Abstract: We included 12 studies (430 participants) in the review: seven RCTs and five CCTs where it was not clear whether participants were randomly allocated to groups. We did not include any unpublished studies. Participants included children and adults of both sexes. Only one study included pregnant women. All studies were conducted in high-income countries. The quality of the 11 studies in the initial meta-analysis was moderate, although we classified no study as having a low risk of bias on all criteria. We included 11 studies in the initial meta-analysis of gamma-globulin (concentrated polyclonal immunoglobulins) versus control (saline or no treatment) for rubella cases. The result favoured the intervention group (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.45 to 0.83) but was heterogenous (Chi² test = 36.59, df = 10 (P value < 0.0001); I² statistic = 73%). Heterogeneity was explained by subgrouping studies according to the estimated volume of gamma-globulin administered per pound of bodyweight and then removing those studies where the intervention was administered more than five days after participant exposure to rubella (post hoc analysis). The test of subgroup differences demonstrated heterogeneity between subgroups according to our protocol definition (P value < 0.1; I² statistic > 60%) and there appeared to be greater effectiveness of the intervention when a greater volume of gamma-globulin was administered ('0.027 to 0.037 ml/lb' RR 1.60 (95% CI 0.57 to 4.52); '0.1 to 0.15 ml/lb' RR 0.53 (95% CI 0.29 to 0.99); '0.2 to 0.5 ml/lb' RR 0.20 (95% CI 0.04 to 1.00)). None of the studies reported the outcome 'congenital rubella infection'. One included study reported on congenital rubella syndrome, with no cases among participants who were fewer than nine weeks pregnant at enrolment and who were randomised to one of two gamma-globulin groups ('high' or 'low' rubella titre). However, the study did not report how congenital rubella syndrome was measured and did not report the length of follow-up according to intervention group. This study did not include a non-treatment group. No included study measured adverse events. Compared to no treatment, polyclonal immunoglobulins seem to be of benefit for preventing rubella. The available evidence suggests that this intervention may be of benefit up to five days after exposure, and that effectiveness is dependent on dose. Considering the attack rate for rubella cases in the control group of the highest volume gamma-globulin subgroup (333 per 1000), the absolute risk reduction (calculated from the RR) for this volume of gamma-globulin was 266 (95% CI 0 to 320) and the number needed to treat to benefit is four (95% CI 3 to incalculable). The included studies did not measure rubella-specific antibodies in the immunoglobulin products used in a standard way and thus estimation of the dose of rubella-specific antibodies in international units administered was not possible. As the concentration of rubella-specific antibodies in today's polyclonal immunoglobulin products may vary from those products used in the studies in the review, the volume required per pound of bodyweight to produce similar results may also vary. There is insufficient evidence to make direct conclusions about the effectiveness of polyclonal immunoglobulins for preventing congenital rubella syndrome. This is an area requiring further research.

Plain-language summary: The evidence is current to August 2014. We included 12 studies (430 participants). People of all ages were included in the studies, which were conducted in high-income countries. Eleven studies (389 participants) compared injecting antibodies into the muscle or vein of participants to injecting salt water or giving no treatment. The study participants did not have their own antibodies. They had been in contact with rubella between one and 28 days prior to receiving the antibodies. The antibodies seemed to be effective at preventing participants from catching rubella, with those receiving antibodies 39% less likely to develop rubella than those not given antibodies. In an analysis of the seven studies (89 participants) where participants had been in contact with rubella only up to five days earlier, people given the highest doses used in the studies were 80% less likely to develop rubella than those not given antibodies. The studies assessing the prevention of rubella were of moderate quality because of some methodological issues and the fairly small number of participants. It is important to consider that the amount of rubella antibodies in today's blood donations may differ from those used in the studies. Therefore, doses given today may need to vary from those of the studies in order to obtain the same effect. Only one study included pregnant women. All of the women were given one of two different doses of antibodies. They did not measure whether the babies born to the women were infected with rubella, but did consider whether birth defects that may be related to rubella were present. Key details about the study methods were missing and unobtainable, so the quality of this study was unclear. None of the babies born to these women were identified as having birth defects related to rubella. However, we cannot draw direct conclusions from this single study about the effectiveness of injecting antibodies after contact with rubella for preventing rubella-related birth defects in pregnant women. This is an area that needs further research. The included studies did not report adverse events. Future studies should report this outcome.