Concise description of the clinical features and management of anaemia of prematurity

1. Anaemia of
Prematurity
UBAKA CHUKWUKA

2. OUTLINE
INTRODUCTION
EPIDEMIOLOGY
PATHOPHYSIOLOGY
CLINICAL FEATURES
DIAGNOSIS
TREATMENT
CONCLUSION
REFERENCES

3. INTRODUCTION
Anaemia of prematurity (AOP) is an exaggerated, pathologic
response of the preterm infant. AOP is a normocytic,
normochromic anemia characterized by low serum EPO
levels.
Due to the overlap in the pathophysiologic mechanisms of
AOP and physiologic anaemia, some claim AOP is a
physiologic process.

4. EPIDEMIOLOGY
The risk of anaemia of prematurity (AOP) is inversely
related to gestational maturity and birthweight. As many as
half of infants of less than 32 weeks gestation develop AOP.
Race and sex have no influence on the incidence of AOP.
Testosterone is believed to be at least partially responsible
for a slightly higher hemoglobin level in male infants at
birth, but this effect is of no significance with regard to risk
of AOP.

5. PATHOPHYSIOLOGY
Physiologic anaemia usually occurs in the term at 6th to 8th week of life
with PCV reducing up to 27%. While in preterm, it usually occurs in the
3rd to 4th week of life with PCV reducing up to 21%.
This occurs due to:
1. Rapid growth and expansion of plasma volume.
2. Relative quiescence of bone marrow activity.
3. Shorter life span of fetal erythrocytes.
4. Slow transition of hepatic to renal production of erythropoietin.

6. PATHOPHYSIOLOGY
In AOP, there is an exaggerated response of the normal physiologic
process due to:
1. Relatively rapid rate of erythropoietin
2. Nutritional deficiencies of folic acid, Vit. B12, Vit. E.
3. Increased rate of haemolysis.
4. Reduced RBC life span (35-50 days) due to
Increased susceptibility to lipid peroxidation
Increased susceptibility of the cell membrane to fragmentation
Decreased levels of intracellular ATP.

7. AETIOLOGY
Three basic mechanisms for the development of anemia of prematurity
(AOP) include:
◦ inadequate RBC production
Nutritional deficiencies, reduced erythropoietin levels, infections
◦ shortened RBC life span
Incompatibility, hereditary disorders
◦ blood loss
Iatrogenic, feto-placental transfusion, twin to twin transfusion

8. CLINICAL FEATURES
Many clinical findings have been attributed to anemia of
prematurity (AOP), but they are neither specific nor
diagnostic. These symptoms may include the following:
◦ Poor weight gain despite adequate caloric intake
◦ Cardiorespiratory symptoms such as tachycardia, tachypnea, and
flow murmurs
◦ Decreased activity, lethargy, and difficulty with oral feeding
◦ Pallor
◦ Increase in apneic and bradycardic episodes, and worsened periodic
breathing

9. DIAGNOSIS
From clinical features and Blood work up
PCV of less than 21%
PBF revealing a normocytic, normochromic anaemia
Reduced erythropoietin levels
Metabolic acidemia - Increased lactic acid secondary to increased
cellular anaerobic metabolism in relatively hypoxic tissues

10. Treatment
Medical treatment options:
Blood transfusion(s)
Recombinant erythropoietin (EPO)
Observation.

11. Observation
Observation may be the best course of action for
infants who are asymptomatic, not acutely ill, and
are receiving adequate nutrition.
Adequate amounts of vitamin E, vitamin B-12,
folate, and iron are important to blunt the
expected decline in hemoglobin levels in the
premature infant.
Periodic measurements of the hematocrit level in
infants with AOP are necessary.

12. BLOOD TRANSFUSION
Further research is required to establish appropriate blood
transfusion
thresholds for preterm infants. Transfuse if clinically indicated.
Volume
to transfuse (mL) = desired rise in Hb (g/dL) x weight (kg) x [4
(packed cells) or 6 (whole blood)]. Alternatively, give 20mL/kg over
4hrs.

13. PRBC Transfusions
The frequency of blood transfusion varies with gestational age, degree
of illness, and, interestingly, the hospital evaluated. There is
considerable disagreement about the indication, timing, and efficacy of
PRBC transfusion.
The decision to give a transfusion should not be made lightly, because
significant infectious (HIV, Hep C, Hep B), hematologic, immunologic,
and metabolic complications are possible.
Late-onset necrotizing enterocolitis has been reported in stable-growing
premature infants electively transfused for AOP.
Transfusions also transiently decrease erythropoiesis and EPO levels.
There is also agreement that the number of transfusions, as well as the
number of donor exposures, should be reduced as much as possible.

14. Non-transfusion Approaches
Decrease lab draws
Enteral iron
Delayed cord clamping

15. Recombinant Erythropoetin
Multiple investigations have established that
premature infants respond to exogenously
administered recombinant human EPO and
supplemental iron with a brisk reticulocytosis.
Although EPO cannot prevent early transfusions,
modest decreases in the frequency of late PRBC
transfusions have been documented.
Additional iron supplementation is necessary
during exogenous EPO treatment.

16. EPOgen (cont)
Studies and a Cochrane Neonatal Systemic review suggest an
association between exogenous EPO administration and retinopathy of
prematurity.
Yasmeen et al studied 60 preterm low birth weight infants and
concluded that short-term recombinant human erythropoietin with iron
and folic acid was effective in preventing anemia of prematurity.
EPO with iron does not adversely affect growth or developmental
outcomes, but the impact on the number of transfusions a premature
infant receives ranges from nonexistent to small.
At this time, no agreement regarding the safety, timing, dosing, route,
or duration of therapy has been established. In short, the cost-benefit
ratio for EPO has yet to be clearly established, and this medication is not
universally accepted as a standard therapy for an infant with AOP.

17. CONCLUSION
Anaemia of prematurity is basically due to the unprepared body system
of the preterm baby to the relative hyperoxic state of extra uterine life.
It is a diagnosis of exclusion but should be considered early so that its
progression in severity might be blunted.
It usually resolves spontaneously in 60-80% of preterm babies.

18. REFERENCES
1. Paediatrics and child health in a tropical region by Azubike and
Nkaginieme
2. Oxford handbook of paediatrics
3. Anaemia of prmaturity/Medscape by George cassandy