Anaemia of Prematurity

Anaemia of prematurity is the exaggerated and early physiological fall in haemoglobin in preterm infants. Haemoglobin reaches a nadir at 4 to 8 weeks after birth, often 70 to 90 g/L, lower and earlier than in term infants, and may cause symptoms.

It affects most infants born under 32 weeks, and most extremely low birth weight infants are transfused at least once. Blood sampling in the first weeks is the commonest contributor.

Contributing factors are low erythropoietin production (the liver is the main site in the preterm infant and is less responsive to anaemia), short red cell survival (45 to 70 days), rapid growth with expanding blood volume, iatrogenic blood loss and low iron stores.

Pathophysiology.

After birth oxygen delivery rises and erythropoietin falls, suppressing red cell production. Preterm red cells live only about half as long as adult cells, and growth expands the blood volume.

Frequent blood sampling removes red cells and iron, and iron stores that are laid down mostly in the third trimester are limited in preterm infants.

• Pallor, tachycardia, tachypnoea, apnoea, poor weight gain, poor feeding and lethargy.
• Raised lactate and increased oxygen requirement in severe anaemia.
• Many infants are asymptomatic at haemoglobin levels of 70 to 90 g/L.

Red flags.

• Acute fall in haemoglobin: consider intraventricular haemorrhage, subgaleal haemorrhage, pulmonary haemorrhage or occult bleeding.
• Haemolysis with jaundice, or fever with a low reticulocyte count (infection or parvovirus).

• Full blood count, reticulocyte count (low), blood film, and mean corpuscular volume.
• Ferritin and iron studies at 4 to 6 weeks, vitamin B12 and folate if macrocytic, and direct antiglobulin test with bilirubin to exclude haemolysis.
• CRP and culture when infection is suspected, and cranial ultrasound and abdominal examination for concealed bleeding.

Differential diagnosis. Blood loss (iatrogenic, intraventricular haemorrhage, fetomaternal haemorrhage), haemolytic disease, iron deficiency, infection, and rarely congenital hypoplastic anaemia.

Prevention.

• Delayed cord clamping for 30 to 60 seconds, or cord milking where clamping cannot be delayed.
• Minimise blood sampling by using micro-sampling, non-invasive monitoring and batching tests, and return of blood in lines.
• Iron: elemental iron 2 to 3 mg/kg/day orally from 2 to 6 weeks of age once on full enteral feeds, continued until 6 to 12 months of age. Adjust to ferritin and haemoglobin.

Transfusion.

• Use restrictive thresholds. Typical thresholds are haemoglobin under 70 to 80 g/L in stable infants without respiratory support, and under 100 g/L in infants needing ventilation or with severe cardiorespiratory disease in the first 2 weeks, with higher thresholds for symptomatic infants.
• Transfuse leucodepleted, CMV-safe red cells 15 mL/kg over 3 to 4 hours, and avoid giving a diuretic routinely.

Erythropoiesis stimulating agents. Erythropoietin 250 units/kg SC or IV 3 times each week reduces transfusion slightly but is not advised routinely because of limited benefit and concern about retinopathy.

Monitoring. Haemoglobin and reticulocyte count every 1 to 2 weeks in the neonatal unit, then at follow up. Ferritin at 4 to 6 weeks and before stopping iron.

Referral and escalation. Refer to haematology for persistent anaemia despite iron, macrocytosis, haemolysis or a low reticulocyte count with no cause.

Special groups. Extremely low birth weight infants and those needing frequent sampling have the highest transfusion need.