Prediction of the severity of haemolytic disease of the newborn. Quantitative IgG anti-D subclass determinations explain the correlation with functional assay results.

Sera containing anti-D, taken from 44 RhD-negative women with RhD-positive infants, were tested in antibody-dependent cellular cytotoxicity (ADCC) and monocyte monolayer assays (MMA) which used similar target and effector cell populations. In addition, the anti-D concentration was measured in the Auto Analyzer and the number of IgG1 and IgG3 anti-D molecules bound to the target red cells was measured by flow cytometry. The results of the functional assays and Auto Analyzer quantitation were examined for correlation with IgG subclass quantitation and all results were compared for their ability to predict the severity of haemolytic disease of the newborn (HDN). ADCC correctly predicted HDN in 39/44 (88.6%) cases, Auto Analyzer quantitation in 35/44 (79.5%) and the MMA in 32/44 (72.7%). For all three assays, the number of correct predictions was highest when the maternal serum contained both IgG1 and IgG3 anti-D. ADCC activity and HDN were correlated with the number of cell-bound IgG1 molecules (r > or = 0.58), but MMA activity was most closely correlated with the number of cell-bound IgG3 molecules (r = 0.68). Hence the superior predictive value of ADCC is due to its ability to reflect the IgG1 component of maternal anti-D, which has a better correlation than IgG3 anti-D with the severity of HDN.

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.

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.

Prevention of Rh haemolytic disease.

Between 1970 and 1976 in the Yorkshire region the incidence of Rh antibodies in Rh-negative pregnant women fell by 70%. This decrease occurred in both old (long-standing) and new (first-affected) cases, which emphasised that the reduction in numbers was as much due to fewer pregnancies among Rh-negative mothers as to administration of anti-D immunoglobulin. Nevertheless, the incidence has begun to level out. The continued incidence of first-affected cases is caused by three main factors: failure of administration of anti-D immunoglobulin after normal deliveries and abortions; a steady incidence of antibodies in primigravidae; and cases in which administration of anti-D immunoglobulin had failed to protect. Administering anti-D antenatally might reduce the incidence of new cases among primigravidae who are sensitised before anti-D is normally given. Even without routine antenatal administration of anti-D, the incidence of severely affected Rh babies in the Yorkshire region could be reduced to one or two isolated cases a year in a population of three to four million by administering anti-D after all Rh-negative deliveries and after every abortion.