Home Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants
Article
Licensed
Unlicensed Requires Authentication

Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants

  • Corrine Hanson EMAIL logo , Elizabeth Lyden , Amy Nelson , Melissa Thoene , Julie Wagner , Amy Wu , Stephen Rennard and Ann Anderson-Berry
Published/Copyright: May 30, 2015
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 9-10

Abstract

Objective: The objective of this study was to evaluate the relationship between 25(OH)D, Vitamin D Binding Protein (DBP), and free vitamin D in premature infants.

Methods: Thirty-two infants <32 weeks’ gestation were randomized to two different levels of vitamin D3 supplementation (400 vs. 800 IU/day). 25(OH)D levels were measured by LC-MS/MS; DBP was measured by validated ELISA. Free vitamin D was calculated using molar ratios of 25(OH)D and DBP. The Wilcoxon signed rank test was used to compare DBP, free D and 25(OH)D levels; Spearman’s correlation coefficients were used to assess correlations.

Results: The mean gestational age at birth was 30.5 weeks; mean birth weight was 1405 g. Mean 25(OH)D levels at birth were 17.3 ng/mL; DBP levels were 297 mg/L, and estimated free vitamin D levels were 18.9. There was a statistically significant change in 25(OH)D levels after 8 weeks (24.6 vs. 39.1 ng/mL in the 400 vs. 800 group, respectively, p=0.02). DBP levels from birth to 8 weeks showed a statistically significant decrease (267 vs. 208, p=0.04). Estimated free 25(OH)D concentrations increased over the study period, from 18.9 at birth to 64.7 at 8 weeks of age (p=0.0001). Free vitamin D levels at birth were associated with global DEXA bone mineral content at discharge from the NICU (r=0.58, p=0.05).

Conclusion: Supplementation with vitamin D3 increased the free portion of the vitamin D metabolite, providing increased bioavailable substrate. Improved free vitamin D levels may improve measurable outcomes such as bone mineral content and deserve further evaluation.

Keywords: nutrition; prematurity; vitamin D
Corresponding author: Corrine Hanson, PhD, RD, University of Nebraska Medical Center, School of Allied Health Professionals, Medical Nutrition Education, Omaha, NE, USA, Phone: +402-559-3658, Fax: +402-559-7565, E-mail:

Acknowledgments

The authors would like to acknowledge Dr. Glenville Jones and Dr. Martin Kaufmann, Department of Biomedical and Molecular Sciences, Queen’s University, Ontario, Canada, for the measurements of 25(OH)D.

Funding: Edna Ittner Foundation and the Clinical Research Center at the University of Nebraska Medical Center.

References

1. Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007;85:788–95.10.1093/ajcn/85.3.788Search in Google Scholar

2. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500–3.10.1016/S0140-6736(01)06580-1Search in Google Scholar

3. Erkkola M, Kaila M, Nwaru BI, Kronberg-Kippilä C, Ahonen S, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy 2009;39:875–82.10.1111/j.1365-2222.2009.03234.xSearch in Google Scholar PubMed

4. Karatekin G, Kaya A, Salihoglu O, Balci H, Nuhoglu A. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. Eur J Clin Nutr 2009;63:473–7.10.1038/sj.ejcn.1602960Search in Google Scholar PubMed

5. Mormile R. Vitamin D intake and premature infants with intraventricular hemorrhage: how advisable is it? J Pediatr Endocrinol Metab 2014;27:799–800.10.1515/jpem-2013-0418Search in Google Scholar PubMed

6. Hanson C, Armas L, Lyden E, Anderson-Berry A. Vitamin D status and associations in newborn formula-fed infants during initial hospitalization. J Am Diet Assoc 2011;111:1836–43.10.1016/j.jada.2011.09.010Search in Google Scholar PubMed

7. Taylor SN, Wagner CL, Fanning D, Quinones L, Hollis BW. Vitamin D status as related to race and feeding type in preterm infants. Breastfeed Med 2006;1:156–63.10.1089/bfm.2006.1.156Search in Google Scholar PubMed

8. Monangi N, Slaughter JL, Dawodu A, Smith C, Akinbi HT. Vitamin D status of early preterm infants and the effects of vitamin D intake during hospital stay. Arch Dis Child Fetal Neonatal Ed 2014;99:F166–8.10.1136/archdischild-2013-303999Search in Google Scholar PubMed PubMed Central

9. Burris HH, Van Marter LJ, McElrath TF, Tabatabai P, Litonjua AA, et al. Vitamin D status among preterm and full-term infants at birth. Pediatr Res 2014;75:75–80.10.1038/pr.2013.174Search in Google Scholar PubMed PubMed Central

10. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes calcium and vitamin D. Washington DC: National Academy of Sciences, 2011.Search in Google Scholar

11. Ponda MP, McGee D, Breslow JL. Vitamin D-binding protein levels do not influence the effect of vitamin D repletion on serum PTH and calcium: data from a randomized, controlled trial. J Clin Endocrinol Metab 2014;99:2494–9.10.1210/jc.2014-1181Search in Google Scholar PubMed PubMed Central

12. Nimitphong H, Saetung S, Chanprasertyotin S, Chailurkit LO, Ongphiphadhanakul B. Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D(3) or D(2)supplementation. Nutr J 2013;12:39-2891-12-39.10.1186/1475-2891-12-39Search in Google Scholar

13. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 2010;19:2739–45.10.1093/hmg/ddq155Search in Google Scholar

14. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 2010;376:180–8.10.1016/S0140-6736(10)60588-0Search in Google Scholar

15. Engelman CD, Meyers KJ, Iyengar SK, Liu Z, Karki CK, et al. Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations. J Nutr 2013;143:17–26.10.3945/jn.112.169482Search in Google Scholar

16. Arnaud J, Constans J. Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet 1993;92:183–8.10.1007/BF00219689Search in Google Scholar

17. Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, et al. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011;26:1609–16.10.1002/jbmr.387Search in Google Scholar

18. Kaufmann M, Gallagher C, Peacock M, Schlingmann KP, Konrad M, et al. Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D & 24,25-dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD. J Clin Endocrinol Metab. 2014;99:2567–74.10.1210/jc.2013-4388Search in Google Scholar

19. Rennard SI, Berg R, Martin GR, Foidart JM, Robey PG. Enzyme-linked immunoassay (ELISA) for connective tissue components. Anal Biochem 1980;104:205–14.10.1016/0003-2697(80)90300-0Search in Google Scholar

20. White P, Cooke N. The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab 2000;11:320–7.10.1016/S1043-2760(00)00317-9Search in Google Scholar

21. Al-oanzi ZH, Tuck SP, Raj N, Harrop JS, Summers GD, et al. Assessment of vitamin D status in male osteoporosis. Clin Chem 2006;52:248–54.10.1373/clinchem.2005.059568Search in Google Scholar PubMed

22. Bouillon R, Van Baelen H. Transport of vitamin D: significance of free and total concentrations of the vitamin D metabolites. Calcif Tissue Int 1981;33:451–3.10.1007/BF02409472Search in Google Scholar PubMed

23. Nyomba BL, Bouillon R, Bidingija M, Kandjingu K, De Moor P. Vitamin D metabolites and their binding protein in adult diabetic patients. Diabetes 1986;35:911–5.10.2337/diab.35.8.911Search in Google Scholar PubMed

24. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the fenton growth chart for preterm infants. BMC Pediatr 2013;13:59-2431-13-59.10.1186/1471-2431-13-59Search in Google Scholar PubMed PubMed Central

25. Fenton TR. A new growth chart for preterm babies: Babson and Benda’s chart updated with recent data and a new format. BMC Pediatr 2003;3:13.10.1186/1471-2431-3-13Search in Google Scholar PubMed PubMed Central

26. Hillman LS, Haddad JG. Serial analyses of serum vitamin D-binding protein in preterm infants from birth to postconceptual maturity. J Clin Endocrinol Metab 1983;56:189–91.10.1210/jcem-56-1-189Search in Google Scholar PubMed

27. Carpenter TO, Zhang JH, Parra E, Ellis BK, Simpson C, et al. Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers. J Bone MinerI Res 2013;28:213–21.10.1002/jbmr.1735Search in Google Scholar PubMed PubMed Central

28. Schwartz JB, Lai J, Lizaola B, Kane L, Markova S, et al. A comparison of measured and calculated free 25(OH) vitamin D levels in clinical populations. J Clin Endocrinol Metab 2014;99:1631–7.10.1210/jc.2013-3874Search in Google Scholar PubMed PubMed Central

29. Zhang JY, Lucey AJ, Horgan R, Kenny LC, Kiely M. Impact of pregnancy on vitamin D status: a longitudinal study. Br J Nutr 2014;112:1081–7.10.1017/S0007114514001883Search in Google Scholar PubMed

30. Hoogenboezem T, Degenhart HJ, de Muinck Keizer-Schrama SM, Bouillon R, Grose WF, et al. Vitamin D metabolism in breast-fed infants and their mothers. Pediatr Res 1989;25:623–8.10.1203/00006450-198906000-00014Search in Google Scholar PubMed

31. Powe CE, Seely EW, Rana S, Bhan I, Ecker J, et al. First trimester vitamin D, vitamin D binding protein, and subsequent preeclampsia. Hypertension 2010;56:758–63.10.1161/HYPERTENSIONAHA.110.158238Search in Google Scholar PubMed PubMed Central

32. Berg I, Hanson C, Sayles H, Romberger D, Nelson A, et al. Vitamin D, vitamin D binding protein, lung function and structure in COPD. Respir Med 2013;107:1578–88.10.1016/j.rmed.2013.05.010Search in Google Scholar PubMed

33. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, et al. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 1986;63:954–9.10.1210/jcem-63-4-954Search in Google Scholar PubMed

34. Speeckaert M, Huang G, Delanghe JR, Taes YE. Biological and clinical aspects of the vitamin D binding protein (gc-globulin) and its polymorphism. Clin Chim Acta 2006;372:33–42.10.1016/j.cca.2006.03.011Search in Google Scholar PubMed

35. Powe CE, Karumanchi SA, Thadhani R. Vitamin D-binding protein and vitamin D in Blacks and Whites. N Engl J Med 2014;370:880–1.Search in Google Scholar

36. Saintonge S, Bang H, Gerber LM. Implications of a new definition of vitamin D deficiency in a multiracial us adolescent population: the National Health and Nutrition Examination Survey III. Pediatrics 2009;123:797–803.10.1542/peds.2008-1195Search in Google Scholar PubMed

37. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med 2009;169:626–32.10.1001/archinternmed.2008.604Search in Google Scholar PubMed PubMed Central

38. Nesby-O’Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, et al. Hypovitaminosis D prevalence and determinants among African American and White women of reproductive age: Third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2002;76:187–92.10.1093/ajcn/76.1.187Search in Google Scholar PubMed

39. Speeckaert MM, Speeckaert R, van Geel N, Delanghe JR. Vitamin D binding protein: a multifunctional protein of clinical importance. Adv Clin Chem 2014;63:1–57.10.1016/B978-0-12-800094-6.00001-7Search in Google Scholar PubMed

40. Safadi FF, Thornton P, Magiera H, Hollis BW, Gentile M, et al. Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. J Clin Invest 1999;103:239–51.10.1172/JCI5244Search in Google Scholar PubMed PubMed Central

41. Mendel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 1989;10:232–74.10.1210/edrv-10-3-232Search in Google Scholar PubMed

42. Bikle DD, Gee E. Free, and not total, 1,25-dihydroxyvitamin D regulates 25-hydroxyvitamin D metabolism by keratinocytes. Endocrinology 1989;124:649–54.10.1210/endo-124-2-649Search in Google Scholar PubMed

43. Bouillon R, Van Baelen H, De Moor P. 25-hydroxyvitamin D and its binding protein in maternal and cord serum. J Clin Endocrinol Metab 1977;45:679–84.10.1210/jcem-45-4-679Search in Google Scholar

44. Brunvand L, Haug E. The estimated free concentration of calcidiol is higher in venous cord blood than in maternal blood. Scand J Clin Lab Invest 1994;54:563–6.10.3109/00365519409088569Search in Google Scholar

45. Chun RF, Peercy BE, Adams JS, Hewison M. Vitamin d binding protein and monocyte response to 25-hydroxyvitamin d and 1,25-dihydroxyvitamin D: analysis by mathematical modeling. PLoS One 2012;7:e30773.10.1371/journal.pone.0030773Search in Google Scholar

46. Rowling MJ, Kemmis CM, Taffany DA, Welsh J. Megalin-mediated endocytosis of vitamin D binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells. J Nutr 2006;136:2754–9.10.1093/jn/136.11.2754Search in Google Scholar

47. Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell 1999;96:507–15.10.1016/S0092-8674(00)80655-8Search in Google Scholar

48. Abboud M, Gordon-Thomson C, Hoy AJ, Balaban S, Rybchyn MS, et al. Uptake of 25-hydroxyvitamin D by muscle and fat cells. J Steroid Biochem Mol Biol 2014;144 Pt A:232–6.10.1016/j.jsbmb.2013.10.020Search in Google Scholar PubMed

49. Gartner LM, Greer FR, Section on Breastfeeding and Committee on Nutrition. American Academy of Pediatrics. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics 2003;111(4 Pt 1):908–10.10.1542/peds.111.4.908Search in Google Scholar PubMed

Received: 2015-2-17
Accepted: 2015-4-9
Published Online: 2015-5-30
Published in Print: 2015-9-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Growth hormone
  3. Growth hormone and growth hormone deficiency – still a lot to learn
  4. Dynamic changes in the hypothalamic- pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study
  5. Pituitary gland size is a useful marker in diagnosing isolated growth hormone deficiency in short children
  6. Carotid intima-media thickness in children treated with growth hormone
  7. The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency
  8. Growth impairment and growth hormone-IGF-1 axis in infantile anorexia nervosa
  9. Growth hormone deficiency in a patient with mitochondrial disease
  10. Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder
  11. Review articles
  12. Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets
  13. Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development
  14. Original articles
  15. Carotid intimal medial thickness and its relation to endothelial dysfunction and echocardiographic changes in adolescents with type 1 diabetes
  16. Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth
  17. Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood
  18. Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study
  19. Role of circulating adipocytokines vaspin, apelin, and visfatin in the loss of appetite in underweight children: a pilot trial
  20. Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family
  21. Waist-to-height ratio as a screening measure for identifying adolescents with hypertriglyceridemic waist phenotype
  22. Assessment and relation of total and regional fat mass with bone mineral content among Indian urban adolescents
  23. Evaluation of the relationship between serum adropin levels and blood pressure in obese children
  24. Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function
  25. Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants
  26. Can school health check-ups serve as screening tool for growth anomalies and obesity in children?
  27. The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia
  28. Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
  29. Clinical characteristics of children referred for signs of early puberty before age 3
  30. Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty
  31. Anti-Müllerian hormone in children: a ten-year prospective longitudinal study (EarlyBird 39)
  32. Patient reports
  33. A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation
  34. Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old girl with Graves’ disease
  35. Dyshormonogenesis seems to be more frequent in a group of Cameroonian children with congenital hypothyroidism
  36. Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up
  37. Cerebral infarction and femoral venous thrombosis detected in a patient with diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G mutations
  38. Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency
  39. Short communication
  40. Tamoxifen-associated hirsutism: an unusual side effect in a 5-year-old girl with McCune-Albright syndrome
  41. Letters to the Editor
  42. Psychiatric disorders are associated with increased risk for developing hyponatraemia in children
  43. Rett syndrome and precocious puberty association
https://doi.org/10.1515/jpem-2015-0089
Keywords for this article
nutrition; prematurity; vitamin D

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Growth hormone
  3. Growth hormone and growth hormone deficiency – still a lot to learn
  4. Dynamic changes in the hypothalamic- pituitary-adrenal axis during growth hormone therapy in children with growth hormone deficiency: a multicenter retrospective study
  5. Pituitary gland size is a useful marker in diagnosing isolated growth hormone deficiency in short children
  6. Carotid intima-media thickness in children treated with growth hormone
  7. The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency
  8. Growth impairment and growth hormone-IGF-1 axis in infantile anorexia nervosa
  9. Growth hormone deficiency in a patient with mitochondrial disease
  10. Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder
  11. Review articles
  12. Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets
  13. Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development
  14. Original articles
  15. Carotid intimal medial thickness and its relation to endothelial dysfunction and echocardiographic changes in adolescents with type 1 diabetes
  16. Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth
  17. Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood
  18. Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study
  19. Role of circulating adipocytokines vaspin, apelin, and visfatin in the loss of appetite in underweight children: a pilot trial
  20. Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family
  21. Waist-to-height ratio as a screening measure for identifying adolescents with hypertriglyceridemic waist phenotype
  22. Assessment and relation of total and regional fat mass with bone mineral content among Indian urban adolescents
  23. Evaluation of the relationship between serum adropin levels and blood pressure in obese children
  24. Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function
  25. Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants
  26. Can school health check-ups serve as screening tool for growth anomalies and obesity in children?
  27. The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia
  28. Clinical and molecular characterization of five Spanish kindreds with X-linked adrenal hypoplasia congenita: atypical findings and a novel mutation in NR0B1
  29. Clinical characteristics of children referred for signs of early puberty before age 3
  30. Effects of GnRH analogue treatment on anterior pituitary hormones in children with central precocious puberty
  31. Anti-Müllerian hormone in children: a ten-year prospective longitudinal study (EarlyBird 39)
  32. Patient reports
  33. A rare cause of fatal pulmonary alveolar proteinosis: Niemann-Pick disease type C2 and a novel mutation
  34. Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old girl with Graves’ disease
  35. Dyshormonogenesis seems to be more frequent in a group of Cameroonian children with congenital hypothyroidism
  36. Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up
  37. Cerebral infarction and femoral venous thrombosis detected in a patient with diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G mutations
  38. Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency
  39. Short communication
  40. Tamoxifen-associated hirsutism: an unusual side effect in a 5-year-old girl with McCune-Albright syndrome
  41. Letters to the Editor
  42. Psychiatric disorders are associated with increased risk for developing hyponatraemia in children
  43. Rett syndrome and precocious puberty association
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 1.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2015-0089/html
Scroll to top button