Robertjan H. Meerman

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.

Ultrasonographic fetal spleen measurements in red blood cell-alloimmunized pregnancies

OBJECTIVES This study was performed to evaluate the possible relationship between fetal spleen size and fetal hemoglobin levels and to assess the predictive value of ultrasonographically measured fetal spleen size as an estimate of the severity of fetal hemolytic anemia. STUDY DESIGN Before 85 consecutive fetal blood samples in 28 red blood cell-alloimmunized pregnancies ultrasonographic fetal spleen measurements were performed. Results were compared with our own longitudinally derived reference ranges and were correlated with fetal hemoglobin deficit. RESULTS A significant positive correlation was found between spleen perimeter and fetal hemoglobin deficit. The ultrasonographic finding of splenomegaly correctly predicted severe fetal anemia (hemoglobin deficit > 5 SD from normal mean) in 44 of 47 cases, a positive predictive value of 94%. At first transfusion all fetuses showing splenomegaly were severely anemic. CONCLUSION Fetal spleen measurements may be a useful adjunct to ultrasonographic evaluation in the management of severe red blood cell-alloimmunized pregnancies.

Obstetric history and antibody titer in estimating severity of Kell alloimmunization in pregnancy.

OBJECTIVE: To evaluate the usefulness of the obstetric history and the maternal serum Kell antibody titer in the management of pregnancies with Kell alloimmunization. METHODS: In a retrospective cohort study of 41 pregnancies complicated by Kell alloimmunization, the obstetric history, divided into presence or absence of a previous Kell-positive child, and Kell antibody titers in the index pregnancy were correlated with the gestational age at the onset of fetal anemia. RESULTS: Women with a previous Kell-positive child had a lower gestational age at the first intrauterine transfusion compared with those without a previous Kell-positive child (P=.01). However, in two of 29 pregnancies in the latter group, severe fetal anemia requiring transfusion was detected before 20 weeks of gestation. In neither group were maternal Kell antibody titers significantly correlated with gestational age at first intrauterine transfusion (P=.62 and P=.72, respectively). In all but two pregnancies (1:2 and 1:4, respectively), antibody titers were at least 1:32 before the first intrauterine transfusion. CONCLUSION: For timely detection of all cases of severe fetal anemia, Kell-alloimmunized pregnancies with a Kell-positive fetus and titers greater than or equal to 1:2 should be closely monitored from 16 to 17 weeks of gestation onward. LEVEL OF EVIDENCE: II

Fetal cardiac contractility before and after intrauterine transfusion

To evaluate the effect of fetal anemia and intrauterine transfusion on ventricular shortening fraction.

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

OBJECTIVE To assess the diagnostic accuracy of amniotic fluid Δ 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 Δ OD 450 values were plotted on an extrapolated Lileys chart. Sensitivity and specificity were calculated for two commonly used cutoff levels, Lileys zone 3 and the upper third of Lileys 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 Lileys 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 Δ OD 450 values in Lileys zone 3 or the upper third of Lileys zone 2 was 95% (95% CI 74, 100) before and 98% (95% CI 89, 100) after 27 weeks. CONCLUSION Lileys extrapolated curve predicts severe fetal anemia with reasonable accuracy and high sensitivity.

Implementation of routine screening for Kell antibodies: does it improve perinatal survival?

BACKGROUND: In 1998 a national program for first‐trimester screening for red cell (RBC) antibodies in all pregnant women was implemented. The aim of our study was to assess the impact on perinatal mortality caused by Kell alloimmunization

Effect of an Increase of the Hematocrit on Middle Cerebral Artery Peak and Umbilical Vein Maximum Velocities in Anemic Fetuses

Objective: To measure the effects of acute large increases of the hematocrit on fetal peak arterial and maximum venous blood flow velocities. Methods: Middle cerebral artery peak flow velocities and umbilical vein maximum flow velocities were measured before, immediately after, and 12–24 h after intrauterine transfusions. All measurements were standardized for gestational age. Results: Complete measurements were obtained at 60 intrauterine transfusions. The mean hematocrit before intrauterine transfusion was 0.19 l/l and after 0.40 l/l. The middle cerebral artery peak flow velocity decreased immediately after transfusion in 59 of the 60 cases. There was a rise in umbilical vein maximum flow velocity immediately after intrauterine transfusion in 37 of the 60 cases. The sensitivity of middle cerebral artery peak flow velocity for severe anemia before intrauterine transfusion was 54% and the specificity 57%. The sensitivity of umbilical vein maximum flow velocity for severe anemia before intrauterine transfusion was 67% and the specificity 57%. Conclusions: An acute large increase of the fetal hematocrit significantly decreases middle cerebral artery peak flow velocity. The effect on umbilical vein maximum velocity is, however, unpredictable.

Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation

Severe alloimmune hemolytic disease of the fetus is treated with intrauterine transfusions (IUTs). Despite C, c, E, e, and K matching between mother and donor, IUT results in new antibodies in approximately 25% of women. Newly formed Fya, Fyb, Jka, Jkb, and S antibodies are in 83% presumably induced by the IUT donor. Therefore, we intentionally extended matching between mother and IUT donor for these additional antigens. The results, after almost 8 years of applying this protocol, are reported.

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.