Haemolytic disease of the newborn (HDN) Flashcards
Define HDN.
Haemolytic disease of the fetus and newborn (HDFN) is a condition which results from transplacental passage of maternal antibodies which cause immune haemolysis of fetal/neonatal red blood cells.
Explain the aetiology of HDN.
Foetal cells enter woman’s circiulation -> mother develops antibodies against a component in foetuses’ blood -> Ab most often responsible is anti-D, therefore always transfuse RhD negative blood to RhD negative women of childbearing age.
ONLY IgG CAN CROSS PLACENTA.
If the rate of red cell destruction exceeds the rate of production it results in fetal anaemia which, if severe, can lead to fetal heart failure, fluid retention and swelling (hydrops). Red cell breakdown results in bilirubin release which is not a problem during fetal life as it is cleared by the placenta. After birth, however, the immature neonatal liver is not capable of handling a high bilirubin load and this can result in severe neonatal jaundice. High levels of jaundice if untreated can result in permanent brain damage (kernicterus) because of deposition of bilirubin in certain areas of the neonatal brain.
What are risk factors for HDN?
- Alloimmunisation during first pregnancy.
- Alloimmunisation during second or subsequent pregnancy.
- Failed prophylaxis.
Over 99% of women have an fetal-maternal haemorrhage (FMH) of less than 4 ml at delivery. 50% of women (who have larger FMHs) have them after normal deliveries. However, the following clinical circumstances are more likely to be associated with large FMH:
- Traumatic deliveries including caesarean section.
- Manual removal of the placenta.
- Stillbirths and intrauterine deaths.
- Abdominal trauma during the third trimester.
- Multiple pregnancies (at delivery).
- Unexplained by hydrops fetali.
Summarise the epidemiology of HDN.
Anti-D prophylaxis (mostly administered postnatally) and advances in neonatal care have reduced the frequency of HDN by almost a factor of 10 to 1 in 21,000 births.
What are presenting symptoms of HDN?
Antenatally, the first indication of the condition is the presence of anti-D antibodies in the mother as detected by the indirect Coombs’ test. All rhesus-negative women have this test performed in the UK at the first antenatal visit.
What are the signs of HDN?
Foetal anaemia and jaundice.
Infants born to alloimmunised mothers may appear clinically normal in mild cases. Diagnostic findings include jaundice (yellow amniotic fluid, yellow vermix, yellow skin), pallor and hepatosplenomegaly. Kernicterus (bilirubin encephalopathy) is a serious risk and hypoglycaemia is common.
Hydrops fetalis may present antenatally as polyhydramnios (excessive amniotic fluid) or postnatally with subcutaneous oedema, pericardial effusion, pleural effusion, ascites and hepatosplenomegaly. The placenta may be thickened.
What are some appropriate investigations for HDN?
Indirect Coombs’ test should be performed at the first antenatal visit, for all rhesus-negative mothers. If the test is positive, antibody titres should be monitored with serial samples. Another option is non-invasive rhesus genotyping of the fetus using free cell fetal DNA obtained from maternal blood, which identifies pregnancies at risk of sensitisation. This can be reliably done and is available in the UK but is not currently universal practice
Antenatal USS: Doppler ultrasound of the middle cerebral artery has largely replaced fetal blood sampling as an initial test for the detection of fetal anaemia.
Fetal blood sampling: If the Doppler scan confirms anaemia, fetal blood sampling should be considered.
FBC and biochemistry.
Postnatal diagnosis.
What is the management plan for HDN in utero?
As soon as the blood samples confirm anaemia, transfusion should be commenced with group O negative packed cells cross-matched with maternal blood. This is best done at 18 weeks but samples can be taken at 16 weeks if necessary. Intravenous transfusion under ultrasound guidance via the umbilical vein is to be preferred to the intraperitoneal route, as the latter is more difficult in an hydropic fetus and causes more complications. Further transfusions should be dictated by serial Doppler scans. Following successful transfusion, delivery should be anticipated between 37-38 weeks. If complications arise, delivery at 32 weeks should be considered. The mode of delivery can be dictated by obstetric considerations
What is the management plan for HDN post-natally?
- 50% of babies born to mothers with high maternal antibody titres have normal haemoglobin and bilirubin levels but should be monitored for the onset of late anaemia at 6-8 weeks.
- 25% have moderate disease and may require transfusion. Significant hyperbilirubinaemia may develop within the first 24 hours after birth, which may require phototherapy to avoid kernicterus.
- The remaining 25% will have severe disease and either be stillborn or have hydrops fetalis.
When severe HDFN is anticipated, the birth should be attended by a paediatrician trained in neonatal resuscitation and fresh O negative blood should be immediately available. The baby with severe haemolytic disease requires immediate resuscitation and supportive treatment including temperature stabilisation followed by exchange transfusion. Further top-up blood transfusions and phototherapy may be needed.
How is HDN prevented?
Routine antenatal anti-D prophylaxis (RAADP) using anti-D immunoglobulin should be given to all rhesus-negative women who have not already been sensitised. It can be given as two doses of anti-D immunoglobulin of at least 500 IU at 28 and 34 weeks or as a large single dose of 1500 IU at 28 weeks gestation.
Treatment is also indicated after other sensitising events such as abortion, miscarriage, amniocentesis, ectopic pregnancy, and abdominal trauma.
Following birth ABO and Rh D typing should be done on cord blood and if baby is confirmed to be D positive, all D negative, previously non-sensitised women should be offered at least 500 IU of anti-D iimmunoglobulin within 72 hours of delivery. Maternal blood samples should be checked for FMH and additional dose given guided by FMH results.
