Severe Red Cell Alloimmunization Research Articles

Relationship between maternal antibody type and antenatal course following intrauterine transfusion for red cell alloimmunisation

ObjectiveTo determine the antenatal course of severe red cell alloimmunisation in pregnancies requiring intrauterine fetal transfusion. Study designA retrospective cohort study over 16 years in a single national quaternary fetal medicine centre. From 1996 to 2011, 242 red cell intrauterine transfusions (IUT) were performed in 102 alloimmunised pregnancies. Antibody type was categorized into Rh(D) and non-Rh(D) (including Rh(c), Kell and Rh(E)). Women with Rh(D) antibodies were further stratified into those with and without additional red cell antibodies. Data were compared using the Mann–Whitney U and Fisher's exact tests. Two-tailed P values at the 5% level were considered significant. ResultsComparing Rh(D) and non-Rh(D) pregnancies, there were no differences in either gestational age or fetal haemoglobin at first IUT, number of transfusions required, gestation at delivery, caesarean delivery rates or perinatal losses. In women sensitized to Rh(D), the presence of additional antibodies did not influence the degree of fetal anaemia or the first transfusion-delivery interval, although rates of fetal hydrops were higher in the presence of multiple antibodies. The “procedure-related” loss rate was 1.7% per procedure in our institution. ConclusionAntibody status does not appear to influence clinical outcomes following fetal transfusion for alloimmunisation.

Therapeutic management of fetal anemia: review of standard practice and alternative treatment options

Fetal anemia, mainly due to red cell alloimmunization, is still a significant cause of fetal and neonatal mortality and morbidity. The focus of current clinical research has shifted from an invasive approach to non-invasive management and treatment of affected pregnancies, and the progress in this field is associated with a major improvement in perinatal outcome. During the last 50 years, intrauterine red cells transfusion (IUT), fi rst via the intraperitoneal route and later directly to fetal circulation, is the standard practice in most centers, with survival rates that exceed 90 % , particularly if anemia is diagnosed early and treated in a timely manner. In addition, plasmapheresis and intravenous administration of highdose immunoglobulin have been implicated in the treatment of pregnancies complicated with early-onset severe red cell alloimmunization, alone or in combination with IUTs before the 20(th) week of pregnancy, but there are still issues to be clarified further. This review article aims to provide an overview of the current standard therapeutic management and alternative treatment modalities in pregnancies complicated by fetal anemia.

412: Increased risk of intravascular intrauterine transfusion before 20 weeks gestation in the treatment of severe red cell alloimmunization

412: Increased risk of intravascular intrauterine transfusion before 20 weeks gestation in the treatment of severe red cell alloimmunization

Re: IVIG – Is it the answer? Maternal administration of immunoglobulin for severe red cell alloimmunisation during pregnancy: a case series. Connan K, Kornman L, Savoia H et al. 2009; 49: 612–618

Re: IVIG – Is it the answer? Maternal administration of immunoglobulin for severe red cell alloimmunisation during pregnancy: a case series. Connan K, Kornman L, Savoia H <i>et al.</i> 2009; 49: 612–618

Intérêt pratique du pic systolique de vélocité à l’artère cérébrale moyenne dans la prise en charge des anémies fœtales par allo-immunisation érythrocytaire

To assess the peak systolic velocity in the middle cerebral artery (PSV-MCA) in the prediction of fetal anemia in case of severe red-cell alloimmunization. A prospective study, from January 2003 to April 2006, of 47 consecutive pregnancies with severe alloimmunization. Fetal surveillance was based on titration and dosage of antibodies, ultrasound scans, and doppler for PSV-MCA measurement up to twice a week. A fetal blood sampling and in utero transfusion was performed in case of increase in PSV-MCA above 1.5 multiples of the median (MoM), and/or signs of hydrops on ultrasound. Severe fetal anemia was defined by fetal hemoglobin below 0.55MoM for gestational age. Analyses performed included the correlation between PSV-MCA and fetal hemoglobin, the value of PSV-MCA in the prediction of severe fetal anemia, and the determination of adequate threshold for intervention based on ROC curve analysis. Four hundred and eighty-five PSV-MCA were performed in 47 high-risk pregnancies, of which 125 were coupled with hemoglobin measurement by fetal blood sampling. There is a significant negative correlation between PSV-MCA and fetal hemoglobin (R2=0.6545 ; p<0.0001). Based on all prospective data, the negative predictive value of PSV-MCA was 97.8 %, sensitivity was 86.7 %, with a false positive rate of 12.2%. Area under the ROC curve was 0.85 (IC 95 %, 0.742-0.927 ; p<0.0001), suggesting an excellent value of this test. When switching the threshold for intervention from 1.5 to 1.6MoM, the positive predictive value increased, without decrease in sensitivity or negative predictive value. This study confirms the correlation between PSV-MCA and fetal hemoglobin. It allows a decrease of invasive procedures in the follow-up of pregnancies with severe red-cell alloimmunization.

Combined plasmapheresis and intravenous immune globulin for the treatment of severe maternal red cell alloimmunization

The objective of the study was to report the maternal and perinatal outcome in patients with severe red cell alloimmunization in pregnancy who were treated with immunomodulation therapy. This was a retrospective multicenter case series. Patients with a history of early second-trimester fetal loss secondary to severe maternal red cell alloimmunization or patients with markedly elevated maternal antired cell titers felt to be consistent with poor fetal outcome were offered treatment. Therapy consisted of serial plasmapheresis followed by weekly infusions of intravenous immune globulin (IVIG). Maternal titers were measured before and after plasmapheresis. Pregnant patients with either a history of a previous perinatal loss (n = 7) or markedly elevated maternal antibody titers (n = 2) were treated with combined plasmapheresis and IVIG. All 9 fetuses subsequently required intrauterine transfusions (median 4; range 3-8). All infants survived with a mean gestational age at delivery of 34 weeks (range 26-38 weeks). Maternal antired cell titers were significantly reduced after plasmapheresis (P < .01) and remained decreased during IVIG therapy. Serial peak middle cerebral artery velocities remained below the threshold for moderate to severe fetal anemia during therapy. Combined immunomodulation with plasmapheresis and IVIG represents a successful approach to the treatment of severe maternal red cell alloimmunization.

Advantages of Larger Volume, Less Frequent Intrauterine Red Blood Cell Transfusions for Maternal Red Cell Alloimmunization

Larger volume intravascular transfusions to manage severe maternal red cell alloimmunization in pregnancy may prolong the interval between procedures without increasing maternal, fetal, or neonatal complications. A retrospective cohort study compared the management and outcome of 19 patients with severe red cell alloimmunization managed at two facilities with different intravascular transfusion protocols. The volume of blood transfused, pre- and post-transfusion fetal hematocrit, and interval (days) between intravascular transfusions were compared. The respective maternal, fetal, and neonatal results were compared. The red blood cell volume transfused per procedure and the post- but not pre-transfusion fetal hematocrits were higher at New York Hospital than at Westchester County Medical Center. The interval between transfusions at New York Hospital (25.2 +/- 8.65 days) was longer than at Westchester County Medical Center (13.5 +/- 6.0 days, p < 0.0001). Although larger volume transfusion was occasionally associated with transient fetal bradycardia, all red blood cell transfusions were completed without complication. The adverse outcomes, complication rates, and neonatal outcomes were otherwise similar in both management protocols. It is possible to significantly increase the interval between intravascular transfusions with larger transfusion volumes for the management of severe maternal red cell alloimmunization without undue risk. The overall risk for the fetus and mother may be reduced by performing fewer transfusions and avoiding additional blood product exposures.

Noninvasive assessment of fetal anaemia

In pregnancies complicated by severe red cell alloimmunization, fetal haemolytic anaemia can lead to intrauterine demise as early as 17 weeks' gestation. Intrauterine intraperitoneal blood transfusion, introduced by Liley in 1963, proved to be the first successful example of fetal therapy. The use of this complex procedure, involving X-ray guided puncture of the fetal peritoneal cavity, was limited to fetuses with a gestational age ranging from 24 to 33 weeks. When performed below 26 weeks, survival rates were as low as 16%. The need for intrauterine transfusion was mainly based on determination of bilirubin levels in amniotic fluid, and plotting the results in a three-zone chart devised by Liley. This chart was based on correlations of amniotic fluid bilirubin concentrations with the degree of neonatal anaemia, and ranged from 27 to 41 weeks' gestation. In the 1980s, with the introduction of ultrasound-guided intravascular transfusion, treatment became possible from 17–18 weeks' gestation onwards. Consequently, there was a need for diagnostic tests to assess the degree of anaemia in the second trimester fetus. The use of the Liley chart was shown to be unreliable in the prediction of disease severity before 27 weeks' gestation. Ultrasonographic detection of fetal hydrops in these pregnancies reliably indicates severe anaemia, but for reasons that are still unclear, a significant number of severely anaemic fetuses do not show ultrasonographic signs of hydrops. In 1988, Nicolaides et al studied the use of several ultrasonographic parameters to predict anaemia in nonhydropic fetuses. Their results were disappointing, and they concluded that the only reliable diagnostic test to assess the degree of fetal disease was fetal blood sampling.

Doppler assessment of renal blood flow velocity waveforms in the anemic fetus before and after intravascular transfusion for severe red cell alloimmunization

Image-directed pulsed Doppler ultrasonography demonstrated a decrease in the pulsatility index of the renal artery in 9 anemic fetuses (less than 30 weeks, menstrual age) soon after intravascular transfusion. The pulsatility index returned to pretransfusion values the day following the transfusion. End diastolic blood velocity in the renal artery could not be measured before the transfusion, was detectable immediately after the procedure, and was again nonmeasurable one day after the transfusion. These data suggest an increase in renal blood flow in the anemic fetus soon after intravascular transfusion to eliminate excess fluid.

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.

Comparison of Four Types of Intrauterine Transfusion: Effect on Fetal Hematocrit

The advent of cordocentesis has made it possible to treat fetuses affected by severe red cell alloimmunization by infusing red cells into umbilical vessels. In addition, serial hematocrits can be followed between transfusions. Twenty fetuses underwent a total of 118 intrauterine procedures. Four transfusion techniques were compared to assess the effect of each method on the stability of the fetal hematocrit between procedures. The change in hematocrit per day for direct intravascular transfusion was -1.06 +/- 0.68%, for intraperitoneal transfusion: +0.03 +/- 0.6%, for combined exchange intravascular and intraperitoneal transfusion: +0.02 +/- 0.3% and for combined direct intravascular and intraperitoneal technique: -0.01 +/- 0.4%. The greatest fall in hematocrit was noted with the use of the direct intravascular technique alone (p less than 0.001). The combined direct intravascular/intraperitoneal approach produces a stable hematocrit between procedures and offers the possibility of performing intrauterine transfusions at less frequent intervals.