History and exam

Key diagnostic factors

common

presence of risk factors

Strong risk factors for maternal sensitization to RhD antigen include: history of delivery of an Rh-positive fetus to an Rh-negative mother; fetomaternal hemorrhage; invasive fetal procedures; placental trauma; abortion (threatened, spontaneous, or induced); omission (or inadequate dosing) of appropriate Rh immunoprophylaxis following a potentially immunizing 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, sensitize their RhD-negative mothers to produce anti-D antibodies.

fetomaternal hemorrhage

Fetomaternal hemorrhage (FMH) is common and detectable in 65% of pregnancies either prenatally or in the early postpartum period.[15] RhD antigen is 50 times more immunogenic than other Rh antigens. Sensitization 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.[21]

invasive fetal procedures

Small amounts of FMH (>0.1 mL) are potentially immunizing and occur in 2% of patients undergoing amniocentesis.[21][22]​​ The incidence of FMH at the time of chorionic villus sampling is about 14%.[23]​ Other invasive procedures, such as cordocentesis, can also cause FMH.

placental trauma

Placental trauma of varying degrees may lead to sensitizing FMH.

abortion

An episode of threatened, spontaneous, or induced abortion can sensitize RhD-negative women, but the risk of RhD alloimmunization is very low with pregnancy loss before 12 weeks’ gestation.[25]

multiparity

Although the primary maternal immune response to sensitization 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 anemia and hydrops increases with increasing parity.[2][24][29]

omission of Rh immunoprophylaxis

Omission (or inadequate dosing) of appropriate Rh immunoprophylaxis following potentially sensitizing obstetric events, such as unrecognized FMH, in a previous or current pregnancy can lead to maternal sensitization 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.[20]

molar pregnancy

Risk of RhD alloimmunization is low in complete molar pregnancy because of absent or incomplete vascularization of villi and absence of D antigen. Conversely, a partial mole should be viewed as a risk factor for sensitization.[21]​​​[24][27]

ectopic pregnancy

Alloimmunization has been reported after ectopic pregnancy, and 24% of patients with ruptured ectopic pregnancy have fetal RBCs detectable in the maternal circulation.[26]

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