In-utero Transfusion Research Articles

Does strengths of a positive direct antiglobulin test predicts the need for phototherapy and duration of phototherapy? – a single center, retrospective study

Background Use of Direct Antiglobulin test (DAT) in management of neonatal hyperbilirubinemia is conflicting. Objective whether strength of positive DAT predicts the need for phototherapy, duration of phototherapy and need for major interventions. Methods We retrospectively collected data on all DAT positive neonates with birth gestational age ≥32 weeks over six years (2014–2019). Data regarding blood group, DAT and clinical details were obtained from a hospital database. We also collected data on serial hemoglobin and other relevant laboratory parameters. We also collected data on infants receiving major interventions such as exchange transfusion, in-utero transfusion, immunoglobulins, and postnatal transfusion for the duration of the study period. All of these infants were electronically followed up for a period of 6 weeks. This study was approved by institutional audit authority. All the statistics were performed using SPSS software. Results Out of 1285 DAT tests performed, only 91 infants were positive (7%), and 78 DAT positive infants were available for analysis. There were 54 infants with DAT (1+), 15 infants with DAT (2+), 7 infants with DAT (3+) and 2 infants with DAT (4+). There was no significant statistical difference in terms of need for phototherapy, duration of phototherapy, need for major interventions and hemoglobin levels at different time points between the groups (DAT 1+ Vs DAT ≥2+; DAT ≤2+ Vs DAT >2). A Total of 10 infants received major intervention, with one infant receiving all three interventions (DAT 3+ with significant maternal antibodies), 2 additional infants (both DAT1+) received exchange transfusion, 6 additional infants received immunoglobulin (2 infants: DAT 2+; 4 infants: DAT 1+) and one additional infant (DAT 1+) with significant maternal antibodies received a postnatal transfusion. Conclusion Strength of a DAT did not predict the need for phototherapy, duration of phototherapy, and the need for major hemolysis related intervention in the first 6 weeks of life.

Anti-RH1 alloimmunization: At what maternal antibody threshold is there a risk of severe fetal anemia?

To define a threshold of maternal antibodies at risk of severe fetal anemia in patients followed for anti-RH1 alloimmunization (AI). We conducted a retrospective study of patients followed for anti-RH1 AI at the Lille University Hospital. The first group, severe anemia, included patients who received one or more in utero transfusions (IUT) or who were induced before 37 weeks of pregnancy for suspected severe fetal anemia. The second group, absence of severe anemia, corresponded to patients without intervention during pregnancy related to AI. Sensitivities, specificities, and positive and negative predictive values for screening for severe fetal anemia were calculated for the antibody thresholds of 3.5 and 5IU/ml for the quantification. Between 2000 and 2018, 207 patients were included 135 in the severe anemia group and 72 in the no severe anemia group. No severe anemia was observed for an antibody titer below 16. For an antibody threshold of 3.5IU/ml, the sensitivity was 98.2%, with 30.2% false positives. All severe anemias were detected in the second trimester; two cases of severe anemia were not detected in the third trimester. For an antibody threshold of 5IU/ml, the sensitivity was lower at 95.6%, with five cases of severe anemia not detected. The antibody threshold of 3.5IU/ml for the quantification and 16 for the titration allow targeting patients requiring close monitoring by an experienced team in case of anti-RH1 AI.

RETRACTED: Peak systolic velocity of fetal middle cerebral artery to predict anemia in Red Cell Alloimmunization in un-transfused and transfused fetuses

Abstract objectiveTo assess the accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) in prediction of severe fetal anemia resulting from Red Cell Alloimmunization (Anti-D) in un-transfused and transfused fetuses. In addition to comparing the accuracy of MCA-PSV and the estimation of the daily decline of fetal hemoglobin (Hb), to determine the appropriate time of subsequent transfusions. Study designThis was a retrospective study of a series of 84 anaemic fetuses due to Red Cell alloimmunization. During each in-utero transfusion session, measurements of (1)MCA-PSV, (2)pre- and (3)post-transfusion Hb levels were recorded. Receiveroperating characteristics (ROC) curves, negative and positive predictive values of MCA-PSV in predicting severe fetal anemia were calculated. Regression analysis assesses the correlation between fetal HB and MCA-PSV, and between observed and expected fetal hemoglobin levels. ResultsEighty four anemic fetuses were included in the study and had an in-utero transfusion. The positive predictive value (PPV) of MCAPSV decreased sharply from 86.0 % at the first IUT, to 52.0 % and 52.1 % at the second and third IUTs respectively. According to the ROC curves, setting the cut-off at 1.70 MoM would provide the best performance of MCA-PSV with respect to the timing of the second and third IUT. Setting a higher threshold of 1.70 MoM for the 2nd and 3rd transfusions would increase the PPV from 52.0 % to 96.4 % at the second IUT, and from 52.1%–99.8 % at the third IUT. ConclusionIn this study we suggest that a higher MCA-PSV (MoM 1.7 in compared to 1.5MOM) can accurately predict the recurrence of severe fetal anemia requiring serial IUTs. In transfused fetuses, MCAPSV accuracy to detect severe anemia decline slightly with increase number of IUT. In addition to that, the mean projected daily decrease in fetal hemoglobin has a similar accuracy to MCA-PSV in predicting moderate to severe fetal anemia.

In Utero Stem Cell Transplantation in Patients with Alpha Thalassemia Major: Interim Results of a Phase 1 Clinical Trial

Introduction: In utero hematopoietic cell transplantation (IUHCT) has the potential to treat patients with blood disorders by taking advantage of bidirectional maternal-fetal tolerance during pregnancy. Although engraftment has only been seen in immunodeficient patients in the past, recent preclinical studies indicate that a higher dose of maternal cells should be given intravascularly to maximize engraftment in other settings. We hypothesized that: 1) fetuses will tolerate a maternal IUHCT without conditioning and develop low engraftment with sustained tolerance to maternal alloantigens; and 2) tolerant patients could receive a postnatal booster maternal transplant with minimal immunoablative conditioning and thereby achieve a cure. To test the first of these hypotheses in a controlled setting, we have initiated a phase 1 clinical trial of IUHCT in fetuses with alpha thalassemia major (ATM), who already require a fetal intervention (in utero transfusions (IUT)) to survive the pregnancy. We present interim results from the first two patients. Methods: After obtaining IND approval, we initiated the clinical trial in 2017 (NCT02986698). Fetuses with ATM between 18-26 weeks' gestation without other major anomalies were included. To date, we have evaluated 19 patients for possible inclusion: 15 patients terminated the pregnancy, 2 patients were outside the inclusion window and underwent IUT alone, and 2 have been transplanted and completed the 1 year follow up. For IUHCT, 300 ml of maternal bone marrow was harvested, CD34+ cells were selected and transplanted fresh into the fetus via the umbilical vein, along with a standard IUT. IUTs were repeated every 3 weeks until delivery. Maternal cell chimerism was detected using qRT-PCR for non-inherited maternal HLA-DR alleles on sorted cell populations in cord blood and after birth. Mixed lymphocyte reactions (MLRs) were performed by culturing CFSE-labeled host CD4 and CD8 responder cells with maternal (or third-party) derived antigen presenting cells (APC; direct pathway) or self APC/maternal lysate (indirect pathway). Results: Both fetuses were diagnosed with severe hydrops on ultrasound and received an initial IUT prior to the IUHCT. Patient 1 was transplanted at 23 weeks with 1x 108CD34+ cells/kg + 1 x 107T cells/kg and Patient 2 was transplanted at 25 weeks with 5x 107CD34+ cells/kg + 5 x 106T cells/kg; both received 4 more IUTs until birth. Prenatal hydrops resolved in both and neonatal hospitalizations were 16 and 13 days, respectively. Maternal chimerism was detected in both patients, but levels were higher and persisted throughout the year only in patient 1 (Fig 1A). We detected 70-fold higher levels of erythrocyte precursors (Fig 1B) but normal levels of CD34+ cells in the cord blood of patients compared to healthy controls, highlighting a potential barrier to engraftment in a disease with prenatal hypoxia. Patient 1 demonstrated sustained tolerance to maternal antigens by MLR throughout the year, whereas patient 2 showed reactivity against maternal antigens (Fig 1C). HLA antibodies were negative in both. Based on the finding of donor-specific tolerance in patient 1, we offered a booster transplant with maternal cells but the parents declined. Both patients are undergoing monthly transfusions and have had normal development and Bayley neurologic testing at 1 year. There were no unanticipated safety events in either mother/child pair. Conclusions: These results demonstrate the safety of IUHCT in fetuses with ATM and the potential of fetal transplantation in the second trimester to sustain tolerance to maternal cells after birth. Low engraftment levels are predicted in the setting of host hyperproliferation and lack of space-making conditioning, confirming the need for a two-step strategy (IUHCT and postnatal booster transplant) for a definitive cure. The earlier transplantation in patient 1 enabled a higher dose of cells and may explain the improved outcome observed. Implementation of earlier screening in at-risk patient groups could allow earlier diagnosis and enrollment in the future. Although parents of fetuses with ATM are commonly counseled for pregnancy termination due to concern for poor outcomes, our results indicate that fetal therapy with IUTs can result in survival to term and excellent quality of life. This strategy of maternal IUHCT could be employed to treat fetuses with other hematologic disorders in the future. Figure 1 Disclosures MacKenzie: Acrigen: Membership on an entity's Board of Directors or advisory committees; Ultragenyx: Research Funding. Vichinsky:Global Blood Therapeutics: Consultancy; Agios: Research Funding; Pfizer: Research Funding.

Doppler middle cerebral artery peak systolic velocity measurement as diagnostic tool for fetal anemia after in-utero transfusions in red blood cell alloimmunisation

Background/Aim. Doppler sonography of fetal middle cerebral artery peak systolic velocity (MCA-PSV) can be used to predict fetal anemia and the need for in utero intravascular transfusion (IUIT) in red blood cell (RBC) alloimmunisation pregnancies. The aim of this study was to evaluate whether measurement of MCA-PSV in fetuses that had undergone one to three transfusions is a good diagnostic tool for fetal anemia. Methods. Study included 36 pregnancies treated due to RBC alloimmunisation in our tertiary referral center during the 5-year period (2012?2017). We measured MCA-PSV and hematocrit (Hct) in all patients. In seven pregnancies there was a need to perform sequential IUITs for correction of fetal anemia. In these patients we compared MCA-PSV and Hct values before and after every transfusion. Results. Hct and MCA-PSV correlated negatively before transfusion therapy (p = 0.035) and after the second transfusion (p = 0.046). Contrary, after the first (p = 0.954), before the second (p = 0.738), as well as before (p = 0.092) and after (p = 0,741) the third transfusions there were no significant correlations between Hct and MCAPSV values. Hct values before and after transfusions were positively associated (p = 0.001), but MCA-PSV were not (p = 0.296). According to performed receiver operating characteristic (ROC) analysis the cut-off point of MCA-PSV for investigated patients was 1.22 multiples of its median (MoM). Conclusion. There is a reduction in MCA-PSV accuracy for assessing fetal anemia in previously transfused fetuses. Larger studies are needed to explain the reasons for these findings and potentially set new referral values of MCA-PSV for better diagnostics of fetal anemia.

Prevalence and obstetric outcome of women with red cell antibodies in pregnancy at the Leeds Teaching Hospitals NHS Trust, West Yorkshire, England

ObjectiveThe prevalence of red cell antibodies in pregnancy varies with ethnicity and geographical location, while the obstetric outcome depends on the available standard of care. Despite being the tertiary fetal medicine centre in West Yorkshire, the prevalence of red cell antibodies, and the outcome of pregnancies associated with these antibodies at the Leeds University Teaching Hospitals Trust remains unreported. This article aims to provide this information for the purpose of patient education and counselling. Study designThe data of pregnant women with red cell antibodies between January 2011 and December 2016 was obtained from the Trust's database and reconciled with the Fetal Medicine Unit records using Viewpoint©. Fetal anaemia requiring in utero transfusion (IUT) was defined as a Middle Cerebral Artery Peak Systolic Velocities ≥ 1.5multiple of the median expected for gestational age. The mean gestational age at delivery, and perinatal outcomes of the pregnancies were recorded. ResultOverall, 398 of the 96, 692 pregnant women that were screened had red cell antibodies, giving a prevalence of 1: 242 pregnancies. The Anti- E and Anti-M antibodies were the most common (114 women; 28.6%, and 112 women; 28.1% respectively), but did not cause fetal anaemia in isolation, while anti-D alloimmunization was the predominant indication for in-utero transfusion (IUT). Anti-DE and anti-Kell antibodies had the highest mean number of transfusions per pregnancy. The mean gestational age at delivery was 34 ± 2weeks. Post-transfusion fetal demise was recorded in two hydropic fetuses, both at a gestational age of 25 weeks; giving a transfusion-related mortality rate of 2.5%. ConclusionThe prevalence of red cell antibodies at West Yorkshire is lower compared with reports from other Caucasian populations.Nevertheless, these antibodies are important causes of iatrogenic preterm delivery and fetal morbidity. The prognosis is however good with prompt diagnosis and management.

525: Decline in fetal hemoglobin after in-utero transfusion in alloimmunized patients

Few studies have described the expected decline in hemoglobin after in-utero transfusions (IUT). We aimed to calculate the average decline in fetal hemoglobin after first and second IUTs in alloimmunized patients and to characterize them by anti-D status. This is a retrospective cohort study. All patients undergoing percutaneous umbilical cord blood sampling (PUBS) for suspected fetal anemia from 2000-2016 were eligible. To be included, patients had to be alloimmunized and have undergone at least one IUT followed by a subsequent PUBS or delivery at least 7 days later with documented fetal or neonatal hemoglobin values from both procedures. Patients were categorized into anti-D or non-anti-D antibody status. The median change in hemoglobin over time was computed. The hemoglobin changes were compared by antibody type with the Mann-Whitney-U test. There were 25 patients who met inclusion criteria. The median interval between PUBS and the second measurement was 15 days (interquartile range [IQR] 11-21). The median rate of decline in fetal hemoglobin after the first IUT was 0.29 g/dL /day (IQR 0.17, 0.43). There was no difference by antibody type (p=0.21). There were 15 patients with a second IUT and followup hemoglobin values. The median interval between the second IUT and the followup PUBS or delivery was 14 days (IQR 11-17). The median decline in hemoglobin after this IUT was 0.36 g/dL/day (IQR 0.07, 0.49), which significantly differed by antibody type (p=0.016). After the first IUT the rate of hemoglobin decline in this small cohort was somewhat lower than reported previously, while it was somewhat higher after the second. This was associated with antibody type after the second transfusion but not after the first transfusion. This information can be used to anticipate the interval between PUBS/IUT in alloimmunized patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

524: Fetal thrombocytopenia in alloimmunized patients

The objective of this study was to characterize the patterns of platelet counts in a modern cohort of fetuses undergoing percutaneous umbilical cord blood sampling (PUBS) for alloimmunization. This is a retrospective cohort study of all patients undergoing PUBS at our institution from 2000-2017. Demographic and clinical data were abstracted from the medical record. Patients were categorized into anti-D alone, anti-D and other antibodies, or other antibodies only. The primary outcome was fetal thrombocytopenia, defined as platelet count <150 x 109/L and classified as moderate (50 - 150 x 109/L) or severe (<50 x 109/L). The associations between antibody group and fetal thrombocytopenia, as well as between thrombocytopenia and fetal hemoglobin level, were determined using mixed models to account for repeated measures (i.e. PUBS procedures) in each patient. Of the 50 patients in the study, 15 patients had anti-D alone, 15 had anti-D and other antibodies, and 20 had other antibodies only. A total of 158 PUBS procedures were performed with 143 in-utero transfusions. Opening platelet counts (range 8-485 x 109/L) were available for 120 PUBS. Of these, 71 (59.2%) had no thrombocytopenia, 36 (30.0%) had moderate thrombocytopenia, and 13 (10.8%) had severe thrombocytopenia. Thrombocytopenia was found in 44.4% of PUBS in patients with anti-D antibodies only, in 27.8% % of PUBS in patients with anti-D and other antibodies, and in 47.9% of PUBS in patients with only other kinds of antibodies (p=0.17). There was no significant association between antibody class and degree of fetal thrombocytopenia (p=0.30). The mean hemoglobin in the thrombocytopenic group was 6.8 g/dL (standard deviation 2.8 g/dL); while in the non-thrombocytopenic group it was 8.1 g/dL (standard deviation 3.1 g/dL), p=0.02. This association was not modified by antibody type (p for interaction 0.19). Thrombocytopenia is common in fetuses undergoing PUBS for alloimmunization, regardless of antibody type. The presence of thrombocytopenia is associated with more severe fetal anemia. More work is needed to understand the biological mechanism and consequences of this finding.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection.

Objective To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered non-recovery and categorized as an adverse outcome. Results The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the non-recovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study.

Determination of optimal timing of serial in-utero transfusions in red-cell alloimmunization.

To assess the performance of middle cerebral artery peak systolic velocity (MCA-PSV) and of the expected daily decrease in fetal hemoglobin in determining the timing of serial in-utero transfusions (IUT) in red-cell alloimmunization. This was a retrospective study of a continuous series of suspected anemic fetuses undergoing IUT between June 2003 and December 2012. Doppler measurement of MCA-PSV and pre- and post-transfusion hemoglobin levels were recorded at the time of the first, second and third IUT. Receiver-operating characteristics (ROC) curves and negative and positive predictive values of MCA-PSV in the prediction of severe fetal anemia were calculated. The daily decrease of fetal hemoglobin (Hb) between IUTs was calculated. Regression analysis was used to assess the correlation between pretransfusion fetal hemoglobin and MCA-PSV, and between observed and expected (by projection of daily decreases) pretransfusion fetal hemoglobin levels. One hundred and eleven fetuses required an IUT, of which 96 and 67 received a second and third IUT, respectively. The area under the ROC curve for MCA-PSV in the prediction of severe fetal anemia was not different for each rank of transfusion. The positive predictive value of MCA-PSV decreased from 75.3% at the first IUT, to 46.7% and 48.8% at the second and third IUTs, respectively, while the negative predictive value for a 1.5-MoM threshold remained high (88.9% at the second and 91.7% at the third IUT). The mean daily decrease in hemoglobin following each transfusion was 0.45, 0.35 and 0.32 g/dL, respectively. There was a persistent linear correlation between fetal hemoglobin and MCA-PSV and between observed and expected fetal hemoglobin levels. Both MCA-PSV and projection of daily decrease in hemoglobin are reliable means of diagnosing fetal anemia following previous IUTs. The high negative predictive value of MCA-PSV could allow subsequent IUTs to be postponed in selected cases.

Management of severe fetal anemia by Doppler measurement of middle cerebral artery: are there other benefits than reducing invasive procedures?

ObjectiveDoppler measurement of peak velocity of systolic blood flow in the middle cerebral artery (PVS-MCA) can safely replace invasive testing in the diagnosis of fetal anemia in Rh-alloimmunized pregnancies and PSV-MCA is now the reference technique. However, no study has evaluated its impact in antenatal care and in survival rate. Our objective was to evaluate the impact of the measurement of PVS-MCA in antenatal management and neonatal outcome in maternal red cell alloimmunization requiring in utero transfusion (IUT). Study designRetrospective study between January 1999 and January 2013. We excluded all cases of hydrops without follow-up before first IUT. From 1999 to 2006, an IUT was indicated on the optical index at 450nm (Period 1) and was then replaced by the use of PVS-MCA (Period 2). Results77 patients were included, 39 in Period 1 (104 IUT) and 38 in Period 2 (89 IUT). 5 cases of hydrops fetalis (12.8%) were diagnosed during the follow up in Period 1 and none during Period 2. The average number of IUT, the delays between 2 IUT and between last IUET and birth were comparable. The total rate of complication per IUT during the first period was 9.6% vs 1.1% during the second one (p=0.01). The overall survival rate in our population was 34/39 (86.8%) during Period 1 vs 38/38 (100%) during Period 2. ConclusionPSV-ACM allowed an improved monitoring with fewer occurrences of hydrops. Conversely, it did not modify antenatal management and timing of delivery.

Neonatal outcome after fetal anemia managed by intrauterine transfusion.

In-utero transfusion is now well under control and improves the survival of foetuses monitored for fetal anemia with a survival rate of more than 80%. The aim was to evaluate short-term neonatal outcome after fetal severe anemia managed by intrauterine transfusions. We did a retrospective study of all neonates born after management of severe fetal anemia (n = 93) between January 1999 and January 2013 in our regional center. The two main causes of anemia were maternal red blood cell alloimmunization (N = 81, 87%) and Parvovirus B19 infection (N = 10, 10.8%). In the alloimmunization group, phototherapy was implemented in 85.2% of cases with a maximum level of bilirubin of 114.4 ± 60.7 (mg/dl). Transfusion and exchange transfusion were, respectively, required in 51.9% and in 34.6% of cases. One neonate presented a convulsive episode, and we observed three neonatal deaths. In the parvovirus group, none of the child had anemia at birth and no management was necessary. Contemporary management of Rhesus disease is associated with encouraging neonatal outcomes. In case of Parvovirus infection, no specific management is necessary at. But, in all cases of fetal anemia, children should be followed up with particular attention to neurologic development. • In-utero transfusion is now well under control and improves the survival of fetuses monitored for fetal anemia. • Limited studies are available on the effect of IUT on postnatal outcome in infants with a history of fetal anemia. What is New: • Contemporary management of severe Rhesus disease is associated with encouraging neonatal outcomes. • The majority of infants can be managed with phototherapy and a limited number of top-up transfusions and exchange transfusions. In case of Parvovirus infection, the short-term neonatal outcome is excellent.

Fetal Intracardiac Transfusions in Hydropic Fetuses with Severe Anemia

Introduction: Fetal anemia can have significant perinatal morbidity and mortality, particularly with onset prior to 20 weeks of gestation. Materials and Methods: We detail a case-cohort study (n = 8) of all women who underwent fetal in-utero, intracardiac transfusion prior to 24 weeks of gestation (7 women before 20 + 1 weeks), between March 2004 and September 2014, in a supraregional Fetal Medicine Center in the United Kingdom, comprising 2.2% of all transfusions performed during this period. All the fetuses were hydropic, with high maternal BMI, and had severe anemia as an indicator for transfusion. It was an attempt to perform intravascular transfusion when other common routes of fetal vascular access had failed. Results: There were 2 intrauterine deaths (25%), both of which were associated with in-utero transfusion and fulminant parvovirus B19 infection. The perinatal survival rate was 75% (6/8). Discussion: Fetal in-utero, intravascular transfusion by the intracardiac route may be used to correct severe early-onset anemia. It is particularly useful when technical issues of fetal size, early gestation (<20 weeks), maternal adiposity, and hydrops fetalis make umbilical cord or intrahepatic vein puncture technically difficult. Survival rates appear comparable to other series of pregnancies where in-utero transfusion is performed at early gestation.

PS-192 Neonatal Transfusions In New South Wales, Australia: A Population Based Study

Background Previous reports of transfusion practices in neonates have focused predominantly on premature neonates admitted to neonatal intensive care units (NICU). Population data on neonatal transfusions is limited. Methods This study used linked population-based data from New South Wales (NSW) birth and hospital discharge data to determine rates of blood and blood product transfusion in the first 28 days of life. The study included all livebirths of at least 23 weeks gestation in NSW between 2001 and 2011, providing data on one-third of all Australian births. Results Of 989491 livebirths, 6436 received a blood product transfusion (6.5 per 1000 births). 56% were born 32 weeks gestation (n = 2842, 2.9/1000 births). 8% received transfusions in a hospital without a neonatal or paediatric ICU. The rate of transfusions of blood and blood products in neonates increased between 2001 and 2011 (5.7/1000 to 7.0/1000, p High transfusion rates were seen in neonates with a prior in-utero transfusion (667/1000), congenital anomaly requiring surgery (437/1000) or haemolytic disorder (132/1000). 48% received red cells alone, 29% received red cells plus other blood products and 24% received other blood products without red cells. Conclusions High rates of transfusions are seen in preterm neonates and in those undergoing surgery or with haemolytic disorders. Rates of neonatal transfusion increased in NSW between 2001 and 2011, primarily due to reported increased use of plasma and gamma globulin.

P21.09: Improving outcome of in utero fetal transfusion by increasing the target fetal hematocrit

Improve fetal outcome and reduce the number of fetal intervention after Rh alloimmunization by reducing the number of inutero transfusion by increasing the target fetal hematocrit. Rh alloimmunization is common in India and western world. To improve the outcome and make it available across the country, we have tried many strategies. One of them is to reduce the number of Inutero transfusion by increasing the target fetal hematocrit to 55 % rather than standard 45%. Other aims are to reduce the over all cost of the IUT so that many more people will be able to afford it. We have analyzed the data of our center (Paras Advanced Center for Fetal Medicine, Ahmedabad, India) between January 2008 to December 2013. We retrospectively analyzed 314 fetal transfusions and found better fetal outcome with this strategy - Group A -74% v/s Group B 86 % (Group A -45% target v/s Group B - 55 %). Over all 21% fetal transfusion rate was reduced. Complications and cost related to IUT was also reduced. While doing inutero fetal transfusion procedure, target of fetal hematocrit should be increased from 45% to 55% ( 20% Approximately). Over all procedure rate and complication rate was reduced and fetal outcome is also improved. Long-term outcome up to 3 years shows NO difference in outcome between 2 groups.

PFM.11 Treatment of severe fetal anaemia before twenty weeks by intracardiac transfusion

BackgroundSevere alloimmunisation or parvovirus B19 infection (HPVB19) may cause fetal hydrops and severe anaemia at an early gestational age (GA). Fetal anaemia is associated with significant mortality but may be...

395: Isoimmunization to minor red blood cell antigens in pregnancy: management, monitoring and outcomes

in pregnancy: management, monitoring and outcomes Sharmilee Thota, Srinivas Ketharaju, Carolyn Salafia, Aleksandr Fuks Bronx-Lebanon Hospital Center, OB/GYN, Bronx, NY, Bronx-Lebanon Hospital Center, OB/GYN, Bronx, NY, New York Methodist Hospital Cornell Presbyterian, OB/GYN, Pathology, Pediatrics, Brooklyn, NY, Queens Hospital Center, OB/GYN, Queens, NY OBJECTIVE: To examine fetal and neonatal outcomes of pregnancies complicated by isoimmunization to minor red blood cell (RBC) antigens and managed by serial antibody titer and MCA-peal systolic velocity (MCA-PSV) assessments. STUDY DESIGN: Retrospective cohort study of all patients isoimmunized to minor RBC antigens managed at Bronx-Lebanon Hospital Center, 2008-2011. Inclusion criteria: live singleton gestataion, presence of minor RBC antibodies, gestational age 24 0/7 36 0/7 weeks. Exclusion criteria: multiple gestations, Kell and major RBC antibodies, fetal malformations and chromosomal abnormalities. All patients were managed with serial antibody titer and MCA-PSV assessments. Outcome parameters were assessed: birthweight, fetal bilirubin concentration, cord gas base excess, fetal hematocrit, NICU stay duration. RESULTS: 24 patients fit study inclusion criteria. Demographic and outcome parameters are summarized in the Table below. None of the patients in the study had MCA-PSV values in the range of severe fetal anemia requiring PUBS and in-utero transfusion. None of the neonates required RBC transfusion and only 2 newborns were Coombs positive and required phototherapy. CONCLUSION: Patients with alloimmunization to minor RBC antigens and antibody titers less than critical value (1:32) do not appear to be at risk for sever fetal anemia. In those patients, serial MCA-PSV assessments do not influence management decisions and outcomes of pregnancy and forgoing such evaluation might be suitable.

Procedure related complications of fetal blood sampling and in-utero transfusion

In utero transfusion (IUT) was first performed by Liley in 1963. Since then the procedure has become a recognised treatment of both fetal anaemia and thrombocytopaenia. Initially, transfusions were performed...

1202 Outcomes of Babies with Severe Rhesus Disease Following In-Utero Transfusions - a 10 Year Experience

Background: In-utero transfusion (IUT) has transformed the management and outcome of severe Rhesus disease. Objective: To assess the outcomes of babies that had IUT in a tertiary Fetal Medicine and red cell alloimmunization Centre. Methods: Retrospective analysis of all cases of IUT for severe Rhesus disease over a 10 year period. Results: 263 IUT were performed in 80 pregnancies. Median IUT was 3 (range 1-8). Antibodies involved were: anti-D (84%); anti-Kell (13%) and anti-c (3%). 19 (24%) cases were hydropic: of these 3 were intra-uterine deaths, 2 neonatal deaths and 3 were born elsewhere. 74 were live births (92.5%); median gestation 34 weeks (range 24-38), 11 babies ≤30 weeks, 5 born elsewhere. Of the 69 infants born in our centre, 3 died in the neonatal period and 1 infant at 19 months (SIDS). Median cord haemoglobin was 10.7g/dL (range 5.7-20.9). 29/69 (42%) babies required 45 exchange transfusions (range 1-5). 57/69 (83%) babies required 151 top-up blood transfusions (median 2, range 1-20). Of those ≤30 weeks, 9/11 survived (82%), 2 had retinopathy of prematurity and 3 had cranial ultrasound abnormalities. At 2 years, 7/9 babies were normal and 2 had developmental delay. 53/56 (95%) surviving babies >30 weeks had normal neurodevelopment at 1 year except one with sensori-neural deafness. Conclusion: IUT is safe and does not appear to increase postnatal morbidity. In our experience, it has reduced the need for postnatal exchange transfusions. However, top-up transfusions are more likely.

Le point sur le suivi des allo-immunisations érythrocytaires

Anti-RhD allo-immunisation has become rare since anti-D prophylaxis was introduced in the seventies; however, it remains the first cause of fetal anemia. It may cause severe fetal complications such as fetal hydrops, cerebral anoxic lesions and fetal death. In the neonatal period, severe jaundices and anemias requiring transfusion or exsanguino-transfusion are still common in case of severe allo-immunisation. Neonatal death and sequellae due to bilirubin encephalopathy have not fully disappeared. Follow-up of pregnancies with maternal allo-immunisation requires identification of the antibody (anti-RhD, anti-Kell and anti-c are the most frequently responsible for fetal complications), dosage and titration. In RhD allo-immunization, feto-maternal incompatibility may be confirmed by non-invasive RHD genotyping of the fetus in maternal blood. In cases at risk for fetal anemia, weekly Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV) allows identification of fetal anemia before the occurrence of fetal hydrops. The reference treatment of fetal anemia is in utero fetal transfusion. The risk of fetal loss due to in utero transfusion (IUT) is 3% per procedure. The cumulated risk of fetal loss can thus exceed 10% in case of early occurrence of fetal anemia requiring up to five or six IUTs in a single pregnancy.