Maternal ABO Discrepancy Caused by Massive Fetomaternal Hemorrhage: a Case Report.

BACKGROUND: Fetomaternal hemorrhage (FMH) can lead to severe, life-threatening fetal anemia depending on the amount of blood loss. FMH may be underdiagnosed as it is not routinely tested. In our report, we present a rare case of obvious mixed-field agglutination of maternal ABO forward typing caused by massive fetomaternal hemorrhage. METHODS: We retrospectively evaluated the clinical information of a 42-year-old pregnant woman who was admitted to our hospital at gestational week (GW) 36_5/7 due to fetal distress. She later delivered a male infant with severe anemia by cesarean section. RESULTS: This case had an unusual maternal hemoglobin elevation before delivery and the maternal blood type identification showed ABO discrepancy. After other causes were excluded, FMH was suspected. The Kleihauer-Betke (K-B) test was done on the mother's blood, indicating a massive FMH. CONCLUSIONS: Massive FMH may be a cause of ABO discrepancy of pregnant woman. FMH should be considered when we get a result of a mixed-field agglutination of pregnant woman with other possible causes excluded.

Case Report of Anemia Following Fetal-Maternal Hemorrhage.

BACKGROUND: Any maternal history of blood loss, ABO or Rh incompatibility, and hydrops fetalis often leads to suspicion of neonatal anemia postnatally. When maternal history consists only of decreased fetal movement, recognition of neonatal anemia can be problematic. CLINICAL FINDINGS: This case was a transported late preterm neonate who presented initially with persistent hypoxia unresponsive to usual respiratory support. On examination, mild paleness was noted. PRIMARY DIAGNOSIS: Anemia caused by fetal-maternal hemorrhage was the ultimate diagnosis confirmed by a Kleihauer-Betke test on maternal serum examining fetal cells. INTERVENTIONS: Neonatal resuscitation included positive pressure ventilation, oxygen, and intubation. However, oxygenation did not improve prompting consultation with the neonatologist. Sedation and a paralytic were given. A chest radiograph ruled out pneumothoraces and pleural effusions as causative. Initiation of inhaled nitric oxide produced a mild response. Eventually, the transport nurse obtained a complete blood count indicating severe anemia, which prompted an emergent blood transfusion. The accepting neonatology team consulted with the obstetrician and a Kleihauer-Betke test was performed on mother's blood confirming a large fetal-maternal hemorrhage. OUTCOMES: This neonate responded well to blood transfusions, a pressor, and respiratory support and was discharged home at 7 days of life. PRACTICE RECOMMENDATIONS: Recognition of postnatal anemia is vital to sustaining life and this can occur in the transport environment. When maternal history is nonspecific and a neonate is hypoxic, uncommon causes of hypoxia can be identified with consultation and a complete blood count.

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.

Untimely diagnosis of fetomaternal hemorrhage: what went wrong?

Fetomaternal hemorrhage (FMH) is an obstetrical challenge. It is defined as a passage of fetal blood into the maternal circulation or vice versa, which might complicate pregnancy or delivery. Most cases of acute and chronic FMH are idiopathic in origin and involve uncomplicated near-term pregnancies. Yet, due to the lack of universal screening, heterogeneous clinical presentation and insufficient clinicians awareness, in some cases FMH may present as immediate fetal compromise or even stillbirth as the most devastating consequence. We made a review of the literature of the FMH clinical cases of fetal/neonatal death in order to focus on the available diagnostic tools and their limitations. Cardiotocography, biophysical profile, middle cerebral artery peak systolic volume and current laboratory tests were studied and evaluated as diagnostic tools for FMH. International guidelines are needed to help clinicians make a prompt identification of FMH. Moreover, a standardized management protocol is essential in order to improve fetal-neonatal outcomes.

Characterisation of maternal human leukocyte antigen class I antibodies in suspected foetal and neonatal alloimmune thrombocytopenia.

OBJECTIVES: To investigate the specificities and level of HLA class I antibodies in selected cases referred for suspected foetal and neonatal alloimmune thrombocytopenia (FNAIT). BACKGROUND: FNAIT occurs in 1 : 1-2000 live births, whereas maternal immunisation against human leukocyte antigen (HLA) class I is common. Whether HLA class I antibodies alone can cause FNAIT is debatable. MATERIAL AND METHODS: A total of 260 patient samples were referred between 2007 and 2012. Referrals with maternal HLA class I antibodies and no other cause for the neonatal thrombocytopenia were included for analysis (cases, n = 23). HPA-1a negative mothers were excluded. Control groups were screened positive mothers of healthy neonates (controls, n = 33) and female blood donors (blood donors, n = 19). LABScreen single antigen HLA class I beads was used for antibody analysis. Clinical records were reviewed for cases. RESULTS: All groups had broad antibody reactivity. Cases had more antibodies with high SFI levels compared with the controls (SFI>9999; medians 26, 6 and 0; P < 0·05) and higher overall median HLA-ABC and HLA-B SFI (P < 0·05). Many of the antibodies were reactive with rare alleles. When reviewing the clinical records, several of the cases had other contributing factors to the thrombocytopenia. There was no correlation between foetal platelet count and antibody levels. CONCLUSION: Mothers of thrombocytopenic neonates had higher levels of HLA class I antibodies compared with control groups of women with healthy children and female blood donors. However, clinical outcome and antibody response correlated poorly in the heterogeneous case group, indicating a multifactorial cause to the thrombocytopenia in the majority of cases.

Occult fetomaternal hemorrhage in women with pathological placenta with respect to permeability.

AIM: Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. METHODS: Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the ß-γ system with two monoclonal antibodies against hemoglobin ß-chain and hemoglobin γ-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin γ-chain alone accounted for ≥0.02% of the total cell population on scatter plots. RESULTS: FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P =  0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P =  1.000). CONCLUSION: The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.

[A case of fetal death resulting from a massive fetomaternal hemorrhage]. / LE CAS CLINIQUE DU MOIS. Mort foetale in utero due à une hémorragie foeto-maternelle massive.

We report the case of a late stillbirth which unexpectedly occurred in a patient without any medical history and after a meticulous obstetrical follow up. Stillbirth is unfortunately not unusual and implies a complete etiological work up. In the present observation, the Kleihauer test and anatomoclinical examination concluded that the death was due to an acute cerebral anoxy resulting from a massive fetomaternal hemorrhage (HFM). HFM is rarely considered as the cause of a late stillbirth, but its occurrence is certainly underestimated. Yet, if HFM is identified before fetal death, an .adequate management could considerably improve the fetal prognosis and, sometines, save the child's life.

Massive fetomaternal hemorrhage in a monochorionic-diamniotic twin pregnancy: a case report.

Fetomaternal hemorrhage (FMH) result into severe, life-threatening fetal anemia and cause intrauterine death of the fetus. It is tough for an early diagnosis of FMH before pregnancy and few authors reported FMH in a twin pregnancy. Therefore, we reported a case of massive FMH. The patient felt a decrease in fetal movements at 33+5 gestational weeks. Cardiotocography showed sinusoidal heart rate patterns in one fetus. The fetal hemoglobin level in maternal blood was 6.4% (normal range for single pregnancy, 0.0%-2.0%). Since the patient was diagnosed with fetal distress, cesarean section was performed and both babies delivered to receive neonatal treatment. Severe anemia was apparent in both neonates, based on red blood cell count, hemoglobin concentration, and hematocrit of 0.75 × 1012/L and 0.61 × 1012/L, 2.8 g/dL and 2.4 g/dL, and 10.0% and 8.4%, respectively. The neonates were admitted to the intensive care unit for prematurity care and presently are well. In our experience, an early diagnosis of FMH contributed to saving fetus. Obstetricians should highlight fetal movements counting to every patient. Once massive FMH occurs in monochorionic twins, both fetuses may develop severe anemia and require emergency intervention.

Maternal and fetal outcomes of intraplacental choriocarcinoma complicated by fetomaternal hemorrhage: a systematic review.

INTRODUCTION: Intraplacental choriocarcinoma is a gestational trophoblastic neoplasia located within the placenta. Due to the usual silent presentation, more than half of the cases are diagnosed incidentally. It has been demonstrated that this pathology is linked to feto-maternal hemorrhage (FMH), stillbirth, and intrauterine growth restriction. The aim of our review was to establish if there are recurrent signs that might lead to an early diagnosis and better management in cases complicated by FMH. MATERIALS AND METHODS: We performed a systematic review of the literature from 2000 up to March 2023. The adopted research strategy included the following terms: (gestational choriocarcinoma obstetrics outcome) AND (intraplacental choriocarcinoma) AND (gestational choriocarcinoma). The MEDLINE (PubMed), Google Scholar, and Scopus databases were searched. RESULTS: The research strategy identified 19 cases of FMH coexisting with intraplacental choriocarcinoma (IC), as described in 17 studies. The perinatal mortality rate was 36.8%. In eight cases, histological diagnosis of IC was made post-delivery. Metastatic lesions were found in 75% (6/8) of described cases. One case of maternal death has been described. Chemotherapy was necessary in seven cases. Sporadical prenatal ultrasound signs were described. DISCUSSION: The diagnosis of IC is usually delayed, mostly due to aspecific symptoms and signs. Histological analysis of the placenta, when not routinely performed, should be performed when warning symptoms are encountered. The maternal prognosis was good, with a mortality rate of 5.5%. A fertility-sparing approach is always possible even in the presence of metastasis. Chemotherapy seems to be useful in cases of maternal and neonatal metastasis.

Fetomaternal hemorrhage in the second trimester.

AIMS: To investigate fetomaternal hemorrhage (FMH) rate and quantity in the second trimester of pregnancies with fetal anomalies and to assess the impact of invasive prenatal and termination procedures. METHODS: Blood samples from women before termination of pregnancy were collected and analyzed by dual-color flow cytometry. Various clinical parameters were studied for their association with FMH. RESULTS: In total, 67 women were recruited; pre- and post-termination pairs were collected for 31 women. HbF cells were present in 91.0% of specimens, in 29.9% the transfused blood volume was ≥4.2 mL. FMH ≥30 mL was found in 3.0%, and chronic FMH, defined as FMH ≥40% of fetoplacental blood volume in 7.5%. At the limit of quantification (0.1%) none of the clinical parameters was associated with the presence of HbF cells, nor was there a difference in HbF cell concentrations between pre- and post-termination blood samples. CONCLUSIONS: Compared to normal term pregnancy, transfer of fetal red blood cells into the maternal circulation is increased in second-trimester pregnancies with fetal anomalies. FMH is not associated with invasive procedures or surgery performed in the context of termination. We hypothesize that the abnormal pregnancy itself, by means of an abnormal uteroplacental interface, is causing the increased transfer.

Chronic massive fetomaternal hemorrhage in a newborn from immigrants. Clinical and organizational implications.

Fetomaternal hemorrhage (FMH) refers to the entry of fetal blood into the maternal bloodstream before or during delivery. FMH of more than 30 mL occurs with the frequency of about 1/300. Fetal outcomes may be compromised by still births, hydrops fetalis, cardiac complications, and increased rates of postpartum infant death. In most cases, the cause is not identified. Clinical manifestations of FMH depend on the volume of blood lost and the rate that it occurred. We report a case of chronic massive FMH in a newborn of an immigrant mother with a favorable outcome. Medical visits and tests during pregnancy, including ultrasound scans, were not performed. The baby was hemodynamically stable after birth, manifesting only pallor. The complete blood count revealed severe hypochromic anemia (hemoglobin 3,8 g/dl, hematocrit 14,4%) and reticulocytosis (reticulocyte 25,2%). There was no ABO blood type incompatibility and the result of direct Coomb's test was negative. The Kleihauer-Betke test revealed 5% of fetal erythrocytes in the maternal bloodstream equivalent to 180 mL. The fact that FMH can occur without prior risk factors, and the diagnosis is often postnatal, underscores the importance of heightened of medical suspicion particularly in infants born to immigrants where there is often the lack of prenatal visits.

Fetomaternal hemorrhage: a clue to intraplacental choriocarcinoma and neonatal malignancy.

Fetomaternal hemorrhage (FMH) is a known cause of neonatal anemia due to fetal blood loss to the maternal circulation, occurring when the maternal-fetal barrier is disrupted. Several causes must be considered, although in most cases the etiology remains unknown. Intraplacental choriocarcinoma (ICC) is a rare entity and has been related with massive FMH, intrauterine fetal demise, severe neonatal anemia and metastatic choriocarcinoma in both mother and infant. There are 25 cases of histopathologically confirmed ICC complicated with FMH described in the literature. Because FMH occurs unexpectedly and the majority of patients with ICC are asymptomatic, this diagnosis may be missed. Once FMH is confirmed, underlying malignancy should be kept in mind. The authors present a case report of severe neonatal anemia following FMH related to ICC and highlight the importance of serum ß-hCG monitoring in cases of massive FMH.

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.

Large fetomaternal hemorrhage: prenatal predictive factors for perinatal outcome.

We sought to identify prenatal predictive factors for perinatal outcome and to estimate fetal hemoglobin (Hb) levels in large fetomaternal hemorrhages (transfused blood volume [TBV] > 20 mL) by performing a case-series study ( N = 32). Perinatal outcome was favorable (F group, N = 22) and poor (P group, N = 10: four fetal deaths, three postnatal deaths, three cases of severe anemia). Median TBV was 25 mL for the F group and 325 mL for the P group ( P < 0.0001) and median Hb concentration at birth was 15 g/dL for the F group and 5 g/dL for the P group ( P < 0.0001). Receiver operating characteristic analysis revealed that a Kleihauer-Betke test value above 2.5% was the best threshold for predicting adverse outcome, with sensitivity of 100% (95% confidence interval [CI] 76 to 100) and specificity of 96% (95% CI 77 to 100). In utero estimated Hb concentration best correlated with Hb level at birth when calculated using TBV corrected for fetoplacental weight ( P < 0.0001, R(2) = 0.874). The value obtained in the Kleihauer-Betke test was a prognostic factor, and TBV corrected for fetoplacental weight was the best biological marker for assessing fetal Hb level.

[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.

[Severe neonatal anemia due to fetomaternal hemorrhage: an ilustrative case]. / Anemia neonatal grave secundaria a transfusion feto-materna: a proposito de un caso.

Fetomaternal transfusion (FMT) is defined by the transfer of fetal blood into the maternal circulation. The incidence of massive FMT is estimated to be approximately 0.2-0.9 % of births. Although a number of etiologies have been associated with FMT, most causes remain unidentified and the pregnancy is usually asymptomatic. The most frequent symptom is the decrease in fetal movements (26 %) in relation to severe anemia. Several diagnostic modalities for FMT are described (Kleihauer stain, flow cytometry). We describe a case of a newborn with chronic anemia secondary to FMT who, after treatment with transfusions of red blood cells, presented volume overload and clinical worsening as a complication. In this case, our patient needed exchange transfusion for definitive improvement without disability.

La transfusión feto-materna es el paso de eritrocitos fetales a la circulación materna. Cuando es masiva, tiene una incidencia aproximada del 0,2-0,9 %. Generalmente, se desconoce el agente desencadenante, pero, en ocasiones, se pueden identificar factores de riesgo. En el embarazo, suele ser asintomática; el síntoma más frecuente es la disminución de los movimientos fetales (el 26 %) en relación con la anemia grave. Se diagnostica mediante la detección de hemoglobina fetal en la sangre materna (test de Kleihauer o citometría de flujo). Se presenta a un recién nacido con anemia crónica secundaria a la transfusión fetomaterna, que, después del tratamiento con transfusión de concentrado de hematíes, tuvo como complicación síntomas de sobrecarga de volumen y empeoramiento clínico. Tras la realización de una exanguinotransfusión, evolucionó favorablemente, sin secuelas.