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854 Part VI: The Erythrocyte Chapter 55: Alloimmune Hemolytic Disease of the Fetus and Newborn 855

colleagues also noted that a titer of 32 or greater was present in 16 of ULTRASONOGRAPHY
17 severely affected pregnancies, but 1 patient with a titer of 1:8 had Ultrasonography is noninvasive, can be performed serially, and can be
61
a grossly hydropic fetus at 23 weeks’ gestation. Some authors recom- combined with other diagnostic studies to assess the fetal condition,
mend further testing of the fetus if a critical titer of 8 is attained and estimate the need for further aggressive management, and obtain a bio-
76
paternal red cell typing is Kell-positive. In a case series of women with physical profile of the fetus to determine fetal well-being. As hydrops
anti-c isoimmunization, a titer of 32 or greater was invariably associated develops in the anemic fetus, a consistent pattern may be noted on
with severe fetal or neonatal disease. 78 ultrasonography. Polyhydramnios appears first, followed by placental
The imperfect predictive value of serologic tests has led to the enlargement, hepatomegaly, pericardial effusion, ascites, scalp edema,
development of functional cellular assays that measure the ability of and pleural effusions in succession. Nevertheless, in the absence of overt
maternal antibodies to cause red cell destruction, thus providing bet- hydrops, ultrasonographic parameters, such as intrahepatic and extra-
ter noninvasive differentiation of pregnancies at increased risk of fetal hepatic vein diameters, abdominal and head circumference, head-to-ab-
anemia. In these assays, RBCs sensitized with maternal antibodies are dominal-circumference ratio, intraperitoneal volume, splenic size, and
incubated with effector cells carrying Fcγ receptors, such as lympho- liver length have not been reliable in distinguishing mild from severe
cytes or monocytes, to measure cellular interaction, such as binding, fetal anemia. 82
79
phagocytosis, or cytotoxic lysis. Some authors have reported on the In addition to traditional ultrasonography, measurement of fetal
superiority of the monocyte monolayer assay, the chemiluminescence cerebral blood flow has become an extremely valuable technique in
test, and the antibody-dependent cell-mediated cytotoxicity assay, com- assessing fetal anemia. Decreased viscosity of the blood and increased
pared to serologic tests, in predicting severity of HDFN. However, these cardiovascular output in the anemic fetus lead to a hyperdynamic circu-
tests are complex, difficult to standardize, and are not widely used in the lation; hypoxia further increases blood flow velocity. Values greater than
United States.
1.5 multiples of the median for gestational age highly correlate with
moderate or severe fetal anemia (Fig. 55–3). Doppler measurement
86
FETAL BLOOD SAMPLING of peak velocity of systolic blood flow in the middle cerebral artery is
Fetal blood sampling (also called percutaneous umbilical blood sampling more sensitive and accurate for detecting severe fetal anemia than mea-
85
or cordocentesis) allows direct measurement of blood indices to specif- surement of amniotic fluid ΔOD . Measurements may be initiated
450
ically evaluate the degree of severity of fetal hemolytic disease as early as early as 18 weeks of gestation and repeated at 1- to 2-week intervals
as 17 to 18 weeks’ gestation. Indications for fetal blood sampling in until 35 weeks’ gestation. After 38 weeks, a higher false-positive rate in
80
alloimmunized pregnancies include fetal blood typing, confirmation of the detection of fetal anemia necessitates amniocentesis for ΔOD and
450
severe fetal anemia suspected based on elevated peak middle cerebral fetal lung maturity testing if elevated levels are noted. 76
artery Doppler velocities, or ultrasonographic evidence of early or frank
hydrops Historically, fetal blood samples were obtained when amnio-
centesis results returned with ΔOD (change in optical density at 450 THERAPY
450
nm) measurements in Liley zone 3 or in the “intrauterine death zone” in
the Queenan graph. 76,81,82 The procedure is performed under local anes- ANTENATAL MANAGEMENT
thesia. A 20- to 22-gauge spinal needle is inserted into the umbilical vein
at the level of cord insertion into the placenta under ultrasonographic Intrauterine Transfusion
guidance. Specimens of fetal blood are obtained for direct measurement Prior to the institution of IUTs, many severely affected fetuses died in
of complete blood count, reticulocyte count, red cell antigen phenotyp- utero or soon after birth. IUT corrects fetal anemia and reduce the risk
ing, DAT, bilirubin, blood gases, and lactate to assess acid–base status. of congestive heart failure and hydrops fetalis. Fetal bilirubin is cleared
Blood should be available for immediate IUT when the procedure is very efficiently by the placenta and the mother, so bilirubin removal
being performed for suspected severe fetal anemia. Complications of is not necessary until after birth. Percutaneous intraperitoneal fetal
5
fetal blood sampling include fetal loss, with procedure-related rates transfusion, pioneered by Liley in the 1960s, has been largely replaced
ranging from 0 to 4.9 percent, umbilical cord bleeding, chorioamnioni- by ultrasound-guided direct intravascular transfusion into the umbil-
tis, and significant risk of FMH with anamnestic maternal sensitization ical vein. 80,87 The intravascular technique circumvents the problem of
or the formation of additional alloantibodies. 83,84 erratic and often poor absorption of RBCs from the peritoneal cavity in
such fetuses. However, intraperitoneal transfusions may be necessary
when intravascular access is difficult, as in early pregnancy when the
AMNIOTIC FLUID SPECTROPHOTOMETRY umbilical vessels are narrow or later when increased fetal size prevents
Amniotic fluid spectrophotometry has been used for the last half cen- access to the umbilical cord. 88,89 The first fetal blood sampling with
tury using bilirubin as an indicator to measure fetal hemolysis. Although transfusion ideally is performed before hydrops develops. Transfusions
briefly reviewed here for historical perspective, this method has now are given at fetal hematocrit levels of 25 to 30 percent or less, or if the
largely been replaced by noninvasive fetal monitoring techniques. 76,85,86 fetal hemoglobin is 4 to 6 standard deviations below the mean for gesta-
Elevations of ΔOD by spectrophotometry reflect the concentration tional age. Generally, the hematocrit drops by 1 to 2 percent per day in
450
81
of amniotic fluid bilirubin, which is derived from the fetus. The orig- the transfused hydropic fetus. The fall in hematocrit is rapid in fetuses
inal Liley chart, from 27 weeks to term, defined three zones: readings with severe hemolytic disease, often necessitating a second transfusion
in zone 3, the upper zone, indicate severe fetal disease with hydrops or within 7 to 14 days. The interval between subsequent transfusions var-
impending fetal death; readings in zone 1, the lowest zone, indicate mild ies, but may be 21 to 28 days. The nonhydropic fetus can tolerate rapid
or no hemolytic disease with a 10 percent risk of needing a postnatal RBC infusions of 5 to 7 mL/min because of the capacitance of the pla-
exchange transfusion; and readings in zone 2 indicate moderate disease. centa. The hydropic fetus requires slower transfusion rates and can tol-
The Liley chart was later modified by Queenan to include data from 14 erate only smaller, more frequent transfusions. Very low pretransfusion
to 40 weeks gestation and had 4 zones, with the lowest zone represent- fetal hematocrit levels, rapid large increases in posttransfusion hemat-
ing unaffected fetuses and the highest zone associated with increased ocrit level, and increases in umbilical venous pressure during IUTs are
risk of intrauterine death. 81 associated with fetal death after transfusion. 90,91

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