Rhesus disease (haemolytic disease of the fetus and newborn)
Rhesus disease is the situation in which antibodies from the mother's blood cross the placenta and destroy the baby's red blood cells.
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Medicines commonly prescribed for Rhesus disease (haemolytic disease of the fetus and newborn)
For informational purposes only. Always consult a doctor before using any medicine.
Dosage form: INJECTABLE, 750 IU/mlActive substance: anti-D (rh) immunoglobulinManufacturer: Instituto Grifols S.A.Prescription requiredDosage form: INJECTABLE, 300 mcg (1500 IU)Active substance: anti-D (rh) immunoglobulinManufacturer: Csl Behring GmbhPrescription required
Rhesus disease is the situation in which antibodies from the mother's blood cross the placenta and destroy the baby's red blood cells. It does no harm to the mother and she feels nothing at all: it is the baby who is affected. The main thing to know about it today is that it is almost entirely preventable. There is a medicine, anti-D immunoglobulin, that stops the problem arising in the first place, and wherever it is used properly severe cases have become a rarity. So most of this page is about when exactly that injection is needed and why it must not be missed.
What happens in rhesus disease
Red blood cells may or may not carry a protein known as the rhesus factor, or D antigen. If it is there, the blood is RhD positive; if it is not, RhD negative. Roughly fifteen people in a hundred have no rhesus factor. It is not an illness and has no bearing on health.
Rhesus status is inherited from both parents. An RhD negative woman can only have an RhD positive baby if the father is positive, and even then not necessarily: it depends on whether he carries one copy of the gene or two.
There is only one dangerous combination: the mother is RhD negative, the baby is RhD positive, and the mother's body has already met RhD positive blood at some earlier point. That earlier meeting is called sensitisation. On encountering a foreign protein the immune system treats it as a threat and makes antibodies. Those antibodies are small and pass freely through the placenta. Once in the baby's bloodstream they attach to its red cells, which are then destroyed faster than the bone marrow can replace them. The result is anaemia — not the kind caused by lack of iron, but haemolytic anaemia, caused by blood cells breaking down. The process can carry on for some weeks after birth.
A rhesus mismatch on its own threatens nothing. Everything turns on whether sensitisation has happened.
Why it is usually not the first baby that suffers
The blood of mother and baby does not normally mix; the placenta keeps them apart. But during birth, and sometimes earlier, a small amount of the baby's blood does get into the mother's circulation. The immune response to that is slow, and the antibodies usually do not arrive in time to harm the very baby who prompted them. That is why a first pregnancy in an RhD negative woman almost always goes smoothly.
What follows is the awkward property of immunity: it remembers. At the next encounter with RhD positive blood the antibodies appear at once, quickly and in quantity. That is why it is the second and later pregnancies that are at risk, and why the problem usually gets more severe with each one.
From this comes the practical point people get wrong most often. Prophylaxis must not be skipped on the grounds that "nothing went wrong last time". It is precisely on that occasion when nothing went wrong that sensitisation may have taken place, silently and without a single symptom. The injection is not given because something is going wrong now, but so that a child who does not yet exist is not harmed later.
A second consequence: if an RhD negative girl or woman is ever given a blood transfusion, the blood must be RhD negative. A mistaken transfusion is a rare but real cause of sensitisation long before a first pregnancy.
When anti-D immunoglobulin is needed
Anti-D immunoglobulin is ready-made antibody given as an injection into the muscle. It clears away the baby's red cells that have got into the mother's blood before her own immune system notices and memorises them: sensitisation does not occur, and the next pregnancy is safe.
Two occasions are planned in advance: the injection is given in the third trimester and again after the birth if the baby is RhD positive. But there are events after which the baby's blood may reach the mother at any point, and after each of them the injection is needed separately, outside any schedule:
- any bleeding during pregnancy, even if it is slight and stops quickly;
- miscarriage and termination of pregnancy, including early and medical ones;
- ectopic pregnancy;
- amniocentesis, chorionic villus sampling, fetal blood sampling — any procedure involving a needle;
- injury to the abdomen: a fall, a blow, a road accident, including one where the seat belt took the impact and nothing shows on the outside;
- external cephalic version, when a breech baby is turned by hand through the abdomen;
- death of the baby in the womb.
Timing matters here: the sooner the injection is given the more reliable it is, and the count is in hours rather than days. So after any of the above, contact a doctor straight away and say out loud that you are RhD negative — do not wait for the next scheduled appointment. Exact doses and time limits differ between countries and are set out in national maternity protocols; your part is simply not to let the trigger pass unnoticed.
And one limitation worth knowing: if sensitisation has already happened and antibodies are present in the blood, the immunoglobulin will not help. It prevents; it does not treat.
What is checked during pregnancy
Blood group and rhesus status are established at the very beginning of pregnancy, at the first set of tests. If the rhesus is negative, the blood is also screened for anti-D antibodies, and that test is repeated as the pregnancy goes on.
If there are no antibodies, the pregnancy is managed like any other with the planned prophylaxis added. Sometimes the father's blood group is offered: if he is RhD negative too, the baby will certainly be negative. There is something more precise still — the baby's rhesus can be worked out from an ordinary blood sample taken from the mother, in which a small amount of fetal DNA circulates. It is safe for both and reliable from early on, and if the baby turns out to be RhD negative, further measures fall away.
If antibodies are found, monitoring becomes close. Their level is tracked over time and the baby is assessed by ultrasound, including a Doppler measurement of blood flow in an artery in the brain: with anaemia the blood becomes thinner and moves faster, and this shows up long before any swelling appears. If there are signs of anaemia, blood may be taken from the baby with a needle through the abdomen — in a specialist centre and only when the result will change what is done, because the procedure carries a small risk of losing the pregnancy.
How it affects the baby
Severity varies enormously. In around half of affected babies it stays mild and is straightforward to treat.
Before birth the main danger is anaemia that keeps getting worse. The baby gives off no "signals" of it: it can only be picked up on tests. If the anaemia becomes severe, the heart can no longer cope and fluid leaks into the tissues and body cavities — that is hydrops fetalis, and it is life-threatening.
After the birth jaundice comes to the fore. Red cells breaking down produce a great deal of bilirubin, and a newborn's liver processes it slowly. If the bilirubin climbs too high it gets into the brain: this is kernicterus, and the damage lasts a lifetime — deafness, movement disorders, developmental delay. It is precisely to stop that happening that bilirubin is watched so closely.
What should worry parents once they are at home:
- jaundice in the first twenty-four hours of life — at that stage it is never normal and needs assessment immediately;
- jaundice that deepens quickly or reaches the tummy, palms and soles; on darker skin look at the whites of the eyes, the palms and the soles;
- a baby who is listless, feeds poorly and is hard to wake for feeds;
- an unusually high-pitched cry, arching of the back with the head thrown back, seizures — reason to call an ambulance (in Europe, the single number 112);
- marked pallor, fast breathing and lethargy in the first weeks — this is how late anaemia shows itself, and it can appear after discharge.
How it is treated
If the problem is picked up before birth and the baby has severe anaemia, blood is transfused while the baby is still in the womb: a needle is guided by ultrasound through the mother's abdomen into a vessel in the cord. Transfusions are repeated as needed until the baby is mature enough to be born. This is only done in specialist centres, so a woman is often referred to a hospital other than the one where she planned to give birth.
After the birth the mainstay is phototherapy: the baby is placed under a lamp with the eyes covered, or on a light-emitting blanket. The light alters bilirubin so that it becomes water-soluble and can be got rid of without passing through the liver. Babies lose more fluid during phototherapy, so they are fed more often or given fluids through a drip.
If the bilirubin keeps climbing fast, an exchange transfusion is carried out: the baby's blood is replaced in small portions with donor blood. That removes the bilirubin and the mother's antibodies along with it. Sometimes intravenous immunoglobulin is given instead or in addition, which slows the destruction of red cells. Later, after discharge, a straightforward top-up transfusion of red cells may be needed because of late anaemia, which is why these babies are followed up with blood tests for a while.
With timely treatment the outlook is good, and serious lasting damage is rare today.
If antibodies have already appeared
This is not a verdict and not a bar to having children, but the pregnancy is managed differently: prophylaxis no longer works, its place is taken by the monitoring described above, and the pregnancy is best looked after at a centre where intrauterine transfusions are done.
What is worth doing yourself:
- mention the antibodies at the very first appointment of every new pregnancy, rather than waiting for the tests to reveal them;
- discuss planning in advance, before conceiving: it helps the doctor to know how previous pregnancies went and at what stage problems arose;
- carry the details of your blood group and antibodies with you — they matter for any transfusion.
Even with antibodies already present, current monitoring and treatment make it perfectly possible to carry a pregnancy to term and give birth safely. The difference is that such a pregnancy needs more attention and does not tolerate missed appointments.
Online consultation
A remote appointment works well for the things that most often stay unclear after a short visit. The doctor will look at your results, explain what the antibody test means and why it is repeated, and draw up with you the list of situations in which you should ring straight away and ask for the immunoglobulin. It is also the right setting to talk through planning a further pregnancy.
It is worth booking separately if something has already happened: bleeding, a fall, a blow to the abdomen. The doctor will say whether the injection is needed and what the time limit is. With bleeding, abdominal pain or suspected jaundice in a newborn during the first day, an in-person assessment is needed the same day, and with the signs listed above, an ambulance.
This material is for information only and does not replace medical advice.
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