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348 A. Lysikiewicz
selection of the level of measurement outside the bifurcation
of the MCA from the circle of Willis. An insonation
angle of < 308 allows for minimal error.
Other blood flow measurements await clinical validation
before they can be adopted as clinical tools;
some already have been shown to be ineffective. For
example, the umbilical artery blood flow indices are
not informative in alloimmunization and normal values
do not represent useful clinical information. A
study reported by Bilardo et al. [34] found no correlation
between umbilical artery pulsatility index and
fetal anemia. A highly specialized measurement of
flow velocities within the splenic artery requires specific
techniques and experience that may not be universally
available. This method of interrogation has
not been widely used in clinical management. A study
by Dukkler et al. [39] did not show intrahepatic vein
velocity to be more predictive than the MCA peak velocity.
Without reliable estimation of fetal blood vessel
size, attempts to quantitatively measure fetal blood
flow do not yield any new information. In addition,
with no changes in vessel size in the process of fetal
anemia, blood flow measurements will provide no
more information than peak velocities.
Middle cerebral artery peak velocity appears to
contain the most accurate information on fetal circulation
to allow for noninvasive diagnosis of fetal hyperdynamic
circulation in fetal anemia and to select
patients for invasive procedures.
A review by Divakaran included eight primary
studies with 362 pregnancies affected by red cell alloimmunization
evaluated by noninvasive methods. The
cumulative metaanalysis of studies with the highest
methodologic quality reported a positive likelihood
ratio of 8.45 (95% CI 4.69±15.56) and negative likelihood
ratio of 0.02 (95% CI 0.001±0.025) [8]. Although
those results are encouraging, more clinical data may
be needed before Doppler velocimetry will be recommended
as a primary standard evaluation of fetal
anemia.
Diagnostic Invasive Procedures to Detect
Fetal Anemia and Doppler Velocimetry
Diagnostic procedures have to be weighted between
risk of procedure and quality of information obtained
for fetal anemia in alloimmunization.
Amniocentesis is considered a safe procedure with
a complication rate of less than 1%. A major risk in
using this method lies in the low accuracy of predictions.
According to Queenan et al. [5], if used for detection
of fetal anemia in combination with the OD
curve, it is only 89% specific, whereas 21% of anemic
fetuses remain undetected. Frigoletto et al. [50] conservatively
managed 11 zone-III fetuses with no adverse
fetal outcomes. Fetal Doppler velocimetry of the
MCA has the potential to replace amniocentesis in diagnosis
of fetal anemia (Fig. 22.8).
Cordocentesis is the most accurate procedure for
detection of fetal anemia. It is also the most risky of
all procedures with associated fetal loss of 1% [1]
and as high as 4%. If cordocentesis is used as a primary
diagnosis, a large number of fetuses will be exposed
to this risk unnecessarily since only 25% of all
fetuses develop severe anemia requiring fetal blood
transfusion, but all will have multiple cordocenteses
to confirm normal hemoglobin concentration.
With five diagnostic cordocenteses during pregnancy
the cumulative fetal mortality risk may reach
10%±20%, too high for a diagnostic procedure.
Clearly, fetal Doppler velocimetry may not be as
accurate but is safer and should be considered as an
alternative to cordocentesis.
Doppler Monitoring During
Cordocentesis
Fetal Intravascular Transfusions
Accurate estimation of fetal anemia by cordocentesis,
before and after intravascular blood transfusion, can
be compared with Doppler velocimetry and numerous
cross-sectional data sets were obtained in this
fashion.
Fetal MCA Doppler velocimetry can detect fetal
anemia and provide timing for initiation of intravascular
transfusion prior to the development of fetal hydrops.
The role of Doppler velocimetry is to guide
timing of transfusions frequently enough to maintain
sufficient fetal hemoglobin levels, but not too often,
in order to avoid unnecessary risks from the procedure.
Clinical guidance for fetal intravascular transfusions
currently rely on clinical findings and the observation
that fetal hematocrit decreases at the rate of
0.3%±1.0% per day. Using mathematical formulas and
known hematocrit at the time of cordocentesis, an estimate
can be made regarding appropriate amount of
time for repeated intrauterine intravascular fetal
transfusion. Longitudinal Doppler velocimetry assessment
of fetal anemia is the other alternative in guiding
frequency and timing of fetal intravascular transfusions.
Several management schemes have been developed
to guide frequency of transfusions. Less frequent,
larger volume transfusions can be safer by reducing
the total number of fetal intravascular blood transfusions
[51], thereby reducing the risk of fetal blood
volume overload [52]. Use of Doppler velocimetry
during transfusion to assess fetal condition has not