Introduction

Assessing the maternal Rhesus status is an important part of any pregnancy. Rhesus positive babies born to Rhesus negative mothers can be affected by haemolytic disease of the newborn. This can be easily prevented by appropriate screening and timely intervention.

• The rhesus antigen (Rh(D)) is a protein on the surface of red blood cells
• When assessing a blood group, results given as positive or negative
  • Positive refers to the presence of the Rhesus antigen – “Rhesus positive”
  • Negative refers to the absence of the Rhesus antigen – “Rhesus negative”
• This is important in the compatibility of blood
• Just like blood type (A,B or O) needs to be matched when giving a blood transfusion, care must also be made to consider the Rhesus status
  • If you do not have the Rhesus antigen, then if you receive blood that contains this antigen, your immune system will mount a response against the antigen – like it would against any pathogen, and destroy the red blood cells with this on their surface
  • If you have the rhesus antigen, then your immune system does not see it as “foreign” and will not mount a response against it
  • Rhesus negative individuals should only received Rhesus negative blood
  • Rhesus positive individuals can receive blood from anybody
• 85% of the population have the rhesus antigen; therefore only 15% of people are Rhesus negative

Implications in pregnancy

Rhesus status should be checked at the start of all pregnancies – by assessing the patient’s blood group.

• Mothers who are Rh(D) positive need not worry
• Mothers who are Rh(D) negative may need intervention at some stage in the pregnancy

The fetal blood type is determined by the mothers and father’s blood types. If the mother is Rh(D) negative, and the father is Rh(D) positive then there is a possibility that the fetal is Rh(D) positive

The risk in pregnancy is that if mixing of baby’s and mother’s blood occurs, then Rhesus sensitization can occur

• Blood does not cross the placenta – mother’s and baby’s blood do not mix – UNLESS:
  • Abdominal trauma – which can cause placental bleeding
  • Miscarriage (especially after 12 weeks)
  • Termination of pregnancy
  • Amniocentesis or chorionic villus sampling procedure
  • PV bleeding at any point in pregnancy
  • Mixing of blood occurs during birth
  • These scenarios are known as sensitizing events, and the process is sometimes referred to as alloimunisation. 
• Maternal blood testing is able to detect fetal DNA fragments and is able to determine if the fetus is Rh(D) positive or negative for Rh(D) negative mothers
  • This is not yet routine practice to perform this test

Sensitization is a scenario where the baby’s Rh(D) positive blood enters the maternal blood stream, and then the mother’s immune system produces Rhesus antibodies against Rhesus positive red blood cells

• Although blood can’t cross the placenta, antibodies can
• These antibodies can then activate the baby’s own immune system against the red blood cells – resulting in haemolytic disease of the fetus and newborn
• Rhesus sensitization occurs in roughly 1 in 1000 pregnancies
• Because it takes time for the immune response to develop, a mother’s first baby is not usually affected
• It is during subsequent pregnancies – when the immune system is already primed and producing antibodies that haemolytic disease in the fetus and newborn can occur
  • Each subsequent pregnancy increases the risk further

Management

Rhesus sensitization – the production of Rhesus antibodies can be prevented if Rh(D) immune globulin – more commonly known as Anti-D is given at the time of any sensitizing event.

• So, if there is any abdominal trauma during pregnancy, OR a miscarriage after 12 weeks – then the mother should receive a dose of anti-D
  • Should be given as soon as possible after the sensitizing event
  • Needs to be given within 72 hours to be effective
    • Not required for miscarriage <12 weeks, unless instrumentation is used
    • At sensitizing events at <20 weeks gestation 250 units may be used
    • At events after 20 weeks gestation, 500 units should be used
    • Doses given at birth are based on estimated maternal blood loss. Standard dose is 500 units, may be increased if larger blood loss
• At birth, the newborn is tested for blood group. If rhesus positive, then anti-D is given to the mother at the time of birth.
  • If testing is unavailable, a dose of anti-D should be given to the mother regardless
• Explain to all Rhesus negative mothers when they are identified as such that it is important that they tell all doctors involved with their care that they are Rhesus negative, and that if they have a miscarriage after 12 weeks, or any abdominal trauma during pregnancy they need to receive a dose of anti-D

This method only aims to prevent sensitization. If sensitization has already occurred, then in subsequent pregnancies, mothers should be monitored closely (see below)

Haemolytic disease of the newborn (HDN)

• Can be caused by any type of incompatibility of blood
• Traditionally is was most commonly cause by Rhesus incompatibility, but the widespread treatment of this has dramatically reduced the incidence
  • Before prophylaxis, 1% of babies were affected, and about 1 in 2000 live births died from the disease
  • Now, it affects only about 1 in 21,000 live births
• HDN can lead to permanent brain damage (kernicterus) as a direct result of high bilirubin levels
  • Bilirubin is released when red blood cells break down
  • The newborn liver is not very effective at removing bilirubin
• HDN can only occur in previously sensitized mothers

Previously sensitized mothers

• Any mother who is Rh(D) negative – as identified on the pregnancy screening bloods at the first antenatal visit should have the Coombs test
• If positive Coombs test – perform Rhesus antibody titres
  • Some centres now recommend proceeding straight to anti-body titres immediately if identified as Rh(D) negative
• If negative – repeat Coombs or antibody titre at 28 weeks
• If confirmed that mother is producing Rhesus antibodies, then the baby needs to be screened for anaemia
  • USS of the middle cerebral artery of the fetus can detect anaemia in the fetus
    • These should be performed serially to keep screening the baby for haemolytic disease
  • Alternatively, a fetal blood sample can be taken under USS guidance – carries several risks, including 20% fetal blood loss, infection and miscarriage
  • If anaemia is detected in the fetus, then blood transfusion should be attempted into the fetal umbilical vein, under USS guidance
  • If complications arise, delivery may be attempted at 32 weeks
  • If no complications, delivery should be attempted at 37 weeks
• 50% of babies born to sensitized mothers have normal Hb and bilirubin (when checked at birth)
• 25% have moderate disease and require transfusion
  • Significant jaundice may develop and
• 25% have severe disease and may be stillborn or have hydrops fetalis

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