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The care of premature infants
T I l E CARE OF P R E M A T U R E INFANTS*" MAL~SlI W. P00LE, M.D. AND TI~O~,~AS B. CooI~EG M.D. DETROIT
I E care of i m m a t u r e infants has ahvays been difficult and r a t h e r T tcostly because of the length of time necessary to bring' t h e m to the point where they could be t r e a t e d as normal, h e a l t h y babies. At the Children"s H o s p i t a l of Michigan we have passed t h r o u g h several phases d u r i n g which different methods were used, a n d it is o u r purpose in this p a p e r to describe the" experiences of the p a s t two years. I n r e a d i n g the l i t e r a t u r e one is s t r u c k by the variations in opinion as to the m o s t suitable methods of care neeessary to achieve the best results with p r e m a t u r e or i m m a t u r e infants. I t woMd seem t h a t w h a t is s a t i s f a c t o r y in one place is quite unsuitable in another. M a n y faet o t s m u s t be t a k e n into consideration, such as the t y p e of hospital, the social status of the parents, the facilities f o r following the patients a f t e r they leave the hospital, and the climate. In this hospital, for instance, we have to face several difficulties over which we have no control and which all t e n d to m a k e our results u n s a t i s f a c t o r y and disc o u r a g i n g even at the best. The first of these is the f a c t t h a t the inf a n t s are delivered at home or in o t h e r institutions a n d r e a c h our incubators only a f t e r a considerable length of time, r a n g i n g f r o m a few hours to several weeks. As a result our m o r t a l i t y will a h v a y s be high because a b o u t 35 p e r cent of the infants a d m i t t e d die within the fir.st forty-eight hours a f t e r they reach the hospital. Hess, and Chamberlain ~ in t h e i r analysis o~ 266 cases f r o m the S a r a h Morris P r e m a t u r e Station emphasized the high m o r t a l i t y in the g r o u p of p a t i e n t s born at home, p a r t i c u l a r l y within the first f o r t y - e i g h t hours a f t e r admission. The seeond u n f a v o r a b l e f a c t o r is t h a t m a n y of the homes are grossly overc r o w d e d and l a c k i n g in all the facilities necessary to raise even vigorous children, so t h a t when the i n f a n t s are r e t u r n e d to t h e i r p a r e n t s their life is t h r e a t e n e d b y infection, lack of air and sunshine, as well as b y ignorance of p r o p e r care. Lastly, we are. Situated in a climate w h e r e r a p i d fluctuations of t e m p e r a t u r e and humidity are of frequent occurrence, both of which add g r e a t l y to the incidence of r e s p i r a t o r y infections. Since 1926 there has been a special p r e m a t u r e cubicle in use and all infants weighing less t h a n 2500 gin. are sent there directly f r o m the *Submitted for publication, May 13, 1932. 16
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admitting d e p a r t m e n t if they are believed free from infections. This room has am~le light from large windows at aII times of the day, and the windows are also a r r a n g e d so that when desired the air can be heated before it enters. A direct steam line insures an adequate amount of heat, .free from fluctuation, whenever it is needed, thus making possible an u n v a r y i n g t e m p e r a t u r e of about 80 ~ F. D u r i n g the fall, winter, and spring months a humidifier is k e p t in almost constant operation (Fig. 1). The individual incubators have been designed for simplicity, ease of operation and safety. Each incubator consists of a regulation size
F i g . 1.
infant cot, with an accessory f r a m e w o r k made of small sized p i p i n g fitted on the top, the whole s t r u c t u r e being covered b y btal~kets and sheets pinned in such a way as to leave an opening on the top directly over the b a b y ' s head. t t e a t is supplied b y two carbon filament e l e c t r i c bulbs so t h a t it is a v e r y simple p r o c e d u r e to v a r y their size or t u r n them off to obtain, any needed temperatm'e. The baby's eyes are proteeted from t h e lights by a curtain which is dropped f r o m the top of the f r a m e w o r k to the baby's neck. The advan.tages of such an incubator are: (1) mechanical simplicity , which gives almost foolproof operation; (.2) the infant's head is p r o t e c t e d from any d r a f t s which may arise in the room ; (3) the baby may be fed and eared for without
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the dangers incidental to removing it from the heated tent. Baths of w a r m oil are given daily while soap and water' baths are administered only once a week. As has been stated above, we t r y to keep the t e m p e r a t u r e of the p r e m a t u r e room as dose as possible to 80 ~. This can be done very readily in the cooler months, b u t in the very hot months of summer it f r e q u e n t l y rises above this point as there is no method of cooling the air. The t e m p e r a t u r e of the individual incubators is kept at a point sufficient to p r e v e n t loss of body heat so that the b a b y ' s temp e r a t u r e is kept between 98.5 ~ and 100 ~ Newly born infants of very small weight will f r e q u e n t l y require an incubator t e m p e r a t u r e of over 100 ~ but this can be g r a d u a l l y lowered until at the end of three to f o u r weeks 80 ~ to 85 ~ is sufficient. D u r i n g the summer months in the Detroit area, at which time the average mean temperatures were somewhat comparable to the average t e m p e r a t u r e of the p r e m a t u r e room, official figures obtained from the w e a t h e r b u r e a u (1930) showed t h a t in June, J u l y and A u g u s t the relative h u m i d i t y varied from (t2 t o 68 per cent with mean temperature ranges f r o m 79.6 ~ to 65 ~. I n the smnmer of 1929 the relative hllmidity a v e r a g e d a trifle more with somewhat lower t e m p e r a t u r e levels. Hence in our a t t e m p t to keep the relative h u m i d i t y close to 60 p e r cent we have been keeping" near the level it n a t u r a l l y assumes during" the time of year in which we find the least a m o u n t of respirat o r y infection and when the average child's health is at its best. W i t h a t e m p e r a t u r e of 80 ~ and a relative h u m i d i t y of 55 to 60 per cent, the atmosphere is f o u n d to be v e r y comfortable b y the nurses and others going into the p r e m a t u r e room. A t this point, too, loss of b o d y heat is reduced to a minimum when slight fluctuations occur in the room temperature. The question of temperature and humidity has received consideration from numbers of workers but exact information as to the ideal levels (particularly humidity) is surprisingly scarce. La F e t r a 2 stated that his results were much improved at Bellevue Hospital b y raising' the h u m i d i t y and lowering the t e m p e r a t u r e but gave no definite figures on humidity. Sinclair a advocated a basket t e m p e r a t u r e of from 80 ~ to 90 ~ with a relative h u m i d i t y of 60 to 70 per cent. Talbot advocated a t e m p e r a t u r e of 80 ~ with h u m i d i t y of 30 per cent while Blackfan and his associates; ~ in seeking the optimum conditions for maintaining a constant body t e m p e r a t u r e of 98.6 ~ f o u n d two points at which this could be done, (a) t e m p e r a t u r e of 80 ~ relative humidity 30 per cent, (b) t e m p e r a t u r e 77 ~ relative h u m i d i t y 65 per' cent, and stated t h a t until more data was obtained, conclusions as to which was ideal, were not justified. A b t 5 gives 55 per cent as the optimum
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humidity at 80 ~ F., and M o r g a n t h a i e r ~ in describing a bed having' an individual humidifier stated t h a t it was k e p t at 80 ~ to 85 ~ with 50 to 65 per cent relative h u m i d i t y and a t t r i b u t e d the success of the bed to the f a c t t h a t it was possible to m a i n t a i n a n o r m a l h u m i d i t y in the chambers. Strict isolation of the p r e m a t u r e cubicle is m a i n t a i n e d at all times so t h a t t h e r e is the m i n i m u m of contact with the r e m a i n d e r of the institution. Gowns a n d m a s k s are provided, in the a n t e c h a m b e r , f o r everyone e n t e r i n g the room, and no one is allo+ced to go in except in absolute necessity. The nurses looking a f t e r these babies have no other duties in order t h a t there m a y not be the possibility of crossinfection. Despite all a t t e m p t s at asepsis, however, we are not successful at all times, with the result that infections, particularly respiratory, continue to present the greatest problem.
Respiratory infections in premature infants are sufficiently different from those found in other infants to merit particular mention and some of our observations have cleared up problems 'that we could not previously solve. I t was o~lr not i n f r e q u e n t experience t h a t babies who h a d been thriving" would begin to show a slight rise in t e m p e r a ture with a c c o m p a n y i n g vomiting, d i a r r h e a or abdominal distention and w i t h o u t a n y v e r y positive physical findings to explain the upset. Some such p a t i e n t s died a f t e r a v e r y short illness, while others, a f t e r a brief illness, r e s u m e d their n o r m a l course. (See C h a r t I.) A f t e r finding u n s u s p e c t e d b r o n e h o p n e u m o n i a s a t autopsy, we b e g a n to t a k e cultures f r o m b o t h the nose a n d t h r o a t on all the infants. Most of those in good health showed only staphylococcus in the cultures, while the r e p o r t s of t h o s e w i t h the s y m p t o m s described almost i n v a r i a b l y were r e t u r n e d f r o m the l a b o r a t o r y with the notation t h a t lVlieroeoecus eatarrhalis or a strain of streptococcus was also present. ~We therefore concluded t h a t definite infections of the nose and t h r o a t m i g h t be p r e s e n t w i t h o u t our being able to see a n y a b n o r m a l congestion, t h a t b r o n e h o p n e u m o n i a f r e q u e n t l y resulted w i t h o u t m a r k e d elevation of t e m p e r a t u r e a n d t h a t death followed before the physical signs in the chest became v e r y evident. This failure of i m m a t u r e infants to localize and to resist infection was emphasized by Capper ~ in his review of 437 such patients. The susceptibility to infection of the r e s p i r a t o r y t r a c t is of course well k n o w n and has b e e n spoken of b y n e a r l y evel'y one who has h a d a l a r g e n u m b e r of eases. I n contrast, m a y be cited the experience of Cook s in California, who r e p o r t e d only f o u r deaths h ' 0 m r e s p i r a t o r y complications in a series of 77 p r e m a t u r e s . This f o r t u n a t e result was p r o b a b l y f a v o r e d b y climatic conditions.
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As all the infants received daily doses, of cod liver oil in what we felt to be adequate amounts (as well as irradiation with the quartz iight twice weekly), there did not a p p e a r to be a n y t h i n g more to be done f r o m a dietary s t a n d p o i n t to establish immunity.
F o r a time we fed
powdered b r e w e r ' s yeast to see w h e t h e r it would exert a favorable influenee, but were unable to note a n y result as f a r as i m m u n i t y to infection was concerned.
The question of p r o p h y l a c t i c vaccine ther-
a p y was then raised so this was tried on a n u m b e r of infants.
A
mixed c a t a r r h a l vaccine was given in increasing doses without apparent beneficial results and it oceasionally caused reactions which were higSIy undesirable. Cod liver oil of high vitamin D potency has been added to the formulas at the time of their p r e p a r a t i o n in the f o r m u l a room in the _~, VE.
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Chart I.--Showing
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t h e effect of u p p e r r e s p i r a t o r y i n f e c t i o n u p o n a premature infant.
t h e wei2~'ht c u r v e of
p r o p o r t i o n of a dram to each pint of breast milk, or two drains to the pint in evaporated milk mixtures. I n this w a y eaeh infant received a daily dose of the oil from the day of admission, the dosage depending upon its ability to take food.
Nor a considerable time we
had a r o e n t g e n o g r a m taken of each b a b y ' s wrists and ankles when it was r e a d y to leave the hospital and f o u n d that in practically every instance there was no evidence of active rickets either in white or colored infants.
IIence we concluded that d u r i n g the period of hos-
pitalization o~r infants were protected by cod liver oil supplemented with irradiation by quartz light. The only exceptions seemed to be those babies who had severe infections lasting over a considerable period. In such infants craniotabes was m a r k e d and they did not respond to even increased doses of God liver oil. We felt that in such
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infants y e a s t seemed to cause a definite i m p r o v e m e n t in the calcification of tile bones w h e n given w i t h the oil, p r o b a b l y due to the f a e t t h a t the a d m i n i s t r a t i o n of y e a s t f a v o r s r e t e n t i o n of calcium in the body as has been shown by M a e y 9 a n d others in experiments on rats. G e r s t e n b e r g e r a n d Nourse 1~ d e m o n s t r a t e d t h a t riekets could be prevented b y small doses of cod liver oil and t h o u g h t t h a t their results were p a r t l y due to the f a c t t h a t the oil was s t a r t e d early. Despite the pessimistic view t a k e n b y other observers, n, 12, la who feel t h a t rickets is an inevitable occurrence even with adequate doses oi" oil, it would a p p e a r t h a t protection is s e c u r e d / w h e r e a good s t a n d a r d i z e d b r a n d of eod liver oil is s t a r t e d e a r l y and t h a t the doses do n o t h a v e to be large. A f t e r their r e t u r n home t h e r e were f o u r patients who developed severe rickets, possibly the result of m o t h e r s giving" the oiI at i r r e g u l a r intervals. One white child, however, required the persistent use of the quartz light to heal a m o d e r a t e l y severe riekets t h a t developed while it was receiving two teaspoons of oil daily. A n e m i a has not been a p r o m i n e n t clinieal finding" so we h a v e not felt t h a t it was necessary to g'ive iron to our patients routinely. To avoid handling, blood cot.rots and hemoglobin estimations were n o t made except w h e n special indieations p r e s e n t e d themselves. I n the infants who were t a k i n g food well and g a i n i n g in weight the n u m b e r who developed anemia of sufficient degree to be suspeeted on physical examination was p r a c t i c a l l y negligible. W h e n mild s e c o n d a r y anemia was suspected and verified by blood examination, the c o n d i t i o n responded r e a d i l y to the a d m i n i s t r a t i o n of small doses of s a e e h a r a t e d ferrous c a r b o n a t e given in the feedings. C o n t r a s t e d with these, however, were the anemias t h a t developed d u r i n g the course of infections. T h e y p r o g r e s s e d v e r y rapidly, the hemoglobin, and the red blood cell counts fell to low levels quickly, a n d they did not r e a e t well to the a d m i n i s t r a t i o n of iron. Transfusion of blood relieved the condition at once b u t it was often necessary to give small amounts of blood two or m o r e times because we f o u n d t h a t the benefit was only t e m p o r a r y while the infection, continued. We hope at a f u t u r e time to m a k e naore detailed observations based u p o n bloo& studies in a n u m b e r of such infants. M a c k a y ' s studies ~ of nutritional anemia r e c e n t l y pt~blished give some v e r y suggestive statistics on the effeet of iron a d m i n i s t r a t i o n in f o r e s t a l l i n g infection during the period of " p h y s i o l o g i c " anemia. As this anemia is especially evident in i n f a n t s p r e m a t u r e I y born, routine iron a d m i n i s t r a t i o n m a y p r o v e t~) be of value here. Char* I I shows the weight curves, o.f seventeen infants whose weight on admission to the pr'emature ward r ang'ed f r o m about 1000 gm. to 2200 g~n. As will be n o t e d f r o m a s t u d y of the individual curves ini-
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tial loss of weight is n o t constant, being shown only in six of the seventeen. This is doubtless explained by the f a c t that feedings were started on r e g u l a r schedule within six hours of admission, while glucose solution (5 per cent) was commenced at once, 1~ and in many, subcutaneous injections of normal saline or 5 per cent glucose solution were given because of inability to take fluids well by mouth. I n looking at the curves designated A, B, and C, it will be noted that there is a close parallelism up to the s i x t h or seventh week. They represent the g r o w t h of three infants receiving breast milk without any alterations except g r a d u a l increase in q u a n t i t y up to the time mentioned above. I n Chart I I I the same type is seen in curves D, E, and F where the gain in weight d u r i n g the early weeks was v e r y slight. This is due to tile fact that on breast milk alone the infants
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Chart III.--Infants G and H, breast milk and I only evaporated
represented by curves D. Ej and F were fed only breast milk; followed by diluted evaporated milk with added carbohydrate, milk formula.
are not able to take an amount o f feeding sufficient in calorie value or protein content. That this is true p a r t i c u l a r l y in the very smallest infants is illustrated by the eurves A and D, while the patient represented b y the curve F being ]arger, and eonsequently more vigorous, was able to consume sufficient breast milk, a f t e r about two and one half weeks, to maintain a very satisfactory gain. Their curves serve merely to point out that unmodified breast milk is not an entirely satisfactory food f o r the smallest prematures. They sleep almost continually and the nurse experiences diffieulty in rousing them sufficiently to take food so in the early weeks three to four drams per feeding is about the most that can be given unless g a r a g e is resorted to. Most elinicians agree that it is undesirable to disturb the infants f o r feeding oftener t h a n every three hours, hence it m a y readily be seen t h a t the caloric intake in t w e n t y - f o u r hours will not be sufficient
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to more t h a n m a i n t a i n weight. M a n y methods have been used to remedy this defect, f o r example, r e d u c i n g the w a t e r content of the breast milk b y evaporation, ~6 using dried b r e a s t milk, 17 or a d d i n g c a r b o h y d r a t e or protein. 18, ~9 We have f o u n d that the addition of 2 per cent calcium caseinate to the milk m a k e s an e x t r e m e l y s a t i s f a c t o r y f o r m u l a f o r our small infants, a n d it is now routine practice in this clinic to use this highprotein breast m i l k on all infants weighing ]ess t h a n 1800 g i n . until a satisfactory gain is established. A f t e r the i n f a n t is seen to be thriving, an evaporated milk formula is substituted in gradually increasing
quantities until the breast milk formula is entirely stopped. The evaporated milk formula is continued during the remainder of the patient's stay in the hospital and afterward while it is being supervised by the out-patient department.
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Chart v.--nlustratinr
the g r o w t h
curves of p r e m a t u r e twins.
C h a r t I V shows in a graphic w a y the p r o g r e s s of two p a t i e n t s a n d indicates the various changes t h a t were m a d e in the formulas. The first p a t i e n t ( r e p r e s e n t e d by the lower curve) was a d m i t t e d at the age of t w e n t y - f o u r hours, w e i g h i n g 1050 gin. I t w a s given highprotein b r e a s t m i l k f o r m u l a and gained satisfactorily until the second w e e k a f t e r an initial loss of 100 gin. H a l f s k i m m e d lactic acid milk was then tried, but as progress was not satisfactory, the b a b y was again p u t on the b r e a s t m i l k f o r m u l a . A t seven and one-half weeks (1550 gin. weight) t h e s u b s t i t u t i o n of diluted u n s w e e t e n e d e v a p o r a t e d milk with added c a r b o h y d r a t e was c o m m e n c e d until at about nine and one-half weeks (weight a p p r o x i m a t e l y 2000 gin.) a f o r m u l a of one-third unsweetened e v a p o r a t e d milk, two-thirds water, with 5 per cent added c a r b o h y d r a t e was being used. The second
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child was a d m i t t e d at nine days of age weighing 1110 gin. E x c e p t for m i n o r differences the plan of feeding was the same and the p a t i e n t followed a course closely parallel to the first. The a m o t m t of food consumed b y the first child was g r e a t e r t h a n t h a t t a k e n b y the second t h r o u g h o u t its entire course with a consequently higher caloric intake despite the close parallelism of their weights. This difference in prem a t u r e s is f r e q u e n t l y observed, m a n y being' able to gain quite satisf a c t o r i l y on s u r p r i s i n g l y small amounts. (See also C h a r t V.) Most of our i n f a n t s received f r o m 100 to 160 calories p e r k i l o g r a m and we have f o u n d t h a t the m a j o r i t y gain well on 120 to 140 calories p e r kilo. 1 This figure is l o w e r t h a n m a n y authors s feel is essential to p r o p e r g r o w t h in p r e m a t u r e infants and we feel t h a t the difference m a y be due to several factors, first, the n u r s e ' s ability to give p l e n t y of w a t e r between feedings, second, a m i n i m u m of h a n d l i n g of these infants, and third, the r e l a t i v e l y higtl protein content of the feedings. I n f a n t s w e i g h i n g over 1800 gin. are s t a r t e d directly upon diluted e v a p o r a t e d m i l k f o r m u l a s if the m o t h e r is not s u p p l y i n g b r e a s t m i l k . W e h a v e f o u n d the m a j o r i t y of such babies gain v e r y r a p i d l y a n d do so with few g a s t r o i n t e s t i n a l upsets. A f t e r t r y i n g o a t b o t h acidified and nonaeidified f o r m u l a s we have g r a d u a l l y discontinued almost all of the acidified milk so t h a t we are now using the acid f o r m u l a s only when there is a special indication. The sweet f o r m u l a s seem to be e n t i r e l y s a t i s f a c t o r y in almost every, instance a n d the nurses r e p o r t t h a t there is less discomfort and less vomiting t h a n when acidified milk is used. In beginning f o r m u l a s of e v a p o r a t e d milk in such patients we h a v e f o u n d t h a t g a s t r o i n t e s t i n a l upsets can largely be avoided by s t a r t i n g with a f o r m u l a of one p a r t of u n s w e e t e n e d evapor a t e d milk to three p a r t s of water with 7 p e r cent carbohydra.te added and increasing g r a d u a l l y up to equal p a r t s of unsweetened e v a p o r a t e d m i l k a n d w a t e r with the addition of 5 to 7 per cent c a r b o h y d r a t e . This can be done f a i r l y r a p i d l y so t h a t gain in w e i g h t is not delayed a n d by g r a d u a l addition in this w a y the feeble digestive powers of the p r e m a t u r e i n f a n t are not overtaxed. As few of our mothers are able to s u p p l y sufficient b r e a s t milk during the entire time their b a b y is in the hospital, we find t h a t the majority are getting p a r t o.r M1 artificial feeding after the third or fourth week. By using u n s w e e t e n e d e v a p o r a t e d milk f o r m u l a s a large sum of m o n e y has been s a v e d because of our not h a v i n g to b u y b r e a s t milk. R e f e r r i n g a g a i n to Charts I I and I i i , it will be seen t h a t gain in w e i g h t is e x t r e m e l y s a t i s f a c t o r y in the l a t e r weeks. Also in the weight curves of infants o v e r 1800' gin., most of w h o m get evapor a t e d milk formulas, it will be n o t e d t h a t the gain is v e r y rapid,
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a v e r a g i n g a b o u t 27 gin. per d a y with some gaining as much as 35 gin. per day. These figures are m a t e r i a l l y higher than those f o r infants receiving umnodified b r e a s t milk. B y g r o w i n g at this rate the child's hospitalization is shortened so t h a t it: can be sent home to be eared f o r by our follow-up service. I n this w a y the p r e m a t u r e population of the w a r d is k e p t to the minimum, which helps to reduce the chances of epidemics of r e s p i r a t o r y disease. F i v e t h r i v i n g p r e m a t u r e infants were given their r e g u l a r a m o u n t of f o r n m l a with b a r i u m added so t h a t the progress of the meal could be observed w i t h x-ray. E a c h child was given a test meal of b r e a s t Oooi
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$
~
g r o w t h c u r v e s of five i n f a n t s b r e w e r ' s y e a s t in t h e i r diets.
gwho
2,
received powdered
milk and on a n o t h e r occasion a test meal. of nonacidified e v a p o r a t e d milk f o r m u l a so t h a t the e m p t y i n g t i m e of the stomach could be det e r m i n e d with each type of feeding. W e could see little difference between the b r e a s t milk f o r m u l a and the e v a p o r a t e d milk f o r m u l a in this respect, as a considerable p a r t of the meal left the stomach within the first h a l f h o u r and there was little r e m a i n i n g in the stomach at three hours. Samples of gastric contents f o r d e t e r m i n a t i o n of hydrogen-ion c o n c e n t r a t i o n were also t a k e n on three of these same i n f a n t s two hours a f t e r m e a s u r e d test meals of b r e a s t milk f o r m u l a a n d nonacidified e v a p o r a t e d milk f o r m u l a had been given. T h i r t y d e t e r m i n a -
28
T H E J O U R N A L OF P E D I A T R I C S
tions (eolorimetrie method) in all were made, the r a n g e being f r o m Pu 4.0 to FH 5.0 with the m a j o r i t y being PH 4.4 a n d PH 4.6 for both types of feeding. C h a r t V I r e p r e s e n t s the weights of infants who were given powd e r e d b r e w e r ' s y e a s t as an addition to the f o r m u l a s of high-protein b r e a s t milk and e v a p o r a t e d milk. The a v e r a g e daily gain f o r this g r o u p was 25.3 gin., which is v e r y close to the rate for those on evapor a t e d milk f o r m u l a s w i t h o u t yeast. Hess ~~ and Bloxom 21 have demons t r a t e d the effect of y e a s t upon growth, but in our infants the increase in the r a t e of g r o w t h was not striking so t h a t the addition of y e a s t to the diet was not a d o p t e d as a routine procedure. A survey was made by the social service d e p a r t m e n t prior to J a n u a r y , 1930, which showed t h a t few of the p r e m a t u r e infants discharged f r o m the hospital during" 1928 and 19'29 were living at the time the inquiry was made, and we assumed t h a t this was due to the living conditions in the homes and the indifferent care t h a t the babies had received. This led to the f o r m a t i o n of out" present fol]ow-up service which has w o r k e d out a d m i r a b l y and resulted in a m u c h different outlook f o r these babies in t h e i r homes. Two nurses devote almost their entire time to this w o r k outside the hospital. T h e y begin their contacts with the m o t h e r s i m m e d i a t e l y a f t e r a p r e m a t u r e i n f a n t is b r o u g h t in to the hospital. T h e y strive to see t h a t the m o t h e r is being p r o p e r l y cared for, t h e y teach her the method of e x p r e s s i n g breast milk a n d d e m o n s t r a t e its p r o p e r care prior to its being b r o u g h t in f o r the b a b y ' s use. Repeated home calls are usually necessary as m a n y of the m o t h e r s tire of collecting milk and s t a r t b r i n g i n g it to the hospital at irregular intervals. Stimulation of the m o t h e r ' s breasts b y massage is used along" with d i e t a r y instruction to keep up the milk s u p p l y as long as possible. S h o r t l y before the b a b y is r e a d y to leave tile p r e m a t u r e w a r d n u m e r o u s calls are m a d e to p r e p a r e the home for the b a b y ' s arrival. A cot or bassinet is p r e p a r e d , suitable f o r a small infant. I t is placed so as to be as close as possible to a constant supply of heat and a w a y f r o m windows a n d doors so as to minimize drafts. Directions are given regarding, the p r o p e r t e m p e r a t u r e and h u m i d i t y of the rooms, and the necessity f o r isolation of the p a t i e n t is stressed. As soon as the home p r e p a r a t i o n s are completed the m o t h e r is b r o u g h t to the w a r d where t h o r o u g h instruction is given in handling the baby. The p r o p e r method of bathing, and f e e d i n g the i n f a n t is t a u g h t her, as well as the p r e p a r a t i o n of the f o r m u l a if the child is not to be f e d entirely on the m o t h e r ' s b r e a s t milk. Sufficient f o r m u l a is sent home with each i n f a n t to last f o r t w e n t y - f o u r hours.
POOLE AND
COOLEY:
PREMATURE
INFANTS
29
The n u m b e r of home calls necessary, a f t e r the p a t i e n t leaves the ward, is d e t e r m i n e d by the circumstances in each case. The a v e r a g e is six calls d u r i n g the first week following discharge, three d u r i n g the second week, two d u r i n g the t h i r d a n d f o u r t h weeks, with one call weekly t h e r e a f t e r as long as it is deemed necessary, d e p e n d i n g upon the progress of the p a t i e n t and the cooperation secured in the home. The babies are b r o u g h t b a c k to the o u t - p a t i e n t clinic e v e r y two weeks f o r the first two months, then once a m o n t h until t h e y are a y e a r old, a f t e r which the u are made only e v e r y two months. In the clinic weights and m e a s u r e m e n t s are taken, feedings checked, cod liver oil and orange juice (or t o m a t o juice) increased as needed. Most o.f the illness in the homes ha~ been the res.ult o~ r e s p i r a t o r y infections, or the acute specific infectious diseases. In the t w o - y e a r period there have been only six i n f a n t s r e a d m i t t e d to the Children's Hospital, and one a d m i t t e d to the City Contagious Hospital. There were three deaths at home in the s a m e length of time, one due to diarrhea (after leaving Detroit), one expired v e r y suddenly and we were unable to determine the cause, while the t h i r d child a p p a r e n t l y choked to deattt when left alone wit~a, its bottle. We feel t h a t these results in earing' for a g r o u p of seventy p r e m a ture infants u n d e r r a t h e r indifferent home conditions h a v e been highly satisfactory. There has been a v e r y noticeable i m p r o v e m e n t , too, during t h e second y e a r of this routine as c o m p a r e d w i t h the first, despite the fact that aid from the welfare department to m a n y of these families had been greatly reduced. In the last twelve months there have been thirty-eig'ht infants discharged with only two. readmitred and no deaths at home. Our infants w h o have reached a year or over compare very favorably with children born at full term as Fig'. 2 will help to show. More than half of them reach accepted standards for weight and height-at a year, and practically all of them do so before one and a half years of age. As r e g a r d s their ability to sit up, to walk, and to begin saying' words we h a v e not noted a n y p a r t i c u l a r delay. Quite striking, t~owever, is the slowness in dentition. ]t is unnsual for a n y teeth to e r u p t before the ninth month, and it is often as late as the eleventh or twelfth m o n t h before t h e y appear. W e f e d t h a t this bears a direct relation to the degree of p r e m a t n r i t y and t h a t the period up to their n o r m a l b i r t h time should be t a k e n into consideration before deciding' t h a t the teeth h a v e not e r u p t e d at tl~e a v e r a g e time.
One of our children is definitely a Mongolian idiot, a n o t h e r who had an occult spina bifida is not m a k i n g n o r m a l progress mentally, and there have been two deaths in the w a r d of the infants on w h o m a diag-
30
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nosis of cerebral i n j u r y with s p a s t i e i t y was made. I t would appear, t h e r e f o r e , t h a t a r r e s t e d cerebral d e v e l o p m e n t has not p l a y e d a v e r y conspicuous p a r t in the infants who have survived. CapperS in his rSsum5 t o o k a r a t h e r pessimistic view concerning the nlental developm e n t of this t y p e of child and f o u n d a much h i g h e r p e r c e n t a g e showing evidence of cortical injury. He also pointed out the t e n d e n c y of the p r e m a t u r e to spont~meous h e m o r r h a g e . W e h a v e h a d one death of bleeding f r o m the cord s t u m p in an infant, which could not be s t o p p e d b y transfusion. In two other instances bleeding' was quickly a r r e s t e d b y small amounts of blood given i n t r a v e n o u s l y before alarming s y m p t o m s appeared. There was no recurrence of h e m o r r h a g e in either child.
Fig. 2.
SU1V[~[ARY
D u r i n g the last two years we have been striving to develop niett~ods of care f o r our p r e m a t u r e (and i m m a t u r e ) babies which would (1) reduce the m o r t a l i t y a m o n g these infants a f t e r their r e t u r n to their homes, a n d (2) decrease the cost of t h e i r care while in the w a r d s of the hospital. The f o r m e r has been accomplished by close supervision of the home care, m a d e possible b y our two visiting nurses and b y f r e q u e n t cheek.. ups in the o u t - p a t i e n t clinic. There have been seventy infants eared for in this w a y with most g r a t i f y i n g results. W h e n p r e s e n t economic conditions are t a k e n into consideration the i m p r o v e m e n t in the mort a l i t y at honie becomes even more outstanding. A g r e a t m a n y of these families are entirely d e p e n d e n t upon the city welfare organizations for support, which means t h a t only the bare necessities can be procured. The r e d u c t i o n in cost to the hospital has been accomplished b y the persistent efforts of the nurses in h a v i n g the m o t h e r s b r i n g in their
POODE
AND
COOLEY:
Pr~EMATUI~E
INFANTS
31
breast milk, by the early substitution of evaporated milk formulas where the mother is unable to supply enough breast milk, and by sending the infants home when they reach five pounds (approximately 2300 gin.) in weight. As has been previously stated, 35 per cent of all our admissions of premature infants die within f o r t y - e i g h t hours of the time: of arrival, while 8 per cent are in an obviously m o r i b u n d condition w h e n reeeived. This unfavorable situation could doubtless be improved by educating" the a t t e n d i n g physicians and the laity in r e g a r d to the necessity of g r e a t e r care in h a n d l i n g p r e m a t u r e infants, and possibly also by malting available a heated carrier for u s e . i n an ambulance such as the one devised b y Itess TM a n d f o u n d v e r y s a t i s f a c t o r y in Chicago. The need f o r such i n f o r m a t i o n and care is emphasized by the fact t h a t among the infants who died 68 per cent had a rectal temperature of 97 ~ F., or below, w h i l e in only 23 per cent was the temperature between 97 ~ and 100 ~ F. * C;bIAR'T' V I I CAIJSIfS O,P DEATII (After 48 horn's from time of admission) PEI~ OEN92
Prematurity Acute respiratory infection (Including bronehopnemnonia) ~Diarrhea Inanition Birth injury Fetal ateleetasis Gonorrheal opthalmia Congenital abnormality o f heart
Hemorrhage Syphilis
Spina bifida and other abnormalities Erysipelas Moribund on admission Total mortality (after 48 hours) 1930 Total mortality (after 48 hours) 1931 *Most of these were parenteral diarrhea due to respiratory infection,
44 22 6 3 5 3 '2.5
2 1 1
2 0.5 8
4=4 33
A s t u d y of the causes of death in our series shows that in 44 per cent we were unable to find any other cause than p r e m a t u r i t y to account for their demise. The less, of course, will be the chance for survival, tile smaller the b a b y and the greater the degree of prematurity, so t h a t in babies weighing 1.000 gm. or' less the m o r t a l i t y is about 95 per cent. =, ~ R e s p i r a t o r y infection caused 22 per cent of our deaths, the n u m b e r d y i n g front this cause being much higher in the cool months than in the summer. The deaths ascribed to gonorrheal ophthalmia are the result of the ihandling and exposure made
32
THE JOURNAL OF PEDIATRICS
necessary for proper treatment of the eye condition. The intestinal upsets were practically all due to infection of the respiratory tract, but as diarrhea was the most prominent symptom the deaths have been listed under that heading. During the two-year period there have been fifty-two premature infants admitted to the general wards of the hospital because they were suffering from some type of infection when admitted, and of these f o r t y died (77 per cent). The mortality among the babies admitted to the special premature room, exclusive of those dying within the first forty-eight hours after admission, was 44 per cent during 1930, and 33 per cent during 1931. CONCLUSIONS
1. The supervised care of premature infants in their own homes has proved ver y satisfactory. 2. The mortality in the posthospital period has been reduced by this method. 3. The period of hospitalization has been shortened with consequent reduction of cost. 4. I~ickets can be prevented in premature infants by small doses of cod liver oil (supplemented by ultraviolet irradiation) if started early. 5. Breast milk with added calcium caseinate has been found the most satisfactory feeding for infants under 1400 gm. in weight. 6. Infants over this weight thrive well when a diluted unsweetened evaporated milk formula, with added carbohydrate, is gradually and carefully substituted for the modified breast milk. 7. Nonacidified evaporated milk has been found satisfactory for the larger prematures and during the period of after-care in the homes. 8. Gastrointestinal upsets were of infrequent occurrence in infants who were not suffering from infection. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
Hess and Chamberlain: Am. J. Dis. Child. 34: 571, 1927. La F e t r a : Arch. Pediat. 24: 22, 1917. Sinclair: Arch. Pediat. 37: 139, 1920. Yaglou, Drinker, and Blackfan: Am. Soe. H e a t i n g and V e n t i l a t i n g Engineers J. Sect. ttcating, Piping and Air Conditioning 2: 605, 1930. Abt: P e d i a t r i c s : Vol. II, p. 486. Morganthaler: Am. J. Obst. & Gynee. 8: 622, 1924. Capper: Am. J. Dis. Child. 35: 262, 1928. Cook: Arch. Pedlar. 38: 201, 1921. Macy: Not published. Gerstenberger and Nourse: J . A . M . A . 87: 1108, 1926. F r a m m : Ztsehr. f. Geburtsh. u. Gyni~k. 88: 319, 1924. Wyman: Boston M. & S. J. 194: 202, 1926. Garland: Ibid. 192: 581, 1925. Mackay, I:L M..: ~V[edica] l~eseareh Council /~ep. No. 157: London, 1931. I~ess, J. It.: M. Clin. North America 3: 1709, 1920.
POOLE AND COOLEY: 16. 17. 18. 19. 20. 21.
PREh~[ATUi~E INFANTS
T h o m p s o n : A r c h . P e d i a t . 43: 303, 1926. E m e r s o n a n d S m i t h : A m . J. Dis. Child. 31: 1, 1926. Langer: Ztschr. f. K i n d e r h . 41: 598, 1927. H e s s , J. H . : J . A. 1~. A. 80: 1313, 1923. Hess, A.F.: A m . J. Dis. Child. 13: 98, 1917. B ] o x o m : A m . J . Dis. Chi]d. 37: 1161i 1929. 22. E d e n : L a n c e t 2: 127, 1921. 23. P u l f o r d a n d B l e v i n s : A m . J. ])is. Child. 34: 797, 1928. 953 FISCHER BLDG.
33
I E care of i m m a t u r e infants has ahvays been difficult and r a t h e r T tcostly because of the length of time necessary to bring' t h e m to the point where they could be t r e a t e d as normal, h e a l t h y babies. At the Children"s H o s p i t a l of Michigan we have passed t h r o u g h several phases d u r i n g which different methods were used, a n d it is o u r purpose in this p a p e r to describe the" experiences of the p a s t two years. I n r e a d i n g the l i t e r a t u r e one is s t r u c k by the variations in opinion as to the m o s t suitable methods of care neeessary to achieve the best results with p r e m a t u r e or i m m a t u r e infants. I t woMd seem t h a t w h a t is s a t i s f a c t o r y in one place is quite unsuitable in another. M a n y faet o t s m u s t be t a k e n into consideration, such as the t y p e of hospital, the social status of the parents, the facilities f o r following the patients a f t e r they leave the hospital, and the climate. In this hospital, for instance, we have to face several difficulties over which we have no control and which all t e n d to m a k e our results u n s a t i s f a c t o r y and disc o u r a g i n g even at the best. The first of these is the f a c t t h a t the inf a n t s are delivered at home or in o t h e r institutions a n d r e a c h our incubators only a f t e r a considerable length of time, r a n g i n g f r o m a few hours to several weeks. As a result our m o r t a l i t y will a h v a y s be high because a b o u t 35 p e r cent of the infants a d m i t t e d die within the fir.st forty-eight hours a f t e r they reach the hospital. Hess, and Chamberlain ~ in t h e i r analysis o~ 266 cases f r o m the S a r a h Morris P r e m a t u r e Station emphasized the high m o r t a l i t y in the g r o u p of p a t i e n t s born at home, p a r t i c u l a r l y within the first f o r t y - e i g h t hours a f t e r admission. The seeond u n f a v o r a b l e f a c t o r is t h a t m a n y of the homes are grossly overc r o w d e d and l a c k i n g in all the facilities necessary to raise even vigorous children, so t h a t when the i n f a n t s are r e t u r n e d to t h e i r p a r e n t s their life is t h r e a t e n e d b y infection, lack of air and sunshine, as well as b y ignorance of p r o p e r care. Lastly, we are. Situated in a climate w h e r e r a p i d fluctuations of t e m p e r a t u r e and humidity are of frequent occurrence, both of which add g r e a t l y to the incidence of r e s p i r a t o r y infections. Since 1926 there has been a special p r e m a t u r e cubicle in use and all infants weighing less t h a n 2500 gin. are sent there directly f r o m the *Submitted for publication, May 13, 1932. 16
FOOLE AND COOLEY:
PblEN[ATUI~E I N F A N T S
17
admitting d e p a r t m e n t if they are believed free from infections. This room has am~le light from large windows at aII times of the day, and the windows are also a r r a n g e d so that when desired the air can be heated before it enters. A direct steam line insures an adequate amount of heat, .free from fluctuation, whenever it is needed, thus making possible an u n v a r y i n g t e m p e r a t u r e of about 80 ~ F. D u r i n g the fall, winter, and spring months a humidifier is k e p t in almost constant operation (Fig. 1). The individual incubators have been designed for simplicity, ease of operation and safety. Each incubator consists of a regulation size
F i g . 1.
infant cot, with an accessory f r a m e w o r k made of small sized p i p i n g fitted on the top, the whole s t r u c t u r e being covered b y btal~kets and sheets pinned in such a way as to leave an opening on the top directly over the b a b y ' s head. t t e a t is supplied b y two carbon filament e l e c t r i c bulbs so t h a t it is a v e r y simple p r o c e d u r e to v a r y their size or t u r n them off to obtain, any needed temperatm'e. The baby's eyes are proteeted from t h e lights by a curtain which is dropped f r o m the top of the f r a m e w o r k to the baby's neck. The advan.tages of such an incubator are: (1) mechanical simplicity , which gives almost foolproof operation; (.2) the infant's head is p r o t e c t e d from any d r a f t s which may arise in the room ; (3) the baby may be fed and eared for without
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the dangers incidental to removing it from the heated tent. Baths of w a r m oil are given daily while soap and water' baths are administered only once a week. As has been stated above, we t r y to keep the t e m p e r a t u r e of the p r e m a t u r e room as dose as possible to 80 ~. This can be done very readily in the cooler months, b u t in the very hot months of summer it f r e q u e n t l y rises above this point as there is no method of cooling the air. The t e m p e r a t u r e of the individual incubators is kept at a point sufficient to p r e v e n t loss of body heat so that the b a b y ' s temp e r a t u r e is kept between 98.5 ~ and 100 ~ Newly born infants of very small weight will f r e q u e n t l y require an incubator t e m p e r a t u r e of over 100 ~ but this can be g r a d u a l l y lowered until at the end of three to f o u r weeks 80 ~ to 85 ~ is sufficient. D u r i n g the summer months in the Detroit area, at which time the average mean temperatures were somewhat comparable to the average t e m p e r a t u r e of the p r e m a t u r e room, official figures obtained from the w e a t h e r b u r e a u (1930) showed t h a t in June, J u l y and A u g u s t the relative h u m i d i t y varied from (t2 t o 68 per cent with mean temperature ranges f r o m 79.6 ~ to 65 ~. I n the smnmer of 1929 the relative hllmidity a v e r a g e d a trifle more with somewhat lower t e m p e r a t u r e levels. Hence in our a t t e m p t to keep the relative h u m i d i t y close to 60 p e r cent we have been keeping" near the level it n a t u r a l l y assumes during" the time of year in which we find the least a m o u n t of respirat o r y infection and when the average child's health is at its best. W i t h a t e m p e r a t u r e of 80 ~ and a relative h u m i d i t y of 55 to 60 per cent, the atmosphere is f o u n d to be v e r y comfortable b y the nurses and others going into the p r e m a t u r e room. A t this point, too, loss of b o d y heat is reduced to a minimum when slight fluctuations occur in the room temperature. The question of temperature and humidity has received consideration from numbers of workers but exact information as to the ideal levels (particularly humidity) is surprisingly scarce. La F e t r a 2 stated that his results were much improved at Bellevue Hospital b y raising' the h u m i d i t y and lowering the t e m p e r a t u r e but gave no definite figures on humidity. Sinclair a advocated a basket t e m p e r a t u r e of from 80 ~ to 90 ~ with a relative h u m i d i t y of 60 to 70 per cent. Talbot advocated a t e m p e r a t u r e of 80 ~ with h u m i d i t y of 30 per cent while Blackfan and his associates; ~ in seeking the optimum conditions for maintaining a constant body t e m p e r a t u r e of 98.6 ~ f o u n d two points at which this could be done, (a) t e m p e r a t u r e of 80 ~ relative humidity 30 per cent, (b) t e m p e r a t u r e 77 ~ relative h u m i d i t y 65 per' cent, and stated t h a t until more data was obtained, conclusions as to which was ideal, were not justified. A b t 5 gives 55 per cent as the optimum
POOLE AND COOLEY:
P R E M A T U R E INSTANTS
19
humidity at 80 ~ F., and M o r g a n t h a i e r ~ in describing a bed having' an individual humidifier stated t h a t it was k e p t at 80 ~ to 85 ~ with 50 to 65 per cent relative h u m i d i t y and a t t r i b u t e d the success of the bed to the f a c t t h a t it was possible to m a i n t a i n a n o r m a l h u m i d i t y in the chambers. Strict isolation of the p r e m a t u r e cubicle is m a i n t a i n e d at all times so t h a t t h e r e is the m i n i m u m of contact with the r e m a i n d e r of the institution. Gowns a n d m a s k s are provided, in the a n t e c h a m b e r , f o r everyone e n t e r i n g the room, and no one is allo+ced to go in except in absolute necessity. The nurses looking a f t e r these babies have no other duties in order t h a t there m a y not be the possibility of crossinfection. Despite all a t t e m p t s at asepsis, however, we are not successful at all times, with the result that infections, particularly respiratory, continue to present the greatest problem.
Respiratory infections in premature infants are sufficiently different from those found in other infants to merit particular mention and some of our observations have cleared up problems 'that we could not previously solve. I t was o~lr not i n f r e q u e n t experience t h a t babies who h a d been thriving" would begin to show a slight rise in t e m p e r a ture with a c c o m p a n y i n g vomiting, d i a r r h e a or abdominal distention and w i t h o u t a n y v e r y positive physical findings to explain the upset. Some such p a t i e n t s died a f t e r a v e r y short illness, while others, a f t e r a brief illness, r e s u m e d their n o r m a l course. (See C h a r t I.) A f t e r finding u n s u s p e c t e d b r o n e h o p n e u m o n i a s a t autopsy, we b e g a n to t a k e cultures f r o m b o t h the nose a n d t h r o a t on all the infants. Most of those in good health showed only staphylococcus in the cultures, while the r e p o r t s of t h o s e w i t h the s y m p t o m s described almost i n v a r i a b l y were r e t u r n e d f r o m the l a b o r a t o r y with the notation t h a t lVlieroeoecus eatarrhalis or a strain of streptococcus was also present. ~We therefore concluded t h a t definite infections of the nose and t h r o a t m i g h t be p r e s e n t w i t h o u t our being able to see a n y a b n o r m a l congestion, t h a t b r o n e h o p n e u m o n i a f r e q u e n t l y resulted w i t h o u t m a r k e d elevation of t e m p e r a t u r e a n d t h a t death followed before the physical signs in the chest became v e r y evident. This failure of i m m a t u r e infants to localize and to resist infection was emphasized by Capper ~ in his review of 437 such patients. The susceptibility to infection of the r e s p i r a t o r y t r a c t is of course well k n o w n and has b e e n spoken of b y n e a r l y evel'y one who has h a d a l a r g e n u m b e r of eases. I n contrast, m a y be cited the experience of Cook s in California, who r e p o r t e d only f o u r deaths h ' 0 m r e s p i r a t o r y complications in a series of 77 p r e m a t u r e s . This f o r t u n a t e result was p r o b a b l y f a v o r e d b y climatic conditions.
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As all the infants received daily doses, of cod liver oil in what we felt to be adequate amounts (as well as irradiation with the quartz iight twice weekly), there did not a p p e a r to be a n y t h i n g more to be done f r o m a dietary s t a n d p o i n t to establish immunity.
F o r a time we fed
powdered b r e w e r ' s yeast to see w h e t h e r it would exert a favorable influenee, but were unable to note a n y result as f a r as i m m u n i t y to infection was concerned.
The question of p r o p h y l a c t i c vaccine ther-
a p y was then raised so this was tried on a n u m b e r of infants.
A
mixed c a t a r r h a l vaccine was given in increasing doses without apparent beneficial results and it oceasionally caused reactions which were higSIy undesirable. Cod liver oil of high vitamin D potency has been added to the formulas at the time of their p r e p a r a t i o n in the f o r m u l a room in the _~, VE.
o 4 e on o q m i ~ s / o ~ - ~ ~A's.
/or
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Chart I.--Showing
~Y'~OP'
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t h e effect of u p p e r r e s p i r a t o r y i n f e c t i o n u p o n a premature infant.
t h e wei2~'ht c u r v e of
p r o p o r t i o n of a dram to each pint of breast milk, or two drains to the pint in evaporated milk mixtures. I n this w a y eaeh infant received a daily dose of the oil from the day of admission, the dosage depending upon its ability to take food.
Nor a considerable time we
had a r o e n t g e n o g r a m taken of each b a b y ' s wrists and ankles when it was r e a d y to leave the hospital and f o u n d that in practically every instance there was no evidence of active rickets either in white or colored infants.
IIence we concluded that d u r i n g the period of hos-
pitalization o~r infants were protected by cod liver oil supplemented with irradiation by quartz light. The only exceptions seemed to be those babies who had severe infections lasting over a considerable period. In such infants craniotabes was m a r k e d and they did not respond to even increased doses of God liver oil. We felt that in such
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21
infants y e a s t seemed to cause a definite i m p r o v e m e n t in the calcification of tile bones w h e n given w i t h the oil, p r o b a b l y due to the f a e t t h a t the a d m i n i s t r a t i o n of y e a s t f a v o r s r e t e n t i o n of calcium in the body as has been shown by M a e y 9 a n d others in experiments on rats. G e r s t e n b e r g e r a n d Nourse 1~ d e m o n s t r a t e d t h a t riekets could be prevented b y small doses of cod liver oil and t h o u g h t t h a t their results were p a r t l y due to the f a c t t h a t the oil was s t a r t e d early. Despite the pessimistic view t a k e n b y other observers, n, 12, la who feel t h a t rickets is an inevitable occurrence even with adequate doses oi" oil, it would a p p e a r t h a t protection is s e c u r e d / w h e r e a good s t a n d a r d i z e d b r a n d of eod liver oil is s t a r t e d e a r l y and t h a t the doses do n o t h a v e to be large. A f t e r their r e t u r n home t h e r e were f o u r patients who developed severe rickets, possibly the result of m o t h e r s giving" the oiI at i r r e g u l a r intervals. One white child, however, required the persistent use of the quartz light to heal a m o d e r a t e l y severe riekets t h a t developed while it was receiving two teaspoons of oil daily. A n e m i a has not been a p r o m i n e n t clinieal finding" so we h a v e not felt t h a t it was necessary to g'ive iron to our patients routinely. To avoid handling, blood cot.rots and hemoglobin estimations were n o t made except w h e n special indieations p r e s e n t e d themselves. I n the infants who were t a k i n g food well and g a i n i n g in weight the n u m b e r who developed anemia of sufficient degree to be suspeeted on physical examination was p r a c t i c a l l y negligible. W h e n mild s e c o n d a r y anemia was suspected and verified by blood examination, the c o n d i t i o n responded r e a d i l y to the a d m i n i s t r a t i o n of small doses of s a e e h a r a t e d ferrous c a r b o n a t e given in the feedings. C o n t r a s t e d with these, however, were the anemias t h a t developed d u r i n g the course of infections. T h e y p r o g r e s s e d v e r y rapidly, the hemoglobin, and the red blood cell counts fell to low levels quickly, a n d they did not r e a e t well to the a d m i n i s t r a t i o n of iron. Transfusion of blood relieved the condition at once b u t it was often necessary to give small amounts of blood two or m o r e times because we f o u n d t h a t the benefit was only t e m p o r a r y while the infection, continued. We hope at a f u t u r e time to m a k e naore detailed observations based u p o n bloo& studies in a n u m b e r of such infants. M a c k a y ' s studies ~ of nutritional anemia r e c e n t l y pt~blished give some v e r y suggestive statistics on the effeet of iron a d m i n i s t r a t i o n in f o r e s t a l l i n g infection during the period of " p h y s i o l o g i c " anemia. As this anemia is especially evident in i n f a n t s p r e m a t u r e I y born, routine iron a d m i n i s t r a t i o n m a y p r o v e t~) be of value here. Char* I I shows the weight curves, o.f seventeen infants whose weight on admission to the pr'emature ward r ang'ed f r o m about 1000 gm. to 2200 g~n. As will be n o t e d f r o m a s t u d y of the individual curves ini-
22
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O~ ~ P E D I A T R I C S
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\ q) o~
,12 9
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PREMATURE INFANTS
23
tial loss of weight is n o t constant, being shown only in six of the seventeen. This is doubtless explained by the f a c t that feedings were started on r e g u l a r schedule within six hours of admission, while glucose solution (5 per cent) was commenced at once, 1~ and in many, subcutaneous injections of normal saline or 5 per cent glucose solution were given because of inability to take fluids well by mouth. I n looking at the curves designated A, B, and C, it will be noted that there is a close parallelism up to the s i x t h or seventh week. They represent the g r o w t h of three infants receiving breast milk without any alterations except g r a d u a l increase in q u a n t i t y up to the time mentioned above. I n Chart I I I the same type is seen in curves D, E, and F where the gain in weight d u r i n g the early weeks was v e r y slight. This is due to tile fact that on breast milk alone the infants
tooc /7o9 q6~
k
Chart III.--Infants G and H, breast milk and I only evaporated
represented by curves D. Ej and F were fed only breast milk; followed by diluted evaporated milk with added carbohydrate, milk formula.
are not able to take an amount o f feeding sufficient in calorie value or protein content. That this is true p a r t i c u l a r l y in the very smallest infants is illustrated by the eurves A and D, while the patient represented b y the curve F being ]arger, and eonsequently more vigorous, was able to consume sufficient breast milk, a f t e r about two and one half weeks, to maintain a very satisfactory gain. Their curves serve merely to point out that unmodified breast milk is not an entirely satisfactory food f o r the smallest prematures. They sleep almost continually and the nurse experiences diffieulty in rousing them sufficiently to take food so in the early weeks three to four drams per feeding is about the most that can be given unless g a r a g e is resorted to. Most elinicians agree that it is undesirable to disturb the infants f o r feeding oftener t h a n every three hours, hence it m a y readily be seen t h a t the caloric intake in t w e n t y - f o u r hours will not be sufficient
24
THE
JOUI~NAI~
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PEDIATRICS
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POOLE AND COOLEY:
PRE~IATURE
INFANTS
25
to more t h a n m a i n t a i n weight. M a n y methods have been used to remedy this defect, f o r example, r e d u c i n g the w a t e r content of the breast milk b y evaporation, ~6 using dried b r e a s t milk, 17 or a d d i n g c a r b o h y d r a t e or protein. 18, ~9 We have f o u n d that the addition of 2 per cent calcium caseinate to the milk m a k e s an e x t r e m e l y s a t i s f a c t o r y f o r m u l a f o r our small infants, a n d it is now routine practice in this clinic to use this highprotein breast m i l k on all infants weighing ]ess t h a n 1800 g i n . until a satisfactory gain is established. A f t e r the i n f a n t is seen to be thriving, an evaporated milk formula is substituted in gradually increasing
quantities until the breast milk formula is entirely stopped. The evaporated milk formula is continued during the remainder of the patient's stay in the hospital and afterward while it is being supervised by the out-patient department.
,~?oc ,~6oc
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Chart v.--nlustratinr
the g r o w t h
curves of p r e m a t u r e twins.
C h a r t I V shows in a graphic w a y the p r o g r e s s of two p a t i e n t s a n d indicates the various changes t h a t were m a d e in the formulas. The first p a t i e n t ( r e p r e s e n t e d by the lower curve) was a d m i t t e d at the age of t w e n t y - f o u r hours, w e i g h i n g 1050 gin. I t w a s given highprotein b r e a s t m i l k f o r m u l a and gained satisfactorily until the second w e e k a f t e r an initial loss of 100 gin. H a l f s k i m m e d lactic acid milk was then tried, but as progress was not satisfactory, the b a b y was again p u t on the b r e a s t m i l k f o r m u l a . A t seven and one-half weeks (1550 gin. weight) t h e s u b s t i t u t i o n of diluted u n s w e e t e n e d e v a p o r a t e d milk with added c a r b o h y d r a t e was c o m m e n c e d until at about nine and one-half weeks (weight a p p r o x i m a t e l y 2000 gin.) a f o r m u l a of one-third unsweetened e v a p o r a t e d milk, two-thirds water, with 5 per cent added c a r b o h y d r a t e was being used. The second
26
T]~IE J O U R N A L OlV PEDIATRICS
child was a d m i t t e d at nine days of age weighing 1110 gin. E x c e p t for m i n o r differences the plan of feeding was the same and the p a t i e n t followed a course closely parallel to the first. The a m o t m t of food consumed b y the first child was g r e a t e r t h a n t h a t t a k e n b y the second t h r o u g h o u t its entire course with a consequently higher caloric intake despite the close parallelism of their weights. This difference in prem a t u r e s is f r e q u e n t l y observed, m a n y being' able to gain quite satisf a c t o r i l y on s u r p r i s i n g l y small amounts. (See also C h a r t V.) Most of our i n f a n t s received f r o m 100 to 160 calories p e r k i l o g r a m and we have f o u n d t h a t the m a j o r i t y gain well on 120 to 140 calories p e r kilo. 1 This figure is l o w e r t h a n m a n y authors s feel is essential to p r o p e r g r o w t h in p r e m a t u r e infants and we feel t h a t the difference m a y be due to several factors, first, the n u r s e ' s ability to give p l e n t y of w a t e r between feedings, second, a m i n i m u m of h a n d l i n g of these infants, and third, the r e l a t i v e l y higtl protein content of the feedings. I n f a n t s w e i g h i n g over 1800 gin. are s t a r t e d directly upon diluted e v a p o r a t e d m i l k f o r m u l a s if the m o t h e r is not s u p p l y i n g b r e a s t m i l k . W e h a v e f o u n d the m a j o r i t y of such babies gain v e r y r a p i d l y a n d do so with few g a s t r o i n t e s t i n a l upsets. A f t e r t r y i n g o a t b o t h acidified and nonaeidified f o r m u l a s we have g r a d u a l l y discontinued almost all of the acidified milk so t h a t we are now using the acid f o r m u l a s only when there is a special indication. The sweet f o r m u l a s seem to be e n t i r e l y s a t i s f a c t o r y in almost every, instance a n d the nurses r e p o r t t h a t there is less discomfort and less vomiting t h a n when acidified milk is used. In beginning f o r m u l a s of e v a p o r a t e d milk in such patients we h a v e f o u n d t h a t g a s t r o i n t e s t i n a l upsets can largely be avoided by s t a r t i n g with a f o r m u l a of one p a r t of u n s w e e t e n e d evapor a t e d milk to three p a r t s of water with 7 p e r cent carbohydra.te added and increasing g r a d u a l l y up to equal p a r t s of unsweetened e v a p o r a t e d m i l k a n d w a t e r with the addition of 5 to 7 per cent c a r b o h y d r a t e . This can be done f a i r l y r a p i d l y so t h a t gain in w e i g h t is not delayed a n d by g r a d u a l addition in this w a y the feeble digestive powers of the p r e m a t u r e i n f a n t are not overtaxed. As few of our mothers are able to s u p p l y sufficient b r e a s t milk during the entire time their b a b y is in the hospital, we find t h a t the majority are getting p a r t o.r M1 artificial feeding after the third or fourth week. By using u n s w e e t e n e d e v a p o r a t e d milk f o r m u l a s a large sum of m o n e y has been s a v e d because of our not h a v i n g to b u y b r e a s t milk. R e f e r r i n g a g a i n to Charts I I and I i i , it will be seen t h a t gain in w e i g h t is e x t r e m e l y s a t i s f a c t o r y in the l a t e r weeks. Also in the weight curves of infants o v e r 1800' gin., most of w h o m get evapor a t e d milk formulas, it will be n o t e d t h a t the gain is v e r y rapid,
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27
PREMATURE INFANTS
a v e r a g i n g a b o u t 27 gin. per d a y with some gaining as much as 35 gin. per day. These figures are m a t e r i a l l y higher than those f o r infants receiving umnodified b r e a s t milk. B y g r o w i n g at this rate the child's hospitalization is shortened so t h a t it: can be sent home to be eared f o r by our follow-up service. I n this w a y the p r e m a t u r e population of the w a r d is k e p t to the minimum, which helps to reduce the chances of epidemics of r e s p i r a t o r y disease. F i v e t h r i v i n g p r e m a t u r e infants were given their r e g u l a r a m o u n t of f o r n m l a with b a r i u m added so t h a t the progress of the meal could be observed w i t h x-ray. E a c h child was given a test meal of b r e a s t Oooi
-
i
*v..,r Chart u
~
i the
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~
g r o w t h c u r v e s of five i n f a n t s b r e w e r ' s y e a s t in t h e i r diets.
gwho
2,
received powdered
milk and on a n o t h e r occasion a test meal. of nonacidified e v a p o r a t e d milk f o r m u l a so t h a t the e m p t y i n g t i m e of the stomach could be det e r m i n e d with each type of feeding. W e could see little difference between the b r e a s t milk f o r m u l a and the e v a p o r a t e d milk f o r m u l a in this respect, as a considerable p a r t of the meal left the stomach within the first h a l f h o u r and there was little r e m a i n i n g in the stomach at three hours. Samples of gastric contents f o r d e t e r m i n a t i o n of hydrogen-ion c o n c e n t r a t i o n were also t a k e n on three of these same i n f a n t s two hours a f t e r m e a s u r e d test meals of b r e a s t milk f o r m u l a a n d nonacidified e v a p o r a t e d milk f o r m u l a had been given. T h i r t y d e t e r m i n a -
28
T H E J O U R N A L OF P E D I A T R I C S
tions (eolorimetrie method) in all were made, the r a n g e being f r o m Pu 4.0 to FH 5.0 with the m a j o r i t y being PH 4.4 a n d PH 4.6 for both types of feeding. C h a r t V I r e p r e s e n t s the weights of infants who were given powd e r e d b r e w e r ' s y e a s t as an addition to the f o r m u l a s of high-protein b r e a s t milk and e v a p o r a t e d milk. The a v e r a g e daily gain f o r this g r o u p was 25.3 gin., which is v e r y close to the rate for those on evapor a t e d milk f o r m u l a s w i t h o u t yeast. Hess ~~ and Bloxom 21 have demons t r a t e d the effect of y e a s t upon growth, but in our infants the increase in the r a t e of g r o w t h was not striking so t h a t the addition of y e a s t to the diet was not a d o p t e d as a routine procedure. A survey was made by the social service d e p a r t m e n t prior to J a n u a r y , 1930, which showed t h a t few of the p r e m a t u r e infants discharged f r o m the hospital during" 1928 and 19'29 were living at the time the inquiry was made, and we assumed t h a t this was due to the living conditions in the homes and the indifferent care t h a t the babies had received. This led to the f o r m a t i o n of out" present fol]ow-up service which has w o r k e d out a d m i r a b l y and resulted in a m u c h different outlook f o r these babies in t h e i r homes. Two nurses devote almost their entire time to this w o r k outside the hospital. T h e y begin their contacts with the m o t h e r s i m m e d i a t e l y a f t e r a p r e m a t u r e i n f a n t is b r o u g h t in to the hospital. T h e y strive to see t h a t the m o t h e r is being p r o p e r l y cared for, t h e y teach her the method of e x p r e s s i n g breast milk a n d d e m o n s t r a t e its p r o p e r care prior to its being b r o u g h t in f o r the b a b y ' s use. Repeated home calls are usually necessary as m a n y of the m o t h e r s tire of collecting milk and s t a r t b r i n g i n g it to the hospital at irregular intervals. Stimulation of the m o t h e r ' s breasts b y massage is used along" with d i e t a r y instruction to keep up the milk s u p p l y as long as possible. S h o r t l y before the b a b y is r e a d y to leave tile p r e m a t u r e w a r d n u m e r o u s calls are m a d e to p r e p a r e the home for the b a b y ' s arrival. A cot or bassinet is p r e p a r e d , suitable f o r a small infant. I t is placed so as to be as close as possible to a constant supply of heat and a w a y f r o m windows a n d doors so as to minimize drafts. Directions are given regarding, the p r o p e r t e m p e r a t u r e and h u m i d i t y of the rooms, and the necessity f o r isolation of the p a t i e n t is stressed. As soon as the home p r e p a r a t i o n s are completed the m o t h e r is b r o u g h t to the w a r d where t h o r o u g h instruction is given in handling the baby. The p r o p e r method of bathing, and f e e d i n g the i n f a n t is t a u g h t her, as well as the p r e p a r a t i o n of the f o r m u l a if the child is not to be f e d entirely on the m o t h e r ' s b r e a s t milk. Sufficient f o r m u l a is sent home with each i n f a n t to last f o r t w e n t y - f o u r hours.
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The n u m b e r of home calls necessary, a f t e r the p a t i e n t leaves the ward, is d e t e r m i n e d by the circumstances in each case. The a v e r a g e is six calls d u r i n g the first week following discharge, three d u r i n g the second week, two d u r i n g the t h i r d a n d f o u r t h weeks, with one call weekly t h e r e a f t e r as long as it is deemed necessary, d e p e n d i n g upon the progress of the p a t i e n t and the cooperation secured in the home. The babies are b r o u g h t b a c k to the o u t - p a t i e n t clinic e v e r y two weeks f o r the first two months, then once a m o n t h until t h e y are a y e a r old, a f t e r which the u are made only e v e r y two months. In the clinic weights and m e a s u r e m e n t s are taken, feedings checked, cod liver oil and orange juice (or t o m a t o juice) increased as needed. Most o.f the illness in the homes ha~ been the res.ult o~ r e s p i r a t o r y infections, or the acute specific infectious diseases. In the t w o - y e a r period there have been only six i n f a n t s r e a d m i t t e d to the Children's Hospital, and one a d m i t t e d to the City Contagious Hospital. There were three deaths at home in the s a m e length of time, one due to diarrhea (after leaving Detroit), one expired v e r y suddenly and we were unable to determine the cause, while the t h i r d child a p p a r e n t l y choked to deattt when left alone wit~a, its bottle. We feel t h a t these results in earing' for a g r o u p of seventy p r e m a ture infants u n d e r r a t h e r indifferent home conditions h a v e been highly satisfactory. There has been a v e r y noticeable i m p r o v e m e n t , too, during t h e second y e a r of this routine as c o m p a r e d w i t h the first, despite the fact that aid from the welfare department to m a n y of these families had been greatly reduced. In the last twelve months there have been thirty-eig'ht infants discharged with only two. readmitred and no deaths at home. Our infants w h o have reached a year or over compare very favorably with children born at full term as Fig'. 2 will help to show. More than half of them reach accepted standards for weight and height-at a year, and practically all of them do so before one and a half years of age. As r e g a r d s their ability to sit up, to walk, and to begin saying' words we h a v e not noted a n y p a r t i c u l a r delay. Quite striking, t~owever, is the slowness in dentition. ]t is unnsual for a n y teeth to e r u p t before the ninth month, and it is often as late as the eleventh or twelfth m o n t h before t h e y appear. W e f e d t h a t this bears a direct relation to the degree of p r e m a t n r i t y and t h a t the period up to their n o r m a l b i r t h time should be t a k e n into consideration before deciding' t h a t the teeth h a v e not e r u p t e d at tl~e a v e r a g e time.
One of our children is definitely a Mongolian idiot, a n o t h e r who had an occult spina bifida is not m a k i n g n o r m a l progress mentally, and there have been two deaths in the w a r d of the infants on w h o m a diag-
30
THE
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nosis of cerebral i n j u r y with s p a s t i e i t y was made. I t would appear, t h e r e f o r e , t h a t a r r e s t e d cerebral d e v e l o p m e n t has not p l a y e d a v e r y conspicuous p a r t in the infants who have survived. CapperS in his rSsum5 t o o k a r a t h e r pessimistic view concerning the nlental developm e n t of this t y p e of child and f o u n d a much h i g h e r p e r c e n t a g e showing evidence of cortical injury. He also pointed out the t e n d e n c y of the p r e m a t u r e to spont~meous h e m o r r h a g e . W e h a v e h a d one death of bleeding f r o m the cord s t u m p in an infant, which could not be s t o p p e d b y transfusion. In two other instances bleeding' was quickly a r r e s t e d b y small amounts of blood given i n t r a v e n o u s l y before alarming s y m p t o m s appeared. There was no recurrence of h e m o r r h a g e in either child.
Fig. 2.
SU1V[~[ARY
D u r i n g the last two years we have been striving to develop niett~ods of care f o r our p r e m a t u r e (and i m m a t u r e ) babies which would (1) reduce the m o r t a l i t y a m o n g these infants a f t e r their r e t u r n to their homes, a n d (2) decrease the cost of t h e i r care while in the w a r d s of the hospital. The f o r m e r has been accomplished by close supervision of the home care, m a d e possible b y our two visiting nurses and b y f r e q u e n t cheek.. ups in the o u t - p a t i e n t clinic. There have been seventy infants eared for in this w a y with most g r a t i f y i n g results. W h e n p r e s e n t economic conditions are t a k e n into consideration the i m p r o v e m e n t in the mort a l i t y at honie becomes even more outstanding. A g r e a t m a n y of these families are entirely d e p e n d e n t upon the city welfare organizations for support, which means t h a t only the bare necessities can be procured. The r e d u c t i o n in cost to the hospital has been accomplished b y the persistent efforts of the nurses in h a v i n g the m o t h e r s b r i n g in their
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INFANTS
31
breast milk, by the early substitution of evaporated milk formulas where the mother is unable to supply enough breast milk, and by sending the infants home when they reach five pounds (approximately 2300 gin.) in weight. As has been previously stated, 35 per cent of all our admissions of premature infants die within f o r t y - e i g h t hours of the time: of arrival, while 8 per cent are in an obviously m o r i b u n d condition w h e n reeeived. This unfavorable situation could doubtless be improved by educating" the a t t e n d i n g physicians and the laity in r e g a r d to the necessity of g r e a t e r care in h a n d l i n g p r e m a t u r e infants, and possibly also by malting available a heated carrier for u s e . i n an ambulance such as the one devised b y Itess TM a n d f o u n d v e r y s a t i s f a c t o r y in Chicago. The need f o r such i n f o r m a t i o n and care is emphasized by the fact t h a t among the infants who died 68 per cent had a rectal temperature of 97 ~ F., or below, w h i l e in only 23 per cent was the temperature between 97 ~ and 100 ~ F. * C;bIAR'T' V I I CAIJSIfS O,P DEATII (After 48 horn's from time of admission) PEI~ OEN92
Prematurity Acute respiratory infection (Including bronehopnemnonia) ~Diarrhea Inanition Birth injury Fetal ateleetasis Gonorrheal opthalmia Congenital abnormality o f heart
Hemorrhage Syphilis
Spina bifida and other abnormalities Erysipelas Moribund on admission Total mortality (after 48 hours) 1930 Total mortality (after 48 hours) 1931 *Most of these were parenteral diarrhea due to respiratory infection,
44 22 6 3 5 3 '2.5
2 1 1
2 0.5 8
4=4 33
A s t u d y of the causes of death in our series shows that in 44 per cent we were unable to find any other cause than p r e m a t u r i t y to account for their demise. The less, of course, will be the chance for survival, tile smaller the b a b y and the greater the degree of prematurity, so t h a t in babies weighing 1.000 gm. or' less the m o r t a l i t y is about 95 per cent. =, ~ R e s p i r a t o r y infection caused 22 per cent of our deaths, the n u m b e r d y i n g front this cause being much higher in the cool months than in the summer. The deaths ascribed to gonorrheal ophthalmia are the result of the ihandling and exposure made
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THE JOURNAL OF PEDIATRICS
necessary for proper treatment of the eye condition. The intestinal upsets were practically all due to infection of the respiratory tract, but as diarrhea was the most prominent symptom the deaths have been listed under that heading. During the two-year period there have been fifty-two premature infants admitted to the general wards of the hospital because they were suffering from some type of infection when admitted, and of these f o r t y died (77 per cent). The mortality among the babies admitted to the special premature room, exclusive of those dying within the first forty-eight hours after admission, was 44 per cent during 1930, and 33 per cent during 1931. CONCLUSIONS
1. The supervised care of premature infants in their own homes has proved ver y satisfactory. 2. The mortality in the posthospital period has been reduced by this method. 3. The period of hospitalization has been shortened with consequent reduction of cost. 4. I~ickets can be prevented in premature infants by small doses of cod liver oil (supplemented by ultraviolet irradiation) if started early. 5. Breast milk with added calcium caseinate has been found the most satisfactory feeding for infants under 1400 gm. in weight. 6. Infants over this weight thrive well when a diluted unsweetened evaporated milk formula, with added carbohydrate, is gradually and carefully substituted for the modified breast milk. 7. Nonacidified evaporated milk has been found satisfactory for the larger prematures and during the period of after-care in the homes. 8. Gastrointestinal upsets were of infrequent occurrence in infants who were not suffering from infection. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.
Hess and Chamberlain: Am. J. Dis. Child. 34: 571, 1927. La F e t r a : Arch. Pediat. 24: 22, 1917. Sinclair: Arch. Pediat. 37: 139, 1920. Yaglou, Drinker, and Blackfan: Am. Soe. H e a t i n g and V e n t i l a t i n g Engineers J. Sect. ttcating, Piping and Air Conditioning 2: 605, 1930. Abt: P e d i a t r i c s : Vol. II, p. 486. Morganthaler: Am. J. Obst. & Gynee. 8: 622, 1924. Capper: Am. J. Dis. Child. 35: 262, 1928. Cook: Arch. Pedlar. 38: 201, 1921. Macy: Not published. Gerstenberger and Nourse: J . A . M . A . 87: 1108, 1926. F r a m m : Ztsehr. f. Geburtsh. u. Gyni~k. 88: 319, 1924. Wyman: Boston M. & S. J. 194: 202, 1926. Garland: Ibid. 192: 581, 1925. Mackay, I:L M..: ~V[edica] l~eseareh Council /~ep. No. 157: London, 1931. I~ess, J. It.: M. Clin. North America 3: 1709, 1920.
POOLE AND COOLEY: 16. 17. 18. 19. 20. 21.
PREh~[ATUi~E INFANTS
T h o m p s o n : A r c h . P e d i a t . 43: 303, 1926. E m e r s o n a n d S m i t h : A m . J. Dis. Child. 31: 1, 1926. Langer: Ztschr. f. K i n d e r h . 41: 598, 1927. H e s s , J. H . : J . A. 1~. A. 80: 1313, 1923. Hess, A.F.: A m . J. Dis. Child. 13: 98, 1917. B ] o x o m : A m . J . Dis. Chi]d. 37: 1161i 1929. 22. E d e n : L a n c e t 2: 127, 1921. 23. P u l f o r d a n d B l e v i n s : A m . J. ])is. Child. 34: 797, 1928. 953 FISCHER BLDG.
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