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Anti-D (1941 and 1968)

It is 1609 and a French midwife called Louise Bourgeois is assisting at the birth of twins and things are not going well. The first twin is decidedly hydropic (swelling due to excess fluid) with excessive fluid in the embryonic chambers and is delivered almost dead. The second develops severe jaundice within hours of birth and is dead within three days. Louise writes about the birth in her memoirs and in doing so provides probably the first account of a neonatal condition that became known as rhesus disease.

We now know that rhesus disease is caused when a pregnant woman with rhesus (RhD) negative blood is exposed to the RhD positive blood of her developing baby and develops an immune response to it. The antibodies she produces then find their way back into the developing foetus, resulting in developmental abnormalities.

Blood is known as RhD positive when it has a molecule called immunoglobulin D (Ig-D) on the surface of its red blood cells. RhD negative blood lacks the Ig-D immunoglobulin.

Although the rhesus blood type was discovered in 1937, by immunising rabbits with the red blood cells of rhesus monkeys, it was not until 1941 when Philip Levine and colleagues recognised its importance in causing the condition where some women suffer from repeated miscarriages or stillbirths. Levine essentially demonstrated that it was down to some kind of immune reaction between the blood types of mother and baby.

The breakthrough occurred in the 1960s when it became possible to develop the rhesus Ig-D immunoglobulin. The intention was to inject pregnant rhesus-negative women with Ig-D antibodies – called anti-D –  so that their own immune systems don’t make it themselves when exposed to foetal blood.

The anti-D immunoglobulins neutralise any RhD positive antigens from the baby that may have entered the mother’s blood during pregnancy. Because the developing baby’s antigens have been neutralised, the mother won’t produce antibodies herself and so there is no risk of these antibodies passing back into the foetus across the placenta to trigger rhesus disease.

The first reported treatment with anti-D was a New Jersey woman called Marianne Cummins in 1968 while receiving medical care at Holy Name Hospital in Teaneck. Within a year, half a million more Rh negative women were offered the prophylactic injections and now they are a routine procedure both during and immediately after giving birth to prevent rhesus disease in subsequent pregnancies.

In the 1950s there were about 1,000 deaths each year due to rhesus disease in England alone. Now the incidence is vanishingly small thanks to anti-D immunoprophylaxis.