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Spontaneous massive fetomaternal hemorrhage

Spontaneous massive fetomaternal hemorrhage
Author:
Kenneth J Moise Jr, MD
Section Editors:
Charles J Lockwood, MD, MHCM
Lynne Uhl, MD
Deputy Editor:
Vanessa A Barss, MD, FACOG
Literature review current through: Dec 2022. | This topic last updated: Aug 10, 2022.

INTRODUCTION — Spontaneous fetomaternal hemorrhage (FMH) is defined as fetomaternal bleeding with no antecedent history of trauma and no clinical/histopathological evidence of abruption. The vast majority of spontaneous FMHs are small volume bleeds of no hemodynamic significance, but they may lead to alloimmunization. The frequency and volume of these types of bleeds increase with advancing gestational age and are highest at birth [1].

Spontaneous massive (also called large) FMH is much less common. If FMH is acute and massive, it can result in rapid fetal hemodynamic collapse and death. If FMH is not massive but chronic (ie, intermittent repetitive), it can result in fetal anemia and hydrops fetalis over time, depending on the ability of the fetus to increase red cell production and compensate for ongoing blood loss.

This topic will review the clinical presentation, diagnosis, management, and prognosis of pregnancies complicated by spontaneous massive FMH. Small-volume FMH related to abruption and trauma and issues related to alloimmunization are reviewed separately:

(See "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences".)

(See "Initial evaluation and management of major trauma in pregnancy".)

(See "RhD alloimmunization in pregnancy: Overview".)

(See "RhD alloimmunization in pregnancy: Management".)

(See "RhD alloimmunization: Prevention in pregnant and postpartum patients".)

(See "Management of non-RhD red blood cell alloantibodies during pregnancy".)

DEFINITION/DIAGNOSIS — We define massive FMH as one or both of the following:

FMH ≥20 percent of fetal blood volume, because this degree of blood loss is associated with fetal morbidity or mortality. (See 'Outcome' below.)

FMH associated with middle cerebral artery peak systolic velocity (MCA-PSV) ≥1.5 multiples of the median (MoMs), because this correlates with moderate to severe fetal anemia. (See "RhD alloimmunization in pregnancy: Management", section on 'Assess for severe anemia using MCA-PSV in fetuses at risk'.)

A limitation of these definitions is that they do not account for the rate of blood loss or the chronicity of bleeding, which are additional but unmeasurable factors that affect fetal outcome.

There is no universally accepted threshold defining the volume of fetal erythrocytes in the maternal circulation that constitutes a small versus massive FMH. Although volumes up to 150 mL have been proposed to define massive FMH [2], we believe the volume of the bleed should be interpreted in relation to total fetoplacental blood volume, which correlates with fetal size and gestational age. Fetoplacental blood volume is approximately 120 mL/kg estimated fetal weight before 32 weeks of gestation and 100 mL/kg after 32 weeks [3]. Thus, a FMH of 40 mL for a 33 week fetus estimated to weigh 2000 grams represents a bleed of 20 mL/kg, which is 20 percent of its fetoplacental blood volume.

INCIDENCE — The incidence of spontaneous massive FMH is unknown because it is uncommon, unpredictable, and signs and symptoms are neither specific nor reliably present [4]. In addition, studies have varied in their definition of massive FMH, types of patients (high versus low risk for FMH), and time in gestation when testing for FMH was performed (first, second, third trimester, or peripartum).

When large numbers of RhD-negative patients were routinely tested for FMH after birth, the frequency of FMH >80 mL ranged from 1/1146 to 1/1429 births [2,5].

In a retrospective study of over 20,000 pregnancies within the Kaiser Permanente Northern California healthcare system in which flow cytometry analysis for fetal hemoglobin was performed over a 10-year period, there were 340 cases of clinically important FMH (approximately 1 in 1100 births) [6].

PATHOGENESIS — Bidirectional passage of minute numbers of red blood cells across the placenta is a normal physiologic event, even though the placenta is considered to be a barrier separating the maternal and fetal circulations [1,7-13]. The pathogenesis of spontaneous massive FMH is unclear. In a histologic study of placentas, parenchymal and retroplacental hemorrhage, intervillous thrombi, and infarction increased the likelihood that fetal cells would be found in the maternal circulation, and the extent of the abnormality correlated with the size of the hemorrhage [14]. However, many questions remain about the origin of these lesions and the factors that determine the number and volume of bleeding episodes.

CLINICAL PRESENTATION — Spontaneous massive FMH can occur at any time in pregnancy or at birth. Fetal death may be the presenting sign of a massive acute bleed. Hydrops and/or abnormal fetal heart rate (FHR) patterns and/or decreased fetal movement may be the presenting signs of a massive but nonlethal acute FMH or chronic intermittent FMH resulting in a large cumulative blood loss over time. Some massive FMHs have no signs or symptoms.

Clinical scenarios that have led to a diagnosis of massive FMH include:

Decreased or absent fetal movement, which is the most common presenting symptom of massive FMH, reported by 27 and 54 percent of patients in two series [15,16]. The mother is usually otherwise asymptomatic, but symptoms suggestive of a transfusion reaction (fever, chills, nausea) occasionally occur [15,17,18]. During the course of the routine evaluation of decreased fetal movement, a sinusoidal FHR pattern (waveform 1) and/or hydrops fetalis may be noted. Additional FHR patterns that have been described include absence of accelerations, recurrent late decelerations [15,16,19,20], and fetal tachycardia [21]. However, if the fetus is able to sufficiently compensate for the blood loss, the FHR pattern and biophysical profile score may be normal. (See "Decreased fetal movement: Diagnosis, evaluation, and management".)

Unexplained neonatal anemia [15,22] – Massive peripartum FMH resulting in neonatal anemia has been described in approximately 1 in 9000 deliveries [16]. In severe cases, the newborn may be pale and in circulatory collapse at delivery. Laboratory results showing increased production of red blood cell precursors and increased circulating reticulocyte counts suggest that FMH occurred one to two days before birth [11].

Unexpected fetal demise/stillbirth – Testing for FMH may be part of the evaluation of unexpected fetal demise. Up to 15 percent of fetal deaths are associated with massive FMH [5,15,23]. Causation is supported by FMH >20 to 25 mL/kg fetal weight, and especially >40 mL/kg fetal weight. In one series of 34 fetal deaths attributed to FMH, the mean total FMH was 67 mL/kg (55 percent of blood volume) and FMH exceeded 20 mL/kg (30 percent of blood volume) in 79 percent of cases [24]. (See "Stillbirth: Incidence, risk factors, etiology, and prevention" and "Stillbirth: Maternal and fetal evaluation".)

Nonimmune hydrops fetalis (NIHF) – NIHF may be discovered incidentally during prenatal sonography performed for standard obstetric indications, during a work-up for decreased fetal movement or abnormal results on antepartum fetal surveillance, during a work-up for uterine size greater than dates, or during monitoring of fetuses with, or at risk for, disorders associated with hydrops. The evaluation of NIHF may reveal severe fetal anemia (MCA-PSV ≥1.5 MoMs), and subsequent evaluation may reveal massive FMH as the cause [25]. (See "Nonimmune hydrops fetalis", section on 'Anemia'.)

Sinusoidal FHR pattern – A sinusoidal FHR pattern (waveform 1) is strongly associated with severe fetal anemia from any cause and may be one of the first manifestations of massive FMH [26]. In a systematic review of 32 cases of severe fetal anemia (fetal or neonatal hemoglobin 1.9 to 7.2 g/dL [normal >11 g/dL]) associated with FMH, the FHR pattern was reported as sinusoidal in 17 of the 24 cases in which a cardiotocogram was available; 5/24 patterns were nonreactive, 1/24 showed decelerations, and 1/24 showed tachycardia [20].

A sinusoidal pattern may also be associated with hypoxia, acidosis, and asphyxia. (See "Intrapartum category I, II, and III fetal heart rate tracings: Management", section on 'Category III pattern: Abnormal'.)

Of note, patterns closely resembling a sinusoidal pattern, termed pseudosinusoidal, have been described; however, there is no consensus on the exact definition of this pattern [27]. This pattern may be related to maternal opioid or sedative administration and is typically transient and associated with a good fetal outcome [28]. When the diagnosis of a sinusoidal versus pseudosinusoidal pattern is uncertain, fetal well-being is suggested by periods of moderate variability, occasional FHR accelerations, and/or a reassuring biophysical profile score.

Routine postpartum Kleihauer-Betke testing – This is performed to look for significant fetomaternal bleeding prior to anti-D-immune globulin administration in RhD-negative mothers [29,30]. (See "RhD alloimmunization: Prevention in pregnant and postpartum patients".)

CANDIDATES FOR FMH TESTING — Massive FMH will only be detected if clinicians are aware of the clinical scenarios associated with the disorder and test for FMH [22]. Most of these clinical scenarios reflect the most severe end of the clinical spectrum; less severe cases are likely to be missed because they do not present with abnormal clinical findings and testing for FMH is not a routine prenatal or postnatal laboratory test.

Testing for massive FMH is appropriate in the following clinical settings, unless the reason for the finding is known [31,32]:

Nonimmune hydrops fetalis with MCA-PSV ≥1.5 MoMs

Sinusoidal fetal heart rate (FHR) pattern with MCA-PSV ≥1.5 MoMs

Fetal demise/stillbirth

Neonatal anemia

We also test RhD-negative patients after birth to ensure that they receive the appropriate dose of anti-D immune globulin. (See "RhD alloimmunization: Prevention in pregnant and postpartum patients", section on 'Testing for fetomaternal bleeding'.)

We do not routinely perform a maternal assay to detect FMH in all pregnancies with decreased fetal movement. We test for FMH as part of the evaluation of pregnant patients who present with decreased fetal movement who also have signs of fetal anemia (eg, sinusoidal FHR pattern, fetal hydrops with MCA-PSV ≥1.5 MoMs). Although some clinicians test for FMH in all cases of persistently decreased fetal movement, the cost-effectiveness of this approach has not been established [33,34]. (See "Decreased fetal movement: Diagnosis, evaluation, and management".)

MEASURING THE VOLUME OF FMH — Two tests are available for estimating the volume of FMH: the Kleihauer-Betke acid elution assay and flow cytometry [35]. A survey of 2067 laboratories indicated that 96 percent use the Kleihauer-Betke assay, and only 4 percent use flow cytometry in cases of FMH [36].

Both assays are based on identification of hemoglobin F, the predominant fetal hemoglobin. However, up to 1 percent of adult hemoglobin is hemoglobin F. The hemoglobin F is produced by a small number of erythroid precursors; their progeny in the blood are called "F cells" and also contain hemoglobin A. These F cells can lead to overestimation of the volume of fetal blood in maternal blood. Differentiating adult F cells from fetal hemoglobin F containing red blood cells is especially important in pregnancies of patients with some hematologic disorders, such as sickle cell disease, which can be associated with a large number of F cells. For this reason and because of other factors that may affect the estimated volume of FMH (discussed below), consultation with the Blood Bank can be helpful when the clinician receives a report of FMH. (See "Structure and function of normal hemoglobins" and "Fetal hemoglobin (hemoglobin F) in health and disease".)

Kleihauer-Betke assay — The Kleihauer-Betke acid elution assay historically has been the main diagnostic test for detection and quantitation of FMH [37]. Red blood cells from the maternal circulation are fixed to a slide that is exposed to an acidic pH solution. Adult red blood cells become "ghost" cells since hemoglobin A is soluble and eluted across membrane defects at a low pH. Fetal red blood cells remain pink because hemoglobin F is stable at pHs in this range (picture 1).

A laboratory technician looking through a microscope counts a minimum of 2000 cells and reports the result as the percentage of fetal red blood cells in the total sample. The percentage is represented as a decimal fraction (ie, 5 percent = 0.05). The volume of fetal whole blood (mL) in the maternal circulation is: (decimal fraction of fetal cells) X (maternal hematocrit [%] divided by fetal hematocrit [%]) X (maternal blood volume mL).

In the usual clinical scenario, the maternal blood volume and the fetal hematocrit are not known, and most laboratories do not request the maternal hematocrit for the calculation. The maternal blood volume is often assumed to be 5000 mL, yielding the following formula to calculate the volume of fetal whole blood (mL) in the maternal circulation: (decimal fraction of fetal cells) X 5000 mL. Thus, if the Kleihauer-Betke result is 0.1 percent, the FMH calculation is (0.001 X 5000) = 5 mL of fetal whole blood.

Several factors can be associated with an underestimation of the volume of the FMH. The test is labor intensive with significant interoperator and intraoperator variability. Technical issues, such as smears that are too thick, inadequate drying times, or short buffering times, can contribute to poor fetal cell staining [36]. A decreasing fetal hemoglobin concentration in the fetal red cells with advancing gestational age may also contribute to poor staining of these cells [33]. Another factor that may distort the estimate is that the lifespan of fetal red blood cells in the maternal circulation is shortened if there is ABO incompatibility or alloimmunization. Finally, the use of an assumed maternal blood volume of 5 liters in the usual calculations will underestimate the actual volume of the FMH in the overweight pregnant patient.

Overestimation of the FMH volume can also occur. The presence of fetal hemoglobin in maternal red cells increases with advancing gestational age, reaching levels as high as 7 percent by 32 weeks gestation in 25 percent of pregnant patients [38]. The use of an assumed maternal blood volume of 5 liters in the usual calculations will overestimate the actual volume of the FMH in the underweight pregnant patient.

Variations in the formula for estimating FMH and in the assumptions used in the calculating of FMH have been published. A comparison of these formulas when fetal cells comprised 3 percent of cells in the maternal sample yielded FMH estimates ranging from 108 to 162 mL [33].

Flow cytometry — Flow cytometry is another assay for detecting and quantitating FMH [39]. A monoclonal antibody to hemoglobin F is conjugated to a fluorochrome and used to detect fetal hemoglobin in permeabilized cells as they pass through the channel of a flow cytometer. Comparative analysis of flow cytometry and the Kleihauer-Betke test has shown that flow cytometry is more accurate, more reproducible, and less labor intensive [40]. For this reason, many laboratories have converted to this assay for detecting FMH.

Calculation of FMH using flow cytometry is subject to the same limitations as the Kleihauer-Betke test: inability to measure the maternal blood volume and interference with persistence of fetal hemoglobin in some adult red blood cells (F cells). Dual-parameter flow cytometry can alleviate the issue with maternal F cells noted in such disease states as hemoglobinopathies and thalassemias. A second antibody is used to detect erythrocyte antigens unique to adult red cells, such as carbonic anhydrase: adult red cells are carbonic anhydrase positive, whether hemoglobin F positive or negative. Fetal cells are negative for carbonic anhydrase; thus, hemoglobin F positive/carbonic anhydrase negative cells are fetal and gated for a positive response. However, this system can be imprecise because some adults with hemoglobinopathies appear to have some F cells with a fetal phenotype (hemoglobin F positive/carbonic anhydrase negative) [41,42].

The flow cytometry equation for calculating the volume (mL) of fetal packed red blood cells in the maternal circulation is [39]: (% positive events) X (1800 mL) divided by 100 X (122/100), where 1800 mL is the estimated average maternal red blood cell volume based on a maternal hematocrit of 36 percent and 122/100 is an adjustment to take into account that fetal red blood cells are usually approximately 20 percent larger than adult red blood cells. Multiplying this value by a factor of two yields the volume (mL) of whole blood FMH since the normal fetal hematocrit is approximately 50 percent. As an example, a flow cytometry result of 0.1 percent positive events would result in the following calculation: (0.1 X 1800)/100 = 1.8 X 122/100 = 2.16 mL X 2 = 4.32 mL whole blood volume FMH. The estimated total fetoplacental blood volume can be calculated by multiplying the estimated fetal weight in kilograms (based on ultrasound parameters) by 100 mL/kg (the fetoplacental blood volume per kilogram fetal weight after 32 weeks) or 125 mL/kg (the fetoplacental blood volume per kilogram fetal weight before 32 weeks). The percent of fetoplacental blood volume represented by the FMH would be (whole blood volume of FMH in mL) divided by (estimated fetal weight in kg) X (100 or 125 mL/kg).

MANAGEMENT OF CASES DETECTED ANTENATALLY — The author's approach to management of antenatally detected cases of spontaneous massive FMH is illustrated by the following algorithm (algorithm 1) and discussed below. Management depends on fetal status, degree of anemia, and gestational age.

Nonreassuring tests of fetal well-being — Patients who present with nonreassuring standard tests of fetal well-being (biophysical profile, nonstress test) typically require urgent delivery, regardless of the cause.

MCA-PSV ≥1.5 MoMs, FMH >20 percent, and reassuring fetal testing — The author's approach in these cases (algorithm 1) is based on expert opinion and guided by personal experience with a few cases of massive FMH, review of published case reports and small case series, extrapolation of principles of management of fetal anemia from other causes, available resources, and shared decision making that considers the morbidity of preterm birth, the morbidity of in utero therapy, and the uncertain clinical course of expectant management.

≥32 weeks of gestation – For pregnancies ≥32 weeks with middle cerebral artery peak systolic velocity (MCA-PSV) ≥1.5 multiples of the median (MoMs) and FMH ≥20 percent of the fetal blood volume, we perform immediate cesarean birth, with blood available for prompt neonatal transfusion. The morbidity of preterm birth at this gestational age is probably less than the risk of in utero transfusion or recurrent FMH during expectant management.

<32 weeks of gestation – For pregnancies <32 weeks of gestation with FMH ≥20 percent of blood volume, especially with signs of severe anemia (ie, MCA-PSV ≥1.5 plus hydrops fetalis), we perform an intravascular transfusion (IVT) of donor red blood cells to acutely correct fetal anemia, as transfusion is probably associated with lower morbidity and mortality than birth <32 weeks [43-45]. A course of antenatal corticosteroids is administered at the same time because these pregnancies are at increased risk for preterm birth. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)

A second IVT may be needed, but timing is difficult to determine. We perform daily Kleihauer-Betke or flow cytometry testing, MCA-PSV, and biophysical profiles until IVTs are no longer deemed necessary, which we consider to be after seven consecutive days of stable or improving results and reassuring biophysical profile scores [45-47]. Diagnosis of ongoing FMH is challenging after transfusion because the transfused cells contain adult hemoglobin and thus are not detected by Kleihauer-Betke or flow cytometry tests.

The MCA-PSV should drop within 24 hours of correction of the fetal anemia by the IVT. If we observe MCA-PSV≥1.5 MoMs or a 5 percentage point increase in FMH (eg, from 22 percent to 27 percent) at any time during the seven days, we assume there is ongoing fetomaternal bleeding and perform a second IVT. Daily Kleihauer-Betke or flow cytometry testing, MCA-PSV, and biophysical profiles are performed for another seven days. If MCA-PSV≥1.5 MoMs or a 5 percentage point increase in FMH occurs again at any time during the seven days, we deliver the fetus because we believe repeated IVTs are unlikely to be successful in cases with ongoing FMH [48]. The success rate in significantly prolonging gestation to term after two IVTs for FMH appears to be approximately 50 percent.

In patients with seven consecutive days of stable or improving results after one or two IVTs, we monitor the fetus closely until birth. These cases are rare and no guidelines for antepartum fetal surveillance exist. The author performs a nonstress test or biophysical profile twice weekly and Doppler ultrasound MCA-PSV weekly until delivery in an attempt to identify recurrent significant FMH.

A review of chronic massive FMH with fetal hydrops treated by IVT reported overall perinatal survival in 12 of 14 cases (86 percent survival) [49]. Ten patients required two transfusions, and five required at least three procedures. The gestational age at onset was 26.6±2.1 weeks, and the gestational age at birth was 34.2±4.2 weeks. Although these results are promising, the series is small, and other clinicians have reported unsuccessful outcomes, including perinatal death and long-term disability [33,48]. Therefore, use of such therapy should be limited to centers with experience in both serial MCA Doppler assessment and IVTs.

MCA-PSV ≥1.5 MoMs, FMH <20 percent, and reassuring fetal testing — These pregnancies are evaluated with daily Kleihauer-Betke or flow cytometry testing, MCA-PSV, and biophysical profiles for seven days. A repeat MCA-PSV ≥1.5 MoM or a 5 percent absolute increase in FMH at any time during the seven days is a sign of chronic FMH. We manage such patients as described above: deliver if ≥32 weeks and perform IVT if <32 weeks (algorithm 1).

If the MCA-PSV and Kleihauer-Betke or flow cytometry testing results improve during the seven days, we follow the fetus closely until birth with a nonstress test or biophysical profile twice weekly and Doppler ultrasound MCA-PSV weekly in an attempt to identify recurrent significant FMH.

DELIVERY — We recommend cesarean birth to prevent any further deterioration in the fetal status due to ongoing intrapartum FMH. In addition:

The pediatric team should be notified about the potential for neonatal anemia. Red cells crossmatched to maternal serum should be available for immediate neonatal transfusion. This should include standard processing of blood for neonatal transfusions (leukoreduction and irradiation).

The placenta should be sent for histopathologic evaluation, which might suggest a cause for the FMH. Although rare, massive FMH has been associated with intraplacental choriocarcinoma [50-55].

OUTCOME

Maternal — The mother is at risk of alloimmunization to red cell antigens. (See "Management of non-RhD red blood cell alloantibodies during pregnancy".)

There is a single case report of severe preeclampsia and HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome developing within 24 hours after blunt abdominal trauma with massive FMH and fetal intracranial bleeding [56].

Fetal/neonatal — Fetal/neonatal outcome depends upon the rapidity of fetal blood loss and the volume of the hemorrhage relative to total fetoplacental blood volume [57,58]. As discussed above, massive FMH is more likely to be fatal if blood loss occurs over minutes rather than hours, days, or weeks. Although a critical prognostic factor, the rate of fetomaternal bleeding in human pregnancies is generally impossible to assess clinically, unless the fetus is hydropic, which suggests chronic anemia.

Reported morbidity and mortality rates were derived from case reports and case series involving a range of gestational ages, both acute and chronic bleeds, and wide diversity in clinical presentation and management (in utero transfusion, expectant management, early delivery).

The range of short-term outcomes reported in the literature is illustrated by the following examples:

In a French study, the fetal death rate was 25 percent (two of eight fetuses) for FMH 40 to 80 mL/kg and 66 percent (four of six fetuses) for FMH ≥80 mL/kg (fetoplacental blood volume averages approximately 100 mL/kg fetal weight [59,60]).

Morbidity occurred primarily in the 23 fetuses calculated to have bled ≥20 mL/kg (ie, >20 percent of fetoplacental blood volume) and included: induced preterm birth (17 percent), admission to the neonatal intensive care unit (35 percent), and neonatal transfusion (22 percent).

In another French study, 42 children were delivered of pregnancies complicated by ≥20 mL FMH, and 23 had FMH ≥20 mL/kg [5]. In the short-term, FMH 20 to 40 mL/kg was associated with an adverse outcome in five of nine cases, FMH 40 to 80 mL/kg was associated with an adverse outcome in five of eight cases (including two stillbirths), and FMH >80 mL/kg resulted in adverse outcome in all six cases (including four stillbirths).

For FMH ≥150 mL, pooled data from two studies yielded a perinatal death rate of 37 percent (25 of 67) [2,11].

A review of 134 cases of FMH >50 mL noted that 13 live-born infants had evidence of neurologic dysfunction, 10 had respiratory distress syndrome, 7 had persistent pulmonary hypertension, 4 developed disseminated intravascular coagulation, and 2 each developed pulmonary hemorrhage, cardiomegaly, and renal dysfunction [15]. Seventeen intrauterine fetal transfusions were performed in nine fetuses, eight of whom survived.

Long-term pediatric outcome after massive FMH is less well described. In one French series, 31 children were available for follow-up at a median age of 59 months (range 18 to 107 months) [5]. No long-term neurologic sequelae related to FMH were noted; however, the authors acknowledged their small sample size and a resulting wide confidence interval limited their ability to detect poor outcome (95% CI 0-11.6 percent). Other series have described neurologic injury in 0 to 35 percent of surviving infants [2,11,16]. In survivors of hemodynamic collapse from massive FMH, an increased risk for long-term neurodevelopmental impairment is certainly plausible. (See "Etiology and pathogenesis of neonatal encephalopathy" and "Clinical features, diagnosis, and treatment of neonatal encephalopathy".)

RECURRENCE — Recurrent significant FMH in successive pregnancies has been described primarily in case reports [61-63]. In a series of 143 patients with FMH who had 210 subsequent pregnancies, fetomaternal hemorrhage recurred in one pregnancy (0.5 percent) [6].

There is no evidence on which to base a recommendation for following these patients. Attention to fetal activity and prompt evaluation of decreased fetal activity is a reasonable approach [33]. (See "Decreased fetal movement: Diagnosis, evaluation, and management".)

SUMMARY AND RECOMMENDATIONS

Definition/diagnosis – We define massive fetomaternal hemorrhage (FMH) as one or both of the following:

FMH ≥20 percent of fetal blood volume, because this degree of blood loss is associated with fetal morbidity or mortality. (See 'Outcome' above.)

FMH associated with middle cerebral artery peak systolic velocity (MCA-PSV) ≥1.5 multiples of the median (MoMs), because this correlates with moderate to severe fetal anemia. (See 'Definition/diagnosis' above.)

Clinical presentation – Spontaneous massive FMH can occur at any time during pregnancy or at birth. Fetal death may be the presenting sign of a massive acute bleed. Hydrops and/or abnormal fetal heart rate (FHR) patterns and/or decreased fetal movement may be the presenting signs of a massive but nonlethal acute FMH or intermittent FMH resulting in a large cumulative blood loss over time. Some massive FMHs have no signs or symptoms. In the antepartum period, decreased or absent fetal movement is the most common presenting symptom. (See 'Clinical presentation' above.)

Candidates for evaluation for FMH – Massive FMH will only be detected if clinicians are aware of the clinical scenarios associated with the disorder and test for FMH. Most of these clinical scenarios reflect the most severe end of the clinical spectrum; less severe cases are likely to be missed because they do not present with abnormal clinical findings and testing for FMH is not a routine prenatal or postnatal laboratory test.

We suggest testing for massive FMH in the following clinical settings, unless the reason for the finding is known:

Nonimmune hydrops fetalis with MCA-PSV ≥1.5 MoMs

Sinusoidal FHR pattern with MCA-PSV ≥1.5 MoMs

Fetal demise/stillbirth

Neonatal anemia

We also test RhD-negative patients after birth to ensure that they receive the appropriate dose of anti-D immune globulin. (See 'Candidates for FMH testing' above.)

Tests for FMH – Either a Kleihauer-Betke acid elution assay or flow cytometry can be used for diagnosing FMH. The volume of fetal blood loss should be calculated as a percentage of the estimated fetoplacental blood volume. (See 'Measuring the volume of FMH' above.)

Management – Our approach to suspected spontaneous FMH with reassuring fetal testing is illustrated by the algorithm (algorithm 1). Patients with nonreassuring fetal testing typically require urgent delivery, regardless of the cause. (See 'Management of cases detected antenatally' above.)

Delivery – We recommend cesarean birth to prevent any further deterioration in the fetal status due to ongoing FMH. The pediatric team should be notified about the potential for neonatal anemia and the placenta should be sent for histopathologic evaluation. (See 'Delivery' above.)

Outcome – Fetal/neonatal outcome depends upon the rapidity of fetal blood loss and the volume of the hemorrhage relative to total fetoplacental blood volume. (See 'Outcome' above.)

Recurrence – Recurrent significant FMH in successive pregnancies has been described in case reports. (See 'Recurrence' above.)

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Topic 6806 Version 34.0

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