, Volume 59, Issue 1, pp 164–174 | Cite as

Adiponectin and vitamin D-binding protein are independently associated at birth in both mothers and neonates

  • Spyridon N. Karras
  • Stergios A. Polyzos
  • Danforth A. Newton
  • Carol L. Wagner
  • Bruce W. Hollis
  • Jody van den Ouweland
  • Erdinc Dursun
  • Duygu Gezen-Ak
  • Kalliopi Kotsa
  • Cedric Annweiler
  • Declan P. Naughton
Original Article



Adult body fat is associated with birth anthropometry, suggesting a role for metabolic regulators including vitamin D and the adipokines—adiponectin and irisin—which have been reported to interact but, as yet, data remain controversial.


To study (i) the relationship between vitamin D, its binding protein (VDBP) and the adipokines, adiponectin, and irisin in mothers and neonates at birth and (ii) their effects on neonate anthropometric outcomes.


Cross-sectional study for healthy mothers with full-term and uncomplicated births.


Primary care.


Seventy pairs of newly delivered neonates and their mothers.

Main outcomes features

Biochemical markers from maternal and cord: VDBP, adiponectin, irisin, calcium, albumin, parathyroid hormone, 25OHD, 1,25(OH)2D. Maternal demographic and social characteristics and neonate anthropometric parameters were recorded.


Maternal VDBP levels (364.1 ± 11.9 μg/ml) demonstrated a strong positive correlation with maternal adiponectin (4.4 ± 0.4 μg/ml) and irisin (308.8 ± 50.8 ng/ml) concentrations, which remained significant (p < 0.001 and p < 0.041, respectively) after adjustment with multiple parameters, including weeks of gestation, maternal age, and BMI. The finding of a strong association of VDBP (355.3 ± 29.2 μg/ml) and adiponectin (11.9 ± 2.0 μg/ml) but not irisin (174.4 ± 26.0 ng/ml) was also evident in neonates (p = 0.03 and p = 0.94, respectively). No association was observed in both maternal and neonatal vitamin D, adiponectin, and irisin.


The main findings of this study are (i) the perspective of a potential independent interaction of VDBP and adiponectin in both mothers and neonates and (ii) the lack of a causative model effect of both maternal/neonatal vitamin D status and adipokine profile on neonatal anthropometry at birth, as a surrogate marker of future metabolic health of the offspring.


Adipokines Adiponectin Irisin Neonates Vitamin D Vitamin D-binding protein 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    A.S. Dusso, A.J. Brown, E. Slatopolsky, Vitamin D. Am. J. Physiol. Ren. Physiol. 289, F8–F28 (2005)CrossRefGoogle Scholar
  2. 2.
    M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357, 266–281 (2007)CrossRefPubMedGoogle Scholar
  3. 3.
    K. Rajakumar, S.L. Greenspan, S.B. Thomas, F.M. Holick, Solar ultraviolet radiation and vitamin D: a historical perspective. Am. J. Public Health 97, 1746–1754 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    G. Block, C.M. Dresser, A.M. Hartman, M.D. Carroll, Nutrient sources in the American diet: quantitative data from the NHANES II survey. I. Vitamins and minerals. Am. J. Epidemiol. 122(1), 13–26 (1985)CrossRefPubMedGoogle Scholar
  5. 5.
    D.E. Prosser, G. Jones, Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 29, 664–673 (2004)CrossRefPubMedGoogle Scholar
  6. 6.
    S.N. Karras, H. Fakhoury, G. Muscogiuri, W.B. Grant, J.M. van den Ouweland, A.M. Colao, K. Kotsa, Maternal vitamin D levels during pregnancy and neonatal health: evidence to date and clinical implications. Ther. Adv. Musculoskelet. Dis. 8(4), 124–135 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    L.L. Ritterhouse, R. Lu, H.B. Shah, J.M. Robertson, D.A. Fife, H.T. Maecker, H. Du, C.G. Fathman, E.F. Chakravarty, R.H. Scofield, D.L. Kamen, J.M. Guthridge, J.A. James, Vitamin d deficiency in a multiethnic healthy control cohort and altered immune response in vitamin D deficient European-American healthy controls. PLoS ONE 9(4), e94500 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    C. Palacios, L. Gonzalez, Is vitamin D deficiency a major global public health problem? J. Steroid Biochem. Mol. Biol. 144(Pt A), 138–145 (2014)CrossRefPubMedGoogle Scholar
  9. 9.
    J.L. Jackson, S.E. Judd, B. Panwar, V.J. Howard, V.G. Wadley, N.S. Jenny, O.M. Gutiérreza, Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults. J. Clin. Trans. Endocrinol. 5, 21–25 (2016)Google Scholar
  10. 10.
    R. Dhaliwal, M. Mikhail, M. Feuerman, J.F. Aloia, The vitamin D dose response in obesity. Endocr. Pract. 20, 1258–1264 (2014)PubMedGoogle Scholar
  11. 11.
    M. Mangin, R. Sinha, K. Fincher, Inflammation and vitamin D: the infection connection. Inflamm. Res. 63, 803–819 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    M. Grammatiki, E. Rapti, S. Karras, R.A. Ajjan, K. Kotsa, Vitamin D and diabetes mellitus: causal or casual association? Rev. Endocr. Metab. Disord. (2017).
  13. 13.
    I. Shah, A. Petroczi, D.P. Naughton, Exploring the role of vitamin D in type 1 diabetes, rheumatoid arthritis, and Alzheimer disease: new insights from accurate analysis of 10 forms. J. Clin. Endocrinol. Metab. 99, 808–816 (2014)CrossRefPubMedGoogle Scholar
  14. 14.
    L.J. Black, D. Anderson, M.W. Clarke, A.L. Ponsonby, R.M. Lucas, Ausimmune Investigator Group, Analytical bias in the measurement of serum 25-hydroxyvitamin D concentrations impairs assessment of vitamin D status in clinical and research settings. PLoS ONE 10, e0135478 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    R.F. Chun, B.E. Peercy, E.S. Orwoll, C.M. Nielson, J.S. Adams, M. Hewison, Vitamin D and DBP: the free hormone hypothesis revisited. J. Steroid Biochem. Mol. Biol. 144(Pt A), 132–137 (2014)CrossRefPubMedGoogle Scholar
  16. 16.
    J.R. Delanghe, R. Speeckaert, M.M. Speeckaert, Behind the scenes of vitamin D binding protein: more than vitamin D binding. Best. Pract. Res. Clin. Endocrinol. Metab. 29(5), 773–786 (2015)CrossRefPubMedGoogle Scholar
  17. 17.
    T. Kadowaki, T. Yamauchi, Adiponectin and adiponectin receptors. Endocr. Rev. 26(3), 439–451 (2005)CrossRefPubMedGoogle Scholar
  18. 18.
    G.E. Walker, R. Ricotti, M. Roccio, S. Moia, S. Bellone, F. Prodam, G. Bona, Pediatric obesity and vitamin D deficiency: a proteomic approach identifies multimeric adiponectin as a key link between these conditions. PLoS ONE 9(1), e83685 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    M. Dinca, M.C. Serban, A. Sahebkar, D.P. Mikhailidis, P.P. Toth, S.S. Martin, M.J. Blaha, M. Blüher, C. Gurban, P. Penson, E.D. Michos, A.V. Hernandez, S.R. Jones, M. Banach; for Lipid Blood Pressure Meta-analysis Collaboration LBPMC Group, Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials. Pharmacol. Res. 107, 360–371 (2016)CrossRefPubMedGoogle Scholar
  20. 20.
    M.A. Abbas, Physiological functions of Vitamin D in adipose tissue. J. Steroid Biochem. Mol. Biol. 165(Pt B), 369–381 (2017)CrossRefPubMedGoogle Scholar
  21. 21.
    E. Keleş, F.F. Turan, Evaluation of cord blood irisin levels in term newborns with small gestational age and appropriate gestational age. Springerplus 5(1), 1757 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    N.M. Al-Daghri, S. Rahman, S. Sabico, O.E. Amer, K. Wani, O.S. Al-Attas, M.S. Alokail, Impact of vitamin D correction on circulating irisin: a 12 month interventional study. Int J. Clin. Exp. Med. 9(7), 13086–13092 (2016)Google Scholar
  23. 23.
    J. Simpson, A.D. Smith, A. Fraser, N. Sattar, R.S. Lindsay, S.M. Ring, K. Tilling, G. Davey Smith, D.A. Lawlor, S.M. Nelson, Programming of adiposity in childhood and adolescence: associations with birth weight and cord blood adipokines. J. Clin. Endocrinol. Metab. 102(2), 499–506 (2017)PubMedGoogle Scholar
  24. 24.
    J.J. McGrath, D. Keeping, S. Saha, D.C. Chant, D.E. Lieberman, M.J. O’Callaghan, Seasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape? Early Hum. Dev. 81, 609–618 (2005)CrossRefPubMedGoogle Scholar
  25. 25.
    J.D. Keeping. Determinants and Components of Size at Birth (University of Aberdeen, Scotland, 1981)Google Scholar
  26. 26.
    Calcium, Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D, A.C. Ross, C.L. Taylor, A.L. Yaktine, H.B. Del Valle, Dietary Reference Intakes for Calcium and Vitamin D. Dietary Reference Intakes for Calcium and Vitamin D (National Academies Press (US), Washington, DC, 2011)Google Scholar
  27. 27.
    Z.Q. Zhang, Q.G. Lu, J. Huang, C.Y. Jiao, S.M. Huang, L.M. Mao, Maternal and cord blood adiponectin levels in relation to post-natal body size in infants in the first year of life: a prospective study. BMC Pregnancy Childbirth 16(1), 189 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Y. Kotani, I. Yokota, S. Kitamura, J. Matsuda, E. Naito, Y. Kuroda, Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight. Clin. Endocrinol. (Oxf.) 61(4), 418–423 (2004)CrossRefGoogle Scholar
  29. 29.
    M. Hernandez-Trejo, G. Garcia-Rivas, A. Torres-Quintanilla, E. Laresgoiti-Servitje, Relationship between irisin concentration and serum cytokines in mother and newborn. PLoS ONE 11, e0165229 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    R. Bouillon, H. van Baelen, P. de Moor, The measurement of the vitamin D-binding protein in human serum. J. Clin. Endocrinol. Metab. 45, 225–231 (1977)CrossRefPubMedGoogle Scholar
  31. 31.
    L.C. Pop, S.A. Shapses, B. Chang, W. Sun, X. Wang, Vitamin D –binding protein in healthy pre- and postmenopausal women:relationship with estradiol concentrations. Endocr. Pract. 21(8), 936–942 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Z. Krivošíková, M. Gajdoš, K. Šebeková, Vitamin D levels decline with rising number of cardiometabolic risk factors in healthy adults: Association with adipokines, inflammation, oxidative stress and advanced glycation markers. PLoS ONE 10(6), e0131753 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    A. Vaidya, J.S. Williams, J.P. Forman, The independent association between 25-hydroxyvitamin D and adiponectin and its relation with BMI in two large cohorts: the NHS and the HPFS. Obesity (Silver Spring). 20(1), 186–191 (2012)CrossRefPubMedGoogle Scholar
  34. 34.
    R. McManus, K. Summers, B. de Vrijer, N. Cohen, A. Thompson, I. Giroux, Maternal, umbilical arterial and umbilical venous 25-hydroxyvitamin D and adipocytokine concentrations in pregnancies with and without gestational diabetes. Clin. Endocrinol. (Oxf.) 80(5), 635–641 (2014)CrossRefGoogle Scholar
  35. 35.
    Z.C. Luo, A.M. Nuyt, E. Delvin, W.D. Fraser, P. Julien, F. Audibert, I. Girard, B. Shatenstein, C. Deal, E. Grenier, C. Garofalo, E. Levy, Maternal and fetal leptin, adiponectin levels and associations with fetal insulin sensitivity. Obesity (Silver Spring). 21(1), 210–216 (2013)CrossRefPubMedGoogle Scholar
  36. 36.
    E. Sivan, S. Mazaki-Tovi, C. Pariente, Y. Efraty, E. Schiff, R. Hemi, H. Kanety, Adiponectin in human cord blood: relation to fetal birth weight and gender. J. Clin. Endocrinol. Metab. 88(12), 5656–5660 (2003).CrossRefPubMedGoogle Scholar
  37. 37.
    R. Morley, J.B. Carlin, J.A. Pasco, J.D. Wark, Maternal 25 hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J. Clin. Endocrinol. Metab. 91(3), 906–912 (2006)CrossRefPubMedGoogle Scholar
  38. 38.
    C.L. Wagner, B.W. Hollis, K. Kotsa, H. Fakhoury, S.N. Karras, Vitamin D administration during pregnancy as prevention for pregnancy, neonatal and postnatal complications. Rev. Endocr. Metab. Disord. (2017).
  39. 39.
    S. Karras, P. Anagnostis, C. Annweiler, D.P. Naughton, A. Petroczi, E. Bili, V. Harizopoulou, B.C. Tarlatzis, A. Persinaki, F. Papadopoulou, D.G. Goulis, Maternal vitamin D status during pregnancy: the Mediterranean reality. Eur. J. Clin. Nutr. 68, 864–869 (2014)CrossRefPubMedGoogle Scholar
  40. 40.
    S. Karras, S.A. Paschou, E. Kandaraki, P. Anagnostis, C. Annweiler, B.C. Tarlatzis, B.W. Hollis, W.B. Grant, D.G. Goulis, Hypovitaminosis D in pregnancy in the Mediterranean region: a systematic review. Eur. J. Clin. Nutr. 70(9), 979–986 (2016)CrossRefPubMedGoogle Scholar
  41. 41.
    C.S. Kovacs, The role of vitamin D in pregnancy and lactation: insights from animal models and clinical studies. Annu. Rev. Nutr. 32, 97–123 (2012)CrossRefPubMedGoogle Scholar
  42. 42.
    S.N. Karras, I. Shah, A. Petroczi, D.G. Goulis, H. Bili, F. Papadopoulou, V. Harizopoulou, B.C. Tarlatzis, D.P. Naughton, An observational study reveals that neonatal vitamin D is primarily determined by maternal contributions: implications of a new assay on the roles of vitamin D forms. Nutr. J. 12, 77 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    C.C. Grant, A.W. Stewart, R. Scragg, T. Milne, J. Rowden, A. Ekeroma, C. Wall, E.A. Mitchell, S. Crengle, A. Trenholme, J. Crane, C.A. Camargo Jr, Vitamin D during pregnancy and infancy and infant serum 25-hydroxyvitamin D concentration. Pediatrics 133, e143–e153 (2014)CrossRefPubMedGoogle Scholar
  44. 44.
    C.L. Wagner, B.W. Hollis, K. Kotsa, H. Fakhoury, S.N. Karras, Vitamin D administration during pregnancy as prevention for pregnancy, neonatal and postnatal complications. Rev. Endocr. Metab. Disord. 18(3), 307–322 (2017).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Spyridon N. Karras
    • 1
  • Stergios A. Polyzos
    • 2
  • Danforth A. Newton
    • 3
  • Carol L. Wagner
    • 3
  • Bruce W. Hollis
    • 3
  • Jody van den Ouweland
    • 4
  • Erdinc Dursun
    • 5
  • Duygu Gezen-Ak
    • 5
  • Kalliopi Kotsa
    • 1
  • Cedric Annweiler
    • 6
    • 7
    • 8
  • Declan P. Naughton
    • 9
  1. 1.Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical SchoolAristotle University of Thessaloniki, AHEPA HospitalThessalonikiGreece
  2. 2.First Department of Pharmacology, Medical SchoolAristotle University of ThessalonikiThessalonikiGreece
  3. 3.Division of Neonatology, Department of PediatricsMedical University of South CarolinaCharlestonUSA
  4. 4.Department of Clinical ChemistryCanisius Wilhelmina HospitalNijmegenThe Netherlands
  5. 5.Department of Medical Biology, Cerrahpasa Faculty of MedicineIstanbul UniversityIstanbulTurkey
  6. 6.Department of Neuroscience, Division of Geriatric MedicineAngers University HospitalAngersFrance
  7. 7.University Memory Clinic, UPRES EA 4638University of Angers, UNAMAngersFrance
  8. 8.Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and DentistryUniversity of Western OntarioLondonCanada
  9. 9.School of Life Sciences, Pharmacy and ChemistryKingston UniversitySurreyUK

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