1. Iron-deficiency Anaemia Faith Henning (ST3)

2. Epidemiology  Iron-deficiency anaemia is as prevalent in infants in inner city populations as it is in developing countries.  Evidence has supported a causal link between iron-deficiency anaemia and developmental delay.  Over the past 20 years, the US has successfully reduced the incidence in iron-deficiency anaemia in socioeconomically disadvantaged groups. The UK lags behind.  It has been suggested that 12% of 1.5-2 year-olds have IDA and 28% have iron-deficiency in the UK.

3. Hb course  Mean Hb in infants falls by the 8 th week of life due to adjustment in coming from a relatively hypoxic intrauterine environment (approx 110g/dl).  This level rises to approx 125g/dl by 4 months of age. By this stage, neonatal iron stores will have been halved and exogenous iron is essential.  Hb should gradually increase during childhood to 135g/dl in pre-adolescents.  Iron-defiency without anaemia suggests impaired haemoglobin synthesis but no significant fall in haemoglobin concentration.  In these cases, iron-deficiency tends to be detected in low serum ferritin, low MCV or response to oral iron supplementation.  0.8mg iron/day is required from the diet during infancy.

4. IDA and Developmental Delay  Interpretation of data has been difficult as confounding factors exist with IDA occurring in association with psychosocial and economic deprivation.  Additionally, quantifying developmental delay has proved a challenge.  Most studies have used Bayley’s assessment, which has shown to be more impacted than single motor scale assessments.  Largely IDA age-matched children have scored 0.5-1.5 standard deviations below their peers in Bayley’s but still lie within normal range.

5. RCTs  There have been three main groups: 1.Short-term studies, looking at improvement in outcomes after 7-15 days of treatment (oral or im iron) 1.Assessment in long-term treatment of iron deficiency. 1.Longitudinal study with random assignment to iron- supplemental formula and non-iron supplemental formula.

6. Short-term studies  No statistically significant difference in the short-term period between oral and intramuscular iron supplementation.  In a larger study, Lozoff et al, showed an improvement in bayley’s scores in anaemic children who received supplementation but no difference in non-anaemic, iron deficient individuals.

7. Long-term studies  Most longer term studies have concluded favour of significant effect.  In a study from inner city Birmingham, iron deficient toddlers with anaemia were randomly assigned to receive either iron and vitamin C, or vitamin C (as placebo) for 3/12.  31% of the treated group, but only 12% of placebo group, achieved an average rate of development, assessed by the Denver screening test.  The expected rate of development was achieved by 37% of those whose Hb rose by at least 20 g/1, compared with only 16% whose concentration rose by less than 20 g/1.  Some children who showed a haematological response to iron, failed to show an improvement in development, suggesting that factors in addition to iron may be responsible for slower development in inner city children

8. Indonesian Study  12–18 month old Indonesian infants with IDA were randomly allocated to receive oral iron or placebo for 4/12.  Before treatment, the infants with IDA had scores on Bayleys mental and motor scales that were significantly lower than the other two groups.  After treatment, deficits in both mental and motor scales were reversed in the IDA infants who received iron, but were unchanged in the placebo group.  Changes in the scores of the iron deficient, non-anaemic, and iron sufficient subjects were unchanged.  It is possible however, that sample size in this and other studies, was not large enough to detect a developmental delay which was smaller than in the IDA group. Moreover, these data, and those of Aukett et al 8 suggest that IDA among 12–18 month olds causes a developmental delay which can be reversed by treatment.

9. Canadian study  Socioeconomically disadvantaged Native American infants aged 0–2 months, were randomly allocated to receive either an iron fortified or a non-iron fortified formula from birth.  They were followed until 15 months of age.  Stable deterioration in iron status in the group receiving the non- iron supplemented formula by 6 months of age was associated with impaired psychomotor development at 9 months, although this was no longer significant by 15 months.  This corresponded to an improvement in some indices of iron status. Mental development and behaviour were unchanged.

10. Conclusion  Collectively, there is evidence that IDA is causally related to developmental delay but associations between iron- deficiency in non-anaemic patients, is less convincing.  The above is seen to be reversible by long-term iron treatment.

11. Mechanism?  Early iron deficiency may have specific effects on the central nervous system.  Hypotheses from rats: A brief period of iron deficiency during the brain growth spurt (10–28 days) causes a lasting deficit in brain iron, which persists into adulthood despite correction of the anaemia. There is altered neurotransmitter function which effectively reduced serotonin degradation which induces drowsiness, altered attention and cognitive function. Myelination may also be adversely affected. Marked changes in the fatty acid composition of myelin specific lipids, such as cerebrosides, are found that are consistent with reduced desaturase activity.

12. Questions?