Personalized treatment with immunoadsorption and intravenous immunoglobulin in a case of severe Rh alloimmunization during pregnancy unresponsive to plasma - exchange.

INTRODUCTION: Despite prophylaxis, a small proportion of RhD-negative women may develop anti-D antibodies after a sensitizing event occurring during pregnancy or delivery of a D-positive baby. Intrauterine transfusion (IUT) is the treatment of choice in case of fetal anemia, but it cannot be performed early during pregnancy. Combined treatment with therapeutic plasma-exchange (TPE) and intravenous immunoglobulin (IVIG) can avoid or delay IUT. Immunoadsorption (IA) could represent a more effective treatment in selected cases. CASE REPORT: We report a D-negative female with a history of induced abortion and hydrops fetalis, referred at 8 weeks of gestation with a high anti-D titer. Despite implementing a TPE-IVIG protocol, the patient experienced a spontaneous abortion. At the beginning of her fourth pregnancy, only after a partially effective intensive TPE course, cycles of IA-IVIG were performed. Despite a suboptimal response on the anti-D titer, Doppler ultrasonographic measurements of the fetal middle cerebral artery peak systolic velocity first showed evidence of anemia at 30 weeks of gestation and a IUT was required. After the IUT, anemia persisted with a subsequent dramatic rise in titer, requiring an emergent cesarean section. The infant subsequently underwent successful treatment with IVIG, phototherapy and exchange transfusion and was discharged 7 weeks later without neurological deficits. DISCUSSION: The treatment of high titer anti-D antibodies during pregnancy may require a multidisciplinary approach with utilization of different apheresis strategies in order to have a successful pregnancy outcome.

CHAOS in the mirror: Ballantyne (mirror) syndrome related to congenital high upper airway obstruction syndrome.

In the mirror syndrome, maternal edema mirrors fetal edema. The pathogenesis is unknown. The most common etiologic associations are rhesus isoimmunization, twin-twin transfusion syndrome, and viral infections. Less than 10% of reported cases are associated with congenital anomalies. We report a case due to congenital laryngeal stenosis, which also caused congenital high airway obstruction syndrome (CHAOS), characterized by pulmonary hyperplasia and edema or anasarca, related to airway abnormality. The fetal manifestations of the mirror syndrome and CHAOS overlap, but occurrence of the two in the same patient does not seem to have been reported.

Successful management of anti-Jra alloimmunization in pregnancy: a case report.

BACKGROUND: Hemolytic disease of the fetus/newborn due to Jr(a) immunization is very rare and considered to be mild, and only routine obstetrical care is recommended for pregnant women sensitized to the Jr(a) antigen. CASE REPORT: A 20-year-old nulliparous woman was referred to our hospital for perinatal management. Her indirect Coombs test was positive for anti-Jr(a) antibody (1:64). At 33 weeks' gestational age, we observed that fetal growth was mildly restricted and the peak systolic velocity of the fetal middle cerebral artery (PSV-MCA) was above the upper limit of the reference range (1.55 multiples of the median). Amniocentesis was also carried out and the DeltaOD450 value was in the lower mid-zone of the Liley curve. We continued to carefully observe the patient because we observed PSV-MCA values within 1.50-1.60 multiples of the median and no other findings of fetal anemia. She vaginally delivered a female infant weighing 2,136 g at 37 weeks' gestational age. The infant received treatment with both iron and recombinant erythropoietin without developing hyperbilirubinemia and blood transfusion. CONCLUSION: PSV-MCA should be monitored for the detection of fetal anemia, even in pregnant women sensitized to some antigens for which only routine obstetrical care is recommended.

ACOG Practice Bulletin No. 75: Management of alloimmunization during pregnancy.

When any fetal blood group factor inherited from the father is not possessed by the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an immune reaction in the mother Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies, or"alloimmunization,' may lead to various degrees of transplacental passage of these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and untreated, alloimmunization can lead to significant perinatal morbidity and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks to the mother and fetus. Prevention of alloimmunization is addressed in another Practice Bulletin (1).

A case of extreme unconjugated fetal hyperbilirubinemia.

We present an unusual case of severe unconjugated hyperbilirubinemia and normal hemoglobin at birth in a premature newborn with Rh incompatibility. We speculate that the possible mechanism is due to placental dysfunction. To our knowledge, this is the highest reported unconjugated bilirubin level at birth.

Incompatibilidad RH: manejo en ele hospital Patrocinio Peñuela Ruíz en el período 1991 - 2000 / Incompatibility RH: handling in the Hospital Patrocinio Peñuela Ruiz in the period 1991 - 2000

Se realizó un estudio retrospectivo, de tipo descriptivo donde se revisaron 153 historias de pacientes Rh (-). La incidencia en 10 años es de 1.19 por ciento; el 76 por ciento de las gestantes tenia 2 o más gestas. Los exámenes prenatales fueron solicitados en un 21 por ciento; estando 5 de las gestantes sensibilizadas, demostrando títulos de antiaglutininas por encima de 1:32 en el 80 por ciento de los casos, de estas solo se le realizó amniocentésis a un 25 por ciento. Se les solicito 19 tipiajes sanguíneos de parejas, 14 eran Rh incompatible. 83 de la gestantes atendidas reportaban tipiajes de hijos anteriores, de las cuales 69 señalaban por lo menos un hijo cuyo tipiaje era para Rh positivo. Se pudo constatar que las gestantes estudiadas la colocación del Rhogam se cumplió en el 42 por ciento. Hubo 1 caso de reporte de transfusiones sanguíneas. 13 pacientes presentaron hemorragia genital, solo uno de estos reporto coombs indirecto positivo post-parto. Se realizaron 3 amniocentesis. Posterior a estos antecedentes no hay reporte de colocación de Rhogam. Hubo un total de 156 Recién Nacidos. 9 por ciento de los neonatos presentó ictericia por incompatibilidad Rh. La profilaxis con Rhogam en el embarazo actual se cumplió en 93 gestantes (60.7)

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.

[Intrauterine fetal transfusion in twin pregnancy with Rh isoimmunization]. / Intrauterinna transfuziia na ploda pri dvuplodna bremennost s Rh-izoimunizatsiia.

Two women with twin pregnancy and with Rhesus isoimmunization were described. The disease of these women was so grave that intrauterine transfusions were made in both fetuses (from all 86 pregnancies treated with transfusions). Twins of one of the women were born alive, but the other twins died in utero. Difficulties and problems of this rarely encountered combination of two independent one from the other pathologies are discussed.

[Histometric case report of a placenta following intra-uterine therapy of rhesus incompatibility]. / Histometrische Kasuistik einer Plazenta nach intrauteriner Therapie einer Rhesus-Inkompatibilität.

In Rh-incompatibility the human placenta shows a prominent retardation of maturation. The placental insufficiency caused by these changes, combined with the existing hemolysis, represents an additional danger to the fetus. In a patient with severe Rh-incompatibility several Rh-negative blood transfusions were performed between the 26th and 30th weeks of gestation via sonographically guided puncture of the umbilical vein. Morphometric studies of the placenta were performed and the results compared with data already obtained from normal mature placentas and placentas from pregnancies complicated by Rh-incompatibility. Small terminal villi with a surface area identical to normal mature placentas were found. There was no improvement in vascularization when compared with other placentas from Rh-incompatible pregnancies. Nevertheless, isolated rebuilding of epithelial plates was found. The authors interpret these morphological phenomena as a "partial postmaturation" of the placenta as regards the development of the terminal villi. The absence of reproliferation of the villous vessels as well as the lack of any extensive regeneration of the epithelial plates could be due to the short time which elapsed between transfusion therapy and the inevitable indication for caesarean section. Intensive intrauterine therapy reduces the risk to the fetus due to immunologic complications, as well that due to placental insufficiency, as evidenced by the additional differentiation of villi.

[Histometric studies of placental villi in Rh incompatibility]. / Histometrische Untersuchungen an Plazentazotten bei Rh-Inkompatibilität.

The delay in maturation of placental terminal villi in cases of Rh-incompatibility has often been described. The terminal villi of sixteen placentas from pregnancies complicated by Rh-incompatibility histometric were studied. Twenty-two placentas of healthy mothers who had born healthy babies after normal pregnancies served as a control group. The severity of the Rh-incompatibility was classified according to the clinical histories of the newborns and the criteria of Liley. The average area of a cross-section of a terminal villus was 3402 microns 2 (control group 2150 micronsoff; the degree of vascularization was calculated to be 6.5% (control group 30.5%). The other villous parameters measured or calculated show that maturation of the placenta is extremely retarded in cases of Rh-incompatibility. This failure in differentiation can not be compensated for by an enlargement of the organ as a whole. It was shown that the changes in the placental villi are closely correlated to the severity of the fetal disease.

Fetal liver ultrasound measurements in isoimmunized pregnancies.

Sixteen isoimmunized pregnancies at risk for erythroblastosis fetalis were managed by serial amniocenteses for bilirubin delta optical density at 450 nm (delta OD450). Before amniocentesis each fetus was evaluated ultrasonically and the fetal liver size, the abdominal circumference, and the umbilical vein diameter, in both the fetal liver and the umbilical cord, were measured. The ultrasonically determined fetal liver size, as well as its growth rate, was found to be greater than normal during the last two weeks before intervention (intrauterine transfusion or delivery) in all eight fetuses with severe hemolytic disease. The umbilical vein diameter in the fetal liver was above normal in only one fetus, whereas the abdominal circumference was increased in only three of the eight severely affected fetuses. These data suggest that serial fetal liver ultrasound measurements may be useful as an adjunct to amniotic fluid analysis to predict the severely affected fetus in need of prompt intervention (intrauterine transfusion or delivery).

Fetal microcirculation of abnormal human placenta. II. Scanning electron microscopy of placental vascular casts from fetus with severe erythroblastosis fetalis.

The latex injection-corrosion cast technique coupled with scanning electron microscopy was applied to the study of severe Rh sensitization of the placenta. The main observed ultrastructural changes in fetal vasculature in this type of placenta were very similar to those of the small for gestational age placenta; large-sized vessels exhibited less branching than those of the normal placenta, and the capillary network showed numerous vascular buds and "H"-shaped anastomoses. In addition, in Rh-sensitized placentas, the capillary network was remarkably sparse, and the cast also revealed smooth-surfaced veins with distinct U shapes undulating through the placental stroma. These U-shaped veins may be the result of umbilical flow impedance with subsequent umbilical venous hypertension, which stretches the veins into undulating form.

[Fetal membranes of the human. Electron microscopy study]. / Fetalmembranen des Menschen. Elektronenmikroskopische Studie.

The structure of the human fetal membranes was examined after normal and pathological pregnancy. The cellular junctions are desmosomes and gap junctions in the amniotic epithelium, whereas in the chorionic epithelium tight junctions in the form of maculae occludentes are found occasionally in addition to desmosomes and gap junctions. The absence of zonulae occludentes, which could act as an effective permeability barrier, in the fetal membranes indicates that the intercellular spaces of the fetal membranes represent an extracellular route for paraplacental substance exchange. In pathological pregnancy such as diabetes mellitus, rhesus incompatibility and toxemia, the morphological variations of amniotic epithelium compared with normal amnion are manifold and greatly specific. On the contrary, the morphological changes of chorionic epithelium in pathological pregnancy seem nonspecific. They differ in various pathological pregnancies only in quantity. In addition to fibroblasts and Hofbauer cells, the connective tissue of the fetal membranes contain myofibroblasts. Since myofibroblasts possess the ability to contract, we assume that they may contribute to protection of the fetal membranes from overdistension.

Distribution of placental grade in high-risk gravidas.

One hundred twenty-eight high-risk gravidas and 62 normal gravidas who had undergone placental sonography were compared retrospectively according to placental grade, risk category, and stage of pregnancy at the time of the examination. Pregnancies ranged from 28 weeks of gestation to term. For analysis, the group of high-risk patients was subdivided into four categories representing specific disease states: chronic hypertension and/or preeclampsia, intrauterine growth retardation, maternal diabetes, and Rh sensitization. To eliminate gestational age bias, both the normal group and the high-risk subgroups were further subdivided into preterm and term pregnancies. Placental grade distribution was similar between the high-risk group overall and the normal group, but specific disease entities were associated with widely varying distributions of placental grade. In particular, hypertension and intrauterine growth retardation showed a strong correlation with accelerated placental maturation, whereas diabetes and Rh sensitization were associated with delayed maturation of the placenta. These differences were more pronounced in the preterm population.