internal and external biases except Intervention bias. The fitted model was then used to predict the underlying effectiveness odds ratio expected in a future study of any of the seven treatments, including the two on which no direct data are available. Results Study characteristics and extracted results The designs of the ten RAADP studies included in our analyses are summarised in Table 1. The anti-D prophylaxis regimen administered to women in the intervention group varied across studies. Anti-D was given on either one or two occasions, and doses and planned timing of routine prophylaxis differed. There was also substantial variation in the time at which women were Table 2. Potential internal biases identified in the studies. Effectiveness of Antenatal Anti-D Prophylaxis followed up for sensitisation to Rhesus positive antibodies. Sensitisation can be most accurately assessed in a subsequent pregnancy [5], as in the MacKenzie [12] and Mayne [13] studies, but some studies assessed sensitisation immediately after each woman’s first delivery or at 6–12 months postpartum. The study populations varied somewhat across studies in terms of both their geographical locations, and the fact that some studies included non-sensitised multigravidae as well as primigravidae. Table 1 presents the odds ratios extracted from each study, comparing RAADP to control. Six of the studies found evidence of a lower sensitisation rate in women who received RAADP. Odds ratio estimates in the other four studies were also well below 1, but the associated confidence intervals were wide as a consequence of small sample sizes. Substantial differences in design mean that a Study Bowman (1) [6] Bowman (2) [7] Bowman (3) [8] Hermann [9] Huchet [10] Lee [11] MacKenzie [12] Mayne [13] Tovey [14] Trolle[15] Selection bias Historical controls used, and location of women recruited also differed to some extent between groups. Confounding not addressed. Historical controls used in comparison between groups. Confounding not addressed. Historical controls used in comparison between groups. Confounding not addressed. Historical controls used, and very little information on inclusion/exclusion criteria. Confounding not addressed. Contemporary controls used, but allocation to groups was non-random. Confounding not addressed. Contemporary controls used, but location of women recruited differed between groups. Confounding not addressed. Historical controls used. Confounding not addressed. Historical controls used. Confounding not addressed. Historical controls used. Treated group excludes sensitised women at 28 weeks, but control group does not. Confounding not addressed. doi:10.1371/journal.pone.0030711.t002 Performance bias No blinding, so the likelihood of receiving directed anti-D after potentially sensitising events may differ between groups. No blinding, so the likelihood of receiving directed anti-D after potentially sensitising events may differ between groups. No blinding, so the likelihood of receiving directed anti-D after potentially sensitising events may differ between groups. No blinding, so the likelihood of receiving directed anti-D after potentially sensitising events may differ between groups. No blinding, so the likelihood of receiving directed anti-D after potentially sensitising events may differ between groups. No blinding, so the likelihood of receiving directed anti-D after potentially sensitising events may differ between groups. No blinding (as above). No individual follow-up, so women migrating into intervention group area may not have received routine anti-D in first pregnancy. No blinding (as above). No individual follow-up, so women migrating into intervention group area may not have received routine anti-D in first pregnancy. No blinding (as above). No blinding (as above). In addition, some controls may not have received anti-D after delivery, as control period predates routine use of anti-D in Denmark. Attrition bias Unclear – losses to follow-up not reported. Unclear – losses to follow-up not reported. Unclear – losses to follow-up not reported. Some posthoc exclusions in intervention group. No information on losses to follow-up or exclusions in control group. 4% of women lost to follow-up after recruitment. No outcome available for 21% of remaining treated women and 21% of controls. 21% of treated women and 16% controls lost to follow-up after recruitment. No outcome available for 32% of remaining treated women and 38% of controls. Unclear – insufficient details on how sensitisation rates in the two groups were determined. Unclear – insufficient details on how sensitisation rates in the two groups were determined. Unclear – losses to follow-up not reported. 16% of treated women and 9% controls lost to follow-up. Outcome bias Suggestion that outcome assessors couldn’t distinguish between immune and passive antibodies. Suggestion that outcome assessors couldn’t distinguish between immune and passive antibodies in control group. Suggestion that outcome assessors couldn’t distinguish between immune and passive antibodies in control group. Suggestion that outcome assessors couldn’t distinguish between immune and passive antibodies. Possibility that outcome assessors couldn’t distinguish between immune and passive antibodies. PLoS ONE | www.plosone.org 5 February 2012 | Volume 7 | Issue 2 | e30711