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PubMed2002

Amniotic fluid delta OD 450 values accurately predict severe fetal anemia in D-alloimmunization.

OBJECTIVE: To assess the diagnostic accuracy of amniotic fluid Delta OD 450 values in the second and third trimesters of D-alloimmunized pregnancies. METHODS: We searched our database for singleton D-alloimmunized pregnancies with nonhydropic fetuses, where amniocentesis was performed within 4 days of first fetal blood sampling. Amniotic fluid Delta OD 450 values were plotted on an extrapolated Liley's chart. Sensitivity and specificity were calculated for two commonly used cutoff levels, Liley's zone 3 and the upper third of Liley's zone 2. Severe fetal anemia was defined as a hemoglobin concentration of more than 5 standard deviations below the normal mean for corresponding gestational age. RESULTS: Seventy-nine pregnancies met our inclusion criteria. Overall accuracy of the extrapolated Liley's curve in predicting severe fetal anemia was 75% (95% confidence interval [CI] 64, 84) for zone 3 and 86% (95% CI 77, 93) when the upper third of zone 2 was included. Sensitivity of Delta OD 450 values in Liley's zone 3 or the upper third of Liley's zone 2 was 95% (95% CI 74, 100) before and 98% (95% CI 89, 100) after 27 weeks. CONCLUSION: Liley's extrapolated curve predicts severe fetal anemia with reasonable accuracy and high sensitivity.

Adult↗
PubMed1998

The effect of fetal intravascular blood transfusion on plasma endothelin levels in fetuses with rhesus alloimmunization.

OBJECTIVE: To determine if intrauterine intravascular fetal transfusion affects fetal umbilical venous endothelin levels. METHODS: Endothelin concentrations were measured by radioimmunoassay in fetal umbilical venous blood obtained immediately before and after 36 fetal transfusions performed for Rh alloimmune hemolytic anemia. Umbilical venous pressures also were recorded before and after transfusion. RESULTS: The mean (+/- standard deviation [SD]) gestational age at transfusion was 27.0 +/- 4.6 weeks, whereas the initial and post-transfusion hematocrits were 23.3 +/- 8.5% and 41.8 +/- 6.3%, respectively. Post-transfusion endothelin levels correlated significantly with the volume of transfused blood (r = .41; P = .03) and with post-transfusion increases in umbilical vein pressure (r = .86; P < .001). Among fetuses undergoing initial transfusion, there were significant differences between mean (+/- SD) pre- and post-transfusion endothelin levels [3.6 (+/- 2.2) pg/mL versus 6.3 (+/- 4.0) pg/mL, respectively; P = .02]. In contrast, among fetuses undergoing a repeat fetal transfusion, no differences in mean (+/- SD) pre- versus post-transfusion endothelin levels were observed [3.8 (+/- 1.8) pg/mL versus 2.2 (+/- 1.77) pg/mL, respectively; P = .3)]. Step-wise multiple regression analysis identified order of transfusion as a significant predictor of change in endothelin levels from pre- to post-transfusion measurements (adjusted r2 = .26; P = .003). CONCLUSION: Rapid expansion of fetal intravascular volume by intravenous transfusion of packed red blood cells with a high hematocrit enhances fetal endothelin levels in those fetuses undergoing initial but not subsequent transfusions.

Adult↗
PubMed1998

Fetal splenic size in anemia due to Rh-alloimmunization.

OBJECTIVE: To determine whether fetal splenic enlargement predicts anemia in Rh-alloimmunized nonhydropic singleton fetuses. METHODS: Splenic circumference was measured before funipuncture in 21 singleton pregnancies on 47 occasions. The spleen was imaged in an axial section of the fetal abdomen close to the level used for measurement of the abdominal circumference. The splenic length and width were measured and the circumference calculated by the formula (length and width x 1.57). One measurement per patient was used for each analysis. Splenic circumference was measured and expressed as multiples of the normal median (MoM) for gestational age. One hundred twenty-one cases were used to provide cross-sectional normative data. The expected median splenic circumference values were derived from a normal group. Fetal anemia was defined as hemoglobin deficit, ie, mean hemoglobin concentration for gestation minus the measured value. Anemia was defined as hemoglobin deficit exceeding 2 g/dL, and severe anemia as hemoglobin deficit exceeding 5 g/dL. Receiver operator characteristics curves for the prediction of anemia using different splenic circumference (MoM) values were constructed. RESULTS: Splenic circumference was an excellent predictor of severe anemia in cases with no prior transfusion: sensitivity 100% and specificity 94.7% (area under the curve = .97, P < .03). The measurement did not correlate significantly with severe anemia in the group with prior transfusion (area under the curve = .73, P = .19). CONCLUSION: Splenomegaly is sensitive for the detection of severe anemia in nonhydropic Rh sensitized cases without prior transfusion. The splenic enlargement could be explained by extramedullary erythropoiesis.

Adult↗
PubMed1999

Umbilical artery regression: a rare complication of intravascular fetal transfusion.

BACKGROUND: Intravascular fetal transfusion is an important therapeutic advance but is associated with several complications. Regression of an umbilical artery associated with transfusion is rare. CASE: A case of red blood cell alloimmunization managed by serial transfusions was complicated by functional loss of an umbilical artery during pregnancy. Refractory fetal bradycardia occurred during the last transfusion procedure, requiring emergency preterm cesarean delivery. Coagulative necrosis, thrombosis, and focal calcification of one umbilical artery was confirmed after delivery. CONCLUSION: Umbilical artery regression associated with transfusion therapy is rare and may complicate subsequent fetal transfusions.

Adult↗
PubMed1988

Fetal haemoglobin measurement in the assessment of red cell isoimmunisation.

A reference range of fetal haemoglobin concentration (g/dl) was established from umbilical cord blood samples obtained by cordocentesis (n = 200) or at delivery (n = 10). In normal pregnancy the mean fetal haemoglobin increases linearly from 11 g/dl at 17 weeks' gestation to 15 g/dl at 40 weeks' gestation and one standard deviation is approximately 1 g/dl. The haemoglobin was also measured in fetal blood from 154 red cell isoimmunised pregnancies from 17 to 36 weeks' gestation. In 48 fetuses with ultrasound features of hydrops the haemoglobin was 7-10 g/dl below the normal mean for gestation. It is proposed that in pregnancies complicated by red cell isoimmunisation the severity of the disease should be assessed and treated on the basis of the deviation of the fetal haemoglobin from the normal mean for gestation into mild (haemoglobin deficit less than 2 g/dl), moderate (deficit 2-7 g/dl), and severe (deficit greater than 7 g/dl).

Blood Transfusion, Intrauterine↗
PubMed1997

The management of hemolytic disease in the fetus and newborn.

Rh hemolytic disease (HDN) is the prototype of maternal alloimmunization and fetal hemolytic disease. There are other antigens capable of causing alloimmunization and hemolytic disease such as c, Kell, and Fya. Rh immunization is usually caused by a prior Rh positive fetal maternal transplacental hemorrhage, which occurs in at least 75% of pregnancies. Unless treated, hemolytic disease will result in kernicterus or fetal hydrops in 25% of cases, respectively. Neonatal exchange transfusion has eradicated kernicterus. Measures available to predict severity of fetal hemolytic disease are maternal antibody titers, prior history of hemolytic disease, in vitro cell-mediated maternal antibody functional assays, amniotic fluid spectrophotometry, ultrasound fetal assessment, and fetal blood sampling. The Rh or Kell antigen status of the fetus may be determined by amniotic fluid PCR testing. The management of the severely affected fetus consists of early delivery, with or without fetal transfusions, depending on the gestation of the fetus. With the use of these diagnostic and treatment measures, perinatal mortality from hemolytic disease of the fetus and newborn has been reduced in Manitoba, population one million, from 100 per year in the early 1940s to 1 every 3 years in the mid 1990s.

Blood Transfusion, Intrauterine↗
PubMed2000

Invasive versus non-invasive testing in red-cell alloimmunized pregnancies.

Amniocentesis for amniotic fluid bilirubin levels is the most widely used test to predict the severity of fetal disease in red-cell alloimmunization. Many textbooks and guidelines recommend serial amniocentesis to monitor these pregnancies. However, the reliability of amniotic fluid bilirubin measurements has been questioned. Two strategies have been proposed by investigators. Some advocate liberal or primary use of fetal blood sampling, while others promote the use of non-invasive ultrasonography and Doppler. The purpose of this literature review is to examine the usefulness of amniocentesis, ultrasonography and Doppler to predict the degree of fetal hemolytic anemia. The evidence suggests that amniotic fluid bilirubin measurements are of limited value in the second trimester. Furthermore, critical appraisal of the very few prospective studies is hampered by limitations in design or insufficient data given by the authors. Many ultrasound and Doppler parameters have been proposed as useful indicators of fetal anemia. The most promising of these methods are Doppler assessment of umbilical venous and middle cerebral artery flow velocities. We speculate that the accuracy of these non-invasive tests may be good enough to incorporate them in management protocols, possibly replacing amniocentesis. Well-designed prospective studies are needed to prove this hypothesis.

Amniocentesis↗
PubMed2000

Benefits and risks of fetal red-cell transfusion after 32 weeks gestation.

OBJECTIVE: To compare the outcome after intrauterine transfusion (IUT) between fetuses treated before and those treated after 32 weeks gestation. SETTING: National referral center for intrauterine treatment of red-cell alloimmunization in The Netherlands. STUDY DESIGN: Retrospective evaluation of an 11 year period, during which 209 fetuses were treated for alloimmune hemolytic disease with 609 red-cell IUTs. We compared fetal and neonatal outcome in three groups: fetuses only treated before 32 weeks gestation (group A, n=46), those treated both before and after 32 weeks (group B, n=117), and those where IUT was started at or after 32 weeks (group C, n=46). RESULTS: Survival rate was 48% in group A, 100% in group B, and 91% in group C. Moreover, fetuses in group A were hydropic significantly more often. Short-term perinatal loss rate after IUT was 3.4% in the 409 procedures performed before 32 weeks and 1.0% in the 200 procedures performed after 32 weeks gestation. CONCLUSION: Perinatal losses were much more common in fetuses only treated before 32 weeks gestation. Two procedure-related perinatal losses in 200 IUT after 32 weeks remain a matter of concern because of the good prospects of alternative extrauterine treatment.

Blood Transfusion, Intrauterine↗
PubMed2002

The value of middle cerebral artery systolic velocity for initial and subsequent management in fetal anemia.

OBJECTIVE: To evaluate the fetal middle cerebral artery Doppler waveform for the prediciton of anemia in the RhD-alloimmunized fetus. STUDY DESIGN: Doppler velocimetry of the fetal middle cerebral artery peak systolic velocity was measured in 52 non-hydropic, RhD-alloimmunized fetuses who underwent 103 cordocenteses. Normal values were obtained from 70 normal cases. The peak systolic velocity values were expressed as multiples of the median (MoM) for gestation. Hemoglobin threshold for developing hydrops was developed from 22 RhD-alloimmunized hydropic fetuses and severe anemia was defined as Hb< or =0.60 MoM. The most efficient threshold values for the prediction of severe anemia in groups with no prior transfusion and those with prior transfusion were obtained by constructing ROC curves. RESULTS: The mean gestational age (+/-S.D.) at cordocentesis was 28.0 +/- 4.6 weeks. Severe anemia was noted in 53 (51.5%) occasions. At a threshold middle cerebral artery peak systolic velocity value of > or =1.35 MoM, the sensitivity for severe anemia detection was 100% with a false-positive rate of 18%. In sub-analysis, in patients with one or more prior transfusion a sensitivity of 97% and a false-positive rate of 14% obtained at a threshold of > or =1.45 MoM. In patients with no previous transfusion the sensitivity for severe anemia was 100%, with a false-positive rate of 9.1% at a threshold value of > or =1.35 MoM. CONCLUSION: The middle cerebral artery peak systolic velocity can be used to time both the initial diagnostic procedure and retransfusion.

Anemia↗
PubMed2002

Fundamental classification of perinatal death. Validation of a new classification system of perinatal death.

OBJECTIVE: To validate a newly introduced classification system for the registration of perinatal mortality. DESIGN: Descriptive. SETTING: Dutch Healthcare region Delft-Westland-Oostland (DWO). MATERIAL AND METHODS: In a 10-years period (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. Six assessors: four gynaecologists and two paediatricians were asked to classify all cases using a classification model proposed by the authors. This model is based on the underlying cause of death using simple principles of obstetrical and neonatal pathology: birth trauma, infection, placenta or cord pathology, pathology of immune tolerance of mother and fetus, congenital malformation of the fetus and complications of a pre-viable delivery. Therefore, we used the term fundamental classification. The six assessors worked independently of each other in classifying all cases of perinatal death, were not involved in the original development of the system and were unaware of the results of the classification of their colleagues. Agreement beyond chance between assessors was calculated using kappa's coefficient for multiple observers and multiple test results. RESULTS: Overall kappa was 0.70 (95% confidence interval (C.I.) 0.68-0.72). Reproducibility was poor for the categories trauma and unclassifiable, fair for the categories infections and placental/cord pathology, and very good to excellent for the categories maternal immune system pathology, congenital malformations and complications of prematurity. CONCLUSIONS: The proposed system showed a good level of agreement and appeared to be simply applicable. It offers a good insight in the underlying cause of death with the possibility for recognising preventive factors in future pregnancies and will enable (inter)national comparisons in causes of perinatal death. A reliable uniform registration of perinatal death based on the underlying causes should be the basis for improvement of the quality of perinatal care.

Birth Injuries↗
PubMed1999

Amniotic fluid nitric oxide metabolites, cyclic guanosine 3',5' monophosphate and dimethylarginine in alloimmunized pregnancies.

OBJECTIVE: To determine the relationship between gestational age or the Liley index (the severity of fetal hemolysis) and the amniotic fluid total nitrite (NOx), cyclic guanosine 3',5 'monophosphate (cGMP) and dimethylarginine (DMA) concentrations. We hypothesized that the concentrations of these components change because of fetal growth or adaptation to fetal anemia. STUDY DESIGN: Amniotic fluids (n=64) were obtained between 23 and 37 weeks from fifty-three patients at risk for alloimmunization. Amniotic fluids from the pregnancies with a Liley index=1 were considered as controls (n=17). Creatinine (C, microMol) was determined with the Jaffé reagent, nitrite (NOx, microMol) with the Griess reagent, cGMP (nMol) by an enzyme immunoassay and DMA (microMol) after HPLC. Multiple regression analysis was used for separating the effects of growth and the estimated degree of anemia. RESULTS: The concentration of NOx, cGMP and DMA was not related to the Liley index or whether or not the fetuses needed blood transfusions. The concentrations of creatinine (C), NOx and cGMP increased during pregnancy (in weeks;W) (C=-69.2+6.28W; r2=0.532; P<0.0001, NOx=-17.6+1.29W; r2=0.106; P=0.01, cGMP=-20.9+1.05W; r2=0.414; P<0.0001). The DMA concentration (3.8+/-0.8(SD) and the NOx/creatinine ratio (181+/-110 mM/M) did not change with gestational age. The cGMP/creatinine ratios (microM/M) increased (cGMP/C=-41.8+4.31W; r2=0.134; P=0.007) whereas the DMA/creatinine ratio (mM/M) declined during pregnancy (DMA/C=73.1-1.34W; r2=0.278; P=0.0002). Consequently, the NOx/DMA and cGMP/DMA ratios increased (NOx/DMA=-6.96+0.43W; r2=0.105; P=0.02, cGMP/DMA=-5.9+0.29W; r2=0.391; P<0.0001). CONCLUSIONS: The concentrations in amniotic fluid of cGMP and NOX, but not of DMA increase during gestation. The cGMP/creatinine ratio increases also whereas that of DMA decreases. The changes in products of the NO-cGMP pathway are independent of mild to moderate fetal hemolysis and may result from fetal growth as well as from reduced inhibition of NO synthase by DMA. Gestational age related effects should be taken into account when analyzing nitric oxide metabolites in amniotic fluids.

Amniocentesis↗