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 (I²  =  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 (I²  =  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.


CONCLUSIONS
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.
Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom. rebecca.turner@mrc-bsu.cam.ac.uk
Rebecca M
RM
Turner
Myfanwy
M
Lloyd-Jones
Dilly O C
DO
Anumba
Gordon C S
GC
Smith
David J
DJ
Spiegelhalter
Hazel
H
Squires
John W
JW
Stevens
Michael J
MJ
Sweeting
Stanislaw J
SJ
Urbaniak
Robert
R
Webster
Simon G
SG
Thompson
D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000627:therapeutic use*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000517:prevention & control; D011292:Premedication / Q000379:methods*; D012107:Research Design; D012203:Rh Isoimmunization / Q000188:drug therapy / Q000517:prevention & control; D018029:Rho(D) Immune Globulin; D016896:Treatment Outcome
D007518:Isoantibodies; C061961:RHO(D) antibody; D018029:Rho(D) Immune Globulin