Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin.

OBJECTIVE: To measure the safety and efficacy of antenatal treatment with anti-D immunoglobulin. DESIGN: Open study with historical controls. SETTING: Multicentre study in 17 hospitals in West Yorkshire. PATIENTS: 1238 Rh negative women who delivered Rh positive infants after 34 weeks in their first pregnancy in 1980-1 (group 1) and 2000 similar primigravidas from 1978-9 (group 2). Obstetric data were collected for 616 women in group 1 who had a subsequent pregnancy, 536 similar women in group 2, and 410 Rh positive but otherwise similar primigravidas who delivered in the same hospitals in 1978-81 (group C). INTERVENTIONS: Anti-D immunoglobulin 100 micrograms intramuscularly was given at 28 and 34 weeks to the mothers in their first pregnancy who delivered in 1980-1. END POINTS: Detection of anti-D antibody in the first or any subsequent pregnancy in groups 1 and 2. For all three groups having subsequent pregnancies gestation at delivery, birth weight, fetal survival at one month, pre-eclampsia defined as blood pressure greater than 140/90 on two occasions more than 12 hours apart, and proteinuria greater than 0.25 milligram. MEASUREMENTS AND MAIN RESULTS: Antenatal immunisation to Rh(D) occurred in six mothers in group 1 and 32 group 2. Most immunisations occurred in the first or second pregnancy. The rates of abortion, gestation at delivery, birth weight, and fetal survival were not significantly different among the three groups. The incidence of pre-eclampsia was lower in mothers given antenatal anti-D immunoglobulin, but the difference was not significant. CONCLUSIONS: Antenatal prophylaxis with anti-D immunoglobulin is effective, and the effect of giving it in the first pregnancy persists into at least the second pregnancy. It seems to be safe for the fetus in the index and subsequent pregnancies.

Enzyme linked immunosorbent assay (ELISA) for cytomegalovirus antibody in donor plasma.

An adaptation of an enzyme immunoassay technique was developed to screen donor plasma for high titres of antibodies to cytomegalovirus (CMV). The technique uses microtitre plates treated with glutaraldehyde and coated with CMV antigen and an anti-IgG alkaline phosphatase conjugate to detect the captured antibody. Using an anti-CMV standard with a 1/64 titre by complement fixation, 34 (6.8%) of 500 sera were shown to have an antibody titre that was acceptable to the Blood Products Laboratory in England for anti-CMV immunoglobulin production.

False positive results of tests for syphilis and outcome of pregnancy: a retrospective case-control study.

In a retrospective case-control study 64 women yielding a false positive result to a test for syphilis in pregnancy were compared with 128 controls individually matched for age, parity, hospital of delivery, and year of delivery. There were significantly more unsuccessful pregnancies, mainly spontaneous abortions during the first and second trimesters, among women with persistent false positive results. There was no significant difference between groups in the mean birth weights of liveborn infants. The antibodies responsible for the false positive result may indicate the presence of an immunological disturbance. Women who give a false positive result should be carefully managed throughout their pregnancy.

Haemolytic disease of the newborn--the changing scene.

Between 1950 and 1970 there was a steady decline in the number of infant deaths from rhesus haemolytic disease of the newborn in the Yorkshire Region but no decrease in the number of pregnant women with antibodies. Following the introduction of Rh prophylaxis in 1970, the number of pregnant women sensitized has decreased by 70% and the number of infant deaths by 96%. The number of infants requiring exchange transfusion has also decreased by 70%. During the years 1980 to 1983 there were 163 new cases of maternal sensitization to the D antigen in the Yorkshire Region, 36 were due to failures of administration, 75 were failures of protection and 26 were in primigravidae. Eighteen of the failures of administration occurred after abortion, nine of which were surgical terminations. Antenatal prophylaxis may well have protected 64 (40%) of these 163 women. The number of pregnant women with antibodies other than anti-D now exceeds those with anti-D. The effect of these changes in incidence and clinical severity on the management of Rh D negative pregnant women is discussed.

Follow-up of normal individuals with a positive antiglobulin test.

Over a period of 20 yr (1962-1982), 67 apparently fit donors at a Regional Blood Transfusion Service were found to have an unexplained positive direct antiglobulin test (DAT). During 1983, 26 were traced and re-tested. 9 still had a positive DAT only 1 of whom had developed autoimmune haemolytic anaemia. 17 had become negative though in 7 of these an autoantibody could still be detected by an enzyme technique. Unlike patients with established autoimmune disorders, the positive DAT individuals were found to have normal T cell subsets though B cells were significantly increased.

The Yorkshire antenatal anti-D immunoglobulin trial in primigravidae.

2069 Rh(D)-negative women in their first pregnancy received 100 micrograms doses of anti-D immunoglobulin at 28 and 34 weeks' gestation and a further dose at delivery if the infant was Rh(D)-positive. The antibody status was determined at 28 weeks, 34 weeks, at delivery, and 6 months after delivery. The findings were compared with those in a control group of 2000 Rh(D)-negative primigravidae who gave birth to Rh(D)-positive infants and received the standard post-delivery injection of anti-D immunoglobulin. 2 women in the trial group and 18 in the control group became actively immunised during the first pregnancy. 325 women in the trial group have had a further Rh(D)-positive pregnancy and in 2 anti-D antibodies were detected for the first time. 528 control women have had a further Rh(D)-positive pregnancy and anti-D was demonstrable in 29-18 in whom antibodies developed during the first pregnancy and 11 in whom antibodies first appeared during the second. The reduction in the incidence of sensitisation was significant. It is estimated that the extra cost in anti-D immunoglobulin was approximately pounds 1600 for each woman sensitised.

Fetomaternal blood group incompatibility studies in placental intervillous thrombosis.

Samples of maternal and fetal blood from 32 cases of placental intervillous thrombosis have been analysed for blood group incompatibility and compared to a control group of 21 cases. No overall link has been demonstrated between intervillous thrombosis and ABO incompatibility. Red cell antibody reactions of all types probably account for only a small proportion of thrombi and it is suggested that the principle mechanism may be a thromboplastin release from the damaged vasculo-syncytial membrane, causing a coagulation of the mixed maternal and fetal cells.

Development of multiple antibodies in an apparently 'protected' Rh D negative mother.

A case is described of a group O Rh (D) negative woman who received a blood transfusion after the delivery of her first infant, blood group O Rh (D) negative. In her second pregnancy anti-S was detected, presumably due to the prior transfusion. The second infant was D+S+ and the direct antiglobulin test on this infant's cells was positive. As no anti-D antibodies were detectable in this pregnancy, the positive antiglobulin test was presumably due to the anti-S. Anti-D immunoglobulin was administered after this pregnancy, but in spite of this the mother developed a strong anti-D antibody. The significance of this 'failure of protection' is discussed in relation to the augmenting affect of antibody development during pregnancy.

A case for the antenatal administration of anti-D immunoglobulin to primigravidae.

The value and practicability of introducing an antenatal anti-D immunoglobulin programme is a matter of controversy. Those in favour of the programme claim it is the only procedure available which will reduce still further the incidence of Rh sensitisation. Opponents claim it is not cost-effective. An analysis of data collected in the Yorkshire region points to the value of at least giving anti-D antenatally to all Rh-negative primigravidae and, if the baby is found to be Rh-negative, administering anti-D antenatally in the second pregnancy. Mothers developing anti-D antibodies in their first Rh-positive pregnancy are major contributors to the number of infant deaths due to Rh haemolytic disease of the newborn. When anti-D immunoglobulin is given to a mother with no demonstrable antibodies and she develops Rh antibodies in her next Rh-positive pregnancy, the prognosis for the child is good and "failures of protection" of anti-D immunoglobulin rarely result in infant deaths due to Rh antibodies.

Suppression of early rhesus sensitization by passive anti-D immunoglobulin: suppression of early rhesus sensitization.

Anti-D immunoglobulin is an effective prophylactic against rhesus isoimmunization. It is generally regarded as ineffective once antibody production has developed though there have been a number of inconclusive reports suggesting it may suppress early sensitization. Anti-D (100 micrograms) was given after delivery of a rhesus (D) positive child to a rhesus (D) negative mother who was shown to have anti-D antibodies at that time by five tests on two separate specimens in two different laboratories and by a weakly positive direct anti-globulin test on the cord blood. In a further pregnancy with a rhesus (D) positive child no antibody was detected by multiple tests including enzyme technique.