History and exam

Key diagnostic factors

common

presence of risk factors

Strong risk factors for maternal sensitisation to RhD antigen include: history of delivery of an Rh-positive fetus to an Rh-negative mother; fetomaternal haemorrhage; invasive fetal procedures; placental trauma; abortion (threatened, spontaneous, or induced); omission (or inadequate dosing) of appropriate Rh immunoprophylaxis following a potentially immunising obstetric event in a previous or current pregnancy; and multiparity.

Risk factors

strong

history of an RhD-positive fetus in an RhD-negative mother

RhD antigen is highly immunogenic. Only RhD-positive fetuses, from RhD-positive fathers, sensitise their RhD-negative mothers to produce anti-D antibodies.

fetomaternal haemorrhage

Fetomaternal haemorrhage (FMH) is common and detectable in 65% of pregnancies either antenatally or in the early postnatal period.[17] RhD antigen is 50 times more immunogenic than other Rh antigens. Sensitisation of an RhD-negative mother with as little as 0.1 mL of RhD-positive fetal red blood cells (RBCs) may elicit a primary immune response.[23]

invasive fetal procedures

Small amounts of FMH (>0.1 mL) are potentially immunising and occur in 2% of patients undergoing amniocentesis.[23][24]​ The incidence of FMH at the time of chorionic villus sampling is about 14%.[25]​ Other invasive procedures, such as cordocentesis, can also cause FMH.

placental trauma

Placental trauma of varying degrees may lead to sensitising FMH.

abortion

An episode of threatened, spontaneous, or induced abortion can sensitise RhD-negative women, but the risk of RhD alloimmunisation is very low with pregnancy loss before 12 weeks’ gestation.[27]

multiparity

Although the primary maternal immune response to sensitisation by the D antigen is usually weak, it may be greatly enhanced when a secondary immune response is generated by antigenic challenge in a subsequent pregnancy. Hence, the risk for fetal anaemia and hydrops increases with increasing parity.[2][26][31]

omission of Rh immunoprophylaxis

Omission (or inadequate dosing) of appropriate Rh immunoprophylaxis following potentially sensitising obstetric events, such as unrecognised FMH, in a previous or current pregnancy can lead to maternal sensitisation to the D antigen.

weak

external cephalic version

A meta-analysis of 17 studies found FMH (as detected by Kleihauer-Betke test) in 1% of women after external cephalic version.[22]

molar pregnancy

Risk of RhD alloimmunisation is low in complete molar pregnancy because of absent or incomplete vascularisation of villi and absence of D antigen. Conversely, a partial mole should be viewed as a risk factor for sensitisation.[23]​​​[26][29]

ectopic pregnancy

Alloimmunisation has been reported after ectopic pregnancy, and 24% of patients with ruptured ectopic pregnancy have fetal RBCs detectable in the maternal circulation.[28]

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