Prevention of Rh-haemolytic Disease: Results of the Liverpool "Low-risk" Clinical Trial

Abstract

SummaryA clinical trial is reported in which Rh-negative primiparae, just delivered of an Rh-positive ABO-compatible infant and in whom fetal cell counts after delivery suggested less than 02 ml of circulating fetal blood, were treated with about 200 jig of anti-D gammaglobulin.Three (0 36%) out of 844 women thus treated developed anti-D in the subsequent six months; this is 10% of the incidence in untreated controls. Three (1-8%) out of 171 treated mothers had anti-D at the end of the second Rh-positive pregnancy, and this is 18% of the incidence in controls.Possible reasons for the occasional failure of the treatment are discussed and the results of this trial are compared with those of a previous trial in which 1,000 jig or more of anti-D was given to a different group of mothers. The combined results of the two trials lead to the conclusion that the passive administration of anti-D gammaglobulin after delivery affords in this population of Rh-negative women a 95% protection rate in the postdelivery period and an 89% protection rate by the end of the subsequent pregnancy. IntroductionIn our report of a clinical trial to test the effectiveness of about 1,000 F±g of anti-D gammaglobulin in preventing Rh immunization of Rh-negative primiparae (Combined Study, 1966) it was noted that a further trial had been initiated in Liverpool. The plan of this second one was to treat mothers showing less than an estimated 0-2 ml of Rh-positive fetal blood in their circulation after delivery with about 200 Fg of anti-D gammaglobulin. The results of this trial are presented here and some implications discussed.

Antenatal and postpartum prevention of Rh alloimmunization: A systematic review and GRADE analysis

“…Trials were conducted in Argentina, Australia, Canada, France, Germany, the Netherlands, Scotland, the UK, and the USA. Most trials were performed in the 1960’s and 1970’s [ 30 , 33 – 39 ], and several had multiple publications providing data at different time points or from different countries (footnoted in Table 2 ). Six trials evaluated postpartum RhIg [ 30 , 33 – 35 , 38 , 40 ], three trials evaluated antenatal RhIg [ 32 , 41 , 42 ], two trials evaluated RhIg given to women who experienced abortion [ 37 , 39 ], and two trials evaluated antenatal RhIg given either intramuscularly or intravenously [ 43 , 44 ].…”

“…Some trials had companion papers providing additional results for a subgroup of low-risk women [30], or provided additional dosage levels [31]. Study characteristics are summarized in Table 2.…”

“…Three trials followed women until their next Rh-positive pregnancy [30,34,38], with 130 fewer sensitized women per 1,000 who received any dose of RhIg in previous pregnancy compared to no RhIg (95%CI: 117 to 139 fewer; very low certainty) (S6 File: 1.1.2, 1.1.5). When evaluated per dose, in the 200 μg and 1000 μg groups compared to no RhIg, fewer women became sensitized (very low certainty) (S6 File: 1.1.2, 1.1.6).…”

The Risk of Rh Isoimmunization in Ruptured Tubal Pregnancy

“…The prophylactic administration of Rh immunoglobulin is an accepted method of prevention of Rh isoimmunization. Clinical trials have shown that more than 90% of Rh-negative primiparae are protected if the recommended dose of Rh immunoglobulin is injected within 72 hours of the birth of a Rh-positive baby (Combined Study, 1971;Woodrow et al, 1971). In addition to full-term pregnancy abortion has been implicated as a cause of Rh isoimmunization (Matthews and Matthews, 1969;Katz, 1969), and it is recommended that all Rh-negative women who have aborted should receive Rh immunoglobulin prophylactically (Freda et al, 1970; Murray and Barron, 1971).…”

The Risk of Rh Isoimmunization in Ruptured Tubal Pregnancy

“…Clinical trials have shown that more than 90% of Rh-negative primiparae are protected if the recommended dose of Rh immunoglobulin is injected within 72 hours of the birth of a Rh-positive baby (Combined Study, 1971;Woodrow et al, 1971). In addition to full-term pregnancy abortion has been implicated as a cause of Rh isoimmunization (Matthews and Matthews, 1969;Katz, 1969), and it is recommended that all Rh-negative women who have aborted should receive Rh immunoglobulin prophylactically (Freda et al, 1970;Murray and Barron, 1971).…”