Changes in fetal myocardial performance index following intravascular transfusion: preliminary report.

OBJECTIVE: To investigate the changes in fetal left ventricle myocardial performance index (MPI) following intrauterine intravascular transfusion (IUT). METHODS: Prospective study, including 25 IUT performed in 13 singleton pregnancies with maternal Rh D alloimmune disease. Left ventricle MPI was evaluated prior to transfusion and repeated 24 h after each procedure. Delta MPI was calculated as the difference between post- and pre-transfusion MPI z-scores. Multilevel regression analysis was used to examine the association between delta MPI and gestational age at procedure, fetal middle cerebral artery peak velocity MoM, pre- and post-MPI and hemoglobin z-score values, the volume of blood transfused and feto-placental volume percentage expansion. Adjustments were made for repeated measurements within the same fetus, and across different time points. The significance level was set as 0.05. RESULTS: MPI z-score values increased significantly following transfusion (delta MPI = 1.10 ± 2.47, p=0.036). Delta MPI showed a significant correlation with gestational age at transfusion (r= -0.47, p=0.018), pre-transfusion MPI z-score (r= -0.50, p=0.012) and feto-placental volume percentage expansion (r= -0.41, p=0.044). CONCLUSION: Left ventricle MPI increases significantly after intrauterine blood transfusion and greater changes are associated with procedures at an earlier gestational age, lower pre-transfusion MPI z-scores and smaller feto-placental volume expansion.

Nivel de conocimientos de los obstetras acerca del diagnóstico y tratamiento de la isoinmunización materna: Estudio de corte transversal en Bogotá (Colombia), 2012-2013 / Level of knowledge among obstetricians regarding diagnosis and treatment of maternal isoimmunization: Cross-sectional study in Bogotá (Colombia), 2012-2013

Objetivo: describir el nivel de conocimientos acerca del diagnóstico, tratamiento y pronóstico de la isoinmunización materna entre los especialistas de Ginecología y Obstetricia afiliados a la Asociación Bogotana de Perinatología (ABP). Materiales y métodos: estudio descriptivo de corte transversal. Entre noviembre de 2012 y marzo de 2013, se aplicó una encuesta elaborada por especialistas en Medicina Materno-Fetal (MMF). Se excluyeron los profesionales que ejercen su actividad fuera del territorio nacional, aquellos que no han practicado la obstetricia durante los últimos diez años y a quienes no suministraron la totalidad de la información requerida. El instrumento estuvo compuesto por 18 preguntas organizadas en tres dominios: características sociodemográficas, información sobre la práctica clínica y conocimientos. Se utilizó estadística descriptiva para el análisis en la materia. Resultados: el instrumento se aplicó a 220 profesionales de los cuales 127 (57,7 %) respondieron la encuesta en su totalidad y fueron incluidos en el análisis. El 32 % de los obstetras y el 45 % de los especialistas en MMF identificaron correctamente el punto de corte para el coombs indirecto. El 43 y 62 % de los obstetras y especialistas en MMF reconocieron el papel de la velocimetría de la arteria cerebral media para el diagnóstico de anemia fetal, y el 82 y 76 % respectivamente la utilizarían en el seguimiento del feto anémico. Tan solo el 76 % de los obstetras y el 66 % de los especialistas en MMF reconocen las indicaciones de culminar la gestación en caso de anemia fetal, en tanto que el 90 y 97 % (respectivamente) identificaron cuándo realizar cordocentesis y transfusión in utero. Finalmente, el 37 % de los obstetras y el 48 % de los especialistas en MMF no reconocen a la curva de Queenan-Liley como una alternativa cuando no hay acceso al Doppler fetal. Conclusión: existe una importante variabilidad con respecto al nivel de conocimientos de los obstetras y especialistas en MMF en cuanto al diagnóstico, tratamiento y seguimiento de las gestantes con isoinmunización. Se requieren más estudios que caractericen la variabilidad en la práctica clínica acerca del diagnóstico y tratamiento de la isoinmunización materna en Colombia.

Objective: To describe the level of knowledge regarding the diagnosis, treatment and prognosis of maternal isoimmunisation among Gynaecology and Obstetrics specialists, members of ABP (Asociación Bogotana de Perinatología). Materials and methods: Cross-sectional descriptive study. A questionnaire prepared by specialists in Maternal and Foetal Medicine (MFM) was administered between November 2012 and March 2013. Professionals practicing outside the national territory, those who had not practiced over the past ten years, and those who did not provide all the information required were excluded. The tool consisted of 18 questions organized in three domains: socio-demographic characteristics, information about clinical practice, and knowledge of the subject. A descriptive statistical analysis was used. Results: Of the 220 practitioners who were given the questionnaire, 127 (57.7%) completed the survey and were included in the analysis. The cut-off point for the indirect Coombs was correctly identified by 32% of the obstetricians and by 45% of the specialists in MFM. The role of middle cerebral artery velocimetry for the diagnosis of foetal anaemia was recognized by 43% and 62% of obstetricians and specialists in MFM, and 82% and 76%, respectively, would use it for the follow-up of foetuses with anaemia. Only 76% of obstetricians and 66% of MFM specialists recognized the indications for delivering the baby in cases of foetal anaemia, whereas 90% and 97%, respectively, identified the timing for cordocentesis and in utero transfusion. Finally, 37% of obstetricians and 48% of MFM specialists did not recognize the Queenan-Liley curve as an option in cases where there is no access to foetal Doppler. Conclusion: There is an important variability in the level of knowledge among obstetricians and MFM specialists regarding the diagnosis, treatment and follow-up of pregnant women with isoimmunisation. Additional studies are required to characterize the variability in clinical practice regarding the diagnosis and treatment of maternal isoimmunisation in Colombia.

Manejo de la embarazada con isoinmunización por anticuerpos irregulares / Pregnant management by isoimmunized irregular antibodies

La isoinmunización eritrocitaria feto-materna se define como la presencia de anticuerpos maternos dirigidos contra antígenos presentes en los glóbulos rojos fetales. Los anticuerpos maternos pueden atravesar la barrera placentaria y provocar hemólisis de los glóbulos rojos fetales produciendo anemia hemolítica e hiperbilirrubinemia, características de la enfermedad hemolítica perinatal (EHP). La principal causa de EHP es la incompatibilidad ABO, seguida de la isoinmunización por RhD; esta última ha disminuido su incidencia dado el amplio uso de inmunoglobulina anti D. Sin embargo, el glóbulo rojo tiene más de 400 antígenos, muchos de ellos (>50) capaces de producir isoinmunización y EHP. En este artículo, revisamos la evidencia y proponemos un algoritmo de manejo y seguimiento de las embarazadas con isoinmunización por anticuerpos irregulares. En la isoinmunización por anticuerpos irregulares, los títulos de anticuerpos maternos no se correlacionan con la gravedad de la enfermedad. La anemia en la EHP por anticuerpos anti-Kell es secundaria a una supresión de la eritroblastosis fetal a diferencia del resto de los sistemas que producen anemia hemolítica. Recomendamos efectuar tamizaje de todas las pacientes en el control prenatal, solicitando grupo sanguíneo, Rh y test de Coombs indirecto. En las pacientes Rh (+) con test de Coombs indirecto positivo es necesario identificar los anticuerpos irregulares. En caso de tener isoinmunización por anticuerpos irregulares con riesgo de EHP, derivar a una unidad de alto riesgo obstétrico para realizar seguimiento de la aparición de anemia fetal midiendo de modo seriado el peak sistólico de la arteria cerebral media. Si se detecta anemia fetal, debemos planificar una cordocentesis para confirmar el diagnóstico y tratar la anemia.

The fetomaternal erythrocyte isoimmunization is defined as the presence of maternal antibodies directed against antigens present in fetal red blood cells. Maternal antibodies can cross the placenta and cause hemolysis of fetal red blood cells causing hyperbilirubinemia and hemolytic anemia, known as perinatal hemolytic disease (PHD). The main cause of PHD is ABO incompatibility, followed by RhD isoimmunization. The latter has decreased its incidence since the widespread use of anti-D immunoglobulin. However, the red cell has more than 400 antigens; many of them (>50) can lead to isoimmunization and PHD. In this article, we review the evidence and propose an algorithm for the management and monitoring of pregnant women with irregular antibodies isoimmunization. In the isoimmunization by irregular antibodies, maternal antibody titers do not correlate with the severity of the disease. Anemia in PHD by anti-Kell is secondary to suppression of fetal erythroblastosis unlike other systems that produce hemolytic anemia. We suggest the screening of all patients in the prenatal control with blood group, Rh and indirect Coombs test. In the Rh (+) patients with positive indirect Coombs test, irregular antibodies should be identified. In case of immunization by irregular antibodies in risk of PHD, the women should be referred to a high-risk obstetrics where the appearance of fetal anemia should be seek by measuring systolic peak of middle cerebral artery. If anemia is detected full confirmation of diagnosis and treatment should be effected by cordocentesis.

The effect of fetal anemia on fetal cardiac troponin T in pregnancies complicated by RhD alloimmunization.

OBJECTIVE: To study the effect of fetal anemia on fetal cardiac troponin T (cTnT) in pregnancies complicated by RhD alloimmunization. METHOD: Twenty pregnant women complicated by RhD alloimmunization who underwent intrauterine transfusion (IUT) for treatment of fetal anemia were studied. Immediately before IUT, fetal blood was obtained for hemoglobin and cTnT measurements. RESULTS: Complete measurements of hemoglobin and cTnT before IUT were obtained in 49 procedures, of which 20 were first-time. The regression analysis between hemoglobin z-score and cTnT values in 49 procedures showed significant negative correlation (r = -0.43, p = 0.002, Regression equation Log(cTnT) = -1.5057 + -0.07563 Hb z-score). Cardiac TnT values before first IUT were significantly associated with perinatal death. In the group with elevated cTnT (n = 7), fetal or neonatal death was more frequent (2 IUD and 2 NND) when compared to normal cTnT group (n = 13, 1 IUD) (57.1 vs. 7.7%, p = 0.031, Fisher's exact test). CONCLUSION: Fetal blood concentration of cTnT before IUT was negatively correlated to hemoglobin z-score, and levels of cTnT help to manage the pregnancies complicated by RhD alloimmunization.

Resultado neonatal e infantil de niños con y sin transfusión intrauterina por isoinmunización Rh durante el embarazo / Neonatal outcome of children with and without intrauterine transfusion for Rh isoimmunization during pregnancy

Objetivo: Comparar la morbilidad neonatal y a seis meses de vida de hijos de pacientes con isoinmunización Rh que recibieron al menos una transfusión intrauterina (TIU), con aquellos que no la requirieron. Método: Estudio de caso y control de pacientes con diagnóstico de isoinmunización Rh controladas en la Unidad de Medicina Fetal del Hospital Clínico Universidad de Chile. Se comparó el resultado perinatal y hasta 6 meses de vida de recién nacidos (RN) con TIU (9 casos) y sin TIU (14 casos) entre los años 2004 y 2009. Resultados: Aunque la sobrevida a los 6 meses de los fetos con TIU fue alrededor de un 80 por ciento, solo una muerte puede atribuirse a la severidad de su condición de base. Los RN con TIU nacieron a una menor edad gestacional que los que no requirieron este tratamiento (34,4 +/- 2,2 sem vs. 37,4 +/- 0,6 sem; p=0,003). Al evaluar el manejo neonatal inmediato se observa que el 60 por ciento de los RN isoinmunizados sin TIU requirieron ser hospitalizados y requirieron fototerapia, mientras que todos los RN con antecedente de TIU fueron hospitalizados, recibieron fototerapia y 30 por ciento requirió una exanguineo transfusión. A los 6 meses de vida, 75 por ciento y 20 por ciento de los RN isoinmunizados, con y sin TIU, fueron hospitalizados para una nueva transfusión de GR y/o fototerapia, respectivamente. Conclusión: La isoinmunización Rh es una patología de alto riesgo, pero la terapia intrauterina, en los casos con anemia moderada y severa, permite llegar a edades gestacionales que dan una adecuada sobrevida.

Objective: To compare neonatal and six months of life morbidity of babies affected by Rh isoimmunization during pregnancy that required at least one intrauterine blood transfusion, with babies that did not required that procedure. Methods: Case control study of patients with diagnosis of Rh isoimmunization under control in the Fetal Medicine Unit at the University of Chile Hospital. Perinatal and until 6 months of life outcomes of isoimmunized newborns (NB) with (9 cases) and without intrauterine transfusion (IUT) (14 cases) between years 2004 and 2009 were compared. Results: Although six months of life survival of IUT babies was about 80 percent only one death was related to the severity of isoimmunization. Isoimmunized babies with IUT were delivered at a lower gestational age than those without IUT (34.4 +/- 2.2 vs. 37.4 +/- 0.6 weeks; p=0.003). At the immediate neonatal period only 60 percent of isoimmunized babies without IUT required hospitalization and phototherapy, in contrast to IUT babies where all of them were hospitalized and required phototherapy, and 30 percent required exchange transfusion. Until six months of life, 75 percent and 20 percent of NB with and without IUT required another hospitalization for a new transfusion and/or phototherapy respectively. Conclusion: Rh isoimmunization is a high risk disease, but intrauterine therapy in cases with moderate and severe fetal anemia increases gestational age at delivery with good survival rates.

Prediction of the rate of decline in fetal hemoglobin levels between first and second transfusions in red cell alloimmune disease.

OBJECTIVE: To determine variables that predict the rate of decline in fetal hemoglobin levels in alloimmune disease. METHOD: Retrospective review of singleton pregnancies that underwent first and second intrauterine transfusions for treatment of fetal anemia because of maternal Rh alloimmunization in a tertiary referral center. RESULTS: Forty-one first intrauterine transfusions were performed at 26.1 weeks (standard deviation, SD, 4.6), mean volume of blood transfused was 44.4 mL (SD 23.5) and estimated feto-placental volume expansion was 51.3% (SD 14.5%). Between first and second transfusion, hemoglobin levels reduced on average 0.40 g/dl/day (SD 0.25). Stepwise multiple regression analysis demonstrated that this rate significantly correlated with hemoglobin levels after the first transfusion, the interval between both procedures, and middle cerebral artery systolic velocity before the second transfusion. CONCLUSION: The rate of decline in fetal hemoglobin levels between first and second transfusions in alloimmune disease can be predicted by a combination of hemoglobin levels after the first transfusion, interval between both procedures, and middle cerebral artery systolic velocity before the second transfusion.

[Anti-D isoimmunization severe in a twin pregnancy. Case report]. / Isoinmunización grave anti-D en una gestación gemelar. Caso clínico.

Perinatal hemolytic disease occurs secondary to a hemolytic phenomenon of immune origin resulting in fetal or neonatal anemia. A 38-year-old pregnant woman was referred to the Department of high risk Obstetrics, Hospital Universitario La Paz Madrid because of presenting a dichorionic diamniotic twin pregnancy spontaneously, pre-pregnancy diabetes poorly controlled and severe alloinmunization anti-D. Her first pregnancy ended in a normal delivery at term; in the period of 4 years, she has three newborn with 36, 34 and 40 weeks respectively, who die with a week of life. After that, two intrauterine fetal death occur at 26 weeks of gestation. The patient who is RhD negative, suffers anti-D inmunization with a antibody titration of 1/1024 with 14 weeks of gestation. Twelve plasmapheresis, eight doses of anti-D inmunoglobulins and intrauterine transfusions has been the treatment received. A severe anemia is found during the ultrasound control of the middLe cerebral artery peak systolic velocity in both twins since the 16th week. It remains stable thanks to the treatment. Finally at the 28th week of gestation, pregnancy is terminated with a cesarean section. The twins are born alive and premature, but with good general state. The measurement of the middle cerebral artery peak systolic velocity predicts moderate-severe fetal anemia cases, which are the most important in the clinical management because of the need of active treatment or finish the pregnancy.

Predictive factors of perinatal mortality in transfused fetuses due to maternal alloimmunization: what really matters?

INTRODUCTION: Alloimmunization is the main cause of fetal anemia. There are not many consistent analyses associating antenatal parameters to perinatal mortality in transfused fetuses due to maternal alloimmunization. The study aimed to determine the prognostic variables related to perinatal death. MATERIAL AND METHODS: A cohort study analyzed 128 fetuses treated with intrauterine transfusion (IUT), until the early neonatal period. Perinatal mortality was associated with prognostic conditions related to prematurity, severity of fetal anemia and IUT procedure by univariated logistic regression. Multiple logistic regression was used to compute the odds ratio (OR) for adjusting the hemoglobin deficit at the last IUT, gestational age at birth, complications of IUT, antenatal corticosteroid and hydrops. RESULTS: Perinatal mortality rate found in this study was 18.1%. The hemoglobin deficit at the last IUT (OR: 1.26, 95% CI: 1.04-1.53), gestational age at birth (OR: 0.53, 95% CI: 0.38-0.74) and the presence of transfusional complications (OR: 5.43, 95% CI: 142-20.76) were significant in predicting fetal death. CONCLUSION: Perinatal mortality prediction in transfused fetuses is not associated only to severity of anemia, but also to the risks of IUT and prematurity.

Relationship between obstetric history and Rh(D) alloimmunization severity.

BACKGROUND: To evaluate the relationship between obstetric history and Rh(D) alloimmunization severity, employing the gestational age at the first intrauterine fetal transfusion (IUT) as an indicator of this severity. METHODS: From 1996 to 2006, Rh(D) alloimmunized pregnancies submitted to IUT had their data assessed. Gestational age at the first IUT was modeled as a linear outcome. The associations between obstetric history variables, anti-Rh(D) antibodies titer and gestational age at the first IUT were analyzed. Statistics are presented with 95% confidence intervals (P < 0.05). RESULTS: A total of 82 non-hydropic anemic fetuses, ensuing in 92.7% (n = 76) of perinatal survival, were submitted to IUT. Nineteen (23,2%) pregnant women did not present with any previous stillbirth, neonatal death, IUT, hydrops or neonatal exchange transfusion (group 1); and 63 (76.8%) reported at least one of these events (group 2). Gestational age at the first IUT differed significantly between the groups (P = 0.0001). For group 1, it ranged from 24 to 35 weeks (median 32.5 weeks), whereas for group 2 it ranged from 19 to 34 weeks (median 27 weeks). In the multivariated analysis, previous neonatal death (P = 0.040), previous IUT (P = 0.000) and previous neonatal exchange transfusion (P = 0.036) were independently associated with the gestational age at the first IUT. CONCLUSIONS: The evaluation of the obstetrical history is an important diagnostic tool for predicting Rh(D) alloimmunization severity. Alloimmunized pregnant women who reported previous neonatal death(s), neonatal exchange transfusion(s) or IUT(s) should receive a closer fetal surveillance due to the risk of a higher rate of fetal hemolysis and the need of an earlier IUT.

Fetal hematocrit decrease after repeated intravascular transfusions in alloimmunized pregnancies.

BACKGROUND: The aim of this study is to evaluate the fetal hematocrit (Hct) decrease along repeated intravascular intrauterine fetal transfusions (IUTs) and test the hypothesis that, after consecutive IUTs, there is a lower Hct drop off. METHODS: From July 1996 to June 2006, pregnancies submitted to IUT for fetal hemolytic anemia treatment had their data assessed. The daily rate of decrease in fetal Hct was calculated by dividing the difference between the posttransfusion Hct of the previous IUT and the pretransfusion Hct of the current IUT, by the number of days between the transfusions. Fetuses with other abnormalities or submitted to intraperitoneal transfusions were excluded. RESULTS: Eighty-one women were submitted to IUT during the alluded period, ensuing 296 intrauterine transfusions. The perinatal survival was 89.9% (n = 80), with 92.0% (n = 69) of nonhydropic fetuses survival. Hydropic fetuses showed higher hematocrit drop off than nonhydropic ones (P < 0.01). Compared to the interval between the first and second IUT, the daily fetal Hct decline was lower after the third one (P < 0.05). Stratifying by the presence of hydrops, nonhydropic fetuses showed a smaller decrease at the third and fourth intervals (P < 0.01 and P < 0.05, respectively). Among hydropic fetuses, there is a trend of smaller Hct decrease along successive IUTs (interval 3, P = 0.08; interval 4, P = 0.07; and interval 5, P = 0.10). CONCLUSIONS: Following some IUTs, fetal hematocrit decrease is lower and larger intervals between the transfusions could be accomplished. Multicenter studies should investigate an algorithm for timing subsequent IUTs, considering Doppler values, estimated fetal hematocrit decline and other parameters.

Perinatal mortality in Rh alloimmunized patients.

OBJECTIVE: Evaluate and compare the perinatal mortality of Rh-negative pregnancies managed at São Paulo Federal University during a 9-year period, using either amniocentesis or middle cerebral artery peak systolic velocity. METHOD: Descriptive observational study involving 291 consecutive Rh-negative pregnancies managed between January 1995 and January 2004. The perinatal mortality of 99 alloimmunized patients was compared with 192 Rh-negative unimmunized patients (control group). The perinatal mortality of patients managed with amniocenteses was compared to those managed with Doppler studies. RESULTS: There were 74 patients managed with amniocenteses and 25 managed with Doppler studies. Perinatal mortality was significantly higher in the 99 Rh-negative isoimmunized patients than in the 192 unimmunized patients (12.1% versus 1%, p=0.0001) and did not differ according to the management protocol used (amniocentesis 13.5% versus cerebral Doppler 8.0%, p=0.725). Mean gestational age and mean weight at birth in pregnancies managed with amniocenteses (35.7 weeks and 2586 g) did not differ significantly from those managed with Doppler (36.3 weeks and 2647 g). CONCLUSIONS: Perinatal mortality in Rh-negative alloimmunized patients remains high and does not differ whether pregnancies are managed through amniocentesis or cerebral Doppler evaluation.

Isoinmunización Rh: evaluación de la utilidad del Doppler de arteria cerebral media en la predicción y manejo de anemia fetal / Rh isoimmunization: evaluation of the utility of Doppler cerebral artery average in the prediction and handling of fetal anemia

Se presenta la experiencia en el manejo de pacientes altamente sensibilizadas por incompatibilidad Rh, analizando la utilidad de la evaluación de la velocidad circulatoria fetal, por Doppler-color, a través de la medición de la velocidad máxima sistólica (VMS) de la arteria cerebral media (ACM). Se realizan 19 transfusiones intravasculares en 3 casos afectados por esta enfermedad. En 14 de ellas se encontró anemia fetal moderada o leve, la que fue diagnosticada correctamente en 13 oportunidades, (92,8 por ciento) por la medición anteriormente señalada. Se encuentra una adecuada correlación entre la velocidad máxima sistólica de la arteria cerebral media y el grado de anemia fetal moderada o severa, con un índice correlacional (r= (_) 0,78). Se destaca el beneficio de un método no invasivo en el manejo de la anemia fetal de causa inmunológica o asociada a otras condiciones mórbidas y se abre un campo para futuras investigaciones.

Isoinmunización RH: manejo actual / Isoinmunización RH: present handling

La incompatibilidad rh materno fetal es un factor que complica aproximadamente 1 de cada 1000 embarazos en los EE.UU, constituye la principal causa de muerte fetal o neonatal por enfermedad hemolítica. Nuevas técnicas como la cordocentesis, transfusión intrautterina han mejorado el pronóstico en estas pacientes. En la presente revisión comentaremos los avances acerca del manejo de la isoinmunización Rh.

Ictericia neonatal: II tratamiento de la hiperbilirrubinemia no conjugada. Consideraciones fetales y neonatales / Neonatal jaundice: II treatment of unconjugated hyperbilirubinemia

En la segunda parte de esta serie se describen algunas consideraciones con respecto al mecanismo de acción de las principales medidas terapéuticas de la hiperbilirrubinemia neonatal, así como el abordaje del feto con anemia hemolítica y recomendaciones actuales para el manejo del recién nacido sano o enfermo con hiperbilirrubinemia.