VITAMIN B12 IN HUMAN COLOSTRUM AND MILK

Abstract. Samson, R. R. and McClelland, D. B. L. (University Department of Therapeutics and Clinical Pharmacology, Edinburgh, Scotland). Vitamin B₁₂ in human colostrum and milk. Quantitation of the vitamin and its binder and the uptake of bound vitamin B₁₂ by intestinal bacteria. Acta Paediatr Scand, 69:93, 1980.—The concentration of vitamin B₁₂ was measured by microbiological assay in 229 samples of normal human colostrum and milk taken at various stages of lactation. Colostrum obtained within 48 hours of delivery contains high concentrations of vitamin B₁₂ (mean 2431 pg/ml), but within a few days the levels fall to a range similar to the levels in normal serum. The vitamin B₁₂ binding capacity of 111 samples of colostrum and milk was estimated by gel filtration or charcoal binding. Colostrum samples have a mean binding capacity of 72 ng/ml, while the binding capacity in milk is only one third of this value. The ability of a range of intestinal bacteria to take up colostrum-bound vitamin B₁₂, was assessed. All the organisms took up free vitamin B₁₂, but when the vitamin was bound in colostrum, there was little or no uptake even after 24 hours incubation     

VITAMIN D NUTRITIONAL STATUS OF PREMATURE INFANTS SUPPLEMENTED WITH 500 IU VITAMIN D2 PER DAY

ABSTRACT. The vitamin D nutritional status of premature infants was assessed by determining plasma 25-hydroxyvitamin D concentrations before and during supplementation with 500 IU vitamin D₂ per day. Fifty-one samples were collected from 25 healthy infants fed breast milk and a vitamin D₃ fortified formula. Gestational age was 32.2±2.4 weeks (mean ± 1 SD). 25-hydroxyvitamin D levels before supplementation correlated well with maternal values ( r =0.81). The infants' mean plasma concentration increased from 30.6±13.7 nmol/l (mean±1 SD) after birth to 46.3±10.5 nmol/l after 9±1 days ( p <0.0025), and to 65.3±16.6 nmol/l after 37±10 days of vitamin D₂ treatment ( p <0.0005). 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃ were determined separately, and it appeared that the rise was accounted for by the D₂ fraction while 25-hydroxyvitamin D₃ concentrations were unchanged. The results demonstrate that vitamin D₂ is well absorbed and hydroxylated in the 25 position by premature infants free of associated disease, and that a supplementation of 500 IU per day in addition to breast milk and a regular vitamin D fortified formula is adequate to rapidly establish 25-hydroxyvitamin D levels within the normal adult range.     

Nutritionally relevant supplementation of vitamin B6 in lactating women: effect on plasma prolactin

Pharmacologic doses of vitamin B6 administered to lactating women have been reported to suppress plasma prolactin. As a result, some physicians have recommended restriction of vitamin B6 intake for lactating women. In the present investigation, 20 lactating women were given supplemental doses of vitamin B6, 0.5 to 4.0 mg/d, beginning 24 hours after delivery. Plasma prolactin, plasma pyridoxal phosphate, and breast milk total vitamin B6 concentrations were determined during the first 9 months postpartum. Women receiving the supplement of 4.0 mg compared with 0.5 mg of vitamin B6 per day had significantly higher plasma pyridoxal phosphate (P less than .01) and breast milk total vitamin B6 concentrations (P less than .05) beginning at 1 month postpartum and continuing through the duration of the study. Plasma prolactin concentrations were not significantly different between the two groups. The percentage of all women, regardless of treatment, in whom lactation persisted at 1 and 2 weeks and 1, 3, 6, and 9 months were 100%, 100%, 100%, 90%, 80%, and 65%, respectively. All women who ceased to lactate during the study reported doing so by choice. Nutritionally relevant doses of vitamin B6 elevated plasma pyridoxal phosphate and breast milk total vitamin B6 concentrations of lactating women without reducing plasma prolactin concentration or halting lactation.     

PYRIDOXAL PHOSPHATE CONCENTRATION IN BLOOD IN NEWBORN INFANTS AND THEIR MOTHERS COMPARED WITH THE AMOUNT OF EXTRA PYRIDOXOL TAKEN DURING PREGNANCY AND BREAST FEEDING

Abstract. Ejderhamn, J. and Hamfelt, A. (Departments of Paediatrics and Clinical Chemistry, Sundsvalls Hospital, Sundsvall, Sweden.) Pyridoxal phosphate concentration in blood in newborn infants and their mothers compared with the amount of extra pyridoxol taken during pregnancy and breast feeding, Acta Paediatr Scand, 69:327, 1980.—The concentrations of pyridoxal phosphate have been estimated in cord blood and capillary blood samples taken at 3 hours, 2 days, 4 days, 7 days and 6 weeks of age, from eleven fullterm infants. Pyridoxal phosphate concentrations were also determined in venous blood samples taken from the mothers at delivery. A highly significant correlation between pyridoxal phosphate in cord whole blood and venous whole blood taken from the mothers at delivery was found. Infants whose mothers had taken extra pyridoxol during pregnancy had a higher concentration of pyridoxal phosphate at 3 hours of age compared with infants whose mothers had not taken extra pyridoxol. During the first week of life the concentration of pyridoxal phosphate in capillary blood decreases strikingly. At 6 weeks of age the concentration of pyridoxal phosphate is in the same range as that of normal adults. Findings are also discussed which indicates that: 1) Vitamin B₆ is transported in breast milk; 2) The giving of supplemental pyridoxol during pregnancy in ordinary doses (2–6 mg/day) does not have an antilactogenic effect. No correlation between the erythrocyte aspartate aminotransferase activation with pyridoxal phosphate in vitro and pyridoxal phosphate concentration in plasma was found during the first 6 weeks of life.     

Vitamin D Deficiency Rickets and Vitamin B12 Deficiency in Vegetarian Children

ABSTRACT. During the years 1978-83 four vegetarian children have been admitted to the pediatric departments of Ullevaal and Aker Hospitals in Oslo and Haukeland Hospital, Bergen, with the diagnosis of vitamin D deficiency rickets. One had vitamin B₁₂ deficiency as well. All had been fed a vegetarian diet with some cows'milk, but without vitamin supplementation. All had marked hypocalcemia, and three had tetany or convulsions. All responded well to conventional doses of vitamin D therapy. Two of the mothers had vitamin D deficiency, and one of them also had vitamin B₁₂ deficiency. This report describes the case histories of these children, and also discusses predisposing factors of vegetarian diets for the development of nutritional rickets     

Clinical manifestations of infants with nutritional vitamin B deficiency due to maternal dietary deficiency

Aim: In developing countries, nutritional vitamin B₁₂ deficiency in infants due to maternal diet without adequate protein of animal origin has some characteristic clinical features. In this study, haematological, neurological and gastrointestinal characteristics of nutritional vitamin B₁₂ deficiency are presented.
Methods: Hospital records of 27 infants diagnosed in a paediatric haematology unit between 2000 and 2008 were evaluated retrospectively.
Results: The median age at diagnosis was 10.5 months (3–24 months). All the infants were exclusively breast fed and they presented with severe nonspecific manifestations, such as weakness, failure to thrive, refusal to wean, vomiting, developmental delay, irritability and tremor in addition to megaloblastic anaemia. The diagnosis was confirmed by complete blood counts, blood and marrow smears and serum vitamin B₁₂ and folic acid levels. The median haemoglobin level was 6.4 g/dL (3.1–10.6) and mean corpuscular volume (MCV) was 96.8 fL (73–112.3). Some patients also had thrombocytopaenia and neutropaenia. All the infants showed clinical and haematological improvement with vitamin B₁₂ administration. Patients with severe anaemia causing heart failure received packed red blood cell transfusions as the initial therapy.
Conclusion: Paediatricians must consider nutritional vitamin B₁₂ deficiency due to maternal dietary deficiency in the differential diagnosis of some gastrointestinal, haematological, developmental and neurological disorders of infants with poor socioeconomic status. Delay in diagnosis may cause irreversible neurological damage.     

Serum thiamin, pyridoxal, cobalamin and folate concentrations in young infants

Blood samples were obtained from 509 apparently healthy infants between the age of 3 and 54 weeks attending for routine checks at infant health centres. Serum was assayed for thiamin, pyridoxal, cobalamin and folate. Three hundred and five infants were being breast fed and results from these were used to construct a reference range-thiamin 2-17 micrograms/l, pyridoxal 8-39 micrograms/l, cobalamin 120-800 ng/l and folate 7-47 micrograms/l (95 percentile ranges). One hundred and thirty-four infants were being fed a manufactured milk formulation and the serum concentrations of thiamin, pyridoxal and cobalamin were significantly higher than those found in breast fed infants. Thirteen infants were receiving pasteurized cow's milk. This milk was found to have more than 3 times the folate content of human breast milk yet these infants had a significantly reduced serum level of folate.     

The effects of dietary vitamin B12 deficiency on sperm maturation in developing and growing male rats

ABSTRACT  To evaluate the role of vitamin B₁₂ on spermatogenesis, the effects of dietary vitamin B₁₂ deficiency on sperm maturation in developing rat fetuses and young growing rats were examined. The vitamin B₁₂-defi-cient diet was given to all the animals for three different periods: whole period (gestation to mature), gestation period (gestation to weaning), or immature period (3–12 weeks postnatal). Sperm examination revealed that the sperm count was markedly lower in male progeny (F1) that were vitamin B₁₂-deficient during the whole period. In addition, a significantly higher number of abnormal sperm, such as tailless and amorphous sperm, was observed. In male rats that were vitamin B₁₂-deficient during the immature period, the incidence of abnormal sperms was 14.4% and 4.8% for tailless and short tail, respectively. The motion rates, such as path velocity and straight line velocity, were decreased to 20–40% of the control value in rats that were vitamin B₁₂-deficient both during the whole and gestation periods. However, no effects of vitamin B₁₂ deficiency on sperm motility were observed during the immature and mature periods. From these findings, we suggest that dietary vitamin B₁₂ deficiency during pregnancy may induce irreversible damage in the germ cells of embryos and affect the maturation of spermatozoa.     

SEASONAL VARIATION IN SERUM-25-OH-D3 IN MOTHERS AND NEWBORN INFANTS IN NORTHERN FINLAND

ABSTRACT. Two groups, each consisting of twenty Finnish mother-neonate pairs and ten non-pregnant controls were studied for serum calcium, serum phosphate, serum alkaline phosphatase, parathormone index (PTH_ind) and S-25-OH-D₃. The first series was collected in winter and the other in summer. The serum samples were taken on the third day after delivery. The concentrations of S-25-OH-D₃ were significantly lower in the mothers than in the non-pregnant controls in winter, but the difference was not significant in summer. The concentrations of S-25-OH-D₃ in the serum of the mothers were similarly significantly lower in winter than in summer, ten mothers exhibiting a value below the detection line in winter, but only two in summer. The concentrations of S-25-OH-D₃ in the mothers and their newborn infants showed a close relationship, but when extremely low values existed in the mothers, the infant concentrations were slightly higher. The seasonal variation in S-25-OH-D₃ was also significant in the neonates. Although calcium was decreased and alkaline phosphatase elevated when compared with the non-pregnant controls in the mothers in both groups, these values showed no seasonal variation, and the mean levels of serum calcium, phosphate, alkaline phosphatase and PTH_ind in the neonates also remained unaltered between the two groups. The results indicate that additional vitamin D should be supplied during pregnancy in the winter months at this latitude.     

Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1

Abstract: The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K₁ prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K₁, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K₁. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K₁ were to have a longer duration of effect than intravenous vitamin K₁. This may be because intramuscular vitamin K₁ acts as a depot preparation. The findings suggest that intravenous vitamin K₁ is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K₁ should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.     

Does intramuscular vitamin K1 act as an unintended depot preparation?

Objective : To propose a hypothesis that the long duration of effect of intramuscular (i.m.) vitamin K₁ in preventing late onset haemorrhagic disease results from a depot effect after i.m. injection.
Methodology : Review of scientific literature relating to the pharmacology of vitamin K, and the aetiology of late onset haemorrhagic disease.
Results : A single i.m. dose of vitamin K₁ is effective for at least 2 months, whereas the duration of effect of a single oral dose is about 3-4 weeks. The known pharmacological properties of vitamin K₁ are seemingly at variance with the long duration of effect of an i.m. dose. Menaquinones (vitamins K₂) are absent in the newborn liver, but gradually accumulate after birth. This, together with the low concentrations of vitamin K₁ in human breast milk, may explain the peak frequency of late onset haemorrhagic disease at 4-8 weeks. We hypothesize that after i.m. injection, vitamin K₁ acts as a depot preparation by forming a viscous mass in muscle tissue which is slowly absorbed over many weeks. This hypothesis is supported by reports indicating significantly higher plasma vitamin K₁ levels several weeks after i.m., as compared to oral vitamin K₁.
Conclusions : The prolonged efficacy of i.m. vitamin K₁, compared to oral preparations may be due to a depot effect New oral preparations of vitamin K₁, despite greatly improved bioavailability, may have a shorter duration of effect than i.m. vitamin K₁, and therefore be less effective for long-term prophylaxis.     

Serum Thiamin, Pyridoxal, Cobalamin and Folate Concentrations in Young Infants

ABSTRACT. Blood samples were obtained from 509 apparently healthy infants between the age of 3 and 54 weeks attending for routine checks at infant health centres. Serum was assayed for thiamin, pyridoxal, cobalamin and folate. Three hundred and five infants were being breast fed and results from these were used to construct a reference range–thiamin 2-17 μg/1, pyridoxal 8-39 ng/1, cobalamin 120-800 μg/1 and folate 7-47 ng/1 (95 percentile ranges). One hundred and thirty-four infants were being fed a manufactured milk formulation and the serum concentrations of thiamin, pyridoxal and cobalamin were significantly higher than those found in breast fed infants. Thirteen infants were receiving pasteurised cow's milk. This milk was found to have more than 3 times the folate content of human breast milk yet these infants had a significantly reduced serum level of folate.     

EFFECT OF SEASON AND VITAMIN D SUPPLEMENTATION ON PLASMA CONCENTRATIONS OF 25-HYDROXYVITAMIN D IN NORWEGIAN INFANTS

ABSTRACT. Plasma concentrations of 25-hydroxyvitamin D (250HD) were determined in 81 vitamin D supplemented or unsupplemented infants at the end of winter. The values were compared with maternal levels and with concentrations found in 22 unsupplemented infants at the end of summer. The 250HD levels of the neonates were lower, but closely related to maternal values ( r =0.95, p <0.0005). Unsupplemented breast-fed infants had lower 250HD levels at 6 weeks than at 4 days (16±7 vs. 32±15 nmol/l, mean ±1 SD, p <0.0005). The mean 250HD level of vitamin D supplemented 6-12 months old infants was intermediate between those of the unsupplemented nursed groups and the unsupplemented children studied during summer (53±28 vs. 85±28 nmol/l, p <0.0005). Six weeks old infants who had received a milk formula containing 400 IU vitamin D₃ per liter had levels similar to the latter group (92±21 nmol/l). The data suggest that the vitamin D stores acquired during fetal life, or from ultraviolet light exposure during the summer, may be inadequate to maintain safe levels of 250HD throughout the winter, but that a daily supplement of 400 IU is adequate to establish concentrations in the summer range.     

Neonatal plasma vitamin K1 levels following oral and intramuscular administration of vitamin K1

Vitamin K₁ levels were measured by high performance liquid chromatography in cord blood ( n = 33) and at the age of 97–120 h after administration of 2 mg of vitamin K_l orally ( n = 88) or 1 mg of vitamin K₁ by im injection ( n = 88). Vitamin K₁ levels were less than 0.05 μg/l in cord blood. The mean (range), SEM, mode and median values (μg/l) for the infants given oral vitamin K₁ were 17.99 (1–56), 1.25, 8 and 15.5 and those for the infants given im vitamin K_l 15.83(2–57), 1.01, 11and 14, respectively. The t- test showed no significant difference in the mean values ( p = 0.09) in the infants given oral or im vitamin K.     

Cerebrospinal fluid concentrations of leukotriene B4 in bacterial meningitis

We investigated whether leukotriene B₄ (LTB₄), a granulocyte inflammatory mediator, is detectable in cerebrospinal fluid using a high performance liquid chromatographic method. In non-pleocytotic cerebrospinal fluid (n = 5) and in cerebrospinal fluid from children with aseptic meningitis (n = 8). LTB₄ concentrations were below the detection limit (<0.2ngml ¹). In the range 0 20ngml ¹. the recovery rate of LTB₄ that had been added to non-pleocytotic cerebrospinal fluid was >90%. In cerebrospinal fluid with a polymorphonuclear leucocyte (PMN) count higher than 1,000/ml, LTB₄ was detectable in six out of seven specimens with a concentration of 0.35-3.3 ngml⁻¹. LTB₄ concentration was significantly correlated with PMN number. These results, together with observations in animal models, are discussed with regard to a pathophysiological role of LTB₄ in bacterial meningitis.     

Concentrations of LTB4, LTC4, LTD4 and LTE4 in bronchiolitis due to respiratory syncytial virus

Fifty-five infants with bronchiolitis due to respiratory syncytial virus were evaluated for the presence of leukotriene B₄, C₄, D₄ and E₄ in nasopharyngeal secretions. An attempt was made to correlate concentrations of leukotrienes to arterial oxygen tension. Forty participants received conventional therapy consisting primarily of aerosolized albuterol and occasional aminophylline therapy. The other 15 individuals received ribavirin therapy in addition to conventional therapy, and leukotriene concentrations were compared among individuals in these groups. RSV infection was documented by standard methods, and leukotrienes were measured by reverse-phase high pressure liquid chromatography. The leukotriene detected most commonly was LTC₄ (up to 83% of subjects); LTD₄ and LTB₄ were present in approximately 30% of individuals. The mean partial pressure of oxygen was found to be lower in those individuals with detectable LTB₄ than in those without detectable LTB₄ (p < 0.025), and an overall inverse correlation of LTB₄ concentrations with initial pO₂ values was observed (r = 0.318, p < 0.05). The presence and quantity of other leukotrienes did not correlate with the severity of illness. During the first week of illness, the concentration of leukotrienes declined sharply in ribavirin recipients. Individuals receiving conventional therapy during the same time interval exhibited stable or increasing leukotriene concentrations. These observations suggest that LTB₄ may be important in the pathogenesis of bronchiolitis, and that ribavirin therapy may inhibit leukotriene release in the respiratory tract.     

Imerslund-Gräsbeck Anemia

ABSTRACT. A follow-up study has been performed on 14 patients, now aged 6–46 years, with Imerslund-Gräsbeck anemia (congenital, hereditary selective malasorption of vitamin B₁₂). On intramuscular vitamin B₁₂ therapy, the patients are clinically and hematologically normal. Those who had constant proteinuria in childhood continue to excrete protein in the urine. Our patients excrete an average of 750 mg of protein per 24 hours (range 13–1460 mg). The proteinuria is predominantly of glomerular origin, but some is also of tubular origin. Renal biopsies of the two oldest patients were normal on light microscopy. Electron microscopy revealed moderate signs of chronic glomerulopathy of mesangioproliferative type in both patients. The renal lesions do not seem to be progressive.     

Breast milk jaundice in premature infants.

In randomised study of 186 preterm infants those fed on maternal or banked breast milk had a significantly higher peak bilirubin concentration and a more prolonged jaundice than infants fed an artificial preterm formula and were over four times more likely to achieve plasma bilirubin values above 200 mumol/l (11.7 mg/100 ml). This dietary effect was seen even in a high risk subgroup of sick ventilated infants below 1500 g who were receiving restricted enteral intakes. We suggest that breast milk jaundice in preterm infants may increase clinical intervention. Our findings are discussed in the light of epidemiological data suggesting an association between moderate hyperbilirubinaemia (greater than 170 mumol/l) and neurodevelopmental outcome.     

Serum Concentrations of Vitamin D Metabolites in Exclusively Breast-Fed Infants at 70° North

ABSTRACT. The effect of prolonged breast-feeding on the serum concentrations of vitamin D metabolites, calcium, phosphate, and alkaline phosphatase was studied longitudinally in 7 infants from Northern Norway. They were exclusively breast-fed for a median of 71/2 months. Three of the mothers were supplemented with vitamin D throughout lactation. All but one of the infants had 25-hydroxyvitamin D (25-OHD) levels in the rachitic range (< 20 nmol/l) on at least one occasion. Vitamin D supplementation of the mother had no apparent effect on the infants' 25-OHD levels, but the values increased during summer. The infant who had the lowest 25-OHD levels also had decreased 1,25-dihydroxyvitamin D (1,25-(OH)₂D) concentrations, while the others maintained l,25-(OH)₂D levels within normal limits. 24,25-(OH)₂D concentrations were undetectable when the 25-OHD levels were below 35 nmol/l, but the two metabolites were closely correlated for higher values of 25-OHD. Low 25-OHD levels were associated with decreased phosphate concentrations at 6 months. The calcium levels were normal throughout the study period of one year, as were all but two of the alkaline phospatase values. Although none of the infants had clinical or biochemical evidence of rickets, the results suggest that the vitamin D supply from human milk is inadequate, and that routine vitamin D supplementation is advisable for breast-fed infants who are deprived of sunlight exposure.