negative when the concentration decreased to 0.0002 .g or less. The Rh antibodies in immune globulin may cause clinical confusion. Oberman and Beck2 described a small Rh-positive baby, and Lang and Veldhuis3 reported the cases of several Rh-positive children and adults, each of whom had received several doses of immune globulin. Their erythrocytes became positive to direct antiglobulin (direct Coombs') testing. This led to transfusion problems and needless investigation. The patients suffered no harm, which is not surprising, considering that a dose of 300 pg of anti-D Rh immune globulin does not harm an Rh-positive newborn baby.4
Lang and Veldhuis3 examined 14 lots of immune globulin produced by six firms: seven contained anti-D with a titre ranging from 1:4 to 1:32. In 1971 we examined 12 samples produced by nine firms in the years 1967 to 1970. All contained some anti-Rh, but in most cases less than 0.01 .g/ml. Apart from the lot the second patient received (containing 0.6 ,.Lg/ml), the two highest concentrations were about 0.1 ,.g/ml. Immune globulin (human) is not examined routinely for anti-D (health protection branch, Health and Welfare Canada: personal communication, 1975), so errors such as those reported in this paper may still occur.
We are indebted to Dr. S. Steinberg for first offering the correct answer to our puzzle in case 1; to Dr. E. Snell for the samples of immune globulin (human) used locally; and to Dr. Louis Greenberg, then of Ottawa, now of Washington, for the 12 samples we examined later. References 1. POLLACK W, GORMAN 3, FREDA V: Prevention of Rh hemolytic disease, in Progress in Hematology, vol VI, edited by BROwN EB and Mooiut CV, New York and London, Grune, 1969 2. OBERMAN HA, BECK MI: Red blood sensitization due to unexpected Rh antibodies in immune serum globulin. Transfusion 11: 382, 1971 3. LANG GE, VELDHUIS B: Immune serum globulin - a cause for anti-Rh0 (D) passive sensitization. Am I Clin Pathol 60: 205, 1973 4. CHOWN B, BOWMAN 3M, POLLOCK J, et al: The effect of anti-D IgG on D-positive recipients. Can Med Assoc 1 102: 1161, 1970
Vitamin D supplements: requirements in special circumstances in children STATEMENT BY THE NUTRITION COMMITTEE* OF THE CANADIAN PAEDIATRIC SOCIETY
Until recently, vitamin D deficiency was endemic in several regions of Canada."2 Widespread optional fortification with vitamin D2 of homogenized whole and "2%" cow's milk to a concentration of 400 units (10 p.g) per imperial quart (1134 ml) has changed this outlook. As a result, few patients with the typical deficiency syndrome are now seen in the regions where this problem once prevailed. There are, however, some areas of the country where fluid dairy milk is still not fortified with vitamin D. Pediatricians and family physicians must therefore continue to be vigilant to ensure their patients are receiving adequate amounts of vitamin D in their diets, and they must also remain alert to the occurrence of vitamin D deficiency. It is not the purpose of this statement to review the whole subject of vitamin D requirements but rather to draw the attention of pediatricians to two particular groups of children in whom the need for supplementary vitamin D has been recognized recently. First, the rapidly growing low-birthweight infant, who has a limited capacity to ingest vitamin-D-fortified formulas and therefore may not receive sufficient vitamin D.3 The infant's physician should prescribe a supplement, calculating to ensure that the total intake of the vitamin meets the requirement (400 U or 10 p.g of vitamin D2 *Chairm.: J.C. Haworth; members: J.W. Gerrard, R.B. Goldbloom, D.A.I. Grewar, J.R. Hamilton, R. Lachance, J.R. MacLean, P. Marchand, CXC. Roy, C.R. Scriver; consultants: G.W. Beaton, A.L. Forbes, T.K. Murray, z.I. Sabry; liaison, Canadian Dietetic Association, Pamela Lynch Reprint requests to: Canadian Paediatric Society, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Quo. JIH 5N4
or D3 per day). Second, the patient on long-term anticonvulsant therapy with diphenyihydantoin or barbiturates or both.4'5 Blood concentrations of the vitamin D metabolite 25-hydroxy vitamin D in adult epileptic patients on long term anticonvulsant treatment are, on the average, lower than those in controls who have a comparable intake of vitamin D. Mentally retarded children living in institutions and receiving longterm anticonvulsant therapy can have lower values of serum calcium and phosphorus and higher values of serum alkaline phosphatase than similar children not receiving anticonvulsants. Radiologic rickets also has been reported in some of these children despite dietary intakes of vitamin D in excess of the usual requirements. The reason for these findings is believed to be an increase in vitamin D catabolism in the liver or a decrease in biosynthesis of its active polar metabolites in the presence of anticonvulsant drugs. It is recommended that all children receiving long-term anticonvulsant medication be observed carefully for evidence of the vitamin D deficiency syndrome. Regular measurement of serum calcium, phosphorus and alkaline phosphatase is wise, for one may then detect the earliest stage of rickets, in which there is hypocalcemia but not the typical bone changes; estimation of total serum calcium and, when possible, ionized calcium, is particularly important.6 "Resistance" of seizures to anticonvulsant medication may reflect a state of vitamin D depletion; the patient should receive a vitamin D supplement (usually 2000 Uld). We do
1216 CMA JOURNAL/MAY 17, 1975/VOL. 112
not advise, at present, prescribing routinely vitamin D supplements for patients taking anticonvulsant medication because the idiosyncratic response to the medication may have a pharmacogenetic basis. Dietary surveys conducted by Nutrition Canada7 revealed that, among nine nutrients examined, vitamin D outranked all others in the classification "inadequate intake" according to the interpretive standard. This was true not only for children (in two age groups: up to 4 years and 5 to 9 years) of both sexes but also for adolescent boys and girls. The clinical and biochemical consequences, if any, have yet to be identified (abnormal serum calcium values were not found) and it will be necessary to evaluate the relevance of the interpretive standard for the presumed vitamin D requirement in children and adolescents. In the meantime, physicians should continue to be vigilant about vitamin D nutrition in their patients and watch for evidence of unusual forms of deficiency. References 1. CARSWELL H: Rickets and vitamin D deficiency. Medical Post, March 1969
2. SCRIVER CR: Fondements biologiques de la sensibilit6 du rachitisme k la vitamine D.
Union Med 100: 462, 1971 3. LEWIN PK, REID M, REILLY BJ, et al: latrogenic rickets in 16w-birth-weight infants.
J Pediair 78: 207, 1971 4. HAHN TJ, HENDIN BA, Sci.&iu' CR, et al:
Effects of chronic anticonvulsant therapy on serum 25-hydroxycalciferol levels in adults. N Engi / Med 287: 900, 1972 5. LsFsHrn F, MACLAREN NK: Vitamin D-dependent rickets in institutionalized mentally retarded children receiving long-term anticonvulsant therapy. I. A survey of 288 patients. J Pediatr 83: 612, 1973 6. FRASER D, KOOH SW, Sciuvmt CR: Hyperparathyroidism as the cause of hyperaminoaciduria and phosphaturia in human vitamin D deficiency. Pedlatr Res 1: 425, 1967 7. Nutrition Canada: Nutrition: A National Priority. Ottawa, Information Canada, 1973
Lang and Veldhuis3 examined 14 lots of immune globulin produced by six firms: seven contained anti-D with a titre ranging from 1:4 to 1:32. In 1971 we examined 12 samples produced by nine firms in the years 1967 to 1970. All contained some anti-Rh, but in most cases less than 0.01 .g/ml. Apart from the lot the second patient received (containing 0.6 ,.Lg/ml), the two highest concentrations were about 0.1 ,.g/ml. Immune globulin (human) is not examined routinely for anti-D (health protection branch, Health and Welfare Canada: personal communication, 1975), so errors such as those reported in this paper may still occur.
We are indebted to Dr. S. Steinberg for first offering the correct answer to our puzzle in case 1; to Dr. E. Snell for the samples of immune globulin (human) used locally; and to Dr. Louis Greenberg, then of Ottawa, now of Washington, for the 12 samples we examined later. References 1. POLLACK W, GORMAN 3, FREDA V: Prevention of Rh hemolytic disease, in Progress in Hematology, vol VI, edited by BROwN EB and Mooiut CV, New York and London, Grune, 1969 2. OBERMAN HA, BECK MI: Red blood sensitization due to unexpected Rh antibodies in immune serum globulin. Transfusion 11: 382, 1971 3. LANG GE, VELDHUIS B: Immune serum globulin - a cause for anti-Rh0 (D) passive sensitization. Am I Clin Pathol 60: 205, 1973 4. CHOWN B, BOWMAN 3M, POLLOCK J, et al: The effect of anti-D IgG on D-positive recipients. Can Med Assoc 1 102: 1161, 1970
Vitamin D supplements: requirements in special circumstances in children STATEMENT BY THE NUTRITION COMMITTEE* OF THE CANADIAN PAEDIATRIC SOCIETY
Until recently, vitamin D deficiency was endemic in several regions of Canada."2 Widespread optional fortification with vitamin D2 of homogenized whole and "2%" cow's milk to a concentration of 400 units (10 p.g) per imperial quart (1134 ml) has changed this outlook. As a result, few patients with the typical deficiency syndrome are now seen in the regions where this problem once prevailed. There are, however, some areas of the country where fluid dairy milk is still not fortified with vitamin D. Pediatricians and family physicians must therefore continue to be vigilant to ensure their patients are receiving adequate amounts of vitamin D in their diets, and they must also remain alert to the occurrence of vitamin D deficiency. It is not the purpose of this statement to review the whole subject of vitamin D requirements but rather to draw the attention of pediatricians to two particular groups of children in whom the need for supplementary vitamin D has been recognized recently. First, the rapidly growing low-birthweight infant, who has a limited capacity to ingest vitamin-D-fortified formulas and therefore may not receive sufficient vitamin D.3 The infant's physician should prescribe a supplement, calculating to ensure that the total intake of the vitamin meets the requirement (400 U or 10 p.g of vitamin D2 *Chairm.: J.C. Haworth; members: J.W. Gerrard, R.B. Goldbloom, D.A.I. Grewar, J.R. Hamilton, R. Lachance, J.R. MacLean, P. Marchand, CXC. Roy, C.R. Scriver; consultants: G.W. Beaton, A.L. Forbes, T.K. Murray, z.I. Sabry; liaison, Canadian Dietetic Association, Pamela Lynch Reprint requests to: Canadian Paediatric Society, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Quo. JIH 5N4
or D3 per day). Second, the patient on long-term anticonvulsant therapy with diphenyihydantoin or barbiturates or both.4'5 Blood concentrations of the vitamin D metabolite 25-hydroxy vitamin D in adult epileptic patients on long term anticonvulsant treatment are, on the average, lower than those in controls who have a comparable intake of vitamin D. Mentally retarded children living in institutions and receiving longterm anticonvulsant therapy can have lower values of serum calcium and phosphorus and higher values of serum alkaline phosphatase than similar children not receiving anticonvulsants. Radiologic rickets also has been reported in some of these children despite dietary intakes of vitamin D in excess of the usual requirements. The reason for these findings is believed to be an increase in vitamin D catabolism in the liver or a decrease in biosynthesis of its active polar metabolites in the presence of anticonvulsant drugs. It is recommended that all children receiving long-term anticonvulsant medication be observed carefully for evidence of the vitamin D deficiency syndrome. Regular measurement of serum calcium, phosphorus and alkaline phosphatase is wise, for one may then detect the earliest stage of rickets, in which there is hypocalcemia but not the typical bone changes; estimation of total serum calcium and, when possible, ionized calcium, is particularly important.6 "Resistance" of seizures to anticonvulsant medication may reflect a state of vitamin D depletion; the patient should receive a vitamin D supplement (usually 2000 Uld). We do
1216 CMA JOURNAL/MAY 17, 1975/VOL. 112
not advise, at present, prescribing routinely vitamin D supplements for patients taking anticonvulsant medication because the idiosyncratic response to the medication may have a pharmacogenetic basis. Dietary surveys conducted by Nutrition Canada7 revealed that, among nine nutrients examined, vitamin D outranked all others in the classification "inadequate intake" according to the interpretive standard. This was true not only for children (in two age groups: up to 4 years and 5 to 9 years) of both sexes but also for adolescent boys and girls. The clinical and biochemical consequences, if any, have yet to be identified (abnormal serum calcium values were not found) and it will be necessary to evaluate the relevance of the interpretive standard for the presumed vitamin D requirement in children and adolescents. In the meantime, physicians should continue to be vigilant about vitamin D nutrition in their patients and watch for evidence of unusual forms of deficiency. References 1. CARSWELL H: Rickets and vitamin D deficiency. Medical Post, March 1969
2. SCRIVER CR: Fondements biologiques de la sensibilit6 du rachitisme k la vitamine D.
Union Med 100: 462, 1971 3. LEWIN PK, REID M, REILLY BJ, et al: latrogenic rickets in 16w-birth-weight infants.
J Pediair 78: 207, 1971 4. HAHN TJ, HENDIN BA, Sci.&iu' CR, et al:
Effects of chronic anticonvulsant therapy on serum 25-hydroxycalciferol levels in adults. N Engi / Med 287: 900, 1972 5. LsFsHrn F, MACLAREN NK: Vitamin D-dependent rickets in institutionalized mentally retarded children receiving long-term anticonvulsant therapy. I. A survey of 288 patients. J Pediatr 83: 612, 1973 6. FRASER D, KOOH SW, Sciuvmt CR: Hyperparathyroidism as the cause of hyperaminoaciduria and phosphaturia in human vitamin D deficiency. Pedlatr Res 1: 425, 1967 7. Nutrition Canada: Nutrition: A National Priority. Ottawa, Information Canada, 1973
