A descriptive single-centre experience of the management and outcome of maternal alloantibodies in pregnancy.

BACKGROUND: Haemolytic disease of the fetus and newborn (HDFN) occurs when maternal IgG alloantibodies to fetal red blood cell antigens cross the placenta, causing haemolysis in the fetus and/or neonate. After delivery, the main concern is hyperbilirubinaemia, which can cause neurological damage. OBJECTIVES: To summarise our current management and outcome data to inform health-care professionals counselling women whose pregnancies are at risk of HDFN and to compare these data with relevant studies. METHODS: This is a retrospective descriptive study of all high-risk pregnancies at risk of HDFN at Guy's and St. Thomas' NHS Foundation Trust (GSTFT) Maternity Unit over a 7-year period. We defined high-risk pregnancies as those in whom anti-D, anti-c, anti-K or high (>32 or doubling strength) titres of all other antibodies were identified. RESULTS: A total of 130 pregnancies in 112 women were followed up. A single alloantibody was found in 93 pregnancies (71.5%) and multiple alloantibodies in 37 pregnancies (28.5%). Anti-D was most commonly encountered (n = 48, 36.9%), followed by anti-c (n = 31, 23.8%) and anti-E (n = 15, 11.5%). In 65 of 130 pregnancies (50%), antibody concentrations triggered scans to screen for fetal anaemia. Of 130 pregnancies, 6 (4.6%) required intrauterine transfusions, and 31 of 130 (26%) neonates required post-natal intervention. Overall, morbidity was 0.1% and mortality 0.002%. CONCLUSIONS: This study demonstrates that morbidity and mortality caused by HDFN is minimal. These results are reassuring for women at risk of HDFN as even severely affected cases are successfully managed in most instances. Further studies are needed to identify predictors of disease severity.

The importance of antenatal prevention of RhD immunisation in the first pregnancy.

BACKGROUND: The aim of this study was to examine which pregnancies are associated with RhD immunisation and haemolytic disease of foetus and newborn (HDFN) when postnatal RhD prophylaxis is applied. MATERIAL AND METHODS: This retrospective cohort study included pregnancies with RhD immunisation; each of the pregnant women received anti-D immunoglobulin after delivery, miscarriage or invasive antenatal diagnostic procedures. For each pregnancy we analysed the order of pregnancy that caused immunisation as well as the order of the monitored pregnancy and whether the anti-D antibodies caused HDFN. RESULTS: Anti-D antibody was detected in 1.2% of RhD-negative pregnancies. Out of 89 monitored pregnancies, 56 (63%) were immunised by the first pregnancy, 21 (24%) by the second one, and 12 (13%) by subsequent pregnancies. HDFN occurred in 28 cases; 25 of them were the consequence of the immunisation in the first pregnancy. The most severe cases of HDFN, perinatal death (n=2) and intrauterine transfusion (n=7) were consequence of immunisation during the first pregnancy. Significantly more cases of HDFN were caused by immunisation in the first pregnancy than by immunisation in subsequent pregnancies (χ(2)=12, p<0.01). CONCLUSION: RhD immunisation could be reduced in more than half cases by administering anti-D immunoglobulin at the beginning of the third trimester of pregnancy, especially the first pregnancy.

Alloimmunisation during pregnancy in Greece: need for nationwide HDFN prevention programme.

AIM/OBJECTIVES: To access the incidence and specificity of maternal red blood cells alloimmunisation and its relevant clinical impact in Greece. BACKGROUND: The rate of alloimmunisation in pregnant women in Greece is unknown. MATERIALS/METHODS: We performed a 4-year study in two tertiary hospitals in Greece. Demographics, transfusion and obstetric history were analysed. Maternal alloimmunisation was detected with indirect anti-globulin test. RESULTS: We investigated 4368 pregnant women. Of which 3292 (75·37%) were Greek and 1076 (24·63%) were migrants. In 39 alloimmunised women, 41 alloantibodies were detected (0·89%). The incidence of alloimmunisation was 0·66% (22/3292) in Greeks and 1·76% (17/1076) in migrants (P = 0·01). Anti-D was the most frequent alloantibody (0·18%). Anti-D was more frequent in migrants; 5·76% compared to 0·56% in Greek RhD negative women (P = 0·002). Other antibody specificities in declining frequency rank were anti-K, anti-E, anti-Lea, anti-M, anti-c, anti-Ce, anti-Jka, anti-Jkb and anti-C. Primiparae vs para >2 and past history of blood transfusion were significantly associated with alloimmunisation during pregnancy (P = 0·0088, P < 0·0001, respectively). CONCLUSIONS: Our results depict differences in the delivery of health care between migrants and Greek women, as well as the heterogeneity in practices for the prevention of haemolytic disease of foetus and newborn in Greece and highlight the need for the implementation of nationwide guidelines.

[Foeto-maternal haemorrhage--detection and quantification]. / Plodowo-matczyny przeciek krwi--wykrywanie i ocena ilosciowa.

Quantification of foetal RBCs in maternal blood samples should be essential to establish the dose of prophylactic anti-RhD immunoglobulin. In practice, the volume of foetomaternal haemorrhage (FMH) is rarely calculated and routine anti-RhD doses vary in the world from 100 microg to 300 microg. In Poland the postpartum dose of IgG anti-D is 150 microg, and there is no antepartum prophylaxis. The aim of this review paper is to present that detection and quantification of FMH are important and introduction of some tests for it evaluation is necessary in Poland. Taking into consideration many reports and our preliminary experiences we show principles of some methods and techniques, their advantages and limits. As immunohaematologists we indicate very important multidisciplinary problem which concerns transfusiologists, gynaecologists and haematologists.

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

OBJECTIVES: To 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 DESIGN: A 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 142 min 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. RESULTS: In 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 0.50 ml (0.79) before and 0.39 ml (0.58) after delivery. In the 18 women who had a clamped cord, the mean (SD) feto-maternal transfusion was 0.46 ml (0.84) before and 0.78 ml (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). CONCLUSION: Placental drainage does not reduce the amount of feto-maternal transfusion and this method of placental delivery is not recommended to reduce feto-maternal transfusion.

[Immunohematological surveillance of the pregnant woman: new prevention policy]. / Suivi immunohématologique des femmes enceintes: nouvelles recommandations.

Despite the generalization of immunoprophylaxis by anti-RH immunoglobulins over 40 years, fetomaternal incompatibility due to RH1 antigen (RhD) is not completely eradicated, although perinatal consequences might be extremely serious. Additionally, allo-immunizations against other antigens, especially anti-RH4 (anti-c) and anti-KEL1 (anti-Kell), may cause severe haemolytic disease. Follow-up of allo-immunization during pregnancy and its prevention are therefore still a concern for all pregnant women. Immunohaematological tests used in antenatal patients are under practice for a long time. However, despite significant progress, it is clear that these tests provide only an indirect indication and will only help the obstetrician, in conjunction with over fetal parameters, to assess the severity of the haemolytic disease. Since almost two decades, fetal RHD genotyping became a reality, first using amniocytes, but more recently by analyzing fetal DNA present in the maternal plasma. RH prophylaxis concerns RH:-1 women, who are non-sensitized against RH1 antigen during and at the end of their pregnancy with a RH1 child. RH prophylaxis includes targeted prophylaxis after foetomaternal haemorrhage and now routine antenatal RH prophylaxis at 28 gestation weeks. Indications for RH prophylaxis and immunohaematological testing to assure an efficient therapeutic prevention have been summarized in France through specific recommendations of the National College of Gynecologists and Obstetricians.

Resultados del estudio del genotipado RhD fetal en plasma materno / Results of the study of the fetal RHD genotyping in maternal plasma

Introducción. Se evalúa la eficacia en la determinacióndel RhD fetal a partir de sangre materna.Material y métodos. Estudio prospectivo y descriptivo.Se obtuvieron 90 muestras sanguíneas de gestantes RhD negativo con pareja RhD positiva que controlaron su gestación en nuestro centro entre septiembre de 2004 y enero de 2006, previa autorización y consentimiento expreso de las pacientes. Las muestras de sangre materna se enviaron al laboratorio de biología molecular para cuantificar los exones 7 y 10 del gen RHD. Posterior-mente se compararon los resultados obtenidos del genotipado RHD fetal con el fenotipo de RhDde los recién nacidos.Resultados. El genotipado informó de 69 fetos RhD positivo (76,6%) y 21 RhD negativo (23,3%). Se obtuvieron seis falsos positivos y tres falsos negativos. La sensibilidad de la prueba fue del 95,45% y la especificidad del 75%.Discusión. Se detecta una elevada tasa de falsos negativos, que podría explicarse por diferentes razones relacionadas con la obtención y la manipulación de la muestra (semana de gestación, técnica de extracción y técnica de amplificación).Conclusiones. La elevada tasa de falsos negativos en ladeterminación del RhD fetal a partir de sangre materna, que corresponde a casos susceptibles de aloinmunización materna y por tanto de desarrollar enfermedad hemolítica del feto recién nacido, obliga a una correcta reevaluación de la técnica empleada y de la interpre-tación de los resultados

Introduction. We evaluate the effectiveness in thedetermination of the foetal RhD from the mother’s blood.Material and methods. 90 Rh negative pregnant womenwith positive RhD couples allowed us, by signing aconsent form, to use their blood samples for this study. All these patients have been monitored in our centre from September 2004 to January 2006. The maternal blood samples were sent to the molecular biology laboratory for the quantification of exones 7 and 10 of the RhD’s gene. After that, the results obtained from the foetal RhD genotypes were compared with the phenotypes of the newborn’s RhD.Results. The results of the genotyping showed that69 (76,6%) of the foetuses were RhD positive, whereas 21(23,3 %) were RhD negative. The sensitivity of the testwas 95.45% and the specificity 75%. Six tests came outfalse positives and three false negatives.Discussion. Several factors related to the obtainingof the sample and the way it is manipulated (pregnancyweek, the extraction or amplification technique) couldexplain the high rate of false negatives.Conclusion. The high prevalence of false negativesdetected after a foetal RhD test on maternal blood forcesus to reconsider the used technique and to improve theway we interpret the results, taking into account thatthere is a risk of maternal isoimmunization and consequently an haemolytic disease on the newborn (AU)

Placental drainage of fetal blood at cesarean delivery and feto maternal transfusion: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of placental drainage of fetal blood at the time of cesarean delivery on the incidence of feto-maternal transfusion. METHODS: 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. RESULTS: 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). CONCLUSION: Placental drainage of fetal blood before spontaneous placental delivery at the time of cesarean delivery significantly reduces the incidence of feto-maternal transfusion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00470899 LEVEL OF EVIDENCE: I.

Hemorragia fetomaterna masiva. Caso clínico / Massive maternofoetal haemorrhage. A clinical case

La hemorragia fetomaterna masiva es un cuadro clínico grave que, en la mayoría de los casos, acontece en gestaciones cercanas al término sin factores de riesgo; es por ello que este diagnóstico se debería considerar en cualquier paciente con disminución de los movimientos fetales, registro cardiotocográfico con un patrón sinusoidal y un incremento de la velocidad de flujo de la arteria cerebral media (AU)

Massive feto-maternal haemorrhage is a grave clinical picture which, in the majority of cases, happens in gestations near to term with no risk factors. It is for this reason that this diagnosis should be considered in any patient with diminished foetal movements, cardiotocogram with a sinusoidal pattern and an increase in the speed of flow of the middle cerebral artery (AU)

Risk factors for fetal-to-maternal transfusion in Rh D-negative women--results of a prospective study on 942 pregnant women.

AIMS: To investigate the incidence of severe fetal-to-maternal transfusion after delivery and to identify risk factors. MATERIAL AND METHODS: In a prospective study at the Department of Obstetrics, Charité, Campus Virchow-Klinikum, Berlin, Germany, we analyzed the incidence of severe fetal-to-maternal transfusion (>10 ml) and fetal-to-maternal hemorrhage (>25 ml) in Rh D-negative pregnant women after delivery of Rh D-positive infants. 942 women were included in the study and Kleihauer-Betke tests were performed. The results were compared to perinatal data. RESULTS: Fetal-to-maternal hemorrhage occurred in 13 cases out of 942 (incidence of 1.3%) and severe fetal-to-maternal transfusion in 61 cases (6.5%). In all of the cases with fetal-to-maternal hemorrhage, mothers were compatible with their infants in ABO-system. The incidence of fetal-to-maternal transfusion and its severe form was significantly higher in twin pregnancies (7/21 cases and 5/21 cases respectively, 33.3% and 23.8%) than in singleton pregnancies (22.5%, and 5.9%, P<0.001). All other factors, such as maternal age, parity, ethnicity, mode of delivery, presentation, duration of first and second stage of labor, CTG, or Apgar score were not associated with an increased risk of severe fetal-to-maternal transfusion. CONCLUSIONS: Twin pregnancy is the only independent risk factor for severe fetal-to-maternal transfusion. ABO-incompatibility between mother and infant seems to be protective against Rh D-alloimmunization.

Neonato con anemia crónica / Newborn chronic anemia

Introducción. la transfusión feto-materna (TFM) o hemorragia feto-materna (HFM) es una causa infrecuente de anemia en recién nacidos que puede presentarse desde formas asintomáticas hasta otras con importante patología dependiendo del tiempo de instauración. Observación clínica. Recién nacido de minutos de vida, asintomático, que presenta intensa palidez cutánea. En el análisis inicial destacan valores de hemoglobina de 4.9 gr/dL y hematocrito de 16.3%. El test de Kleihauer materno confirman la sospecha diagnóstica de transfusión feto-materna. La terapia transfusional resulta clave para la resolución de la anemia. Comentarios. La TFM es una enfermedad de etiología poco clara que implica el paso de sangre fetal a la madre durante la gestación o en el momento del parto. La presentación clínica es muy diversa y variará según la severidad y rapidez de instauración de la hemorragia. La evolución y el pronóstico dependerán de un buen diagnóstico precoz y de la respuesta al tratamiento con transfusión de concentrado de hematíes. En nuestro caso, la cronicidad del cuadro y el tratamiento con la transfusión han proporcionado una buena evolución (AU)

Introduction. Fetomaternal transfusion (FMT) or fetomaternal hemorrhage (FMH) is a rare cause of neonatal anemia with a wide spectrum of clinical presentations, ranging from no symptoms to severe clinical deterioration, depending on the time of its occurrence. Clinical observation. Newborn with pallor and no other abnormal findings. Laboratory evaluation revealed hemoglobin of 4.9 g/dL and hematocrit of 16.3%. The Kleihauer test performed in the mother confirmed the diagnosis of FMT. Comments. FMT is a phenomenon of unclear etiology that results from the transfer of fetal blood into the mother during the pregnancy or at the time of delivery. The type and severity of the clinical presentation correlates with the amount and timing of the transfusion. An early diagnosis, a judicious use of transfusions of packed red blood cells, and the clinical response to replacement therapy are important prognostic factors. In the case presented here, the chronic nature of the condition and the early diagnosis and treatment resulted in a good outcome (AU)

Is the incidence of fetal-to-maternal hemorrhage increased in patients with third-trimester bleeding?

OBJECTIVE: If a pregnancy is complicated by third-trimester bleeding, is there a higher risk of fetal-to-maternal hemorrhage that might necessitate the administration of additional anti-D immune globulin to prevent alloimmunization in the patient who is Rh D-negative? The study objective was to analyze prospectively the incidence of fetal-to-maternal hemorrhage in pregnancies that were complicated by third trimester bleeding compared with three control groups. STUDY DESIGN: Pregnancies that were complicated by third-trimester bleeding, preterm premature rupture of the membranes, and preterm labor were identified prospectively on admission. A group of preterm patients with no complications was also collected prospectively. Patients with any history and/or clinical evidence of trauma were excluded. Kleihauer-Betke tests were performed with all patients, and the results were blinded until study completion. Sample size calculations were performed to determine the minimum number of cases needed in each group. RESULTS: A total of 403 patients were collected during the study period: 91 patients had third-trimester bleeding, 101 patients had preterm premature rupture of the membranes, 116 patients had preterm labor, and 95 patients were in the no complication group. There was no statistical difference identified in the Kleihauer-Betke test results between any of the study groups. CONCLUSION: The incidence of fetal-to-maternal hemorrhage does not appear to be increased in pregnancies that are complicated by third-trimester bleeding when compared to noncomplicated control subjects or to other obstetrically complicated pregnancies. This information would suggest that the routine administration of additional anti-D immune globulin (beyond the current recommended protocol) to women who are Rh D-negative whose pregnancies are complicated by third-trimester bleeding is not indicated.

Fetal-maternal hemorrhage detection in Ontario.

The results from fetal-maternal hemorrhage (FMH) detection and quantitation external quality assessment surveys conducted in Ontario indicate that the rosette test had a sensitivity and specificity for an FMH of more than 10 mL of 1.0 and 0.75, respectively, compared with 0.96 and 0.92, respectively, for acid elution. With FMH quantitation, the percentage error of the mean from the target FMH was 20% or more in 7 of 8 surveys, and coefficients of variation ranged from 39.5% to 71.8%. Inadequate Rho(D) immune globulin prophylaxis could have occurred in 19.4% of the challenges with an FMH of more than 10 mL. The rosette and acid elution techniques are both effective for the detection or exclusion of FMH, but acid elution lacks adequate accuracy and precision for reliable FMH quantitation. Furthermore, a strategy of prescribing an extra 1,500-IU Rho(D) immune globulin dose, in addition to the dose required to treat the volume of fetal blood detected, is an effective strategy to overcome the limitations of FMH quantitation by acid elution.

Intrapartum fetomaternal bleeding in Rh-negative women.

In a series of 1206 consecutive Rh-negative women who delivered Rh-positive infants, fetal erythrocytes were found in the maternal blood of 175 (14.5%) during the postpartum period. In 12 (1.0%) there was evidence of a larger fetomaternal hamorrhage than would be neutralized by a single 300-microgram dose of Rh-immune globulin. Except for manual removal of the placenta, no correlation was found between large fetomaternal hemorrhages and obstetric manipulations, complications, or surgery. Thus, the authors believe that all Rh-negative patients should be screened post partum to ascertain the adequacy of Rh-immune globulin prophylaxis.