Genevieve Stearns

The effect of vitamin D on linear growth in infancy: II. The effect of intakes above 1,800 U.S.P. units daily

Summary The rate of linear growth of nine infants given from 1,800 to 4,600 units of vitamin D daily has been compared with standard rates of growth, and with the growth of infants given the same dietary regimen but amounts of vitamin D varying from 135 to 340 units daily. The rates of growth with the very high vitamin D intake were similar to or less than those of infants given 135 units daily, and definitely lower than the growth rates of infants given 340 units of vitamin D daily. It is concluded that the effect of vitamin D on increasing linear growth reaches a maximum when the vitamin D intake is greater than 135 and less than 1,800 units, probably in the neighborhood of 340 to 600 units daily. Vitamin A in amounts exceeding those of the food (milk, vegetable, and fruit purees) apparently does not affect linear growth of infants. Factors affecting growth rates of individual infants are discussed. It is concluded that in order to determine the effect of the dietary regimen, growth should be studied well past 6 months of age, preferably during the greater part of infancy. Growth during the first 8 weeks of life may be affected by factors other than the dietary regimen of the infant.

The effect of vitamin D on linear growth in infancy.

Summary The rate of growth in length of infants given one teaspoonful of high grade cod liver oil (340 to 400 U.S.P. units of vitamin D daily) has been compared with the rate of linear growth of infants given the same type of diet, but with the source of vitamin D from irradiated milk (60 to 135 U.S.P. units of vitamin D daily) or its vitamin D equivalent as cod liver oil or cod liver oil concentrate milk, and with standard growth rates reported in the literature. A review of the growth standards shows that the rate of linear growthin infancy is increasing. Standards reported in 1929 and 1933 show rates of growth definitely increased over those of older standards. Infants given 340 to 400 U.S.P. units of vitamin D daily grow at rates definitely more rapid than those of even the recent standards. Infants ingesting from 60 to 135 U.S.P. units of vitamin D daily grow at the same rate as the recent standards. Exposure to sunlight increased the rate of growth in the few infants in whom this measure was tried and who were receiving the lower of the two stated amounts of vitamin D. The increased rate of linear growth is ascribed chiefly to the increased intake of vitamin D and its resultant effect on skeletal growth. Although the influence of vitamin A has not been entirely excluded, certain of the observations recorded indicate that vitamin A was not the limiting factor in the growth of the infants studied.

Further Studies on Lathyrism in the Rat.

Summary 1. Male rats injected subcutaneously with β-aminopropionitrile and aminoacetonitrile developed the same skeletal lesions of lathyrism as did those fed these compounds. 2. Methyleneaminoacetonitrile fed to rats produced very severe skeletal lesions and is probably more active than the aminoacetonitrile. 3. Diets high in casein, gelatin, vit. E. and other antioxidants did not protect the rats fed Lathyrus odoratus seeds from developing skeletal lesions. 4. Radio-autographs of the skeleton after injection of S35 and studies on sulfur excretion of rats fed Lathyrus odoratus peas and rats fed a control diet showed that the metabolism of sulfur is probably not altered in lathyrism.

Vitamin-D resistant rickets. A long-term clinical study of eleven patients.

The regulation of vitamin-D dosage by means of twenty-four-hour urinary calcium values is relatively simple and requires no unusual laboratory procedures. If carefully applied, partial roentgenographic healing can occur and this status can be maintained permitting a nearly normal rate of growth and avoidance of hypervitaminosis D. The importance of avoiding hypervitaminosis D is stressed. Repeated swings from hypovitaminosis to hypervitaminosis D merely alternates one disturbance of bone metabolism for another; both deplete the skeleton. Adequate therapy must maintain the child as nearly normal as possible, despite the chronic hypophosphatemia. Under adequate vitamin-D therapy the leg deformities may improve but in our cases did not correct completely. Surgical correction is usually necessary. However, this is indicated only after regulation with adequate vitamin-D therapy. The deformities often recur if the therapy is interrupted or is grossly inadequate. The parents are always warned that this is a chronic metabolic disease which must be followed throughout life and is especially hazardous during growth for the prevention of deformities and the maintenance of a normal rate of growth, but may recur in later years. The general practitioner should also be informed that children whose rickets does not heal promptly with customary doses of vitamin D are not suffering from simple rickets and should be referred to clinics where their disease can be treated and followed adequately.

Utilization of Calcium Salts by Children

Children 4-12 years of age have been given calcium salts in amounts such that the calcium content was equivalent to that in a pint or quart of milk. The retentions of calcium and phosphorus have been determined and compared with the retentions from the equivalent quantities of milk. The calcium and phosphorus retentions of children from 1 to 4 years of age have been determined when a quart of milk was given as the chief source of calcium, and when a calcium salt was substituted for one pint of the milk. A few studies were made wherein the salt was substituted for all of the milk. The protein intake of each diet was kept approximately constant during the salt and milk periods. The salts used were calcium lactate, carbonate, gluconate, and the di- and tri-phosphates. The latter was given either as the salt or in the form of a purified bone meal. No difference was observed in the relative retentions from the two sources. The results are summarized in Table I. In general, the calcium and phosphorus retentions when the calcium phosphates were fed, were approximately equal to those from equivalent quantities of milk. The very high retentions observed when these salts were fed after periods of low calcium intake indicate that all forms used are well absorbed by the average child of these ages. The retentions with the other calcium salts, the gluconate, lactate and the one study with calcium carbonate, are not so consistent as those obtained with the calcium phosphates. A greater individual variation was observed in the quantity of calcium and phosphorus retained by the different children. In general, it appeared that when the intake levels of calcium and phosphorus were approximately equal, the retentions of both these elements were good in relation to the intake, but that the greater the difference between the intake levels of calcium and phosphorus, the less satisfactory were the relative retentions of these elements.

METABOLIC STUDIES OF CHILDREN WITH IDIOPATHIC SCOLIOSIS

Metabolic studies of calcium, phosphorus, and nitrogen in children with moderate to severe idiopathic scoliosis have been carried out. The findings demonstrated no clear-cut abnormality in mineral metabolism, but did show a serious disturbance in catabolism of protein with excessive wastage of nitrogen through the urine. The metabolic error also appears to involve derivatives of sulphur-containing amino acids. The scoliotic children tended to excrete a larger number of essential amino acids than did normal children of the same age range.

Effectiveness of vitamin D in infancy in relation to the vitamin source.

This report concerns the preliminary findings regarding the utilization by the human infant of vitamin D from different sources. The criterion chosen was the quantity of calcium retained by well infants given the same amount of milk and the same rat unitage of vitamin D. Irradiated evaporated milk containing 50 units,∗ and evaporated milk containing the unsaponifiable fraction of cod liver oil (Zucker concentrate) allowing 150 units per quart of reconstituted milk respectively, were compared with evaporated milk plus vitamin D given separately as a cod liver oil containing 40 units of D per gram. The Zucker concentrate milk was mixed with plain evaporated milk, and the quantities of cod liver oil were so chosen that the vitamin D unitage of each diet was constant for any given intake of milk, and was regulated by the amount present in the irradiated milk. The youngest infants received only 22 units daily, but by 16 weeks of age, all the infants were ingesting approximately 50 units of D daily. The plan of study was to give each of the 3 experimental diets to a group of infants of the same age and milk intake; after a period of about 6 weeks, the diets were changed so that each infant received each diet in turn. At the beginning of the study, 3 infants were from 5 to 8 weeks of age; 3 from 16 to 24 weeks; and one infant a year old was given each diet in turn. The relations observed between calcium intake and retention per kilogram body weight are shown in the chart. The source of vitamin D used in each experiment is indicated by the different symbols. The line shows the average curve of retention :intake obtained from over 200 experiments upon infants having the same age range and milk intakes, but given approximately 125 units of vitamin D daily in the form of cod liver oil.

Retention of calcium by infants fed evaporated milk containing cod liver oil concentrate.

This report concerns the quantities of calcium retained and the growth in length and weight of 5 white infants fed evaporated milk containing the unsaponifiable fraction of cod liver oil (Zucker concentrate) in an amount which allowed 400 U.S.P. units of vitamin D to the reconstituted quart. When the experiment was started one infant was 11 weeks, one 6 weeks, and the remaining 3 infants 10 to 20 days of age. The vitamin D intake of the youngest infants was 245 units daily; the maximum intake was 400 units a day. The intakes and retentions of calcium per kilogram of body weight are plotted on the chart. For comparison are shown average values from former observations. The solid line shows the average calcium retentions of infants given 340 U.S.P. units of vitamin D daily as cod liver oil and represents 200 periods of study of 24 infants; the dotted line shows the average retentions from 135 U.S.P. unit milk (60 to 135 units daily) as determined from 40 periods of study of 7 infants. The quantities of calcium retained from any given intake of the 400 unit milk were within the range observed in infants to whom 340 units of vitamin D as cod liver oil were given daily, and the average values for each intake range is approximately the same as that of the large control group, but about 10 mg. per kilo higher than the average retentions observed when 135 unit milk was given a similar group of infants. 1 The serum calcium values varied from 10.4 to 12 and the serum phosphorus from 5.7 to 7.2 mg. per 100 cc.; the average values were 11.0 and 6.3 mg. per 100 cc., respectively. The rate of growth of each infant, both in length and weight, was above the Kornfeld 2 average, and equal to the average rate of growth of the infants given 340 units of vitamin D daily. No infant developed rickets; dentition was early and muscular development excellent. It is concluded that milk containing cod liver oil concentrate (Zucker) sufficient to allow 400 U.S.P. units of vitamin D to the reconstituted quart, allows high retentions of calcium, prevents the development of rickets, and permits excellent growth and development of the infants.

A Guide to the Adequacy of Therapy in Resistant Rickets due to Familial or Essential Hypophosphatemia

The regulation of vitamin-D dosage in resistant rickets (familial or essential hypophosphatemia) is best accomplished by measuring the twenty-four-hour urinary calcium output against the curve of normal excretion. For such comparison the subjects weight and a fairly close estimate of calcium intake are also necessary. Qualitative tests for urine calcium are of no real value in determining the childs status with respect to vitamin-D therapy. Urinary calcium values before treatment are usually three standard deviations or more below the normal mean excretion value. With high doses of vitamin D, urinary calcium rises toward the mean, the rate of rise paralleling the size of the dose. Maintenance of urine calcium at values approximating the normal mean will promote healing of clinical rickets and avoid hypervitaminosis D. A rise of urinary calcium to approximately three standard deviations above the mean, or higher, means hypervitaminosis, and the dosage should be decreased sharply. The abnormal rise in urinary calcium from overtreatment precedes a rise in serum calcium by days or weeks, except after operative treatment when the child will be thrown into acute hypervitaminosis D unless the vitamin is discontinued for a time starting before operation.

The relation of vitamin D intake to the age of the infant at the time of eruption of the first deciduous incisor

Summary The ages at eruption of the first deciduous lower central incisor of groups of healthy infants with carefully controlled diets having relatively low, intermediate, and high amounts of supplementary vitamin D were compared. The incisors of twenty-two infants given the intermediate vitamin D intake, from 300 to 400 units daily, showed the earliest mean age at eruption, 24.68 weeks. The incisors of seventeen infants with a low vitamin D intake, from 135 to 270 units daily, were delayed in their eruption, appearing at a mean age of 28.29 weeks. Incisors of six infants with a high vitamin D intake, over 1,800 units daily, also seemed delayed in their eruption, appearing at a mean age of 27.16 weeks; however, this is less conclusive because of the small number of infants in this group. In an effort to determine whether early or late eruption is more nearly normal, the dental eruption data of six infants who had the 300- to 400-unit intake but who were subject to illnesses were presented. Although the group is small, the mean age of incisor eruption, 29.0 weeks, seemed to indicate that illness delays tooth eruption and that the earlier eruption age is more nearly normal. The response of dental eruption to variation in vitamin D intake tends to parallel the responses of linear growth and mineral retention to the same influence during infancy.