Intrauterine Intravascular Transfusion Research Articles

SFM Fetal Therapy Practice Guidelines: Intrauterine Blood Transfusion

AbstractDespite routine antenatal anti-D prophylaxis with immunoglobulin, Rh alloimmunization and hemolytic disease of the fetus and newborn continue to occur due to a myriad of reasons. Intrauterine intravascular transfusion (IUT) or fetal blood transfusion is a therapeutic prenatal procedure in which specifically prepared and treated unit of donor red blood cells is injected intravascularly into the umbilical vein under ultrasound guidance. Originally introduced in the year 1963, it continues to be the standard treatment for severe fetal anemia. The objective of this guideline is to provide an evidence-based update of IUT for the perinatal healthcare providers.

Gestation outcomes in various options of help for pregnant women with Rh-immunization

BACKGROUND: To date, several options for helping pregnant women with rhesus immunization are known: (a) active tactics in carrying out methods of efferent therapy in the form of basic operations (plasmapheresis, hemosorption) in combination with adjuvant methods (immunoglobulin, blood photomodification with ultraviolet, laser beams, ozone therapy) to pregnant women; (b) wait-and-see active tactics with observation of the pregnant woman, followed by intrauterine intravascular transfusions of washed donor red blood cells; (c) mixed active tactics with a sequential combination, alternation of these methods. In Russia, only option 2 with fetal transfusions of washed donor red blood cells is accepted as the basis and paid for. The objective of the study is to conduct a comparative analysis of pregnancy outcomes in women with rhesus immunization using different management options.
 MATERIALS AND METHODS: A total of 392 women were followed up at seven different institutions in Russia and at the Donetsk Center for Maternal and Child Health (DNR), of whom 345 pregnant women (Group 1) received efferent therapy, 33 women (Group 2) had fetuses intrauterine bypass surgery, and 14 pregnant women (Group 3) had mixed efferent therapy and fetal PEEP bypass surgery.
 RESULTS: The analysis showed that the most favorable results for the main clinical indicators (premature, operative delivery, fetal hypoxia at birth, etc.) were in Group 1 and 3 women, in which the perinatal mortality was 14.5/1000 and 0/1000, respectively, which was significantly lower than in Group 2 (176.5/1000). It was also found that in Groups 2 and 3 women, the mean intervals between repeated transfusions of washed donor red blood cells were 8.8 0.2 and 21.4 3.8 days (p 0.01), which may be explained by the detoxifying effect of efferent therapy methods, preservation of fetal red blood cells and transfused donor red blood cells to the fetus with prolonged gestation and obtaining healthier and more viable progeny.
 CONCLUSIONS: 1. Severe Rh conflict is a manifestation of a syndrome of systemic effects of aggressive metabolites of specific and nonspecific nature. 2. The etiopathogenetic measure in the prevention and treatment of HDF/HDN in rhesus conflict is efferent therapy methods for the mother, and transfusion of washed donor rhesus-negative red blood cells to the fetus is effective, but a temporary, palliative measure, as is the case in multiple organ failure. 3. In the treatment protocols, efferent therapy methods must be present to prevent fetal red cell destruction and, equally importantly, to prevent destruction of Rh-negative donor red cells transfused to the fetus.

MANAGEMENT OF FETAL ANEMIA AND THROMBOCYTOPENIA WITH INTRAUTERINE BLOOD TRANSFUSION

Fetal anemia and fetal thrombocytopenia are two of the most unsmiling complications in pregnant women, and they can lead to perinatal mortality and morbidity. After long years of study with intravascular intrauterine blood transfusion, a number of varieties of implications have been described. Intrauterine Blood Transfusion (IUBT) is considered the best method in the case of fetal anemia because it is caused by red cell alloimmunization. Not only for red blood cell transfusion, this method can also be used for the transfusion of platelets to thrombocytopenic fetuses in pregnant women. It is generally detected after a child is born who is symptomatic and shows signs of bleeding in the brain and skin. The biggest milestone for the clinician is to give preventive treatment in next pregnancy. Pregnancies at risk require serial monitoring, and Fetal Middle Cerebral arterial (MCA) Doppler is the non-invasive test that is now proving to be the choice for monitoring. IVIG (Intravenous immunoglobulin) is used to manage severe Rh-immunization and is now showing promising effects. Indications like Parvovirus B19, Fetomaternal hemorrhage (FMH), Fetal SacrococcygealTeratoma (SCT), Twin-twin transfusion syndrome, placental chorioangioma diseases, or other infections can be treated with this method. This review covers fetal transfusion techniques and explores current management of fetal anemia and thrombocytopenia.

Complications of intravascular intrauterine transfusion for Rh alloimmunization.

BACKGROUND: Intravascular intrauterine transfusion (IUT) is considered a safe procedure, but complications still occur, including fatalities.OBJECTIVE: Review the outcomes of Rh alloimmunization, including indications and possible complications.DESIGN: Retrospective cohort (medical record review).SETTING: Tertiary care center.PATIENTS AND METHODS: We retrieved the records for all mothers who had an IUT for Rh alloimmunization between January 2009 and August 2019. We collected data on complications, post-transfusion hemoglobin and antibody combinations.MAIN OUTCOME MEASURE: Complications of IUT.SAMPLE SIZE: 119 mothers with 154 fetuses (154 different pregnancies).RESULTS: The 154 fetuses had 560 intrauterine transfusions. The median pre-IUT hemoglobin was a median of 8.0 g/dL while the median post-IUT hemoglobin 16 g/dL. Immediate procedure-related complications included fetal bradycardia in 2.7%, significant bleeding from the cord puncture site (for more than 2 minutes in 0.9%), and contractions in 0.9%. Eight (5.2%) were delivered by cesarean delivery due to IUT-specific complications such as post-procedure fetal bradycardia. Intrauterine fetal death complicated 8.4% of the pregnancies (13 fetuses). Phototherapy was required in 76 (49.4%), postnatal blood transfusions in 17 (11%), and exchange transfusion in 11 (7.1%). Neonatal death occurred 8 (5.2%). Data were insufficient to assess associations of complications with antibody combinations.CONCLUSIONS: Intrauterine transfusion is an effective treatment with high survival rates (around 90% for cases of Rh alloimmunization).LIMITATIONS: Case series.CONFLICT OF INTEREST: None.

Features of the cardiovascular system of fetuses and newborns after intrauterine intravascular blood transfusion

Intrauterine intravascular blood transfusion is an effective and relatively safe treatment method for severe fetal anemia. This technique have been used for more than 30 years already, however, there are no systematic works devoted to the features of the cardiovascular system in fetuses and newborns after intrauterine intravascular blood transfusion. The authors have decided to study this problem and have conducted a prospective trial of fetuses and children (n=34) with hemolytic anemia who underwent intrauterine blood transfusion. To assess the condition of the cardiovascular system, the scientists have carried out an ultrasound examination of the heart, which results have revealed pathological changes: dilatation of the cardiac cavities, myocardial hypertrophy, hydropericardium, cardiomegaly still present in the postnatal period. The scientists have used fetal and neonatal therapy for the patients with these pathologies. In the case of late correction of severe fetal anemia, there was a progressive deterioration in the condition of the fetus and remodeling of the cardiovascular system, which indicates the need for timely diagnosis. Based on the results of the study, the scientists have developed the protocols for ultrasound diagnostics of fetuses and newborns with moderate and severe anemia.

Our Experience of Immune Fetal Hydrops: its Clinical Characteristics and Perinatal Outcome.

Fetal hydrops is a serious condition which has high morbidity and mortality. Incidences of immune hydrops have decreased by manifold after introduction of anti-D immunoglobulin. Intra-uterine fetal blood transfusion revolutionized the treatment of these affected fetuses after diagnosis of immune fetal hydrops. In this study we aim to evaluate the clinical characteristics of immune hydropic fetuses and perinatal outcome after institution of intra-uterine transfusions. A retrospective study was carried out in pregnant women with immune fetal hydrops from October 2004 to December 2019 in our tertiary care hospital. After diagnosis of fetal hydrops, all the fetuses received intra-uterine transfusions. All the newborns were followed up till 3months postdelivery. All the fetuses were divided in two groups: hydrops diagnosed below 32weeks (Group A) and in second group hydrops diagnosed after 32weeks gestation (Group B). Total 63 patients were diagnosed to have hydrops during the study period. Group A had 48 fetuses and Group B had 15 fetuses. Average gestational age of diagnosis of hydrops in group A was 24.2weeks and in group B it was 32.5weeks. All the fetuses received intra-vascular intra-uterine transfusion. Pericardial effusion was found to be significantly associated with group A. Successful perinatal outcome was seen in 92% fetuses. 87% fetuses had complete resolution of hydrops before delivery. All the fetuses received phototherapy and intra-venous immunoglobulin after delivery, and 5 fetuses underwent exchange transfusion. Favourable perinatal outcome was achieved in hydropic fetuses with intra-uterine blood transfusions. Complete resolution of hydrops before delivery increases the chances of perinatal survival. The online version contains supplementary material available at 10.1007/s13224-020-01423-4.

THE ROLE OF MAGNETIC RESONANCE IMAGING IN THE PERINATAL ASSESSMENT OF THE CONDITION FETAL CNS WITH HEMOLYTIC DISEASE, WHO RECEIVED TREATMENT BY INTRAUTERINE INTRAVASCULAR BLOOD TRANSFUSION

Objective: to determine the role of magnetic resonance imaging (MRI) in the pathomorphological evaluation of focal changes in the central nervous system (CNS) of fetuses with hemolytic disease before and after treatment, by intrauterine intravascular blood transfusion, and to compare the MRI data of fetuses with ultrasound neurosonography (NSH) newborns. The study included 45 pregnant women and their 45 newborns. Patients are divided into 2 groups. The main group: 30 pregnant women (mean gestation period 32,1 weeks) with hemolytic disease of the fetus who underwent intrauterine intravascular blood transfusion and their 30 newborns with hemolytic disease of the newborn. In this group, comparative MRI examinations of the central nervous system were performed using a protocol including fast MP sequences based on T1 and T2-weighted images, as well as the DWI pulse sequence, both before treatment (intrauterine intravascular blood transfusion of the fetus), and after treatment (regardless of the multiplicity of intrauterine intravascular transfusion — before delivery). The comparison group comprised 15 pregnant women (mean gestation period of 38,6 weeks) with no signs of hemolytic disease, examined by MRI for other indications (concomitant pathology of pregnancy) and their 15 newborns, comparable in gestational age to the main group. The obstetric anamnesis, the MRI data of the central nervous system of fetuses before the treatment (the first intrauterine intravascular transfusion) and after the treatment (before the delivery) and the results of ultrasound for the first day of life were analyzed. When comparing the MRI data of changes in the central nervous system, in the main group (in fetuses with bladder) in relation to the comparison group before treatment (the first intrauterine, intravascular transfusion), a high incidence of focal changes in the brain substance in the main group was revealed. The use of MRIdiagnostics demonstrates a decrease in the risk of development of PCNC in ischemic type, in dynamics before and after treatment. Based on the MRI diagnostic data of the fetal CNS, it is possible to judge the prognosis of the outcomes of hemolytic disease of the fetus, in comparison with the neonatal neurosonography data for the first day.

Changes in innate and adaptive immunity indicators in the fetuses with hemolytic disease caused by Rh incompatibility, who have undergone a single intrauterine intravascular blood transfusion

Changes in innate and adaptive immunity indicators in the fetuses with hemolytic disease caused by Rh incompatibility, who have undergone a single intrauterine intravascular blood transfusion

Fetal hydrops and middle cerebral artery Doppler in prediction degree of fetal anemia and the best timing for therapy

To determine the role of fetal multiples of the median of middle cerebral artery peak systolic velocity (MoM MCA-PSV), in predicting the degree of fetal anemia for determination of the best timing for the second intrauterine intravascular transfusion (IUIVT) in hydropic fetuses with Rh alloimmunization. Prospective study of 30 monofetal pregnancies with maternal Rh D alloimmunization and hydrops fetalis, from 2005 to 2012 that underwent first and second IUIVT were assessed. Thirty IUIVT were performed at 26.9 weeks (standard deviation, SD 4.3). Mean interval to the second procedure was 11.23 (SD 6.21) days and average hematocrit decline rate was 1.45%/day. The study did not demonstrated statistical significance between MCA-MoM-3 before the second IUIVT, and the mean decline rate in fetal hematocrit levels (expressed in percentage/day) r = 0.220; p = 0.242, and between MCA-MoM-3 and the time interval between both procedures (T) r = -0.157; p = 0.408. The measurements fetal MoM-MCA before every IUIVT cannot be useful as predictor for the best timing for the next IUIVT, but it can be useful in predicting severity of fetal anemia.

Manejo prenatal del teratoma sacrococígeo, a propósito del primer caso sometido a transfusión sanguínea intrauterina en el Perú

El teratoma sacrococcígeo es una enfermedad rara en el feto, pero con alta mortalidad perinatal debido al secuestro de flujo sanguíneo y consiguiente desarrollo de anemia fetal severa. Presentamos el caso de una gestante de 27 semanas referida a nuestro servicio para manejo prenatal de un feto con teratoma sacrococcígeo gigante, que desarrolló anemia fetal severa y fue sometido a una transfusión intrauterina intravascular, la cual pudo prolongar el embarazo y mejorar los resultados perinatales.

Specific features of red blood cell morphology in hemolytic disease neonates undergoing intrauterine intravascular blood transfusion

The paper presents data on the characteristics of red blood cell morphology in infants who have undergone intrauterine intravascular blood transfusion for hemolytic disease of the fetus. The infants are shown to have a reduction in the mean volume of red blood cells and in their mean level of hemoglobin, a decrease in the fraction of fetal hemoglobin and an increase in oxygen tension at half saturation. The above morphological characteristics of red blood cells remain decreased during the neonatal period after exchange transfusion or others, as clinically indicated, which seems to suggest that the compensatory-adaptive mechanisms to regulate hematopoiesis are exhausted and a donor’s red blood cells continue to be predominant.

Middle cerebral artery Doppler in prediction degree of fetal anemia and the best timing for the second intrauterine intravascular transfusion in red cell alloimmune disease

To determine the role of fetal multiples of the median of middle cerebral artery peak systolic velocity (MoM MCA-PSV), predicts the rate of decline in fetal hematocrit (Hct) for determination of the best timing for the second intrauterine intravascular transfusion (IUIVT) in fetuses with Rh alloimmunisation.Retrospective study of 59-monofetal alloimmunized pregnancies from 2005 to 2012 that underwent first and second IUIVT were assessed in Department of Gynecology and Obstetrics, Belgrade, Serbia.There was an inverse statistically significant correlation between measurements MCA MoM-1 and fetal Hct-1 before the first IUIVT r = -0.622; p = 0.001 and MCA-MoM-3 and Hct-3 before the second IUIVT r = -0.381; p = 0.001, also as the significant correlation between the interval between both procedures (expressed in day) and measurement MCA-MoM-3, before the second IUIVT r = -0.284; p = 0.029.The measurements MoM-MCA before every IUIVT can be useful for prediction of the best timing for the next IUIVT.

Changes in fetal myocardial performance index following intravascular transfusion: preliminary report

Objective: To investigate the changes in fetal left ventricle myocardial performance index (MPI) following intrauterine intravascular transfusion (IUT).Methods: Prospective study, including 25 IUT performed in 13 singleton pregnancies with maternal Rh D alloimmune disease. Left ventricle MPI was evaluated prior to transfusion and repeated 24 h after each procedure. Delta MPI was calculated as the difference between post- and pre-transfusion MPI z-scores. Multilevel regression analysis was used to examine the association between delta MPI and gestational age at procedure, fetal middle cerebral artery peak velocity MoM, pre- and post-MPI and hemoglobin z-score values, the volume of blood transfused and feto-placental volume percentage expansion. Adjustments were made for repeated measurements within the same fetus, and across different time points. The significance level was set as 0.05.Results: MPI z-score values increased significantly following transfusion (delta MPI = 1.10 ± 2.47, p=0.036). Delta MPI showed a significant correlation with gestational age at transfusion (r= −0.47, p=0.018), pre-transfusion MPI z-score (r= −0.50, p=0.012) and feto-placental volume percentage expansion (r= −0.41, p=0.044).Conclusion: Left ventricle MPI increases significantly after intrauterine blood transfusion and greater changes are associated with procedures at an earlier gestational age, lower pre-transfusion MPI z-scores and smaller feto-placental volume expansion.

Perinatal survival and procedure-related complications after intrauterine transfusion for red cell alloimmunization.

To study the perinatal survival and procedure-related (PR)complications after intrauterine transfusions in red cell alloimmunization. Prospective data of 102 women with Rh-alloimmunized pregnancy undergoing intrauterine intravascular transfusion for fetal anemia, from January 2011 to October 2014 were analyzed. Main outcome measures were perinatal survival and procedure-related (PR) complications. A total of 303 intrauterine transfusions were performed in 102 women. Of 102 fetuses, 22 were hydropic at first transfusion. The mean period of gestation and hematocrit at first transfusion was 26.9 ± 3.3 weeks (range 19.7-33.8 weeks) and 17 ± 7.82 % (range 5.7-30 %), respectively. Average number of transfusions was 2.97 (range 1-7) per patient. Overall survival was 93 % and mean period of gestation at delivery was 34.5 ± 1.94 (range 28.3-37.4) weeks. Mean hematocrit at delivery was 36.9 ± 8.77 % (range 10-66 %). Fetal death occurred in four cases (3PR), neonatal death occurred in three cases (2PR). Emergency cesarean delivery after transfusion was performed in four pregnancies. The total PR complication rate was 2.97 %, resulting in overall PR loss in 1.65 % per procedure. Our results compare favorably with other studies published in the literature. Intravascular transfusion is a safe procedure improving perinatal survival in fetuses with anemia due to Rh-alloimmunization.

Improving the management and outcome in haemolytic disease of the foetus and newborn.

Improving the management and outcome in haemolytic disease of the foetus and newborn.

Massive Fetomaternal Hemorrhage Secondary to Intrauterine Intravascular Transfusion

Small-volume fetomaternal hemorrhage is frequently observed after intrauterine transfusion. The Kleihauer-Betke test, the reference method for identifying fetomaternal hemorrhage, cannot be used after intrauterine transfusion, because the adult red blood cells used for transfusion cannot be distinguished from maternal red blood cells. Massive fetomaternal hemorrhage secondary to intrauterine transfusion led to fetal hemorrhagic stroke. We used a method based on blood group identification in the maternal blood to confirm and to quantify fetomaternal hemorrhage. Fetal stroke may result from severe hypovolemia and low cerebral blood flow caused by fetomaternal hemorrhage, rather than from fetal anemia itself.

Transfusión intrauterina. Nuestra experiencia en el Hospital Universitario Materno Infantil de Canarias

Objectivesto present intrauterine intravascular transfusions cases performed for fetal anaemia in Fetal Medicine Unit of Canaries University Hospital Maternity Ward. Material and methodprospective descriptive study of cases diagnosed of fetal anaemia that were treated with intrauterine transfusion from may 2007 to June 2009. Resultsduring this period seven cases of fetal anaemia were diagnosed. Four isoimmunization-anaemia and three of non-immune anaemia. Eight intrauterine transfusions were performed in five of cases (in two cases repeated transfusion was required). Two cases did not allow transfusion. Conclusionblood transfusion through umbilical cord seems to be the best option for fetal anaemia treatment. After first intrauterine transfusion in 2007, all indicated cases were carried out.

Quality Control for Intravascular Intrauterine Transfusion Using Cumulative Sum (CUSUM) Analysis for the Monitoring of Individual Performance

Introduction: Intravascular intrauterine transfusion (IUT) is an effective and relatively safe method for the treatment of fetal anemia. Although implemented in centers all over the world in the 1980s, the length and strength of the learning curve for this procedure has never been studied. Cumulative sum (CUSUM) analysis has been increasingly used as a graphical and statistical tool for quality control and learning curve assessment in clinical medicine. We aimed to test the feasibility of CUSUM analysis for quality control in fetal therapy by using this method to monitor individual performance of IUT in the learning phase and over the long term. Methods: IUTs performed in the Dutch referral center for fetal therapy from 1987 to 2009 were retrospectively classified as successful or failed. Failed was defined as no net transfusion or the occurrence of life-threatening procedure-related complications. The CUSUM statistical method was used to estimate individual learning curves and to monitor long-term performance. Four operators who each performed at least 200 procedures were included. Results: Individual CUSUM graphs were easily assessed. Both operators pioneering IUT in the late 1980s had long learning phases. The 2 operators learning IUT in later years in an experienced team performed acceptably from the start and reached a level of competence after 34 and 49 procedures. Discussion: CUSUM analysis is a feasible method for quality control in fetal therapy. In an experienced setting, individual competence may be reached after 30 to 50 IUTs. Our data suggest that operators need at least 10 procedures per year to keep a level of competence.

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

Sonographic findings in severe fetomaternal transfusion

Fetomaternal hemorrhage (FMH) or fetomaternal transfusion syndrome is the leakage of fetal red blood cells into the maternal circulation. Massive FMH can cause substantial fetal morbidity and mortality. Sonographic evidence of severe FMH syndrome includes fetal hydrops and other fetal anemia-related findings. The peak systolic velocity in the middle cerebral artery has extensively been used for the prediction of fetal anemia and for the timing of the first intrauterine intravascular transfusion (IIVT). We present a case of severe FMH syndrome that was diagnosed during the 24th week of pregnancy. A total of eight IIVT were performed. The actual increase in the fetal Hb after each transfusion was much lower than the expected. At 27 weeks of gestation, sonographic evaluation revealed areas of echogenicity around the posterior horns of the lateral ventricles suggesting ischemic damage. Due to these findings, no further IIVTs were offered and the fetus died a week later. The management of fetal anemia caused by severe FMH is difficult, and the anemic fetuses do not respond well to serial IIVTs as the transfer of blood to the maternal circulation continues.