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• Re: Anaemia in hospitalised infants: Iron deficiency?
  Cameron C. Grant
  Published on: 22 March 2016
• Anema in hospitalized infants: Iron deficiency?
  Tomas K Walter
  Published on: 22 March 2016

• Published on: 22 March 2016

  Re: Anaemia in hospitalised infants: Iron deficiency?

  • Cameron C. Grant, Paediatrician
  • Other Contributors:
    • Clare R. Wall, Paediatric Nutritionist, Massey University

  Dear Editor,

  Walter and Olivares question whether the anaemia present in the enrolled children was due to iron deficiency or due to the acute infection that precipitated their admission to hospital. They state that anaemia and all other measures of iron normalize without therapy. Both their reference to their earlier work and other published literature do not support this statement.

  Their referenced study...

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  Dear Editor,

  Walter and Olivares question whether the anaemia present in the enrolled children was due to iron deficiency or due to the acute infection that precipitated their admission to hospital. They state that anaemia and all other measures of iron normalize without therapy. Both their reference to their earlier work and other published literature do not support this statement.

  Their referenced study of 93 infants showed that while haemoglobin and iron saturation decreased and ferritin increased following measles immunisation, mean cell volume did not change significantly.[1] Similarly no decrease in mean cell volume was seen in a study of anaemia associated with Haemophilus influenzae meningitis nor in a study that determined the influence of mild prior infection on haemoglobin and other measures of iron deficiency.[2,3] Therefore, although both iron deficiency and acute infection cause anaemia and low iron saturation, only iron deficiency results in changes in red cell size.

  In our manuscript we reported the data collected on infants with iron deficiency anaemia who were randomised to treatment with iron medicine, iron fortified milk or iron fortified milk formula. We showed that these infants had iron deficiency anaemia on admission and that the proportion with iron deficiency anaemia decreased significantly with each intervention. The enrolment definition of iron deficiency included a measure of red cell size (red cell distribution width) hence we believe these children had anaemia secondary to iron deficiency rather than infection. The significant increase in mean cell volume in the iron- follow-on and iron-milk groups also demonstrates that iron status improved in infants receiving these interventions.

  We also collected data on 70 infants hospitalised with acute illnesses who were not treated for iron deficiency but who did have a follow up blood test performed three months later. This group included infants with iron deficiency anaemia whose caregivers did not want them randomised but did want a follow-up measure of iron status, infants with anaemia but not iron deficiency, and infants with haemoglobin (110 to 119 g/L) and red cell distribution width (13.6 to 14.5%) measurements that were in the lower range of normal.

  On admission, in comparison to the infants with iron deficiency anaemia, these infants had higher mean haemoglobin concentrations (112 vs. 102 g/L, p<0.001), mean cell volumes (76 vs. 71 fL, p<0.001) and median iron saturations (10 vs. 5%, p<0.001), lower median red cell distribution width (15 vs. 16%, p=0.001) and median c-reactive protein concentrations (6 vs. 18 mg/L, p=0.003), and median serum ferritin concentrations that did not differ (36 vs. 42 ug/L, p=0.49). In contrast to the infants treated for iron deficiency anaemia the mean cell volume at follow-up was not significantly different from that at enrolment (Table). Thus abnormal values for parameters that measure red cell size can be used to differentiate iron deficiency anaemia from anaemia secondary to acute infection and to demonstrate response to iron therapy.

  Table. Enrolment and follow up measures of iron status in 70 infants 9 to 23 months of age hospitalised with acute illness who did not receive treatment for iron deficiency.
  

  Variable	Enrolment Median (5, 95th centile)	Follow up Median (5, 95th centile)	Mean difference (95% CI)*
  Haemoglobin (g/L)	113 (97, 125)	119 (106, 133)	7 (5, 10)
  Ferritin (?g/L)	36 (5, 207)†	17 (4, 60)‡	102 (-226, 41)
  Iron saturation (%)	10.5 (3.0, 24.0)	15.0 (3.0, 30.0)§	-5.2 (2.8, 7.6)
  Red cell distribution width (%)	15.0 (14.0, 17.7)	15.0 (13.8, 17.0)||	-0.3 (-0.6, 0.01)
  Mean cell volume (fL)	76 (66, 83)	76 (65, 84)	-0.7 (-1.6, 0.3)
  C-reactive protein mg/L	6 (2, 141)¶	2 (2, 54)**	-18 (-32, -5)

  
  * Except for haemoglobin are geometric means and confidence intervals
  † n = 68
  ‡ n = 67
  § n = 69
  || n = 68
  ¶ n = 61
  ** n = 64

  It is important to remember that infants with prior infections show a greater haemoglobin response to iron therapy than infants with no preceding history of recent illness. This has been demonstrated in a placebo controlled trial.[3] Thus acute infections, which are common in infancy, may cause iron deficiency. Therefore infants hospitalised with acute infection are likely to be a group at increased risk of iron deficiency anaemia. It is important to try to identify these infants and provide additional iron to enable normalisation of iron status as their iron absorption improves with resolution of the acute infection.

  Clare R. Wall, Paediatric Nutritionist, Massey University
  Cameron C. Grant, Paediatrician, University of Auckland

  References:

  1. Olivares M, Walter T, Osorio M, Chadud P, Schlesinger L. Anaemia of a mild viral infection: the measles vaccine as a model. Pediatrics 1989;84:851-5.

  2. O'Brien RT, Santos JI, Glasgow L, Landaw SA. Pathophysiologic basis for anaemia associated with Haemophilus influenzae meningitis: preliminary observations. Journal Pediatr 1981;98:928-31.

  3. Reeves JD, Yip R, Kiley VA, Dallman PR. Iron deficiency in infants: the influence of mild antecedent infection. J Pediatr 1984;105:874-9.

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  Conflict of Interest:
  None declared.

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• Published on: 22 March 2016

  Anema in hospitalized infants: Iron deficiency?

  • Tomas K Walter, Pediatric hematologist
  • Other Contributors:
    • Manuel Olivares

  Dear Editor,

  Wall et al. treated infants with alleged iron deficiency anemia with several iron vehicles. However, anemia in hospitalized ill infants is mostly not due to iron deficiency, but to anemia of infection, present even with mild infections. That's why they find a paradoxical decrease of serum ferritin that rises with infection to fall after convalescence. Anemia and all other measures of iron infection no...

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  Dear Editor,

  Wall et al. treated infants with alleged iron deficiency anemia with several iron vehicles. However, anemia in hospitalized ill infants is mostly not due to iron deficiency, but to anemia of infection, present even with mild infections. That's why they find a paradoxical decrease of serum ferritin that rises with infection to fall after convalescence. Anemia and all other measures of iron infection normalize without therapy.[1] Thus, these results cannot be attributed to treatment. C reactive protein is not completely reliable.

  References

  1. Olivares, M, Walter T et al. Anemia of a mild viral infection: the measles vaccine a model. Pediatrics 84(1) 851-855, 1989.

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  Conflict of Interest:
  None declared.

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