Compliance with postpartum Rh isoimmunization prophylaxis in Alberta

A retrospective review of obstetric records for 1979 in two major Calgary hospitals was undertaken to determine the rate of compliance with postpartum Rh isoimmunization prophylaxis in Alberta. The charts of 4528 women ranging in age from 13 to 46 years were reviewed. The prevalence rate of Rh negativity was found to be 16%. Of the 710 Rh-negative women 490 (69%) were eligible to receive Rh immune globulin (RhIG); that is, they had no anti-D antibodies, and the baby/fetus was Rh-positive or Rh-unknown. RhIG had been administered to 93.6% of the eligible women; the compliance rate ranged from 66.7% for obstetric emergencies (i.e., spontaneous abortion, antepartum or early-pregnancy hemorrhage, or ectopic pregnancy) to 98.2% for postpartum diagnoses. In more than half (54.7%) of the women who underwent amniocentesis Rh type was not determined; the implications of this finding are discussed. Although poor compliance with postpartum RhIG administration is not a reason for withholding antepartum administration of RhIG, maximum compliance with the more cost-effective programs should be attained before antepartum programs are fully implemented.     

Antenatal prophylaxis of Rh isoimmunization: 28-weeks'-gestation service program

Two (0.18%) of 1086 Rh-negative primigravidas or multigravidas treated similarly in all previous pregnancies, who were given a single injection of Rh immune globulin (300 μg) at 28 weeks'' gestation and subsequently were delivered of Rh-positive babies, had demonstrable Rh isoimmunization at the time of that injection and must be considered “logistic” failures of antenatal prophylaxis. The remaining 1084 (who were treated again after delivery) had no evidence of Rh isoimmunization at delivery and none of the 512 screened at 6 months after delivery appeared to be immunized. If the 28th-week injection had not been protective, one would have expected 14 of the 1084 to have been demonstrably Rh isoimmunized and evidence of Rh isoimmunization to have persisted in 6 of the 512 observed 6 months after delivery.Six of 719 Rh-negative multigravidas who had not received Rh immune globulin after previous pregnancies or had been treated only after delivery showed evidence of Rh isoimmunization despite a single injection of Rh immune globulin at 28 weeks in a subsequent pregnancy. In three of the six the cause was most likely “sensibilization” due to previous exposure to Rh-positive blood or an untreated Rh-positive pregnancy. in 3 of the remaining 716 (0.42%) there may have been true failure of antenatal Rh prophylaxis administered at the 28th week. One would have expected this figure to be 12 of 716 if antenatal Rh prophylaxis at 28 weeks'' gestation were totally unsuccessful.It is concluded that a single intramuscular injection of Rh immune globulin, 300 μg, is 88% effective in preventing Rh isoimmunization during pregnancy in Rh-negative primigravidas and in multigravidas treated antenatally in all previous pregnancies, and is 75% effective in preventing Rh isoimmunization in Rh-negative multigravidas untreated during previous pregnancies. The majority of failures are due to Rh isoimmunization during pregnancy prior to antenatal prophylaxis at 28 weeks.     

Rh isoimmunization,Manitoba, 1963-75.

The number of Rh-isoimmunized pregnancies in Manitoba has been reduced from 223 and 228 in the years ending Oct. 31, 1963 and 1964 to 60 and 62 in the years ending Oct. 31, 1974 and 1975. The number per 1000 total births in the same years has decreased from 10.0 and 10.6 to 3.4 and 3.5 Perinatal mortality rates in those years decreased from 13.8 amd 15.7% to 0 and 2.2%, respectively. The number of perinatal deaths has been reduced from 55 in the first 2 years reported to 1 in the last 2 years. Among the 121 isoimmunized women pregnant in the 2-year period ending Oct. 31, 1975, isoimmunization was due to failure to give Rh immune globulin after delivery in 33 and failure to give it during pregnancy in 48. Of the remaining 40, 37 were immunized before Rh immune globulin became available. Complete prevention of Rh isoimmunization and therefore of all perinatal deaths from Rh erythroblastosis can only be achieved through universal Rh testing prenatally and immediately after delivery, and institution of an antenatal Rh prophylaxis program.     

Mechanism of Rh prophylaxis: an experimental study on specificity of immunosuppression.

The mechanism by which Rh immunization is prevented by IgG anti-D was investigated by studying the specificity of immunosuppression. 62 D-negative Kell(K)-negative male volunteers were given two successive stimuli of 1 ml D-positive K-positive red cells. Thirty-one of the volunteers were also given 13-14 mug of IgG anti-K immediately after each stimulus, the others acting as controls. Anti-D developed in 11 of the 31 controls and in one of the 31 volunteers who had received anti-K. This marked suppression of the anti-D response by IgG anti-K was accompanied by the rapid clearance of the injected red cells to the spleen. This shows that the predominant mechanism that must be operating when IgG anti-D prevents Rh immunization is not antigen specific but is one that must involve the whole red cell, probably through destruction within splenic macrophages.     

Routine antenatal anti-D prophylaxis in women who are Rh(D) negative: meta-analyses adjusted for differences in study design and quality

Background

To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted.

Methods

Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects meta-regression analysis.

Results

In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I ² = 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), with no evidence of heterogeneity (I ² = 0%). A meta-regression analysis was performed, which used the data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is most effective and a 76% probability that a single dose of 1500 IU at 28–30 weeks is least effective.

Conclusion

There is strong evidence for the effectiveness of routine antenatal anti-D prophylaxis for prevention of sensitisation, in support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative women. All three licensed dose regimens are expected to be effective.