Fetomaternal Transfusion Research Articles

Fetomaternal macrotransfusion – A case series

Ziel: Already at the beginning of the last century, it was hypothesized that fetal cells might pass into maternal circulation (Dienst A, 1905). In most cases, the passing volume is small, being < 15ml (Sebring et al, 1990). Fetomaternal macrotransfusion, which may lead to life-threatening blood loss, means a transfer of more than 150ml or 50% of the total fetal blood volume. Risk factors include caesarean sections, multiple gestations, abruptions, placental retention, and abdominal version or trauma. Our aim was to retrospectively analyse cases of massive fetomaternal transfusion between XII/2004 and II/2010.

Placental cord drainage after vaginal delivery as part of the management of the third stage of labour

Cord drainage in the third stage of labour involves unclamping the previously clamped and divided umbilical cord and allowing the blood from the placenta to drain freely into an appropriate receptacle. The objective of this review was to assess the specific effects of placental cord drainage on the third stage of labour following vaginal birth, with or without prophylactic use of uterotonics in the management of the third stage of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2010). Randomised controlled trials comparing placental cord draining with no placental cord drainage as part of the management of the third stage of labour. Two review authors independently assessed the quality of trials and extracted data. This was then verified by the third review author who then entered the agreed outcomes to the review. Three studies involving 1257 women met our inclusion criteria. Cord drainage reduced the length of the third stage of labour (mean difference (MD) -2.85 minutes, 95% confidence interval (CI) -4.04 to -1.66; three trials, 1257 women (heterogeneity: T² = 0.87; Chi²P=17.19, I² = 88%)) and reduced the average amount of blood loss (MD -77.00 ml, 95% CI -113.73 to -40.27; one trial, 200 women).No incidence of retained placenta at 30 minutes after birth was observed in the included studies, therefore, it was not possible to compare this outcome. The differences between the cord drainage and the control group were not statistically significant for postpartum haemorrhage or manual removal of the placenta. None of the included studies reported fetomaternal transfusion outcomes and there were no data relating to maternal pain or discomfort during the third stage of labour. There was a small reduction in the length of the third stage of labour and also in the amount of blood loss when cord drainage was applied compared with no cord drainage. The clinical importance of such observed statistically significant reductions, is open to debate. There is no clear difference in the need for manual removal of placenta, blood transfusion or the risk of postpartum haemorrhage. Due to small trials with medium risk of bias, the results should be interpreted with caution.

Hemorragia fetomaterna masiva con patrón cardiotocográfico sinusoidal. Presentación de un caso y revisión de la literatura

Introducción: la transfusión fetomaterna masiva (TFM) es una entidad con una elevada morbilidad y mortalidad fetal, suele cursar con una disminución en la percepción de los movimientos fetales por parte de la madre, y la presencia de un patrón cardiotocográfico sinusoidal fetal, asociado a la anemia fetal. No obstante, ambas situaciones tienen muy baja especificidad. Se presenta un caso clínico con el objetivo de revisar la exactitud del patrón sinusoidal en el diagnóstico de anemia fetal.Materiales y metodos: se presenta el caso de una gestante de 36 semanas que fue atendida en el Hospital Universitario La Paz (complejo hospitalario de tercer nivel que forma parte del conjunto de hospitales públicos en España), en la que tras presentarse un patrón cardiotocográfico no tranquilizador, se realizó una inducción del parto en el que las pruebas habituales de bienestar fetal resultaron insuficientes para el diagnóstico de sufrimiento fetal. Tras un parto eutócico se comprobó la presencia de una anemia neonatal grave, comprobándose la presencia de un gran volumen de sangre fetal en la sangre materna mediante el test de Kleihauer Betke. Se hace una revisión de los artículos publicados en los últimos 10 años en las base de datos Medline vía PubMed, en español e inglés.Conclusión: la monitorización fetal intraparto podría ser útil en el diagnóstico de la hemorragia fetomaterna masiva, aunque se deben hacer estudios más amplios para determinar la exactitud diagnóstica.

Early plasmapheresis followed by high‐dose γ‐globulin treatment saved a severely Rho‐incompatible pregnancy

An alloimmunized pregnancy induces anemia in the fetus and can ultimately lead to fetal hydrops and intrauterine fetal death. A woman with a severe Rho-incompatible pregnancy had experienced frequent pregnancies with fetomaternal transfusion without receiving RhIg and had high anti-D antibody titers present from early pregnancy. We succeeded in long-term inhibition of antibody production using plasmapheresis followed by high-dose γ-globulin treatment in early pregnancy.

Fetomaternal transfusion after amniocentesis and cordocentesis

To compare the extent of fetomaternal transfusion after amniocentesis and cordocentesis. Three-hundred and forty-five amniocentesis and 268 cordocentesis were performed for genetic indications. The extent of fetomaternal transfusion was calculated on the basis of the maternal serum alpha-fetoprotein level changes. The mean fetomaternal transfusion was 6.3 and 62 μL in the amniocentesis and cordocentesis groups, respectively. Transplacental needle passage and longer procedural time were risk factors for fetomaternal transfusion. The frequency of transplacental passage was higher and the procedural time was longer in the cordocentesis group. The fetal loss rate was 1.17% after amniocentesis and 1.2% after cordocentesis, respectively. Cordocentesis causes more injury to the extrafetal compartment, which results in a higher level of fetomaternal transfusion. However, though a nearly ten times higher fetomaternal transfusion was observed after cordocentesis, there was no essential difference in pregnancy outcome between the two groups.

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

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). 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". 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). 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.

Hemoglobinopathies Are on the Increase

Though it is still politically controversial to call Germany an immigration country, the facts related by Kohne and Kleinhauer in their article (1) show that immigration to Germany has led, in recent years, to an increased prevalence of diseases once considered to be exotic. The article represents, in a sense, the scientific life’s work of these two authors, who have spent decades studying the physiology and human pathophysiology of altered hemoglobins. The Kleihauer test for the staining of erythrocytes with fetal hemoglobin is now a part of standard textbook knowledge and is still used for the detection and quantification of feto-maternal transfusion. By making feto-maternal transfusion detectable, this test provided the first rational basis for Rh prophylaxis in pregnant women.

A randomised controlled trial of placental cord drainage to reduce feto-maternal transfusion

ObjectivesTo determine whether placental drainage via the umbilical cord prior to placental delivery reduces the size of feto-maternal transfusion and thus the chance of rhesus isoimmunisation in rhesus negative women. Study designA randomised controlled trial conducted in a tertiary hospital setting in the UK compared 18 rhesus negative women who had placental drainage (10 caesarean section and 8 vaginal deliveries) with 18 rhesus negative women where the cord remained clamped until placental delivery (8 caesarean section and 10 vaginal deliveries). Maternal venous blood samples were taken before delivery and at a mean of 142min after delivery of the placenta, and analysed using flow cytometry to calculate the size of the feto-maternal transfusion. The statistical analysis was performed using SPSS Version 13 statistical software. The main outcome measure was the quantification of the volume of fetal cells in the maternal circulation before and after delivery. ResultsIn the 72 specimens taken, 40 demonstrated measurable amounts of fetal cells in the maternal circulation. In the 18 women who had placental drainage, the mean (SD) size of the feto-maternal transfusion was 0.50ml (0.79) before and 0.39ml (0.58) after delivery. In the 18 women who had a clamped cord, the mean (SD) feto-maternal transfusion was 0.46ml (0.84) before and 0.78ml (1.1) after delivery. There was no significant difference between the net feto-maternal transfusions in the two groups (Mann–Whitney U 122.5, p 0.19). ConclusionPlacental drainage does not reduce the amount of feto-maternal transfusion and this method of placental delivery is not recommended to reduce feto-maternal transfusion.

Impact of delivery mode and gestational age on haematological parameters in Taiwanese preterm infants

Reference ranges of haematological parameters in preterm infants are limited. The aim of this study is to determine the reference values of haematological parameters in preterm infants in Taiwan, and to assess the impact of gestational age and mode of delivery on these parameters. Medical records were retrospectively reviewed in preterm infants admitted to National Taiwan University Hospital from January 2001 to December 2004. The inclusion criteria included infants with <37 weeks of gestation who had blood sampling within 24 h of birth. The exclusion criteria included those with maternal history of antepartum haemorrhage, chorioamnionitis, fever, sepsis, preeclampsia and hypertension; and perinatal history of twin-to-twin transfusion syndrome, feto-maternal transfusion, injury and infection. Of 568 preterm infants with blood cell counts, 337 were available for analysis. There were trends of increase in red blood cell counts, haemoglobin levels and haematocrit values as gestation increased up to 34 weeks. In contrast, a trend of decrease was noted in mean corpuscular volume values. There was an initial trend of decrease in white blood cell counts and then increased after 31 weeks gestation. The platelet counts were essentially unchanged. Infants born by vaginal delivery generally had higher haematological parameters than those born by Caesarean section at different gestational ages except for mean corpuscular volume values. We established the reference ranges of haematological parameters in Taiwanese preterm infants. Health-care professionals must be cautious in clinical application of the haematological values because of varying antenatal and perinatal risk factors.

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.

Blood group serology

Blood group serology

ABO Fetomaternal Compatibility Poses a Risk for Massive Fetomaternal Transplacental Hemorrhage

In the third trimester, fragility of the placental membrane increases the risk of fetomaternal transplacental hemorrhage (FMH), which can result in severe fetal anemia from the hemorrhage itself or from the subsequent effects of isoimmunization. ABO incompatibility between the mother and fetus is associated with a significantly reduced risk of isoimmunization. The investigators hypothesized that this protective effect might be due to reduced risk of fetomaternal hemorrhage in ABO incompatible mother-fetus pairs, and that ABO compatible pairs might be at increased risk of fetomaternal hemorrhage. Investigators evaluated 8 cases of severe fetomaternal transfusion identified among 17,000 deliveries at a tertiary care center between 2003 and 2007. Blood group compatibility between the mother and fetus was evaluated and the perinatal outcome assessed. The Kleihauer-Betke test was used to diagnose FMH. The mean gestational age in the study population was 35 weeks (range 32–39) and the mean fetal weight was 2750 gm (range 2140–3420). All deliveries were operative. Among the 8 infants, 6 (75%) had adverse outcomes after FMH. Four of the infants were affected by posthypoxic damage of varying severity, and there were 2 perinatal deaths. Seven of the 8 cases had fetomaternal ABO compatibility between the mother and fetus. These findings suggest that ABO compatibility between the mother and fetus significantly increases the risk of severe fetomaternal hemorrhage. For cases with severe fetal anemia, the investigators recommend that resuscitation in utero by intrauterine transfusion should be considered before the 33rd week of gestation.

A case of neonatal alloimmune thrombocytopenia from human platelet antigen 5b incompatibility

Anti-human platelet-specific antigen (HPA) antibody often causes neonatal alloimmune thrombocytopenia (NAIT). The antibody is produced due to the feto-maternal transfusion of incompatible platelets. In this case study, anti-HPA-5b was detected in the serum of a 30-year-old female patient. Using blood or amniotic fluid, the patient's HPA-5 phenotype was determined to be a+b-, whereas those of the husband, son and fetus were a+b+. From these findings, we concluded that there was an incompatibility of maternal and fetal HPA. Cordocentesis was performed at 34 weeks of gestation and the fetal platelet count was sufficient for vaginal delivery. A transfusion of HPA-matched platelet was prepared. The baby was delivered by vaginal delivery and there were no physical signs of thrombocytopenia.

Neutropenia in a preterm involved in fetomaternal transfusion syndrome

UENPS.348 Neutropenia in a preterm involved in fetomaternal transfusion syndrome Francesca Birocchi⁎, Maria Antonietta Marcialis, Melania Puddu, Serena Spada, Marcella Testa, Annalisa Cuccu, Fausto Cossu, Vassilios Fanos Istituto di Patologia e Terapia Intensiva Neonatale Azienda Ospedaliera Universitaria, Cagliari, Italy Centro Regionale per le Microcitemie-Regione Sardegna, Cagliari, Italy Background and aim Neutropenia is frequently observed in newborns. It has been reported that neutropenia occurs in as many as 8% of all patients admitted to the Neonatal Intensive Care Units. Neutropenia has previously been described as a result of a fetomaternal transfusion syndrome, in a neonate showing maternal antibodies against neonatal neutrophil antigens. We report a unique case of a premature with severe, prolonged neutropenia and serious anemia due to fetomaternal transfusion syndrome without maternal antineutrophil antibodies, at least those commonly studied at the present. Materials and methods A 1620 g male infant was born at 36 weeks gestation by cesarian delivery to a 43-year-old gravida. Immediately after birth, the infant showed a severe asphyxia due to a serious anemia (Hb value of 5.6 g%) and was sent to our Department. At the admission he was intubated and the correction of the anemic shock was started. His anemia was normocytic and normocromic with high reticulocyte count and required two blood transfusions to be corrected. The newborn also required intravenous dopamine to correct his heart failure. Results During the first few days of age we observed neutropenia (147/mm) without evidence of infection. Intravenous ampicillin and gentamicin therapy was initiated after blood culture were obtained. Antibiotical and antifungine therapy was carried out for a month despite any report of bacterial growth from the blood cultures. Clinical findings were not suggestive of Chediak-Higashi syndrome. Additional evaluation of neutropenia included the research of antineutrophil antibodies in patient and mother blood samples and genetical analysis to exclude Kostmann syndrome was carried out. As the neutropenia persisted (between 0 and 1044/mm) and the infant remained asymptomatic without any evidence of Kostmann syndrome or alloimmune neutropenia, at the end of the first week of age rhG-CSF was started at 10 μg/kg/d. The neutropenia responded to G-CSF treatment. After 2 months a spontaneous neutrophil increase was noted and a normal neutrophil count was maintained without need of further therapy.

ABO fetomaternal compatibility poses a risk for massive fetomaternal transplacental hemorrhage

Severe fetomaternal transplacental hemorrhage increases the risk of fetal anemia. In the third trimester, the syncytiotrophoblast becomes thinner, especially in areas where it comes into intimate contact with villous capillaries, and forms a vasculosyncytial membrane. Our aim was to determine whether ABO compatibility puts the fetus at a greater risk of severe fetomaternal hemorrhage. Case study. A tertiary care center. Sample and methods. Between 2003 and 2007, we evaluated eight cases of severe fetomaternal transfusion. The Kleihauer-Betke test was used for diagnosis of fetomaternal hemorrhage. We evaluated blood group compatibility between the mother and fetus and assessed the perinatal outcome. The Fischer's factorial test was used for testing a hypothesis. The incidence of adverse outcomes following transplacental hemorrhage was 75% (six of eight). There were two perinatal deaths and four infants were affected by post-hypoxic damage of varying severity. Fetomaternal ABO compatibility was present in seven of the eight cases. The risk of severe fetomaternal hemorrhage was significantly increased when there was ABO compatibility between the mother and fetus. This was associated with a very poor perinatal outcome. We recommend that resuscitation in utero by intrauterine transfusion should be considered before the 33rd week of gestation in cases of severe fetal anemia. In later gestation, urgent cesarean section is required with adequate resuscitation of the newborn.

Autumn leaves and assorted findings

Autumn leaves and assorted findings

Index of Suspicion in the Nursery

Index of Suspicion in the Nursery

Placental Drainage of Fetal Blood at Cesarean Delivery and Feto–Maternal Transfusion

To assess the efficacy of placental drainage of fetal blood at the time of cesarean delivery on the incidence of feto-maternal transfusion. This randomized trial includes 86 gravid women who underwent cesarean delivery. Forty-four women were assigned to the placental drainage group and 42 to the no-drainage group. Placental drainage was accomplished by cutting and milking the umbilical cord until no further blood flow occurred. All placentas were spontaneously expelled. The primary outcome variable, as assessed by preoperative and postoperative Kleihauer-Betke tests, was the amount of fetal blood (greater than or equal to 0.5 mL) in the maternal circulation. The group having placental drainage of fetal blood before placental delivery showed a significantly lower incidence (3 of 44, 6.8%) of feto-maternal transfusion (P=.003) as compared with the undrained group (14 of 42, 33%; relative risk 0.20, 95% confidence interval 0.065-0.65; number needed to treat=4). Placental drainage of fetal blood before spontaneous placental delivery at the time of cesarean delivery significantly reduces the incidence of feto-maternal transfusion. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00470899 I.

CLINICO-PATHOLOGIC CONFERENCE: FETOMATERNAL TRANSFUSION

A case is presented of a newborn infant with severe fetomaternal transfusion, which resulted in profound anemia and early demise.

X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival

AbstractX-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID) is an X-linked recessive disease caused by a mutation in the nuclear factor-κB (NF-κB) essential modulator (NEMO). Here we report an XL-EDA-ID patient with atypical features of very few naive-phenotype T cells and defective mitogen-induced proliferation of peripheral blood mononuclear cells (PBMCs). The patient’s NEMO defect was diagnosed by flow cytometric analysis of intracellular NEMO staining. Specific cell lineages (monocytes and neutrophils) expressed reduced levels of NEMO, but 2 populations of T, B, and NK cells were detected with normal and reduced expression of NEMO. Genomic analysis revealed that duplication of a 4.4-kb sequence ranging from intron 3 to exon 6 caused the reduced expression of NEMO. Polymorphism analysis showed that the patient’s B- and T-cell lines with reduced and normal expression of NEMO had the same X chromosome, indicating that the somatic mosaicism was not due to fetomaternal transfusion but was most likely due to postzygotic reversion. This XLEDA-ID case adds to our understanding of NEMO biology, indicating that NEMO is critical for T-cell development and/or survival in humans as well as in mice. (Blood. 2004;103:4565-4572)