anti-D Gamma Globulin Research Articles

Antenatal Rh prophylaxis is unnecessary for “Asia type” DEL women

Background Generally Rh-negative patients need to be transfused with Rh-negative red blood cells. For pregnant women carrying Rh-positive fetus, the antenatal anti-D detection and Rh immunoglobulin prophylaxis are required worldwide. In East Asia, a RhD variant, termed “Asia type” DEL, was found in approximately 30% of apparent Rh-negative individuals. The antigenic and molecular properties of the DEL were previously defined. Few data discuss whether DEL could be immunized by D antigen clinically although DEL was reported arousing alloimmunization to true Rh-negative patients. Study design and methods To determine whether the DEL variant can be immunized to the D antigen, we retrospectively evaluated 104 Rh-negative pregnancies with allo-anti-D antibodies, and we also tracked 199 consecutive apparent Rh-negative pregnant women, with a history of gestations or parturitions but not subject to anti-D gamma-globulin prophylaxis, for evidence of allo-anti-D. The DEL variant was first excluded by ccee phenotypes and then identified through PCR analysis or sequencing. Results In the retrospective study, we expected to find 30 DEL variants, yet none of the anti-D alloimmunized women were DEL-positive. And in the second group, none of 44 DEL-positive women versus 38 of 155 (24.5%) true Rh-negative women (those excluding DEL) formed allo-anti-D. Conclusion The data indicate that the “Asia type” DEL variant does not appear at risk of alloimmunization to the D antigen. It strongly suggests that the antenatal Rh immune globulin prophylaxis is unnecessary for DEL women. Furthermore, it implicates that the “Asia type” DEL may be deemed Rh-positive safely for clinical transfusion therapy.

Sangrado transvaginal durante el embarazo, como factor de riesgo para isoinmunización al antígeno Rhesus-D

The aim of the present study was to evaluate transvaginal bleeding (TVB) as a risk factor for Rhesus isoimmunization during pregnancy, in order to optimize the application of Anti-D gammaglobulin in non-immunized pregnant women, as an alternative to the routine application of Anti-D at 28 weeks of gestation. This case-control study was conducted from 1995 to 2001 at Mexico's National Perinatology Institute. Cases (n = 24) were non-immunized pregnant women who showed positive anti-D antibody seroconversion during pregnancy or during the early puerperium. Controls (n = 24) were non-immunized pregnant women who enrolled after each case, with similar clinical characteristics but who had no anti-D antibody seroconversion during pregnancy. In all cases the newborns were Rh-positive. None of the patients received immunoprophylaxis at 28 weeks of gestation. The presence of TVB was recorded at any stage of pregnancy and before labor. Odds ratios with 95% confidence intervals were used to assess associations. TVB was observed in 18/24 (75%) cases and in 5/24 (20%) controls. Preterm uterine contractions and threatened miscarriage were the most frequent causes of TVB. The presence of one TVB event during pregnancy increased 11.4 times (95% CI 2.9-44.0) the likelihood of Rhesus isoimmunization. TVB after 20 weeks of gestation increased the likelihood 5.0 times (95% CI 1.3-19.1). TVB before 20 weeks of gestation was not significantly associated with Rh isoimmunization (OR = 7.6, 95% CI 0.8-69.5). Prophylaxis with anti-D gammaglobulin should be given to all non-immunized Rhesus-negative pregnant woman with TVB at any stage of pregnancy. The English version of this paper is available at:http://www.insp.mx/salud/index.html.

Prenatal Exposures in Schizophrenia

Prenatal Exposures in Schizophrenia

Prevention of maternal RhD isoimmunization with anti-D gamma isoimmunization

To report our experience in preventing RhD maternal isoimmunization by using anti-D gamma globulin among Rh-negative women. Between 1982 and 1995, immunologic and hematologic data were collected from all Rh-negative women seen at Mexico's National Perinatology Institute. Women at risk of Rh isoimmunization were given a prophylactic dose of 150 micrograms of anti-D gamma globulin. A total of 4,857 Rh-negative women were seen during the study period (4.85% of the total population of women seen at the Institute), 629 (13.0%) of whom developed RhD isoimmunization; 542 (86.2%) of these women were already isoimmunized when first seen at our Institute. Twenty-two women (3.5%) developed isoimmunization even after receiving a proper dose of anti-D gamma globulin. Prophylaxis was given to 2,605 women (53.6%); 2,039 received a single dose, and 475 two doses. Prophylaxis failed in 22 cases; four were women with multiple pregnancy and 18 developed obstetric pathologic conditions. The use of anti-D gamma globulin resulted in a reduction of maternal Rh isoimmunization to less than one case per 1,000 women. Failures to prevent isoimmunization were associated to additional obstetric conditions and to lack of adherence to prevention guidelines.

Anti-D administration in pregnancy for preventing rhesus alloimmunisation.

A woman may develop Rh-negative antibodies during her first pregnancy when her fetus is Rh-positive. Antibodies develop most frequently after the 28th week of gestation. The objective of this review was to asses the effects of giving antenatal anti-D immunoglobulin at 28 weeks or more of pregnancy on the incidence of RhD alloimmunisation when given to Rhesus negative mothers without anti-D antibodies. We searched the Cochrane Pregnancy and Childbirth Group trials register, Cochrane Controlled Trials Register, and bibliographies. Date of last search: December 1998. Randomised trials in Rhesus negative women without anti-D antibodies given anti-D after 28 weeks of pregnancy, compared with no treatment or placebo. Data were extracted by one reviewer and double entered. Two eligible trials, which involved over 4500 women, compared anti-D prophylaxis with no treatment. Although the data suggested, when women receive anti-D at 28 and 34 weeks gestation, a reduced incidence of immunisation during pregnancy (0R O.44, 95% CI 0.18-1.12), after the birth of a Rhesus positive infant (OR 0.44, 95% CI 0.18-1.12), and within 12 months after birth of a Rhesus positive infant (OR 0.44, 95% CI 0.19-1.01), none of these differences were statistically significant. In the trial, which used the larger dose of anti-D (100ug; 500IU), there was a clear reduction in the incidence of immunisation at 2-12 months following birth in women who had received Anti-D at 28 and 34 weeks (OR 0.22 95% CI 0.05-0.88). No data were available for the risk of RhD alloimmunisation in a subsequent pregnancy. No differences were observed in the incidence of neonatal jaundice. The risk of RhD alloimmunisation during or immediately after a first pregnancy is about 1.5%. Administration of 100ug (500IU) anti-D at 28 weeks and 34 weeks gestation to women in their first pregnancy can reduce this risk to about 0.2% without, to date, any adverse effects. Although such a policy is unlikely to confer benefit or improve outcome in the present pregnancy, fewer women will have Rhesus D antibodies in their next pregnancy. Adoption of such a policy will need to consider the costs of prophylaxis against the costs of care for women who become sensitised and their affected infants, and local adequacy of supply of anti-D gammaglobulin.

Intravenous Anti-D Gammaglobulin for the Prevention of Rhesus Isoimmunization Caused by Platelet Transfusions in Patients with Malignant Diseases

Previous studies of sensitization to RhD by RhD-positive platelet transfusions in RhD-negative cancer patients have shown different frequencies of alloimmunization (max. 19%). We studied 37 RhD-negative patients who received RhD-incompatible platelet transfusions and simultaneously anti-D-immune globulin. We provide evidence that in this setting RhD-prophylaxis is highly effective in preventing alloimmunization due to RhD antigen, since none of the patients studied developed anti-D. Detection of other red blood cell antibodies than anti-D proves the possibility of immunization in these patients. Prevention of isoimmunization in patients with malignant diseases is recommended especially in young females, since an increasing number of patients are having successful pregnancies, despite prior or even during cytotoxic therapy.

Bleeding as a Consequence of Chorion Villus Sampling

A series of 4 separate studies were conducted to assess the incidence and short term consequence of bleeding associated with chorion villus sampling. Results support previous reports that risk of foetal-maternal transfusion as suggested by a rise in maternal serum alpha-fetoprotein (MSAFP) can occur. This occurrence is not consistent and need not be obvious even after therapeutic abortion. It is also transient and did not complicate mid-trimester neural tube screening or subsequent course of pregnancy. Eighty-seven percent of blood contaminating villus samples are of maternal origin. Following diagnosis 37% of patients reported some vaginal bleeding. This is mainly in the form of spotting which did not preclude normal pregnancy. Foetal loss occurred in 4 of the patients when bleeding considered heavier than spotting continued. In rhesus negative patients prophylactic anti-D gamma-globulin is advised, since neither Kleihauer counts nor MSAFP estimation reliably detect all foetal-maternal transfusions.

Fetal-maternal macrotransfusion--a study of 400 postpartum women.

The results of postpartum fetal cell counting in 400 Rh-negative patients delivering Rh-positive infants are presented and correlated with the mode of delivery and the ABO blood group relationship of baby and mother. Manipulative procedures, especially Caesarean section, are shown to increase the incidence of macrotransfusion. To make the most economical use of the new 125 microgram doses of anti-D gamma globulin, quantitation of fetal-maternal transfusions is shown to be vital if the existing level of protection from rhesus sensitization is to be maintained or increased.

Prevention of Rh-haemolytic Disease: Final Results of the "High-risk" Clinical Trial: A COMBINED STUDY FROM CENTRES IN ENGLAND AND BALTIMORE

The final results are reported of a trial of about 1,000 mug of anti-D gammaglobulin given intramuscularly to a selected high-risk group of Rh-negative primiparae just delivered of an ABO-compatible Rh-positive baby, the aim being to prevent them becoming immunized to Rh. Six months after delivery only 1 out of 173 treated mothers had been immunized as against 38 out of 176 controls. The crucial test of the prophylactic therapy depends on the presence or otherwise of anti-D at the end of a second Rh-positive pregnancy. Of 86 treated mothers two had antibodies at this time compared with 20 out of 65 controls.The results show a high degree of protection in this group of mothers.

Results of an antibody screening programme at an antenatal clinic: relevance to haemolytic disease of the newborn and blood transfusion reaction

Results of a routine antenatal antibody screening programme from March 1967 to March 1970 were presented. 5,354 sera from 4,724 pregnancies were screened. The indirect antiglobulin and saline techniques at 37° on separate selected commercially available screening cells were used throughout. All patients were screened at their first visit and Rh negative patients again at approximately 28 and 36 wk. gestation. Antibodies were identified with commercial cell panels. Eighty sera contained detectable antibodies (1.7%). In 44 pregnancies (41 patients) the sera contained anti-D or anti-C + D and in 36 there were other antibodies. In 12 of these (2 anti-C, 2 anti-E, 1 anti-c, 6 anti-Kell (5 patients) and 1 anti-Fya) the antibody was capable of causing haemolytic disease of the newborn but only 2 babies from this group were affected and only one (an anti-Kell) required exchange transfusion. The remaining non-rhesus antibodies could have caused transfusion reactions or cross-matching difficulties (17 anti-Lewis and 7 unidentified antibodies). Of the 44 pregnancies in which anti-D or anti-E + D were found, 12 were negative, 8 were positive at the initial antibody screen and 24 were known from previous pregnancies. Some of the 12 developing detectable antibodies during the pregnancy produced quite severe haemolytic disease. There was a decreasing rate of appearance of new examples of anti-D in each year of the programme and only one of the 20 cases developing anti-D for the first time had had anti-D gamma globulin with her last pregnancy. The yield of antibodies relevant to haemolytic disease was small but the screening of all antenatal patients for antibodies was felt to be worthwhile for the anticipation of cross-matching difficulties and for its effect in improving standards.

The place for anti-D gamma globulin in abortion.

SummaryA study was made of the incidence and volume of feto‐maternal haemorrhage in 129 patients with threatened or incomplete abortion, and in a control group of 110 healthy pregnant women. The incidence of feto‐maternal haemorrhage was 15.5% in the abortion group and 3.6% in the control group. The incidence of significant feto‐maternal haemorrhage was 14.3% in patients with incomplete abortion. The significant of these findings is discussed and it is concluuded that prophylactic anti‐D gamma globulin should be given to all non‐immunised rhesus negative women having any type of abortion.

INTENSIVE PLASMAPHERESIS AS A THERAPEUTIC MEASURE IN RHESUS-IMMUNISED WOMEN

Intensive plasmapheresis of pregnant and non-pregnant women, immunised to the Rh or Kell isoantigen, lowered the concentration of plasma-proteins, including total IgG and individual antibodies. The lowering of antibody concentration was detected by a method using radioactive anti-D gamma-globulin but not by a conventional agglutination technique. In general, the antibody content mirrored the IgG level during plasmapheresis, although in one pregnant woman the serum anti-D antibody content fluctuated despite a consistent fall in IgG. This patient may have been undergoing stimulation by Rh-positive fetal erythrocytes at the time of plasmapheresis. In all, eight pregnant women were treated by plasmapheresis in addition to conventional therapy. Of these, five gave birth to live infants, of which four survived the early postnatal period. Three non-pregnant women also received plasmapheresis.

Radiological aspects of fetal intrauterine transfusion.

WITHIN THE past few years, considerable progress has been made in the management of erythroblastosis fetalis. Although introduction of high-titer anti-D gamma globulin (RhrrGam)2 will inevitably decrease the potential population who might require intrauterine transfusion (IUT), the already highly sensitized mother cannot be treated with RhoGam and must still be controlled by IUT. Therefore, further development and refinement of procedures must be continued. Intrauterine transfusion is dependent upon several roentgenographic technics— radioisotopic localization of the placenta, grid localization of the fetus, localization of the fetal abdominal structures by injection of radiopaque medium, and fluoro-scopic placement of the transfusion needle. Ease of performance and low morbidity (to both mother and fetus) of the aforementioned procedures are just as important as the quality and quantity of information that can be obtained. Since intrauterine transfusion is still in the adjustment phase and newer approaches must be devised to overcome problems of the current technic, the authors will present the roentgenographic methods employed at the Yale-New Haven Medical Center. Results and complications related to these radiographic procedures will be discussed. Materials and Methods All patients who exhibited Rh sensitization (positive maternal blood Coombs titer of 1:8 or greater) in the current pregnancy or in a previous one were considered candidates for further evaluation by amnio-centesis and spectrophotometric analysis of the amniotic fluid. The initial step for each patient was localization of the placenta by radioisotopic scanning. The patient was given Lugol's solution followed by an injection of 10 µCi of albumin-tagged 131I. After fifteen minutes a scintillation scan of the abdomen was obtained. The area of the placenta was revealed by elevated counts. Whenever possible, amniocentesis was initially undertaken at twenty weeks gestation and at appropriate intervals thereafter. If spectrophotometric analysis revealed an optical density difference in the upper quarter of Zone II or in Zone III in a pregnancy of less than thirty-two weeks gestation, the patient was considered a candidate for repeat amniocentesis and possible intrauterine transfusion. Once the clinical and laboratory findings indicated the necessity for intrauterine fetal transfusion, the next step was the determination of the lie of the fetus and the location of the fetal abdomen. A wire grid was placed over the maternal abdomen (Fig. 1, A), and an anteroposterior radiograph was taken (Fig. 1, B). The fetal skeletal structures could thus be related to the grid markings. If the fetus was in a direct anteroposterior lie, a lateral film was obtained to determine whether the spine was anterior or posterior (Fig. 1, C).

Association between foeto-maternal bleeding and hypertension in pregnancy.

A blind prospective survey of foeto-maternal bleeding in 200 primiparous pregnancies was carried out in an investigation of a possible association between foeto-maternal bleeding and hypertension in pregnancy. Evidence of foeto-maternal bleeding was found in 61% of 36 hypertensive pregnancies, and in 51% of 160 normotensive pregnancies, a difference which is not statistically significant.Significant differences between the hypertensive and the normotensive groups were found when foeto-maternal bleeding was related to gestation. In pregnancies that became hypertensive more foetal cells were found in the maternal circulation before week 36 than in normotensive pregnancies. In patients with oedema of the abdominal wall during pregnancy the incidence of foeto-maternal bleeding was significantly increased.These findings seem to explain why pre-eclamptic toxaemia is a significant predisposing factor in women who later develop Rh antibodies. It is recommended that anti-D gammaglobulin should be offered to all Rh-negative women with Rh-positive infants following a hypertensive pregnancy. Consideration should also be given to the question of administering anti-D gammaglobulin during Rh-negative hypertensive pregnancies if this procedure is proved to be both safe to mother and foetus and effective.The results provide contributory evidence that the placental vascular changes in toxaemic pregnancies precede the clinical signs and are not the result of hypertension.

Immunization against Rh.

Clinical trials involving thousands of patients at risk have shown anti-D gamma globulin to be safe and effective in preventing Rh sensitization. Candidates for prophylaxis are women whose immune response has not yet been activated.

Rh-immunization by pregnancy: results of a survey and their relevance to prophylactic therapy.

A series of Rh-negative primiparae has been studied in order to gain further insight into the process of immunization by pregnancy. The distribution of foetal cell counts in blood samples taken after delivery was determined for 2,029 mothers giving birth to ABO-compatible babies and for 417 mothers with ABO-incompatible babies.A total of 760 mothers were tested for the development of Rh antibodies six months after the delivery of an ABO-compatible Rh-positive baby and 236 were further followed up through a second Rh-positive pregnancy. The incidence of anti-D six months after delivery is estimated to be 8.5%, and there is evidence of a direct relation between the count of foetal cells after delivery and the risk of developing antibodies. A further 8.5% of mothers were estimated to develop anti-D by the end of the second pregnancy, and it is postulated that these individuals had been primed by the first pregnancy. There is some evidence that the larger stimuli of Rh-positive blood in the first pregnancy are more likely to result in overt antibody formation, while the smaller stimuli are more likely to prime, antibodies not being detected until a second stimulus occurs during the second pregnancy.These findings are relevant to the programme for preventing Rh-immunization by injecting anti-D gammaglobulin.