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.

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.

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.

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.

[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.

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.

Establishing the Cause of Anemia in a Premature Newborn Infant.

The three major causes of anemia in neonates are blood loss, decreased red blood cell production, and increased degradation of erythrocytes. Establishing the cause of anemia in a neonate born prematurely can be challenging. Clinically, fetomaternal hemorrhage (FMH) can be difficult to diagnose-the condition often presents only after the manifestation of severe fetal anemia. FMH can be confirmed by determining the fetal hemoglobin F fraction in the mother, which is traditionally performed using the Kleihauer-Betke test (KBT). Herein, we present a case study of a newborn baby boy of Dutch ethnicity with massive FMH and negative KBT result. The KBT result appeared to be false-negative due to AO antagonism. However, the results of an additional marker alpha-fetoprotein (AFP) test confirmed the diagnosis of massive FMH. Therefore, measuring AFP in maternal blood can be helpful in confirming FMH in unexplained anemia of the neonate.

Intraplacental choriocarcinoma coexisting with fetomaternal hemorrhage: Case report, chemotherapy management, and literature review.

RATIONALE: Near-term intraplacental choriocarcinoma (IC) coexisting with massive fetomaternal hemorrhage (FMH) is rare, and its clinical course is poorly understood. Here, we report a new case from our hospital, with detailed discussion and literature review. PATIENT CONCERNS: A 21-year-old Chinese female at 35 weeks gestation was admitted to our hospital due to reduced fetal movement. Near-term IC coexisting with massive FMH was diagnosed after delivery. INTERVENTION: The mother and infant were followed 3 months after delivery. Beta-human chorionic gonadotropin (ß-HCG), pathological examination of the placenta, and computed tomography scans were performed for the mother and ß-HCG was performed for the infant. OUTCOMES: The mother's ß-HCG serum level increased from 31,280 IU/L (6 days postdelivery) to 192,070 IU/L (49 days postdelivery), and then steadily fell to 42,468 IU/L (3 months postdelivery) without chemotherapy. The mother died from metastasis and cerebral hemorrhage. The infant survived and his ß-HCG serum level fell to within the normal range without chemotherapy. LESSONS: FMH associated with near-term IC is a rare disease. Measurement of maternal ß-HCG may therefore represent a useful parameter when IC is a possible differential diagnosis. A pathological examination of the placenta should be performed in all cases of FMH to better identify cases of IC. Future research should aim to develop methods of identifying which patients with IC should receive chemotherapy, whether we should use single- or multiagent chemotherapies, and whether there is a positive correlation between chemotherapy regimen and ß-HCG serum levels.

Patrón cardiotocográfico sinusoidal atípico asociado a anemia fetal grave por transfusión feto-materna / Atypical sinusoidal pattern associated with severe fetal anemia caused by fetal-maternal transfusion

El patrón sinusoidal se define como una frecuencia cardíaca fetal que simula una onda sinusoidal suave, con periodicidad de tres a cinco ciclos por minuto y una duración de, al menos, 20 minutos. Es un patrón muy poco frecuente cuyo mecanismo se cree que se produce en respuesta a la hipoxemia fetal moderada, a menudo secundaria a la anemia fetal. La anemia fetal puede ser debida a una hemorragia aguda o a un proceso crónico. Las causas de anemia fetal incluyen hemorragia feto-materna, hemorragia fetal iatrogénica, hemorragia fetal secundaria a rotura de vasa previa o desprendimiento de placenta, la aloinmunización y la infección por parvovirus. Se describen tres casos de anemia neonatal grave, secundarias a transfusión feto-materna, no diagnosticadas durante la gestación, que debutan con un registro con patrón sinusoidal atípico. Lo denominamos atípico, ya que no cumple los criterios estrictos de patrón sinusoidal, y visualmente son registros que podrían pasar inadvertidos, y no ser catalogados como tal, y sin embargo todos los casos se asociaron a cesáreas urgentes por riesgo de pérdida de bienestar fetal y anemias severas en los neonatos (AU)

A sinusoidal heart rate pattern simulates a smooth sine wave, with periodicity of three to five cycles per minute and lasting for at least 20 minutes. It is a very rare pattern whose mechanism is believed to be a response to a moderate fetal hypoxemia, often secondary to fetal anemia. Fetal anemia can be due to acute bleeding or a chronic process; causes include fetomaternal hemorrhage, iatrogenic fetal bleeding, fetal bleeding secondary to vasa previa or placental abruption, alloimmunization, and parvovirus infection. 3 cases of severe neonatal anemia secondary to fetal-maternal transfusion, undiagnosed during pregnancy, debuting with an atypical sinusoidal pattern are described. We call it atypical because it does not meet the strict criteria for sinusoidal pattern, and visually, this kind of fetal heart rate monitoring could pass unnoticed and not be classified as such, but all cases were associated with urgent cesarean for risk fetal and severe anemia in newborns (AU)

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.