Flow velocity waveforms of the umbilical and cerebral arteries before and after intravascular transfusion

Thirteen intravascular transfusions were performed in 13 human fetuses who were anemic because of severe red-cell alloimmunization. To investigate the status of the umbilical and cerebral circulations by pulsed Doppler ultrasound, we studied the fetal middle cerebral artery (N = 13), internal carotid artery (N = 11), anterior cerebral artery (N = 11), and umbilical artery (N = 13) before, within the first 2 hours after, and the day after intravascular transfusion. The gestational age at the time of transfusion was 21-31 weeks (mean +/- SD 25 +/- 3.1). The fetal hematocrits before transfusion ranged from 12-32% (23.4 +/- 6.1), whereas the hematocrit after transfusion was between 25-42% (35 +/- 5). The net blood volume transfused (volume infused--volume removed) ranged between 7.5-31.0 mL (16.0 +/- 7.4). The hematocrit of the transfused blood varied between 68-81% (74 +/- 4). Repeated-measures analysis of variance indicated significant differences in the pulsatility index values of the four vessels studied. The same analysis indicated significant differences in the pulsatility index values at the three time points. Multiple comparison tests showed that the pulsatility index was reduced significantly immediately after transfusion for each vessel studied, but returned to pretransfusion levels by the next day. These data suggest a change in vascular impedance soon after transfusion as a consequence of direct intravascular transfusion.     

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 less than 0.01). Left and right ventricular output declined by 19% and 22%, respectively (p less than 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.     

Pulsed Doppler flow-velocity waveforms before and after intrauterine intravascular transfusion for severe erythroblastosis fetalis

Pulsed Doppler studies of the fetal and maternal circulations were carried out before and after 64 intrauterine transfusions performed on 24 fetuses. A model was derived for the prediction of hematocrit before the first transfusion: Hematocrit = 7.778 - (0.088 x peak velocity in descending aorta) + (0.968 x gestational age [weeks]) - (10.911 if hydrops present) (r = 0.876, p less than 0.0001). An alternative formula, excluding hydrops, was slightly less predictive: Hematocrit = 45.312 - (56.261 x umbilical cord Pourcelot index) - (0.128 x peak velocity in descending aorta) + (1.042 x gestational age) r = 0.822, p less than 0.001). Neither model was accurate in the prediction of hematocrit before second or subsequent transfusions. A third model was derived from second-transfusion data: Hematocrit = 40.524 - (0.045 x peak velocity in descending aorta) - (10.693 x pulsatility index of maternal uterine artery) (r = 0.81, p less than 0.003). However, this model was unable to predict hematocrit before third or later transfusions. No changes in Doppler parameters before and after transfusion were found. We conclude that pulsed Doppler ultrasound may be helpful in the evaluation of isoimmunized pregnancies, in differentiating anemic from normal fetuses. It does not appear to be useful in determining the timing of later transfusions. The lack of change before and after transfusions suggests that these vessels will not provide significant information concerning the effect of rapid volume and hematocrit changes in the fetus.     

The effect of fetal hydrops on the rate of fall of hemoglobin after fetal intravascular transfusion for red cell alloimmunization

OBJECTIVE: We aimed to assess whether there is a difference between hydropic and nonhydropic fetuses in the rate of fall of hemoglobin (Hb) following intravascular transfusions. METHODS: Eighty-three intravascular transfusions in 34 fetuses were analyzed. The pretransfusion and posttransfusion Hb values, the gestational age, the volume of blood transfused, the number of days between transfusions and the rate of fall of Hb per day following a transfusion were assessed. Hb levels were expressed as multiples of standard deviation from the normal mean for gestational age. RESULTS: Eleven fetuses were hydropic at presentation and 23 were not. Twenty-three transfusions were undertaken in the 11 fetuses while they were hydropic and 60 transfusions were performed in nonhydropic fetuses. Comparisons of transfusion variables between the two groups were performed both for the first transfusion only and also for the total number of transfusions. The rate of Hb fall per day following a transfusion was similar in the two groups on both comparisons. The posttransfusion Hb level tended to be lower and the intervals between transfusions were a little shorter in the hydropic group, but these differences were not statistically significant. CONCLUSION: The posttransfusion Hb tended to be lower in the hydropic fetuses, but the fall in Hb was not faster in these cases. Therefore, with a similar rate of daily Hb decline in both groups, the hydropic fetuses are expected to become anemic again sooner than the nonhydropic fetuses only because of the lower posttransfusion Hb. The timing of the next transfusion should therefore be based on the posttransfusion Hb and the normal predicted drop per day irrespective of the presence or absence of hydrops.     

Longitudinal assessment of blood flow velocity waveforms in the healthy human fetus

A longitudinal study was carried out on 30 healthy fetuses in order to assess the modifications of fetal blood flow throughout pregnancy. The pulsatility index was evaluated at two-week intervals by means of pulsed Doppler equipment. In the umbilical artery measurements were performed from 20 weeks onwards, whereas in the descending aorta and internal carotid artery analysis started from 26 weeks onwards. A decrease of the pulsatility index in umbilical artery and in the ratio between the pulsatility indexes in umbilical artery and internal carotid artery was found over the second half of pregnancy.     

In-utero intravascular transfusion of the fetus for the management of severe Rhesus isoimmunization--a reappraisal

Ten fetuses, severely affected by Rhesus (D) haemolytic disease, received one to three intravascular blood transfusions at between 18 and 30 weeks gestation, with the use of fetoscopically guided needles into one of the umbilical cord vessels. Although the technique was successfully accomplished in all cases, the fetal response to the procedure was varied. Only two fetuses survived beyond the neonatal period, and one child subsequently died principally because of the problems resulting from premature delivery. The reason for the low rate of survival has been explored and the continued use of the method described is now questioned.     

The effect of intravascular transfusion for rhesus haemolytic disease on umbilical artery Doppler flow velocity waveforms

Summary. To test the hypothesis that an increase in fetal blood viscosity is associated with an increase in resistance to flow, the effect on Doppler flow velocity waveforms of percutaneous umbilical blood sampling and intravascular transfusion was studied in 20 patients undergoing a total of 35 procedures. All but four of the 22 transfusions were associated with a decrease in resistance to flow, as shown by a reduction in the umbilical artery systolic/diastolic ratio, and this also occurred on 10 of the 13 occasions when blood sampling only was performed. These findings suggest that acute changes in blood viscosity following intravascular transfusion arc not associated with an increase in resistance to flow as assessed by Doppler velocimetry. Umbilical blood sampling per se may be associated with a Immorally mediated reduction in placental vascular resistance to flow.     

Intrauterine intravascular transfusions for severe red blood cell isoimmunization: ultrasound-guided percutaneous approach

Eight pregnancies with severe red blood cell isoimmunization were managed with use of an intravascular approach for intrauterine transfusions. Fetoscopy was not employed, and the procedures were performed percutaneously under direct ultrasound visualization. A total of 16 of 18 attempted transfusions were successfully performed, with four fetuses requiring more than one transfusion. Technical aspects of the procedure as well as its indications, advantages, and drawbacks are discussed.     

The effect of intravascular transfusion for rhesus haemolytic disease on umbilical artery Doppler flow velocity waveforms

To test the hypothesis that an increase in fetal blood viscosity is associated with an increase in resistance to flow, the effect on Doppler flow velocity waveforms of percutaneous umbilical blood sampling and intravascular transfusion was studied in 20 patients undergoing a total of 35 procedures. All but four of the 22 transfusions were associated with a decrease in resistance to flow, as shown by a reduction in the umbilical artery systolic/diastolic ratio, and this also occurred on 10 of the 13 occasions when blood sampling only was performed. These findings suggest that acute changes in blood viscosity following intravascular transfusion are not associated with an increase in resistance to flow as assessed by Doppler velocimetry. Umbilical blood sampling per se may be associated with a humorally mediated reduction in placental vascular resistance to flow.     

In-utero intravascular transfusion of the fetus for the management of severe Rhesus isoimmunization—a reappraisal

Summary. Ten fetuses, severely affected by Rhesus (D) haemolytic disease, received one to three intravascular blood transfusions at between 18 and 30 weeks gestation, with the use of fetoscopically guided needles into one of the umbilical cord vessels. Although the technique was successfully accomplished in all cases, the fetal response to the procedure was varied. Only two fetuses survived beyond the neonatal period, and one child subsequently died principally because of the problems resulting from premature delivery. The reason for the low rate of survival has been explored and the continued use of the method described is now questioned.     

Effect of atracurium or pancuronium on the anemic fetus during and directly after intravascular intrauterine transfusion. A double blind randomized study.

BACKGROUND: To determine the effect of atracurium or pancuronium on onset and duration of fetal paralysis, movements and heart rate parameters directly after transfusion, using computer analyzed fetal heart rate recording (c-FHR). METHODS: Double blind randomized study of 23 RhD alloimmunized pregnant women requiring an intravascular intrauterine fetal blood transfusion (IUT) between 24 and 36 weeks. Atracurium was injected in 11 fetuses at 17 IUT's and pancuronium in 12 fetuses at 19 IUT's. For statistical analysis the Mann-Whitney test was used. RESULTS: No statistical differences were found in fetal heart rate and movements between both groups before transfusion. The fetal movements returned more rapidly in the atracurium group when compared to the pancuronium-group (median 24 vs. 57 min, range 6-55 vs. 4-220; (p<0.02). Fetal movements did not hamper the procedure in any case. The atracurium group showed significantly more fetal movements (p<0.01), more accelerations (0<0.05) but no significant reduction of fetal heart rate variability directly after transfusion which was in direct contrast to the pancuronium group. CONCLUSIONS: Neuromuscular blockade with atracurium produces sufficient paralysis for intrauterine transfusion with minimal disturbance of the parameters used to monitor fetal wellbeing after the procedure. Although the routine use of fetal paralysis during IUT may be questionable, we believe that when it is necessary the use of atracurium is the better choice.     

The effect of intrauterine intravascular blood transfusion on iron metabolism in fetuses with Rh alloimmunization

Fetal plasma ferritin concentrations were measured in 43 normal fetuses at 18-36 weeks and in 78 blood samples collected before transfusion from 23 fetuses with Rh alloimmunization. Among controls, there was a significant correlation between fetal serum ferritin and gestational age (r = 0.39, P = .009), consistent with an increase in fetal storage of iron during normal pregnancy. In Rh-alloimmunized fetuses, the ferritin concentration was above the reference range in 63% of the samples. Before the first transfusion, the fetal ferritin concentration was increased compared with controls (mean multiples of the mean = 2.6, range 1-26) and showed a negative correlation with fetal hematocrit (r = -0.43, P less than .05), suggesting that the worse the fetal anemia, the higher the iron store. Serial transfusions were associated with further increase in serum ferritin, which correlated primarily with the total volume of blood transfused. Three fetuses had plasma serum ferritin concentrations above 1 mg/L, a level compatible with a diagnosis of iron overload in children. These observations suggest that there is a potential risk of iron overload in Rh-alloimmunized fetuses undergoing intrauterine blood transfusion.     

Intravenous fetal exchange transfusion before 22 weeks of gestation in early and severe red-cell fetomaternal alloimmunization

OBJECTIVES: To determine the perinatal outcome in severe red-cell fetomaternal alloimmunization. METHODS: Retrospective series of 32 affected fetuses treated with intravenous fetal exchange transfusion (IFET) before 22 weeks of gestation. The main outcome measures were the degree of fetal anemia, fetal transfusions and perinatal outcome. RESULTS: The first IFET was performed at 19.8 +/- 1.8 weeks of gestation. All fetuses were severely anemic and hemoglobin levels were not different between 20 hydropic and 12 nonhydropic fetuses (4.1 +/- 2.5 vs. 5.6 +/- 2.8 g/dl, p=0.33). The initial maternal anti-D level ranged from 4 to 76 microg/l and was not correlated to fetal anemia (r=-0.07). CONCLUSION: The overall perinatal survival rate was 78% compared to a previous perinatal loss rate excluding first pregnancies of 55.5%.