Intrauterine Transfusion Research Articles

Perinatal outcomes of intrauterine transfusion for the surviving twin in monochorionic twin gestation involving a single fetal demise.

This study aimed to evaluate the feasibility and outcome of intrauterine transfusion (IUT) for the surviving co-twin in monochorionic diamniotic (MCDA) twin gestations involving single intrauterine fetal death (sIUFD). Cases of MCDA twin gestations involving emergent IUT for co-twins experiencing acute feto-fetal hemorrhage (AFFH) subsequent to sIUFD during the second trimester were reviewed. Fetal anemia was confirmed via fetal blood sampling, and perinatal data were retrieved from medical charts to determine the outcomes of surviving co-twins. A poor outcome at 28 days of age was defined as fetal death, neonatal death or neurological impairment such as severe intraventricular hemorrhage or cystic periventricular leukomalacia (PVL). This study included 16 cases of sIUFD diagnosed at a median of 22.5 weeks of gestation (range: 18-25 weeks). The median interval in hours between diagnosis of fetal demise and IUT was approximately 4.2 (0-22) hours. All cases achieved IUT without significant intraoperative complications. Four cases experienced a fetal loss of the co-twin, whereas 12 co-twins were born alive (including 9 preterm births), with only 1 poor outcome in a preterm infant with PVL. IUT may be a feasible prenatal intervention for surviving co-twins with AFFH. However, more extensive or pooled studies are needed to determine the efficacy of this intervention.

Prevalence of red-blood-cell and non-red-blood-cell-targeted autoantibodies in alloimmunized postpartum women.

Alloantibodies against red-blood-cell (RBC) antigens often coincide with alloantibodies against leucocytes and platelets and sometimes with autoantibodies towards various antigens. Chimerism may be one of the factors responsible for the combination of allo- and autoantibodies. Women with alloantibodies against RBC antigens causing haemolytic disease of the fetus and neonate may need to receive intrauterine transfusions. These transfusions increase not only maternal antibody formation but also fetomaternal bleeding and may enhance fetal chimerism. We determined the prevalence of and risk factors for autoantibodies against some common clinical target antigens, in alloimmunized women after IUT. We tested for autoantibodies against RBC, anti-thyroid peroxidase, anti-extractable nuclear antigens, anti-cyclic citrullinated proteins and anti-tissue transglutaminase. Women with and without autoantibodies were compared for age; number of RBC alloantibodies, pregnancies and IUTs, and other factors that may play a role in immunization. Non-RBC-targeted autoantibodies were present in 40 of 258 tested women (15·5%, with 90% anti-TPO specificity), comparable to the prevalence reported in healthy Dutch women of these ages. Surprisingly, compared with women who had a single RBC alloantibody, a significantly higher proportion of women with multiple RBC alloantibodies had autoantibodies (5·3% and 18·4%, respectively; odds ratio 4·06, 95% CI: 1·20-13·7). Other characteristics of women with and without autoantibodies were not different. Multiple RBC alloantibodies after extensive allogeneic exposure during pregnancy and presumed increased fetomaternal chimerism are not associated with (selected) autoantibodies. Lack of allo-RBC multi-responsiveness seems associated with decreased auto(-TPO) antibody formation.

Maternal Respiratory Distress and Successful Reversal With Sugammadex During Intrauterine Transfusion With Fetal Paralysis

(Int J Obstet Anesth. 2019;39:129–140) Intrauterine transfusion (IUT) is a treatment for fetal anemia resulting from Rh(D) alloimmunization. Fetal paralysis is often utilized during an IUT procedure to improve its safety. Fetal bradycardia is one of the most common complications of the procedure, and use of paralysis has been found to significantly decrease the risk of fetal heart rate changes during IUT. There are several neuromuscular blocking agents (NMBA) available for inducing fetal paralysis, and a possible complication during IUT is inadvertent maternal administration of an NMBA. This case report involved maternal respiratory distress secondary to unintended neuromuscular blockade during IUT, which was treated with sugammadex administration.

Maternal-fetal surgery during the coronavirus disease 2019 pandemic

Maternal-fetal surgery during the coronavirus disease 2019 pandemic

Vox Sanguinis International Forum on the selection and preparation of blood components for intrauterine transfusion: Summary.

Vox Sanguinis International Forum on the selection and preparation of blood components for intrauterine transfusion: Summary.

Vox Sanguinis International forum on the selection and preparation of blood components for intrauterine transfusion

Vox Sanguinis International forum on the selection and preparation of blood components for intrauterine transfusion

Intrauterine transfusions for maternofetal red‐blood‐cell incompatibility in monochorionic diamniotic twin pregnancy

Maternal alloimmunization to fetal red-blood-cell (RBC) antigens may cause hemolytic disease in the fetus with severe anemia. Intrauterine transfusions (IUTs) in twin pregnancy represent 1.5% of all fetal transfusions for RBC alloimmunization1, 2. Here, we present a case of a monochorionic diamniotic twin pregnancy complicated by severe anti-D maternofetal incompatibility, monitored by fetal middle cerebral artery (MCA) peak systolic velocity (PSV) and treated successfully by repeat IUTs of a single cotwin. The patient was referred to our center at 24 weeks' gestation for suspected fetal anemia. Fetal middle cerebral artery (MCA) peak systolic velocity (PSV) reached 1.64 multiples of the median (MoM) in Twin A and 2.02 MoM in Twin B. Both fetuses presented with ascites. Twin A was transfused with 30 mL of packed RBC. Pretransfusion hemoglobin (Hb) was 3.0 g/dL, with a Kleihauer–Betke test (KBT) result of 100% in fetal blood3, 4. Post-transfusion Hb increased to 8.8 g/dL and KBT decreased to 18%. MCA-PSV decreased from 1.64 to 1.19 MoM in Twin A and from 2.02 to 1.64 MoM in Twin B. Thirty minutes later, as MCA-PSV remained above 1.5 MoM in Twin B, an IUT of 15 mL was administered to Twin B, which enabled Hb level in Twin B to increase from 8.1 to 11.4 g/dL, and KBT in fetal blood decreased from 17% to 10%. The direct antiglobulin test showed a result of 3+ (high intensity) and cord bilirubin was over 70 µmol/L. These findings were suggestive of ongoing hemolytic disease. For subsequent IUTs at 25 + 4, 27 + 3 and 30 + 3 weeks' gestation, only Twin A was transfused. This strategy allowed for the normalization of MCA-PSV in both fetuses (Figure 1, Table 1). Cesarean section was performed at 31 weeks' gestation for non-reassuring fetal-heart tracing. The first delivered male neonate had birth weight of 1330 g, arterial cord blood pH of 7.37, Hb of 11.3 g/dL and bilirubin of 90 µmol/L. The second neonate had birth weight of 1310 g, arterial cord blood pH of 7.43, Hb of 11.5 g/dL and bilirubin of 88 µmol/L. Placental colored dye injection showed several arterioarterial anastomoses. The twins had respiratory distress syndrome which was treated by non-invasive ventilatory support. Severe jaundice worsened despite intensive phototherapy and albumin infusion, requiring exchange transfusion in both neonates. Two transfusions at 15 and 45 days were also needed. The neonates were discharged at 66 days postpartum. In this case, during the first IUT, transplacental intertwin anastomoses were demonstrated by (1) MCA-PSV values in Twin B decreasing after IUT of Twin A, (2) KBT in fetal blood already being reduced in Twin B after IUT of Twin A but before IUT of Twin B, and (3) Hb in Twin B being similar to that observed in Twin A after IUT of Twin A but before IUT of Twin B. To our knowledge, this is the first reported case demonstrating the contribution of MCA-PSV to monitoring monochorionic twin pregnancy complicated by RBC alloimmunization, treated by repeat IUTs of a single cotwin. One case of a monochorionic twin pregnancy in which IUTs performed in turn in each cotwin has been reported, without using MCA-PSV monitoring2. In cases of fetal anemia caused by Rh alloimmunization in monochorionic twin gestations, it appears sufficient to transfuse only one of the fetuses at 2–3 week intervals.

The Limitations of Middle Cerebral Artery Peak Systolic Velocity and the Need for Certification [38A

INTRODUCTION: In fetuses at risk for anemia, middle cerebral artery-peak systolic velocity (MCA-PSV) may have a 12% false-positive rate. Guidelines suggest MCA-PSV is superior to amniocentesis for detection of anemia, provided the correct technique is used. We aim to describe the limitations of MCA-PSV in the diagnosis of fetal anemia and the need for MCA-PSV certification for tertiary care fetal centers. METHODS: This is a university based single-center retrospective study of 47 sensitized pregnancies suspected to have fetal anemia that underwent amniocentesis. Fetal anemia was suspected on elevated MCA-PSV >1.5 MoM. Amniotic fluid ΔOD450 was measured in all pregnancies. Fetuses with amniotic fluid ΔOD450 in zone 3 on Liley's chart, underwent cordocentesis for the assessment of fetal anemia. Intrauterine fetal transfusion (IUT) was performed in fetuses confirmed with anemia. Fetal anemia indicating IUT was defined as ≥5 SD below the mean for GA and Hematocrit ≤30%. RESULTS: Among sensitized pregnancies with elevated fetal MCA-PSV, 19 (40.4%) had elevated ΔOD450 measurements. Of these 19 fetuses, 15 (78.9%) required IUT. In 28/47 (59.6%) with normal ΔOD450, elevated MCA-PSV incorrectly predicted fetal anemia, increasing the amniocentesis related risks. This is much higher than the published false positive results of 12%. CONCLUSION: The decreased specificity of MCA-PSV for fetal anemia diagnoses may be associated with user variability. While MCA-PSV has clinical benefit for the initial workup, the additional amniocentesis confirmation reduced the need for cordocentesis. Amniocentesis also has risks and to further reduce the need for invasive diagnostic testing, we recommend a Certification for MCA-PSV Doppler sonography.

Short-term outcomes following intrauterine transfusions for fetal anaemia: A retrospective cohort study.

Intrauterine transfusion (IUT) is the accepted standard for management of severe fetal anaemia. However, fetal transfusion may be associated with procedural complications such as fetal demise. There is a paucity of recent data on outcomes for severe fetal anaemia in Australia as compared with published outcomes from large international centres. To review the indications for and the procedural, obstetric and neonatal outcomes following intrauterine transfusion for fetal anaemia conducted at the New South Wales Fetal Therapy Centre (NSW FTC). Retrospective cohort study conducted between 2005 and 2017 of the outcomes of 85 IUT procedures (39 pregnancies). Data collected included maternal demographics, procedural and obstetric details and short-term neonatal outcomes. Complete outcome data were available for 36/39 pregnancies. Red cell antibodies were the main indication for fetal transfusion (79%, predominantly D, Kell and other Rhesus antibodies) with parvovirus accounting for 8% of procedures. IUT was associated with a pregnancy loss rate of 1.2%/procedure, amounting to 2.6%/pregnancy. Fetal losses were limited to those complicated by hydrops prior to IUT (3/10 hydrops vs 0/26 non-hydropic; P=0.003). Procedural outcomes at NSW FTC compare favourably with international centres (1.1-8.7% procedural loss rate). However, this comparison is limited, as no procedures were performed during the last 24months of the study. Given this, a nationwide audit is recommended to help guide appropriate centralisation of procedures and thereby maximise clinician experience and outcome.

Intrauterine transfusion: an international review of practice and policy

BackgroundIntrauterine transfusion (IUT) is a treatment for fetal anemia. This technique involves ultrasound guided needle placement followed by transfusion of a specially prepared blood component. The most common indications include hemolytic disease of the fetus and newborn (HDFN) and prenatal infection.MethodsThe literature was reviewed, and blood component characteristics and preparatory techniques identified. An international survey of IUT was conducted.ResultsComponent preparation for IUT differs from preparation for other transfusions. Differences relate to unique characteristics of the fetus including a small blood volume, invasive access for transfusion and immune deficiency. The techniques for preparation of red blood cells (RBC) are variable with limited evidence. Most use fresh concentrated RBC. Irradiation is uniformly recommended. RBC that are antigen negative for the maternal alloantibody are provided, and the product is selected or modified to minimize risk for cytomegalovirus transmission. Selection of ABO group and the degree of additional prophylactic phenotype matching are variable. While maternal RBC transfusion may be used, compatible allogeneic RBC are more common. For maternal antibodies to high prevalence antigens rare phenotype deglycerolized RBC may be used. There are challenges in providing RBC for IUT. Pre and post transfusion blood samples must be correctly managed in the medical record. Hemovigilance requires that both the fetus and the mother be documented as recipients. Preparation may be urgent, and sterile technique is required. Records of IUT must be conveyed to neonatal care providers as the transfused blood may mask the true blood group for weeks to months post transfusion, and component modifications may be required for any postnatal transfusion in neonates who were treated with IUT.

Prenatal Embolisation of Giant Chorioangioma Using n-Butyl Cyanoacrylate: Technique, Clinical Course and Perinatal Outcome

AbstractGiant Chorioangiomas, although rare, can be associated with serious fetal complications due to blood cell sequestration, shunt physiology or both. Prenatal treatment is aimed to counter the primary complication, usually an intrauterine transfusion to treat anemia or occlusion of the feeder artery to negate the shunt physiology. We describe a case of giant chorioangioma complicated by high output cardiac dysfunction with imminent hydrops that was treated with embolisation of the feeder artery using n-butyl cyanoacrylate and discuss how one modality may not fit all cases.

Impact of intrauterine transfusion on fetal coagulation physiology by thromboelastography.

Thromboelastography (TEG) is a point-of-care device used to evaluate whole blood coagulation function. The TEG is unique as a test of coagulation function in that it measures the interaction of all components of clot formation, which is different than traditional laboratory-based tests that measure isolated components of coagulation. Little is known about fetal coagulation physiology. We sought to evaluate the impact of severe fetal anemia and intrauterine transfusion (IUT) on fetal coagulation physiology by use of the TEG and to compare fetal TEG values to those of healthy neonates and adults. One milliliter of fetal blood was collected immediately before (pre) and after (post) IUT of packed red blood cells (PRBCs). Sampling and transfusion were performed for fetal anemia due to hemolytic disease of the fetus and newborn. Samples were run in duplicate. For descriptive summary, duplicate pre-IUT and post-IUT values were averaged. Values for R (initiation of clot in minutes), K (clot firmness in minutes), angle (kinetics of clot development in degrees), and MA (maximum strength in mm) were obtained for each sample and presented using mean ± SE. Pre-IUT values for R, K, angle, and MA were compared with post-IUT values using linear mixed-effect model to account for clustering due to repeated observation from the same fetus. Pre-IUT values are compared with normal healthy term neonates and healthy adults using Wald test. The study was approved by the University of Pittsburgh Institutional Review Board (PRO14050051). Four fetuses underwent nine IUTs rendering 17 pre-IUT and 17 post-IUT specimens. The mean gestational age at IUT was 31 weeks 2 days (25 weeks 4 days to 35 weeks 2 days). The mean IUT volume transfused was 69 mL (30-170 mL). The mean estimated percent intravascular volume transfused was 33.4% (19%-52%). Of the four variables analyzed, only R showed a significant difference, with the initiation of clot formation being modestly delayed after transfusion by an estimated 2.87 minutes (95% CI, 0.82-4.92, P = .0480). Pre-IUT values were compared with 100 normal term neonates and 118 healthy adults. Compared with pre-IUT, only R was affected (shorter) compared with term neonates (mean ± SE = 5.46 ± 0.16 minute, P < .001) and healthy adults (mean ± SE = 6.8 ± 0.13 minute, P < .001). OTHER THAN A MODEST PROLONGATION OF CLOT FORMATION TIME, IUT OF PRBCS OF UP TO 52% OF THE ESTIMATED INTRAVASCULAR VOLUME DID NOT AFFECT FETAL COAGULATION FUNCTION BY TEG. OTHER THAN A SHORTER CLOT FORMATION TIME (R), THERE IS NO DIFFERENCE IN TEG VALUES BETWEEN ANEMIC PRETERM FETUSES AND HEALTHY TERM NEONATES AND HEALTHY ADULTS. BEYOND GENERALIZABLE KNOWLEDGE, THIS INFORMATION COULD BE EXPLOITED FOR FUTURE FETAL INTERVENTION TECHNIQUES.

Prediction of Fetal Anemia in Subsequent Transfusions: Is There a Need to Change the Threshold of the Peak Systolic Velocity of the Middle Cerebral Artery?

Introduction: Peak systolic velocity (PSV) of the middle cerebral artery (MCA) shows 100% sensitivity for predicting fetal anemia before the first intrauterine transfusion (IUT). However, its ability to predict subsequent transfusions has remained mostly controversial. Objectives: To assess if there is a need to change the threshold of MCA-PSV from 1.5 to 1.69 multiples of the median (MoM) to predict fetal anemia and the need for subsequent IUT. Methods: This is a retrospective audit, wherein case records of mothers who underwent IUT at the Bangalore Fetal Medicine Centre between April 2008 and May 2017 were reviewed; 86 cases were included, and the data were analyzed using MS Excel. The MCA-PSV and pretransfusion Hb were converted into MoM. 40 fetuses that had more than 1 IUT were included in the analysis. ­Results: 31/40 fetuses that had >1 IUT had an MCA-PSV >1.5 MoM, of which 29 were anemic according to the post-IUT Hb MoM. 20/29 (69%) had an MCA-PSV >1.69, whereas 9/29 (31%) had an MCA-PSV between 1.5 and 1.69 MoM. Our study shows that changing the MCA-PSV threshold from 1.5 to 1.69 MoM will reduce the detection of fetal anemia and hence the need for repeat IUT by 31%. Conclusions: Increasing the fetal MCA-PSV threshold from 1.5 to 1.69 will miss out one-third of the fetuses that will require a 2nd, 3rd, or 4th IUT. This is more relevant in geographical areas where the parents must travel long distances for IUTs, which are performed in tertiary fetal care centers.

A rare case of intra-uterine blood transfusion for fetal anemia caused by a giant placental chorioangioma

AbstractObjectivesChorioangiomas (CAs) are the most frequent tumor-like-lesions of the placenta. Giant CAs (more than 4–5 cm in diameter) is rare and may result in severe maternal fetal complications.Case presentationA 38-year-old multigravida presented at 31 weeks’ gestation with contractions. Upon evaluation, contractions were spontaneously ceased, and the cervix was closed. Ultrasound examination revealed a single viable fetus, polyhydramnios and a 75 x 48 x 82 mm vascular lesion located on the placental surface near the cord insertion. Doppler assessment was suggestive of fetal anemia with middle cerebral artery-peak systolic velocity (MCA-PSV) 1.8 MoM’s. Fetal heart rate monitoring and biophysical scores were reassuring. Following betamethasone fetal cord sampling that revealed fetal hemoglobin level of 8.8 g/dL, 57 cc of blood was transfused resulting in final hemoglobin level of 14.3 g/dL measured prior to needle extraction. MCA-PSV was normalized immediately after the procedure, however aggravated at the following day with MCA-PSV 65 cm/s (1.46 MoM’s). No other intervention was taken and MCA-PSV continued to fluctuate from slight to severe anemia spontaneously over a period of two weeks. At 34 gestational weeks, the women delivered a healthy baby. Fetal hemoglobin level at delivery was 21 g/dL.ConclusionsFetal blood transfusion is a reasonable treatment for fetal anemia in cases of giant chorioangiomas. Following transfusion, MCA-PSV may act unexpectedly reflecting various mechanisms affecting the flow.

Suppression of compensatory erythropoiesis in hemolytic disease of the fetus and newborn due to intrauterine transfusions

Infants with severe hemolytic disease of the fetus and newborn often require 1 or multiple intrauterine transfusions to treat fetal anemia. Intrauterine transfusions may have an inhibiting effect on fetal and neonatal erythropoiesis. To quantify the effect of 1 or multiple intrauterine transfusions on the fetal erythropoiesis by assessing the fetal reticulocyte counts in a population with severe hemolytic disease of the fetus and newborn. This was an observational cohort study in infants admitted to the Leiden University Medical Center who received 1 or multiple intrauterine transfusions for hemolytic disease of the fetus and newborn caused by (Rh)D or Kell antibodies and were born between January 2005 and December2018. A total of 235 patients were included, of whom 189 were patients with D-mediated hemolytic disease of the fetus and newborn and 46 with Kell-mediated hemolytic disease of the fetus and newborn. Absolute fetal reticulocyte count in D-mediated hemolytic disease of the fetus and newborn declined exponentially over the course of consecutive intrauterine transfusions, with a 62% decline after 1 intrauterine transfusion (95% confidence interval, 56-67). A similar exponential decline was observed in Kell-mediated hemolytic disease of the fetus and newborn, with 32% (95% confidence interval, 19-45) decline after 1 intrauterine transfusion. This decline was not associated with the varying gestational age at the time of the first intrauterine transfusion or the total number of intrauterine transfusions. The number of red blood cell transfusions for postnatal anemia was greater for infants with D and Kell-mediated hemolytic disease of the fetus and newborn with >2 intrauterine transfusions (median of 3 [interquartile range, 2-3] vs 2 [interquartile range, 1-3], P=.035, in D-mediated disease and median of 2 [interquartile range, 1-2] vs 1 [interquartile range, 1-1], P<.001, in Kell-mediated disease). Infants born after >2 intrauterine transfusions less often required exchange transfusion in D-mediated hemolytic disease of the fetus and newborn (19/89 [21%] vs 31/100 [31%], P=.039), compared with infants with 1-2 intrauterine transfusions. Treatment with intrauterine transfusions causes an exponential decrease in fetal reticulocyte counts in both D- and Kell-mediated hemolytic disease of the fetus and newborn. Suppression of the compensatory erythropoiesis leads to prolonged postnatal anemia and an increased requirement of red blood cell transfusions after birth.

Hidrops fetal: La información cruda anonimizada se compartirá a solicitud por el autor corresponsal. . Los autores declaran que no hubo financiamiento para la realización de este trabajo. .La información cruda anonimizada se compartirá a solicitud por el autor corresponsal.

31-year-old patient, G2A1P0, 29 weeks and 4 days pregnant. He comes with an ultrasound diagnosis of hydrops fetalis. There was a male fetus with severe ascites, subcutaneous edema, polyhydramnios, and placecentomegaly. No other malformations were found. His obstetric history was consistent with Rh isoimmunization. The pregnancy was prolonged until week 32 with intrauterine transfusions and plasmapheresis. Due to associated vulvar edema, she is born by cesarean section. Hydropic newborn with 3g / dl of hemoglobin at birth, consistent with amenorrhea. Satisfactory evolution in her perinatal period.

Hematoma subcapsular hepatico en sindrome de HELLP: La información cruda anonimizada se compartirá a solicitud por el autor corresponsal. . Los autores declaran que no hubo financiamiento para la realización de este trabajo. .La información cruda anonimizada se compartirá a solicitud por el autor corresponsal.

31-year-old patient, G2A1P0, 29 weeks and 4 days pregnant. He comes with an ultrasound diagnosis of hydrops fetalis. There was a male fetus with severe ascites, subcutaneous edema, polyhydramnios, and placecentomegaly. No other malformations were found. His obstetric history was consistent with Rh isoimmunization. The pregnancy was prolonged until week 32 with intrauterine transfusions and plasmapheresis. Due to associated vulvar edema, she is born by cesarean section. Hydropic newborn with 3g / dl of hemoglobin at birth, consistent with amenorrhea. Satisfactory evolution in her perinatal period.

Perinatal Management of Bart's Hemoglobinopathy: Paradoxical Effects of Intrauterine, Transplacental, and Partial Exchange Transfusions

We describe a fetus at 24 3/7 weeks' gestation that showed ultrasound evidence of anemia, hydrops, and severe growth restriction. Both parents were known to be cis heterozygous carriers for SEA α-thalassemia deletion (αα/–). Cordocentesis confirmed fetal anemia and homozygous α-thalassemia (−/−) in the fetus. Fetal intrauterine transfusions corrected the anemia, treated the hydrops, and improved fetal growth. The postnatal course was complicated by hypoxic respiratory failure and persistent pulmonary hypertension of the newborn, which resolved only after partial volume exchange transfusion. This case report is presented to point out the potential unintended outcomes with transplacental transfusion via delayed cord clamping and cord milking at delivery in the setting of congenital Bart's hemoglobinopathy, and demonstrates that partial exchange transfusion of the newborn may optimize oxygen delivery due to the more favorable oxygen affinity of transfused adult hemoglobin compared with the Bart's hemoglobin.

Severe Late-onset Anemia Associated with Rhesus D Alloimmunization

Rhesus D (RhD) alloimmunization is the most severe cause of hemolytic disease of the fetus and newborn (HDFN). However, owing to medical advances, pediatricians are likely to encounter only a few relatively mild cases. Therefore, although late-onset anemia is a well-recognized complication of HDFN, it may be overlooked in evaluations for post-discharge surveillance. Herein, we report a case of severe late-onset anemia associated with RhD HDFN. A 37-day-old male infant presented with a marked pale appearance. During the fetal period, he had received intrauterine transfusion six times for the treatment of severe anemia induced by RhD HDFN. However, during the neonatal period, he had no significant clinical manifestations, except mild jaundice. The laboratory findings on the day of presentation showed severe hemolytic anemia with reticulocytosis, which was treated with red blood cell transfusion. Our case report emphasizes that regardless of the initial disease severity during the neonatal period, regular follow-up visits and close monitoring for late-onset anemia in the first several weeks after birth are vital in infants with HDFN.

185: Recurrent Hemoglobin H hydrops Caused by a Compound Heterozygosity of HBA2: c.* 93_* 94delAA and ɑ0- thalassemia (-- SEA)

We report Hb H hydrops fetalis resulting from non-deletional ɑ-thalassemia mutations, a polyadenylation (polyA) mutation (AATAAA → AATA--) of the ɑ2 globin gene (HBA2: c.*93_*94delAA), and ɑ0-thalassemia (--SEA) in 2 subsequent pregnancies from a Thai family living in Nakhon Pathom. Case Report In the first pregnancy, a 20 years old woman, GA 28+4 weeks, was referred to our hospital due to fetal cardiomegaly, marked anemia and pericardial effusion. She was ɑ0-thalassemia carrier (--SEA/ɑɑ), but her husband who had low mean cell volume (MCV) of 74 fL was negative for common ɑ-thalassemia mutation test. Therefore, they were not identified as a couple at risk for Hb Bart’s hydrops fetalis (--/--). Intrauterine transfusion (IUT), Hb typing, and complete ɑ-globin gene analysis were performed. The results showed that this fetus carried this rare ɑ globin genotype (--SEA/ɑPAɑ). The baby boy was born at 34+6 weeks, and subsequently died at 2 days of life owing to severe hydropic features and multiple organ failure. In the second pregnancy, the mother was detected with fetal cardiomegaly, pericardial effusion and marked fetal anemia at 30+1 weeks. We performed a fetal blood sampling and demonstrated a high level of Hb Bart (70.6%) and confirmed the same ɑ globin genotype again. Due to the grave prognosis of this genetic interaction, the couple decided for a termination of pregnancy rather than IUT, and our postmortem study revealed a full-blown hydrops fetalis in this female stillborn baby. Although recent publications have revealed a variety of clinical severity associated with this polyA mutation, varying from mild non-transfusion dependent to transfusion dependent, to the best of our knowledge, this is for the first time that this polyA mutation is associated with Hb H hydrops. Our probands were far more severe than those reported earlier even though they all had identical genotype, suggesting that there would be additional genetic and/or epigenetic determinants that might supersede or further deteriorating the clinical severity leading to hydropic development.