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.

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.

The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

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.

Neonatal outcomes following intrauterine transfusion for hemolytic disease of the fetus and newborn: a twenty-year service review.

OBJECTIVE: The primary objective was to explore perinatal and neonatal outcomes amongst infants who received intrauterine transfusion (IUT) for the management of hemolytic disease of the fetus and newborn (HDFN). The secondary objective was to evaluate the role of key investigations in the fetus at risk of HDFN and assess the relationship with neonatal outcomes. We hypothesized that middle cerebral artery peak systolic velocity (MCA-PSV) and corresponding multiples of the median (MoM) would be predictive of neonatal course. METHODS: This was a retrospective observational study conducted at a tertiary center in the United Kingdom between January 2000 and August 2020. Trust approval was obtained to conduct this service review. Pregnancies requiring IUT for HDFN were identified using the fetal medicine department database. Inclusion criteria were infants who received IUT for HDFN. 67 pregnancies were eligible for inclusion in the study with 156 IUT events. Data were extracted using healthcare records. Statistical analysis was performed using SPSS version 28.0, data were assessed for normality and Spearman's correlation analysis was performed with p values < .05 considered significant. RESULTS: 67 pregnancies were included in the study which led to the live birth of 68 infants (one twin pregnancy). There were no fetal deaths following IUT. There was one neonatal death due to extreme prematurity following spontaneous vaginal delivery at 23 + 4 weeks gestation, occurring three days following IUT. 97% of infants required admission to the neonatal intensive care unit and 88% required phototherapy. 25% of infants required readmission for red blood cell transfusion due to anemia. There was a significant correlation between maternal anti-D antibody levels and length of neonatal admission r = 0.477, p = .014. MCA-PSV and MoM measured prior to the last IUT had a significant positive correlation with the duration of phototherapy: r = 0.527 (p < .001) and r = 0.313 (p < .05) respectively. Linear regression analysis demonstrated a significant positive relationship between MCA-PSV and corresponding MoM recorded prior to the last IUT with r2= 0.177 (p = .003) and r2= 0.101 (p = .029). CONCLUSION: HDFN is an important cause of fetal anemia associated with significant neonatal morbidity. MCA-PSV and MoM may be predictive of neonatal phototherapy requirements. The predictive value of MCA-PSV appears to be dependent on the timing of measurement during the antenatal period and more research is needed. Multicentre collaboration is required to generate a reliable large-scale database to further delineate the value of MCA-PSV and MoM and predict neonatal outcomes in cases of HDFN requiring IUT. This data would assist clinicians in antenatal planning and enable more informed counseling of parents in the antenatal period.

Fetal and Neonatal Reticulocyte Count Response to Intrauterine Transfusion for the Treatment of Red Blood Cell Alloimmunization.

Management of hemolytic disease of the fetus and newborn relies on monitoring of maternal antibody titers, fetal ultrasound, and fetal middle cerebral artery peak systolic velocity studies and is generally treated by intrauterine transfusion (IUT). Few studies have explored fetal and neonate physiological responses to IUT. Our objective was to examine fetal erythropoietic response and to examine neonatal erythropoietic effects after treatment. Thirty-six patients treated from 2005 to 2015 were identified retroactively. The time course of treatment, including gestational age and number of IUT, and timing of delivery were reviewed. Fetal reticulocyte count and neonatal hemoglobin and reticulocyte counts were analyzed for each IUT. For each gestational week, reticulocyte count decreased by ∼8.6% (95% confidence interval [CI]: 5.3-12.0). In the neonatal period, there was significant correlation between hemoglobin at birth and number of transfusions (Spearman correlation 0.473, 95% CI: 0.113-0.715, P =0.01) as well as reticulocyte count at birth and number of transfusions (Spearman correlation: 0.393, 95% CI: 0.058-0.642, P =0.02). IUT appears to have a direct and measurable effect on fetal reticulocyte production which persists in neonates.

HDFN Resulting from Anti-U: Alternatives to Allogeneic Intrauterine Transfusion.

Hemolytic disease of the fetus and newborn (HDFN) carries significant fetal mortality risks. Although anti-D as a source of HDFN has been prevented for decades using D-specific immunoglobulin to prevent alloimmunization between fetus and mother, minor blood groups may still result in disease, with potentially disastrous consequences if left untreated. Strategies such as intrauterine transfusion, early delivery, and vigilant serologic monitoring of fetal anemia have been the standards of care for alloimmunized patients, but beyond this not much more is possible. Mothers with rare phenotypes who are alloimmunized against extremely common red blood cell antigens may find access to rare antigen-negative blood units limited. This case study presents a healthy G10P6 woman with known anti-U presenting for treatment via intrauterine transfusion in the second trimester and follows the patient through successful delivery. Difficulties in obtaining rare blood for the patient because of concomitant delivery events involving 2 patients with anti-U at the facility opened discussions about the difficulties of and alternatives to intrauterine transfusion where rare blood phenotypes are involved.

Complications of intravascular intrauterine transfusion for Rh alloimmunization.

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

Perinatal outcomes and central nervous system abnormalities following intrauterine fetal transfusion: 17 years' experience in a tertiary center.

BACKGROUND: This study aimed to describe the perinatal outcome and central nervous system (CNS) anomalies in fetuses undergoing red blood cell (RBC) intrauterine transfusion (IUT). METHODS AND MATERIALS: This was an observational single-cohort study carried out at Vall d'Hebron University Hospital in Barcelona, Spain, between 2002 and 2018 in women undergoing RBC IUT for suspected fetal anemia. Primary outcomes were adverse perinatal outcome (intrauterine or neonatal death and termination of pregnancy [TOP]), prenatal or postnatal CNS anomalies, and significant neurological impairment. RESULTS: A total of 145 RBC transfusions were performed in 68 pregnancies of 60 women. The median gestational age for the first transfusion was 26 weeks (range, 18-32). Twenty-two (32%) fetuses were hydropic at the first transfusion. Fifty-eight pregnancies (85.3%) resulted in live births and 10 (14.7%) in adverse perinatal outcomes. Adverse perinatal outcomes were associated with hydrops (odds ratio [OR], 6.69; 95% confidence interval [CI], 1.53-29.23; P = .012) and gestational age at first transfusion (OR, 0.69; 95% CI, 0.54-0.89; P = .04). Four (5.9%) cases of cerebellar hemorrhage were diagnosed prenatally. In 14 (35%) of the 41 neonates undergoing brain ultrasound and/or magnetic resonance imaging (MRI) abnormalities were reported. The median follow-up was 6.5 years (range, 3 months to 19 years). Significant neurological impairment was reported in two cases (4.2%). CONCLUSION: In fetuses undergoing intrauterine RBC transfusion, the survival rate is high, particularly in the absence of hydrops and if the gestational age at first transfusion is above 22 weeks. Significant neurological impairment is uncommon, despite the fact that postnatal CNS anomalies at ultrasound or MRI are frequent.

Red blood cell alloimmunization prevalence and hemolytic disease of the fetus and newborn in Israel: A retrospective study.

Hemolytic disease of the fetus and newborn (HDFN) is a severe form of anemia caused by maternal antibodies against fetal red blood cells (RBC) that can cause intrauterine and perinatal morbidity and mortality. The prevalence and specificities of alloantibodies among Israeli pregnant women and clinical outcomes for their fetuses and newborns are unknown. STUDY DESIGN AND METHODS: A retrospective study of women who gave birth between January 1, 2011, and December 31, 2011, was performed. Data were obtained for obstetric admissions from 16 of 27 hospitals, which included results of maternal ABO, D, antibody screens, antibody identification, and requirements for intrauterine or newborn exchange transfusions. RESULTS: Data on 90 948 women representing 70% of all births during 2011 were analyzed. Antibody screen was positive in 5245 (5.8%) women. Alloantibodies, excluding anti-D titer (<16) were identified in 900 (1.0%) women. Of 191 D- women, 75 (39.3%) had anti-D titer of 16 or greater. Other common clinically significant antibodies were anti-E (204, 23%), anti-K (145, 16%), and anti-c (97, 10.8%) alone or in antibody combinations. Multiple alloantibodies were observed in 132 of 900 (15%) of women. Severe HDFN developed in 6.8% (9/132) of these pregnancies. Seventeen fetuses and newborns (0.02% of births) including one set of twins required RBC transfusions. Two fetuses whose mothers had multiple alloantibodies received intrauterine transfusions; one of them was hydropic and died. CONCLUSION: The prevalence of RBC alloantibodies was 1.0% among Israeli pregnant women. Transfusion was required in 0.02% of the fetuses and newborns. Severe HDFN developed in 6.8% of pregnancies with multiple maternal alloantibodies.

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

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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 December 2018. RESULTS: 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. CONCLUSION: 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.

Perinatal outcomes of intrauterine transfusion for foetal anaemia due to red blood cell alloimmunisation.

The aim of this study was to evaluate the maternal and neonatal outcomes of patients who underwent intrauterine transfusion (IUT) for foetal anaemia due to red blood cell alloimmunisation and to determine the factors that affected the outcomes. All pregnancies that were treated with IUT due to Rh immunisation between January 2015 and June 2018 in the Kanuni Sultan Süleyman Training and Research Hospital, Department of Obstetrics and Gynaecology, were evaluated retrospectively. IUT due to non-Rh alloimmunisation, parvovirus B19 infection, chronic fetomaternal haemorrhage and foetal anaemia due to homozygous alpha-thalassemia were not included in the study. The perinatal and neonatal outcomes of the patients were retrospectively analysed. The gestational age, ultrasonography findings before and after IUT, laboratory results, complications related to IUT, and data on the newborns were recorded. The cases were divided into two groups, those with complication and those without complications, and their perinatal outcomes were compared. A total of 110 IUTs were performed in 42 foetuses. The survival rate after transfusion was 80.95%. Procedure-related complications were found in 12.7% of cases. There were no significant differences between the demographic and clinical characteristics of the patients with and without complications. The survival rate was lower and perinatal mortality was higher in foetuses with hydrops fetalis. IUT is a safe and effective procedure that can be used in the treatment of foetal anaemia in experienced centres. Survival rates can be increased by referring patients to experienced perinatology centres, by improving the IUT technique, and by reducing technique-related complications.Impact statementWhat is already known on this subject? The predominant use of IUT is to treat foetal anaemia due to red blood cell alloimmunisation. Despite the decrease after anti-D immune globulin prophylaxis, Rh immunisation is still a major cause of foetal anaemia. However, foetal survival rates have increased with the use of IUT.What do the results of this study add? The survival rates were increased after the development of a high-resolution ultrasound. Because foetal monitoring can be performed by ultrasonography, cord accidents and overload findings can be detected during transfusion, which allows for early interventions and increases survival rates.What are the implications of these findings for clinical practice and/or further research? The IUT procedure can be used in the treatment of foetal anaemia in experienced centres. After the technique was improved, the complication rates related to the procedure were decreased and foetal survival rates were increased. Further studies on the use of different IUT techniques will extend our findings.

Managing the Unusual Causes of Fetal Anemia.

BACKGROUND: Rare causes of fetal anemia requiring intrauterine transfusion (IUT) are challenging for fetal medicine specialists. OBJECTIVES: The aim of this study was to describe the perinatal patterns and prognosis in a consecutive series of fetuses transfused for fetal anemia of rare or unknown etiology, and to propose a protocol of investigation for fetal anemia of undetermined cause and for the management of subsequent pregnancies. METHOD: We conducted a retrospective descriptive study on fetuses transfused for severe anemia of rare or unknown etiology managed in our national referral center (Centre National de Référence d'Hémobiologie Périnatale) and born between 2010 and 2017. RESULTS: During the study period, 584 IUT were performed in 253 fetuses. Among those IUT, 23 (3.9%) were performed for a rare or unknown cause of anemia in 13 fetuses (5.1% of transfused fetuses). The median gestational age at diagnosis was 26 weeks of gestation (WG; range 21-33). Hemoglobin levels ranged from 1.6 to 9.1 g/dL (0.18-0.83 multiples of median) before the first IUT. The fetuses received between 1 and 6 IUT (39% received at least 2 IUT). The definitive etiologies for central anemia were: congenital syphilis, neonatal poikilocytosis, type II congenital dyserythropoietic anemia (CDA), and neonatal hemochromatosis. There was 1 case with suspected type I CDA and 1 with suspected Diamond-Blackfan anemia. There was 1 case of peripheral anemia, secondary to cerebral hemorrhages of different ages, related to a variant of the COL4A1 gene. In 6 fetuses corresponding to 4 mothers, no precise diagnosis was found despite a complete workup. In our series, there were 8 live births, 4 terminations of pregnancy, and 1 intrauterine fetal death. CONCLUSIONS: Fetal anemia of rare or unknown diagnosis represents 5% of all transfused fetuses in our cohort. Fetal and neonatal anemias can be recurrent in further pregnancies, with variable expressivity.

Clinical Characteristics of Jra Alloimmunization in Pregnancy: A Case Series.

Only few studies have reported on Jra alloimmunization in pregnancy, and its clinical course remains unclear. We reviewed our cases to clarify the change in the peak systolic velocity of the middle cerebral artery (MCA-PSV) during pregnancy and the critical anti-Jra antibody titer to predict fetal anemia. We collected the data of pregnant women with anti-Jra antibody from two hospitals between 2010 and 2017. We extracted data on maternal information, number of intrauterine blood transfusions (IUT), trend of anti-Jra antibody titer, changes of MCA-PSV, and neonatal outcome. We had 16 cases. IUTs were performed in 6 fetuses with severe anemia between 27 and 32 weeks' gestation. The MCA-PSV did not increase more than 1.5 multiples of the median (MoM) after 32 weeks' gestation. No significant difference was found in the maximum titer between cases with IUT and those without IUT. All pregnancies but one delivered at term. No neonates developed severe anemia or jaundice. MCA-PSV did not increase higher than 1.5 MoM later during the pregnancy. A critical titer to predict fetal anemia did not exist. Spontaneous term delivery could be expected even in fetuses who underwent IUT before 32 weeks' gestation.

Predicting Intrauterine Transfusion Interval and Perinatal Outcomes in Alloimmunized Pregnancies: Time-to-Event Survival Analysis.

BACKGROUND: The risk factors determining the frequency of intrauterine transfusions (IUTs) for severely affected red blood cell alloimmunized singleton pregnancies are not well known. OBJECTIVE: To assess factors associated with IUT frequency and adverse pregnancy outcomes in transfused pregnancies. METHODS: Retrospective cohort analysis of 246 consecutive cases between 1991 and 2014. Time-to-event survival analysis for repeated events was used to evaluate risk of subsequent IUT. Multivariable logistic regression assessed odds of a composite adverse pregnancy outcome (intrauterine fetal death, termination of pregnancy, neonatal death, preterm birth <34 weeks' gestation). RESULTS: Full information was available on232 cases (94.3%) and 716 IUTs. Fetal hydrops was associated with increased frequency (hazard ratio [HR] 1.29 [95% CIs 1.15-1.47, p < 0.001]) while higher fetal hemoglobin (Hb) pre-IUT (HR) 0.99 (95% CI 0.99-1.00, p = 0.021) and post-IUT (HR 0.99 [95% CI 0.99-1.00] p = 0.042), and higher transfused blood volume (HR 0.98 [95% CI 0.97-0.99] p < 0.001) were associated with reduced IUT frequency. Adverse pregnancy outcomes were more likely with lower gestational age (GA) at initial IUT. Antibody type was not associated with IUT frequency or adverse pregnancy outcomes. CONCLUSIONS: Hydrops is associated with increased IUT frequency while lower GA at initial IUT is associated with higher adverse pregnancy outcomes in alloimmunized pregnancies.Higher transfused blood volumes, pre- and post-IUT Hb are associated with lower IUT frequency.

Fetal exposure to mercury and lead from intrauterine blood transfusions.

BACKGROUND: Mercury (Hg) and lead (Pb) exposure during childhood is associated with irreversible neurodevelopmental effects. Fetal exposure to Hg and Pb from intrauterine blood transfusion (IUBT) has not been reported. METHODS: Fetal exposure was estimated based on transfusion volume and metal concentration in donor packed red blood cell (PRBCs). As biomarkers to quantify prenatal exposure are unknown, Hg and Pb in donor PRBCs were compared to estimated intravenous (IV) RfDs based on gastrointestinal absorption. RESULTS: Three pregnant women received 8 single-donor IUBTs with volumes ranging from 19 to 120 mL/kg. Hg and Pb were present in all donor PRBC units. In all, 1/8 IUBT resulted in Hg dose five times higher than the estimated IV RfD. Median Pb dose in one fetus who received 5 single-donor IUBTs between 20-32 weeks gestation was 3.4 µg/kg (range 0.5-7.9 µg/kg). One donor unit contained 12.9 µg/dL of Pb, resulting in a fetal dose of 7.9 µg/kg, 40 times higher than the estimated IV RfD at 20 weeks gestation. CONCLUSION: This is the first study documenting inadvertent exposure to Hg and Pb from IUBT and quantifying the magnitude of exposure. Screening of donor blood is warranted to prevent toxic effects from Hg and Pb to the developing fetus.

Performance of fetal middle cerebral artery peak systolic velocity for prediction of anemia in untransfused and transfused fetuses: systematic review and meta-analysis.

OBJECTIVE: To evaluate the performance of fetal middle cerebral artery peak systolic velocity (MCA-PSV) ≥ 1.5 multiples of the median (MoM) for the prediction of moderate-severe anemia, in untransfused and transfused fetuses. METHODS: A systematic search was performed to identify relevant observational studies reported in the period 2008-2018 that evaluated the performance of MCA-PSV, using a threshold of 1.5 MoM for the prediction of fetal anemia. Diagnosis of fetal anemia by blood sampling was the reference standard. A hierarchical summary receiver-operating characteristics (hSROC) curve was constructed using random-effects modeling. Subgroup and meta-regression analyses, according to the number of previous intrauterine transfusions, were performed. RESULTS: Twelve studies and 696 fetuses were included in the meta-analysis. The area under the hSROC curve (AUC) for moderate-severe anemia was 83%. Pooled sensitivity and specificity (95% CI) were 79% (70-86%) and 73% (62-82%), respectively, and positive and negative likelihood ratios were 2.94 (95% CI, 2.13-4.00) and 0.272 (95% CI, 0.188-0.371). When considering only untransfused fetuses, prediction improved, achieving an AUC of 87%, sensitivity of 86% (95% CI, 75-93%) and specificity of 71% (95% CI, 49-87%). A decline in sensitivity for the prediction of moderate-severe anemia by MCA-PSV ≥1.5 MoM was observed (estimate, -5.5% (95% CI, -10.7 to -0.3%), P = 0.039) as the number of previous transfusions increased. CONCLUSIONS: MCA-PSV ≥ 1.5 MoM for the prediction of moderate-severe anemia in untransfused fetuses shows moderate accuracy (86% sensitivity and 71% specificity), which declines with increasing number of intrauterine transfusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Rendimiento de la velocidad sistólica máxima de la arteria cerebral media fetal para la predicción de la anemia en fetos sometidos a transfusión y no sometidos: revisión sistemática y metaanálisis OBJETIVOS: Estimar las diferencias en la frecuencia del diagnóstico del útero septo mediante tres definiciones diferentes y determinar si estas diferencias son significativas en la práctica clínica, y examinar la relación entre el diagnóstico del útero septo, por medio de cada una de las tres definiciones, y la infertilidad o el aborto espontáneo previo, así como con el costo de la recomendación de cirugía. MÉTODOS: Este estudio fue un análisis secundario de los datos de un estudio prospectivo de 261 mujeres en edad reproductiva que asisten de forma consecutiva a una clínica privada especializada en el diagnóstico y tratamiento de las malformaciones congénitas del útero. El nuevo análisis de los conjuntos de datos se realizó de acuerdo con tres maneras diferentes de definir el útero septo: siguiendo las recomendaciones de la Sociedad Americana de Medicina Reproductiva (ASRM, por sus siglas en inglés), una actualización de 2016 de las de la Sociedad Americana de la Fertilidad de 1988 (ASRM-2016: profundidad de la hendidura interna del fondo uterino ≥1,5 cm, ángulo de la hendidura interna <90o y profundidad de la hendidura externa <1 cm); con base en las recomendaciones de la Sociedad Europea para la Reproducción Humana y Embriología/Sociedad Europea de Endoscopía Ginecológica (ESHRE/ESGE, por sus siglas en inglés), publicadas en 2013 y revisadas en 2016 (ESHRE/ESGE-2016: profundidad de la hendidura interna del fondo uterino >50% del espesor de la pared uterina y profundidad de la hendidura externa <50% del espesor de la pared uterina, cuando se mide el espesor de la pared uterina por encima de la línea interostial/intercornual); y utilizando una definición publicada el año pasado que se basaba en la decisión tomada con mayor frecuencia por un grupo de expertos (Malformación Uterina Congénita según los Expertos; CUME, por sus siglas en inglés) (CUME-2018: profundidad de la hendidura interna del fondo uterino ≥1 cm y profundidad de la hendidura externa del fondo uterino <1cm). Se comparó la tasa de diagnóstico del útero septo utilizando cada una de estas tres definiciones y, para cada una, se estimó la relación entre el diagnóstico y la infertilidad y/o el aborto espontáneo previo, y se anticiparon los costos asociados con su implementación mediante un método de estimación conjetural. RESULTADOS: Aunque el 32,6% (85/261) de las mujeres cumplieron con los criterios de una de las tres definiciones de útero septo, sólo el 2,7% (7/261) de ellas se pudieron definir como con útero septo de acuerdo con las tres definiciones. Significativamente, se diagnosticaron más casos de útero septo usando los criterios de ESHRE/ESGE-2016 que usando los de ASRM-2016 (31% vs 5%, riesgo relativo (RR)=6,7, P<0.0001) o de CUME-2018 (31% vs 12%, RR=2,6, P<0.0001). También se observaron casos frecuentes que no pudieron ser clasificados definitivamente por ASRM-2016 (zona gris: ni normal/arcuado ni septo; 6,5%). No hubo diferencias significativas (P>0,05) en la prevalencia de útero septo en mujeres con infertilidad vs mujeres fértiles, según ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) o CUME-2018 (11% vs 12%). El diagnóstico del útero septo fue significativamente más frecuente en mujeres con aborto espontáneo previo, según los criterios de ASRM-2016 (11% vs 3%; P=0,04) y de CUME-2018 (22 vs 10%; P=0,04), pero no según los criterios de ESHRE/ESGE-2016 (42% vs 28%; P=0,8). Los cálculos mostraron que los costos globales para el sistema de salud dependerían en gran medida de los criterios utilizados desde el punto de vista clínico para definir el útero septo, siendo los costos asociados con la definición de ESHRE/ESGE-2016 potencialmente de 100-200 mil millones de dólares adicionales durante 5 años, en comparación con los asociados a las definiciones ASRM-2016 y CUME-2018. CONCLUSIONES: La prevalencia del útero septo según las definiciones de ESHRE/ESGE-2016, ASRM-2016 y CUME-2018 difiere considerablemente. Una limitación importante de la clasificación ASRM, que debe ser abordada, es la alta proporción de casos no clasificables originalmente denominados, por nosotros, como en la 'zona gris'. La alta tasa de sobrediagnóstico del útero septo en función de ESHRE/ESGE-2016 puede llevar a un uso innecesario de la cirugía y, por lo tanto, a un riesgo innecesario en estas mujeres y puede imponer una carga financiera considerable a los sistemas sanitarios. Se deben fomentar los esfuerzos para definir criterios clínicamente significativos y aplicables de forma universal para el diagnóstico del útero septo.

Hyperferritinaemia following intrauterine transfusions for Rh isoimmunisation.

Intrauterine transfusion is one of the mainstays of treatment in isoimmunised pregnancies guided by the changes in middle cerebral artery Doppler of the fetus. The common postnatal complications associated with Rh isoimmunisation are high unconjugated bilirubin requiring blood exchange transfusions, cholestasis due to bile inspissation, thrombocytopenia and anaemia. Hyperferritinaemia is an uncommon adverse effect observed in Rh isoimmunised pregnancies. In this case report, we describe the clinical course of a Rh isoimmunised neonate with hyperferritinaemia and transfusion acquired cytomegalovirus disease which resolved. Iron chelation therapy was not necessary.

Maternal respiratory distress and successful reversal with sugammadex during intrauterine transfusion with fetal paralysis.

A 70 kg, 34-year-old woman at 29 weeks-of-gestation required intrauterine transfusion for Rh (D) alloimmunization. In the ambulatory treatment clinic, 19 mg of rocuronium was administered intramuscularly in split doses into the fetal buttock. The fetus moved and inadvertent maternal neuromuscular blockade occurred, leading to respiratory distress. The patient was transferred to the operating room where she had poor muscle tone, dyspnea and dysphonia. Sugammadex 100 mg was administered intravenously and complete resolution of neuromuscular blockade was demonstrated using a Neuromuscular Transmission™ monitor. When neuromuscular blocking agents are administered in ambulatory settings, management protocols, reversal agents, and skilled assistance should be immediately available for managing potentially life-threatening complications.

Fetal anemia: Diagnosis and management.

Fetal anemia has been known for many years as a dangerous complication of pregnancy. Its most common causes are maternal alloimmunization and parvovirus B19 infection, although it can be associated with many different pathological conditions including fetal aneuploidies, vascular tumors, and arteriovenous malformations of the fetus or placenta and inherited conditions such as alpha-thalassemia or genetic metabolic disorders. Doppler ultrasonographic assessment of the peak velocity of systolic blood flow in the middle cerebral artery for the diagnosis of fetal anemia and intravascular intrauterine transfusion for its treatment are the current practice standards. Live birth rates as high as 95% have been reported in recent years. The additional role of intravenous immunoglobulin therapy and the long-term consequences of the condition are the subjects of active ongoing research.