THE Cornell University Library RG 600.S6 The nutrition of the *et"S, 3 1924 003 464 710 LIBRARY OF THE NEW YORK STATE COLLEGE OF HOME ECONOMICS CORNELL UNIVERSIT-Y- ITHACA, NEW YORK Cornell University Library The original of tliis bool< is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924003464710 THE NUTRITION OF THE FETUS THE NUTRITION OF THE FETUS BY J. MORRIS SLEMONS NEW HAVEN YALE UNIVERSITY PRESS LONDON: HUMPHREY MILFORD: OXFORD UNIVERSITY PRESS MDCCCCXIX Copyright, 1919, by The American Journal of Obstetrics COPYBIOHT, 1919, BY Yale University Press THE INVESTIGATIONS BY THE AUTHOR AND HIS COLLABOEATOES WHICH AEE THE BASIS OF THIS EEPOET WEEB MADE IN THE / DEPAETMENT OF 0BSTETEIG8 AND GYNECOLOGY YALE MEDICAL SCHOOL THEOUGH THE USE OF THE JULIA E. BEOOKEE F^D THE NUTRITION OF THE FETUS* Pbegnancy is essentially^ a , problem in nutrition, and at this time the dominant metabolic forces are those which favor growth. The mother's gradual but con- sistent gain in weight amounts finally to about 30 pounds; exceptionally, it is as little as 10 to 15 pounds, and at the other extreme as much as 40 to 50 pounds. With individuals inclined to be stout the in- crease is greater; and it is relatively greater in later pregnancies than in the first. During the early months of gesta- tion the weight generally remains station- ary or suffers a slight loss ; even in those instances in which the weight begins to increase shortly after conception, the gain is less marked in the early months than later. For the last three months the aver- age monthly gain has been found to be be- tween 3.5 and 5.5 pounds. The mother's increase in weight is at- *The Oration in Obstetrics before the Ontario Medi- cal Association at Toronto, May, 1919. Eeprinted from the American Journal of Obstetrics. 8 THE NUTRITION OP THE FETUS tributable in part to the fetus, the placenta, the amniotic fluid, the uterus, and the breasts; but to some extent all the ma- ternal tissues respond to the stimulus toward growth. Probably the relative im- portance of this last factor is too easily overlooked, for, naturally, the special de- velopment of the ovum first seizes upon and is likely to monopolize the attention. On the other hand, the extent of the par- ticipation of the mother's body in the growth of the gestation period may be shown by a simple arithmetical calculation. Thus, if the weight of the product of con- ception at full term together with that of the parturient uterus is deducted from the mother's total gain in weight, it appears that only about half of her increase is ac- counted for. Obviously, the remainder must be ascribed to her body tissues in general. This fact suggests the correct answer to a question which physiologists have often submitted to experiment, namely, "Does the material provided for the growth of the ovum come from the mother's tissues or from her food?" At first it was believed that, for the mother, pregnancy constituted a period of sacrifice and that fetal growth occurred at the expense of her tissues. Exceptio n- ally, if the m othe r ^s food is inadequate, this may be true. It is conceivable, too, that small amounts of various materials derived from the mother's tissues may be contributed regularly to the ovum while its implantation is in progress, but in a quantitative sense the requirements of the very early stages of development are neg- ligible, and the period itself is a brief one, probably no longer than the time required for adjustment between the blastocyst and the uterine circulation. With data at hand to support it, the cur- rent view holds that pregnancy repre- sents for the mother a period of gain, rather than of sacrifice, and accordingly that her tissues are not deprived of ma- terial to supply the new organism. Both animal experiments and observations upon women indicate that the mother's "food 10 THE NUTRITION OP THE FETUS furnishes the substances ^incorporated in the body of the fetus. Thus, in the case of dogs, elaborate analyses of the food on the one hand and of the excreta on the other teach that a notable storage of the foodstuffs is characteristic of pregnancy. Furthermore, if this storage is compared with the amount of material contained in the bodies of the young it appears that the mother's food is sufficient not onlyjo^meet her own requirements, but also t hose of fetal development. Similar studies in which Bar selected rabbits as the subject of experiment led to an identical conclu- sion. And with regard to women, Wilson concludes from his extensive studies of nitrogenous^ietabolism during pregnancy that an ordinary diet provides for every fet al re tirement and permits storage to begin in the maternal organism at a much earlier period than was generally sup- posedj perhaps it begins at the very outset of pregnancy. What are the substances required for fetal nutrition? This question may be an- swered in two ways. On the one hand, we may infer the needs of the fetus from those of the newborn infant which, of course, is THE NUTRITION OP THE FETUS 11 sustained by its mother/s milk, a fluid of familiar composition. Or, on the other hand, upon the fair assumption that the substances found in the~ fetus represent its requirements for growth we may resort to the analysis of its body. From informa- tion of this kind we conclude that there is no great difference between the fetus and the adult so far as the quality of the food they require is concerned: in their life processes both use the same organic and inorganic substancies which are a,lways available in the circulating blood of the mother. The constitutents of the mother's blood include nutrient nitrogenous substances, carbohydrate, fat, oxygen, water, and in- organic salts; together these meet all the requirements for tissue growth and en- ergy production. That they are at the dis- posal of the fetus, there call be no question, but it is equally certain that none of these materials may pass directly into its circu- lation. Aeros s^the path tra,versed by these subs tances on thei r way from the parent to her_offspring lies, a coi^l^^organ, the placenta, composed partly of a specialized uterine tissue but mainly of elements de- 12 THE NUTRITION OF THE FETUS rived from the luxuriant development of a portion of the fetal membranes — the cho- rion frondosum. The obstructive action of the placenta was demonstrated by the ex- periments of John and William Hunter, These investigators proved that the mother's blood never enters the fetus and also that the reverse phenomenon is impos- sible. More recently, and especially after the invention of the microscope and im- provements in histological technique, em- bryology has gradually accumulated the facts which now make the chapter on the morphology of the placenta both intimate and nearly complete. The architectural arrangement of this organ which accommodates simultaneously the fetal and maternal circulations, yet holds them apart, is so well known that there is no longer any doubt regarding the path each follows. Venous blood from the fetus enters the placenta by way of the um- bilical arteries, which divide i again and again to form a multitude of capillaries. Subsequently, these reunite into a single vessel, the umbilical vein, through which the arterialized blood returns to the fetal heart. THE NUTRITION OF THE FETUS 13 Chiefly by the division and subdivisioh of the fetal vessels in the placenta, an ex^ tensive vascular bed is created. The bed is notably enlarged by the arrangement of the smallest of these vessels, which form loops hanging toward the maternal blood. With this, however, the fetal vessels do not come into direct contact, for they are covered with connective tissue and this in turn with embryonic epithelium. To- gether with their enclosing layers of tissue the capillary loops constitute the chorionic villi. During the early months of preg- nancy the epithelial covering of the villi forms two layers but later is reduced to a single layer of about the thickness of endo- thelium. Thus, the thickness and complex- ity of the placental partition varies in- versely with the nutritional requirements of the new organism, for at first the material requirements of the embryo are infinitesimal. Although they increase gradually, these requirements are insig- nificant in a quantitative sense until after the 18th to 20th week of pregnancy; and about this time also the simplification of the placental partition takes place. In- deed, it is not unlikely that the anatomical 14 THE NUTRITION OF THE FETUS transition is intended to promote the physiological interchange between the fetal and maternal circulations, thus to secure for the new organism a more rapid rate of growth. ThaJBiatejeaai- blood, whifih„ suppUes Jhe fetus with everything it needs. , and ooijici- dently removes its excretory products, en- ters the placenta through the branches of the uterine arteries and departs through the uterine veins. As it passes through this organ, the mother's blood comes into contact with the surface of the villi where the requisite exchange of foodstuffs and waste products takes place. Certain sub- stances pass in one direction while others are passing in the opposite direction; but all traverse the same placental partition which, as we have seen, consists in the latter half of pregnancy of a thin covering of epithelium, a layer of connective tissue and, within this, the delicate wall of the fetal capillary. How substances pass through the pla- cental partition is a question answered, thus far, only hypothetically. There has been no lack of speculation on the subject. In the main two antagonistic theories have THE NUTRITION OF THE FETUS 15 been developed ; one of these, the vitalistic, assumes that the wall of the chorionic vil- lus takes an active part in the placental interchange;' the other, the mechanistic, regards this wall as a passive, semi-perme- able membrane conforming with the laws of osmosis and diffusion. 1. The Vitalistic Hypothesis. That the placenta actually digests the food of the fetus was suggested by William Harvey, who attempted to establish a complete analogy between the chorionic and the intestinal villi. This view gained many ad- herents after Hofbauer and others demon- strated the presence of enzymes in the placenta, though it was never shown that these lipolytic, diastatic, and proteolytic enzymes are agents in the placental inter- change. On the contrary, it is likely that they have to do only with the living pro- cesses of the cells which contain them. 2. The Mechanistic Hypothesis. In the transmission of a few substances, it has been positively proved that the placental partition plays a passive role and behaves as a semi-permeable membrane. Thus, oxygen and carbon dioxide, we are taught by the experiments of Cohnstein and 16 THE NUTRITION OF THE FETUS Zuntz, pass equally well from mother to fetus or in the opposite direction, and al- ways move from the point of higher to that of lower concentration. Probably the laws of diffusion apply to the placental trans- mission of the anaesthetics, chloroform, ether, and nitrous oxide; though they do not apply to gases, like carbon monoxide, which enter into chemical combination with haemoglobin. Cohnstein and Zuntz found also that sodium chloride passed the placenta by osmosis. The evidence they obtained relative to the transmission of glucose was not conclusive, though it seemed likely that osmosis was the process concerned. II One fundamental fact regarding pla- cental transmission was established by the experiments of Grnsserow and his associ- ates, namely, provided the placenta is normal, no insoluble substance may pass it. The formed elements of the blood are con- fined to that circulation in which they originate; consequently, an infant whose mother is suffering from leukaemia, pre- sents a normal blood picture. Moreover, cinnabar, barium sulphate, and other insol- uble compounds, when introduced into either the mother or the fetus, are effectu- ally confined within the circulation where they are introduced. On the other hand, a variety of soluble substances when in- jected into the mother may be detected later in the fetus ; and the reverse experi- ment yields analogous results. From re- ports of such tests, Kehrer stated in 1907 that of 73 substances examined 43 were found to pass readily through the placenta. Many of the latter substances are poison- ous and, indeed, were selected for that 18 THE NUTRITION OP THE FETUS reason, because a toxic action often assists in determining the result of such an experi- ment. Thus, strychnine, hydrocyanic acid, nicotine, curare, pilocarpine, physostig- mine, phloridzine, sodium sulphate, methy- lene blue, and epinephrine have been dem- onstrated in the mother after they were injected into the fetus. With the exception of carbon dioxide, no fetal excretory product has been the sub- ject of serious investigation. The sugges- tion of Halban and Fleck, that the chori- onic villi elaborate an internal secretion which controls fetal excretion, proceeds entirely from theoretical considerations. "At present," we read in "Doderlein's Handbuch der Geburtshiilfe (1915)," "it is impossible to say more than that fetal waste products make their way to the pla- centa and through it reach the maternal organism which subsequently eliminates them. ' ' Since so little is known of the principles involved in the placental interchange, and direct study of the problem by means of animal experimentation is limited by almost insurmountable diflSculties, we have turned to clinical observations in the hope THE NUTRITION OF THE FETUS 19 of learning what is the character of the mechanism in question. We secured speci- mens of maternal and fetal blood simulta- neously, just after the infant was born. The fetal blood was obtained from the pla- cental end of the severed cord, the mater- nal from one of the veins in the forearm. Current methods of chemical analysis yield accurate results even with small specimens of blood. Therefore, at times, in a given specimen we were able to es- timate a number of its ingredients, but more frequently we were restricted to the estimation of one or two. Although this limitation has made progress slow, it has had the effect of increasing the number of cases studied and thus broadened our ex- perience. We have gathered data, thus far, relative to the organic foodstuffs, pro- tein, carbohydrate, and fat; and it will be convenient to discuss them separately, in the order named, considering the waste products of nitrogenous metabolism along with the foodstuffs from which they are derived. Ill Protein, distinguished among the food- stuffs because it contains the chemical ele- ment, nitrogen, may not be utilized di- rectly by our tissues. Intestinal digestion breaks down protein into much simpler ni- trogenous compounds, the amino acids, which are absorbed into the blood stream and distributed to every part of the body. The amino acids are used both for con- struction and repair ; and, according to the organ which employs them, they are built into one variety of protein or another, probably of a very different character from that of the protein in the diet which originally supplied them. Now, tissue metabolism, which is the name given the intricate and poorly under- stood phenomenon just referred to, has another side. As long as life lasts tissue protein is being torn down, or perhaps burned down, with the result that chemical compounds are formed which our bodies are incapable of utilizing; therefore, they are called waste products. These com- THE NUTRITION OF THE FETUS 21 NON-PEOTEIN NITROGEN AND UEEA NITROGEN OP THE WHOLE BLOOD Urea- N.P.N. nitro- ■ No. Source Para mg. per 100 cc. sen mgr. per 100 oc. Remarks 1 Mother Fetus I 20.2 20.5 9.3 8.9 No anaesthetic. 2 Mother Fetus I 26.5 27.2 9.8 10.7 Whiffs of chloroform. 3 Mother Fetus I 21.7 20.0 9.3 8.4 Whiffs of chloroform. 4 Mother Fetus I 20.0 19.0 9.8 11.7 Deep chloroform. 5 Mother Fetus n 22.5 22.0 9.8 9.8 No anaesthetic. 6 Mother Fetus n 23.5 20.0 10.3 8.9 No anaesthetic. 7 Mother Fetus 11 21.7 21.7 10.2 9.3 No anaesthetic. ,8 Mother Fetus n 21.2 22.5 8.9 10.3 Whiffs of chloroform. 9 Mother Fetus n 28.2 26.5 13.5 12.1 Whiffs of chloroform. 10 Mother Fetus n 19.5 19.2 8.4 7.9 Whiffs of chloroform. 11 Mother Fetus n 18.5 18.5 8.4 9.3 Whiffs of chloroform. 12 Mother Fetus m 26.5 27.5 10.8 11.7 Whiffs of chloroform. 13 Mother Fetus rv 27.7 27.2 13.1 13.5 Whiffs of chloroform. 14 Mother Fetus V 29.7 24.2 14.0 13.5 Whiffs of chloroform. 15 Mother Fetus vm 27.7 24.7 11.2 9.8 No anaesthetic. 16 Mother Fetus IX 27.7 27.5 12.6 11.7 Whiffs of chloroform. 22 THE NUTRITION OF THE FETUS pounds, too, are much simpler in structure than protein though, like it, they are char- acterized by the presence of nitrogen in their molecules. Besides certain well-known proteins, then, our blood contains a number of other nitrogenous substances. Perhaps, it is fair to regard the blood protein as reserve material and to regard the non-protein compounds as those momentarily engaged in nitrogenous metabolism. The latter, as I have indicated, differ greatly, since they include both nutritive material and waste products ; but on account of a certain simi- larity in chemical behavior they may be es- timated collectively, and when grouped in this way are designated as the non-protein nitrogen of the blood. For the estimation of the non-protein ni- trogen a remarkably accurate and satis- factory method was devised by Folin. We have employed it in 35 cases in which nor- mal pregnancy concluded with a sponta- neous delivery ; we found in the case of the mother an average of 25.2 mg. of non-pro- tein nitrogen per 100 cc. of blood and in the case of the fetus 24.9 mg. The impressive resemblance between THE NUTRITION OP THE FETUS 23 these figures does not depend upon the fact that they represent a mean value. The results are expressed in that form merely as a matter of convenience, for, examined individually, the cases exhibit the same equality of maternal and fetal non-protein nitrogen. Thus, in 20 cases the results for the two organisms did not differ by more than a milligram and in the others the dif- ference was usually less than two milli- grams. The most instructive illustration of this similarity in the composition of ma- ternal and fetal blood is afforded by a case of twins in which the mother presented 30 mg. and each infant 30.2 mg. of non-pro- tein nitrogen per 100 cc. of blood. The equality of the non-protein nitro- gen in maternal and fetal blood indicates that its various constituents, belonging in part to the class of foods and in part to the class of waste products, pass freely through the placental partition. Indeed, our findings suggest even more than that. There must be a regulatory mechanism which maintains the same concentration of non-protein nitrogen in the two circula- tions ; and such a strict equality of concen- tration, we are at a loss to explain on any 24 THE NUTRITION OF THE FETUS other basis than that of simple diffusion. This process, as we know, permits the ready passage of certain substances through a semi-permeable membrane, and to secure an equal concentration on both sides of the partition may be said to be its very aim. However, without further evi- dence of a more detailed character, it would be hazardous to announce a final conclusion, for each of the substances in- cluded in the non-protein nitrogen should be studied separately. As that has been done, we may proceed to examine, indi- vidually, the amino acids, urea, ammonia, uric acid and creatinine; for, besides pro- tein, these are the ingredients of the blood, distinguished by the fact that they contain nitrogen. IV The amino acids are crystalline, more or less soluble compounds ; and on account of these and other physical and chemical properties they :would be expected to be diffusible substances. They actually are, as Abel showed by means of collodion tubes ingeniously contrived to accommo- date an artifical circulation of the blood and to arrange for the collection of sub- stances escaping by diffusion through the tube wall. Other experimenters have con- firmed Abel's statement that amino acids pass readily across such a permeable par- tition, and that in general amino acids pass into the body tissues by the process of diffusion. Until very recently, it was not suspected that amino acids, supplied by the mother, are the material out of which fetal protein is constructed. Albumoses were thought to serve this purpose, for, although they were not demonstrable in either maternal or fetal blood, they were isolated from the placenta itself. These findings were ae- 26 THE NUTRITION OF THE FETUS cepted in support of the view that the pla- centa is a digestive organ, at first breaking down maternal protein and later assem- bling the fragments into fetal protein. AMINO ACID NITEOGEN OP THE PLASMA* Amino acid No. Source Para nitro- gen mg. per 100 CO. Remarks 1 Mother Fetus I 5.3 7.0 Bemarks. 2 Mother Fetus II 5.9 7.9 No anaesthesia. 3 Mother Fetus ni 5.3 7.8 No anaesthesia. 4 Mother Fetus IV 6.5 8.2 No anaesthesia. 5 Mother Fetus V 7.2 11.9 No anaesthesia. 6 Mother I 5.6 No anaesthesia. Fetus 7.6 Premature infant: 8th month. 7 Mother Fetus n 6.6 8.3 Whiffs of chloroform. 8 Mother Fetus n 4.9 6.8 Whiffs of chloroform. 9 Mother Fetus I 5.0 6.4 Whiffs of chloroform. 10 Mother Fetus I 5.6 7.3 Morphine and tyramine. 11 Mother Fetus I 4.5 6.2 Low forceps: Deep chloroform. * Analyses made by A. H. Morse. THE NUTRITION OF THE FETUS 27 But this hypothesis was never satisfactory and, probably, would not have been an- nounced if, at the time, it had been known that amino acids are abundant in the blood. The proof of this very fundamental fact wrought revolutionary changes in our con- ception of tissue metabolism and, in par- ticular, left no room for doubt regarding the elementary substances the mother con- tributes to the new organism for the manu- facture of its protein. At present, there is not the slightest excuse for assuming that the placenta synthesizes protein for the fe- tus. This function the fetal tissues per- form for themselves. The requisite amino acids, having been acquired from the mother, are available in the fetal blood. Of this we are sure ; but how do they pass through the placental partition? Let us see what light blood analysis throws upon the subject. It is pertinent that the blood corpuscles are richer in amino acids than the blood- plasma, and also that the corpuscles of the fetus are richer than those of the adult. What part these facts may ultimately play in the detailed explanation of tissue me- tabolism it is impossible to predict; but I 28 THE NUTRITION OF THE FETUS am doubtful that they have any signifi- cance for our immediate problem, since only substances in solution — substances in the plasma — take part in the placental in- terchange. Furthermore, though many technical intricacies could be enumerated, perhaps, it is sufficient to state that no analytical method at hand includes all of the amino acids in the blood. The method devised by Van Slyke takes into account most of them and this procedure was used in our investigations. An excess of amino acids amounting to about 2 mg. of nitrogen appears uniformly in favor of the fetal plasma. Even such a small difference in concentration implies that, so far as the amino acids are con- cerned, some process is added to that of simple diffusion in the regulatory mechan- ism of the placental interchange. Similar results in connection with the passage of amino acids into various tissues led Van Slyke to give the name "absorption" to the phenomenon in question. This inves- tigator found that if amino acids were in- jected into the circulation they diffused into the tissues rapidly and an equilibrium was reached when the tissues contained THE NUTRITION OF THE FETUS 29 about ten times as much amino acid nitro- gen as the plasma. An equilibrium is reached between maternal and fetal blood when there is only a slight difference of concentration in the two circulations, while the excess of amino acids in fetal plasma indicates that the placenta is capable of ab- sorbing them and also of preventing their departure from the fetus. Until the time of birth, the fetus does not employ the same channels as the adult to get rid of the excretory products formed by the utilization of food. The typical ac- tion of the lungs, for example, begins when breathing becomes established in the new- born ; previously, the elimination of carbon dioxide has been conducted through the placenta, and this gas, after reaching the mother's circulation, is excreted by her lungs. Similarly, the placenta takes the place of the fetal kidneys. Urea, ammonia, uric acid, creatine and creatinine, the waste products derived from the use of protein by the fetus, are borne back to the placenta, transferred from the fetal to the maternal circulation and finally thrown off in the mother's urine. The mechanism re- sponsible for the transfer of these sub- stances from one circulation to the other, and that alone is of interest here, becomes quite clear in the light of blood analysis, for the results obtained in this way estab- lish the fact that the fetal nitrogenous THE NUTRITION OF THE FETUS 31 waste products pass through the placenta in accord with the principles of diffusion. Urea, the most abundant of the nitrog- enous waste products, is so readily dif- fusible that its concentration in the blood UBIC ACID OF THE WHOLE BLOOD* Uric No. Source Para acid mg. per 100 cc. Remarks 1 Mother Fetus 6.8 5.0 Chloroform. 2 Mother Fetus 4.8 4.5 Chloroform. 3 Mother Fetus 4.3 4.3 Chloroform. 4 Mother Fetus 8.0 8.1 Chloroform. 5 Mother Fetus 5.9 5.6 Chloroform. 6 Mother Fetus n 2.3 2.5 No anaesthesia. 7 Mother Fetus II 1.8 1.8 Chloroform. 8 Mother Fetus m 2.2 2.0 No anaesthesia. 9 Mother Fetus ni 3.0 3.3 Chloroform. 10 Mother Fetus IV 2.0 2.7 Chloroform. 11 Mother Fetus V 2.2 2.4 No anaesthesia. 12 Mother Fetus X 2.8 2.2 No anaesthesia. * Analyses made by L. J. Bogert. 32 THE NUTRITION OF THE FETUS plasma, the corpuscles and the tissues of our bodies is always the same. Conse- quently, before the facts were actually determined, it would have been a safe prediction that identical quantities of urea would be found per unit volume of the blood of each organism. Our observations verify this prediction, for in a series of 16 normal cases the results gave an average of 10.5 mg. of urea per 100 cc. in the blood of the mother and 10.4 mg. in the fetus. Furthermore, in the presence of a compli- cation, as nephritis, where a relatively large quantity of urea occurs in the mater- nal blood, a similar value obtains in the fetal blood. The evidence is conclusive, then, that the placenta takes no active part in the elimination of fetal urea, but be- haves as a semi-permeable membrane. "TOTAL" CEEATININB OP THE PLASMA Author Mother mg. per 100 cc. Fetus mg. per 100 cc. Number of Cases Hunter and Campbell Plass 1.67 1.70 1.75 1.73 18 12 THE NUTEITION OF THE FETUS 33 As the method we employed to deter- mine the quantity of urea really includes the ammonia which is present in the blood in extremely small amounts, the analytical results just referred to are doubly signifi- cant. They make it certain that ammonia, as well as urea, passes through the pla- centa by diffusion. That the same expla- nation also holds for uric acid is clear from our figures in the table on page 31; and these are confirmed by the results of Kingsbury and Sedgwick. Finally, the evidence regarding creatinine and creatine which have been studied by Hunter and Campbell and by Plass agrees perfectly with the conclusions just reached. There- fore, we are confident of the passive role of the placenta in the transmission of all the nitrogenous fetal waste products. They enter the maternal circulation as freely as if the placenta did not exist, and ordinarily the estimation of the quantity of them in the mother's blood holds valid for the blood of the fetus. VI Carbohydeate, the second of the organic foodstuffs to be studied, becomes avail- able for intermediary metabolism in the form of glucose, the blood sugar. An excel- lent method for its determination devised by Benedict was the one employed in our series of cases. For the mother, the mean value found was 0.132%, and for the fetus 0.115%. Slightly higher values occurred in the maternal blood in 19 of our 24 cases, while the values were identical in both cir- culations in five cases. Bergsma states that the sugar content of the blood in the two organisms is always the same. How^ ever, his work is open to criticism, for the specimen from the mother and that from the infant were not obtained simultane- ously; in some instances an interval of twenty minutes elapsed between the times when the specimens were secured. These facts do not support a hypothesis requiring the action of a placental enzyme. That doctrine advocated by Hofbauer rests chiefly upon his demonstration of fer- jefiECENTAGE OF SUGAE IN THE WHOLE BLOOD* No. Source Para Blood-sugar Remarks 1 Mother Fetus 0.143 0.124 Whiffs of ohloroform. 2 Mother Fetus 0.097 0.10 Morphine and tyramine. 3 Mother Fetus 0.161 0.131 Morphine and tyramine. 4 Mother Fetus 0.137 0.141 ■Whiffs of ohloroform. 5 Mother Fetus 0.125 0.108 Whiffs of chloroform. 6 Mother Fetus 0.155 0.112 Whiffs of chloroform. 7 Mother Fetus 0.142 0.106 Whiffs of chloroform. 8 Mother Fetus 0.155 0.124 Whiffs of chloroform. 9 Mother Fetus n 0.126 0.11 No anaesthetic. 10 Mother Fetus n 0.156 0.124 Whiffs of chloroform. 11 Mother Fetus n 0.146 0.108 Whiffs of chloroform. 12 Mother Fetus n 0.115 0.103 Whiffs of chloroform. 13 Mother Fetus n 0.112 0.086 Whiffs of chloroform. 14 Mother Fetus n 0.11 0.075 Whiffs of chloroform. 15 Mother Fetus n 0.125 0.101 Whiffs of ohloroform. 16 Mother Fetus in 0.105 0.096 No anaesthetic. 17 Mother Fetus m 0.126 0.105 Whiffs of chloroform. 18 Mother Fetus IV 0.172 0.122 Whiffs of chloroform. 19 Mother Fetus IV 0.124 0.095 Whiffs of chloroform. 20 Mother Fetus IV 0.126 0.094 No anaesthetic. '21 Mother Fetus V 0.132 0.112 Whiffs of chloroform. 22 Mother Fetus V 0.126 0.13 No anaesthetic. 23 Mother Fetus VI 0.089 0.06 Whiffs of chloroform. 24 Mother Fetus vin 0.185 0.185 Whiffs of ohloroform. *Analyses made by W. H. Morriss. 36 THE NUTRITION OF THE FETUS ments whose function, in all probability, is the preparation of the glycogen, stored in the decidua, for passage to the fetus. The results of blood analysis certainly do not indicate that enzymes are responsible for the transportation of glucose through the placenta, but, on the contrary, speak strongly against it. Thus, in a case of double-ovum twins, where each fetus had its own placenta, the blood sugar of one was 0.099% and of the other 0.096%, while that of the mother was 0.12%. Such find- ings are inexplicable except on the basis of diffusion, and on this basis higher maternal values promote a steady flow of glucose toward the fetus. In this arrangement to guarantee an adequate supply of carbo- hydrate to the fetus there is an intimation of its great importance before birth; and when we learn, as we shall, that this infer- ence has the support of facts regarding the fats and lipoids, it becomes even more ap- parent that the fetus depends to an un- usual degree upon the maternal contribu- tion of glucose for the maintenance of its nutrition. VII Fbom a long series of observations we obtained analytical data relative to the fats and lipoids whicb is illustrated by the re- sults in the table. These substances are more abundant in the mother and rela- tively large maternal values are accompa- nied by large fetal values; otherwise, the most notable feature of our findings con- sists in the disparity between the quanti- ties of fats and lipoids in the two circula- tions. Between the plasmas a similar dis- parity exists. Here the difference between the maternal and the fetal figures is so great that we may not entertain the possi- bility of fat passing through the placenta in the way other substances do. Toward explaining such results two alternatives come to mind; either the fats and lipoids cross the placenta with the aid of an en- zyme, or they do not cross at all. Although our data would accord with either explana- tion, leaving the question open, there are at hand observations of a very different kind which decide the matter and teach that the latter interpretation is correct. 02 O M o § o m la o H Whiffs of chloroform. Whiffs of chloroform. Whiffs of chloroform. o o 1-1 a. i Whiffs of chloroform. Whiffs of chloroform. Whiffs of chloroform. i O 1) 1-3 O O iO O W l£3 lO to lO lO -^ b- CQ (M CO (M (M r-l o oo o o m t- O 00 O ■* rH (M CM o (M ira O CO 00 00 T-l rH iH i-H (A t- ■£ (0 to O O lO lO lO iH (M .H CO ^ (M r-1 iH iH O O O O O O 00 CO ;D Tt< 00 t-4 tH iH i-H ■a O O »C O lO lO 00 t- lO «DCa (N CI rH Cq W CM 1-1 o o o o o m O 00 CD l> CD OS CO rH (M rH IM S h O O W O O IC (M OS QO t^ -^ t^ t-l b- OO CD Ol t* O O lO in O O ■^ ^ -rH .-( CO 00 cq 00 m t- o> t- 1— ( i CO 5 CO § 03 § « Mother Fetus Mother Fetus Mother Fetus 6 iH (M CO iH (M CO THE NUTRITION OF THE FETUS 39 Following the investigations of Hof- bauer and of Gage, Mendel and Daniels re- sorted to vital staining and employed Sudan III, which colors fat red. The an- imals selected, pregnant rats, were treated by injection of the dye into the maternal circulation. Invariably, as these investi- gators find, the maternal fat is stained, and not the fetal. Between the tissue affected and that not affected the line of demarca- tion in the region of the placenta is very sharp. Stained fat pannot be traced in transit through the organ and there is no staining of the fetal fat. Now, these obser- vations, especially in conjunction with the disparity we note between the amount of fat in the blood of the mother and that of the fetus, demonstrate in a convincing way that fat is not included among the mate- rials contributed by the parent to her off- spring. The fat of the body of the fetus is manufactured there, almost certainly man- ufactured from carbohydrate with which the new organism is supplied abundantly. In theory, then, there is no necessity for fats and their derivatives, the lipoids, to pass the placental partition; and the evi- dence gathered both from biological and 40 THE NUTRITION OF THE FETUS chemical studies substantiates our conclu- sion that they have no part in the placental interchange. VIII Without certain reservations, we may not infer that what we have found true for the placental interchange at full term also pertains to the early months of pregnancy, a period when the thickness and complex- ity of the walls of the chorionic villi are notably greater than they are later. The simplification of the placental partition oc- curs at about the 18th to 20th week of preg- nancy, and this date marks the beginning of a more rapid rate of fetal growth. Dur- ing the latter part of pregnancy, at least, the placental partition is passive and be- haves like a semi-permeable membrane; the facts at hand, in other words, support the mechanistic hypothesis of placental function. Thus, the amino acids, from which fetal protein is built, and glucose, which supplies the requisite energy for tis- sue construction, pass freely to the new or- ganism in accord with the principles of dif- fusion. While in the mother's blood, these substances are not more accessible to her own tissues than to the fetus ; and probably 42 THE NUTRITION OF THE FETUS the quantity of them which reaches the fetus is regulated by the rate of their con- sumption in its body. The interchange of water between the two organisms and of most, if not of all, of the inorganic salts, including cal- cium, magnesium, sodium, and potassium, takes place in accord with the principles of diffusion. With regard to iron it is im- possible, at present, to affirm what ar- rangements are made for its transporta- tion through the placenta. This intricate and unsolved problem occupies a unique position among the factors of fetal nutri- tion. Stored in the newly born infant there is a large quantity of iron, so large, indeed, that the quantity is proportion- ately much greater than in the adult. The purpose of this storage in the newborn, Bunge believes, is to compensate for the inadequate amount of iron in human milk. The fats and lipoids of the mother's blood, as we have seen, are held in check by the placenta; the fetus manufactures fats out of some other material, most likely out of the glucose contributed by the mother. The manifest difference between maternal and fetal blood in this respect THE NUTRITION OP THE FETUS 43 stimulates our curiosity with regard to the fat metabolism of pregnancy, and this at- titude is in harmony with the times, for everywhere at present there is a lively in- terest in the nutritional role of the fats and the lipoids, cholesterol and lecithin. The purpose and fate of the latter, physiolo- gists have not made out satisfactorily, even with regard to animal metabolism in general. But, tempting as speculation is, at the moment we may go no further than the facts ; there is a high fat content in the blood of the pregnant woman, a much lower one in the blood of the fetus, and be- tween the two circulations there is no in- terchange of fats or related substances. All fetal waste products, including car- bon dioxide, which was the first to be thoroughly studied, pass the placenta by diffusion. Active elimination of these sub- stances on the part of the mother's excre- tory organs maintains their proper concen- tration in her blood and, simultaneously, there proceeds a steady purification of the blood of the fetus. Less favorable condi- tions prevail in cases of nephritis and of organic cardiac disease when an unusually large amount of excretory products ap- 44 THE NUTRITION OP THE FETUS pears in the mother's blood, and their concentration in both maternal and fetal circulations is always the same. It is not unlikely, therefore, that in the presence of such maternal complications intra-uterine death may be explained on the basis of an inefficient removal of fetal waste. IX In the final analysis, the nutrition of the fetus involves two factors, namely, the peculiar activity of its own organs and the supply of food it receives. The first is the more fascinating, and also the more dif- ficult of study because the isolation of the fetus baflSes the most ingenious experi- menters. In the absence of specific knowl- edge regarding the intermediary fetal me- tabolism our nearest approach to the facts is to accept an analogy with adult nutri- tional processes. And yet, in doing so, we are conscious of not being logical, for the unusual prominence of certain organs, as the thymus gland, indicates the existence of radical differences between the metab- olism of the immature organism and that of the adult. The second factor in the nutrition of the fetus — ^its food supply — ^has been brought within the range of direct observations; and some of the conclusions derived from the study of the origin and the variety of materials incorporated in its body have a 46 THE NUTRITION OF THE FETUS practical application. Thus, there is no diet specifically adapted to the state of pregnancy; the prospective mother may exercise the same freedom as any one else in the selection of food. She should, how- ever, choose what will agree with her and avoid that which she cannot digest and as- similate. Personal experience in the main must guide everyone as to what to eat and most women follow the dictates of appetite after they become pregnant as safely as they did before. In a practical sense the quantity of the mother's food is more influential than its quality. Popular opinion holds jftat_dJir- ing pregnancy the motherJishouldjeat Jqe. two." This doctrine is erroneous. A diet which has previously been ample will like- wise be sufficient throughout pregnancy. And it is not unimportant to emphasize this view, which has the unqualified sup- port of painstaking, scientific investiga- tions, because overeating during preg- nancy is much more likely to provoke discomfort than insufficient nourishment. On the other hand, there can be no justifi- cation for measures intended to restrict the growth of the fetus, for when rigidly THE NUTRITION OP THE FETUS 47 carried out they tend to weaken the mother. She may be careful, in other words, to avoid overgrowth of the fetus, but should not adopt a diet so limited as to interfere with normal development. So long as her health is properly maintained no thought may be given as to what the size of the fetus is likely ^to be. At present, provided the physician determines by a thorough, preliminary examination the ex- istence of any disproportion between the size of the fetus and the capacity of the mother's pelvis, he is qualified to decide what the appropriate treatment should be in order to bring pregnancy to a successful termination. REFERENCES Gage, S. H. and S. P. : Coloration of the milk in laetating animals and staining of the growing adipose tissue in the suckling young. Anat. Record, 1909, III, 203. Hunter and Campbell: Placental transmission of creatinine and creatine. Jour. Biol. Chem., 1918, xxxiv, 5. Mendel and Daniels: Behavior of fat soluble dyes and stained fat in the animal organism. Jour. Biol. Chem., 1912, XIII, 71. Morriss: The obstetrical significance of the blood-sugar with special reference to the pla- cental interchange. Bull. Johns Hopkins Hosp., 1917, xxviii, 140. Morse : The amino-aeid nitrogen of the blood in cases of normal and complicated pregnancy and also in the new-born infant. Bull. Johns Hopkins Hosp., 1917, xxviii, 199. Murlin: Metabolism of mother and offspring. Am. Jour. Obst., 1917, Ixxv, 913. Plass: Placental transmission: Total creati- nine in plasma, whole blood and corpuscles of mother and fetus. Bull. Johns Hopkins Hosp., 1917, xxviii, 297. THE NUTRITION OF THE FETUS 49 Slemons: Analysis of the blood in eclampsia and allied intoxications. Am. Jour. Obst., 1918, Ixxvii, 797. Slemons and Bogert. The uric acid content of maternal and fetal blood. Jour, of Biol. Chem., 1917, xxxii, 63. Slemons and Curtis: Cholesterol in the blood of mother and fetus ; a preliminary note. Am. Jour. Obst., 1917, Ixxv, 569. Slemons and Morriss : The non-protein nitro- gen and urea in the maternal and fetal blood at the time of birth. Bull. Johns Hopkins Hosp., 1916, xxvii, 343. Slemons and Stander: The fats and lipoids in the blood of mother and fetus. Trans. Am. Soc. for Advancement of Clinical Investiga- tion, 1918. "Wilson: Nitrogen metabolism during preg- nancy. Bull. Johns Hopkins Hosp., 1916, xxvii, 121.