Intrauterine Intravascular Transfusion Research Articles

Intrauterine transfusions influence fetal leukocyte counts and subsets

The objective of this study was to determine the effect of intravascular intrauterine transfusion (IUT) on fetal leukocyte counts and subsets. For this purpose, pre- and post-transfusion blood samples of 81 fetuses, receiving a total of 253 IUTs, were compared. Immediately after the IUT procedure an average decrease in fetal leukocyte count of 4 per cent was observed. When corrected for the dilutional effect of IUT, the average increase in leukocyte count was 41 per cent (n=180), indicating that IUT resulted in a relative leukocytosis. This was in contrast to the statistically significant average decrease in platelet count of 62 per cent (P<0·0001) immediately after IUT, suggesting that the relative increase in leukocyte count was lineage-specific. Differential leukocyte counts revealed that the changes in fetal leukocyte count, in terms of percentage, after IUT were the result of an increase in monocytes and basophils and a decrease in lymphocytes. Flow cytometric analysis demonstrated that the decrease in lymphocytes was evenly distributed among the different subpopulations and not the result of a specific down-regulation of one or more lymphocyte subsets. We observed only a modest relation between the duration of the transfusion and the degree of relative leukocytosis, suggesting that the onset of the leukocytosis probably occurred within minutes after the start of the transfusion. The observed effects appeared transient since the pre-transfusion leukocyte count between each consecutive IUT did not reveal significant alterations during the course of IUT treatment. © 1998 John Wiley & Sons, Ltd.

The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal.

To determine the proportional reduction per day in the number of fetal and donor red blood cells from the fetal circulation after intrauterine intravascular transfusions. A retrospective study of 302 transfusions in 101 fetuses. The Department of Obstetrics and Gynaecology of the University Medical Centre Leiden, The Netherlands. We measured the haematocrit in fetal samples both before and after repeated intravascular intrauterine transfusion in fetuses with alloimmune disease. The percentage of fetal erythrocytes was determined in Kleihauer-Betke stained smears. The decline of fetal, donor and mixed red blood cells was calculated by dividing the proportional decrease of the haematocrit values of the number of days between transfusions, also after correction for changes in fetoplacental volumes. Results (given as mean [SD]) are derived from the proportional changes of haematocrit per day. The interval between the first and second transfusion (15.5 days [SD 5.2]) was shorter than between subsequent transfusions (means ranging from 21.4 to 21.9 days; P < or = 0.0001). The decline per day of mixed, and of donor red blood cells, calculated without corrections for volume changes did not differ from those corrected for volume changes resulting from the transfusion and from fetal growth (correction factor 1.1 [SD 0.4]). Since the coefficient of variance is smaller for the uncorrected decline values, this type of calculation is preferable for clinical purposes. The disappearance of fetal erythrocytes after the first transfusion (6.1%/day [SD 2.9]) was faster than that of mixed fetal and donor red blood cells (3.2%/day [SD 1.2]; P < 0.0001) and of donor cells alone (1.4%/day [SD 1.6]; P < 0.0001). The decline of the mixed red blood cell population became the same as that of the donor cells (2.2%/day [SD 0.8]) after the second transfusion. This decline of donor cells was higher than after the first transfusion (1.4%/day [SD 1.6]; P < 0.05). After the first transfusion the fetal erythrocytes disappeared faster after transplacental puncture of the umbilical cord (6.6%/day [SD 2.8]) than after transamniotic punctures (5.4%/day [SD 2.7]; P = 0.05). The mixed red blood cell also decreased faster (3.5%/day [SD 1.3] versus 2.8%/day [SD 0.9]; P < 0.01). The fast disappearance of fetal erythrocytes, especially after transplacental punctures, shows that the interval between the first and second transfusion needs to be shorter than that for intervals between subsequent transfusions. The number of donor erythrocytes declines by approximately 2% per day.

Intrauterine therapy for homozygous α-thalassemia

Alpha-thalassemia is one of the most common genetic disorders in the world and is becoming more common in the United States with the increase in immigration of susceptible populations. This disease has been stated previously to be incompatible with extrauterine life. A Filipino woman with a prior loss due to hemoglobin Bart's underwent prenatal diagnosis that confirmed recurrence in the index pregnancy. Intravascular intrauterine exchange transfusions maintained appropriate fetal growth. A cesarean delivery yielded a 2190-g male infant with minor malformations. The postnatal course was characterized by mild respiratory insufficiency. Postnatal chronic transfusion therapy is underway pending consideration for bone marrow transplantation. Antenatal diagnosis and therapy of homozygous alpha-thalassemia can prevent the prenatal consequences of hydrops and fetal death. New technologies such as stem cell transplantation may help to avert both prenatal and postnatal consequences.

Evaluation of standard parameters to predict exchange transfusions in the erythroblastotic newborn.

During the time period 1983-90, 91,300 consecutive pregnancies were monitored for red cell alloimmunization. Once revealed, the immunizations were followed by means of repeated maternal antibody titers, maternal anti-D quantitation in D-immunized women, amniotic fluid bilirubin levels and fetal hemoglobin concentrations. High dose intravenous immunoglobulin and/or intrauterine intravascular transfusion was given to prevent or treat fetal anemia. Delivery was induced for all before term when antibody titers were > or = 16. Nevertheless, exchange transfusions were performed in 41 newborns with mothers alloimmunized to Rh(D), Rh(c), Rh(E) and Kell antigens. Eight of the mothers were Rh(D) positive. Phototherapy alone was given to 35 newborns. Both maternal antibody titers and amniotic fluid bilirubin levels were found to be unreliable to predict the need of exchange transfusions in the newborns. Quantitation of maternal anti-D concentration was found to be significantly better predicting 62% at a cut-off level of 0.7 microgram/mL. Analysis of fetal hemoglobin concentration by cordocentesis is the only direct method to evaluate the degree of fetal affection, and should probably be performed when maternal antibody titers are > or = 64, anti-D concentration is > or = 0.7 microgram/mL and data indicate an aggravation of the immunization.

Basal ganglia and thalamic calcification following intrauterine intravascular transfusion.

In recent years intrauterine intravascular transfusion has become the method of choice for the treatment of severe fetal erythroblastosis. Despite the association of the procedure with fetal complications such as bradycardia and overtransfusion, later neonatal neurological consequences have been only rarely reported. A case is described of a neonate who underwent repeated intrauterine intravascular transfusion for treatment of erythroblastosis and who later developed calcification in the thalamus and the basal ganglia. The possible pathogenetic mechanisms are discussed.

Developmental outcome after intravascular intrauterine transfusion for rhesus haemolytic disease.

The development outcome of 16 infants who had rhesus disease was assessed at 18 months. Eight had received intravascular intrauterine transfusion and eight postnatal exchange transfusions. There was no difference in developmental outcome and neither group was different from the population as a whole.

Intrauterine intravascular transfusion for fetal haemolytic anaemia: the Western Australian experience.

To report the first four years' clinical experience with fetal intravascular blood transfusion for the treatment of fetal haemolytic anaemia in Western Australia. King Edward Memorial Hospital, Perth, which is the sole tertiary level perinatal centre in Western Australia with a referral base of approximately 25,000 pregnancies each year. Transfusion was by injection of packed cells from Rh-negative donors into the fetal umbilical vein near the site of insertion into the placenta. Fetal haemoglobin levels were measured before and after each transfusion. In most cases, the fetus was paralysed by intramuscular tubocurarine. Sixty intravenous transfusions were performed in 20 pregnancies. At the time of the initial transfusion, the mean haemoglobin level was 5.8 g/dL (range, 2.5-8.5 g/dL) and six fetuses had signs of hydrops. The case survival rate was 80% and the procedure survival rate was 93%. Three of the deaths occurred in the first five cases. Caesarean section was performed during two of the procedures, one because of bleeding from the cord puncture site and one because of tamponade of the umbilical vessels. Fetal intravascular transfusion is a highly effective treatment for fetal alloimmunisation and allows pregnancies to continue to term and to be delivered vaginally. However, the procedure may be difficult and requires a team approach with ready access to fetal monitoring and emergency caesarean section. Our results suggest that increasing experience of the team is a major factor in improved outcome.

The Severely Anemic and Hydropic Isoimmune Fetus

Hydrops caused by isoimmune hemolytic anemia is frequently associated with fetal death following intrauterine intravascular transfusion. To identify possible predictors of procedure-related fetal death, we examined changes in fetal blood volume and hematocrit resulting from the initial transfusion performed on 19 severely anemic, hydropic fetuses. Seven fetuses (36.8%) died at 24-72 hours after transfusion, but in no case was the procedure associated with fetal distress. There were no significant differences between fetuses who died and those who survived in terms of total volume of blood transfused, volume transfused as a percentage of total fetoplacental blood volume, hematocrit of transfused blood, post-transfusion hematocrit, umbilical vein pH, or gestational age at transfusion. Significant differences were noted between hydropic fetuses who died compared with those who survived in the mean pretransfusion hematocrit, 6.7% (+/- 2.0) versus 8.7% (+/- 1.6) (P = .03), and the relative increase in post- over pre-transfusion hematocrit, 5.5-fold (+/- 1.4) versus 3.5-fold (+/- 0.8) (P = .001). Stepwise logistic regression analysis confirmed that only the relative increase in hematocrit was predictive of fetal loss. Moreover, six of seven fetal deaths occurred when the relative increase in hematocrit was greater than fourfold, whereas ten of 12 surviving fetuses had relative increases of less than fourfold. We conclude that large, acute increases in fetal hematocrit following intrauterine transfusion are associated with substantial mortality in hydropic fetuses.

Evaluation of standard parameters to predict exchange transfusions in the erythroblastotic newborn

During the time period 1983-90, 91,300 consecutive pregnancies were monitored for red cell alloimmunization. Once revealed, the immunizations were followed by means of repeated maternal antibody titers, maternal anti-D quantitation in D-immunized women, amniotic fluid bilirubin levels and fetal hemoglobin concentrations. High dose intravenous immunoglobulin and/or intrauterine intravascular transfusion was given to prevent or treat fetal anemia. Delivery was induced for all before term when antibody titers were 16. Nevertheless, exchange transfusions were performed in 41 newborns with mothers alloimmunized to Rh(D), Rh(c), Rh(E) and Kell antigens. Eight of the mothers were Rh(D) positive. Phototherapy alone was given to 35 newborns. Both maternal antibody titers and amniotic fluid bilirubin levels were found to be unreliable to predict the need of exchange transfusions in the newborns. Quantitation of maternal anti-D concentration was found to be significantly better predicting 62% at a cut-off level of 0...

Necrotizing enterocolitis following intrauterine blood transfusion

Intravascular intrauterine transfusion allows a more sophisticated and exact approach to the management of severe Rh hemolytic disease. This technique involves direct manipulation of the fetal umbilical vessels; its hazards include umbilical cord trauma and thrombosis or emboli. The consequences of such events in utero are largely unknown. In this case necrotizing enterocolitis occured in a full-term infant after three intrauterine intravascular transfusions.

Absence of hyperinsulinemia in isoimmunized fetuses treated with intravascular transfusion

We serially sampled blood from fetuses of five severely isoimmunized pregnancies at the time of each intrauterine intravascular transfusion and at birth. We were unable to demonstrate either an elevation in the plasma insulin/glucose ratio or a relationship between the insulin/glucose ratio and hemoglobin concentration at any time period. Plasma total glutathione concentration, however, decreased dramatically from the initial to the second transfusion (323 ± 114 to 43 ± 9 ng/ml; t = -5.06, p < 0.01). We speculate that intrauterine transfusion may modify or prevent the previously reported fetal pancreatic β-cell hyperplasia and hyperinsulinemia associated with isoimmunization by decreasing red blood cell hemolysis and thereby circulating glutathione. (AM J OBSTET GYNECOL 1991;165:1737-40.)

Porencephalic cyst: A complication of fetal intravascular transfusion

A case of unilateral porencephalic cyst as a result of intravascular intrauterine transfusion is reported. Although other factors may have contributed, fetal bradycardia and relative hyperviscosity as a result of increased fetal hematocrit value were considered to be related to this event. Because some authors recommend direct intravascular transfusion to supraphysiologic hematocrits to prolong the interval between procedures, we would caution the use of this approach on the basis of theoretic considerations and the occurrence of this complication.

Intrauterine intravascular transfusion for severe erythroblastosis fetalis: How much to transfuse?

Intrauterine intravascular transfusion is now believed to be a more precise method for treating fetal anemia in erythroblastosis fetalis than is intraperitoneal transfusion. Previously established guidelines for the volume of blood to be given in intraperitoneal transfusion at a specific gestational age are not applicable for intravascular transfusion. In 28 patients, intravascular transfusion was performed on 81 occasions between 19-34 weeks' gestation. The total number of transfusions ranged from one to six per patient. The aim at each procedure was to achieve a final hematocrit of 35-50%. Factors examined as likely to determine the volume of blood required included pre-transfusion hematocrit, post-minus pre-transfusion hematocrit (hematocrit increase), the hematocrit of the transfused blood, gestational age, estimated fetal weight, and interval from last transfusion. The factors found to be most predictive of total volume of blood required for transfusion were the hematocrit increase and either estimated fetal weight or gestational age.

Management of Severe Hemolytic Disease with Ultrasound‐Guided Intravascular Fetal Transfusions

Between January 1987 and March 1989, 22 fetuses with severe hemolytic disease were treated with 64 ultrasound-guided intrauterine intravascular transfusions. Eighteen infants survived and are doing well. In 12 fetuses, hydropic changes were present at the first transfusion; 9 of these survived. In 8 of the 10 fetuses with a gestational age less than 26 weeks, intrauterine treatment was successful.

Acute fetal hemodynamic alterations after intrauterine transfusion for treatment of severe red blood cell alloimmunization

One of the compensatory hemodynamic mechanisms seen in the anemic human fetus is an increased cardiac output. With Doppler techniques, cardiac output was measured in 21 fetuses before and immediately after 38 intrauterine transfusions for severe red cell alloimmunization. Umbilical venous pressures were measured before and after transfusion; amniotic fluid pressure was also quantitated. After subtraction of amniotic pressure, umbilical venous pressure increased by 1.7 ± 2.8 mm Hg (p < 0.01). Left and right ventricular output declined by 19% and 22%, respectively (p < 0.001). Four factors are known to affect cardiac output: heart rate, cardiac contractility, preload, and afterload. Fetal heart rate and mean acceleration, a measure of myocardial contractility, were unchanged after transfusion. A calculated mean increase in the fetoplacental volume of 18% in conjunction with an increase in umbilical venous pressure would indicate that cardiac preload was increased. We propose that intravascular intrauterine transfusion leads to an increased cardiac afterload, possibly by increasing blood viscosity. The fetal heart responds to the increased afterload by a decrease in stroke volume, leading to a fall in cardiac output.

Placental transfer of cefazolin and piperacillin in pregnancies remote from term complicated by Rh isoimmunization

Although the administration of prophylactic antibodies for intrauterine transfusion is controversial, little information is available regarding placental transfer of antibiotics administered to the mother, or whether the presence of hydrops affects this placental transfer. Sixteen intravascular intrauterine transfusions were performed in 10 patients. Seven (10 procedures) patients were given 2 gm of cefazolin before the procedure and samples were obtained by fetal vascular access. Three patients (six procedures) were given 4 gm of piperacillin and samples were similarly obtained. Specimens were obtained for fetal serum, maternal serum, and amniotic fluid antibiotic concentration. The mean serum cefazolin concentration in hydropic fetuses was 18.04 ± 3.37 (ig/ml, and in nonhydropic fetuses the concentration was 21.02 ± 17.8 µg/ml (p = 0.72). The mean fetal serum concentration of piperacillin was 22 ± 12 (xg/ml. The placental transfer of both drugs was similar. We conclude that the transplacental passage of these antibiotics is prompt and that the presence of hydrops does not significantly impair the passage of cefazolin.

Short communications

A case of hydrops fetalis caused by massive fetomaternal hemorrhage was initially successfully treated by intrauterine intravascular transfusion. Unexplained intrauterine death occurred 2 weeks afterwards. The investigation of fetomaternal hemorrhage by fetal blood sampling and the management are discussed.

Management of Severe Hemolytic Disease with Ultrasound-Guided Intravascular Fetal Transfusions

Between January 1987 and March 1989, 22 fetuses with severe hemolytic disease were treated with 64 ultrasound-guided intrauterine intravascular transfusions. Eighteen infants survived and are doing well. In 12 fetuses, hydropic changes were present at the first transfusion; 9 of these survived. In 8 of the 10 fetuses with a gestational age < 26 weeks, intrauterine treatment was successful.

Fetal Cardiac Output in the Isoimmunized Pregnancy: A Pulsed Doppler-Echocardiographic Study of Patients Undergoing Intravascular Intrauterine Transfusion

Fetal Cardiac Output in the Isoimmunized Pregnancy: A Pulsed Doppler-Echocardiographic Study of Patients Undergoing Intravascular Intrauterine Transfusion

Fetal cardiac output in the isoimmunized pregnancy: A pulsed Doppler-echocardiographic study of patients undergoing intravascular intrauterine transfusion

The mechanism of development of hydrops fetalis in severe isoimmunization has been subject to speculation. We performed pulsed Doppler assessment of cardiac output in 13 severely isoimmunized fetuses before and after intravascular transfusion and compared the results with 37 control fetuses between 20 and 34 weeks' gestation. The cardiac index of the anemic fetuses was significantly greater than that of the control group. A significant (right ventricle, p less than 0.01; left ventricle, p less than 0.02) increase in indexed output was noted from both ventricles and in the combined ventricular output (mean +/- SEM 644 +/- 35.3 ml/kg/min in control fetuses versus 879 +/- 86.0 ml/kg/min in anemic fetuses, p less than 0.006). An increase in cardiac output was also noted when anemic fetuses were compared with gestational age-specific norms. We conclude that severely anemic fetuses of isoimmunized pregnancies tend to have significantly higher cardiac output than do unaffected fetuses and that this high output state may play a part in the development of hydrops fetalis.