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346 A. Lysikiewicz
Scalp edema and generalized edema are nonspecific
changes that may not be related to fetal anemia
and changes of Doppler velocimetry.
In summary, it appears that fetal hydropic changes
occur as a result of severe fetal anemia. They should
not be used as predictors of fetal disease because of
their poor predictive value [11, 45]. Abnormal Doppler
velocimetry detects changes in fetal circulation
that precede fetal hydrops and therefore can detect fetal
anemia early. According to data by Mari et al. [35]
early detection of fetal anemia is feasible using fetal
cardiovascular monitoring with Doppler velocimetry.
A finding of severe fetal hydrops in isoimmunization
should be considered as evidence of advanced fetal
disease but may be avoidable with intensive fetal
diagnosis and active clinical management.
Fetal Blood Redistribution and
Fetal Hypoxia in Alloimmunization
Fetal blood redistribution in chronic fetal hypoxia
has been reported in growth-restricted fetuses. With
decreased oxygen-carrying capacity in fetal anemia,
similar findings could be expected due to presumed
fetal hypoxia. Initial response to fetal hypoxia is an
increase in fetal heart rate [21]. In alloimmunization,
however, this heart rate increase may more likely be
related to the blood volume increase and blood viscosity
decrease resulting in increased fetal circulation
[16]. Contrary to expectations, fetal hypoxia is not
common in isoimmunized fetuses. Fetal hemoglobin,
even if diluted, is able to transport oxygen without
developing significant fetal hypoxia [48]. There is no
evidence that fetal blood redistribution plays a significant
role in fetal cardiovascular changes in isoimmunization
[16].
Doppler Velocimetry in Clinical
Management of Alloimmunization
Fetal anemia determines the management of alloimmunization.
Use of specific Doppler velocimetry measurements
requires a selective, evidence-based approach in
choice of measurements. Multiple Doppler-detectable
changes of the fetal circulation do not have equal diagnostic
value. Methods not adequately studied
should only be used with caution, if at all, for diagnostic
purposes as those findings often prompt major
therapeutic interventions.
The standard of care in alloimmunization has been
changing rapidly. The traditional biochemical monitoring
is being supplemented by fetal Doppler velocimetry
supported by clinical studies.
History of Previous Pregnancy
A history positive for a previous pregnancy with
complications should increase the index of suspicion
as it is predictive of the general severity of fetal involvement.
Maternal history of alloimmunization, previous
affected pregnancy or previous neonatal disease
are risk factors for development of fetal anemia.
Although the correlation is strong, history alone is
not sufficient to guide obstetrical management.
Maternal Antibody Titer
Maternal antibody titer has been a landmark in management
of alloimmunization for several decades. Maternal
antibody, if present, should prompt paternal
blood type zygosity evaluation to determine the likelihood
of the presence of an antigen in the fetal
blood. If such a risk is not 100%, as in paternal
homozygosity, then fetal blood typing should be carried
out. Absence of an antigen in the fetal blood
rules out fetal involvement and makes further testing
unnecessary (Fig. 22.8).
Maternal antibody concentration has been correlated
with the presence and severity of fetal disease
but is not accurate in prediction of specific cases.
High initial titer or rising titer indicates the possibility
of fetal anemia, but specific critical titers requiring
intervention are difficult to define. Depending on laboratory
methods, commonly, values 1 : 16 or higher
are being investigated because of the probability of
fetal hemolytic anemia. In this range fetal anemia
and hemodynamic changes may be better detected by
Doppler velocimetry than by antibody titer alone [7].
Amniotic Fluid Densitometry
A change in optical density at 450 nm wavelength detects
the presence of bilirubin, an end product of fetal
hemolysis. It has been used for four decades in combination
with standards developed by Liley [3] to predict
severely anemic fetuses that could benefit from
intervention. A recent review of values by Queenan et
al. improved accuracy of the curve, especially for
early pregnancy [5]. According to their report, specificity
of detecting severe anemia was 79%. In 21% of
fetuses, however, severe anemia would not be detected
by this method. This low accuracy of the Liley curves
has been a concern in management of fetal anemia
[5]. Doppler velocimetry is expected to improve accuracy
of this diagnosis.
Detecting Fetal Anemia
For management of alloimmunization an accurate diagnosis
of fetal anemia is essential. High specificity is
mandatory for this testing to avoid development of