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.

Severe neonatal anemia affected by massive fetomaternal hemorrhage: a single-center retrospective observational study.

OBJECTIVES: Massive fetomaternal hemorrhage (FMH) is a rare but sometimes life-threatening event, and surviving neonates may suffer major neurological complications. Severe neonatal anemia (SNA) affected by massive FMH is less reported in the literature. This study aims to explore the clinical characteristics, laboratory diagnoses, treatments and outcomes of SNA affected by massive FMH. METHODS: Data were collected retrospectively from the hospital's electronic medical record system. All neonates born in the hospital and admitted to the neonatal unit diagnosed as SNA affected by massive FMH from 1 January 2013 to 31 June 2017 were included. RESULTS: A total of 8 cases of SNA affected by FMH were identified among 6825 neonates admitted to the neonatal unit. They all presented with pallor but without hydrops at birth. Median gestational age and birthweight were 375/7 (360/7‒401/7) weeks and 2,625 (2300‒3050) g, respectively. Median hemoglobin level was 39.5 (25‒53) g/L at birth and 109.5 (94-127) g/L at discharge. Median maternal serum alpha-fetoprotein (AFP) was 3958.5 (1606‒14,330) ng/mL, which was significantly increased. Three out of eight cases manifested as antenatal decreased fetal movement. Only 1 with the lowest initial hemoglobin 25 g/L manifested as characteristic sinusoidal fetal heart rate tracing and suffered severe neonatal asphyxia and hypovolemic shock. Having experienced resuscitation, he was admitted to the neonatal unit and received twice transfusion of cross-matched red blood cells there. Another case with the initial hemoglobin 45 g/L received positive pressure ventilation and once transfusion. All cases were successfully discharged with a median hospital stay of 8 (5-12) days. Follow-up was available for 6 (75%) of 8 neonates (age range 13 months to 50 months), and all infants were observed to be in good condition with normal neurological status. In our series of eight cases, there were no neonatal deaths. CONCLUSION: This study strengthens the idea that maternal AFP testing is valuable to confirm massive fetomaternal hemorrhage. Surviving neonates of massive FMH might have a good outcome despite severe anemia at birth.

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.

ACOG Practice Bulletin No. 192 Summary: Management of Alloimmunization During Pregnancy.

When any fetal blood group factor inherited from the father is not possessed by the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an immune reaction in the mother. Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies, or "alloimmunization," may lead to various degrees of transplacental passage of these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and untreated, alloimmunization can lead to significant perinatal morbidity and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks to the mother and fetus. Prevention of alloimmunization is addressed in another Practice Bulletin ().

ACOG Practice Bulletin No. 192: Management of Alloimmunization During Pregnancy.

When any fetal blood group factor inherited from the father is not possessed by the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an immune reaction in the mother. Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies, or "alloimmunization," may lead to various degrees of transplacental passage of these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and untreated, alloimmunization can lead to significant perinatal morbidity and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks to the mother and fetus. Prevention of alloimmunization is addressed in another Practice Bulletin ().

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.

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.

Massive fetomaternal hemorrhage as a cause of severe fetal anemia.

Introduction: Fetomaternal hemorrhage (FMH) is a transfu-sion of fetal blood into the maternal circulation. A volume of transfused fetal blood required to cause severe, life-threatening fetal anemia, is not clearly defined. Some authors suggest vol-umes of 80 mL and 150 mL as a threshold which defines mas-sive FMH. Therefore, a rate of massive FMH is 1 : 1,000 and 1 : 5,000 births, respectively. Fetal and neonatal anemia is one of the most serious complications of the FMH. Clinical manifesta-tions of FMH are nonspecific, and mostly it presented as re-duced fetal movements and changes in cardiotocography (CTG). The standard for diagnosing FMH is Kleihaurer-Betke test. Case report: A 34-year-old gravida (G) 1, para (P) 1 was hospitalized due to uterine contractions at 39 weeks of gesta-tion. CTG monitoring revealed sinusoidal fetal heart rate and clinical examination showed complete cervical dilatation. Im-mediately after admission, the women delivered vaginally. Ap-gar scores were 1 and 2 at the first and fifth minute, respec-tively. Immediately baby was intubated and mechanical ventila-tion started. Initial analysis revealed pronounced acidosis and severe anemia. The patient received intravenous fluid therapy with sodium-bicarbonate as well as red cell transfusion. With all measures, the condition of the baby improved with normaliza-tion of hemoglobin level and blood pH. Kleihaurer-Betke test revealed the presence of fetal red cells in maternal circulation, equivalent to 531 mL blood loss. The level of maternal fetal hemoglobin (HbF) and elevated alpha fetoprotein also con-firmed the diagnosis of massive FMH. Conclusion: For the successful diagnosis and management of FMH direct commu-nication between the obstetrician and the pediatrician is neces-sary as presented in this report.

A Case Report of Decreased Fetal Movement During Fetomaternal Hemorrhage.

Fetomaternal hemorrhage is a rare, potentially catastrophic event for a fetus.  Leakage of the fetus's blood into the mother's circulation can cause fetal anemia, hydrops, and even death.  The prevailing symptom is decreased fetal movement, and signs can include a sinusoidal electronic fetal monitor pattern, a positive Kleihauer-Betke test, or changes in fetal Doppler blood flow.  A mother's report or perception of decreased fetal movement coupled with a nonreactive nonstress test or abnormal ultrasound findings should prompt an investigation into underlying causes.

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.

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.