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PubMed2001

The severity of immune fetal hydrops is predictive of fetal outcome after intrauterine treatment.

OBJECTIVE: This study was undertaken to test the hypothesis that the degree of immune fetal hydrops predicts outcome in red blood cell-alloimmunized pregnancies. STUDY DESIGN: In an 11-year period, 213 fetuses received 599 intrauterine transfusions. The outcome of 208 pregnancies, including two pairs of twins, was analyzed in a retrospective study. Eighty fetuses demonstrated ultrasonographic signs of hydrops at the start of treatment; 42 of these were classified as mildly hydropic and 38 were classified as severely hydropic. Reversal of hydrops as a result of treatment, survival, and neonatal morbidity was studied. RESULTS: The overall survival rate of fetuses with hydrops was 78%. Of the fetuses with mild hydrops, 98% survived, whereas in cases of severe hydrops the survival rate was 55%. Intrauterine reversal of hydrops occurred in 65% of the fetuses with hydrops. The reversal rate was 88% in fetuses with mild hydrops and 39% in fetuses classified as severely hydropic. After reversal of hydrops, almost all of the fetuses survived (98%), whereas in cases of persistent hydrops outcome was unfavorable, with a survival rate of 39% for all fetuses and 26% for fetuses classified as severely hydropic. CONCLUSION: In contrast with severe hydrops, there is a high rate of reversal of mild hydrops after adequate treatment. In our study 98% of fetuses survived after reversal of hydrops. To improve the outcome of red blood cell-alloimmunized pregnancies, early diagnosis of fetal anemia and referral to a specialized center are important; these steps enable the start of intrauterine treatment when hydrops is absent or still mild.

Blood Transfusion, Intrauterine↗
PubMed2002

Doppler ultrasonographic evaluation of twins discordant for Rh alloimmunization.

Minimally invasive methods have been used successfully to diagnose and treat maternal red blood cell alloimmunization. We present a case of a dizygotic twin pregnancy discordant for the Rh allele. Serial Doppler ultrasonography helped to diagnose the fetus that was at-risk for anemia caused by Rh alloimmunization and to direct treatment.

Adult↗
PubMed2002

Paternal leukocyte alloimmunization as a treatment for hemolytic disease of the newborn in a rabbit model.

OBJECTIVE: The purpose of this study was to evaluate maternal alloimmunization to paternal leukocytes as a treatment for hemolytic disease of the fetus/newborn in a rabbit model. STUDY DESIGN: Twelve does and paired red blood cell-incompatible bucks underwent the experimental protocol. Fetal hematologic parameters that were obtained by ultrasound-guided intracardiac sampling were compared from unaffected, compatible litters; from affected, incompatible litters (after alloimmunization to red blood cell antigens); and from affected, incompatible litters after alloimmunization to paternal leukocytes. Generalized estimation equations were used for statistical analysis. A probability value of <.05 was considered significant. RESULTS: Six of 12 does had at least one affected litter after alloimmunization to paternal leukocytes. After an adjustment for the mating cycle, the fetuses of does that underwent white blood cell immunization exhibited higher hemoglobin and hematocrit levels (beta = 4.6, P <.001, and beta = 11.6, P =.006, respectively) compared with the fetuses of does that were immunized only to red blood cells. CONCLUSION: Maternal alloimmunization to paternal leukocytes decreases the severity of hemolytic disease and may play a role in the treatment of severe hemolytic disease of the newborn in humans.

Animals↗
PubMed2003

Noninvasive tests to predict fetal anemia: a study comparing Doppler and ultrasound parameters.

OBJECTIVE: This study was undertaken to compare test characteristics of ultrasound and Doppler parameters in the prediction of fetal anemia in alloimmunized pregnancies. STUDY DESIGN: In a prospective cohort study, 16 nonhydropic fetuses with red blood cell alloimmunization were evaluated with ultrasound and Doppler imaging. Middle cerebral artery (MCA) peak systolic velocity, intrahepatic umbilical venous (IHUV) maximum velocity, liver length, and spleen perimeter were measured. Results before first fetal blood sampling (FBS) or delivery were analyzed. Fetal anemia was defined as hemoglobin deficit 5 SD or greater. Sensitivity and specificity were calculated. RESULTS: Six fetuses were anemic and required intrauterine transfusion, and 10 were not severely anemic at birth. MCA Doppler imaging was the best predictor of fetal anemia (100%), followed by IHUV (83%). Sensitivity was low for spleen perimeter (66%) and liver length (33%). CONCLUSION: Doppler evaluation of MCA peak systolic velocity is better than IHUV maximum velocity, liver, or spleen size in the prediction of fetal anemia in red blood cell alloimmunization.

Blood Transfusion, Intrauterine↗
PubMed2003

Conventional management of maternal red cell alloimmunization compared with management by Doppler assessment of middle cerebral artery peak systolic velocity.

OBJECTIVE: This study was undertaken to compare management of red blood cell alloimmunization by Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) to conventional management with amniocentesis. STUDY DESIGN: A historical cohort of 28 fetuses at risk for anemia caused by red blood cell alloimmunization was followed between 1999 and 2002 at a single institution. The decision to perform percutaneous umbilical cord blood sampling (PUBS) was based on conventional management. MCA-PSV Doppler was measured before amniocentesis or PUBS but not used clinically. RESULTS: Twenty-eight fetuses were followed up: 4 had severe anemia, 1 had moderate anemia, 3 had mild anemia, and 20 were nonanemic. Conventional management had a sensitivity and positive predictive value for moderate-to-severe anemia of 80% and 44%, with a false-positive rate of 56%. In the same patients, MCA-PSV Doppler had a sensitivity and positive predictive value for moderate-to-severe anemia of 100% and 71%, with a false-positive rate of 28%. CONCLUSION: Compared with conventional management, MCA-PSV Doppler may have a better predictive accuracy for moderate-to-severe fetal anemia in red blood cell alloimmunization. Management by MCA-PSV Doppler may eliminate the need for amniocentesis and reduce the number of PUBS performed in red blood cell-alloimmunized pregnancies.

Amniocentesis↗
PubMed2003

Minimizing red blood cell contamination while isolating mononuclear cells from whole blood: the next step for the treatment of severe hemolytic disease of the fetus/newborn.

OBJECTIVE: We examined whether mononuclear cell purification of human blood could be done while minimizing contamination with RhD-positive red blood cells to treat hemolytic disease of the fetus/newborn that was caused by rhesus disease. STUDY DESIGN: Whole blood from 16 individuals who tested rhesus positive was diluted and centrifuged over a Ficoll gradient. The cell pellet was incubated with red blood cell lysis buffer, divided into three samples, and analyzed for cell count, mononuclear cell yield, and RhD-positive red cell contamination by flow cytometry. RESULTS: Mean RhD-positive red cell contamination was 0.24% (range, 0%-1.9%). The average yield of mononuclear cells was 11.5% (range, 1.8%-23.6%). Through regression analysis, 34 to 180 mL of paternal whole blood would be necessary to achieve an antigen load that is sufficient for an HLA antibody response. CONCLUSION: Purification of human blood is possible to produce reasonable mononuclear cell yields with minimal rhesus activity, which makes paternal leukocyte therapy a plausible treatment for severe rhesus alloimmunization.

Blood Component Removal↗
PubMed1994

Erythroblastosis fetalis--the discovery and partial elimination of rhesus incompatibility--the origins of exchange transfusion in Australia.

The first 2 exchange transfusions in Australia for Rhesus-induced erythroblastosis (hemolytic disease of the newborn) were conducted in the 9 mth period from December 1945 to August 1946. These pioneering endeavours in medical research were undertaken by 3 transfusionists who were, or had been, directors of the Red Cross Blood Transfusion Service in Australia. Called "substitution transfusion" or "exsanguination transfusion" they were conducted prior to the international publication of the first case series of exchange transfusions for "Rhesus Disease". The first successful exchange transfusion in Australia, and one of the first in the world, was performed by Dr George Kelsall at the King Edward Memorial Hospital for Women, in Perth. Dr Kelsall had monitored pregnancies with serum raised himself from blood from a Rhesus monkey in the Perth Zoo. The second exchange transfusion, and the first with volume-monitoring, was successfully undertaken in Brisbane by Dr Eric Shaw, pathologist and Director of the Queensland Red Cross Blood Transfusion Service, and Dr Noel Gutteridge, a former Director and senior pathologist of Brisbane. Dr Kelsall's pioneering transfusion in Perth was a direct non-anticoagulated transfusion which was undertaken within minutes of birth and was completed within 5 min. The first volume-controlled exchange transfusion, in which the input-discard volumes were matched, used a plastic tube obtained from the Telephone Branch of the Postmaster General's Department, and employed citrated blood. These heroic exchanges (heroic for the infants and families concerned as well as for the operators) form a significant milestone in the history of blood transfusion, serology and preventive medicine in Australia.

Australia↗
PubMed2001

Successful treatment of neonatal rhesus hemolytic anemia with high doses of recombinant human erythropoietin.

The authors report the use of high-dose recombinant erythropoietin (r-HuEPO) in a full-term newborn baby with severe postnatal rhesus hemolytic anemia (RHA). Hemoglobin (Hb) value and reticulocyte count at day 13 of life were 59 g/L and 234 x 10(9)/L, respectively. Three days after the r-HuEPO (870 U/kg/d) administration, reticulocyte count had increased more than 4-fold and Hb rose to 73 g/L. r-HuEPO was gradually decreased after 18 days of treatment. No major side effect was observed. In selected cases of severe anemia due to hemolytic disorders, transfusions may be avoided by the use of high doses of r-HuEPO.

Anemia, Hemolytic, Congenital↗
PubMed2003

Intrauterine transfusion for rhesus alloimmunization elevates fetal beta2-microglobulin levels.

BACKGROUND: Intrauterine transfusions for rhesus alloimmunization leads to alterations in circulating T-cell populations. Given that elevations in circulating beta2-microglobulin are a marker of T-cell-mediated organ transplant rejection, we evaluated the effect of intrauterine transfusion on fetal beta2-microglobulin levels. METHODS: Umbilical venous samples were obtained immediately prior to initial transfusion in ten anemic fetuses and in 12 fetuses with prior transfusions. Samples were also obtained from 18 gestational age-matched non-anemic fetuses and eight healthy neonates. RESULTS: The median concentration of beta2-microglobulin was significantly higher in fetuses with prior transfusions compared with non-anemic controls. In non-anemic controls, and in transfused fetuses, beta2-microglobulin levels decreased throughout gestation (r = -0.69, p = 0.01; and r = -0.80, p = 0.01, respectively). Among anemic and transfused fetuses, beta2-microglobulin levels displayed a negative correlation with fetal hematocrit (r = -0.62, p < 0.05; and r = -0.58, p = 0.04, respectively). CONCLUSIONS: We conclude that intrauterine transfusion for fetal anemia is associated with increased beta2-microglobulin levels, suggesting immunomodulatory effects of intrauterine transfusion on host immune responses to donor leukocyte antigens.

Anemia↗
PubMed1996

Tubo-peritoneal factor infertility: a distant sequel to intrauterine transfusion for rhesus disease.

A patient presented with infertility 28 years after receiving four intrauterine transfusions as a fetus for rhesus haemolytic disease. Extensive adhesions were found in the peritoneal cavity affecting in particular the ovarian retrieval mechanism. No other possible cause for the situation could be discerned. Patients who have undergone pioneering techniques such as this are now adults and may be trying to conceive. When confronted by such a history there is therefore a need for early thorough investigation of the tubal peritoneal factor.

Adult↗
PubMed2000

Pregnancy and pregnancy outcome in hepatitis C type 1b.

A large cohort of rhesus-negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti-D immunoglobulin in 1977-8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age- and parity-matched control group of rhesus-positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme-linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV-RNA-positive (type 1b) on PCR testing. In the 20 years post-infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR-positive women. Of the children born to HCV-RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV-RNA-positive mothers apart from one single exception in the antibody-positive HCV-RNA-negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

Adult↗
PubMed2004

Fetal anemia: new technologies.

PURPOSE OF REVIEW: The purpose of this review is to summarize recently published studies on noninvasive diagnosis of fetal anemia in order to give recommendations for the use of these new tools. RECENT FINDINGS: Red cell alloimmunization remains one of the most common causes of fetal anemia. Amniocentesis and cordocentesis have been used for many years to diagnose fetal anemia due to red cell aloimmunization. These techniques, however, are invasive and many complications are associated with their use. Noninvasive diagnosis of fetal anemia has been performed with Doppler ultrasonography. Based on robust data, several authors recommend the use of middle cerebral artery peak systolic velocity in the management of fetuses at risk for anemia because of red cell alloimmunization. This Doppler parameter can also diagnose fetal anemia due to other conditions. SUMMARY: Middle cerebral artery peak systolic velocity appears to be the best test for the noninvasive diagnosis of fetal anemia. It is important to emphasize that training of sonographers and sonologists is the 'conditio sine qua non' for the correct sampling of the middle cerebral artery.

Amniocentesis↗
PubMed1985

Ectopic pregnancy.

The diagnosis of ectopic pregnancy has become precise and reliable. Consequently, the management of ectopic pregnancy has progressed to the point where the physician is often able to preserve fertility. Therefore, conservative surgery is indicated if the patient desires future fertility and conditions are appropriate. The combination of ultrasound, beta-hCG pregnancy testing, and laparoscopy has led to a rising incidence of diagnosed ectopic pregnancy prior to rupture. This has greatly facilitated the use of the conservative approach to the management of tubal pregnancy. Although ectopic pregnancy can be diagnosed early and managed conservatively, it is, and will remain a potentially life-threatening disease and must be approached as such. Table 3 summarizes our proposed surgical management of tubal pregnancy. Table 4 summarizes the results of conservative surgery for tubal pregnancy.

Chorionic Gonadotropin↗
PubMed1991

Antenatal suppression of Rh alloimmunization.

For more than the past decade, attempts have been made to suppress HDN by the administration of drugs or biologic materials to the Rh-immunized pregnant woman. With the possible exceptions of IGIV therapy and plasma exchange substitution of IGIV for maternal IgG, all such attempts have been ineffective. On the other hand, antenatal administration of RhIg (300 micrograms at 28-30 weeks' gestation) to the pregnant, unimmunized Rh-negative woman is very effective in preventing Rh immunization and is now the accepted standard of obstetric care. Physicians who neglect to carry out antenatal prophylaxis neglect to do so at their patient's and their own peril.

Erythroblastosis, Fetal↗
PubMed1999

Clinical uses of intravenous immunoglobulin in pregnancy.

The obstetric literature contains numerous reports of IVIG therapy for various conditions encountered during pregnancy. The mechanisms of action of IVIG are uncertain and may vary depending on the specific disorder. Immunoglobulin G infusions appear to be well tolerated by the parturient. The occurrence of major and minor side effects is uncommon, and infectious morbidity is low. Further research will be necessary to elucidate the specific mechanisms of action of IVIG in certain disease states. Determining the exact "therapeutic agent" in IVIG for each specific disease state may allow for a more tailored approach to treatment (i.e., isolation or production of the particular antibody). Outcome assessment, long-term positive and negative effects, cost-benefit analysis, and effects on fetal and neonatal immune function require further study through randomized trials.

Antiphospholipid Syndrome↗