Intrauterine transfusion under fetal analgesia: the evaluation of perinatal outcomes.

Introduction: Intrauterine transfusion is the treatment for fetal anemia resulting from maternal alloimmunization, infections (parvovirus B19 and cytomegalovirus), single demise of a monochorionic twin, chorioangioma, and other rare conditions. Fetal analgesia is mandatory to reduce movement and pain perception during the procedure. This study aims to evaluate perinatal outcomes for such procedures, following the routine use of fetal analgesia in our clinical practice. Materials and methods: Retrospective analysis of cases from 2009 to 2022, including all confirmed fetal anemia with fetal blood sampling. After fetal analgesia, Rh-negative concentrated red blood cells were transfused, with ultrasonographic follow-up 24 h and 1 week later. In case of suspected brain lesion, magnetic resonance imaging was performed. Elective delivery was considered in case of persistent anemia after 34 weeks. Post-natal follow-up and comprehensive obstetric and perinatal outcomes data were collected. Results: Altogether 59 anemic fetuses were included, with 34 (57.6%) being hydropic. The causes of anemia were maternal alloimmunization (22, 37.3%), infections (13, 22%), monochorionicity (10, 16.9%), rare conditions (9, 15.3%), and two chorioangiomas (3.4%). The median gestational age at the procedure was 25.2 weeks (18-32 weeks), with no related preterm premature rupture of membranes (<48 h), or side effects from fetal analgesia. Gestational age at delivery was 33 weeks (26-41 weeks), with survival rate of 90%. There were four fetal demises, two termination of pregnancies, and eight neonatal deaths due to persistent severe anemia after preterm delivery. The main contributors to adverse outcome were the type of anemia, and the management with a preterm delivery. Conclusion: Intrauterine transfusion of red blood cells under analgesia is safe, with low incidence of obstetric complication.

Maternal isoimmunization associated fetal anemia: A case report.

Maternal isoimmunization occurs when a pregnant woman develops an immune reaction due to the inheritance of a red-cell antigen, which is paternally derived and can result in fetal anemia, hemolysis, fetal death, and hydrops fetalis as the antibodies might travel through the placenta and get adhered to the antigens present in the erythrocytes of the fetus. This report highlights a rare case of Rh isoimmunization leading to fetal anemia in a 26-year-old female and evaluates the impact of intrauterine transfusion (IUT) in terms of the gestational age at delivery along with the mode of delivery, procedural complications, and overall survival rate of the fetus. In conclusion, the most frequent cause of fetal anemia is Rh alloimmunization, which should be taken into consideration while making a differential diagnosis throughout the assessment. Improvements in IUT procedures and earlier detection of the MCA-PSV by Doppler ultrasonographic examination have also contributed to better results.

Glucose-6-phosphate dehydrogenase deficiency as a cause for nonimmune hydrops fetalis and severe fetal anemia: A systematic review.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia. METHODS: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed. RESULTS: Five cases of G6PD-related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD-deficient patients. Exposures to substances known to cause G6PD deficiency-related hemolysis occurred in 3/6 (50%) cases. CONCLUSION: Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X-linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative.

Elevated Middle Cerebral Artery Peak Systolic Velocity in Non-Anemic Fetuses: Providing a Better Understanding of Enigmatic Middle Cerebral Artery Peak Systolic Velocity.

INTRODUCTION: Our aim was to investigate the incidence, comorbidities, and outcomes of fetuses with an elevated middle cerebral artery peak systolic velocity (MCA-PSV) >1.5 multiples of median (MoM), despite normal hemoglobin (Hgb) levels on fetal blood sampling (FBS). METHODS: A single-center observational retrospective cohort study of all fetuses undergoing FBS and MCA-PSV >1.5 MoM. Only those fetuses with no or mild anemia were included. Indications for Doppler assessment, associated anomalies, and neonatal outcomes were collected. RESULTS: Overall, 383 fetuses had an MCA-PSV >1.5 MoM and underwent FBS. Twenty-three (6%) fetuses met our inclusion criteria and had no or only mild anemia. Associations with elevated MCA-PSV were elucidated in 12 of the 23 cases (52.2%) and included mild anemia (n = 2), intracranial hemorrhage (n = 3), genetic disease (n = 1), idiopathic nonimmune hydrops (NIH, n = 1), hypoxic-ischemic encephalopathy (n = 1), maternal and or fetal acidosis (n = 3), and fetal growth restriction (n = 1). Favorable perinatal outcomes were observed in truly unexplained 11 cases with no additional anomalies (47.8%). CONCLUSION: Elevated MCA-PSV >1.5 MoM with normal Hgb levels is seen in 6% of pregnancies undergoing FBS and is often associated with other significant maternal or fetal problems. Those with unexplained and isolated MCA-PSV elevation have normal outcomes.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

Fetal and Placental Causes of Elevated Serum Alpha-Fetoprotein Levels in Pregnant Women.

The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein began. In times when ultrasonography was not yet technically advanced, the detection of high levels of AFP in maternal serum (MS-AFP) and amniotic fluid was the basis for suspecting neural tube defects. In cases where there was no confirmation of NTD, other causes were sought. It has been established that high titers of MS-AFP could originate in other defects or diseases, such as (1) increased proteinuria in severe fetal kidney diseases; (2) pathological overproduction in liver diseases; (3) penetration through the membranes of gastrointestinal organs exposed to amniotic fluid; (4) passage through the walls of skin vessels; and as a side effect of (5) hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia. This article provides a review of the current literature on congenital defects and genetic diseases in the fetus where an elevated level of MS-AFP may serve as the initial diagnostic clue for their detection.

Middle cerebral artery peak systolic velocity monitoring of fetal anemia during chemotherapy in pregnancy.

INTRODUCTION: Chemotherapy during pregnancy can increase the risk of fetal anemia. Severe fetal anemia can lead to the development of hydrops fetalis and potentially fetal demise. Hence, it is imperative to implement consistent monitoring methods in the context of chemotherapy treatment. This study aimed to diagnose and monitor fetal anemia using middle cerebral artery peak systolic velocity (MCA-PSV) as a diagnostic tool during chemotherapy in pregnant women. MATERIAL AND METHODS: The study employed a prospective analysis involving a case series of 15 patients diagnosed with cancer during pregnancy and subsequently underwent chemotherapy. MCA-PSV was used to identify fetal anemia. The patients were scheduled for ultrasound examinations of the MCA-PSV. The first examination was performed on the same day as the administration of chemotherapy, while the second occurred on the 10th day after chemotherapy. The measurement technique used in the study was based on the methodology proposed by Mari and Barr. The multiples of the median were calculated using the calculators provided by Medicina Fetal Barcelona. Based on these values anemia severity was determined. When moderate or severe anemia was identified, chemotherapy was individually modified. Additionally, a blood count analysis was conducted immediately after the delivery of the newborn. RESULTS: Five patients were diagnosed with fetal or newborn anemia. With MCA-PSV, we identified moderate fetal anemia in two patients and severe fetal anemia in one. The complete blood count testing of newborns revealed mild anemia in three patients. One case was unrelated to chemotherapy-induced anemia. During treatment, fetal anemia did not corelate with maternal anemia. CONCLUSIONS: In four cases of anemia the combination of cisplatin and iphosphamide was used as a chemotherapy agent. No anemia was observed in other drug combinations. Our findings suggest that MCA-PSV is a reliable method for identifying anemia and should be included in the treatment protocol for chemotherapy-induced fetal anemia.

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.

Third-trimester fetoscopic ablation therapy for types II and III vasa previa.

BACKGROUND: Vasa previa is an obstetrical condition in which fetal vessels located near the cervix traverse the fetal membranes unprotected by underlying placenta. Type I vasa previa arises directly from a velamentous cord root, whereas types II and III arise from an accessory lobe or a distal lobe of the same placenta, respectively. Fetoscopic laser ablation for types II and III vasa previa is a novel therapeutic option with benefits that include surgical resolution of the vasa previa, avoidance of prolonged hospitalization, and opportunity for a term vaginal delivery. The potential risks of fetoscopy can be mitigated by delaying laser surgery until a gestational age of 31 to 33 weeks, immediately before anticipated hospitalized surveillance. OBJECTIVE: This study aimed to assess feasibility and outcomes of types II and III vasa previa patients treated via fetoscopic laser ablation in the third trimester. STUDY DESIGN: This is a retrospective study of singleton pregnancies with types II and III vasa previa treated with fetoscopic laser ablation at a gestational age ≥31 weeks at a single center between 2006 and 2022. Pregnancy and newborn outcomes were assessed. Continuous variables are expressed as mean±standard deviation. RESULTS: Of 84 patients referred for vasa previa, 57 did not undergo laser ablation: 19 either had no or resolved vasa previa, 25 had type I vasa previa (laser-contraindicated), and 13 had type II or III vasa previa but declined laser treatment. Of the remaining 27 patients who underwent laser ablation, 7 were excluded (laser performed at <31 weeks and/or twins), leaving 20 study patients. The mean gestational age at fetoscopic laser ablation was 32.0±0.6 weeks, and total operative time was 62.1±19.6 minutes. There were no perioperative complications. All patients had successful occlusion of the vasa previa vessels (1 required a second procedure). All patients were subsequently managed as outpatients. The mean gestational age at delivery was 37.2±1.8 weeks, the mean birthweight was 2795±465 g, and 70% delivered vaginally. Neonatal intensive care unit admission occurred in 3 cases: 1 for respiratory distress syndrome and 2 for hyperbilirubinemia requiring phototherapy. There were no cases of neonatal transfusion, intraventricular hemorrhage, sepsis, patent ductus arteriosus, or death. CONCLUSION: Laser ablation for types II and III vasa previa at 31 to 33 gestational weeks was technically achievable and resulted in favorable outcomes.

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.

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.

Transfusión intrauterina, hidrops fetal no inmune: reporte de un caso / Intrauterine transfusion, non-immune fetal hydrops: case report / Transfusão intrauterina, hidropisia fetal não imune: relato de caso

Introducción: el hidrops fetal es grave, de mal pronóstico y alta morbimortalidad, a pesar de mejoras diagnósticas y terapéuticas desarrolladas en los últimos tiempos. El pronóstico estará determinado por la etiología y posibilidades terapéuticas asociadas a mejores resultados, a la edad gestacional, al diagnóstico y al nacimiento, si bien cabe destacar que no existen suficientes estudios de seguimiento a largo plazo. El diagnóstico ecográfico es confirmatorio, siendo la principal complejidad identificar la etiología y plantear la estrategia terapéutica adecuada. Descripción del caso: presentamos una paciente con diagnóstico de hidrops fetal de tipo no inmune y su abordaje terapéutico. La causa del hidrops correspondió a anemia fetal severa, requiriendo la realización de tres procedimientos con exanguinotransfusión parcial intrauterina mediante cordocentesis. A las 33 semanas, se decidió la finalización del embarazo, con buena evolución neonatal. Conclusión: el hidrops fetal aumenta la morbimortalidad fetal y neonatal, siendo un enorme desafío para el equipo tratante, que requiere de un equipo asistencial interdisciplinario. El conocimiento de esta patología permite realizar un abordaje completo, orientar a la etiología, realizando un diagnóstico oportuno y la selección adecuada del tratamiento. Como en este caso, al identificar la anemia severa como causa del hidrops, es mandatorio definir el manejo para los fetos candidatos a terapia intrauterina.

Introduction: fetal hydrops is a serious condition with a poor prognosis and high morbidity and mortality, despite improvements in diagnostics and therapeutics in recent years. Prognosis is determined by the etiology and therapeutic options associated with better outcomes, gestational age, diagnosis, and birth, although it should be noted that there are not enough long-term follow-up studies. Ultrasound diagnosis is confirmatory, with the main challenge being to identify the etiology and propose the appropriate therapeutic strategy. Description of the case: we present a patient diagnosed with non-immune fetal hydrops and its therapeutic approach. The cause of hydrops was severe fetal anemia, requiring 3 procedures with intrauterine partial exsanguination transfusion through Cordocentesis. At 33 weeks, the decision was made to terminate the pregnancy, with good neonatal outcomes. Conclusions: fetal hydrops increases fetal and neonatal morbidity and mortality, posing a significant challenge for the treating team and requiring an interdisciplinary healthcare team. Understanding this condition allows for a comprehensive approach, guiding the etiology, providing timely diagnosis, and selecting appropriate treatment. As in this case, identifying severe anemia as the cause of hydrops mandates defining the management for fetuses eligible for intrauterine therapy.

Introdução: a hidropisia fetal é grave, com mau prognóstico e elevada morbimortalidade, apesar das melhorias diagnósticas e terapêuticas desenvolvidas nos últimos tempos. O prognóstico será determinado pela etiologia e possibilidades terapêuticas associadas a melhores resultados, idade gestacional, diagnóstico e nascimento, embora se deva salientar que não existem estudos suficientes de seguimento a longo prazo. O diagnóstico ultrassonográfico é confirmatório, sendo a principal complexidade identificar a etiologia e propor a estratégia terapêutica adequada. Descrição do caso: apresentamos uma paciente com diagnóstico de hidropisia fetal não imune e sua abordagem terapêutica. A causa da hidropisia correspondeu a anemia fetal grave, sendo necessária a realização de 3 procedimentos com exsanguineotransfusão intrauterina parcial por meio de cordocentese. Às 33 semanas foi decidida a interrupção da gravidez, com boa evolução neonatal. Conclusão: a hidropisia fetal aumenta a morbimortalidade fetal e neonatal, sendo um enorme desafio para a equipe responsável pelo tratamento, necessitando de uma equipe de atendimento interdisciplinar. O conhecimento desta patologia permite uma abordagem completa, orientação sobre a etiologia, diagnóstico atempado e seleção do tratamento adequado. Assim como neste caso, quando se identifica anemia grave como causa da hidropisia, é obrigatória a definição do manejo para os fetos candidatos à terapia intrauterina.

Double/Triple Intrauterine Blood Transfusion in Rh-isoimmunized Anemic Fetuses in Multiple Pregnancies with Favorable Outcome.

Background: Multiple pregnancies have increased with the use of assisted reproduction, and we expect more women reporting with Rh isoimmunization among multiple gestation in near future. Intrauterine transfusion in singleton itself is technically difficult and requires a lot of skill and precision. Performing double/triple transfusion in twins/triplets is expected to be more demanding. Aim: To create awareness on the technical difficulties encountered in intrauterine transfusion in twins and triplets. Methodology: We report a case series of four Rh-isoimmunized twins/triplets in 5 years who presented with severe anemia requiring intrauterine transfusion. Results: Each of the four sets of cases had their own intricacies that needed to be pondered before tackling them as not much was available in the literature. In Case 1, the first twin intrauterine transfusion in our 20-year-long experience, the difficulty in the approach to the first twin due to a posteriorly placed placenta has been highlighted. Case 2 was rare due to the concomitant presence of atypical antibodies in the mother in addition to Rh-D isoimmunization that made it difficult to cross match any donor blood for intrauterine transfusion. The third case was exclusive due to its monochorionic-diamniotic nature of the twins where the impact of inter-twin anastomosis on the transfusion was to be taken into consideration. Fourth case was a triplet gestation where the difficulty of which cord to be assigned to which fetus, the crowded space for intervention, as well as the risk of prolonged operative time and associated risk of preterm/premature rupture of membranes were our concern. Conclusion: Intrauterine transfusion (IUT) in twins/triplets is challenging. Difficulties encountered during IUT in multifetal gestation are due to different or uncertain chorionicity, intraplacental anastomosis between vessels, different degree of anemia in twins, difficult to ascertain cord-fetus relationship and difficulty to reach placental insertion site due to crowding by multiple fetal parts.

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.

Accuracy of a portable hemoglobinometer (HemoCue) to measure fetal hemoglobin values during in utero transfusion.

OBJECTIVES: The current recommended treatment for severe fetal anemia is in utero transfusion (IUT). During this procedure, the evaluation of the necessary volume of transfused blood is based on regular measurement of fetal hemoglobin (FHb) concentration. The gold standard measurement is performed in the biology laboratory. A rapid medical test such as HemoCue® is an effective way to predict FHb concentration. It would reduce the time to obtain results and therefore the procedure duration. To evaluate the accuracy of HemoCue® to measure FHb during IUT, we compared Hb levels obtained by HemoCue® and by our biology laboratory. METHODS: This retrospective study involved all pregnant women who had undergone an IUT in the university hospital of Clermont-Ferrand, France, during the period from 1 January 2010 to 6 June 2021. The FHb level was evaluated by two methods, a rapid medical test, HemoCue®, and a standard method in the biology laboratory. RESULTS: We obtained 244 pairs of results from HemoCue® and our laboratory, of 90 IUT procedures. The correlation between the two sets of results was excellent, with Lin's concordance correlation coefficient of 0.979. However, we established that the measurements were not significantly modified by IUT number, puncture time, cause of fetal anemia, estimated fetal weight, gestational age, and delay between two IUT or middle cerebral artery peak systolic velocity values. CONCLUSION: Our results allowed to extend the relevance of FHb measurements by HemoCue® during IUT.

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Case 1 presented with severe anemia and received an intrauterine blood cell transfusion at 33 weeks of gestation. The anemia spontaneously improved in early infancy. Case 2, the father of Case 1, had an uneventful birth with no evidence of anemia, though microcytic anemia was observed during childhood. The genetic analysis of the ß-globin gene cluster identified a novel heterozygous deletion of DNA extending from the Gγ-globin gene downstream to the ß-globin gene, confirming a diagnosis of (G γA γδß)0 -thalassemia. In cases where thalassemia is suspected based on blood tests, a genetic diagnosis should be performed for the sake of the offspring.

Intravenous immunoglobulin treatment of congenital parvovirus B19 induced anemia - a case report.

BACKGROUND: Parvovirus is a common childhood infection that could be very dangerous to the fetus, if pregnant women become infected. The spectrum of effects range from pure red blood cell aplasia with hydrops fetalis to meningoencephalitis, with many symptoms in between. Severe anemia in the setting of pure red blood cell aplasia is one of the more common effects that neonatal experience (if infected intrapartum), with the current gold standard treatment being intrauterine or postnatal packed red blood cell (PRBC) transfusions, yet intravenous immunoglobulin (IVIG) may be a superior treatment option. CASE PRESENTATION: A preterm infant was born at 26th week of gestational age via emergency Cesarean section due to hydrops fetalis, with parvovirus B19 exposure one month prior. The infant tested positive for IgM antibodies against parvovirus B19. Among many other serious complications of both hydrops fetalis and premature delivery, the infant had severe unremitting anemia, and received many PRBC transfusion over the course of his 71-day-long neonatal intensive care unit stay. During a follow up appointments as outpatient, his blood tests showed persistent high copies of parvovirus B19. He was then supported with PRBC transfusions and treated with IVIG. After three doses of IVIG, the infant's parvovirus B19 viral copy numbers have dramatically reduced and the infant did not require any more PRBC transfusions. CONCLUSIONS: IVIG infusion effectively treated the parvovirus B19 infection and restored erythropoiesis making the child transfusion independent. Furthermore, since IVIG is safe and readily crosses the placenta, further studies are needed to determine if IVIG should be considered as an alternative prenatal treatment for congenital parvovirus B19 infection.

[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.

Velocity Time Integral: A Novel Method for Assessing Fetal Anemia.

The velocity time integral (VTI) is a clinical Doppler ultrasound measurement of blood flow, measured by the area under the wave curve and equivalent to the distance traveled by the blood. This retrospective study assessed the middle cerebral artery (MCA) VTI of fetuses in pregnancies complicated by maternal alloimmunization. Doppler indices of the MCA were retrieved from electronic medical records. Systolic deceleration-diastolic time, systolic acceleration time, VTI, and peak systolic velocity (PSV) were measured at 16-40 weeks gestation. Cases with PSV indicating fetal anemia (cutoff 1.5 MoM) and normal PSV were compared. The study included 255 Doppler ultrasound examinations. Of these, 41 were at 16-24 weeks (group A), 100 were at 25-32 weeks (group B), and 114 were at 33-40 weeks (group C). VTI increased throughout gestation (5.5 cm, 8.6 cm, and 12.1 cm in groups A, B, and C, respectively, p = 0.003). VTI was higher in waveforms calculated to have MCA-PSV ≥ 1.5 MoM compared to those with MCA-PSV < 1.5 MoM (9.1 cm vs. 14.1 cm, respectively, p < 0.001), as was VTI/s (22.04 cm/s vs. 33.75 cm/s, respectively; p < 0.001). The results indicate that the MCA VTI increases significantly among fetuses with suspected anemia, indicating higher perfusion of hemodiluted blood to the brain. This feasible measurement might provide a novel additional marker for the development of fetal anemia.

Fetoscopic demonstration of feto-fetal hemorrhage before actual demise of a monochorionic twin, successful antenatal treatment, and narrative review of the literature.

Feto-fetal hemorrhage (FFH) through placental vascular anastomoses is believed to be responsible for the death or damage of a "second twin" after the demise of a "first twin (co-twin)" in monochorionic twin pregnancies. However, the timing of FFH has been difficult to determine. The resulting anemia in the surviving twin can be suspected by the finding of an elevated middle cerebral artery peak-systolic velocity (MCA-PSV), but this elevation may lag for at least 4 h after the demise of the first twin. Knowledge of the timing of FFH may have important clinical implications, as it may dictate if and when attempts to prevent death or damage to the second twin by delivery or intrauterine fetal transfusion would be warranted. We present a case that supports the notion that FFH occurs before the actual demise of the first twin. A review of the literature was also conducted.