Blood Groups, a Miscarriage and a Second Pregnancy
A couple attends a district hospital. The woman is blood group B, Rh negative; her husband is group A, Rh positive. His mother is Rh positive and his father Rh negative. Their first child, now three years old, is group O, Rh positive and developed jaundice and anaemia within 24 hours of birth, needing a transfusion. Three years before that birth the woman had a miscarriage at ten weeks and received no injection afterwards. The husband's mother insists that a group O child cannot be born to a B mother and an A father and questions the child's paternity. The woman is now 12 weeks pregnant with a second child and has come for advice. No anti-D immunoglobulin was given after the first delivery either, and the hospital has recorded her antibody titres as rising.
1. Using genotypes, show whether a group O child is possible for this couple, and state the probability.
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Yes, it is entirely possible, and the mother-in-law is confusing group with genotype.
The ABO locus has three alleles: I^A, I^B and i. I^A and I^B are codominant and both are dominant over i.
- A group B mother may be I^B I^B or I^B i. For an O child she must be I^B i.
- A group A father may be I^A I^A or I^A i. For an O child he must be I^A i.
The cross I^B i × I^A i gives four equally likely genotypes: I^A I^B (group AB), I^A i (group A), I^B i (group B) and ii (group O).
So a group O child has a 25% (1 in 4) probability for each pregnancy, and group O offspring are perfectly compatible with a B mother and an A father. The child's phenotype is real evidence, but it does not exclude paternity; if there were genuine doubt, the correct approach is genotyping or DNA profiling, not a single blood group. Note also that ABO grouping is not used as proof of paternity for exactly this reason.
2. Explain why the first child was affected at birth, even though Rh haemolytic disease is usually said to spare the first pregnancy.
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The usual statement assumes the first pregnancy is the first sensitising event. Here it was not.
The woman is Rh negative (dd) and her husband is Rh positive but almost certainly heterozygous Dd, because his father is Rh negative; a Dd father transmits D to about half his children. The first child is Rh positive, so fetal red cells carrying the D antigen entered the maternal circulation. Ordinarily this happens mainly at delivery, which is why the first baby escapes.
But this woman had a miscarriage at ten weeks three years earlier and received no anti-D. Even early pregnancy loss can allow fetomaternal haemorrhage, so she was already sensitised and had formed anti-D IgG before the first full-term pregnancy.
Antibody class explains the timing. Naturally occurring anti-A and anti-B are IgM and do not cross the placenta; the ABO difference in this family (group B mother, group O baby) therefore cannot explain severe neonatal disease, and ABO haemolytic disease is in any case usually mild and often affects the first child. Anti-D is IgG, which is actively transported across the placenta, so haemolysis of fetal red cells began in utero, giving jaundice and anaemia within 24 hours of birth.
3. What should be done for the current pregnancy, and why is anti-D injection no longer the answer?
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The first judgement is that anti-D is prophylaxis, not treatment. It works by binding D antigen on fetal cells before the mother's immune system can respond, and it must be given before sensitisation. This woman already has circulating anti-D with rising titres from her earlier miscarriage and delivery, so giving anti-D now will not neutralise her existing antibodies, will not protect the fetus, and should not be presented to the family as a cure.
Management of the current pregnancy therefore turns on monitoring severity:
- Establish the father's Rh genotype if possible - if he were dd, the fetus could not be Rh positive and the pregnancy would be safe; because he is Dd, the fetus has roughly a 50% chance of being Rh positive.
- Measure maternal anti-D titres serially; a rising or high titre indicates a fetus at risk.
- Assess fetal anaemia non-invasively by middle cerebral artery Doppler peak systolic velocity, with amniotic fluid bilirubin estimation or cordocentesis if indicated.
- Plan delivery in a centre with neonatal intensive care; intrauterine transfusion may be needed for severe anaemia, and exchange transfusion or phototherapy after birth.
The teaching point: the missed anti-D after the miscarriage is the preventable error, and prevention must be given at the right moment - there is no way to go back and give it later.