739
of the second D.F. test. Both these factors might be expected to reduce the observed differences between control and infusion tests. The highest absorption values were seen in patients with thalassaemia intermedia and congenital sideroblastic anaemia who had the lowest transfusion load and in whom ineffective erythropoiesis was more marked. The variation in absorption in the patients with thalassxmia intermedia cannot be explained solely by differences in ascorbate status. This finding, the wide range of values for serum ferritin, iron, and total iron binding capacity, and the urinary iron excretion with a standard infusion of D.F. (table I), all indicate how difficult it can be to assess iron stores in these patients. Possible differences in the severity of iron loading will need careful assessment before long term, expensive, and laborious chelation programmes are started, for it is in this group of nontransfusion-dependent thalassasmics that reduction of both existing iron stores and further iron absorption might be most beneficial. It is not clear whether subcutaneous D.F. prevents iron uptake by the gastrointestinal mucosal cells, prevents transfer from the cells to the plasma, or promotes early re-excretion of absorbed iron either in urine (as in several of our patients) or in faeces. It may well be that several mechanisms, of varying importance in different patients, are involved. It is unlikely that the pronounced reduction in iron retention in the thalassaemia maior patients was entirely due to re-excretion of absorbed iron, for unlike the patients with thalasssemia intermedia the amount of urinary excretion was negligible. In these patients binding of iron as ferrioxamine either in the gut, after biliary excretion of D.F. or its metabolites,!’ or in mucosal cells which are later shed into the gut, may be more important. The absence of effect in the patient with congenital red-cell aplasia is unexplained though the very low levels of iron absorption in very severe anxmia are consistent with the total absence of erythroid activity. Previous workers have shown that part of the iron chelated with parenteral D.F. appears in the stools.18,’9 This fsecal iron has been to be derived directly from the liver because 59Fe ferrioxamine given intravenously does not appear in the faeces.20,21 However, biliary iron excretion may not be sufficient to account for the entire faecal excretion,22 and our results suggest that decreased iron absorption may be partly responsible for an apparent increased iron excretion. Food iron is present either as inorganic (mainly ferric) iron, whose absorption depends on many intraluminal factors,23 or as haem iron. Our results with inorganic iron which is maintained in the reduced ferrous form (optimal for absorption) by ascorbates do no more than indicate the direction of change that s.c. D.F. infusions may produce in absorption of iron in the food. However, concern that more effective iron chelation regimens based on continuous D.F. infusions in ascorbate replete patients will increase absorption appears unfounded, and indeed there may be an unexpected bonus of a reduction in this source of iron loading. We are grateful to Dr E. A. Letsky and Dr B. Modell for referring patients for investigation, and to Mrs Mary Payne for her technical assistance. This work was supported by grants from the Oxford Area Health Authority (T), the Medical Research Council, London, and the
thought
,
Wellcome Trust, London. Requests for reprints should be addressed to M. J. P.
VITAMIN D AND HUMAN LACTATION
ANGELA FAIRNEY
Department of Chemical Pathology, St. Mary’s Hospital Medical School, London W2 1PG
T. E. OPPÉ
EILEEN NAUGHTEN
Pœdiatric Unit, St. Mary’s Hospital Medical School, London W2 1PG
Summary
Circulating serum-25-hydroxyvitamin-D
concentration was measured in recently delivered mothers who were breast-feeding and in those who were not. 4-6 weeks’ lactation produced no significant change. Basal and 4-6-week values in the breastfeeding group were significantly higher than in those who were not breast-feeding. There was no evidence that lactation was an indication for supplementary vitamin D.
Introduction THERE is little information on the effect of lactation vitamin-D status in lactating women. Human breast milk contains sufficient vitamin D, as vitamin-D sulphate (a water-soluble compound), to meet the needs of the young infant.’ This implies that during lactation the mother will lose significant amounts of vitamin D, and hence her vitamin-D requirement during this period might increase. In addition there is evidence that prolactin may be important in the physiological regulation of vitamin D,2 and circulating prolactin concentrations are on
high during lactation.3 We therefore investigated the vitamin-D status of lactating and non-lactating mothers. Serum-25-hydroxyvitamin-D (25-OHD), the most readily available indicator of vitamin-D status, was measured in lactating and
1. Wolman, I. J., Ortolani, M. Ann. N.Y. Acad. Sci. 1969, 165, 415. 2. Engle, M. A. ibid. 1964, 119, 694. 3. Modell, C. B., Beck, J. ibid. 1974, 232, 201. 4. Propper, R. D., Shurin, S. B., Nathan, D. G. New Engl. J. Med. 1976, 294, 1421. 5. Hussain, M. A. M., Flynn, D. M., Green, N., Hussein, S., Hoffbrand, A. V. Lancet, 1976, ii, 1278. 6. Propper, R. D., Rosenthal, A., Cooper, B., Rufo, R. R., Bunn, H. F., Neinhuis, A. W., Anderson, W. F., Nathan, D. G. New Engl. J. Med. 1977,
7.
297, 418. Pippard, M. J., Callender,
the press). 8. Hussain, M. A. M.,
Flynn,
S.
T., Weatherall, D. J. Clin. Sci. mol. Med. (in
D.
M., Green, N., Hoffbrand, A.
V.
Lancet, 1977,
i, 977. A. A., Lynch, S. R., Charlton, R. W., Seftel, H. C., Bothwell, T. H. Br. J. Hœmat. 1969, 17, 563. 10. Heinrich, H. C., Gabbe, E. E., Oppitz, K. H., Whang, D. H., Bender-Götze, Ch., Shäfer, K. H., Schröter, W., Pfau, A. A. Z. Kinderheilk, 1973, 115, 1. 11. Hwang, Y-F., Brown, E. B. Lancet, 1965, i, 135. 12. Moore, C. V. Am.J. clin. Nutr. 1955, 3, 3. 13. Glover, J. M., Jones, P. R., Greenman, D. A., Hughes, R. E., Jacobs, A. Br. J. exp. Path. 1972, 53, 295. 14. Callender, S. T., Witts, L. J., Warner, G. T., Oliver, R. Br. J. Haemat. 1966, 12, 276. 15. Hubmann, B., Monnier, D., Roth, M. Clinica chim. Acta. 1969, 25, 161. 16. Jacobs, A., Kaye, M.D., Trevett, D. J. Lab. clin. Med. 1969, 74, 212. 17. Keberle, H. Ann. N.Y. Acad. Sci. 1964, 119, 758. 18. Harker, L. A., Funk, D. D., Finch, C. A. Am. J. Med. 1968, 45, 105. 19. Cumming, R. L. C., Millar, J. A., Smith, J. A., Goldberg, A. Br. J. Haemat. 1969, 17, 257. 20. Bannerman, R. M., Callender, S. T., Williams, D. L. Br med. J. 1962, ii, 9.
Wapnick,
1973.
Walsh, J. R., Mass, R. E., Smith, F. W., Lange, V. Archs intern. Med. 1964, 113, 435. 22. Brown, E. B., Hwang, Y-F, Allgood, J. W. J. Lab. clin. Med. 1967, 69, 382. 23. Jacobs, A., Worwood, M. Br. J. Haemat. 1975, 31 (suppl.) 89. 21.
740
non-lactating groups drawn from a large sample women newly delivered in February, 1977.
of
Methods 10 ml of venous blood (sample 1) was taken from ninety-two unselected mothers within the first three days after delivery. This was done in two maternity departments in north-west London during a two-week period in February, 1977. The samples were separated and stored in glass bottles at -20°C. Each woman gave informed consent. Eighty-five of these mothers were visited at home 4-6 weeks later and a further blood-sample (sample 2) was taken and stored as before; (three mothers had moved from the district and four could not be traced). In addition mothers were asked about their method of feeding, supplementary vitamin-D intake, exposure to sunlight before and during pregnancy, diet, and ethnic origin. Before the biochemical analyses were performed, the sera from ten White women, known to have been giving at least three breast feeds daily, were examined. In addition, sera from ten White women who were not lactating were chosen for comparison. Serum-25-OHD was estimated in the paired samples from the lactating and comparison groups and in the 72 remaining sample-1 specimens. In addition, serum calcium and phosphate were estimated in sample 2 of the lactation and the comparison group specimens. Serum-25-OHD was measured by a modification of the method of McLaughlin et a1.4 The coefficient of variation within and between assays was not greater than 8.7%. The ’
method
measures
and 24,25-dihydroxycholecalciferol. Serum25-OHD measured by this assay in a group of men and nonpregnant women in March, 1974, ranged from 9 to 27 ng/ml. Serum-calcium was measured by the Technicon AA II method and serum-phosphate by an AA II modification of the sequential multiple analyser method.
calciferol,
25-hydroxycholecalciferol, 25-hydroxyergo-
’
Results A wide range of 25-OHD values
I
found in mothers immediately post partum (fig. 1). Eight (90%) of the lowest 10% were from Asian mothers. 26% of mothers in the whole study were Asian. Values for the two groups of White mothers are given in fig 2. In the lactating group samples 1 and 2 contained significantly more 25-OHD than corresponding samples in the non-lactating women (p
of the second D.F. test. Both these factors might be expected to reduce the observed differences between control and infusion tests. The highest absorption values were seen in patients with thalassaemia intermedia and congenital sideroblastic anaemia who had the lowest transfusion load and in whom ineffective erythropoiesis was more marked. The variation in absorption in the patients with thalassxmia intermedia cannot be explained solely by differences in ascorbate status. This finding, the wide range of values for serum ferritin, iron, and total iron binding capacity, and the urinary iron excretion with a standard infusion of D.F. (table I), all indicate how difficult it can be to assess iron stores in these patients. Possible differences in the severity of iron loading will need careful assessment before long term, expensive, and laborious chelation programmes are started, for it is in this group of nontransfusion-dependent thalassasmics that reduction of both existing iron stores and further iron absorption might be most beneficial. It is not clear whether subcutaneous D.F. prevents iron uptake by the gastrointestinal mucosal cells, prevents transfer from the cells to the plasma, or promotes early re-excretion of absorbed iron either in urine (as in several of our patients) or in faeces. It may well be that several mechanisms, of varying importance in different patients, are involved. It is unlikely that the pronounced reduction in iron retention in the thalassaemia maior patients was entirely due to re-excretion of absorbed iron, for unlike the patients with thalasssemia intermedia the amount of urinary excretion was negligible. In these patients binding of iron as ferrioxamine either in the gut, after biliary excretion of D.F. or its metabolites,!’ or in mucosal cells which are later shed into the gut, may be more important. The absence of effect in the patient with congenital red-cell aplasia is unexplained though the very low levels of iron absorption in very severe anxmia are consistent with the total absence of erythroid activity. Previous workers have shown that part of the iron chelated with parenteral D.F. appears in the stools.18,’9 This fsecal iron has been to be derived directly from the liver because 59Fe ferrioxamine given intravenously does not appear in the faeces.20,21 However, biliary iron excretion may not be sufficient to account for the entire faecal excretion,22 and our results suggest that decreased iron absorption may be partly responsible for an apparent increased iron excretion. Food iron is present either as inorganic (mainly ferric) iron, whose absorption depends on many intraluminal factors,23 or as haem iron. Our results with inorganic iron which is maintained in the reduced ferrous form (optimal for absorption) by ascorbates do no more than indicate the direction of change that s.c. D.F. infusions may produce in absorption of iron in the food. However, concern that more effective iron chelation regimens based on continuous D.F. infusions in ascorbate replete patients will increase absorption appears unfounded, and indeed there may be an unexpected bonus of a reduction in this source of iron loading. We are grateful to Dr E. A. Letsky and Dr B. Modell for referring patients for investigation, and to Mrs Mary Payne for her technical assistance. This work was supported by grants from the Oxford Area Health Authority (T), the Medical Research Council, London, and the
thought
,
Wellcome Trust, London. Requests for reprints should be addressed to M. J. P.
VITAMIN D AND HUMAN LACTATION
ANGELA FAIRNEY
Department of Chemical Pathology, St. Mary’s Hospital Medical School, London W2 1PG
T. E. OPPÉ
EILEEN NAUGHTEN
Pœdiatric Unit, St. Mary’s Hospital Medical School, London W2 1PG
Summary
Circulating serum-25-hydroxyvitamin-D
concentration was measured in recently delivered mothers who were breast-feeding and in those who were not. 4-6 weeks’ lactation produced no significant change. Basal and 4-6-week values in the breastfeeding group were significantly higher than in those who were not breast-feeding. There was no evidence that lactation was an indication for supplementary vitamin D.
Introduction THERE is little information on the effect of lactation vitamin-D status in lactating women. Human breast milk contains sufficient vitamin D, as vitamin-D sulphate (a water-soluble compound), to meet the needs of the young infant.’ This implies that during lactation the mother will lose significant amounts of vitamin D, and hence her vitamin-D requirement during this period might increase. In addition there is evidence that prolactin may be important in the physiological regulation of vitamin D,2 and circulating prolactin concentrations are on
high during lactation.3 We therefore investigated the vitamin-D status of lactating and non-lactating mothers. Serum-25-hydroxyvitamin-D (25-OHD), the most readily available indicator of vitamin-D status, was measured in lactating and
1. Wolman, I. J., Ortolani, M. Ann. N.Y. Acad. Sci. 1969, 165, 415. 2. Engle, M. A. ibid. 1964, 119, 694. 3. Modell, C. B., Beck, J. ibid. 1974, 232, 201. 4. Propper, R. D., Shurin, S. B., Nathan, D. G. New Engl. J. Med. 1976, 294, 1421. 5. Hussain, M. A. M., Flynn, D. M., Green, N., Hussein, S., Hoffbrand, A. V. Lancet, 1976, ii, 1278. 6. Propper, R. D., Rosenthal, A., Cooper, B., Rufo, R. R., Bunn, H. F., Neinhuis, A. W., Anderson, W. F., Nathan, D. G. New Engl. J. Med. 1977,
7.
297, 418. Pippard, M. J., Callender,
the press). 8. Hussain, M. A. M.,
Flynn,
S.
T., Weatherall, D. J. Clin. Sci. mol. Med. (in
D.
M., Green, N., Hoffbrand, A.
V.
Lancet, 1977,
i, 977. A. A., Lynch, S. R., Charlton, R. W., Seftel, H. C., Bothwell, T. H. Br. J. Hœmat. 1969, 17, 563. 10. Heinrich, H. C., Gabbe, E. E., Oppitz, K. H., Whang, D. H., Bender-Götze, Ch., Shäfer, K. H., Schröter, W., Pfau, A. A. Z. Kinderheilk, 1973, 115, 1. 11. Hwang, Y-F., Brown, E. B. Lancet, 1965, i, 135. 12. Moore, C. V. Am.J. clin. Nutr. 1955, 3, 3. 13. Glover, J. M., Jones, P. R., Greenman, D. A., Hughes, R. E., Jacobs, A. Br. J. exp. Path. 1972, 53, 295. 14. Callender, S. T., Witts, L. J., Warner, G. T., Oliver, R. Br. J. Haemat. 1966, 12, 276. 15. Hubmann, B., Monnier, D., Roth, M. Clinica chim. Acta. 1969, 25, 161. 16. Jacobs, A., Kaye, M.D., Trevett, D. J. Lab. clin. Med. 1969, 74, 212. 17. Keberle, H. Ann. N.Y. Acad. Sci. 1964, 119, 758. 18. Harker, L. A., Funk, D. D., Finch, C. A. Am. J. Med. 1968, 45, 105. 19. Cumming, R. L. C., Millar, J. A., Smith, J. A., Goldberg, A. Br. J. Haemat. 1969, 17, 257. 20. Bannerman, R. M., Callender, S. T., Williams, D. L. Br med. J. 1962, ii, 9.
Wapnick,
1973.
Walsh, J. R., Mass, R. E., Smith, F. W., Lange, V. Archs intern. Med. 1964, 113, 435. 22. Brown, E. B., Hwang, Y-F, Allgood, J. W. J. Lab. clin. Med. 1967, 69, 382. 23. Jacobs, A., Worwood, M. Br. J. Haemat. 1975, 31 (suppl.) 89. 21.
740
non-lactating groups drawn from a large sample women newly delivered in February, 1977.
of
Methods 10 ml of venous blood (sample 1) was taken from ninety-two unselected mothers within the first three days after delivery. This was done in two maternity departments in north-west London during a two-week period in February, 1977. The samples were separated and stored in glass bottles at -20°C. Each woman gave informed consent. Eighty-five of these mothers were visited at home 4-6 weeks later and a further blood-sample (sample 2) was taken and stored as before; (three mothers had moved from the district and four could not be traced). In addition mothers were asked about their method of feeding, supplementary vitamin-D intake, exposure to sunlight before and during pregnancy, diet, and ethnic origin. Before the biochemical analyses were performed, the sera from ten White women, known to have been giving at least three breast feeds daily, were examined. In addition, sera from ten White women who were not lactating were chosen for comparison. Serum-25-OHD was estimated in the paired samples from the lactating and comparison groups and in the 72 remaining sample-1 specimens. In addition, serum calcium and phosphate were estimated in sample 2 of the lactation and the comparison group specimens. Serum-25-OHD was measured by a modification of the method of McLaughlin et a1.4 The coefficient of variation within and between assays was not greater than 8.7%. The ’
method
measures
and 24,25-dihydroxycholecalciferol. Serum25-OHD measured by this assay in a group of men and nonpregnant women in March, 1974, ranged from 9 to 27 ng/ml. Serum-calcium was measured by the Technicon AA II method and serum-phosphate by an AA II modification of the sequential multiple analyser method.
calciferol,
25-hydroxycholecalciferol, 25-hydroxyergo-
’
Results A wide range of 25-OHD values
I
found in mothers immediately post partum (fig. 1). Eight (90%) of the lowest 10% were from Asian mothers. 26% of mothers in the whole study were Asian. Values for the two groups of White mothers are given in fig 2. In the lactating group samples 1 and 2 contained significantly more 25-OHD than corresponding samples in the non-lactating women (p
