Fetal Anaemia

Fetal anaemia is a haemoglobin concentration more than 2 standard deviations (or below 0.65 multiples of the median) under the mean for gestational age. Causes:

• Alloimmunisation: Rh (D), Kell, c, E and others
• Infections: parvovirus B19 (infects erythroid progenitors; severe aplastic crisis in 5 to 10% of infected fetuses, with hydrops most likely at 9 to 20 weeks), CMV, toxoplasmosis, syphilis
• Haemoglobinopathies: alpha thalassaemia major (Hb Bart hydrops)
• Fetomaternal haemorrhage (about 1 in 1,000 pregnancies for severe cases; sudden reduced movements and a sinusoidal heart rate pattern), twin anaemia polycythaemia sequence, chronic bleeding into a placental or tumour site
• Red cell enzyme and membrane disorders (G6PD, pyruvate kinase), Diamond-Blackfan anaemia, and fetal tumours (sacrococcygeal teratoma, haemangioma)

• The mother is often asymptomatic; reduced fetal movements in acute fetomaternal haemorrhage
• Ultrasound: cardiomegaly, ascites, pleural and pericardial effusions, polyhydramnios, thick placenta, hepatosplenomegaly, hydrops
• Sinusoidal fetal heart rate pattern on cardiotocography in severe anaemia
• Raised MCA-PSV from low blood viscosity and high cardiac output
• Maternal parvovirus features (rash, arthralgia); mirror syndrome (maternal pre-eclampsia-like illness with fetal hydrops)

• MCA-PSV Doppler is the main non-invasive test: above 1.5 multiples of the median predicts moderate to severe anaemia with sensitivity of 88 to 100% and a false positive rate of about 12%; it is less reliable after 35 weeks and after intrauterine transfusions
• Maternal tests: blood group and antibody screen, Kleihauer-Betke test or flow cytometry with HbF measurement for fetomaternal haemorrhage, parvovirus B19 IgG, IgM and PCR, CMV and toxoplasma serology, haemoglobin electrophoresis with parental testing, G6PD
• Fetal blood sampling by cordocentesis for haemoglobin, haematocrit, reticulocytes, direct Coombs test, blood group, platelets and karyotype, done with blood immediately available for transfusion
• Fetal echocardiography and a detailed anatomy scan

• Treat the cause: for alloimmunisation, serial MCA-PSV, intrauterine transfusion and delivery at 37 to 38 weeks (32 to 35 weeks for severe disease); for parvovirus, which often resolves spontaneously, transfuse for hydrops or MCA-PSV above 1.5 multiples of the median (survival 85 to 90% with transfusion); for fetomaternal haemorrhage, transfuse or deliver according to gestation; for alpha thalassaemia major, repeated intrauterine transfusions followed by stem cell transplantation, or termination after counselling
• Intrauterine transfusion: intravascular through the umbilical vein at the placental cord insertion, or the intrahepatic vein, between 18 and 35 weeks. Use group O RhD-negative, CMV-negative, leucodepleted, irradiated red cells packed to a haematocrit of 75 to 85%, with volume calculated from fetal weight and target haematocrit (40 to 45%). Fetal paralysis with pancuronium or vecuronium 0.1 mg/kg is optional. Complications: fetal loss 1 to 2% per procedure, ruptured membranes, bradycardia, infection, preterm delivery. Repeat every 1 to 3 weeks; haemoglobin falls about 0.3 g/dL per day after the first transfusion and about 0.1 g/dL per day after repeated transfusions
• Betamethasone 12 mg IM, two doses 24 hours apart, at 24 to 34 weeks before expected delivery
• Delivery timing: 35 to 37 weeks after the last transfusion in alloimmunisation, with the neonatal team and blood available; earlier for hydrops, abnormal cardiotocography or cardiac failure
• Postnatal: transfusion, phototherapy, exchange transfusion for hyperbilirubinaemia, and follow up for late anaemia