The association between ketoacidosis and 25(OH)-vitamin D levels at presentation in children with type 1 diabetes mellitus

Background:  There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D₃ and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM.
Objective:  To determine the relationship between measured 25(OH)-vitamin D₃ levels and the degree of acidosis in children at diagnosis with T1DM.
Subjects:  Children presenting with new-onset T1DM at a tertiary children's hospital.
Methods:  25(OH)-vitamin D₃ and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D₃ levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation.
Results:  Fourteen of the 64 children had low 25(OH)-vitamin D₃ levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r² = 0.20, p < 0.001) and ethnic background a further 10% (partial r² = 0.10, p = 0.002). The levels of 25(OH)-vitamin D₃ increased in 10 of the 11 children with resolution of the acidosis.
Conclusions:  Acid–base status should be considered when interpreting 25(OH)-vitamin D₃ levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child's risk of presenting with DKA.     

Nutritional rickets and z scores for height in the United Arab Emirates: To D or not to D?

Background: Vitamin D deficiency is still prevalent worldwide, including the Middle East. A cohort of patients with nutritional rickets was treated with vitamin D₂ (ergocalciferol) alone. After this intervention, patients were followed to document changes in z scores for height after treatment. The secondary aim was to determine the proportion of affected children who had vitamin D deficiency or calcium deficiency.
Methods: Z score for height was calculated as the difference between the observed value and the median value, divided by the SD of the population. Z scores were compared in patients before and after treatment.
Results: The improvement in z score after treatment was 0.86 ± 0.95. The 95% confidence interval for the mean difference was 1.32–0.40 ( t  = 3.95, P  < 0.001). With a diagnostic cut-off for 25 hydroxyvitamin D₃ (25D) deficiency of <25 nmol/L, only half were diagnosed with severe vitamin D deficiency. The remaining patients had presumable calcium deficiency. The alkaline phosphatase (ALP) was negatively correlated to z scores, implying that higher ALP concentrations predicted severe bone disease (lower z scores). The variables 25D and age were moderately and positively correlated (Pearson's r  = 0.59, 95%CI: 0.15–0.84; P  = 0.01), indicating that younger infants had the lowest 25D levels.
Conclusion: Vitamin D alone was efficient in resolving radiological and biochemical disturbances as well as improving z scores for height in a cohort of children with nutritional rickets, which included patients with 25D deficiency as well as calcium deficiency. The results support the hypothesis of the interplay and continuum of 25D deficiency and calcium deficiency in the pathogenesis of 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.     

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     

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.     

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.     

Vitamin D in infants with cystic fibrosis diagnosed by newborn screening

Aims:   Screening enables early nutritional deficiencies to be detected in those with cystic fibrosis (CF). Although vitamin deficiency is considered unlikely in older subjects with normal vitamin E levels, few studies have determined vitamin D status at diagnosis and its relationship to other fat-soluble vitamins.
Methods:   We reviewed vitamin levels in infants diagnosed with CF by newborn screening over a 5-year period in Melbourne, Australia. Vitamin D levels were determined using the IDS gamma-B 25-OH Vitamin D radio-immunoassay (Immunodiagnostic Systems Limited, Boldon, UK). Vitamins A and E were evaluated by high-performance liquid chromatography. We assessed the association between vitamin D level and sex, month of birth, pancreatic status, and vitamin A and E levels.
Results:   Fifty-eight infants were diagnosed at a median age of 1 month (range: 0–3 months). Initial vitamin D levels were assessed between 0.2 and 3.5 months in 30 (vitamin D) and 45 (vitamins A and E) infants. The number of infants deficient with vitamins D, E and A were 11 (37%), 7 (16%) and 27 (60%), respectively. Vitamin D levels were unrelated to sex, vitamin A or E levels, month of birth or pancreatic status, whereas vitamin A and E levels were significantly lower in those who were pancreatic insufficient. With supplementation, vitamin D increased over time.
Conclusions:   Vitamin D deficiency is common in infants newly diagnosed with CF by newborn screening and is unrelated to pancreatic status or predicted low vitamin E levels. Vitamin D deficiency is less common over time following treatment.     

Clinical Follow-up and Parental Attitudes Towards Neonatal Screening

ABSTRACT. Sveger, T. and Thelin, T. (Departments of Paediatrics and Psychiatry, University of Lund, Malmö General Hospital, Malmö, Sweden). Four-year-old children with α₁-antitrypsin deficiency. Acta Paediatr Scand, 70:171, 1980. –Two hundred thousand infants born in Sweden between November 1972 and September 1974 were screened at birth for a,-antitrypsin (a, AT) deficiency. At age 4 years 172 of 183 children with a, AT deficiency were examined and compared with 80 randomly selected control children. The children with a, AT deficiency had the following Pi types: 118 PiZ, 50 PiSZ, 2 PiZ-, 1 PiS-, and 1 PiFZ. Two PiZ children have severe liver cirrhosis and 1 PiZ boy had died of aplastic anemia. Abnormal levels of serum alanine aminotransferase (S-ALAT) were found in one PiSZ and 47 PiZ children. Upper and lower respiratory infections, otitis, eczema, urinary infections or complications of child diseases did not occur more often in children with α₁ AT deficiency than in controls. More parents of α₁ AT deficient children had stopped smoking and their fathers smoked significantly less. Forty parents of children with α₁ AT deficiency PiZ answered a questionnaire concerning their reaction to, knowledge about and attitudes towards neonatal screening for α₁ AT deficiency. Many parents reported having reacted with lack of understanding, shock or depression upon learning that the child had α₁ AT deficiency. About 4 years later 44 % reported still lack of understanding, and 18 % depression or feelings of guilt. About two-thirds had not fully understood why a , AT deficiency had been identified, despite the fact that they had seen their doctor 3–4 times for check-ups and counselling since birth.     

Nutritional Vitamin B12 Deficiency in a Breastfed Infant Following Maternal Gastric Bypass

Breasfed infants of women who have had gastric or intestinal bypass procedures may develop nutritional deficiencies. We describe a 10-month-old exclusively breastfed white male infant who presented with vomiting, failure to thrive, and megaloblastic anemia. He was found to have vitamin B₁₂ deficiency. His mother had undergone a gastric bypass procedure for morbid obesity 2 years Prior to her pregnancy with this child. She had subclinical vitamin B₁₂ deficiency, with an abnormal Schilling test that corrected with the addition of intrinsic factor. Therefore, we believe that the mother's gastric bypass had caused a decrease in available intrinsic factor, resulting in subclinical vitamin B₁₂ deficiency and decreased breast milk B₁₂. Although she was asymptomatic, her breastfed infant developed symptomatic B₁₂ deficiency. This is the first reported case of a maternal gastric bypass resulting in vitamin B₁₂ deficiency in an infant. These mothers should receive vitamin supplements, including vitamin B₁₂ during and after pregnancy, and my require parenterally administered vitamin B₁₂.     

Prevention of vitamin K deficiency in infancy by weekly administration of vitamin K

Vitamin K prophylaxis has been developed to prevent classic haemorrhagic disease of the newborn. Single vitamin K administration after birth has been reported to fail, resulting in late haemorrhagic disease of the newborn. The preventive effect of oral administration of vitamin K₁ 1 mg, repeated weekly during the first three months of life, was studied in 48 healthy breast-fed infants, by determination of thrombotest, PIVKA-II and vitamin K₁ concentrations at the age of 4, 8 and 12 weeks. All infants showed normal thrombotcst values and PIVKA-II was not detectable. Vitamin K₁ concentrations were negatively correlated with the number of days elapsed since the most recent vitamin K administration. Six to seven days after the latest application, mean levels were 1223,927 and 748 pg/ml at ages 4, 8 and 12 weeks, respectively. In conclusion, weekly administration of vitamin K₁ 1 mg offers complete protection against vitamin K deficiency and does not result in an accumulation of vitamin K₁ in the blood.     

Analysis of various types of chronic granulomatous disease with the monoclonal antibody 7D5 directed against the small subunit of surface cytochrome b558

Four different types of chronic granulomatous disease (CGD) were analysed with the monoclonal antibody, 7D5, directed against the small 23 kD subunit of cytochrome b₅₅₈ using a flow cytometric fluorescence analytical method. 7D5 immunofluorescent surface staining of granulocytes was absent in 12 patients with X-linked cytochrome b₅₅₈ deficiency, in 2 patients with variant X-linked CGD with residual (X-forming activity and in 2 patients with autosomal recessive cytochrome b₅₅₈ deficiency. The mothers of the patients with the X-linked form of CGD had 2 cell populations, one 7D5 negative or weakly positive and one 7D5 positive. The granulocytes of both parents of one patient with autosomal recessive cytochrome b₅₅₈ deficiency had slightly reduced fluorescence intensity comparable to their reduced cytochrome b₅₅₈ content. Three CGD patients with normal cytochrome b₅₅₈ and their parents had granulocytes normally stained with antibody 7D5. 7D5 antibody enables rapid detection and classification of CGD patients with cytochrome b₅₅₈ deficiency as well as rapid identification of heterozygous carriers.     

Prevention of vitamin K deficiency in infancy by weekly administration of vitamin K

Vitamin K prophylaxis has been developed to prevent classic haemorrhagic disease of the newborn. Single vitamin K administration after birth has been reported to fail, resulting in late haemorrhagic disease of the newborn. The preventive effect of oral administration of vitamin K₁ 1 mg, repeated weekly during the first three months of life, was studied in 48 healthy breast-fed infants, by determination of thrombotest, PIVKA-II and vitamin K₁ concentrations at the age of 4, 8 and 12 weeks. All infants showed normal thrombotcst values and PIVKA-II was not detectable. Vitamin K₁ concentrations were negatively correlated with the number of days elapsed since the most recent vitamin K administration. Six to seven days after the latest application, mean levels were 1223,927 and 748 pg/ml at ages 4, 8 and 12 weeks, respectively. In conclusion, weekly administration of vitamin K₁ 1 mg offers complete protection against vitamin K deficiency and does not result in an accumulation of vitamin K₁ in the blood.     

THE PLASMA LEVELS OF 25-HYDROXYVITAMIN D IN PATIENTS WITH VARIOUS LIVER DISEASES AND THE RESPONSE OF 25-HYDROXYVITAMIN D TO VITAMIN D TREATMENT

ABSTRACT. The mean plasma levels of 25-hydroxyvitamin D (25-OH-D) were measured before and after the administration of 2000 units of daily oral vitamin D₂ for a period of 2 weeks in 9 normal infants and children, 7 infants with neonatal hepatitis and persistent neonatal hepatitis, and 4 infants with congenital biliary atresia. The mean plasma level of 25-OH-D increased significantly from 19.5±3.7 (S.E.) ng/ml to 34.0±6.8 (S.E.) ng/ml after administration of vitamin D₂ in controls ( p <0.05). The mean plasma level of 25-OH-D also increased from 8.0±2.1 (S.E.) ng/ml to 22.1±2.6 (S.E.) ng/ml after vitamin D treatment in hepatitis group ( p <0.05). In patients with congenital biliary atresia, vitamin D treatment did not affect the plasma levels of 25-OH-D.     

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.     

High and low dose initial thyroxine therapy for congenital hypothyroidism

Objective : To assess factors influencing thyroxine (T₄ levels 1 month after initiating replacement therapy for congenital primary hypothyroidism.
Methodology : A retrospective review of 41 children with congenital hypothyroidism who received either high or low dose initial T₄ therapy. Thyroid scintiscan was performed, and T₄ levels determined before starting treatment and after 1 month.
Results : T₄ levels at 1 month were correlated ( r ²=0.38, P <0.001) with the pretreatment T₄ level ( r = 0.48), as well as with the T₄ dose ( r = 0.46). Suboptimal treated T₄ levels (<130nmol/L) were seen with greater frequency in infants with thyroid agenesis (7/11) rather than ectopia (7/28, P <0.03), despite receiving similar doses of thyroxine. Infants with suboptimal treated T₄ levels had lower pretreatment T₄ levels than those with optimal levels (21±7 vs 48±34nmol/L, P <0.02). Biochemical hyperthyroidism (T₄ >216nmol/L) occurred in six patients: four of six had ectopia.
Conclusions : These data suggest that infants with little residual thyroid function should receive higher initial T₄ doses than those with significant ectopia.     

Nutritional Vitamin B12 Deficiency in Infancy: Three Case Reports and a Review of the Literature

Three cases of vitamin B₁₂ deficiency that occurred during infancy are presented. These cases appeared to be the result of pre-existing maternal deficiency. All three infants demonstrated evidence of neurodevelopmental delay at presentation, and one had sustained loss of milestones and developed involuntary motor movements. Prior to the initiation of therapy, all three infants were anemic: one was thrombocytopenic and one pancytopenic. In all three cases the hematologic and neurologic abnormalities were corrected with vitamin B₁₂ therapy. The literature is reviewed and discussed with respect to the mechanism of the infants' vitamin B₁₂ deficiency and neurodevelopmental manifestations.     

REDUCED SERUM 1,25-(OH)2 VITAMIN D3 LEVELS IN PREDNISONE-TREATED ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract. The serum levels of 1,25-(OH)₂ vitamin D₃ were assayed in samples from 12 adolescent patients with SLE. Subnormal levels were observed in 7 of these 12 patients. Low levels of the metabolically active polar metabolite of vitamin D₃ may contribute to the development of osteopenia observed in this disease. The cumulative effects of the osteoporotic and anti vitamin D effects of long term steroid therapy in children with SLE may require the cautious administration of supplemental vitamin D.     

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.     

Nutritional vitamin B12 deficiency in hospitalized young children

The authors sought to determine prevalence, social, economic, and dietary patterns of young children (n = 20) identified as having vitamin B₁₂ deficiency anemia after admission to their hospital in the last 3 years. The diagnosis of vitamin B₁₂ deficiency was based on symptoms and clinical findings, findings on peripheral blood films and bone marrow aspirates, and serum levels of vitamin B₁₂. The children had been exclusively breast-fed without any animal food supplementation. Serum vitamin B₁₂ levels were also measured in the sera of mothers and found to be low. The authors concluded that vitamin B₁₂ deficiency might be an important health problem among children of mothers who do not consume animal foods adequately.     

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.