The selection and preparation of red cell components for intrauterine transfusion: A national survey.

BACKGROUND AND OBJECTIVES: The practice regarding the selection and preparation of red blood cells (RBCs) for intrauterine transfusion (IUT) is variable reflecting historical practice and expert opinion rather than evidence-based recommendations. The aim of this survey was to assess Canadian hospital blood bank practice with respect to red cell IUT. MATERIALS AND METHODS: A survey was sent to nine hospital laboratories known to perform red cell IUT. Questions regarding component selection, processing, foetal pre-transfusion testing, transfusion administration, documentation and traceability were assessed. RESULTS: The median annual number of IUTs performed in Canada was 109 (interquartile range, 103-118). RBC selection criteria included allogeneic, Cytomegalovirus seronegative, irradiated, fresh units with most sites preferentially providing HbS negative, group O, RhD negative, Kell negative and units lacking the corresponding maternal antibody without extended matching to the maternal phenotype. Red cell processing varied with respect to target haematocrit, use of saline reconstitution (n = 4), use of an automated procedure for red cell concentration (n = 1) and incorporation of a wash step (n = 2). Foetal pre-transfusion testing uniformly included haemoglobin measurement, but additional serologic testing varied. A variety of strategies were used to link the IUT event to the neonate post-delivery, including the creation of a unique foetal blood bank identifier at three sites. CONCLUSION: This survey reviews current practice and highlights the need for standardized national guidelines regarding the selection and preparation of RBCs for IUT. This study has prompted a re-examination of priorities for RBC selection for IUT and highlighted strategies for transfusion traceability in this unique setting.

Severity of haemolytic disease of the fetus and newborn in patients with a history of intrauterine transfusions in a previous pregnancy: A nationwide retrospective cohort study.

OBJECTIVE: Pregnant women who received at least one intrauterine transfusion (IUT) for haemolytic disease of the fetus and newborn (HDFN) in the preceding pregnancy are presumed to have a high likelihood of requiring IUTs again, often starting at an earlier gestational age. Our aim was to quantify these risks in a large national cohort. DESIGN: Retrospective cohort study of a nationwide Dutch database. SETTING: The Netherlands. POPULATION: All women treated in The Netherlands with IUTs for Rhesus D (RhD)- or Kell-mediated HDFN between 1999 and 2017 and their follow-up pregnancies were included. Pregnancies with an antigen-negative fetus were excluded. METHODS: Electronic patient files were searched for the number and gestational age of each IUT, and analysed using descriptive statistics and linear regression. MAIN OUTCOME MEASURES: Percentage of women requiring one or more IUTs again in the subsequent pregnancy, and gestational age at first IUT in both pregnancies. RESULTS: Of the 321 women in our study population, 21% (69) had a subsequent ongoing pregnancy at risk. IUTs were administered in 86% (59/69) of cases. In subsequent pregnancies, the median gestational age at first IUT was 3 weeks earlier (interquartile range -6.8 to 0.4) than in the preceding pregnancy. CONCLUSIONS: Our study shows that pregnant women with a history of IUTs in the previous pregnancy are highly likely to require IUTs again, and on average 3 weeks earlier. Clinicians need to be aware of these risks and ensure timely referral, and close surveillance from early pregnancy onwards. Additionally, for women with a history of IUT and their caregivers, this information is essential to enable adequate preconception counselling.

Case of Hemolytic Disease of the Fetus and Newborn Treated Without Blood Products.

Hemolytic disease of the fetus and newborn (HDFN) affects 3/100,000 to 80/100,000 patients yearly and can cause severe anemia and hyperbilirubinemia. Recombinant human erythropoietin has been used as an adjunct therapy in patients with HDFN and hypo-regenerative anemia in the setting of receiving intrauterine blood transfusions. This case describes a patient with HDFN, in which the family were Jehovah Witnesses, and blood transfusions were declined. The patient had symptomatic anemia with a hematocrit nadir of 18.6%. The patient was successfully treated with recombinant human erythropoietin, ferrous sulfate, and folic acid, avoiding the need for transfusion.

Successful management of severe Kell alloimmunization in pregnancy with intravenous immune globulin.

Hemolytic Disease of the Fetus and Newborn (HDFN) is a condition that affects 1 to 2 out of 1000 patients during pregnancy (1). When an alloantibody is present, it is essential to identify its nature in order to organize appropriate follow-up. Kell-mediated HDFN is rare; it occurs in about 5% of Kell alloimmunized pregnant women. It is important to note that in case of anti-Kell immunization, the severity of HDFN is not correlated with maternal antibody titers, and anemia tends to occur earlier and more severely. Therefore, early diagnosing and management of this condition is crucial. In the management of severe fetal anemia due to Kell immunization, available treatments include in utero transfusion (IUT), immunoglobulin therapy. Other alternative treatments exist, such as plasmapheresis. Intravenous immunoglobulin (IVIG), a noninvasive therapeutic approach, acts through multiple mechanisms. IVIG has been evaluated in cases of RhD immunization with high maternal antibody titers and a history of pregnancies involving early hydrops or intrauterine death. Regarding the potential benefits of intravenous IgG therapy, it may delay the need for early IUT, reduce the overall reliance on IUT, and have a positive impact on obstetric outcomes. This case of IV IgG therapy of anti-Kell immunization offers a thought-provoking avenue for future exploration.

Automated quantitative evaluation of fetal atrioventricular annular plane systolic excursion before and after intrauterine blood transfusion in pregnancies affected by red blood cell alloimmunization.

INTRODUCTION: Maternal red blood cell alloimmunization during pregnancy can lead to hemolysis and various degrees of fetal anemia, which can be treated with intrauterine blood transfusion (IUT) to prevent adverse outcomes. Knowledge about fetal myocardial function and adaptation is limited. The aim of the present study was to measure fetal atrioventricular plane displacement before and after IUT and compare these measurements with previously established reference ranges. MATERIAL AND METHODS: An observational study was conducted on pregnant women affected by red blood cell alloimmunization. Fetal echocardiography was performed before and after IUT. The atrioventricular plane displacement of the left and right ventricular walls and interventricular septum, described as mitral, septal, and tricuspid annular plane systolic excursion (MAPSE, SAPSE, and TAPSE, respectively), was assessed using color tissue Doppler imaging with automated analysis software. A Mann-Whitney U test was used to compare the z scores to the normal mean before and after IUT. RESULTS: Twenty-seven fetuses were included. The mean z score for pre-IUT MAPSE was significantly increased compared with the reference ranges, +0.46 (95% confidence interval [CI] +0.17 to +0.75; p = 0.039), while the mean z scores for post-IUT SAPSE and TAPSE were significantly decreased, -0.65 (95% CI -1.11 to -0.19; p < 0.001) and -0.60 (95% CI -1.04 to -0.17; p = 0.003), respectively. The difference in atrioventricular plane displacement z scores before and after IUT was statistically significant in all three locations. The median difference between the pre-IUT and post-IUT z scores was -0.66 (95% CI -1.03 to -0.33, p < 0.001) for MAPSE, -1.05 (95% CI -1.43 to -0.61, p < 0.001) for SAPSE, and -0.60 (95% CI -1.19 to -0.01, p = 0.046) for TAPSE. CONCLUSIONS: This study suggests that atrioventricular plane displacement, when determined using automated analysis software, may represent a quantitative parameter, describing fetal myocardial function and adaptation before and after IUT.

Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment.

PURPOSE: In adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group. METHODS: We analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group. RESULTS: In the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = - 74.04, T = - 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological. CONCLUSION: NT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.

Fetal Anemia: Determinants and Perinatal Outcomes according to the Method of Intrauterine Blood Transfusion.

INTRODUCTION: Fetal anemia from hemolytic disease treated by intrauterine transfusion (IUT) can be performed by intraperitoneal, intracardiac, and intravascular transfusion (IVT). Objective of our study was to compare different transfusion techniques. METHODS: Retrospective review of IUT secondary to red cell alloimmunization was conducted at eight international centers from 2012 to 2020. Severe anemia suspected if middle cerebral artery peaks systolic velocity ≥1.5 multiples of the median. Demographic, delivery, and postnatal variables were analyzed. RESULTS: Total of 344 procedures, 325 IVT and 19 other techniques (non-IVT) included. No difference in demographics, history of stillbirth (20.5 vs. 15.8%, p = 0.7), prior pregnancy IUT (25.6 vs. 31.6%, p = 0.5) or neonatal transfusion (36.1 vs. 43.8%, p = 0.5). At first IUT, non-IVT had higher hydrops (42.1% vs. 20.4%, p = 0.03), lower starting hematocrit (13.3% [±6] vs. 17.7% [±8.2], p = 0.04), and trend toward lower gestational age (24.6 [20.1-27] vs. 26.4 [23.2-29.6] weeks, p = 0.08). No difference in birthweight, neonatal phototherapy, exchange, or simple transfusion was observed. CONCLUSION: This is one of the largest studies comparing techniques to treat fetal anemia. IVT was most performed, other techniques were more likely performed in hydrops, and lower starting hematocrit was seen. Neither technique affected outcomes. This study may suggest that physician's experience may be the strongest contributor of outcomes.

Placental Histopathologic Findings in Fetal Hereditary Pyropoikilocytosis after Undergoing Successful Intrauterine Transfusion.

Background: The available literature on intrauterine transfusion focuses largely on its application in fetal alloimmunization rather than hereditary red cell disorders, with limited illustration of its associated histopathologic findings. Case report: We present the histologic findings in a placenta associated with preterm delivery of an infant with autosomal SPTA1 mutation following multiple intrauterine transfusions, including appropriate villous maturation, subchorionic organizing hematomas, hemosiderin-laden macrophages, and dysmorphic fetal erythrocytes within villous capillaries. Conclusion: Intrauterine transfusion is associated with placental histologic findings that reflect procedural changes without significant disruption of placental membranes or villous maturation.

Intravenous immunoglobulin in the management of severe early onset red blood cell alloimmunisation.

Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case-control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti-D or anti-K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti-D in 17 women and anti-K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8-53.2, p = 0.0013) and improved perinatal survival (eight of eight vs. none of six, p = 0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early-onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.

Immunomodulation for early-onset haemolytic disease of the fetus/newborn: Can we delay the need for intrauterine transfusions?

When cases of severe fetal anaemia due to maternal red-cell alloimmunization present in the early second trimester, standard treatment with intrauterine transfusion often results in fetal loss. The report by Vlachodimitropoulou et al. offers new insight into the use of maternal intravenous immune globulin to delay the need for intrauterine transfusion. Performing these procedures at a later gestational age increases the likelihood of technical success and subsequent perinatal survival. Commentary on: Vlachodimitropoulou et al. Intravenous immune globulin in the management of severe early onset of red cell alloimmunization. Br J Haematol 2023; 200:97-103.

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

BACKGROUND: To define a threshold of maternal antibodies at risk of severe fetal anemia in patients followed for anti-RH1 alloimmunization (AI). STUDY, DESIGN, AND METHODS: 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 5 IU/ml for the quantification. RESULTS: 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 3.5 IU/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 5 IU/ml, the sensitivity was lower at 95.6%, with five cases of severe anemia not detected. CONCLUSION: The antibody threshold of 3.5 IU/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.

How do we perform intrauterine transfusions?

BACKGROUND: Intrauterine transfusion (IUT) is an invasive but critical and potentially life-saving intervention for severe fetal anemia with demonstrated improvement in outcomes. The fetus is vulnerable to hemodynamic alterations and transfusion-related adverse events; therefore, special consideration must be given to blood component selection and modification. There is widespread IUT practice variability, and existing guidance primarily relies on expert opinion and single center experiences. STUDY DESIGN AND METHODS: Experts in Maternal Fetal Medicine, Pediatric Hematology, and Transfusion Medicine from centers across the United States, collectively performing about 120 IUT annually, offer a multidisciplinary perspective on the performance of IUT and preparation of blood components. This perspective includes strategies for identifying an at-risk fetus, communicating between disciplines, determining the necessary blood volume, selecting and processing blood components, documenting the procedure in medical record, and managing the neonate. RESULTS: Identifying an at-risk fetus relies on review of the clinical history, non-invasive monitoring, and laboratory evaluation. We recommend the use of relatively fresh, group O, cytomegalovirus-safe, freshly irradiated, red blood cells (RBC) that are Hemoglobin S negative and antigen-negative for any maternal antibody, if indicated. These RBC units should be concentrated to remove additives and increase the hematocrit thus minimizing fluctuations in fetal volume status. The units intended for IUT should be labeled clearly and the documentation of transfusion differentiated in the maternal medical record. DISCUSSION: An awareness of the technical, logistical, and regulatory considerations for IUT performance will facilitate improved communication and patient care, especially when rare units of RBC are required.

Prenatal management of fetal anemia due to pyruvate kinase deficiency: A case report.

BACKGROUND: Pyruvate Kinase (PK) deficiency is the most common enzyme defect of glycolysis, leading to congenital hemolytic anemia, which can occur during the neonatal period. STUDY DESIGN AND METHODS: We report the prenatal management of fetal anemia related to PK deficiency in a family with a severe proband. RESULTS: The couple had a first child born with hydrops, whose PK deficiency was diagnosed at 18 months of life. He was treated with allogeneic bone marrow transplantation. The second child was free from disease. For the third pregnancy, the amniocentesis revealed a PK deficiency. Weekly ultrasound monitoring of the middle cerebral artery velocity allowed the detection of severe fetal anemia. Two intrauterine red blood cell transfusions (IUTs) were performed, raising the fetal hemoglobin from 6.6 to 14.5 g/dl at 28 weeks' gestation and from 8.9 to 15.3 g/dl at 31 weeks. A hematopoietic stem cell allograft was discussed prenatally but not chosen, as it would not have significantly changed the perinatal prognosis. The patient delivered a 2730 g girl at 37 weeks, with hemoglobin of 13.6 g/dl. The child presented with neonatal jaundice treated with phototherapy and received postnatal transfusions. DISCUSSION: When a proband is identified in a family, fetal investigation is warranted, to set up third-trimester ultrasound surveillance and perinatal management. In case of fetal severe anemia of unknown etiology, the workup on fetal blood sampling before IUT should comprise the search for erythrocytes enzymopathies, such as PK deficiency. IUTs allow safer full-term delivery in cases with PK deficiency.

Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.

BACKGROUND: Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research. METHODS: We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality. RESULTS: We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks. CONCLUSION: These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.

Second systolic peak in fetal middle cerebral artery Doppler after intrauterine transfusion.

OBJECTIVE: To evaluate functional relationship between fetal circulatory response to intrauterine transfusion (IUT) as a circulatory challenge and appearance of second systolic peak (P2) in middle cerebral artery (MCA) based on hemodynamic principles. METHODS: According to the concept of pulse wave (PW) propagation and reflection in adults, PWs arrive twice at cerebral circulation, as primary wave caused by left ventricle ejection and secondary after reflection in peripheral arteries. Thus adults show a biphasic contour of systolic blood flow in cerebral arteries. Similar waveforms may appear in fetal MCA-Doppler, as a response to IUT as a circulatory challenge. This is a proof-of-principle study, applying classical hemodynamic principles to fetal circulation. Accordingly, appearance of MCA-P2 may indicate vasoconstriction with increased PW reflection and timing of P2(Δt) should agree with the additional PW travel time down to reflection and return (Tr). To test this agreement, we searched our database for IUTs performed for severe fetal anemia, and compared Δt, obtained by Doppler, with Tr, obtained by hemodynamic calculation using human fetal data. Level of agreement was assessed using Bland-Altman-Plots. RESULTS: We identified 21 fetuses with adequate Doppler quality for Δt evaluation. In four cases (19%) MCA-P2 was observed before the intervention, and in 17 interventions (81%) thereafter; a highly significant association between IUT and P2 appearance (p < 0.001). In these 17 interventions good agreement of P2 timing was found between Doppler assessment: Δt = 80 ± 8 ms, and hemodynamic calculation: Tr = 76 ± 4 ms. CONCLUSION: P2 appearance in fetal MCA-Doppler seems to indicate PW reflection due to increased vasoconstriction after IUT. Thus hemodynamic considerations might enable Doppler monitoring of fetal vasoconstriction.

Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study.

PURPOSE: Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20+0 weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection. METHODS: A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results. RESULTS: A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19+3 (13+0-31+4) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20+0 weeks of gestation. CONCLUSION: IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.

Intrauterine Blood Transfusion for Parvo B19-Induced Fetal Anemia: Neuroimaging Findings and Long-Term Neurological Outcomes.

INTRODUCTION: We aimed to evaluate the neuroimaging findings and long-term neurodevelopmental outcomes of fetuses and children following intrauterine blood transfusion (IUT) for parvo B19 infection-induced anemia compared to those with RBC alloimmunization. METHODS: We conducted a retrospective cohort study including women who underwent an IUT due to fetal anemia between 2006 and 2019 in a tertiary, university-affiliated medical center. The cohort was divided into two groups: a study group - fetuses affected by congenital parvo B19 infection; and a control group - fetuses affected by RBC alloimmunization. Retrospective data such as antenatal sonographic evaluations, fetal brain MRI results, and short-term fetal and neonatal outcomes were collected. All children underwent a neurodevelopmental evaluation after birth using a Vineland questionnaire. Primary outcome was defined as the presence or absence of neurodevelopmental delay. Secondary outcome was defined as the presence of abnormal fetal neuroimaging findings such as cerebellar hypoplasia, polymicrogyria, intracranial hemorrhage, or severe ventriculomegaly. RESULTS: Overall, 71 fetuses requiring at least one IUT were included in the study. Of these, 18 were affected by parvo B19 infection and 53 by RBC alloimmunization with various associated antibodies. Fetuses in the parvo B19 group presented at an earlier gestational age (22.91 ± 3.36 weeks vs. 27.37 ± 4.67 weeks, p = 0.002) and were more affected by hydrops (93.33% vs. 16.98%, p < 0.001). Three fetuses out of the 18 (16.67%) fetuses in the parvo B19 group died in utero following the IUT. Abnormal neuroimaging findings were detected in 4/15 (26.7%) of the parvo B19 survivors versus 2/53 (3.8%) of fetuses affected by RBC alloimmunization (p = 0.005). There was no difference in long-term neurodevelopmental delay rates between the children in the study and control groups, as assessed at the average age of 3.65 and 6.53 years, accordingly. CONCLUSION: Fetal anemia due to parvo B19, treated with IUT, might be associated with increased rates of abnormal neurosonographic findings. The correlation between those findings and long-term adverse neurodevelopmental outcomes requires further investigation.

[Clinical Efficacy and Nursing Care of Fetal Intrauterine Blood Transfusion: Previous Experience Review].

Objective: To summarize the clinical efficacy and nursing experience of intrauterine blood transfusion (IUT) treatment for fetal anemia cases. Methods: The clinical data of 4 fetal anemia cases receiving IUT in Beijing Obstetrics and Gynecology Hospital, Capital Medical University between 2020 and 2022 were collected. Four pregnant women aged 24-38 years were included in the study. They carried fetuses with anemia of unknown causes. The four pregnant women developed anxiety after they were informed of the diagnosis of fetal anemia. One-on-one psychological counseling before the IUT procedure and one-on-one companionship over the course of the surgery were provided for the pregnant women. In addition, they were closely monitored for blood transfusion reactions. Postprocedural observation of the puncture site and 24-hour monitoring of the newborns were also conducted. Results: The four pregnant women underwent 1-3 times of IUT in the second and third trimesters, with the minimum gestational age at the time of IUT being 25 + weeks and the blood transfusion volume being 20-107 mL/time. Two pregnant women experienced irregular uterine contractions during IUT in the third trimester. Other than that, all other IUT treatments were successful. After IUT, there was a significant improvement in fetal hemoglobin, peak systolic velocity of the middle cerebral artery (MCA-PSV), and cardiothoracic area ratio. One case did not give birth in our hospital and the outcome of the fetus was not known. The other three fetuses achieved good outcomes. Conclusion: Positive preprocedural psychological counseling for pregnant women, close intraoprocedural and postprocedural pregnancy monitoring, and the prevention of maternal and fetal complications are the key to improving the clinical efficacy of IUT and achieving a good fetal outcome.

Outcome predictors for maternal red blood cell alloimmunisation with anti-K and anti-D managed with intrauterine blood transfusion.

Red blood cell (RBC) alloimmunisation with anti-D and anti-K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion (IUT). Few studies have investigated which haematological parameters can predict adverse fetal or neonatal outcomes. The aim of the present study was to identify predictors of adverse outcome, including preterm birth, intrauterine fetal demise (IUFD), neonatal death (NND) and/or neonatal transfusion. We reviewed the records of all pregnancies alloimmunised with anti-K and anti-D, requiring IUT over 27 years at a quaternary fetal centre. We reviewed data for 128 pregnancies in 116 women undergoing 425 IUTs. The median gestational age (GA) at first IUT was significantly earlier for anti-K than for anti-D (24·3 vs. 28·7 weeks, P = 0·004). Women with anti-K required more IUTs than women with anti-D (3·84 vs. 3·12 mean IUTs, P = 0·036) and the fetal haemoglobin (Hb) at first IUT was significantly lower (51.0 vs. 70.5 g/l, P = 0·001). The mean estimated daily decrease in Hb did not differ between the two groups. A greater number of IUTs and a slower daily decrease in Hb (g/l/day) between first and second IUTs were predictive of a longer period in utero. Earlier GA at first IUT and a shorter interval from the first IUT until delivery predicted IUFD/NND. Earlier GA and lower Hb at first IUT significantly predicted need for phototherapy and/or blood product use in the neonate. In the anti-K group, a greater number of IUTs was required in women with a higher titre. Furthermore, the higher the titre, the earlier the GA at which an IUT was required in both groups. The rate of fall in fetal Hb between IUTs decreased, as the number of transfusions increased. Our present study identified pregnancies at considerable risk of an unfavourable outcome with anti-D and anti-K RBC alloimmunisation. Identifying such patients can guide pregnancy management, facilitates patient counselling, and can optimise resource use. Prospective studies can also incorporate these characteristics, in addition to laboratory markers, to further identify and improve the outcomes of these pregnancies.

A comparative study on perinatal outcomes of red blood cell-alloimmunized pregnancies with anti-RhD in combination and anti-RhD alone in China.

BACKGROUND AND OBJECTIVES: The advent of intrauterine transfusion (IUT) has improved the survival of severe foetal anaemia. The aim of this study was to compare the perinatal outcomes of red blood cell (RBC)-alloimmunized pregnancies with anti-RhD in combination and anti-RhD alone in China. MATERIALS AND METHODS: A retrospective study was conducted involving RBC-alloimmunized pregnancies with anti-RhD in combination and anti-RhD alone admitted to The First Affiliated Hospital, Sun Yat-sen University, between January 2007 and December 2019. Obstetric data and neonatal outcomes were compared. RESULTS: A total of 165 alloimmunized pregnancies were identified, with 32 pregnancies in the anti-RhD-in-combination group (25 pregnancies with anti-RhD + anti-RhC and 7 pregnancies with anti-RhD + anti-RhE) and 133 pregnancies in the anti-RhD-alone group. The anti-RhD-in-combination group had significantly higher frequency of IUTs than the anti-RhD-alone group (59.4% [19/32] vs. 30.1% [40/133]; p < 0.01). The postnatal frequency of top-up transfusions was significantly higher in the anti-RhD in combination group than the anti-RhD-alone group (90.6% [29/32] vs. 70.7% [94/133]; p = 0.02). There was no significant difference in the frequency of exchange transfusions (ETs) between the two groups (15.6% [5/32] vs. 17.3% [23/133]; p = 0.82). CONCLUSIONS: Compared to alloimmunized pregnancies with anti-RhD alone, pregnancies with anti-RhD in combination with anti-RhC or anti-RhE have an increased requirement for antenatal IUTs and postnatal top-up transfusions but do not have an increased need for ETs.