCMOCOO5 COC<|i-irHiObOOb-COOOOOCOeO-rHrHOOOO CO CO CO CO CO O i-H CO CO CO rH <* 3 S (N (N STATISTICS OF OBSERVATIONS. 55 Colostrum. Do. (Breasts beginning to fill; cried throughout observation, as if very hungry. 1 * 8 axilla 2 o o *o & Breasts filling. *The ages here given are at the beginning of the period of observation. "Calculated from the weight of carbon dioxide produced during the period. For infants over 2 days old the age is given to the nearest half The preliminary periods for all days are omitted in computing day. the minimum metabolism. See table 12, page 95. 3 Died subsequently of inanition. . . jC * * * " * ^ ^ o b- co 05 rH CO CO CO 00 b- Tf< O5 O5 00 CO CD CD *O CD CD CO CO CO CO CO CO CO CO 05 CO CO 05 1 * t b- 00 00 CO O5 CO CO CO CD CO CO CD CD CO rH , > CO * 00 CO rH 1-H (N rH (N O O5 O TtH O CO O * rH CO CO CO C5 l> rH_00 t < ^ b- b- b- b- 00 t> 00 :gl oo ic -^ iO ^f ^O O rH C-l rH b- iO 00 CO CD b- b* 00 CO C^ rH C*l rH IO ^ ^O * O5 O5 ^ C^ O5 rH rH O*OiO -lOCO iOCO'O -COCO 'T^Ttl -iOiOO -OCO %% ' ?5 rH rH O5 O5 rH rH CD rH (M (N O* W CD rH CO C^ CO ^ ^O CO O5 CO CO CO O C^l GO O CO O5 O 00 00 rH GO OO O5 b 00 CO CO 00 b O5 ' b* O ;^o ' ^ ' - '-^ ^-^-s ' . . .rH CDb-Tt*(NTpO5O5l>rHCOeOOrH(N(N Q> G> 8 :gS .-i fr o g O> CD S :S CO CO CO : 3 S-S^Sg.9 a a 5? a o >%%% II ^3^C^S8?r^^^?5 CC O '~ CO CO CO SS* - a CM CO tO X Io r STATISTICS OF OBSERVATIONS. a 4 ion the Colostrum utes bef <5 a | I & & Tji(NrHCOOOCOt>OOCOOiOCNCOrHO>COOOOO5lN.C^OJ'^COO5 CMCOCOCttrHrHrHrHNrHIMCqrHCMrHrHrHrHOOrHeOCMOO Sl "# O5 00 00 rH O T}< 8 o co t> CO JO CO t^ * rH U3 O CO CO CO 8 S iS8^S^2 CO CO *O ^ ^ ^ O ^O ^ ^^ ^ GO fH CM ^ Cb O Os O) O) O CO O CO rH CO - rH -l iH (M (M iH i- ^ct^^lfg^^^^cl^i^t^^^g^^^^^^c5c^iS^g s s CO CO s 8 58 PHYSIOLOGY OF THE NEW-BORN INFANT. .5 > to begi B & fB \ Breast-milk; two days pre CO . O -8-2 tem- re. tal -qo jo pug CO CO CO -aasqo jo CO CO CD Oi l^* *O CD ^ !> C^ C^ Oi *O !> CO O 00 CO CO 00 l>* 00 *O Tj* 1 s ** 00 *O O ^H ^Oi^C^C^C^Oi^OC5O-Hi-H'- CD CO CD tO CO CD i-iCO -r-iTt< -COCO -COOO -COtO -OOCO -tOi-i -t^t* CDOO ^'^ -tO-^ -TjlcD -CDOO -tOt* -tOcD --^CO o'B O 'rt ti C3 ^ &2 *C^(N(NC- Tt< X O5 T}< CO 'UOI^BA -jasqo jo OS (N O CO CO W r-t rH iH -COQO -IOO 8 : O CO O5 -OS t>. t^ CO t^. . ON lO CN CO rH >0 Tj< rH 1 CO N CN CO CM llowing day because of high tem- orrhagic disease of the new-born. o CO : 8 i i 8 8 CO CO CO CO . <=>"< & il^l^ >^ a.-g ^ CM 00 CO 00 O5 CO b^ CO CO 05 O CO CO ^ T^ CO ^ CO CO CO CO 8 c8 'g O d -^ ilfll sla^S i CO CO CO b- b-' CO CO CO CO O CO CO CO CO CO b- b- 00 b- CO CO CO CO CO b- | 1|3|^' -5 ^3 a d 2 ^ CO tO CO CO 10 00 CM JO O rH O rH rH W 00 30 O CO CO CO b* 00 Tt* CO CO b- O5 (N CO CO CO O rCOOOO5b-CMtOCMCOCOC<> rHrHtOtOrHrHT^OOrH rH b- rH O O O ^lltf O O M ft > CO b co b- b- b- CO to CO CO CO ;;ii; OS ^ bt to CO b- CO C 1 ^ rH tO CO O O ' rH^ T-* CO CM . l| 1^5 II 525 1 ,o S :5S OO 00 CO O5 rH ^ CO Tt^ to tO to b- O O to to to to "* b- -CO Tp Ttf O to to O ^ 00 ^ to CO * CO CO P ? 9 'SoS CO tO rH O5 Tt< rH CO CO CO w -b;^ CM CO CO 33 ' ' 'S3 O5 rH CO CO , , ^^_, ^^ ^ ^ ^ ^ ^_, 5 ^I '^3 T3 'C -i 3 CO CO 05 00 O -to O CO O5 00 CD $ g J: to ^8 JI fe 53 t,^ ^g V -* s ie--5 '^ * N '^-^-N ' / '^-x ' "r-^^ > 'r-^ > ^^_^ Jill Tj< rH tO b- CM CO CO (N CO (M b- to CO b- O5 to 00 O rH 00 CO tO j g *, 05 rH CM CO Tfl (N CO -^ CO CO s S 1 1 a i? B rt d 53 1 1 1 1 1 1 & f-* > > > > 1 1 1 1 o SZ5 QQ 2 ^ t> -*a ^3 d d finl ft ^ g *l|jj m PR H "5 - S rH ! 1 g 5 62 PHYSIOLOGY OF THE NEW-BORN INFANT. a o S 1 I 8 tal -qo jo pug -jssqo jo 8uiuui3ag CO is ggg ted) mpu 24 ho m -bs -OH 3 ! II o ^ ^co 00 t> JJ I* O5 O CO 00 IO ^ CO l> M . [Colostrum; regurgitating in mid- \ die of preliminary period. Colostrum and breast-milk. No food or water. Do. Colostrum. & \ a 6 6 Q Q The ages here given are at the beginning of the period of observation. Calculated from the weight of carbon dioxide produced during the period. For infants over 2 days old the age is given to the nearest half The preliminary periods for all days are omitted in computing day. the minimum metabolism. See table 12, page 95. *Minutes. CO 8 iO 8 : i ooo CO CO CO rH o o CO CO CO b- CO b- CO 8 o H CO % rH OS CO CO 1> 1> CO CO CO CO CO O CO CO o b- % b- 00 CO co CO CO -> > rH CD CO O rH CO CO i * / * / * \i CO b- _ A w f, % OS rH O >0 OJ rH rH rH %$ g 8S22 s 8 CO rH 00 CO iO O :38 :S?S :3S : b- b- rH CO rH rH O O :^3 : (N b- cO CO %% :rn : %% rH rH os co OS >O C_^ ^^_, , , , , ^^_^ ^^_^ ^^_, , , ,_^, ^- v -' ^-^ * CO rH rH 00 : g : fc S3 ? ' 00 b- t> 2 : 3 V-.L '^-, ',_^ '^_, V-^-a V- > \ -^ ', -^ V^-, j , ',-~-^ ', S883 b- rH (N rH CO rH rH rH CO rH rH rH iO O CO rH OS 00 o .... rH O ' rH * Ci 00 t>* o O "^ -2 aj CO co co b- i> CO CO CO CO CO !> CD t"* CD CD CO CO CO CO CO co c^ Ml ^ |&s ^ O CO *- T}I> -t^CO -COCO !> -I>iO O CO OS 00 CO CO CO OS CO CO co co * co fs oo i I o d ~* .H c3 k-t 5*! O CO 00 OS b- b- 10 b- tO to :gS3 :S^ :^^ :S :^5 CO CO CO to CO to o S :3 rH IO Ol Tf l> CO CO OS 0* 05 CO CO 01 OS tO to OlrH -OOO1 -Olt^ -Ol -lOrH r^rt< --^CO -COO1 --^ -OOtO OS 00 CO CO t> IO CO rH tO CO 00 J> ,__, --^ -^- -^- ^z ^_, ^__^ v_^_, V__^ v_^_, ^_, ^^ d -3 13 OS O1 -CO -00 to 00 -00 -OS -CO CO . ^ r| o 03 ^ > w O fH , r-^- -s ^- x , * / * / . / ^ * / ^i ^^-^ , , , , , , t r> q^ to ^ co o t> b- OtOb-COrHrHCO^TtllO ss ^T^OOi-HCOCD^iOi-H C^ 1 s * t"* ^H Oi t>- O5 !> i> Oi 00 CO CO O Ol O 00 rH rH O tO Tt< tO OS CO OS O CO Tj< CO fl o^ CO 0* 01 COOIOICOCOCOCOOIOIOI rH 00 co co co OS^iO^tOOOOcOCOOl CO CO CO CO CO T^ 01 CO CO CO 00 O co co cococooicocooicococscoiococo 01 CD 00 CO CO Ol Ol CO Ol rH -^1 (M * co co co co co Id a ^ j*i rH 01 OS 01 00 Ol Ol tO to 01 00 S! 3! 5 ; *tf Tj< Ol Ol Ol Ol Ol CO CO co co cj IO 00 CO * CO 00 HIM rH CO CO rH Ol CO * rH CO rH rH Ol rH' Ol ^ fi ii j to to tO : ] SL !* ^01 Q d 5 o SjP.jp Q Q P Q Q Q p 8 p p > a '5c^ -< -t^ -Ot> -lO ^- . 10 CO -OO5 -O3 -C^ CO -COCO -lOiO -CO OO5 -3 T*cO-O>COCOl N CO<^C s J liCO ^ CO 0^-00 CO CO CO "^CO CO CO CO COCOW CO CO CO CN CO CO CO CN 1 s A STATISTICS OF OBSERVATIONS. * 1 2 1 6 66-* 1 1 1 Q Q P 1 M u & Colostrum. /Colostrum; breasts beginning to 1 fill. Breast-milk. [Breast-milk ; sterile water 4 min- \ utes before the observation. Colostrum. a o o o o co co co co g CO rH rH s CO (N rH O CO CO CO CO CO CO CO rH CO O (N CO CO CO CO CO CO CO rH CO b- b- O CD (N b- CD CO CO b- CD CD cp cp co co cp cp cp CO 01 b- CD co co . ( l> O CD l> CO CO rH ss I * \r o j COCOOlCOCOlOOCDrHClOOO-^rHOlrHOCOfNCNlO rH rH O C^C^C^OlC^'^rHC^IrH CO CO rH CO Tt* CO rH O rH SOI O O O O Ol Tt< rH CO (N rH CO O CO Tf , . Qj rJH CO O * Tj< O CO b- CM ^O Olb- CO't l b OiOb- rH b- -GCTtt -rHCO CO CD CO CD CD b* CO CO b- CO b* b CO CO IO rH rH iO 00 Ol rH 0} l> Js, 2 CO CO CO "# i-T rH ^ CO i 1 :$3 : S 3 :9 33$ '-SI ;SS :SS Ol Ol * CO C^ CD IO rH CO >O b- >o b- *CC^ 'O5(N 'C^l -Oit^-O 'OO *COiO - ' '*-*-* ' ' ' ' > T)HCOClTtHiOOl(MCOOOCOCOb-OOOliOiO'*- C^CNrHrH N rH CO C0 CO ' O J O O Cj O CO O CO CO CO CO CO CO CO Ol O O O CO CO S b? CO CO 8 CO S .C^(MOCJrHCOrHOrHCOCO CO CO CO CO CO CO ^ CO "^ CO ^* CO CO CO CO I- t3 CO rH 00 fl r. "6 w STATISTICS OF OBSERVATIONS. 6 Q ? 6 6 66 S Q Q P Q c3 O 6 Breast-milk. No food or water. Colostrum. oi o -3 PQ o 8 o o o o o CO CO CO CO CO 10 f TH i % % : CO CD co t^. a i> TH oo co i> CO CO cO CO 4 s * CO CO CO CO CO CO O CO b CO CO CO CO co O O CO t> !> O CO f- CO l> TH 00 00 co co co co co co l> CD co co | TH OS O b- CO t> CO CO CO rH OOCOCOOsOrH (N b- CO rH W rH O rH b-(NCDb-THlOCDCO (N(NCO(NCOOO (N O CO 00 b- 11 ; ill rH 00 10 -bo - GO CO CD CD GO O TH iO TH -COTH -COCO - 4 v ^_ t ^^ / > ',-^-> OS CO (N IOTHOOOTHCOCOCO>OTHTHTHTHCO OSTHO3O(Nb-COCDOOOS(MOb-OSCDCOOOCOCO X> O iO O CO O 3S CO CO TH CO b- CO O OS CO CO rH OS rH Ob-COCOTHTHCOb- COb-lOOOSCOCOOS N (N THTHTHCOC<>THTHNrHrHC<|rHrHrHTHTHTHi IrH H rH rH (N rH rH (N (N rH (N THrH CO CO 0 rH rH j :::**:: : 9 i i i 9 00 O CO ^ &O (N CS| CO CO TH CO 00 00 q 1 1 J 1 J I 1 ^ 3 r? rH PH PH 1 1 p^ CD V V PH PH PH PH h PH s S 5 70 PHYSIOLOGY OF THE NEW-BOKN INFANT. & & 6 1 l tem ture. -qo jo pug CO CO -aasqo jo sis rHOrHCOCOCOC(NCO tN. 05 CO rH IO CO l^ rH rH CO rH (N (N -CO :3 : u : fc 00 -00 tN * 04 CO U5 CO rH O (N tN CO CO 2 S SI 1 A I I 6 r o ** J5 "Z STATISTICS OF OBSERVATIONS. jj ^5 | | H3 . rt # . 2 d a d iljllxiil 6o ^o Colostrum. f Colostrum and breast-milk; \ breasts filling. Breasts filled. Colostrum. o o o * o o o o CO CO CO CO CO CO CO CO TH CO ^ ,noosT-!t^t>i>.c-t^C h co t* : 8 _^ __^ ^ ^ ' ' ' f -^-^ ' , , ' r-^ ^ -, % ' f _^^ , ^_ =3 Ic^a COtHOO(NCOTHOSCN'THTH(Nt^OTHTtOSt^OOkCOCOOOOTi-CCO5THTH-I>tM TH TH TH TH TH TH CO-*TH oo S S 'UOtJ'BA -aasqo jo d ^ % CO -4< s s as 28 CN H 2 H 05 |R 11 s -ui -bs O5 O5 I s * CO t^- ^* CO C4 ^ i-H -t^CO -OOlO -OICO -t-ICO CO CO ^O O CO Tt< Tf lO 1-1 CO O -b-b- -COCO -O5^ -COO5 ->OT^C '_c^=i '_C~=3 L==3 L=3 Lci3 L=3 ' ' L==J L^3 ^^^8 00 CO b^ Tf rH Tt< CO O C5 O 05 iO b- 00 OOOOCOCOT^OOcOrHCOb-COr^- S S 2 S2 ^ O5 CO CO rH CO CO CO 00 ^ t>* O CO l> tv Oi CO ^ i* O5 00 00 ^ CO C^ COCO-^COCOCO CO COCO "l-sH .IS'iZ^ CO CO CO CO rH CO CO (N rH -CO lll'ai CO CO rH CO CO 111- 8 a ., 3 "s a : S CO b- CO rH O O * 10 O -10 S oa ^a 5 ^^.s-g Hi!l 05 O rH eoiocob-ooo5 05 coco S lild JI t> fl a 1 1 1 O3o3o3o3o3o3 c3 Se3 ssssss % ss l^^ag Ssfil g 3 1 *1 S fe g fe ^ fe- ^ g bj" 00 O5 O rH 1 1 6 1 S> 74 PHYSIOLOGY OF THE NEW-BORN INFANT. i 1 S * s s 1 1 1 1 113 Breast-milk. No food or water. f S : : 8 -' CO : I $ | -qo jo pug CN CO o CD !** t^" CO CO CO -M O t>! o co co 1 UOT^A Q, -jasqo jo t^ CD CO i i i ^ mi SS833$SS3gS82S ?8S28g88885: d O O5 ^ O5 IS- t^ *"H CO ^O O5 C^l I s " OO O5 ^ -t^OOrt O <-H 00 (MOO O l> 10 iO CD 00 t"* *O *O V 111 -onT^ad ^ -iCCOt^OO 00-ii-ii-i GO GO O COO CO CO CO .t>. a^M o ^^ 'I A 6 A S it *i oJOO-oS^X^ g88888S8oi JCOT^CTSCQi-tCOCJOfMrtt 5COW5000000WOt^OO & "O 43 'a^^^^^^^c^^^^ttttc^^,^ *O i ^ ^ 'S "^ _j ff r CN CO CO (>. CO Tf i 3 111] < ^ S* N He* l-H CD ^ 1 8 5 8 ': * 1 =S I i CO S a a 1 s s ^ If s s SB STATISTICS OP OBSERVATIONS. f Colostrum and breast-milk; \ mostly breast-milk. 1 s o 1 X ill 1 o 2 o -| K & fc No food. No food. Colostrum. /Colostrum and breast-milk; \ breasts beginning to fill. J The ages here given are at the beginning of the period of observation. 3 For the age from period to period, see table 10, p. 81. For infants over 2 days old the age is given to the nearest half day. 4 The average respiratory quotient obtained during the entire period of Calculated from the weight of carbon dioxide produced during the period. observation has been used in computing the heat-production. The preliminary periods for all days are omitted in computing the minimum metabolism. See table 12, page 95. CO IO rH 05 05 8 CO l> rH 04 CD b- 05 rH CD CO CO 1> CO CO CO CO / * N CO CO , * < CO b- CO rH 10 co co t^ CO CO CO CO rH 1>- 00 t^ 1 * CO CO CO CO SrH IO 04 rH 82g rH CO CO ^ !> 00 CO to 04 to ^ rH to CO O CO t** ^ CD O O rH O O5 O5 rH rH CO ^ O4 04 CM T^ rH rH rH rH O b-iOCOb-iOOCMtOOOOSCO C5O5rHOrHO4rHrHr-IO4O4 to CO 00 CO : rt^OS -COO5 O5''tflOOCOTflt>"00 -OOOtO O4O4 -COrH rtlO4O'* | GOOOO -00004 tOCO -t>t^ tOt^OCDtOcDO5 -COCOt^ !>. 00 O5 C4 t^ CO to O COCO to iO -tOCO -t>CO :S9 10 rH COCO -CMrH COt^cOO400Orfi -T^lcOOO CO-* -toto COrt*CO-^COT}I> :^ :fc :2?$ : o ; eg tO rf< -CO -tO rH 33 tO O5 O CO rH rHiOCOCOiOi-HtOCOrHOOCMCOl>OOO500O5CO OOlOOOOOO5O5COOt>.l>.^rHO4l^OO5OrHO4 b O5 IT** O5 CO rH CO CO O to O5 iOiOO5tOCO04cOGOO4OOO 040404 C4 (M 04 rHi-lrHO4rHrHCO-^T}H'rH' CO-*Tj CO CO CO CO C4 * O4 CO CO O4 rH O 04 CO CO CO CO 05 *> 04 rH ,0 CO rH CO b- CO O4 rH r- 1 04 s S : 5 tO to b- O5 1 co CM si O 04 rH rH CO CO 1 1 1 i * ^ s < OCNb-b-OOCOb-OOCOOO(NCOOiOO5b-CO 'COCN(NO^CNCNCNC S O O w * w "6 * " 1 8. S a 00 . CO OS 3*2 Nlii GO CO -I CO o3 fc rH T ( ^ l 1 II 1 :SS5SSS JS^S^RS^ :gg :3g338S8 SS83fe3 fLi pE< EH iQ O CD *O !> I s * O O *O CD C^ CO *O O5 CO C^ ' *O O I s * C^ O CO Oi CO O CO ^ O O5 CO fl >T3 fl 1 ,* ^^^ .au.^^-.-,-, Us> o 1 o ieu , usi o .2 * .2 : OOl>b-OOt>t^.OO t>OOOObOSOOt- l>- XOOGOOOb-OOOS OSOOOSOOOOCOCO 5 53 , fcj | ' i ' ll" ^SSSo?Sc5^2S^^g^S&^Scit:^ggSSo^gt28 M fl "o o ^3 *I*11 os^ 3 -g a^ g^>>! c5 c^ M S, a ft B 1 f J J o ^ .S S p*jil "*a1U Jo o ft '3 S S fe h Jiii 8 - | S 8 bC c3 J ^ 5 78 PHYSIOLOGY OF THE NEW-BORN INFANT. . = 3 -qo jo pag -aasqo jo vy KT t/j ill i-H C^ T^ i~< CO CO I s * CO CD O5 OOdi-.rHT^O5 t-H fl b- N ^J e W -S 1 ; O t^ O5 O CO (N 00 O5 g o- X 00 00 00 00 00 00 : cj ' ^StSSo > cCO(N*OCO*Ot>-COiOiOi-i S 58 STATISTICS OF OBSERVATIONS. 79 111 t c; ^ ooo fc ^ ^ No food. 1 & ee table 10, p. 81. btained during the entire period oi i computing the heat -production, -a +3 -o 3-8] 33 o, o d co co co CO CO CO ftj 111 *& b- O CO O CD co co co CD CO i i g^^^^^22J232833^^^^^S^S^ TjOiO -CMrHOOiOCOCD -lOCOOOOT^OOJ O3 iO -^ (M CO CO CN O rH rH b- CO sssssss d >>T3 M ^^.^^.^^^ ., ^.^^^^^.^ ,0 03 _0 O5OTt<(MrHCOCO -COOeOCNrHCNC O ^H i4 iH (N ft ft ft s s s & a S ft jjjjfj s s ^ s a lllSl 2 i 2 2 1 J 1 80 PHYSIOLOGY OF THE NEW-BORN INFANT. DISCUSSION OF RESULTS. The data we have accumulated in this study of new-born infants permit a reasonably complete discussion of several phases of infant katabolism, particularly the character and the amount of the katabo- lism and the physiological needs of infants during the first week after birth. CHARACTER OF THE KATABOLISM. Though previous observations with adults and animals give us no rea- son to expect any particular kind of katabolism with new-born infants, except that which may be due to the character of the food-supply and possibly to muscular work as in severe crying, nevertheless since it is commonly believed that there is an excess of glycogen in the body of the new-born infant, it is necessary to examine carefully the character of the katabolism during the first week, if not, indeed, during the first hours of life. Such a study will give evidence as to the probable gly- cogen content of the body, or, more specifically, the availability of the glycogen content for supplying the needs of the body in the absence of the ingestion of food. It was possible to determine the respiratory exchange of the infants by means of the respiration apparatus, and from these data to calculate the respiratory quotient for practically all of our observations. As has already been pointed out in our description of the technique, the greatest errors are liable to appear in the determination of the oxygen consumption, as this requires an exact knowledge of the temperature, humidity, and barometric pressure inside the chamber. Since this error may be minimized by measuring the oxygen consumption in long periods, it has been our custom to determine the oxygen consump- tion for the entire time that the infant was inside the chamber, sub- dividing the observations into periods upon the basis of the carbon- dioxide measurements. In certain observations these periods were made long enough to obtain fairly accurate respiratory quotients for the individual periods. This is particularly the case with the infants studied immediately after birth. Our data are therefore sufficiently extended to permit us to discuss the respiratory quotient of the new- born infant during the first week of life and particularly during the first 24 hours following birth. RESPIRATORY QUOTIENT DURING THE FIRST 24 HOURS OF LIFE. The greater part of our evidence in regard to the respiratory quotient during the first 24 hours of life was obtained in those observations which were specifically designed to study this question, namely, those in which the infants were observed almost immediately after birth. The periods were for the most part 1 hour long and therefore may rea- sonably be expected to give satisfactory determinations of the oxygen consumption. The results are given in abstract in table 10. CHARACTEE OF THE KATABOLISM. 81 TABLE 10. Respiratory quotients of infants during early hours after birth. Relative Relative Sub- ject No. Sex. Age at begin- ning of period. Respi- ratory quo- tient. 1 Car- bon diox- ide per hour. activity 2 estimated from kymo- graph records. Sub- ject No. Sex. Age at begin- ning of period. Respi- ratory quo- tient. 1 Car- bon diox- ide per hour. activity 2 estimated from Kymo- graph records. Obs. Obs. Obs. Obs. I. II. I. II. h. m. Qvn. h. m. gm. 80 M. 2 . . 0.75 2.14 B ' B 95 F. 4 15 0.83 1.71 B B 3 . . .78 1.76 A A 5 15 .70 1.41 A A 4 . . .90 3.99 D C 6 15 .84 1.58 B B 6 .. 3 .78 2.39 C B 7 15 [.93] 2.09 E D 82 M. 3 .. .76 1.28 A A 96 F. 1 15 .93 .87 F D 4 15 .78 1.60 B B 2 15 .85 .75 D C 5 15 .83 1.75 B B 3 30 .91 .65 A A 6 15 .80 1.77 C B 4 30 .89 .95 C B 83 M. 2 30 .80 2.06 A A 5 30 .80 .75 A A 3 30 .90 2.21 A A 6 30 .86 .88 B B 4 30 .83 2.22 B B 7 30 .86 .09 E E 5 30 .83 2.20 C C 97 F. 2 . . .85 .82 F F 6 30 .85 2.24 B B 3 .. .84 .75 E E 7 30 .79 2.39 D D 4 . . .82 .58 A A 8 30 [.99] 3.55 E E 5 .. .87 .61 B B 84 F. 2 . . .76 1.82 B A 6 . . .87 .65 D E 3 .. .83 1.81 A A 7 .. .86 .84 C D 4 . . .80 2.26 D C 8 .. .86 .80 C C 5 . . .86 3.09 F D 98 F. 2 . . 0.77 .33 D C 6 .. .83 2.70 E C 3 .. .90 .93 F D 7 .. .75 2.02 C B 4 . . .90 .22 E E 8 .. .77 2.04 C B 5 .. .74 .50 C B 87 M. 1 30 .79 2.06 A A 6 .. .74 .37 B A 2 45 [1.05] 2.71 D C 7 .. .79 .38 A A 3 30 [-90] 3.78 F D 8 15 .85 .50 B A 4 45 .81 2.42 B B 99 M. 1 30 .79 2.09 B B 5 45 .76 2.18 A A 2 30 .83 1.78 A A 6 45 .84 2.27 C B 3 30 .93 3.09 D C 7 45 [-96] 3.70 E D 4 30 .90 2.33 C B 93 M. 1 .83 2.69 F F 6 . . .83 2.00 A A 2 .. .77 1.86 D C 7 .. .89 2.81 D D 3 .. .79 2.01 C D 7 45 .87 3.25 E E 4 .. .87 2.69 E E 100 M. 1 15 .90 3.47 D E 5 .. .76 1.89 B A 2 15 .98 3.43 D F 6 . . .77 1.89 A A 3 15 1.00 4.36 E G 7 . . .86 2.07 B B 4 15 .85 2.86 C D 94 M. 1 15 .76 2.09 C D 5 15 .87 2.96 A B 2 15 .87 2.16 D D 6 15 .91 2.81 A A 3 15 .81 1.89 A A 7 15 .82 3.12 B C 4 15 .75 2.12 C B 101 M. 1 15 .89 2.34 C C 5 15 [-96] 3.24 F E 2 15 1.00 2.69 F E 6 15 .80 2.29 C C 3 15 .94 2.73 E E 7 15 .79 2.07 B B 4 15 .82 1.90 B B 95 F. 1 15 .89 1.90 D C 5 15 .81 1.87 A A 2 15 .80 1.54 C B 6 15 .88 2.27 D D 3 15 .84 1.65 B B 7 15 .86 2.29 D D Duration of periods about 1 hour in practically all cases. J The designations here used indicate only that the activity in one period is greater or less than in the other periods, the letter A being applied to the period of least activity in each case. The designations are not comparable for the different subjects. 8 This quotient was obtained following an interval in which the cover of the chamber was removed to give the baby a small amount of sterile water and after a second preliminary period. 82 PHYSIOLOGY OF THE NEW-BORN INFANT. TABLE 10. Respiratory quotients of infants during early hours after birth Continued. Relative Relative Sub- ject No. Sex. Age at begin- ning of period. Respi- ratory quo- tient. 1 Car- bon diox- ide per hour. activity 2 estimated from kymo- graph records. Sub- ject No. Sex. Age at begin- ning of period. Respi- ratory quo- tient. 1 Car- bon diox- ide per hour. activity 2 estimated from kymo- graph records. Obs. Obs. Obs. Obs. I. II. I. II. h. m. gm. h. m. gm. 102 M. 2 15 0.83 1.76 D C 104 M. 1 45 0.92 1.90 D C 3 15 .80 1.55 C C 2 45 .85 1.55 B A 4 15 .82 1.43 A A 3 45 .96 1.68 A A 5 15 .78 1.49 B B 5 .. .89 1.65 C B 6 15 .88 2.19 E D 6 .. .88 2.58 E D 7 30 .80 1.89 D C 7 .. .82 1.95 C C 8 30 .81 2.28 F E 105 M. 3 15 .83 1.85 A A 103 F. 1 15 .89 2.25 A A 4 30 .89 2.12 E D 2 15 .78 1.87 A B 5 30 .89 2.33 D E 3 15 .91 2.63 D D 6 30 .82 1.90 A A 4 15 .85 2.96 E D 7 30 .81 2.02 C B 5 15 .81 2.15 B C 8 30 .82 2.41 D E 6 15 .88 2.99 D D 9 30 .82 2.04 C C 7 15 .85 2.82 C D 1 Duration of periods about 1 hour in practically all cases. 2 The designations here used indicate only that the activity in one period is greater or less than in the other periods, the letter A being applied to the period of least activity in each case. The designations are not comparable for the different subjects. When we examine the individual quotients for each day, we find that at times there are great fluctuations, as, for instance, in the case of subject 83, in which there was an increase in the last period from 0.79 to 0.99. Since the infant had had no previous nourishment and was without food during the whole time that it lay in the respiration chamber, it is of course inconceivable that after 8J hours of fasting subsequent to birth there should have been this qualitative alteration to a metabolism which would be indicative of pure carbohydrate com- bustion. On several other days similar abnormal respiratory quotients are found, these being indicated in the table by brackets. These brackets are not used to differentiate sharply between the correct and incorrect quotients, but merely to point out the most strikingly defective quotients. There may be two reasons for these defective quotients. In the first place, they may be due to excessive carbon-dioxide excretion, unaccompanied by a corresponding increase in the oxygen absorption, or they may be due to a defect in the measurement of the oxygen, particularly of the residual oxygen inside the chamber. If we examine the values given in this table for the total carbon-dioxide production, we find that at times there are very great increases. Thus, with infant No. 80, there was an increase of over 100 per cent in the carbon- dioxide production from the second to the third period of the observa- tion, this being accompanied by an increase of 0.12 in the respiratory CHARACTER OF THE KATABOLISM. 83 quotient. With practically all of the quotients which are inclosed in brackets we find very great increases in the carbon-dioxide production over that of the preceding period; hence we may ascribe at least a portion of this change in the quotient to an excess carbon-dioxide excretion. It is not impossible that a certain amount of the carbon dioxide thus excreted may be due to actual over-ventilation of the lungs of the infant, produced by excessive crying; this can not, how- ever, account for the entire increase. For a partial explanation of these variations in the carbon-dioxide production, we may with profit examine the kymograph records accom- panying each period. It is impracticable to publish all of the records obtained in this series of observations; accordingly two skilled observers have examined them independently and have indicated the relative activity by ascribing a letter to each individual period. This classi- fication is not intended as a comparison of the activity of one infant with another, nor do the letters designate arbitrary degrees of muscular repose. They apply only to the activity of each infant by itself and show the muscular repose of the individual periods as related to that of the other periods, A being used to designate the greatest degree of muscular repose. If there are two periods in an observation when the muscular repose is of exactly the same degree, they are given the same letter. (See infant No. 82.) The estimations made by Observer I and Observer II never differ more than one unit in classification and usually they are identical. It will be seen that in practically all of the instances in which abnormally high quotients were found, there was a great increase in the activity as shown by the kymograph record. While a variation in the degree of muscular repose is not always accompanied by a variation in the respiratory quotient, nevertheless this is true in the majority of cases. In view of these considerations, we must accept with reserve the respiratory quotients which do not lie within reasonable limits of the average quotient for the day. If the infant organism were surcharged with glycogen we would normally expect to find a high respiratory quotient shortly after birth, with a gradual decrease throughout the day. A critical examination of all of the values in table 10 shows a distinct, though slight, tendency for the quotient to fall off during the day; on the other hand, the initial quotients are not extremely high, being for the most part considerably less than 0.90. We may there- fore properly conclude that while the quotients have a tendency to decrease as the period of inanition lengthens, since the quotients are rarely as high as 0.90, even when obvious technical errors are eliminated, we can not infer that the katabolism is chiefly that of carbohydrate during the observation period. According to the table of Zuntz and Schumburg, a non-protein respirato^ quotient of 0.90 corresponds to a combustion in which 66 per cent of the total energy is derived from carbohydrate and 34 84 PHYSIOLOGY OF THE NEW-BORN INFANT. per cent from fat. While with these infants we have not been able to secure a non-protein respiratory quotient, we may safely disregard this fact and assume that a quotient of 0.90 with these infants cor- responds to a katabolism in which approximately two-thirds of the maintenance metabolism is derived from carbohydrate. To obtain the average respiratory quotient for these infants on the first day of life, we may best examine the values given in table 11, in which all of the respiratory quotients on the first day have been brought together and averaged. We find that the average respiratory quotient for 74 infants on the first day of life was 0.80, a value materi- ally lower than the quotient of 0.90 occasionally appearing in the first few hours of life. This value of 0.80 represents a fasting value not widely different from that observed during the first 24 hours with fasting man, a previous publication from this laboratory showing that the aver- age respiratory quotient in 14 experiments with 10 men was 0.79 on the first day. 1 Benedict, Carnegie Inst. Wash. Pub. No. 77, 1907, p. 451. CHARACTER OP THE KATABOLISM. 85 -i> -00 CO O >l> CO S&T^" II M 4 s i> co j t^ ^ CO CO CO CO 3i 2| m 5 : t> t>- O O -COIN r-l -0p -CO GO 10 Tt< -COTji -CO -(NCO O C - iO"tfOO.lOCO -t>-lOCOO(NO 1>GO'HCO CO t>. CO CO t^. t^ CO t*. . l> .CO t l> l> CO *'*'*.* * * * * . CO *2 O-^t^b- -OOCOTHOr-l -r}HGO * "^ CO ^ CO CO CO CO CO PHYSIOLOGY OF THE NEW-BORN INFANT. T3 B 5 5 * 5 : : : : :g ::::::::: H UJ b- CO CO rt< I Mil bt X C* U3 CO r-l x x oO x r-i *O "t O b- -00 -O 0> "* O <* 05 05 "5 CO -I O -I kC -CO -OifNOiN -TtO5 -O -O3 -O -b-b- '^Oi ^ CO t> CD -CO b- b- -O CO -U5OOiO5 -iCW -OiCO^THiCOO -CO -COCO -O5O -OOO - b- X b- OS b- b- 00 b- 00 b- 00 b- 00 b- -Ob- 00 b- 51 I * !2 COOO'O -rH^ b. ** CHAKACTER OF THE KATABOLISM. 87 CO b- 00 iO ^ CD b- rH CO '' CO CO i CO o b- OS CO ?3 IO CO IO O 00 U3 CO b- 00 . ** O OS CO b- CO 00 Tt< CO 00 CO O i-l CO coco -co N -coco co -co B . * * * *#** ...... 00 b- CO : ' * ff . . * . . ' * 30 2.50 2.70 2.90 3.10 3.30 3.50 3.70 3.90 4.10 4.30 4.50 4.70 4.90 5. Body Weight. Kilos. G. 2. Respiratory quotient of infants in first 24 hours referred to total body-weight. against the respiratory quotients obtained for the same period. A careful examination of the chart shows no tendency toward a variation in the average quotient as the weight varies. We must therefore infer that the respiratory quotient is independent of the weight. I.UU . . 1 . * - . S * TQ * ' V '" ' . ' .60 ' .082 .085 .052 .055 .058 .0.61 .064- .067 .070 .073 .076 .079 Body Weight per Cm. of Length. Kilo. FIG. 3. Respiratory quotient of infants in first 24 hours referred to body-weight per unit of length of infant. .094 92 PHYSIOLOGY OF THE NEW-BORN INFANT. Since, however, infants of approximately the same weight but of varying length may differ in the degree of nourishment, the relationship between the weight and the length of the infants may be of significance hi this connection; the weight per unit of length may thus be a better basis for comparison than the actual weight. The values have there- fore been compared on this basis in figure 3, in which the respiratory quotients have been plotted against the weight per unit of length. Using the average respiratory quotient of 0.80 as a base-line, we find no distinct tendency toward a grouping of the values. Such differences as may be apparent are not sufficiently striking to allow us to make any other deduction than that the respiratory quotient appears to be abso- lutely independent of the weight and the state of nutrition. Unfortu- nately our hospital and other data do not provide definite information regarding the degree of nutrition of the mothers. No relationship can therefore be established between the nature of the katabolism of the new-born inf ant in the first few hours after birth and the state of nutri- tion of the mother. GENERAL CONCLUSIONS AS TO CHARACTER OF KATABOLISM OF NEW-BORN INFANTS. From the results obtained in our experiments we are unable to verify Hasselbalch's conclusion that the metabolism of the new-born infant in the first few hours is chiefly of carbohydrate material. It is true that in practically none of our observations were we able to secure data so soon after birth as did Hasselbalch. Thus, while he frequently records observations beginning 30 to 45 minutes after birth and, indeed, in one instance 15 minutes after birth, our values were rarely obtained in observations less than an hour after birth, and for the most part they were 2 or more hours after birth. On the other hand, the time relations in our observations are fully comparable to the fragmentary data published by Bailey and Murlin, since in only two of their cases were observations made as early as 6 hours after birth, and there was but one period in each case. If we examine the data published by Hasselbalch, particularly the values given in table 2 (see page 21), we find that a great decrease in the respiratory quotient is accompanied by a very large decrease in the total katabolism as indicated by the carbon-dioxide production. Thus in his observation No. 17 the carbon-dioxide production per kilo- gram per hour was 344 c.c. and the respiratory quotient was 0.933, while the next period showed a carbon-dioxide production per kilogram per hour of only 275 c.c. and a respiratory quotient of 0.854. A similar relationship between the variations in the metabolism as indicated by CHARACTER OF THE KATABOLISM. 93 the carbon-dioxide production and the respiratory quotient is shown in observations Nos. 13-14 and 19-20. It will be remembered that in our consideration of the values in table 10 (see page 81), a like increase in the metabolism was found to accom- pany the abnormal increase in the respiratory quotient and that the conclusion was drawn that this increase was in part due to the muscular activity of the infant, and specifically to the excess carbon-dioxide produced in crying. The notes accompanying Hasselbalch's protocols specify that the infant was not crying; nevertheless we know too little at present regarding the ventilation of the lungs of new-born infants not to assume that there may certainly have been a distinctly excessive ventila- tion, with an accompanying increase in the carbon-dioxide excretion. We have here, then, an actual increase in the katabolism of considerable magnitude, with the high probability of there being somewhat more car- bon dioxide produced than oxygen consumed, the difference being suffi- cient to cause a corresponding variation in the respiratory quotient. The fact that in a large number of our observations of long duration these abnormally high quotients appear not only in the first hours, but, later, lends considerable strength to this supposition. We are inclined to believe, therefore, that Hasselbalch's conclusion that the higher respiratory quotients are obtained in those observations which are nearest to the birth is due not to the larger proportion of the glycogen taking part in the combustion, but to an increase in the carbon-dioxide excretion, owing to a disturbance in the mechanics of respiration. On the first day of life there is a gradual decrease in the respiratory quotient which is fully comparable to that experienced with any fasting organism in which the initial supply of glycogen is fairly liberal. On the other hand, the quotients found shortly after birth and the level to which they fall on the first day are not such as to justify the conclu- sion that there is an excessive glycogen storage in the body of the new- born infant. On the second and subsequent days the- respiratory quotients decrease, indicating a somewhat rapid depletion of glycogen until the quotient of 0.73 is reached, this being similar to the metabo- lism of fasting animals. When the milk-flow is fully established, and the body is in consequence supplied more liberally with carbohydrate material, the average respiratory quotient increases until at the end of the first week it is 0.81. No obvious relationship between the respiratory quotient and the size and condition of nourishment can be found from the data obtained. As information is lacking in regard to the degree of nourishment of the mothers, no study can be made of the relationship between the respira- tory quotient and this factor. 94 PHYSIOLOGY OF THE NEW-BORN INFANT. BASAL KATABOLISM. Direct measurements of the heat-production are only possible with extremely complicated and expensive calorimetric devices. Thus far no one has successfully completed such measurements with infants save Rowland. 1 As it was impracticable to make direct measure- ments of the heat-output in our study of the metabolism of new-born infants, we were obliged to content ourselves with the indirect method of computing the energy from the carbon-dioxide elimination and the oxygen consumption. Fortunately the interesting research of Rowland has shown that this method of determining the energy out- put gives results of a high degree of accuracy. On the other hand, it is impossible to compare the results obtained with an infant in half-hour or hour periods at different times of the day unless there was like extraneous muscular activity in the periods compared. It is much less possible to compare the results obtained with different infants without an assurance of complete muscular repose during the time of the observations. From the beginning of our research we have laid emphasis upon graphic records of the degree of muscular repose, and we are glad to note that this is now bearing fruit in that practically all experimenters are to-day of one mind regarding the absolute necessity of using periods of minimum activity for comparison. Even in so extended a series of observations as is reported here, we were not able with all of the infants to secure periods of absolutely minimum muscular activity. A critical examination of all the kymo- graph records was made independently by two skilled observers and periods of practically minimum activity were selected wherever it was possible. In the selection of these periods, however, actual minimum heat values were sought; a careful inspection was therefore made of the heat-production as computed from the carbon dioxide observed. Minimum values were secured for 94 out of the 105 infants. These results have been averaged and are given in table 12. It was rarely necessary to make use of a minimum value obtained from but one period in the series of observations with an infant. These periods of minimum activity and heat-production may be found with comparative ease by referring to the statistical table (see pages 46 to 79). lowland, Proc. Soc. Exp. Biol. and Med., 1911, 8, p. 63; Hoppe-Seyler's Zeitschr. f. Physiol. Chem., 1911, 74, p. 1; Trans. 15th Int. Congress on Hygiene and Demography, Washington, 1913, 2, p. 438. BASAL KATABOLISM. 95 TABLE 12. Minimum heat-production of new-born infants. Heat produced (computed) Average per 24 hours. Body- rectal tem- Per square meter Sub- ject XT Sex. weight with- out Length. Age. perature. Pulse- rate. Per (Lissauer, 10.3 X/W2). No. cloth- Total. kilo- Per ing. gram. Cent. Fahr. Total. centi- meter of i length. 1 kg. cm. cal. cal. cal. cal. 2 F. 3.80 53 6| days 36.8 98.2 99 152 40 606 11.4 3 M. 3.63 52 2 days 37.0 98.6 97 166 46 685 13.2 4 F. 3.28 46.5 2 days 37.2 99.0 105 139 43 612 13.2 5 M. 3.82 52.5 7 hrs. 36.9 98.4 112 137 36 544 6 M. 4.32 52 3 days 37.0 98.6 116 191 44 697 13A 8 M. 3.48 51 2 days 36.8 98.3 117 160 45 673 13.2 9 F. 4.04 51 2 days 37.3 99.2 109 178 44 677 13.3 10 M. 3.45 52 2 days 36.8 98.2 116 162 48 694 13.3 12 F. 4.17 52.5 5 days 37.0 98.6 112 171 41 639 12.2 13 F. 3.25 50 2 days 37.1 98.7 113 138 43 612 12.2 15 M. 3.64 50 4 days 37.0 98.6 122 162 44 665 13.3 16 F. 4.03 53 2| days 37.1 98.8 113 175 44 670 12.6 17 F. 3.66 52.5 15 hrs. 36.8 98.3 118 174 48 713 18 M. 2.84 50.5 7 days 36.6 97.9 105 108 38 519 10.3 19 M. 3.50 53 1^ days 36.9 98.5 114 155 44 653 12.3 20 F. 3.54 52 3| days 36.8 98.3 110 153 43 638 12.3 21 F. 2.92 50 2 days 36.9 98.4 121 136 47 645 12.9 22 F. 2.72 49 1\ days 36.8 98.2 114 128 47 635 13.0 25 M. 3.32 51.5 4 days 36.9 98.5 123 158 47 686 13.3 26 F. 3.46 50 5 days 37.2 98.9 113 151 44 645 12.9 27 M. 3.58 52 4 days 37.1 98.8 111 169 48 703 13.5 29 F. 3.37 50 2^ days 37.4 99.3 112 150 45 652 13.0 30 M. 3.33 51 2 days 37.1 98.7 114 144 43 623 12.2 31 M. 3.56 53.5 4 days 37.1 98.7 117 158 45 662 12.4 32 M. 3.42 47.5 2| days 36.9 98.5 116 140 41 604 12.7 33 M. 3.73 52 5 days 37.1 98.7 129 153 41 617 11.9 34 F. 2.90 50.5 2 days 37.2 98.9 115 134 47 638 12.6 35 F. 4.33 54 4 days 37.2 98.9 109 175 41 640 11.9 36 M. 3.33 53 21 hrs. 37.6 99.6 129 154 46 670 37 F. 2.49 46.5 13 hrs. 36.8 98.3 119 99 40 522 38 F. 3.90 51.5 \\ days 37.4 99.3 127 156 40 610 ii.8 39 F. 2.95 50 9 hrs. 36.5 97.7 105 113 38 533 40 F. 2.78 49.5 4| days 37.4 99.4 111 134 48 655 i3i2 42 F. 3.95 54 3 days 37.2 98.9 113 176 45 684 12.7 43 F. 3.62 50 2 days 37.6 99.6 119 165 46 682 13.6 44 F. 3.57 51 2 hrs. 36.9 98.4 103 136 38 567 45 F. 2.56 46.5 1 day 36.6 97.9 110 107 43 558 46 M. 3.83 51.5 5 hrs. 37.2 99.0 126 152 40 603 47 M. 3.51 52 5 hrs. 37.5 99.5 107 143 41 601 48 F. 4.52 54.5 6 days 36.9 98.4 132 188 42 667 12.2 49 F. 2.75 47.5 4 days 36.9 98.5 114 130 47 638 13.4 50 F. 2.75 48.5 1 day 36.4 97.6 89? 142 52 700 51 M. 3.73 52.5 2 days 36.9 98.5 96 154 42 623 11.9 52 F. 3.54 50 2? days 37.2 99.0 114 138 39 579 11.6 53 M. 2.87 47.5 2 days 37.7 99.9 126 143 50 684 14.4 54 M. 3.31 50 \\ days 37.1 98.7 106 129 39 563 11.3 55 M. 3.45 50 16 hrs. 36.9 98.4 124 151 44 641 56 M. 3.19 51.5 4 days 36.9 98.4 121 150 47 669 13.0 57 M. 3.75 54 22 hrs. 36.9 98.5 105 153 40 611 Computed only for infants of ages between 1| and 6 days inclusive. See fig. 10, p. 107. 96 PHYSIOLOGY OF THE NEW-BORN INFANT. TABLE 12. Minimum heat-production of new-born infants Continued. Age. Heat produced (computed) Average per 24 hours. Sub- ject "NTn Sex. Body- weight with- out Length. rectal tem- perature. Pulse- rate. Per Per square meter (Lissauer 10.3 v'w*). l^i O. cloth- Total. kilo- Per ing. gram. Cent. Fahr. Total. centi- meter of length. 1 kg. cm. cal. cal. cal. cal. 58 F. 3.01 49 1 day 37.2 98.9 Ill 139 46 647 59 F. 3.60 52 IT days 37.1 98.8 112 150 42 621 11.3 60 M. 3.60 52 4 days 37.0 98.6 117 149 42 617 11.9 61 M. 3.26 49.5 21 ^hrs. 36.6 97.8 121 123 38 542 62 M. 3.30 49.5 3 days 36.8 98.3 116 134 41 588 11.9 63 F. 2.37 47.5 3 days 37.2 98.9 125 109 46 596 12.5 64 F. 3.37 48 7 hrs. 36.7 98.1 98 128 38 552 65 F. 2.63 49 2 days 36.8 98.2 116 127 ; 48 644 13.1 66 M. 3.19 51 14 hrs. 36.3 97.4 103 122 1 38 543 67 M. 4.74 54 3 days 37.1 98.7 122 193 . 41 669 12^4 68 M. 2.12 46 4 days 36.8 98.3 113 103 48 604 13.1 69 M. 3.44 50 19 hrs. 36.9 98.5 110 142 ! 42 609 70 M. 3.56 51 2 days 36.9 98.5 109 153 43 640 12.5 71 M. 3.96 53.5 3 days 36.8 98.2 106 172 44 667 12.5 72 M. 3.29 50.5 2\ days 36.7 98.0 110 157 48 687 13.6 73 M. 3.63 50 7 hrs. 36.8 98.2 106 164 45 673 74 M. 3.63 52 2 days 36.8 98.3 94 156 43 640 12^3 75 M. 2.65 47.5 U days 36.6 97.9 100 132 50 664 14.0 76 M. 3.16 50 13 hrs. 36.7 98.0 101 137 44 618 78 M. 2.48 47 12 hrs. 36.4 97.6 101 109 44 577 79 F. 4.14 52.5 4 hrs. 36.9 98.4 116 153 37 575 80 M. 3.47 51.5 3 hrs. 36.4 97.6 109 128 37 542 81 F. 3.29 50 4 hrs. 36.9 98.4 114 167 51 732 82 M. 2.74 49 3 hrs. 36.4 97.6 101 95 35 470 83 M. 3.73 52 3 hrs. 37.2 99.0 131 148 40 597 84 F. 4.11 54 21 hrs. 36.5 97.7 109 133 32 504 85 M. 3.52 52 9 hrs. 36.8 98.2 109 i 144 41 605 86 F. 3.32 51 6 hrs. 36.6 97.8 103 120 36 524 87 M. 3.94 51 3^ hrs. 37.3 99.2 118 146 37 567 88 F. 2.62 47.5 9 hrs. 36.8 98.3 96 122 47 623 89 M. 3.24 49.5 8 hrs. 36.7 98.0 107 124 38 549 90 M. 3.00 50 21 days 36.8 98.2 86 138 46 641 12.S 91 F. 3.33 49.5 13 hrs. 37.4 99.4 113 140 42 609 92 F. 3.78 51 4 hrs. 36.6 97.8 112 157 42 628 93 M. 3.53 50.5 4 hrs. 36.8 98.2 127 136 39 573 94 M. 3.20 50 3i hrs. 36.8 98.2 117 136 43 607 95 F. 2.84 46.5 5^ hrs. 36.2 97.1 123 100 35 483 96 F. 3.23 51.5 3i hrs. 36.6 97.8 99 113 35 502 97 F. 2.82 48 4i hrs. 36.1 96.9 113 112 40 542 98 F. 2.86 47.5 5 hrs. 36.2 97.1 102 98 35 471 99 M. 3.58 51.5 2 \ hrs. 36.9 98.4 103 122 34 508 100 M. 4.65 54 hrs. 37.1 98.8 130 186 40 648 101 M. 3.88 51.5 5J hrs. 36.7 98.0 109 126 32 496 103 F. 3.29 49 2\ hrs. 37.5 99.5 125 130 40 570 104 M. 3.32 51 3 hrs. 36.4 97.6 107 105 32 459 Average of 94 sub- jects. . . 3.40 50.5 2 days 36.9 98.4 112 143 42 612 Computed only for infants of ages between \\ and 6 days inclusive. See fig. 10, p. 107. BASAL KATABOLISM. 97 In table 12 the minimum metabolism is expressed first as the total heat-production in 24 hours; second, as the heat-output per kilogram of body-weight per 24 hours ; and third, as the heat-output per square meter of body-surface per 24 hours. To explain these values further we have added the records for the body-weight without clothing, the length, the age, the average rectal temperature, and the pulse-rate for the periods of observation included in this table. TOTAL MINIMUM HEAT-PRODUCTION PER 24 HOURS. It will be seen that on the basis of the total minimum heat-production per 24 hours new-born infants may range from 193 calories found with subject 67 to a minimum of 95 calories found with subject 82. With so large a number of values as are given in table 12 it is difficult to discover any direct relationship between the body-weight and the total heat-output. The results have therefore been represented graphically in figure 4, in which the total heat-output per 24 hours has been 4.7 4.4 4.1 I 3.8 3,5 3.2 2.9 2.6 2.3 2.0 ^ 90 100 110 120 130 140 150 160 170 180 190 200 Calories per 24 Hours FIG. 4. Minimum heat-production of new-born infants per 24 hours referred to the body-weight. plotted against the actual body-weight of the individual infants at the time the metabolism was measured. The approximate average value is indicated in the chart by a heavy black line. As a matter of fact, this line represents a value of 42 calories per kilogram of body-weight per 24 hours. 98 PHYSIOLOGY OF THE NEW-BORN INFANT. Although one would expect with a large number of normal new-born infants to find a tendency towards constancy in the minimum metabo- lism, this chart shows clearly that there is no such constancy, for while in general there is a rough relationship between the total body-weight and the total minimum metabolism, in that for the most part the infants with the larger body-weight have the larger metabolism, yet wide deviations from the average value are found. Recently it has been the custom among some writers on metabolism to consider a plus or minus metabolism of 10 per cent as a possible nor- mal fluctuation. Although the arbitrary selection of this range seems questionable and we are unable to see what particular value the indi- vidual normal figures may have when the variation may admittedly be =*= 10 per cent, we have indicated these limits on the chart by light lines above and below the heavier line showing the average value. Even under these circumstances we find that a large number of the plotted figures lie outside of the supposedly acceptable limits of varia- tion, for 13 points are above the upper light line and at least 17 points below the lower light line; in other words, some 30 values lie outside of the 10 per cent limits of variation. Perhaps the most striking illustration of this fact is that of an infant weighing 4.1 kilo- grams and having a total heat-output per 24 hours of 133 calories. While the majority of the results obtained were well within the 10 per cent limits, yet, as our observations were made with new-born infants, presumably healthy organisms, which should be perfectly com- parable, it is somewhat surprising that variations are found as large as and, indeed, much larger than =*= 10 per cent. MINIMUM HEAT-OUTPUT PER KILOGRAM OF BODY-WEIGHT PER 24 HOURS. The highest value for the minimum heat-production in this series of observations was secured with infant No. 67, who had a body- weight of 4.74 kg., this being the largest body- weight of any of the infants; the lowest minimum heat-production was found with infant No. 82, whose body-weight was only 2.74 kg., although some of the infants had an even smaller body-weight than this. It is obvious, therefore, that body-weight plays an important r61e in the amount of the katabo- lism and the heat-production per unit of weight must be considered. The values for the heat-production per kilogram of body-weight given in table 12 vary from 52 calories per kilogram with infant No. 50 to 32 calories per kilogram with infants Nos. 84, 101, and 104. It is thus clear that, even per kilogram of body-weight, healthy new-born infants may vary widely in their energy output. Here again the general trend may be more easily seen in the form of a chart, and the values are therefore given on this basis in figure 5, which shows very clearly the wide variations in the values. Prac- tically no approximation to regularity is apparent, although a con- BASAL KATABOLISM. siderable number of the points lie within 10 per cent of the average value of 42 calories. If we draw lines at 38 and 46 to represent these limits of variation, we find that 13 values lie outside of the limits on the one side and 18 values on the other, there being in all some 33 per cent of the total number outside of the limits of variation. To indicate a true average value for a living organism on the basis of weight alone appears, therefore, to be extremely difficult, for even with these normal new-born infants, which are presumably more directly comparable than any other class of human beings, we still find wide variations. 4.7 4.4 4.1 1 3.8 k fa- 5 lu 2.9 2.6 2.3 2 '3 f . . . 1 s : 2 34 36 38 40 42 44 45 48 50 5, Calories per Kilo, per 24 Hours FIG. 5. Minimum heat-production of new-born infants per kilogram per 24 hours referred to the body-weight. MINIMUM HEAT-OUTPUT PER SQUARE METER PER 24 HOURS. Since the cube root of the square of the body-weight represents the general law of growth, and since physiologists, basing their belief upon the observations of Bergmann, 1 Rubner, 2 and Richet, 3 have been inclined to ascribe a particular significance to the relationship between the body-surface and the metabolism, the results computed on the basis of the heat-output per square meter of body-surface per 24 hours have been included in table 12. In our earlier publication 4 it was Bergmann and Leuckart, Anatomisch-physiol. Uebersicht des Thierreichs, Stuttgart, 1852, p. 272. See also, Bergmann, Ueber die Verhaltnisse der Warmeokonomie der Thiere zu ihrer Grosse, Gottingen, 1848, p. 9. 2 Rubner, Zeitschr. f. Biol., 1883, 19, p. 545. 3 Richet, Archives de Physiol. norm, et path., 1885, 15, 3d ser., p. 237. 'Benedict and Talbot, Carnegie Inst. Wash. Pub. No. 201, 1914, p. 166; Benedict and Talbot, Am. Journ. Diseases of Children, 1914, 8, p. 48. 100 PHYSIOLOGY OF THE NEW-BORN INFANT. shown that one of the greatest factors influencing thermogenesis, i. e., the active mass of protoplasmic tissue, probably develops according to the general fundamental law of growth as expressed by the cube root of the square of the body- weight. We feel wholly justified, there- fore, in attempting to study the heat-production of these infants on the empirical basis of the heat-output per square meter of body-surface per 24 hours. The actual measurement of the body-surface of these infants was impossible, as the methods used by Meeh and Lissauer were precluded and no other method giving accurate results was available. At the moment of writing a method which promises well, namely, the Du Bois formula, makes it not at all impossible that body-measurements may be practicable in future investigation of this type. As the data regarding the body-surface of these infants could not be obtained by means of actual measurement, we employed in our calculations the for- mula of Lissauer, in which the constant 10.3 is multiplied by the cube root of the square of the body-weight. The results thus obtained show that the average minimum heat- production per square meter of body-surface for the 94 infants was 612 calories per square meter per 24 hours. The largest minimum value was 732 calories with infant No. 81 and the smallest 459 calories with infant No. 104. Even on this basis, which is supposed to equalize not only all animals of similar species but also animals of different species, we do not find comparable values for these infants throughout the whole series. For a better visualization of the values for the heat-output com- puted on this basis and given in table 12, the minimum heat-production per square meter of body-surface per 24 hours has been plotted against the body-weight. (See fig. 6.) Here also we find very wide deviations from the average value of 612 calories. Using again, for the purpose of discussion, the hypothetical limits of =*= 10 per cent, i. e., 675 calories and 550 calories, respectively, we find that there are 18 values which are more than 10 per cent below the average value and 13 over 10 per cent above the average value. Thus in practically one-third of our observations the results obtained vary more than =*= 10 per cent from the average value. In considering the results obtained with our infants and graphically shown in figure 6, it is of particular interest to refer to the previous conception regarding the heat-production per square meter of body- surface of infants. Although infants have rarely been studied in the first week of post-natal life, the prevailing opinion of physiologists has been that very small and very young animals have proportionally a much larger heat-production than has the adult organism. From the review of the earlier literature given in our first report 1 it will be seen Benedict and Talbot, Carnegie Inst. Wash. Pub. No. 201, 1914, p. 11; also, Am. Journ. Diseases of Children, 1914, 8, p. 3 and 43. BASAL K AT ABOLISH. 101 that the general belief was that infants produced not far from 1,000 calories per square meter of body-surface in common with that sup- posedly produced by other living organisms. The first considerable reduction in this figure is noted in the writings of Schlossmann and Murschhauser, 1 in which they point out that the basal value is 866 calories per square meter. That this compares favorably with values obtained upon man is shown by Schlossmann and Murschhauser in an interesting way from the results of a single period selected from one of the earlier experiments of Atwater and his associates, in which a heat- production of 828 calories per square meter was observed. 4.7 4.4 4.1 3.8 3.5 3.2 2.9 2.6 2.3 2 -2 . . * * ' . , * - - . . . . ' . 50 480 500 520 540 560 580 600 620 640 660 680 700 720 74 Calories per Sq. Meter per 24 Hours FIG. 6. Minimum heat-production of new-born infants per square meter of body-surface per 24 hours referred to the body-weight. We may then say that up to the present time the general opinion has been that young infants had a larger metabolism than adults, that such measurements as were made previous to the observations of Schloss- mann and Murschhauser ascribe to the infant a heat-production of 1,000 calories per square meter of body-surface, and that the figure of Schlossmann and Murschhauser reduces this value to 866 calories per square meter of body-surface. It is of further interest that this value of 866 calories per square meter was obtained and reported by Schloss- mann and Murschhauser in full recognition of the significance of com- plete muscular repose during the observations, as is evidenced by their painstaking ocular notations of the degree of muscular repose which were made by^a specially trained assistant. Schlossmann and Murschhauser, Biochem. Zeitschr., 1910, 26, p. 32. 102 PHYSIOLOGY OF THE NEW-BORN INFANT. By reference to table 12, it will be seen that the vahie of 866 calories is over 100 calories higher than the higVM value there recorded, for only 3 observations are above 700 calories per square meter of body- surface, these being obtained with infants 17, 27, and 81, who had a heat-production per square meter of 713, 703, and 732 calories, respec- tively. The average minimum heat-production of 612 calories per square meter is 254 calories less than the minimum figure of Schloss- rnann and Murschhauser. Perhaps no better illustration than this can be found of the difficul- ties of securing accurate information regarding the probable trend of the metabolism of any group of individuals, in which one case that was carefully and continuously studied gave a value of 866 calories per square nieter of body-surface, and a later research, in which 100 or more cases were studied, gave results very much lower, no value being secured within essentially 130 calories of the minimum obtained by the previous investigators. The cause for this discrepancy may readily be found, we believe, in the inherent difficulties in obtaining metabolism measurements when the experimental periods must of necessity be of several hours duration, as was the cam with Schlossmann and Murschhauser. Had these observers been able to measure the metabolism of their infant in selected half-hour periods, we have no doubt that their value of 866 calories would have been materially reduced. The value of 866 calories reported by Schlossmann and Murschhauser was not obtained with a new-born infant, but at the time their observa- tions were published it was the general impression among pediatricians that the metabolism of the new-born infant would be even higher per unit of surface than that of an infant several months old. Accordingly, the difference between our average minimum value of 612 calories and the minimum value of Schlossmann and Murschhauser of 866 calories per square meter of body-surface is, to say the least, most striking. It should likewise be borne in mind that it is unpractical to use here for comparison the heat-production per square meter per 24 hours recorded for the infants studied in our previous research, 1 for these latter include a large number of atrophic infants whose metabolism is admittedly above normal. Although our material is slowly accumulating for an estimation of the metabolism of perfectly normal infants from the time of birth to the age of 2 years, we are not yet in a position to draw con- clusions that will necessarily withstand subsequent addition of data: we prefer, therefore, to defer the making of general deductions until later. INFLUENCE OF AGE UPON THE KATABOUSM. A general inspection of the values given in table 12 indicates that in the first week of life there is some connection between the age and the ^Benedict and Talbot. Carnegie lust. Wash. Pub. N