PREMATURITY
AND
RICKETS
By S. Eek, M.D., L. H. Gabrielsen, M.D., and S. Halvorsen, M.D.
University Pediatric Clinic, Rikshoitalet, Oslo, Norway
(Submitted December 21, 1956, accepted January 7, 1957.)
ADDRESS: (S.E.) University Clinic, Rikshospitalet, Oslo, Norway.
63
F
OR MANY YEARS human milk has been regarded as the ideal food for prema-ture infants.In recent times another opinion has been upheld by several investigators. Benjamin and co-workers1 investigated the calcium
and phosphorus absorption by premature infants, and found a considerably greater retention of these minerals when cow’s milk
was given instead of human milk. Accord-ingly, they concluded that, if best possible
conditions are to be provided for skeletal development, human milk should be sup-plemented by additional calcium and phosphorus.
Stearns2 maintained that, even in the
case of mature infants, a dietary of human
milk leads to a gradual reduction of the relative mineral content of the skeleton
during the first 6 months of life, and that it is not until about the age of 1 year that
the same percentage figures as those exist-ing at birth are reached. This loss of miner-als will become further accentuated in
pre-mature infants, with their restricted supply of food and rapid growth. Added to all this is the fact that the most important
de-position of calcium and phosphorus during the last months of pregnancy is interrupted
by
the
premature
birth
of these
infants, with the result that the deposits of theseminerals are small from birth.
These conditions have been taken to ac-count for the relatively frequent occurrence and early development of rickets in pre-mature infants.3
Von S#{252}dow4examined a great number of premature infants given human or cow’s milk, with or without a supplement of vita-mm D. In the blood of premature infants fed human milk, he found considerably
lower concentrations of phosphorus and higher of phosphatase than for mature
in-fants. Premature infants given cow’s milk
showed considerably smaller departures from the normal. He observed at the same time that radiologic signs of rickets oc-curred more frequently in the infants fed human milk, and even large doses of
vita-mm D could not apparently prevent this disease with certainty. He suggested that
an extra supply of calcium and phosphorus might possibly counteract the tendency to
rickets in premature infants fed human milk, but he presented no definite evidence in #{149}support of this opinion.
If these remarkable findings were to be confirmed, it would be necessary to under-take a readjustment of the dietary when-ever human milk constitutes the main source of nourishment for premature
in-fants.
At
the Pediatric Clinic in Oslo, wherehuman milk has been given to a large
cx-tent, we have therefore found it of impor-tance to repeat these investigations, but in a
somewhat simplified form and with certain
modifications.
Of
three groups of infants, one was given human milk, another cow’s milk and a third group, human milk supplemented with dried skimmed milk. This latter group was investigated to see if human milk withad-ditional calcium and phosphorus would give a better mineralization of the bones than human milk alone. Dried skimmed milk was chosen as a supplement because it was practical and because it proved
diffi-cult to devise another preparation of cal-cium and phosphorus with more ideal com-position and solubility.
PATIENT MATERIAL AND METHODS
Infants
pre-64
PEDIATRICS-JULY
1957
TABLE I
l)ISTIuBUTI0N OF INFANTS, ACCORDING TO
WEIGHT AT BIRTH
JJ’eight at Birth (gm) human Milk Cow’s Milk
Mr
odified human Milk1000-140 I 3 1
150-1490 6 8 10
1500-1740 8 4 10
175O-200O 6 5 7
Total 1 o 28
sented no disorders other than those commonly associated with prematurity. Table I shows the composition of the material with respect to the weight at birth.
Feedings
The infants studied were distributed among the following three feeding groups:
1. HUMAN MILK. The milk was supplied by the Breast Milk Bank in Oslo. Human milk was given as long as the infants stayed in the hospital, usually to the age of 60 to 100 days.
2. Cow’s MILK. This mixture consisted of equal parts of cow’s milk and water with 7% sugar during the first 8 weeks, later on, of two
parts of cow’s milk and one part of water with 5% sugar.
3. MODIFIED HUMAN MILK. Dried skimmed milk#{176}was added to human milk making a 2% solution. With this supplement the calcium
content of human milk was increased from 0.034% to 0.062% and the phosphorus content from 0.015% to 0.030% as compared with the respective values of 0.061% and 0.045% for the cow’s milk mixture during the first 8 weeks.
The feedings in all groups were started on the second day of life, with a gradual increase
of the quantities of milk up to 60 to 80 cal/kg at the age of 2 to 3 weeks.
The infants in groups 1 and 2 received in addition an amino acid preparation,t starting with 0.5 gm on the fourth day of life and rising to 2 gm from the age of 2 weeks. The infants in group 3 did not receive this
prepa-0 Dried skimmed milk was supplied by De
Norske Melkefabrikker A/S, Oslo.
t Nesmida, supplied by Nestl#{233},Switzerland.
ration because the protein content of the added dried skimmed milk approximated the amount given with the amino acid prepara-tion.
Vitamin D was given to all groups from the fourth day of life in the form of a water-miscible vitamin-D2 preparation#{176} in a quantity corresponding to 800 I.U. daily. A supplement of 25 mg vitamin Ct was given from the same. age, increased to 50 mg from the age of 2 weeks.
TECHNIQUE OF THE Sruny: All the infants were subjected to the following examinations: 1. Analyses of serum for calcium, phosphorus and phosphatase activity, perferably in the first week and later at 2- to 4-week intervals.
2. Radiologic examinations of the forearm as soon as possible without undue risk,
prefer-ably in the first week, and later at 4-week in-tervals.
The infants in groups 1 and 2 were sub-jected to careful clinical examinations for
craniotabes and epiphyseal swellings. These were omitted in the third group because the examiner (L.G.) had left the hospital during this part of the study, and because it was be-lived that examinations performed by another very likely would induce a great possibility of error. Softness of the central parts of the
parietal or occipital bones, with quite evident yielding under pressure, giving the typical
impression of a “ping-pong” ball, was taken to indicate craniotabes and registered as such. Softness in the periphery of these bones, along the sutures, was not regarded as a positive finding.
Methods
Calcium in the serum was determined ac-cording to the method of Schwarzenbach and
co-workers with a modification by Crette,5 0.5 ml serum being used.
Inorganic phosphorus in the serum was
de-termined according to the method of Fiske and Subbarow#{176} using 0. 1 ml of serum.
Phosphatase in the serum was determined according to the King and Armstrong modifica-tion of the method of Buch and Buch using 0.1 ml serum.
0 A-D vit drops, supplied by A/S Farmaceutisk Industri, Oslo.
t Vitamin C “NAF,” supplied by Norsk
TABLE 11
VALUES FOR CALCIUM, PHOSPHORUS AND PHOSPHATAS IN THE SERUM OF PREMATURE
INFANTS ON DIFFERENT FEEDINGS
Age (days)
Human Milk Cow’s Milk Mixture Modified human Milk
No. Determ. Mean
2 No.
Determ.
-____
Mean s2 No.
Determ. Mean 2
Calcium 0- 14 9 10.6 0.471 8 10.15 0.807 12 9.00 1.221
(mg/lOOml) 15- 30 17 9.80
31- 45 46- 60 61- 75 76-100 18 12 16 10 10.26 10.4 10.41 10.7 0.813 0.442 0.514 0.258 19 14 12 6 10.27 10.05 10.56 10.86 0.265 0.623 0.435 0.075 16 18 14 9.57 9.97 10.33 0.436 0.815 0.485
Phosphorus 0- 14 15 4.0 0.797 17 4.69 0.778 12 4.38 1.187
(mg/100 ml) 15- 30 17 4.69
31- 45 46- 60 18 13 3.78 3.97 0.655 1.041 19 12 5.3 5.14 0.677 0.764 16 18 4.95 4.82 0.353 0.292 61- 75 76-100 16 10 3.8 4.0 0.510 0.536 11 7 5.77 6.3 0.889
0.496 14 4.87 0.168
Phosphatase 0- 14 6 13.6 1.479 8 13.36 4.319 9 19.27 62.704
(units) 15- 30 17 21.40
31- 45 46- 60 61- 75 76-100 13 9 15 10 18.3 17.28 20.07 21.32 19.676 22.47 38.26 33.73 17 12 11 5 15.00 17.12 13.8 16.28 7.574 20.892 27.336 34.52 16 18 13 19.64 22.29 17.21 4.398 23.330 21.729 iN
* The variance 2 was calculated from the formula : s
=
- dN
in which d1 represents the deviation from
mean for observation no. 1 and N the number of observations.
RESULTS
Chemical Investigations
Table II gives the results of determina-lions in the serum in the three groups. First the human milk and cow’s milk groups
will be compared. The calcium content of serum in these two groups showed no sta-tistically significant differences. The inor-ganic phosphorus, however, was signifi-cantly#{176} lower in the serum of infants fed
0 During the statistical analysis of the results,
use was made of the students’ t-test for each age group (Hald,8 p. 292), the level of significance being 0.05. The hypothesis var(x) = var(x’) was
tested according to Hald (p. 277) with the result that the variances were not found to be
signifi-canfly different with a level of significance of 0.01. There were a few exceptions which must be taken into consideration when the results of the t-test
are evaluated. This was by comparison of the
human milk alone, and the difference
seemed to increase with age.
The
phosphatase values showed an in-crease in both groups from the neonatal level, being greatest for the human milkgroup at the age of 61 to 100 days. The
difference emerging for the two means is statistically significant.
The infants fed modified human milk showed lower concentrations of calcium in
the serum than both the other groups. The differences were statistically signfficant.
The
values for inorganic phosphorus were higher in the group fed modified humanphosphorus values in groups 1 and 3 at the age 46
66 PEDIATRICS-JULY 1957
milk than with human milk alone, and the
difference was significant. They were, how-ever, lower than in the cow’s milk group,
and this difference was also significant.
The
phosphatase values were higher in the infants fed modified human milk than in both the other groups. The differencewas significant between the cow’s milk and modified human milk groups but not signifi-cant between the modified and human milk
groups.
Clinical Findings
Tm
Cuici ExM,nATIoN: In no casedid the clinical examination at the time of
the radiologic examination reveal any evi-dence of rickets. There were a few cases
presenting slight swelling of the ribs at the junction of cartilage with bone, but this “rachitic rosary” was never so marked that it could be taken as positive proof of rickets. Craniotabes was relatively common
in the infants fed human milk, but was rare in those receiving cow’s milk (Table III).
The
craniotabes usually appeared at the age of about 1% months, increased during the following month, but then after the ageof S to 4 months diminished in most cases.
This
diminution coincided apparently with the change to cow’s milk on discharge from the hospital.GROWTh IN LiGm: The mean daily growth in length of infants fed human milk was 0.104 cm, as compared with 0.116 cm for the infants fed cow’s milk. The
differ-ence
was not statistically significant.Tii
HEALTH AND STATE OF NUTRiTION OFTHE Moi’imns: These factors may
presum-ably
have an influence during pregnancy onTABLE III
FREQUENCY OF CRANIOTABES IN PREMATURE INFANTS
FED DIFFERENT DIETS
Human
Milk
Cow’s
Milk
Considerable craniotabes 12 0
Slight craniotabes 4 3
No craniotabes 4 17
the subsequent development of the infant’s
skeleton. Among the mothers of the infants examined were six who suffered from pro-longed and severe toxemia of pregnancy, nine who suffered from a slighter and more
brief attack of the same disease, four with severe vomiting during the last 3 months
of pregnancy, one with persistent anemia, and two who had several hemorrhages during the last month of pregnancy. These
diseases were distributed equally among the mothers of the different groups of
in-fants.
Data were collected concerning the mothers’ diets, but were difficult to
evalu-ate. However, the diets seem in every case to have been sufficient with regard to the more common foods. There were, however,
great variations in the consumption of milk and in the intake of cod liver oil or other
vitamin D preparation. No definite correla-tion could be established between disease or a deficient diet and the biochemical, radiologic or clinical findings in the
in-fants.
Radiologic Findings
At
the first radiologic examination shortly after birth, all the premature infantsexamined showed a sharply defined
meta-physeal zone of rarefaction, which was
situated just below a smooth but often thickened and sclerotic epiphyseal line. The border between this metaphyseal zone of rarefaction and the constanfly dense dia-physis was always sharp (Figs. la, 2a and Sa). The zones of rarefaction were present
both distally and proximally in the long bones of the forearm, and were also found in both ends of the metacarpals. They are
broadest distally, which is due to a higher growth intensity here than proximally. At birth the zones vary between 0.5 and 4 mm in the distal ends of the radius and ulna, with a mean of 1.2 mm for the whole ma-terial. If the mean growth rate of radius and ulna during the last part of pregnancy
67
During the first
4
to 6 weeks of life thesharp border between the zones of rare-faction and the diaphysis was less and less definite, and after a mean of 7 weeks it had completely disappeared. This
hap-pened irrespective of the dietary. General-ized osteoporosis developed in all feeding groups during the first 10 to 13 weeks after
birth.
The
osteoporosis started distally andproximally in the long bones, and continued
toward the middle third of the bones, which remained well mineralized longest.
After about 5 to 6 months the bone formed in the metaphysis showed, in some
premature infants, increased density, but
the increase was never prominent, and it was difficult to evaluate. There was no
dif-ference between the three feeding groups in this respect.
Periosteal double contours on the radius and ulna were demonstrated at varying ages, 2 to 7 months. In group 1 (human milk group) only 10 showed double con-tours, and they developed later than in the
other two groups (Table IV). This probably means that cow’s milk or supplemented hu-man milk increased mineral deposition in the skeleton earlier than human milk alone
Some of the infants at birth had thick-ened and sclerotic epiphyseal lines in the
bones, which were seen later as “primary” growth lines. They disappeared completely after a mean of 3 to 33 months. New growth lines (“secondary”) were formed during the period of observation in some infants. It
was not always possible to demonstrate any growth-inhibiting factors in these infants.
There was no relation between the width
TABLE IV RAoIowoIc FINDINGS Group 1 Human Milk Group Cow’s Milk Group 3 human Milk and Dried Skimmed Milk Number of Patients Metaphyseal zones of rarefraction
Breadth of the zones .5-2 .0 mm .5-. 40 mm
-
.5-2 .0 mm
-60
Average figures 1.1 mm i .4 turn
---I.2 mm 60
“Primary” transverse growth lines “Secondary” transverse growth lines
No lines 5 patients S Patients 6 patients 14
Appeared after 27-50 days
----21-50 days ----37 days ---23-74 days ---48 days ---54-133 days 46 --- ---.-46 60
Average figures 39 days
Disappeared after 66-21 1 days 57-143 days
Average figures
No secondary lines
104 (lays
15 patients
-86 (lays 108 days
15 patients
---
16 patients
---83-168 days 46
Appeared after 122-468 days 108-199 days 14 60
Periosteal double contours
No double contours 10 patients
-6 patients
-6 patients 22
Appeared after 122-563 days 71-153 days 56-128 days
---38
Average figures 210 days 113 days 105 days 60
GeneraJized osteoporosis
Appeared after 56-210 days 34-210 days 41-118 days
Average figures 89 days 78 days 72 days
%
cm 47cm
j
C
D
mm 61 days 89 days
irowth line
FIG. 1. K.N., female. Birth weight: 1400 gm.
Food: hunian milk. This patient and TN.
(Fig. 2) are twin sisters. (See also next page.)
A
B
9 days 38 days
68
PEDIATRICS-JULY
195’t
of zones of rarefaction and the degree of )rernatIInity.
Rickets vas not observed in any patient (luring the period of observation.
As controls, 100 full-term infants were
examined; in 6 of these metaphyseal zones
of narefaction could be demonstrated. The
mothers of four of these six infants had
signs of toxemia during the last part of
clini-*T&
J
F
167 daysFIG. 1. (Continued.)
G
198 days
ARTICLES
69E
123 days
cally recognizable disease was present. None of the remaining 94 infants had
meta-physeal zones of rarefaction.
DISCUSSION
The biochemical investigations showed
lower values in the serum for phosphorus
and higher for phosphatase on a diet of
human milk alone than on a cow’s milk mixture, whereas the calcium values
showed no differences. The infants fed sup-plemented human milk showed significantly
lower values for calcium than the other
groups; the values for phosphorus in the
serum approximated the values for the
cow’s milk group, whereas the phosphatase
values were higher than in either of the
other groups.
Although there are some differences in
\
I
C
61 days
D
78 daysA
9 days
FIG. 2. T.N., female. Birth weight: 1360 gm.
Food: cow’s milk. (See also next page.)
B
38 days
70 PEDIATRICS-JULY 195k
“u
to the choice of method employed, the present findings tally well with those of ‘on S#{252}dow.‘ The values for inorganic
phos-phorous in the serum in the neonatal period
were rather low for all groups, compared
%h
- .‘
3.
id
0fr
1
H1
k
E
123 days
G
198 days
ARTICLES
7167
daysFIG. 2. (Continued.)
for phosphorus in the serum during the
first weeks of life in full-term infants fed
human milk and cow’s milk.
The differences between the human milk group and the cow’s milk group can be
ex-plained as the result of the higher mineral
content of the latter. The low value for
calcium in the serum of the group fed
sup-plemented human milk cannot be so
satis-factorily explained.
The inorganic phosphorus in the serum
of premature infants fed human milk was
on several occasions found to be so low
that it corresponded to the values usually
found in active rickets. In all groups the
phosphatase values were slightly above
those regarded as normal for older infants,
and they corresponded approximately to the means calculated by von S#{252}dow.4 The rise observed during the first months of life can again be found in these cases also. This
71
5.1cm
SW,
WA
25days
C
82 days
ii
61 days
72
PEDIATRICS-JULY
1957
FIG. 3. MS., female. Birth weight: 1340 gm.
Food: human milk and dried skimmed cow’s milk. (See also next page.)
among the infants fed human milk and
sup-l)l(’mented lmman milk, and they came thus to represent the most obvious differences.
As a general conclusion it may be stated
that these chemical investigations in this
series of premature infants showed
D
E
I24days
I88days
ARTICLES
734?
Fic. 3. (Continued.)
3W
4.9cm
Fic. 4. MO., 1-day-old girl.
active rickets. These variations were more
pronounced in infants fed human milk than
cow’s milk mixtures. The supplementation
of human milk with dried skimmed cow’s
milk did not significantly improve these
variations.
In order to answer the questions as to
whether these chemical changes are
mani-festations of rickets or variations clue to
rapid growth, one must compare the stilts with the radiologic and clinical
find-ings.
74 PEDIATRICS-JULY 1957
which have been described previously by
Lindbl#{243}m1#{176}
and also by von S#{252}dow.4 Von S#{252}dow found these zones most frequentlyabout the age of 1 month, and he noticed that these changes were often, but not in-variably, followed by signs of rickets. He
therefore believed that they were early manifestations of this disease.
Our
observations
are,
however,
contra-dictory. They show that the band-shaped zones of rarefaction in the metaphysis arean almost invariable phenomenon in
pre-mature infants at birth. At such an early
stage these changes cannot have anything
to do with the infants’ dietary. We do not agree with the view that the zones are
precursors of rickets. If they were, they should have healed in a short time
follow-ing the adequate dosage of vitamin D in the same manner as “uncomplicated rick-ets” regularly does. In spite of this vitamin supply the osteoporosis develops, starting from the distinct metaphyseal zones and
progressing towards the midpoint of the diaphysis. The differences between von S#{252}dow’s findings and our own must be
at-tributed in part to the fact that most of the infants he studied were radiologically ex-amined at a later age than the infants we studied, and that some of them received the vitamin D later than in the present
series.
Similar and very conspicuous changes are also demonstrable in the metaphyses of nonviable fetuses, and in congenital
syphilis prominent zones of this kind can
also be 12 They have been
in-terpreted as a product of specific,
inflam-matory tissue situated in the metaphyses,hl
but are more likely to be due to disturb-ances in the process of ossification.13 Similar zones of rarefaction can also be provoked by various morbid processes during growth.
This raises the question as to whether
these zones are the result of disturbances caused by the factor which was responsible for the premature birth itself. Our
investi-gations do not, however, provide any defi-nite evidence to support such a concept.
Infants born of mothers with toxemia of
pregnancy did not, for instance, have more pronounced zones than infants born of
mothers without clinically recognizable disease. We do not know what initiates
birth
in most of the mothers delivering pre-mature infants. It is, however, possible thatthis mechanism, which hitherto has been impossible to register with usual clinical methods, might be due to one or another
pathologic condition in the mother or the fetus which initiates the birth process and at the same time disturbs normal
ossifica-tion,
e.g., hormonal disturbances.The
osteoporotic metaphyseal zones which are found in all premature infants differ very little in width, usually about 1 to 2 mm. This represents the growth ofradius or ulna during 2 to 8 weeks of
intra-uterine life.
A case
report
of a full-term
infant
may
have relevance to the present discussion:M.O.,
a 24-year-old woman, after 7 months of pregnancy developed symptoms and signs of toxemia; albuminuria, hypertension and edema. She was treated with bed rest for 1 month. The signs of intoxication disappeared completely, and 1 month following the cbs-appearance of the symptoms, she gave birth to a full-term infant.On roentgenologic examination (Fig. 4) we found distinct zones of rarefaction in radius and ulna which were 2 mm broad in the distal ends and 1 mm broad in the proximal ends of the bones. The distal zones were situated 2 mm from the epiphyseal lines and must repre-sent a growth disturbance in the period during which the mother had toxemia.
The
epiphyseal lines, which at birth usually are slightly broadened, distinct andsclerotic, are sharply contrasted against
the metaphyseal zones of rarefaction be-low. These sclerotic epiphyseal zones may be the result of a growth-inhibition during
the same period.
ARTICLES 75
absorption of minerals in these infants is so
incomplete and unsatisfactory that the bones lose the calcium already deposited to keep the calcium in the serum at a nor-mal concentration, and so they are
decal-cified. There were no differences in the
de-gre#{233}
of osteoporosis in the three feedinggroups, although the osteoporosis seemed to persist longer in the group fed human
milk. Because of the highly subjective evaluation as to degrees of osteoporosis,
one cannot attach too much importance to this finding.
More definite was the finding of
pen-osteal double contours
( “cortical
thicken-ings,” Caffey11). These double contours made their appearance earlier and more frequently in the groups fed cow’s milk andsupplemented human milk. They are prob-ably the first sign of improved
mineraliza-tion and are more easily detected than is improvement in general osteoporosis. Such double contours are seen in healing rickets, but are also seen in many other conditions such as infections, blood diseases and
cbs-turbances of nutrition. They are accord-ingly not pathognomonic of rickets, but they seem to appear when deposition of minerals increases following a period of
poor
mineralization.The
zones of metaphyseal rarefaction, the general osteoporosis and the periosteal double contours have previously been in-terpreted as indicative of 42 In thematerial of the present study these changes disappeared spontaneously in most of the cases without change in the vitamin
sup-ply, and in no case did we find signs of rickets in the epiphysis.
Neither did we in any case observe defi-nite clinical manifestations of rickets, and
in nearly every case growth in length was satisfactory. The infants fed human milk had to a large extent craniotabes-a finding in conformity with that of other observers.15 This condition has hardly any value in the
diagnosis of rickets during the first half year of life, particularly when the mothers continue to give breast milk. No
correla-tion could be demonstrated between the
abnormal serum values and any increased
occurrence of the radiologic or clinical signs
usually associated with rickets.
Our observations are in conformity with others published earlier. McQuarnie and
co-workerslS found 2 cases of rickets among 48 premature infants, and Glaser and co-workers’7 found 7 such cases out of 166.
The
serum values did not deviate. Both these investigations dealt with infants fedcow’s milk, but with different doses of
vita-minD.
Of
great practical interest are the ques-tions as to whether the risk of rickets, with an adequate supply of vitamin D, is greaterwith the one than with the other form of
feeding, and how great is this risk. Judg-ing by our investigations, the predisposition to rickets seems to be far smaller than
stated by previous investigators. We have
found slight differences in chemical, clini-cal and radiologic findings which support
the belief that cow’s milk gives better mineralization than human milk. We be-lieve that such early mineralization of the skeleton does not necessarily prevent
rick-ets. If infants are getting an adequate amount of vitamin D, the risk of rickets is probably no greater whether the infants
are fed human milk or cow’s milk.
SUMMARY
AND CONCLUSIONS
Sixty-nine premature infants receiving
different dietaries and with birth weights below 2,000 gm were studied with chemi-cal, clinical and radiologic methods. Vita-mm D was given to all infants from the age
of 4 days.
The
concentrations of calcium, phos-phorus and phosphatase in the serumshowed variations toward those seen in ac-tive rickets. These changes were somewhat more marked in infants fed human milk than cow’s milk. Supplementation of hu-man milk with dried skimmed cow’s milk did not significantly alter these changes.
Craniotabes was more frequently seen in premature infants fed human milk than
cow’s milk. Otherwise, no clinical signs of
76
PEDIATRICS-JULY
1957
All the premature infants were born with a metaphyseal zone of rarefaction. These zones are believed to be the result of a
disturbance in ossffication which occured during the last weeks of pregnancy, per-haps caused by a factor which was also responsible for the premature birth. They gradually merge with the general
osteo-porosis developing 10 to 13 weeks after
birth. Later, periosteal double contours are visible. These double contours are the first
signs of an improved mineralization.
There was no correlation between ab-normal chemical findings and the most con-spicuous radiologic or clinical findings. No
case of recognizable rickets was observed among the infants studied.
This risk of rickets, despite an adequate supply of vitamin D, is probably not as
great as stated by previous investigators, and is probably the same whether the infants are fed human milk or cow’s milk.
ACKNOWLEDGMENT
The authors wish to thank Mrs. Alette
Hanssen-Bauer, Lecturer at the University
of Oslo, who performed the statistical analyses.
REFERENCES
1. Benjamin, H. R., Cordon, H. H., and Mar-ples, E. : Calcium and phosphorus re-quirements of premature infants. Am.
J.
Dis. Child., 65:412, 1943.2. Stearns C. : Mineral metabolism of nor-mal infants. Physiol. Rev., 19:415, 1939.
3. Ylpp#{246}, A. : Das Wachstum der
Fruhge-borenen von der Geburt his zum Schul-alter. Ztschr. Kinderh., 24:111, 1919. 4. Von S#{252}dow,G. : A study of the
develop-ment of rickets in premature infants. Acta paediat., 33:suppl.
II, 1946.
5. Grette, K. : Micromethod for the deter-mination of calcium and magnesium in serum. Scandinav.
J.
Clin. & Lab. Invest., 5:151, 1953.6. Fiske, C. H., and Subbarow, Y. : The colorimetric determination of phos-phorus.
J.
Biol. Chem., 66:375, 1929. 7. Buch, I., and Buch, H. : An improvedKing and Armstrong method for the
determination of phosphatase activity in blood serum. Acta med. scandinav.,
101:211,
1943.
8. Hald, A. : Statistiske metoder. Det private ingeniforbund. K#{231}benhvn, 1948. 9. Graham, C. C., Barness, L. A., and
Gyorgy, P. : Serum calcium and inor-ganic phosphate in the newborn infant, and their relation to different feedings.
J.
Pediat., 42:401, 1953.10. Lindblom, K. : Early roentgen signs in rickets. Acta paediat., 25: 170, 1939. 1 1. Caffey,
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: Pediatric X-ray Diagnosis, 2ndEd. Chicago, Yr. Bk. Pub., 1950. 12. Wimberger, H. : Klinisch-radiologische
Diagnostik von Rachitis, Skorbut und Lues congenita im Kindesalter. Ergebn. inn. Med. u. Kinderh., 28:264, 1925. 13. Engeset, A., Eek, S., and Gilje, 0. : On
the significance of growth in the roent-genological skeletal changes in early congenital syphilis. Am.
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14. Malmberg, N. : Occurence and signifi-cance of early periosteal proliferation in the diaphysis of premature infants. Acta paediat., 32:626, 1944.
15. H#{246}jer,
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A.
: Beitrag zur Frage der Bezie-hungen zwischen Rachitis und Kranio-tabes. Acta paediat., 5: 16, 1926. 16. McQuarrie, I., Thompson, W. H., Stoesser,A. V.,
and Rigler, L. C. : The antirachi-tic potency of ergosterol activated by low velocity electrons.J.
Pediat., 10: 295, 1937.17. Glaser, K., Parmelee, A. H., and Hoff-mann, W. S.: Comparative efficacy of vitamin D preparations in prophylactic treatment of premature infants. Am.
J.
Dis. Child., 77 :1, 1949.SUMMARIO
IN INTERLINGUA
Prematuritate e Rachitis
In le curso del plus recente decennios, plure investigationes in re le nutrition de infantes prematur ha rendite problematic le opinion que lacte human es le melior alimento pro iste infantes. Le conclusion esseva formulate (von S#{252}dow)que rachitis es plus frequente in in-fantes nutrite con lacte human que in illes recipiente lacte de vacca. Al Clinica Pediatric del Universitate Oslo, ubi lacte human es usate in le majoritate del casos, nos ha credite im-portante repeter certes del supra-mentionate investigationes.
ARTICLES
77corporee de minus que 2.000 g esseva dividite in tres gruppos. Le prime recipeva lacte
human; le secunde, mixturas de lacte de
vacca; e le tertie, lacte human supplementate per siccate lacte discremate. Vitamina D esseva administrate a omne le infantes a pirtir del
quarte die de br vitas. Le infantes esseva
studiate per methodos chimic, clinic, e
roent-genologic.
Le investigationes chimic del sero revelava valores de calcium, phosphoro, e phosphatase
que deviava ab le valores normal de infantes
de plus alte etates e resimilava le valores
observate in casos de rachitis active. Le in-fantes recipiente lacte human habeva plus basse
valores de phosphoro e plus alte valores de phosphatase que le infantes recipiente lacte de
vacca. Supplementar le lacte human per siccate lacte discremate non effectuava ulle significa-tive melioration de iste deviationes.
Craniotabes esseva vidite plus frequente-mente in infantes prematur recipiente lacte human que in illes recipiente lacte de vacc4.
Alteremente nulle signos de rachitis esseva
constatate.
Brevemente post nato omne le infantes pre-matur revelava nettemente definite zonas meta-physeal de rarefaction situate justo infra un lisie sed frequentemente spissfficate e sclerotic
linea epiphyseal. Durante le prime 4 a 6
septimanas, le acute delineation inter le zona de rarefaction e le diaphyse deveniva progres-sivemente minus definite, e post un intervallo medie de 7 septimanas illo habeva disparite completemente. Osteoporosis generalisate se
disveloppava in omne le gruppos dietari in le curso del prime 10 a 13 septimanas post-natal. Duple contornos periosteal esseva plus
frequente e plus definite in le gruppo
recipi-ente lacte de vacca e in le gruppo recipiente
lacte human con supplemento de siccate lacte
de vacca discremate que in le gruppo
recipi-ente solmente lacte human.
Le resultatos del investigationes chimic se trova in bon accordo cn le conclusiones de previe studios. A parte le casos de craniotabes, nulle signos clinic de rachitis esseva observate. Le zonas metaphvseal de rarefaction ha
pre-viemente essite interpretate como precursores
de rachitis. In nostre experientia, illos esseva quasi semper presente brevemente post nato, e a iste stadio illos non pote haber ullo a facer con le dieta del infantes. Il es nostre hvpothese que ille zonas es causate per le mesme factor que es responsabile pro le nascentia prematur.
Le osteoporosis generalisate es forsan explicabile como resultato de resorption in-complete de minerales e de crescentia rapide. Le duple contornos periosteal, que es vidite in casos de rachitis durante le phase curatori,
occurre etiam in infectiones, morbos del
sanguine, e disturbationes nutritional e non es pathognomonic de rachitis. II es probabile que illos se declara quando le deposition de
mi-nerales se augmenta post un periodo de
mi-neralisation inadequate.
Omne le mentionate alterationes roentgeno-logic dispareva spontaneemente in omne nostre
gruppos e sin modification del supplemento de
vitamina D. Secundo nostre investigationes, le
predisposition a rachitis in le presentia de un
adequate provision de vitamina D es multo minus marcate que lo que ha previemente essite
reportate. Ii es probabile que iste
predisposi-tion es identic si le infantes recipe lacte de
