Maternal vitamin deficiencies and bone disorders in infants

Main Article Content

Colin R Paterson Elspeth C Paterson

Abstract

Recent publications have again drawn attention to long bone fractures in newborn infants with severe vitamin D deficiency due to maternal subnutrition.  This is a reminder of the complete dependence of an infant on maternal nutrition; the bones that fracture in early infancy are formed during gestation.


 


This review covers previous reports of congenital rickets including the difficulties in diagnosis, not least because there may be none of the usual radiological hallmarks of rickets.  It also outlines ways of making a retrospective diagnosis of vitamin D deficiency after the infant’s biochemical findings have become normal.


 


It is likely that similar considerations apply to vitamin C deficiency.  Although overt scurvy is uncommon it is clear that vitamin C subnutrition is widespread even in Western countries.  Vitamin C has many roles but among them is its requirement in the formation of collagen.  Thus it is not surprising that fractures and intracranial bleeding are well-recognised features of vitamin C deficiency.


 


Maternal subnutrition of vitamin D and vitamin C are important conditions in the wide differential diagnosis of unexplained fractures and fracture-like lesions in infancy.

Article Details

How to Cite
PATERSON, Colin R; PATERSON, Elspeth C. Maternal vitamin deficiencies and bone disorders in infants. Medical Research Archives, [S.l.], v. 7, n. 11, nov. 2019. ISSN 2375-1924. Available at: <https://journals.ke-i.org/index.php/mra/article/view/1995>. Date accessed: 08 dec. 2019. doi: https://doi.org/10.18103/mra.v7i11.1995.
Section
Research Articles

References

1. Albertini F, Marquant E, Raynaud R, Lacroze V. Two cases of fractures in neonates associated with maternofetal vitamin D deficiency. Arch Pédiatr 2019; 26: 361-4.

2. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest 2006; 116: 2062-72.

3. Högberg U, Winbo J, Fellman V. Population-based register study of children born in Sweden from 1997 to 2014 showed an increase in rickets during infancy. Acta Paediatr 2019 in press

4. Karras SN, Anagnostis P, Bili E et al. Maternal vitamin D status in pregnancy and offspring bone development: the unmet needs of vitamin D era. Osteoporos Int 2014; 25: 795-805.

5. Cadario F, Savastio S, Magnani C et al. High prevalence of vitamin D deficiency in native versus migrant mothers and newborns in the north of Italy: a call to act with a stronger prevention program. Plos One 2015; 10: e0129586.

6. Darling AL, Hart KH, Macdonald HM et al. Vitamin D deficiency in UK South Asian women of child-bearing age: a comparative longitudinal investigation with UK Caucasian women. Osteoporos Int 2013; 24: 477-88.

7. Salameh K, Al-Janahi NSA, Reedy AM, Dawodu A. Prevalence and risk factors for low vitamin D status among breast-feeding mother-infant dyads in an environment with abundant sunshine. Int J Women’s Health 2016; 8: 529-35.

8. Hauta-alus HH, Holmlund-Suila EM, Rita HJ et al. Season, dietary factors, and physical activity modify 25-hydroxyvitamin D concentration during pregnancy. Eur J Nutr 2018; 57: 1369-79.

9. Wegienka G, Kaur H, Sangha R, Casidy-Bushrow AE. Maternal cord blood vitamin D correlations vary by maternal levels. J Pregnancy 2016; 7474192.

10. Emmerson AJB, Dockery K, Mughal MZ et al. Vitamin D status of white pregnant women and infants at birth and 4 months in north-west England: a cohort study. Matern Child Nutr 2017; e12453.

11. Kasai MS, Cafeo FR, Affonso-Kaufman FA et al. Vitamin D plasma concentrations in pregnant women and their preterm newborns. BMC Pregnancy Childbirth 2018; 18: 412.

12. Weernink MGM, van Wijk RM, Groothuis-Oudshoorn CGM et al. Insufficient vitamin D supplement use during pregnancy and early childhood: a risk factor for positional skull deformation. Matern Child Nutr 2016; 12: 177-88.

13. Högler W. Complications of vitamin D deficiency from the foetus to the infant: one cause, one prevention, but who’s responsibility? Best Practice & Research Clinical Endocrinology & Metabolism 2015; 29: 385-98.

14. Çetinkaya M, Çekmez F, Erener-Ercan T et al. Maternal / Neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms? J Perinatol 2015; 35: 813-7

15. Munns CF, Shaw N, Kiely M et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab 2016; 101: 394-415.

16. Cooper C, Harvey NC, Bishop NJ et al. Maternal gestational vitamin D supplementation and offspring bone health: a multicentre randomised, double-blind, placebo-controlled trial (MAVIDOS). Lancet Diabetes Endocrinol 2016; 4: 393-402.

17. Paterson CR, Ayoub D. Congenital rickets due to vitamin D deficiency in the mothers. Clin Nutr 2015; 34: 793-8.

18. Elidrissy ATH. The return of congenital rickets, are we missing occult cases? Calcif Tissue Int 2016; 99: 227-36

19. Paterson CR. Fractures in rickets due to vitamin D deficiency. Current Orthopaedic Practice 2015; 26: 261-4.

20. Keller KA, Barnes PD. Rickets vs abuse: a national and international epidemic. Pediatr Radiol 2008; 38: 1210-6.

21. Paterson CR. Vitamin D deficiency rickets and allegations of non-accidental injury. Acta Paediatr 2009; 98: 2008-12.

22. Cannell JJ, Holick MF. Multiple unexplained fractures in infants and child physical abuse. J Steroid Biochem Mol Biol 2018; 175: 18-22.

23. Högberg U, Andersson J, Högberg G, Thiblin I. Metabolic bone disease risk factors strongly contributing to long bone and rib fractures in early infancy: a population register study. Plos One 2018; 13: e0208033.

24. Karpiński M, Galicka A, Milewski R et al. Association between vitamin D receptor polymorphism and serum vitamin D levels in children with low-energy fractures. J Amer Coll Nutr 2017; 36: 64-71

25. Fabricant PD, Dy CJ, MacLaren SH et al. Low vitamin D levels in children with fractures: a comparative cohort study. HSSJ 2015; 11: 249-57.

26. Al-Daghri NM, Aljohani N, Rahman S et al. Serum 25-hydroxyvitamin D status among Saudi children with and without a history of fracture. J Endocrinol Invest 2016; 39: 25-30.

27. El-Sakka A, Penon C, Hegazy A et al. Evaluating bone health in Egyptian children with forearm fractures: a case control study. Int J Pediatr 2016: 7297092.

28. Schilling S, Wood JN, Levine MA et al. Vitamin D status in abused and nonabused children younger than 2 years old with fractures. Pediatrics 2011; 127: 835-41.

29. Paterson CR. Vitamin D deficiency and fractures in childhood. Pediatrics 2011; 127: 973-4.

30. Perez-Rossello JM, Feldman HA, Kleinman PK et al. Rachitic changes, demineralization, and fracture risk in healthy infants and toddlers with vitamin D deficiency. Radiology 2012; 262: 234-41.

31. Ayoub D. Fractures: abuse or rickets? Radiology 2012; 264: 614-5.

32. Hyman CJ. Fractures: abuse or rickets? Radiology 2012; 264: 615.

33. Servaes S, States L, Wood J et al. Rachitic change and vitamin D status in young children with fractures. Skeletal Radiol 2019 in press

34. Heaney RP, Holick MF. Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res 2011; 26: 455-7.

35. Lai JKC, Lucas RM, Clements MS et al. Assessing vitamin D status: pitfalls for the unwary. Mol Nutr Food Res 2010; 54: 1062-71.

36. Snellman G, Melhus H, Gedeborg R et al. Determining vitamin D status: a comparison between commercially available assays. Plos One 2010; 5: e11555.

37. Dirks NF, Ackermans MT, Lips P et al. The when, what & how of measuring vitamin D metabolism in clinical medicine. Nutrients 2018; 10: 482

38. Haarburger D, Hoffman M, Erasmus RT, Pillay TS. Relationship between vitamin D, calcium and parathyroid hormone in Cape Town. J Clin Pathol 2009; 62: 567-9.

39. Atapattu N, Shaw N, Högler W et al. Relationship between serum 25-hydroxyvitamin D and parathyroid hormone in the search for a biochemical definition of vitamin D deficiency in children. Pediatr Res 2013; 74: 552-6.

40. Narchi H, Kochiyil J, Zayed R et al. Longitudinal study of vitamin D status in the 1st 6 months of life. Ann Trop Paediatr 2011; 31: 225-30.

41. Brembeck P, Winkvist A, Bååth M et al. Determinants of changes in vitamin D status postpartum in Swedish women. Br J Nutr 2016; 115: 422-30.

42. Kvaskoff D, Ko P, Simila HA, Eyles DW. Distribution of 25-hydroxyvitamin D3 in dried blood spots and implications for its quantitation by tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2012; 901:47-52.

43. Makowski AJ, Rathmacher JA, Horst RL. Simplified 25-hydroxyvitamin D standardization and optimization in dried blood spots by LC-MS/MS. J AOAC Int 2017; 100: 1328-36

44. Kaushal S, Raisingani M, David R, Shah B. Spiral fracture in young infant causing a diagnostic dilemma: nutritional rickets vs child abuse. Case Rep Pediatr 2017: 7213629.

45. Root AW, Vargas A, Duckett GE, Hough G. Hypocalcemia and hypovitaminosis D in an infant from Florida, the sunshine state. J Fla Med Assoc 1980; 67: 933-4.

46. Ahmed AM, Atiq M, Iqbal J et al. Vitamin D deficiency rickets in breast-fed infants presenting with hypocalcaemic seizures. Acta Paediatr 1995; 84: 941-2.

47. Liu D. Pathological and X-ray study of rickets from 124 fetal and infantile autopsies. Zhonghua Yi Xue Za Zhi. 1991; 71: 385-387 (translation available).

48. Cohen MC, Offiah A, Sprigg A, Al-Adnani M. Vitamin D deficiency and sudden unexpected death in infancy and childhood: a cohort study. Pediatr Dev Pathol 2013; 16: 292-300.

49. Scheinberg I, Perry L. Does low vitamin D have a role in pediatric morbidity and mortality? An observational study of vitamin D in a cohort of 52 postmortem examinations. Pediatr Dev Pathol 2014; 17: 455-64.

50. Caffey J. Multiple fractures in the long bones of infants suffering from chronic subdural hematoma. Am J Roentgenol 1946; 56: 163-73.

51. Silverman FN. The roentgen manifestations of unrecognized skeletal trauma in infants. Am J Roentgenol 1953; 69: 413-27

52. Ablin DS, Greenspan A, Reinhart M, Grix A. Differentiation of child abuse from osteogenesis imperfecta. Am J Roentgenol 1990; 154: 1035-46

53. Kleinman PK, Marks SC, Blackbourne B. The metaphyseal lesion in abused infants: a radiologic-histopathologic study. AJR 1986; 146: 895-905.

54. Kleinman PK, Perez-Rossello JM, Newton AW et al. Prevalence of the classic metaphyseal lesion in infants at low versus high risk for abuse. AJR 2011; 197: 1005-8.

55. Wilkinson H, James J. Self-limiting neonatal primary hyperparathyroidism associated with familial hypocalciuric hypercalcaemia. Arch Dis Child 1993; 69: 319-21.

56. Grünebaum M, Horodniceanu C, Steinherz R. The radiographic manifestations of bone changes in copper deficiency. Pediatr Radiol 1980; 9: 101-4.

57. Akinseye ON, Yazdani R, Tornow KA. Imaging findings of Menkes disease, a radiographic mimic of abusive trauma. Radiol Case Rep 2019; 14: 993-6.

58. Caffey J. Pediatric X-ray Diagnosis 7th ed. Chicago: Year Book Medical Publishers, 1978.

59. Rodriguez JI, Garcia-Alix A, Palacios J, Paniagua R. Changes in long bones due to fetal immobility caused by neuromuscular disease. J Bone Joint Surg 1988; 70A: 1052-60.

60. Ayoub DM, Hyman C, Cohen M, Miller M. A critical review of the classic metaphyseal lesion: traumatic or metabolic? AJR 2014; 202: 185-98.

61. Alexander J, Gregg JEM, Quinn MW. Femoral fractures at caesarean section. Br J Obstet Gynaecol 1987; 94: 273

62. Phillips RR, Lee SH. Fractures occurring in neonatal intensive therapy units. BMJ 1990; 301: 225-6.

63. Della Grotta LM, Marine MB, Harris TL, Karmazyn B. Classic metaphyseal lesion acquired during physical therapy. Clinical Imaging 2018; 54: 100-2.

64. Perez-Rossello JM, McDonald AG, Rosenberg AE et al. Absence of rickets in infants with fatal abusive head trauma and classic metaphyseal lesions. Radiology 2015; 275: 810-21.

65. Oestreich AE. Distinguishing child abuse fractures from rickets. Pediatr Radiol 2018; 48: 305-7.

66. Quigley AJ, Stafrace S. Skeletal survey normal variants, artefacts and commonly misinterpreted findings not to be confused with non-accidental injury. Pediatr Radiol 2014; 44: 82-93.

67. Miller M, Mirkin LD. Classical metaphyseal lesions thought to be pathognomonic of child abuse are often artifacts or indicative of metabolic bone disease. Medical Hypotheses 2018; 115: 65-71.

68. Evans PR. Infantile scurvy: the centenary of Barlow’s disease. Br Med J 1983; 287: 18623.

69. Pinnell SR. Regulation of collagen synthesis. J Invest Dermatol 1982; 79: 73s-6s.

70. Sutherland GA. On haematoma of the dura mater associated with scurvy in children. Brain 1894; 17: 27-36.

71. Gilman BB, Tanzer RC. Subdural hematoma in infantile scurvy. JAMA 1932; 99: 989-91.

72. Fain O. Musculoskeletal manifestations of scurvy. Joint Bone Spine 2005; 72: 124-8.

73. Eisele PH, Morgan JP, Line AS, Anderson JH. Skeletal lesions and anemia associated with ascorbic acid deficiency in juvenile rhesus macaques. Lab Animal Sci 1992; 42: 245-9.

74. Berant M, Jacobs J. A ‘pseudo’ battered child. Clin Pediatr (Phila) 1966; 5: 230-7.

75. Paterson CR. Multiple fractures in infancy: scurvy or nonaccidental injury? Orthop Res Rev 2010; 2: 45-8.

76. Lewis D, Carpenter C, Evans A, Thomas P. Rickets and scurvy presenting in a child as apparent non accidental injury. Internet J Orthop Surg 2007; 4:2.

77. Paterson CR. Congenital vitamin C deficiency or fractures due to non-accidental injury? Int J Pediatr Child Health 2018; 6: 23-6.

78. Hagel AF, Albrecht H, Dauth W et al. Plasma concentrations of ascorbic acid in a cross section of the German population. J Int Med Res 2017; 46: 168-74.

79. Robitaille L, Hoffer LJ. A simple method for plasma total vitamin C analysis suitable for routine clinical laboratory use. Nutr J 2016; 15: 40.

80. Paterson CR. Bone disease and fractures in early childhood in Child Abuse ed Turner RA, Rogers HO, New York: Nova, 2012.

81. Paterson CR, Mole PA. Joint laxity in the parents of children with temporary brittle bone disease. Rheumatol Int 2012; 32: 2843-6.

82. Holick MF, Hossein-Nezhad A, Tabatabaei F. Multiple fractures in infants who have Ehlers-Danlos/hypermobility syndrome and or vitamin D deficiency: a case series of 72 infants whose parents were accused of child abuse and neglect. Dermato-endocrinology 2017; 9(1): e1279768.

83. Geggel RL, Pereira GR, Spackman TJ. Fractured ribs: unusual presentation of rickets in premature infants. J Pediatr 1978; 93: 680-2

84. Amir J, Katz K, Grunebaum M, Yosipovich Z et al. Fractures in premature infants. J Pediatr Orthop 1988; 8: 41-4.

85. Wei C, Stevens J, Harrison S, Mott A. Fractures in a tertiary neonatal intensive care unit in Wales. Acta Paediatr 2012; 101: 587-90.

86. Chinoy A, Mughal NZ, Padidela R. Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences. Arch Dis Child Fetal Neonatal Ed 2019; 104: F560-6

87. Droms RJ, Rork JF, McLean R et al. Menkes disease mimicking child abuse. Pediatr Dermatol 2017; 34: 13106

88. Paterson CR, Monk EA. Clinical and laboratory features of temporary brittle bone disease. J Pediatr Endocr Metab 2014; 27: 27-45.

89. Paterson CR. Temporary brittle bone disease: fractures in medical care. Acta Paediatr 2009; 98: 1935-8

90. Paterson CR, Monk EA. Long-term follow-up of children thought to have temporary brittle bone disease. Pediatr Health Med Therapeut 2011; 2: 55-8

91. Miller M, Stolfi A, Ayoub D. Findings of metabolic bone disease in infants with unexplained fractures in contested child abuse investigations: a case series of 75 infants. J Pediatr Endocrinol Metab 2019; 32: 1103-20.

Most read articles by the same author(s)

Obs.: This plugin requires at least one statistics/report plugin to be enabled. If your statistics plugins provide more than one metric then please also select a main metric on the admin's site settings page and/or on the journal manager's settings pages.