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A study of the birthweight of 876 babies affected by rhesus hemolytic disease has shown that this is reduced in the most severely affected cases, when intrauterine transfusion is not required. However, in 259 very severely affected babies where intrauterine transfusion was necessary, the birthweight was similar to that of the mildly affected and unaffected babies.
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Sinusoidal fetal heart rate (SHR) records were obtained in 8 cases, either antepartum (3 cases of fetal Rh disease) or intrapartum (one case with an acute episode of fetomaternal transfusion as possible cause, 2 after meperidine administration to the mother and 2 others without attributable causes). Characteristics of both SHR patterns and related clinical pictures are described and compared to similar cases published elsewhere. The possible underlying mechanisms of SHR are discussed. Two different profiles of SHR patterns (smooth and jagged waveforms) are characterized and correlated with their most usual clinical backgrounds and prognostic significance. A classification of SHR into 2 main types is proposed, with clinical use in mind.
Induction of labour is an important prophylactic procedure in the obstetric practice. Two major types of indications developed: induction because of advanced relevant obstetric complication, and the so called elective induction.
OBJECTIVE: To determine fetal serum and amniotic fluid (AF) levels of interleukin (IL)-3, IL-6, granulocyte-macrophage colony-stimulating factor, stem cell factor, and erythropoietin, and to explore the relationship between cytokines and hemoglobin concentration, white blood cell count (WBC), and platelet count in fetuses affected by Rh immunization. METHODS: Thirty-four consecutive Rh-immunized patients in gestational weeks 19-33 were included. All patients were investigated by funipuncture and 13 by amniocentesis. The levels of IL-3, IL-6, granulocyte-macrophage colony-stimulating factor, stem cell factor, and erythropoietin were estimated using commercially available immunoassays. RESULTS: There was a significant correlation between erythropoietin concentrations in fetal serum and AF (r = 0.54, P < .05), whereas none of the other cytokines showed a positive correlation between these two compartments. Fetal serum contained higher concentrations of IL-3, granulocyte-macrophage colony-stimulating factor, stem cell factor, and erythropoietin compared with AF. In contrast, the IL-6 level was significantly higher in AF compared with fetal serum (P = .002). Erythropoietin and IL-3 levels were both negatively correlated with fetal hemoglobin concentrations (r = -0.75, P = .02, and r = -0.67, P = .045). The fetal WBC correlated significantly with the fetal serum concentration of granulocyte-macrophage colony-stimulating factor (r = 0.38, P = .04). CONCLUSION: Human fetuses with anemia due to erythrocyte immunization exhibit an increased production of erythropoietin and IL-3. Other studied cytokines (such as stem cell factor, granulocyte-macrophage colony-stimulating factor, and IL-6) did not correlate with the degree of fetal anemia. Among the studied cytokines, only erythropoietin showed a positive correlation between fetal serum and AF.
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The pregnancy-associated major basic protein, a protein elevated in the sera of all pregnant women, is virtually identical to the eosinophil granule major basic protein. To determine whether pregnancy-associated major basic protein is present in amniotic fluid, we examined samples from both early and late gestation by a double antibody radioimmunoassay. A total of 112 amniotic fluids were tested and all but three contained levels of pregnancy-associated major basic protein greater than 400 ng/ml. Amniotic fluid pregnancy-associated major basic protein antigenic activity was immunochemically identical to that of the eosinophil granule major basic protein and also had identical physicochemical properties such as heat stability and the need for reduction and alkylation. Although the majority of amniotic fluid samples (90 of 112) were obtained from healthy women with normal gestations, the remaining 21 amniotic fluid samples were from women with Rh sensitization and from one gestation complicated by intrauterine growth retardation.
A reference range of fetal noradrenaline levels related to gestational age was calculated from 27 normal pregnancies between 16 and 36 weeks of gestation. Growth retarded, hypoxic fetuses had significantly elevated noradrenaline levels (P less than 0.01).
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OBJECTIVE: The purpose of this study was to evaluate the quantification of fetomaternal hemorrhage by the manual and automated microscopic analysis of Kleihauer-Betke stained slides and by flow cytometry. STUDY DESIGN: Blood smears were stained and evaluated manually according to the Kleihauer-Betke test. The same slides were used for automated microscopy. In addition, blood flow cytometry was performed by anti-hemaglobin F immunostaining. RESULTS: Fetomaternal hemorrhage >0.1% was detected in 4 patients by manual and automated Kleihauer-Betke test and by blood flow cytometry. Fetomaternal hemorrhage was absent according to all 3 methods in 13 patients; fetomaternal hemorrhage<0.1% was detected in 27 patients by either manual or automated Kleihauer-Betke test or both. Moderate agreement was observed between the manual and automated Kleihauer-Betke test (weighted kappa, 0.56; 95% CI, 0.33-0.78). Agreement between the manual Kleihauer-Betke test and blood flow cytometry was fair (weighted kappa, 0.40; 95% CI, 0.15-0.66). CONCLUSION: Automated microscopic detection of fetal blood cells in clinical samples provides accurate quantification that is comparable to the manual Kleihauer-Betke test in both small and large fetomaternal hemorrhage. Blood flow cytometry is capable only of quantifying fetomaternal hemorrhage of >0.1%.
OBJECTIVE: The middle cerebral artery peak systolic velocity (MCA-PSV) has been successfully used for timing the first 2 transfusions in fetuses at risk for anemia because of maternal red cell alloimmunization. The objective of this study was to assess whether the correlation between the MCA-PSV and fetal hemoglobin is maintained in fetuses that had undergone 2 previous intrauterine transfusions. STUDY DESIGN: Doppler measurement of MCA-PSV was performed before cordocentesis in 39 fetuses. The timing of the third transfusion was based on traditional criteria. The values of MCA-PSV and hemoglobin were expressed as multiples of the median (MoM). Anemia was defined as mild (hemoglobin <0.84 MoM for a given gestational age, moderate (hemoglobin <0.65 MoM), and severe (hemoglobin <0.55 MoM). Regression analysis was used to assess the correlation between the MCA-PSV MoM and fetal hemoglobin MoM. RESULTS: Gestational age at Doppler study ranged from 22 to 35 weeks. Six fetuses (15%) had normal hemoglobin concentration; 21 (53%) had mild anemia; 7 (20%) had moderate anemia; and 5 (12%) had severe anemia. There was a linear correlation between fetal hemoglobin (y) and the MCA-PSV (x): y = 1.185 - 0.341x. CONCLUSION: Previously, concerns have been expressed about the accuracy of Doppler prediction of anemia after previous transfusions. Our data suggest that there is a good correlation between the MCA-PSV and fetal hemoglobin in fetuses that have undergone 2 previous transfusions. Our findings expand the clinical situation in which Doppler can be used to monitor red cell alloimmunized pregnancies.
OBJECTIVE: This study was undertaken to determine the detection of fetal anemia and false-positive rates by fetal middle cerebral artery peak systolic velocity (MCA-PSV) and the estimated daily decrease of hemoglobin (Hb) in red blood cell alloimmunized pregnancies that had previous fetal transfusions. STUDY DESIGN: We examined the relation between MCA-PSV measured before cordocentesis, and fetal Hb at the time of the second (n = 42) and third (n = 31) intrauterine blood transfusions. In addition, the daily Hb drop between the transfusions was calculated. RESULTS: The MCA-PSV provided significant prediction of severe anemia (Hb deficit > or = 6 g/dL) for the second but not for the third transfusion. Detection of 95% of severely anemic fetuses was achieved with a false-positive rate of 37% for the second transfusion and 90% for the third, compared with 14% in our previous study for the first transfusion. In patients who had received 2 previous transfusions, the only significant predictor of fetal anemia was the estimation of the Hb from the measured posttransfusion Hb after the second transfusion and the assumption that the rate of decrease in fetal Hb is 0.3 g/dL per day. CONCLUSION: Prediction of severe fetal anemia after one transfusion is less accurate than in nontransfused fetuses. The MCA-PSV is not useful in predicting severe anemia in fetuses that already had 2 previous transfusions.
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We studied the relationship between bilirubin concentrations in amniotic fluid and fetal blood in 68 non-hydropic rhesus d-alloimmunized anemic fetuses at first blood sampling. In these alloimmunized fetuses, the amniotic fluid/fetal blood ratio for bilirubin decreased from 0.09 at 28 weeks to 0.05 at 33 weeks. In normal fetuses, amniotic fluid/fetal blood ratios for bilirubin, and for albumin, are in the same range and show a similar decrease during gestation. We conclude that amniotic fluid bilirubin concentration is determined, firstly, by fetal blood bilirubin concentration and, secondly, by the amniotic fluid/fetal blood ratio of albumin. Among five possible pathways bilirubin could take to build up a concentration in amniotic fluid (fetal kidneys, lungs, skin, bowel, membranes), the intramembranous pathway is the only one that is compatible with the amniotic fluid/fetal blood ratios for bilirubin that we found and must therefore be the most important.
In the past 20 years, numerous monoclonal anti-D antibodies have been developed in order to replace the human plasma derived anti-D immunoglobulins, using different in vitro functional assays as screening methods. Some of these monoclonal antibodies have been evaluated in exploratory in vivo clinical trials, notably for their ability to mediate the clearance of D-positive red cells. A review of these reported trials is presented and the results are analyzed in the light of the newly published hypothesis conferring an important role to some Fc-FcgammaR interactions and to the glycosylation-dependent potency of the monoclonal anti-D antibodies.