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.

Mild-to-moderate foeto-maternal haemorrhage in the third trimester and at term of pregnancy: quantitative determination and clinical-diagnostic evaluation.

BACKGROUND: Foeto-maternal haemorrhage (FMH), a gestational event that occurs before or during delivery, consists of a loss of foetal blood into the maternal circulation. FMH occurs more frequently during the third trimester or labour both in normal and complicated pregnancies. In the case of alloimmunisation, the maternal immunological response and the severity of the resulting foetal or neonatal disease depend on the amount of foetal blood that passes into the maternal circulation. The aim of this study was to determine FMH in the third trimester and at term of pregnancy and to evaluate the role of clinical and ultrasound markers in the prediction of FMH. MATERIALS AND METHODS: FMH was quantified by cytofluorimetric testing at 28 to 35 weeks of gestation in 223 women and at term in 465 women, all with risk factors. Foetal evaluation included foetal movement profile, middle cerebral artery peak velocity of systolic blood flow (MCA-PSV) and cardiotocographic monitoring. RESULTS: All women tested negative for FMH in the third trimester. Four patients (0.9%) tested positive at term, with estimated volumes of bleeding of 2.2, 8.1, 12.3 and 39.8 mL. Three FMH cases (75%) had a non-reassuring cardiotocography compared to 8.9% (42/461) of women without FMH (p=0.003) and two FMH cases reported a reduction in foetal movements reduction compared to four of those without FMH (p=0.001). Mean MCA-PSV was normal in both the groups with and without FMH (p=0.22). DISCUSSION: FMH is rare in pregnancy and at term. Cytofluorimetric testing is a specific method to detect mild-to-moderate FMH even when the MCA-PSV is not informative. Mild-to-moderate FMH is significantly associated with reduced foetal movements and non-reassuring cardiotocographic monitoring.

Clinical input of anti-D quantitation by continuous-flow analysis on autoanalyzer in the management of high-titer anti-D maternal alloimmunization.

BACKGROUND: In addition to titration by indirect antiglobulin test most widely used, anti-D quantitation by continuous-flow analysis (CFA) may be performed to assess severity of maternal immunization. Only five studies have reported its added value in the management of pregnancies complicated by anti-D immunization. STUDY DESIGN AND METHODS: A retrospective study of 74 severe anti-D-immunized pregnancies was conducted from January 1, 2013, to December 31, 2014, in the Trousseau Hospital in Paris (France). Concentration of maternal anti-D was measured by titration and by CFA two-stages method (2SM; total amount of anti-D) and one-stage method (1SM; high-affinity IgG1 anti-D). These biologic data were analyzed according to the severity of the hemolytic disease of the fetus and the newborn. RESULTS: The value of 5 IU anti-D/mL in maternal serum is validated as a threshold to trigger ultrasonographic and Doppler fetal close follow-up. A high 1SM/2SM ratio was associated with a higher risk of intrauterine transfusion (IUT). For pregnancies requiring IUT and without increasing titer, maternal 1SM anti-D concentration tends to correlate with the precocity of fetal anemia. In the "without-IUT" group 1SM and 2SM anti-D concentrations correlate significantly with cord bilirubin levels of the newborn at birth. CONCLUSION: Altogether our results underline the importance of anti-D quantitation by CFA to optimize the management of anti-D-alloimmunized pregnancies.

Should optimal timing between two intrauterine transfusions be based on estimated daily decrease of hemoglobin or on measurement of fetal middle cerebral artery peak systolic velocity?

BACKGROUND: To best predict the recurrence of fetal anemia after intrauterine transfusion (IUT), the measurement of middle cerebral artery peak systolic velocity (PSV) and the estimation of hemoglobin (Hb) daily decrease are compared. STUDY DESIGN AND METHODS: A retrospective study including 38 patients who had at least two IUTs in a context of red blood cell alloimmunization was conducted. PSV values before first, second, and third IUTs were collected and expected Hb level was calculated according to various Hb daily decrease formulas as proposed in the literature. RESULTS: Comparison of PSV receiver operating characteristic curves with the various Hb levels did not find any significant difference between first and second IUTs. On the other hand, we found a significant difference between the second and third IUTs, with better prediction of fetal anemia through Hb decrease calculation, whatever the formula. Between the second and third IUTs, no formula was significantly better than the others. CONCLUSION: The timing of a second transfusion can be difficult to determine with certainty, but PSV can give an accurate assessment of when to resample the fetus with probably a higher recommended threshold for the diagnosis of fetal anemia. Subsequent to a second transfusion, the intertransfusion interval should be based on estimated Hb decrease rather than PSV thresholds, whatever the chosen formula proposed in the literature. Larger numbers are needed to definitely make this recommendation and it will be interesting to evaluate correlation between different antibodies.

Diagnosis of Severe Fetomaternal Hemorrhage with Fetal Cerebral Doppler: Case Series and Systematic Review.

OBJECTIVES: To analyze the role of middle cerebral artery (MCA) peak systolic velocity (PSV) in the prediction of severe fetomaternal hemorrhage (FMH) and to compare it with standard biophysical assessment. DATA SOURCES: Retrospective review of cases of FMH seen in our unit and systematic review of the literature. RESULTS: We followed the MOOSE guidelines to review the literature. From 838 articles, 16 were selected. In total, 35 women, including 3 cases from our center and 32 obtained from the literature search were included. Diagnosis of FMH was always confirmed by laboratory tests. Patients were seen at 31 ± 5 weeks' gestation (range 16-39) and the most frequent indication for referral was decreased perception of fetal movements. Cardiotocography (CTG) upon admission was sinusoidal in 18 cases, nonreactive in 6, decelerative in 2 and tachycardic in one. MCA-PSV was abnormal in all cases but one. There were 2 perinatal deaths. The mean hemoglobin concentration at birth or at intrauterine transfusion was 4.8 ± 1.9 g/dl. DISCUSSION: The most accurate predictor of FMH was fetal MCA-PSV. CTG was always abnormal but the pattern was frequently nonspecific. We suggest including fetal cerebral Doppler in the evaluation of patients with decreased fetal movements, particularly in those cases with ambiguous results of biophysical testing.

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.

[Prognostic factors of perinatal short-term outcome in severe placental insufficiency using Doppler sonography to assess end-diastolic absent and reverse blood flow in umbilical arteries]. / Prognosefaktoren des perinatalen Kurzzeitergebnisses bei schwerer Plazentainsuffizienz mit dopplersonografisch enddiastolischem Null- und Rückfluss in der Art. umbilicalis.

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

Role of the vascular endothelial growth factor in the inverse relationship between increased nuchal translucency thickness and fetomaternal transfusion.

OBJECTIVE: To elucidate the possible etiological role of the vascular endothelial growth factor (VEGF) in the inverse correlation between nuchal translucency (NT) thickness and fetomaternal transfusion (FMT). METHODS: The level of FMT was determined prospectively in 80 viable, singleton pregnancies in which 10-14-week ultrasonographic scanning, NT thickness measurement; chorionic villus sampling (CVS) for fetal karyotyping and VEGF concentration determination were performed. The grouping procedures were based either on NT thickness (<2 MoM in Group I, and ≥2 MoM in Group II), or on karyotype (euploid in Group A, and aneuploid in Group B). The level of FMT was determined via maternal serum α-fetoprotein levels before and after CVS. The FMT and the VEGF concentration of the chorionic tissue were analysed in comparisons between Groups I and II, and between Groups "A" and "B". RESULTS: The mean level of FMT after CVS was 72.5±21.3 µL and 19.28±5.4 µL in Groups I (n=44) and II (n=36), respectively (P<0.02). The VEGF concentration of the chorionic tissue in Groups I and II was 40.6±16.7 pg/mg protein and 21.1±6.3 pg/mg protein, respectively (P=0.28). The mean level of FMT was 57.9±15.0 µL and 8.1±3.9 µL in Groups A and B, respectively (P<0.003). The VEGF concentration of the chorionic tissue in Groups A and B was 25.9±10.7 pg/mg protein and 21.3±11.3 pg/mg protein, respectively (P=0.77). CONCLUSION: No difference exists in the VEGF concentration in the aspirated chorionic tissue between Groups I and II and between Groups A and B. A higher level of FMT was observed among the aneuploid pregnancies after CVS than among the euploid cases. Chorionic VEGF does not influence the inverse relationship between the pre-CVS NT thickness and FMT.

Sonographic findings in severe fetomaternal transfusion.

Fetomaternal hemorrhage (FMH) or fetomaternal transfusion syndrome is the leakage of fetal red blood cells into the maternal circulation. Massive FMH can cause substantial fetal morbidity and mortality. Sonographic evidence of severe FMH syndrome includes fetal hydrops and other fetal anemia-related findings. The peak systolic velocity in the middle cerebral artery has extensively been used for the prediction of fetal anemia and for the timing of the first intrauterine intravascular transfusion (IIVT). We present a case of severe FMH syndrome that was diagnosed during the 24th week of pregnancy. A total of eight IIVT were performed. The actual increase in the fetal Hb after each transfusion was much lower than the expected. At 27 weeks of gestation, sonographic evaluation revealed areas of echogenicity around the posterior horns of the lateral ventricles suggesting ischemic damage. Due to these findings, no further IIVTs were offered and the fetus died a week later. The management of fetal anemia caused by severe FMH is difficult, and the anemic fetuses do not respond well to serial IIVTs as the transfer of blood to the maternal circulation continues.

[Fetomaternal hemorrhage: practitioner's point of view]. / Hémorragie foetomaternelle : le point de vue du clinicien.

Fetomaternal hemorrhage is known to have a wide spectrum of clinical presentations. This large variability probably explains why there are still neither consensual classification nor management recommendations. Nevertheless, fetomaternal hemorrhage is a serious condition, which may cause life-threatening fetal anemia. Fetal tolerance mainly depends on the quantity of fetal blood loss as well as the rate at which it occurs. Decrease in perceived fetal movements represents the main clinical sign of fetomaternal hemorrhage and justify use of diagnostic tests such as the Kleihauer-Betke test. Large fetomaternal hemorrhages can also induce fetal hydrops and stillbirth. In this review, we emphasize the clinical and biological features of fetomaternal hemorrhages and we highlight the circumstances associated with false-negative and false-positive results of the Kleihauer-Betke test. We also propose an original algorithm for the management of fetomaternal hemorrhages.

Prenatal findings in a case of massive fetomaternal hemorrhage associated with intraplacental choriocarcinoma.

We describe biochemical assessment of maternal circulation in a case of massive fetomaternal hemorrhage at term associated with intraplacental choriocarcinoma. Markedly elevated maternal serum hCG level at 37 weeks of gestation suggested choriocarcinoma as a cause of fetomaternal hemorrhage in this case. Measurement of maternal hCG may be a useful parameter when intraplacental choriocarcinoma is in the differential diagnosis. In addition, the placenta should be examined in all cases of fetomaternal hemorrhage.

Doppler sonography of the fetal middle cerebral artery in the management of massive fetomaternal hemorrhage.

Massive fetomaternal hemorrhage (FMH) is a rare complication in pregnancy that may cause hydrops or can even be life-threatening for the fetus. We report on the case of a 19-year-old gravida I, para 0, who presented to our clinic at 32 weeks of gestation due to decreased fetal movements. The initial fetal heart rate tracing at admission showed a sinusoidal pattern without decelerations. The ultrasound examination performed immediately described a normally developed fetus with normal amounts of amniotic fluid and without abnormities of the placental structure. Doppler sonography of the fetal middle cerebral artery gave rise to the strong suspicion of fetal anemia, so that a cordocentesis was prepared for potential intrauterine blood transfusion. Meanwhile, the rate of fetal hemoglobin (HbF) cells in the maternal blood was found to be markedly increased with 66 per thousand. Correspondingly, cardiotocographic findings worsened with repeated decelerations, thus an immediate cesarean section was performed based on the suspected diagnosis of an acute FMH. A fetus weighing 1,860 g was delivered, who had severe anemia with hemoglobin level of 4.0 g/dl. After a direct blood transfusion, HbF levels normalized rapidly, the fetus stabilized, and a normal recovery has thus far been reported. The presented case demonstrates the successful and straightforward diagnosis, as well as the management of a case of severe FMH and illustrates the special value of Doppler sonography in this context.

Massive feto-maternal hemorrhage: diagnosis by cardiotocography, Doppler ultrasonography and ST waveform analysis of fetal electrocardiography.

A 34-year-old healthy gravida 2 para 1 presented after an uncomplicated pregnancy at term with a 2-day history of diminished fetal movements. Fetal anemia was suspected by fetal heart rate monitoring and Doppler estimation of the fetal peak blood flow velocity of the middle cerebral artery. We were also fortunate to register pathological ST waveform changes of the fetal ECG indicating fetal hypoxia. The diagnosis of a massive feto-maternal hemorrhage was confirmed by an extremely high fraction of erythrocytes containing fetal hemoglobin in maternal blood and, after delivery, by placental histology.

Persistent fetal hemoglobin in maternal circulation complicating the diagnosis of fetomaternal hemorrhage.

BACKGROUND: Transplacental hemorrhage can be life threatening to a fetus and has important maternal treatment implications. In contrast, hereditary persistence of fetal hemoglobin is a condition that has little consequence. The Kleihauer-Betke test, which is routinely used to document transplacental hemorrhage, will be positive in either case. CASES: We report two cases in which maternal persistence of fetal hemoglobin was unknown and led to the erroneous diagnosis of fetomaternal hemorrhage. These cases highlight both the limitations of the Kleihauer-Betke test and the role of flow cytometry in diagnosing fetomaternal hemorrhage. CONCLUSION: The use of flow cytometry can clarify Kleihauer-Betke test results when there is known maternal persistence of fetal hemoglobin and can more precisely quantify a fetomaternal hemorrhage for accurate Rh immune globulin dosing.