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In a previous study of the basal metabolism of premature infants1 it was noted that when the infants were on a diet of human milk the nitrogen in the urine collected for short periods while the infants were in the respiratory chamber represented only 5 per cent of the total heat production.2 When cow's milk was used, the urinary nitrogen increased to represent 17 per cent of the total calories.These findings seemed to confirm the popular conception that the protein of human milk is better suited for retention by the growing human organism than the protein of cow's milk. This conclusion is, however, unwarranted, since the infants on the two types of diet received protein differing not only in quality but also in quantity.Observations were therefore planned in which the retention of nitrogen by premature infants fed human milk and that by premature infants fed formulas

Calorimetric studies of basal metabolism have demonstrated that the human subject from infancy to old age eliminates a constant proportion, approximately 25 per cent, of the heat produced by basal metabolism in the vaporization of water through the skin and lungs.1 Since water vapor forms under basal conditions a relatively fixed fraction of the total insensible perspiration (insensible loss of body weight) as measured with the balance, Benedict and Root2 used the latter as a simple and practical method for predicting the basal metabolism of adults, and Levine, Wilson and Kelly3 subsequently applied this method of prediction to infants in the basal state. The procedure was next extended by Newburgh and his colleagues4 to estimations of the total heat production of adults under maintenance conditions over long periods. These workers5 soon modified their original procedure by utilizing the water vapor alone (H2O) rather

In a previous paper of this series,1 basal standards were presented for the insensible perspiration of normal and marasmic infants. The constancy of these standards was demonstrated within a range of environmental conditions2 analogous to the standard conditions for measuring their basal metabolism. Beyond this range, the extrinsic factors of clothing, temperature, humidity, diet and muscular activity were shown to exert a notable influence on this measurement.With basal standards available for normal infants, the next problem was to investigate the effect of pathologic states on this mechanism during infancy. Since water vapor forms the main component of the insensible perspiration,3 it seemed reasonable to assume that the state of hydration of the body was an important factor in its regulation and that any derangement of the water metabolism might lead to alterations in its measurement. A classic example of deranged water exchange in the infantile organism

In a recent communication1 tentative standards were proposed for the basal insensible perspiration of normal infants analogous to the well known standards at present available for their basal metabolism. Before accepting the newly proposed standards, it seemed advisable to make a comparative study of the reliability of the two series of basal standards. Such a study would also serve to show any correlation that might exist between the two physiologic mechanisms. If the correlation were shown to be of high degree, the data might afford a possible method of predicting the probable metabolism of infants from their measured insensible perspiration. This procedure would be especially valuable since present methods of estimating the respiratory exchange of infants are time-consuming and technically difficult compared with the relatively simple method of weighing for measuring their insensible loss.2 Since evidence of reliability and of correlation in both instances involved the employment of

As part of a study of the role of environmental oxygen on retrolental fibroplasia in premature infants of low birth weight,1 observations were made on the tolerance of these infants to early removal from oxygen. Because of the common occurrence of respiratory irregularities associated with immaturity of the respiratory tree, the respiratory center, and the structures of the thoracic cage and the frequent superimposition of intracranial hemorrhage at birth,2 it has been customary to provide small premature infants with an oxygen-rich environment.3 When evidence began to accumulate of the possible harmful effect of oxygen therapy in the causation of retrolental fibroplasia,* it became important to reexamine the necessity for this form of therapy. PLAN OF STUDY The routine practice in the premature nursery of the New York Hospital was to place infants with a birth weight below 1650 gm. in an incubator supplied with oxygen, regardless of

Quantitative measurements of the water exchange of premature infants are essential for defining their fluid requirements because of their weak appetites and because factors other than feeding contribute so much to their well-being. This paper presents the results of such measurements made on 12 premature infants fed varying diets but studied under constant environmental conditions. APPARATUS AND METHODS A detailed description of the methods employed for analysis of the diet and excreta (urine and feces), for measurement of the twenty-four hour insensible loss from skin and lungs, for determination of the daily respiratory exchange and for calculation of the composition of the metabolic mixture was given in previous papers.1 The "direct," or "metabolic," method2 of calculation of the water exchange was used because it gives information concerning not only the total water balance but also the partition of excretion via urine, feces and skin and lungs. According to

In a recent paper on infant feeding1 the statement is made that one of the problems for further study concerns the best method of feeding the premature infant. The lack of unanimity concerning one aspect of the problem, the proper caloric intake, is indicated in two reviews,2 which state that various authors recommend from 75 to 200 calories or more per kilogram of body weight per day. This wide variability derives from: (1) the difficulty of clinical assessment because of the weak sucking reflex and inadequate manifestations of hunger; (2) the paucity of quantitative data on the total energy exchange of premature infants,3 and (3) the participation of factors other than diet, such as nursing, environmental conditions and infections, in determining the progress of the premature infant. As part of a systematic investigation of the metabolism of premature infants which may ultimately help to define more clearly

The choice of a subject for the opening address to the Society is a traditional prerogative of its president and I have selected "Pediatric Education at the Crossroads" as timely and important.I'd like to begin by telling you what is, unhappily, a true story. Recently I met with a former house officer of the mid 1940s. He was a sensible and well-balanced man, an excellent clinician with a warm love and understanding of children, and he had gone into practice with the highest hopes.I now learned he had given up practice to resume full-time work. For over a decade, it emerged, the practice of pediatrics had somehow never lived up to his earlier expectations. He listed, among other negative aspects: long hours of routine work; continuous harassment by parents, including night telephone calls and daylight nagging, and, most important of all, a lack of intellectual excitement, challenge, and

HUMAN milk is widely regarded as the food of choice for premature infants. Recently summarized laboratory investigations1 have cast doubt on this widely held clinical impression. To reassess the problem, carefully controlled clinical studies were undertaken comparing the progress of premature infants fed isocaloric amounts of human milk or mixtures of cow's milk under comparable conditions of nursing, medical and environmental conditions. The present report compares the gains in weight of 122 premature infants whose weights at birth were between 1,000 and 2,000 grams (2 pounds, 3 ounces and 4 pounds, 6 ounces), all of whom were fed isocaloric amounts of either human milk, a simple mixture of evaporated milk or a mixture of partially skimmed cow's milk. The results indicate that greater gains in weight were achieved with the mixture of partially skimmed milk2 than with evaporated milk, and that both mixtures of cow's milk were superior

The newly born infant must make a number of physiologic adjustments in transit from a parasitic intrauterine to an independent extrauterine existence. The infant who is born at term is usually able to make these adjustments successfully, and in consequence his chances of survival are good. On the other hand, the physiologic immaturity of the prematurely born infant renders his organism less well equipped to cope with the external hazards encountered at birth, with the result that his capacity for satisfactory adaptation is low and his neonatal mortality correspondingly high. It is estimated that of the 2,000,000 full term babies born each year in the United States 95 or 96 of every 100 reach their first birthday, whereas not more than 65 or 70 of every 100 of the 100,000 premature babies born annually survive their first year. The importance of prematurity as a cause of death in the newborn

In this portion of the review, consideration will be given to some important clinical measures which have proved their usefulness in combating the inordinately high death rate of premature infants, especially in the neonatal period. Because the health of the mother and conditions in utero and at delivery are reflected in the well-being of the offspring, a proper supervisory program for the health of premature infants necessarily begins in the antenatal and intranatal periods. Table 1 contains a list of suggested measures designed to lower the mortality of premature infants.These so-called obstetric aids are separated in the table into general prophylactic measures which may be taken during pregnancy to prolong the gestation period of the fetus in utero and specific preventive and therapeutic procedures which may aid in combating some of the commonly impending symptoms.The general measures include institution of an antepartum program of diet, hygiene and general

The importance of water in the preservation of health and in the treatment of disease in infancy and in childhood has been recognized for many years. The infantile organism is especially hydrolabile, probably because of its high content of body water; this content comprises over 70 per cent in the newly born infant, as against less than 60 per cent in the adult. This hydrolabile tendency is exemplified by the wide fluctuations in daily body weight of healthy infants while on constant diets, by the ready development of dehydration fever in newly born and in older infants temporarily deprived of water and by the occurrence of anhydremia as a frequent accompaniment of infantile diarrhea.Despite the importance of water to infants, knowledge of their fluid requirements has in large measure been deduced from measurements of the average amounts of milk voluntarily withdrawn from the breast by nursing infants. These observations

The metabolism of creatine and creatinine has attracted widespread interest in recent years. Although creatinine was first recognized in 1832,1 the impetus to study its metabolism arose from the publication by Folin2 in 1904 of a simple method for its determination. Numerous investigations during the last three decades have established the constancy of the presence of creatinine in the urine and of creatine under certain normal and pathologic conditions. The regularity of the excretion of creatinine indicated that it was a waste product of the body, but the function of creatine remained an open question, although the Eggletons3 and Fiske and Subbarow4 have recently demonstrated the importance of phosphocreatine in muscle metabolism.The classic monograph by Hunter5 summarized the results of studies of creatine and creatinine up to 1928. This was supplemented by the review of Rose6 in 1933. No attempt, therefore, will be

The parenteral administration of fat as a potential source of energy has long appealed to clinical investigators. Evidence of the availability to the organism of fat so administered has for the most part been adduced by indirect methods of approach. Such studies include: chemical analyses of the blood; chemical and histologic examination of the sites of injection, regional lymph nodes and various viscera following parenteral administration of fat; studies of nitrogen balance; studies of absorption and excretion of fat-soluble drugs and dyes; observations on the utilization of fat-soluble vitamins, and finally clinical records of the response of malnourished persons to repeated injections of fat. The results secured from these indirect lines of investigation are far from conclusive, but they suggest that some preparations may be utilized by the organism under certain conditions. The literature covering these studies, which has accumulated since the experiments of von Leube1 in 1895, was

Only an occasional report of twenty-four hour measurements of the energy exchange of infants is available in the literature. The published list comprises three observations by Rubner and Heubner1 and two by Talbot2a on normal infants. Actual balance studies of the total energy requirements of normal infants inclusive of their needs for growth are missing from the literature. The only studies of this nature which are available are those on two premature infants reported by Rubner and Langstein in 1915.2b This paucity of data is undoubtedly ascribable to the many technical difficulties inherent in prolonged measurements of the respiratory metabolism of infants and in concurrent analyses of their diet and excreta. Despite these obstacles, such balance studies are imperative, since the modern systems of feeding infants are predicated in large part on an accurate knowledge of their daily energy needs.The energy supplements which combine to make

The calorigenic action of thyroid extracts in normal infants was demonstrated in the preceding paper of this series.1 The increased expenditure of energy was shown to be due to an accelerated combustion of fat and of carbohydrate in proportions similar to those metabolized under basal conditions, as indicated by the constant levels of the respiratory quotients before and during treatment with the extracts. These results corroborate in part studies of adults2 showing that under the stimulus of an excess of thyroxine the body cells consume at an accelerated rate whatever type of food is brought them.The preceding study, however, gave no information regarding the metabolism of protein, since the nitrogen elimination in the urine was not determined during calorimetric observations. This supplementary study of protein metabolism was therefore undertaken to make available complete data for determining the character of the intermediary metabolism of the essential foodstuffs in

Experimental evidence and clinical experience have fully established the calorifacient action of thyroid substance in thyroidectomized animals and in man with hypothyroidism. Published studies of normal animals1 and of men and women without hypothyroidism2 are not as conclusive, but in general they tend to show that the drug induces a similar but less constant response in these subjects. To our knowledge, the literature contains few references to similar metabolic studies in infants and children without hypothyroidism.3 Such investigations should be of physiologic interest and of clinical assistance in appraising the rôle of thyroid therapy in these subjects in other than hypothyroid states.Another phase of the thyroid problem that merits further study relates to the relative potency of the different commercial preparations in common use. At the present time, the drug is officially standardized according to its iodine content. This method of standardization was adopted chiefly as

Reliable standards have been established for estimating the basal metabolism of adults.1 All workers agree that with careful technic a deviation of ±10 or at most 15 per cent in an adult is indicative of an abnormal basal metabolic rate.No such certainty exists with regard to the generally accepted basal standards for infants and children. Within this age range, the only investigations that define with any precision the reliability and normal limits of variation of the accepted standards are the biometric study of the published data for new-born infants by Harris and Benedict,2 and a statistical analysis of the same data by Murlin.3 To our knowledge, no similar studies are available for older infants and children. In addition, satisfactory standards for estimating the basal metabolism of premature and marasmic infants have not as yet been proposed. These gaps in our knowledge make it extremely difficult for

It is evident from recent work on normal animals that following the administration of insulin in large doses marked changes occur in the glucose, lactic acid,1and inorganic phosphate2content of the blood. Since these constituents seem to be intimately concerned with the metabolism of carbohydrate, it was desirable to extend the study of them to human beings, more especially to diabetics. Also, since the combustion of glucose as well as the formation of lactic acid has a profound influence on the respiratory quotient the metabolism was determined using the respiration calorimeter of the Russell Sage Institute of Pathology.Four patients with uncomplicated diabetes were studied. They varied from extremely mild to moderately severe. In each case the effect of a single intravenous dose varying from 8 to 33 units of insulin (Iletin, Lilly) was observed. The blood was taken before, and between 1 and 2 hours after, the injection, and analyzed for sugar, lactic acid, and inorganic phosphates. The respiratory metabolism was determined in the calorimeter beginning about 15 to 75 minutes after the injection and continuing for 45 minutes. The patient was then removed from the calorimeter, and a blood sample was drawn for analysis. Immediately after, he was returned to the calorimeter and observed for another three hours. For comparison, a three-hour basal observation of the previous day was used.The results in the table clearly demonstrate that the invariable fall of blood glucose following insulin administration is not always accompanied by a rise in lactic acid.Three separate observations were made on patient E. V. In only one instance was the lactic acid concentration increased after insulin. Although the absolute drop in blood sugar was greater in the other two, 214 mg., and 82 mg. per 100 cc. respectively, no rise in the lactic acid was found.