Fetomaternal Hemorrhage and Choriocarcinoma: A Case Report.

BACKGROUND: This case describes chronic anemia of a late preterm infant secondary to maternal-fetal hemorrhage and subsequent findings of maternal choriocarcinoma. CLINICAL FINDINGS: This infant was born at 35 6/7 weeks gestational age via cesarean section for non-reassuring fetal heart tones. The mother presented with decreased fetal movement and the biophysical profile was 4/8. Following delivery, the infant did not require respiratory support, was vigorous with extreme pallor, and had a hemoglobin of less than 5 on cord gas. PRIMARY DIAGNOSIS: Chronic anemia secondary to fetomaternal hemorrhage. INTERVENTIONS: The infant's initial hemoglobin was 2.4 and hematocrit was 8.1. The mother's Kleihauer-Betke test was elevated at 7%. The infant required a partial exchange transfusion following admission to the neonatal intensive care unit. Following the partial exchange transfusion, the infant began to experience increasing respiratory distress and required respiratory support. An echocardiogram showed severe persistent pulmonary hypertension of the neonate. The mother was subsequently diagnosed with choriocarcinoma. OUTCOMES: The infant fully recovered from chronic anemia and persistent pulmonary hypertension of the neonate and was discharged home with the mother. The infant required follow-up testing for choriocarcinoma outpatient. PRACTICE RECOMMENDATIONS: Newborns diagnosed with early chronic anemia should be evaluated, the cause investigated, and appropriate treatment considered. If the cause of blood loss is unknown, a maternal Kleihauer-Betke test should be considered. In this case, a partial exchange transfusion was performed to avoid cardiovascular volume overload, but another course of treatment could include small aliquots of packed red blood cell transfusions.

Massive fetomaternal hemorrhage: A case report.

We present a case with an incidental finding of abnormal cardiotocography (CTG) pattern as well as elevated middle cerebral artery peak systolic velocity (MCA-PSV) in an otherwise inconspicuous pregnancy. Massive fetomaternal hemorrhage (FMH) was detected as the cause by flow cytometry (FC), resulting in multiple cycles of fetal blood sampling (FBS) showing severe anemia, intrauterine transfusions (IUTs), a preterm delivery, and a healthy infant in follow-up examinations.

Fetomaternal hemorrhage: Evidence from a multihospital healthcare system that up to 40% of severe cases are missed.

BACKGROUND: We previously reported fetomaternal hemorrhage (FMH) in 1/9160 births, and only one neonatal death from FMH among 219,853 births. Recent reports indicate FMH is not uncommon among stillbirths. Consequently, we speculated we were missing cases among early neonatal deaths. We began a new FMH initiative to determine the current incidence. METHODS: We analyzed births from 2011 to 2020 where FMH was diagnosed. We also evaluated potential cases among neonates receiving an emergent transfusion just after birth, whose mothers were not tested for FMH. RESULTS: Among 297,403 births, 1375 mothers were tested for FMH (1/216 births). Fourteen percent tested positive (1/1599 births). Of those, we found 25 with clinical and laboratory evidence of FMH adversely affecting the neonate. Twenty-one received one or more emergency transfusions on the day of birth; all but two lived. We found 17 others who received an emergency transfusion on the day of birth where FMH was not tested for, but was likely; eight of those died. The 42 severe (proven + probable) cases equate to 1/7081 births. We judged that 10 of the 42 had an acute FMH, and in the others it likely had more than a day before birth. CONCLUSIONS: We estimate that we fail to diagnose >40% of our severe FMH cases. Needed improvements include (1) education to request maternal FMH testing when neonates are born anemic, (2) education on false-negative FMH tests, and (3) improved FMH communications between neonatology, obstetrics, and blood bank.

Evaluating emergency-release blood transfusion of newborn infants at the Intermountain Healthcare hospitals.

BACKGROUND: An emergency-release blood transfusion (ERBT) protocol (uncrossmatched type O-negative red blood cells, AB plasma, AB platelets) is critical for neonatology practice. However, few reports of emergency transfusions are available. We conducted an ERBT quality improvement project as a basis for progress. STUDY DESIGN AND METHODS: For each ERBT in the past 8 years, we logged indications, products, locations and timing of the transfusions, and outcomes. RESULTS: One hundred forty-nine ERBTs were administered; 42% involved a single blood product, and 58% involved two or more. The incidence was 6.25 ERBT per 10,000 live births, with a higher rate (9.52 ERBT/10,000) in hospitals with a Level 3 neonatal intensive care unit (NICU) (p < 0.001). Seventy percent of ERBTs were administered in a NICU and 30% in a delivery room, operating room, or emergency department. Indications were abruption/previa (32.2%), congenital anemia (i.e., fetomaternal hemorrhage; 15.4%), umbilical cord accident (i.e., velamentous insertion; 15.0%), and bleeding/coagulopathy (12.8%). Fifty-eight percent of those with hemorrhage before birth did not have a hemoglobin value reported on the umbilical cord gas; thus, anemia was not recognized initially. None of the 149 ERBTs were administered using a blood warmer. The mortality rate of recipients was 35%. CONCLUSION: Based on our findings, we recommend including a hemoglobin value with every cord blood gas after emergency delivery to rapidly identify fetal anemia. We also discuss two potential improvements for future testing: 1) the use of a warming device for massive transfusion of neonates and 2) the use of low-titer group O cold-stored whole blood for massive hemorrhage in neonates.

Massive Fetomaternal Hemorrhage Remote from Term: Favorable Outcome after Fetal Resuscitation and Conservative Management.

Fetomaternal hemorrhage (FMH) is a rare condition that requires early diagnosis and appropriate treatment due to its potentially severe consequences. We report a case of massive FMH presenting as decreased fetal movement, fetal hydrops, and intracranial hemorrhage at 24 weeks. Treatment considerations were made and amniocentesis, fetal blood sampling, and fetal blood transfusion via cordocentesis were performed. Recurrent FMH required subsequent fetal transfusion 2 days later. Surveillance was continued twice weekly until the patient delivered a viable infant at 38 weeks after spontaneous labor. Recurrent FMH was unpredictable due to its unclear etiology and absence of precipitating events, however close surveillance proved effective.

The Recurrence Risk of Fetomaternal Hemorrhage.

Massive fetomaternal hemorrhage (FMH) can cause devastating pregnancy outcomes. Perinatal prognosis may be improved by intrauterine transfusion, but the appropriate management for these pregnancies remains unclear. To determine the recurrence risk of FMH after intrauterine transfusion, we performed a systematic review of all case reports/series of patients with proven FMH treated with intrauterine transfusion and who had subsequent follow-up of at least 72 h until delivery. This revealed 13 cases, with 1 additional case from our institution. Ten patients (71.4%) had a second episode of FMH requiring a second intrauterine transfusion. Five patients (35.7%) required at least 3 intrauterine transfusions. The time interval between intrauterine transfusions was progressively reduced. The gestational age at the onset of signs/symptoms was 26.6 ± 2.1 weeks, and gestational age at delivery was 34.2 ± 4.2 weeks. Two cases of fetal demise (14.3%) and no neonatal deaths were recorded. Limited postnatal follow-up on 8 neonates was normal. The mean neonatal hemoglobin and transfusion rates were 13.2 ± 5.7 g/dL and 33.3%, respectively. Close fetal monitoring, likely daily, is necessary to recognize FMH recurrence. Several transfusions may be necessary once FMH is diagnosed if pregnancy is allowed to continue > 72 h.

Persistent pulmonary hypertension of the newborn after fetomaternal hemorrhage.

BACKGROUND: Newborns with anemia are at increased risk of persistent pulmonary hypertension of the newborn (PPHN), yet reports on the association between fetomaternal hemorrhage (FMH) and PPHN are rare. To optimize care for pregnancies complicated by FMH, clinicians should be aware of the risks of FMH and the possible diagnostic and therapeutic options. To increase the current knowledge, the incidence of PPHN and short-term neurologic injury in FMH cases were studied. STUDY DESIGN AND METHODS: We included all FMH cases (≥30 mL fetal blood transfused into the maternal circulation) admitted to our neonatal unit between 2006 and 2018. First, we evaluated the incidence of PPHN and short-term neurologic injury. Second, we studied the potential effect of intrauterine transfusion (IUT). RESULTS: PPHN occurred in 37.9% of newborns (11 of 29), respectively, 14.3% (one of seven) and 45.5% (10 of 22) in the IUT group and no-IUT group (p = 0.20). The mortality rate was 13.8% (4 of 29). Severe brain injury occurred in 34.5% (10 of 29), respectively, and 14.3% (one of seven) and 40.9% (nine of 22) in the IUT group and no-IUT group (p = 0.37). CONCLUSION: Awareness should be raised among perinatologists and neonatologists about the possible life-threatening consequences of FMH, as more than one-third of neonates with anemia due to FMH experience PPHN and suffer from severe brain injury. Antenatal treatment with IUT seems to reduce these risks. Specialists should therefore always consider fetal anemia in FMH cases and refer patients to a fetal therapy center. If anemia is present at birth, it should be corrected promptly and neonatologists should be aware of signs of PPHN.

Fetomaternal hemorrhage complicated pregnancy: risks, identification, and management.

PURPOSE OF REVIEW: This article aims not only to review recent literature about the clinical features of massive fetomaternal hemorrhage (FMH) and identification of risk factors, but also to alert obstetricians and pediatricians to this underdiagnosed and underestimated severe obstetrical issue. In addition, a simplified flow chart for the antenatal management of suspected FMH is proposed. RECENT FINDINGS: Improvements in obstetrical and neonatal care have decreased perinatal morbidity and mortality and the rate of stillbirth. Unfortunately, because of the nonspecific signs on presentation, adverse outcome associated with massive FMH has not followed this trend and still has devastating consequences. As even the definition varies among publications and there is lack of universal screening, the real nature still remains obscure. Improvements in the diagnosis of fetal anemia, laboratory and intrauterine transfusion techniques, and the implementation of prenatal and postnatal neuroprotection give some hope for the better outcome in the most severe cases. Unfortunately, obstetricians' awareness of the massive FMH remains still at an unacceptably low level. SUMMARY: There is an urgent need for the internationally accepted definition, standardized pregnancy management protocol, and structured follow-up of neonates from such pregnancies. We suggest the international registry of massive FMH cases.

Obstetrical transfusion medicine knowledge among faculty and trainee obstetricians: a prospective knowledge assessment study.

OBJECTIVES: To evaluate the current state of transfusion medicine (TM) knowledge among obstetricians using a valid assessment tool. BACKGROUND: Transfusion issues are common in obstetrical patients. METHODS: Knowledge topics were identified and rated by experts in obstetrics, anaesthesia, haematology and TM using a modified Delphi method. A knowledge assessment tool was developed and validated during pilot testing. The assessment tool, consisting of 15 multiple choice questions, was administered electronically to members of the Society of Obstetricians and Gynaecologists of Canada (SOGC). RESULTS: A total of 192 SOGC members completed the assessment tool: 121 faculty obstetricians and 71 trainees. The average score was 65·8% ± 15·5. Scores for faculty were higher than trainees (68·9% ± 13·5 vs 60·6% ± 17·2; P < 0·001). Respondents performed well on questions related to red blood cell (RBC) transfusion and anaemia management but had lower scores on questions related to non-RBC transfusion and management of alloantibodies and fetomaternal haemorrhage (FMH) testing. There was no improvement in scores with increasing trainee level, years of practice, hours of formal TM training or experience with massive haemorrhage. Only self-rated knowledge was associated with scores ['no knowledge' or 'beginner' 63·1% ± 15 vs 'intermediate' or 'advanced' 68·9% ± 13·3 (P = 0·007)]. Of the respondents, 93·8% felt additional training in TM would be helpful. CONCLUSIONS: Overall knowledge assessment scores indicate the need for educational intervention, particularly with respect to non-RBC blood product use, management of FMH and management of pregnancies complicated by alloantibodies. The study also demonstrated a desire for additional TM training.

Flow Cytometry in Detection of Fetal Red Blood Cells and Maternal F Cells to Identify Fetomaternal Hemorrhage.

Accurate detection and quantitation of fetomaternal hemorrhage (FMH) is critical to the obstetric management of rhesus D alloimmunization in Rh-negative pregnant women. The flow cytometry is based on the detection of fetal red blood cells using a monoclonal anti-HbF antibody, and is the method most indicated for this estimation. The objective of this study was to quantify fetal red blood cell levels of pregnant women using flow cytometry. We analyzed 101 peripheral blood samples from Rh-negative and Rh-positive women, whose mean age was 24 years (20-32 years), after vaginal delivery or cesarean section. Our study showed that 53% of pregnant women had fetal red blood cells levels <2.0 mL, 31% between 2.0-3.9 mL, 16% between 4.0-15.0 mL, and 1% >15.0 mL. Accurate quantitation of fetal red blood cells is necessary to determine the appropriate dose of anti-D (RHD) immunoglobulin to be administered to pregnant or postpartum women.

Two cases of asymptomatic massive fetomaternal hemorrhage.

Evaluation of fetomaternal hemorrhage (FMH) in the immediate postpartum period is critical for the timely administration of Rh immunoglobulin (RhIG) prophylaxis to minimize the risk of alloimmunization in D-negative mothers of D-positive newborns. We report a series of two clinically-unsuspected cases of massive FMHs identified at our university medical center. Retrospective records of two cases of massive FMH were investigated using the electronic medical record. After positive fetal bleed screens, flow cytometric analysis for hemoglobin F was performed to quantify the volume of the hemorrhages in both cases. Flow cytometric enumeration with anti-D was also performed in one case. The two patients had 209.5 and 75 mL of fetal blood in circulation, resulting in 8 and 4 doses of RhIG administered, respectively. For the former patient, flow cytometric analysis with anti-D ruled out hereditary persistence of fetal hemoglobin and supported the fetal origin of the red cells. Due to the clinically-silent nature of both hemorrhages, further evaluation of the newborns' blood was not performed. These cases highlight the importance of rapidly obtaining accurate measurements of fetal blood loss via flow cytometric analysis in cases of FMH, particularly in clinically-unsuspected cases, to ensure timely administration of adequate immunoprophylaxis to D-negative mothers.

Perinatal management of neonatal alloimmune thrombocytopenia associated with anti-group A antibody.

OBJECTIVE: To prevent neonatal alloimmune thrombocytopenia due to anti-group A antibody perinatal management was performed. BACKGROUND: We previously reported a case of severe intracranial haemorrhage associated with neonatal alloimmune thrombocytopenia due to anti-group A isoantibody. MATERIAL/METHODS: A 40-year-old Japanese woman, gravida 4 para 1, was pregnant with her second baby. The previous sibling developed severe thrombocytopenia and died 10 days after birth due to intracranial haemorrhage. He was diagnosed with neonatal alloimmune thrombocytopenia; the causative antibody was found to be the anti-group A antibody. Prednisone was started at 7 weeks' gestational age. Intravenous immunoglobulin 1 g kg(-1) week(-1) was started at 29 weeks' gestational age and continued to delivery. Serological studies and genotyping were performed. RESULTS: The second boy was delivered at 33 weeks' gestational age by caesarean section. He was discharged without intracranial haemorrhage or thrombocytopenia. The anti-group A antibody titre in the maternal serum was 2048-4096 (normal range: 4-64). The anti-group A antibody titre in the newborn's serum was 4. Cross-matching between the maternal serum and the paternal platelets was positive. CONCLUSION: Owing to the history of neonatal alloimmune thrombocytopenia causing intracranial haemorrhage and death of the previous sibling, strict follow-up of the subsequent pregnancy was conducted.

Assessment of feto-maternal hemorrhage among rhesus D negative pregnant mothers using the kleihauer-betke test (KBT) and flow cytometry (FCM) in Addis Ababa, Ethiopia.

BACKGROUND: This study aimed to assess fetomaternal hemorrhage (FMH) among RhD negative pregnant mothers using two techniques, Kleihauer-Betke (KBT) and Flow cytometry (FCM). To determine if patient-specific doses of prophylactic anti-D warrant further investigation in Ethiopia and wider Africa. METHODS: Hospital- based cross-sectional study was conducted among 75 RhD negative pregnant mothers using convenient sampling technique. RESULT: FMH has been detected in 52% and 60% by KBT and FCM techniques, respectively. The volume of FMH quantified in the majority of the cases (92.5% and 87%) was <10 mL fetal blood while >30 mL in 1.3% (1/75) and 2.7% (2/75) as calculated by KBT and FCM, respectively. The FMH calculated by the two methods have good correlation; r = 0.828 (p = 0.000) for categorized and r = 0.897 (p = 0.000) for continuous values and the agreement between the FCM and KBT was moderate with kappa (κ) value of 0.53 (p = 0.000). CONCLUSION: Most of FMH calculated (<10 mL) could have been neutralized by lower doses which might have lower costs than administering 300 µg dose which is currently in practice in our country for affording mothers. Besides, it also showed that the volume of FMH was >30 mL in 1.3% and 2.7% of the cases as calculated by KBT and FCM, respectively, which need more than 300 µg dose RhIG for neutralization. Further investigation into the cost- effectiveness and scalability of patient- specific dosing of prophylactic anti-D appears warranted.

Red cell alloimmunisation following intrauterine transfusion and the feasibility of providing extended phenotype-matched red cell units.

OBJECTIVES: To analyse the incidence of additional alloantibody formation following intrauterine red cell transfusion and to evaluate the feasibility of providing extended phenotype-matched red cells in future intrauterine transfusion (IUT). BACKGROUND: IUT is performed in severe, life-threatening fetal anaemia, usually in alloimmunised pregnancies. Its complications include the formation of additional alloantibodies to other red cell antigens. MATERIALS AND METHODS: This was an 11-year retrospective, observational study of additional alloantibody formation in patients receiving IUT in the National Maternity Hospital, Dublin. The study included evaluation of the donor population in the Republic of Ireland (RoI) with regards to the feasibility of providing extended phenotype-matched units in future IUT. RESULTS: Following IUT, 22% of mothers formed additional red cell alloantibodies. In 67% of cases, the transfused donor red cells expressed the cognate antigen. Suitable donors are available for most combinations of Fy, Jk and Ss antigens. CONCLUSIONS: In our population, it is feasible to provide more extensively phenotype-matched red cells for future IUT. These can be supplied from the current donor pool with no significant extra phenotyping required. We consider their provision to be a reasonable proactive step in a known at-risk group.

A correlation between severe haemolytic disease of the fetus and newborn and maternal ABO blood group.

OBJECTIVE: To analyse anti-D quantification levels and frequency of intrauterine transfusion (IUT), per maternal ABO blood group. BACKGROUND: Maternally derived red cell allo-antibodies can target fetal red cell antigens in utero leading to haemolytic disease and fetal anaemia. When a clinically significant allo-antibody is formed the priority is ascertaining the risk to the fetus and maternal ABO blood groups are not considered relevant. MATERIALS AND METHODS: This was a 10-year retrospective, observational study carried out on women referred for anti-D quantification (n = 1106), and women whose fetuses required an IUT to treat fetal anaemia (n = 62) due to anti-D, in the Republic of Ireland. RESULTS: Relative to the overall incidence of RhD allo-immunisation by blood group, women of blood group A were more likely to require IUT compared with those who were blood group O (P = 0.002). CONCLUSION: It is known that ABO feto-maternal compatibility can influence the incidence and level of red cell allo-antibodies in pregnancy; however, it does not account for the significantly high rate of severe haemolytic disease requiring IUT seen in blood group A women.

Intrauterine blood transfusion: current indications and associated risks.

Fetal anemia is a serious complication in pregnancy and associated with perinatal mortality and morbidity. During 25 years of worldwide experience with intravascular intrauterine blood transfusion, a variety of indications have been described. Intrauterine transfusion (IUT) treatment is considered most successful for fetal anemia due to red cell alloimmunization. Moreover, the use of this procedure has also been reported in pregnancies with parvovirus B19 infection, fetomaternal hemorrhage and placental chorioangiomas, for example. This review focuses on the current indications of intrauterine blood transfusions. In addition, we describe the potential complications of IUT treatment.

Fetomaternal hemorrhage with intraplacental chorioangioma.

A 37-year-old Asian woman, gravid 0 para 0, was admitted to our hospital at 34 weeks and 5 days of her pregnancy for management of preeclampsia. A few days after admission, she recognized diminished fetal movement, and a non-stress test revealed a non-reassuring fetal heart rate pattern with decreased variability. A female baby weighing 1840 g was delivered by emergency cesarean section with Apgar scores of 5 and 5 at 1 and 5 min, respectively. Significant neonatal anemia with a hemoglobin level of 4.3 g/dL was observed. The elevated level of hemoglobin F (HbF) in the maternal blood accounted for 4.6% (normal≦0.5%), and was indicative of the presence of fetomaternal hemorrhage (FMH). Microscopic examination of the placenta revealed chorioangioma. We report here a rare case of FMH with intraplacental chorioangioma, and discuss the relationship between these two pathologies.

A Case of Massive Fetal-Maternal Hemorrhage: Lessons Learned in Diagnosis and Treatment.

The use of Rho(D) immune globulin in Rh-negative pregnant women has become standard of care, but many practicing clinicians do not know the dosing recommendations for this essential medication. In this article, we describe a case of a 15-year-old girl who presented with intrauterine fetal demise and was found to have massive fetomaternal hemorrhage. Kleihauer-Betke testing results indicated nearly 460 mL of fetal blood in the maternal circulation. The patient ultimately received 4800 µg of Rho(D) immune globulin, a dose that required close coordination with the obstetrical service and pharmacy. Although this is an unusual case of large-volume, potentially chronic, fetomaternal hemorrhage, it is also an excellent illustration of the principles for diagnosing this condition, as well as providing dosing guidelines for Rho(D) immunoglobulin to prevent alloimmunization.

An evaluation of the ability of leucocyte depletion filters to remove components of amniotic fluid.

Haemorrhage remains an important cause of maternal mortality worldwide. Cell salvage carries a theoretical risk of amniotic fluid embolus syndrome and is too expensive for use in many parts of the world. To explore cheaper options, we investigated whether a leucocyte depletion filter alone removes components of pure amniotic fluid. Amniotic fluid was collected from 10 women during elective caesarean section and passed through a LeukoGuard® RS filter. Pre- and post-filtration samples were compared in the laboratory. Lamellar bodies and fetal squames were almost completely removed (filtration efficacy 96.6% and 99.9%, respectively; p<0.0001 and <0.0004), and hair was completely removed (p=0.002). Filtration had no effect on concentrations of α-fetoprotein, tissue factor or endothelin-1, or on the presence of meconium or vernix. Additional work is required to evaluate whether cell salvage using filtration alone may be useful in maternal haemorrhage in the developing world.

Clinically silent massive fetomaternal hemorrhage: important lessons from an illustrative case.

Massive fetomaternal hemorrhage (FMH) >150 mL is rare and may occur in the absence of high-risk obstetrical events. The significance of FMH in Rh D-negative women is alloimmunization with an increased risk of hemolytic disease of the newborn in subsequent Rh D-positive pregnancies and adverse outcomes for the fetus/neonate. The Kleihauer-Betke (KB) acid elution test is used to quantify fetal erythrocytes in the circulation of Rh D-negative women postpartum and to calculate the dose of Rh immune globulin (RhIG) needed for prophylaxis against alloimmunization. In this case, the KB stain unexpectedly revealed 4.5% fetal cells, a finding consistent with a massive FMH of 225 mL, in the absence of a predisposing cause and clinical signs in the infant. This case underscores the importance of FMH quantification in all Rh D-negative women with Rh D-positive fetuses, uncomplicated pregnancies, and healthy newborns. We discuss factors that can affect KB test performance and caveats in interpretation.