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PubMed1983

Preventing rhesus isoimmunization. Antepartum Rh immune globulin prophylaxis versus a sensitive test for risk identification.

The controversial proposal to use Rho (D) immune globulin (human) prophylactically in pregnancy should not detract from the most expedient approach to further reduction of Rh disease; that is, to ensure that every eligible woman is given Rho (D) immune globulin (human) after delivery, abortion, or ectopic pregnancy. Family planning by Rh-negative women at risk and limiting the number of pregnancies in women already immunized will be additional effective ways to reduce the current incidence of hemolytic disease in most communities. Present evidence shows that blanket antepartum Rho (D) immune globulin (human) prophylactic treatment will be very costly and will place many subjects at potential risk while offering benefit to only a few. Sensitive and practical laboratory testing for fetomaternal hemorrhage is presently only a research tool but will soon be clinically available to provide new data on fetomaternal hemorrhage. In the near future, pregnant women truly at risk for Rh isoimmunization may be identified by analysis of their blood, and this will be a rational basis for antepartum Rho (D) immune globulin (human) treatment. There are compelling advantages in cost, risks, and benefits for an approach of selective antepartum Rho (D) immune globulin (human) therapy as opposed to routine prophylaxis for all Rh-negative gravid women.

Australia↗
PubMedDate not supplied

[Modern diagnosis and prognosis in isoimmunization in the Rh system].

A total of 118 Rh isoimmunized pregnant women were discovered from 1972 to 1981. In diagnosing the disorder, the author draws attention to the examination of bilirubin in the amnionic fluid as the most reliable indicator, to which the dosing of measurable antibodies and echography are, in his opinion, a precious contribution. The administration of corticosteroids, antihistaminics, capillary protectors, and sedatives proved unreliable. A premature delivery was induced in 79 cases, after the assessment of the fetus maturity. The pregnancy was terminated vaginally in 60 and by cesarean section in 19 cases. Twenty-two near-term children ere delivered without major problems. Failure was recorded in 31 (26.3%) cases: 17 deaths in the uterus and 14 deaths of newborns immediately after birth. Out of 87 surviving children, 36 received exsanguinotransfusion 1-4 times.

Amniotic Fluid↗
PubMed2004

Prevention and management of RhD isoimmunization.

An Rh-negative woman is at risk for developing Rh isoimmunization upon exposure to RhD antigens from her Rh-positive baby through fetal-maternal hemorrhage. The incidence of Rh isoimmunization and fetal hemolytic disease has decreased substantially since Rh immune globulin was introduced in 1968. When RhD sensitization does occur, careful follow-up of these mothers and judicious intervention can result in good outcomes for most pregnancies. Both Doppler assessment of middle cerebral artery peak systolic velocity and spectral analysis of amniotic fluid at 450 nm (DeltaOD 450) are useful in the diagnosis and management of fetal anemia.

Female↗
PubMed2002

Role of HLA antigens in Rh (D) alloimmunized pregnant women from Mumbai, Maharashtra, India.

Immunogenetic studies in various diseases provide potential genetic markers. We have studied the incidence of HLA A, B, C, DR and DQ loci antigen in Rh (D) antigen isoimmunized mothers compared to those nonimmunized isoimmunized Rh negative mothers. Seventy six mothers who were immunized to Rh (D) antigen due to pregnancy (responders) and fifty four mothers who did not develop Rh (D) isoimmunization despite positive pregnancies (nonresponders) were selected for the study. Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits. The genotype frequencies of HLA A2, A3, A28, B13, B17, B35, B52, B60, Cw2, Cw6, DR4, and DQ3 were significantly increased, while the frequencies of the HLA A11, A29, A31, B7, B37, B51, Cw1 and DR9 were decreased in the responder women when compared to the non-responder women. HLA A30 (19) split antigen was not identified in immunized women while HLA A23 (9) split antigen was not identified in non immunized women. HLA A3, B17, Cw2 and DR4 showed a significant relative risk among the immunized responder women. When compared with Rh immunized women (responders) reported from USA, England and Hungary the phenotype frequencies of HLA A11, A24, A28, B5, B17, B40, DR2 and DR5 were increased while HLA A23, B8, B18, and DR6 were decreased in the Indian Rh immunized women. Two locus haplotype frequency analysis observed among the responders women revealed that among the significant haplotypes expressed A2-B5, B7-Cw1, DR2-DQ1 were highly significant haplotypes in positive linkage, while A1-B5, and A1-B7 were in significant negative linkage disequilibrium. The haplotype frequencies were <or= one when these common hapoltypes were compared with control population. Thus in the present study it is evident that the inheritance of HLA A3, B17, Cw2 and DR4 increases the relative risk factor by 2.6 times among Indian Rh isoimmunized women. Further, it is evident that there are significant differences in the observed HLA antigen frequencies and two locus haplotypes in Rh isoimmunized women when compared to women from USA, UK and Hungary due to extreme HLA polymorphism in different populations of the world.

Female↗
PubMed1997

Antecedents to and outcomes of Rh(D) isoimmunization: Mater Mothers Hospital, Brisbane, 1988-1995.

We analyzed the antecedents and outcomes of Rh(D) isoimmunization in a local population. Forty-two Rh(D) isoimmunized women attending Mater Mothers Hospital for antenatal care were identified through the Mater Hospital Blood Bank database; their records were reviewed for variables including sensitizing events, obstetric interventions and pregnancy outcomes. In this group, 74% of women became sensitized despite receiving anti-D immune globulin, 17% did not receive anti-D appropriately and the other failed to attend for treatment of bleeding in pregnancy. Antenatal sensitization was implicated in 6 women (14%) and potentially responsible for isoimmunization in another 18. Over half of the 80 viable pregnancies in this study group required some form of obstetric intervention. Thirty pregnancies required amniocentesis and 1 in 3 babies underwent either intrauterine or exchange transfusion. Three fetal deaths occurred as a result of severe disease. This study offers information highlighting circumstances in which immunoprophylaxis guidelines have failed to impart protection against Rh(D) sensitization and the consequences of such failures.

Female↗
PubMed1997

Rhesus isoimmunization: increased hemolysis during early infancy.

The objective of the present study was to determine whether whole blood carboxyhemoglobin (COHb) and plasma bilirubin, two indicators of hemolysis, are elevated in infants with severe Rh isoimmune hemolytic disease during the first months of life. Beginning at 2 wk of age and continuing monthly for 3 mo, serial blood samples were obtained for COHb, plasma bilirubin, Hb, reticulocyte count, plasma erythropoietin, plasma enzymes, and plasma iron. Because control infants (n = 13) and infants with ABO hemolytic disease (n = 5) did not differ from one another in any of the study parameters, these two groups were combined and compared with infants with the Rh isoimmunization. Infants with severe Rh isoimmune hemolytic disease (n = 13) were found to have significantly lower Hb and significantly higher bilirubin, the COHb fraction divided by the Hb concentration (COHb/Hb), and plasma erythropoietin levels at 2 and 6 wk of age, and reticulocyte counts at 6 wk. The remaining parameters were not different between the control-ABO group and Rh-isoimmune group at any of the study intervals. The study's two primary indicators of hemolysis, plasma bilirubin and COHb/Hb, were significantly correlated with one another in the Rh-immunized group (r = 0.66, p < 0.0001), but not in the combined control-ABO group. Serial Rh antibody concentrations measured in the serum of four neonates with Rh isoimmunization demonstrated a mean half-life of 14.3 d. We speculate that, among infants with severe Rh isoimmune hemolytic disease, elevated total bilirubin levels and COHb/Hb ratios identified in the early weeks of life indicate continuing hemolysis due to persistence of maternal Rh antibodies.

ABO Blood-Group System↗
PubMed1993

Erythropoietin in human fetuses with immune hemolytic anemia and hydrops fetalis.

OBJECTIVE: To determine whether plasma erythropoietin is increased in fetuses with anemia due to Rh isoimmunization. METHODS: Hemoglobin and erythropoietin were measured in samples obtained by funipuncture from 15 fetuses with Rh isoimmunization (gestational age 26.2 +/- 5.0 weeks, mean +/- standard deviation) and from 13 control fetuses (23.1 +/- 6.7 weeks). Hemoglobin and erythropoietin also were determined in umbilical cord blood collected at birth from 20 term fetuses delivered by elective cesarean. RESULTS: Fetuses with Rh isoimmunization had lower hemoglobin and higher plasma erythropoietin measurements than mid-gestation controls (6.1 +/- 3.9 versus 10.7 +/- 1.5 g/dL and 105.5 +/- 168.1 versus 12.5 +/- 3.1 mU/mL, P < .05, respectively). Hemoglobin and plasma erythropoietin increased with gestational age in control fetuses. There was an inverse association between hemoglobin and plasma erythropoietin in control and Rh-isoimmunized fetuses (r = -0.56, P < .005). Using multiple linear regression, hemoglobin and gestational age were associated independently with plasma erythropoietin (overall F2,25 = 12.3, multiple r2 = 0.49, P < .001). Despite marked decreases in hemoglobin, fetuses below 24 weeks' gestation had minimal increases in plasma erythropoietin compared to fetuses above that gestational age. Mildly anemic Rh-isoimmunized fetuses (hemoglobin 11.6 +/- 2.0 g/dL) delivered vaginally had significantly higher erythropoietin levels in umbilical cord plasma than Rh-isoimmunized fetuses with comparable hemoglobin (10.9 +/- 3.5 g/dL) delivered by elective cesarean without labor (1246 +/- 856 versus 106 +/- 66 mU/mL, respectively, P < .05). CONCLUSION: Fetuses with anemia at mid to late gestation respond with increases in plasma erythropoietin, but these changes are substantially attenuated before 24 weeks' gestation.

Anemia, Hemolytic, Autoimmune↗
PubMed1989

A new funipuncture technique: two-needle ultrasound- and needle biopsy-guided procedure.

A new technique is presented for funipuncture under ultrasound guidance using a biopsy guide and a 20/25-gauge needle combination. The 20-gauge needle was used for uterine entry and the 25-gauge needle for the actual cord puncture. The method was used for sampling fetal blood in 262 pregnancies with 264 fetuses (two sets of twins) between 17-39 weeks, at risk for beta-thalassemia, chromosomal disorders, TORCH infection, fetal hypoxia, and Rh-isoimmunization. Pure fetal blood was aspirated from 241 fetuses (91.3%), including the twins. The procedure lasted less than 5 minutes in 76.5% of the cases and less than 10 minutes in 90.1% of the cases. Intra-amniotic bleeding was seen in only 23.1% of the cases, and fetal bradycardia was not noted. Forty-four pregnancies were terminated after the diagnosis of genetic or infectious disease. Seven fetuses at risk for Rh-isoimmunization, found to be Rh-positive and anemic, were transfused immediately after blood sampling using the same needle. Of the 220 continuing pregnancies, there were 14 fetal losses (three before 28 weeks and 11 after 28 weeks or during the perinatal period). A probable etiology for the loss was found in 11 cases. These included one severely Rh-isoimmunized hydropic fetus who died in utero after transfusion at 26 weeks, one fetus who died in utero at 31 weeks following a car accident, and nine malformed newborns. The corrected rate for fetal losses probably related to the procedure was thus 0.9% before 28 weeks and 0.8% after 28 weeks. This new funipuncture technique seems to have several advantages over the freehand and/or biopsy-guided single-needle techniques.

Biopsy, Needle↗
PubMedDate not supplied

Umbilical vein blood flow in the human fetus in cases of maternal and fetal anemia and uterine bleeding.

The umbilical vein blood flow (UVBF) of the human fetus was studied by a method combining real-time and Doppler equipment in seven cases of maternal anemia, 20 cases of Rh isoimmunization and 19 cases of uterine bleeding during the third trimester of pregnancy. The last individual UVBF value before delivery had in Rh-isoimmunization a significant negative correlation with the cord hemoglobin level of the newborn infant (p less than 0.01), thus reflecting the severity of fetal hemolytic anemia. Severe isoimmunization (cord hemoglobin less than or equal to 140 g/l) was associated with a significantly higher UVBF, blood velocity in the umbilical vein and umbilical vein diameter than was observed in mild-moderate anemia. Maternal anemia seems to be causally associated with increased UVBF levels. Uterine bleeding, especially before the 34th week, often leads to increased UVBF in the fetus. The method used seems not only to be able to contribute to our knowledge of hemodynamic regulation in the human fetus, but also provides a new practical means of evaluating the severity of fetal affection in cases of Rh isoimmunization.

Anemia↗