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Anti-D administration in pregnancy for preventing Rhesus alloimmunisation

  1. Caroline A Crowther*,
  2. Philippa Middleton,
  3. Rosemary D McBain

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 14 NOV 2012

DOI: 10.1002/14651858.CD000020.pub2

How to Cite

Crowther CA, Middleton P, McBain RD. Anti-D administration in pregnancy for preventing Rhesus alloimmunisation. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD000020. DOI: 10.1002/14651858.CD000020.pub2.

Author Information

  1. The University of Adelaide, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia

*Caroline A Crowther, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Women's and Children's Hospital, 72 King William Road, Adelaide, South Australia, 5006, Australia. caroline.crowther@adelaide.edu.au.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Huchet 1987

MethodsQuasi-randomised trial.


Participants1969 women were randomised from January 1983 to June 1984.

Setting: women were recruited from 23 maternity units in the Paris region, France.

Inclusion criteria: women who were primipara and were Rh-negative.

Exclusion criteria: none detailed.


InterventionsTreatment group (Anti-D) (n = 927)

Women received two anti-D immunoglobulin injections (100 micrograms by intramuscular injection (500 IU)) at 28 and 34 weeks of pregnancy, after blood samples had been taken.

Control group (no Anti-D) (n = 955)

No placebo was given.

In both groups, women who gave birth to a Rhesus positive baby were administered post-partum (intravenously in almost all cases) anti-D immunoglobulin (100 micrograms), with possible re-treatment following review of fetal red blood cell test results.

1450 women were primigravid and 432 were multigravid.


OutcomesIncidence of immunisation during pregnancy, immunisation at 2-12 months following pregnancy, positive Kleihauer during pregnancy, at delivery, or postpartum. Cost-effectiveness data also provided.


NotesFrom the translation received for this manuscript, 1969 women began the study, with 1882 monitored until they went into labour.

The blood groups ABO and Rhesus D were determined using standard techniques.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNot detailed - women were allocated to groups on the basis of their birth year (even/odd)

Allocation concealment (selection bias)High riskAs above.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding was not detailed, however considered unlikely in view of the intervention. The lack of blinding, however, may be considered unlikely to affect the objectively measured outcomes.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskAs above.

Incomplete outcome data (attrition bias)
All outcomes
High riskFrom the translation received - 1969 women began the study, of those 1882 were monitored until they were in labour (the 87 women not followed up to birth were not accounted for).

In the control group, 2/957 women were excluded due to fetal-maternal haemorrhage, leaving 955 who were monitored until labour. Of these women, 590/955 gave birth to a Rh-positive baby, however two died at birth; 468 women were followed up postpartum (no reasons given for the 122 women not followed up postpartum). In the treatment group 599/927 gave birth to a Rh-positive baby; 472 women were followed up postpartum (no reasons given for the 127 women not followed up postpartum).

Selective reporting (reporting bias)Low riskNo clear evidence of selective reporting - outcome measures reported appear to have been pre-specified.

Other biasLow riskNo obvious risk of other bias.

Lee 1995

MethodsRandomised controlled trial.


Participants2541 women were randomised.

Setting: obstetric units throughout the UK.

Inclusion criteria: Rh-negative primigravidae before 28 weeks' gestation.

Exclusion criteria: any woman with anti-D other than passive found at a 28-week blood sample was excluded from the trial. Women who had already received anti-D to cover a potentially sensitising event were not excluded - where such an event took place after 28 weeks, the patient received anti-D in the usual way.


InterventionsTreatment group (Anti-D) (n = 1268)

Women in the treatment group received 50 micrograms (250 IU) anti-D intramuscularly at 28 and 34 weeks' gestation (n = 952).

Control group (no Anti-D) (n = 1068)

Women received no placebo.

Women in both groups "were considered for anti-D Ig in the normal way at delivery".


OutcomesPresence of anti-D at birth and 6 months postpartum (repeated if equivocal); also reported "potentially sensitizing events."


NotesSample size needed to detect five fold reduction in sensitisation: 5200 women.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskGeneration of random sequence was not detailed.

Allocation concealment (selection bias)Unclear riskQuote - "sealed envelopes" were used; no further detail provided regarding how the envelopes were numbered, or whether they were opaque.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding was not detailed, however considered unlikely in view of the intervention. The lack of blinding, however, may be considered unlikely to affect the objectively measured outcomes.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskAs above.

Incomplete outcome data (attrition bias)
All outcomes
High risk1273 women were controls and 1268 were in the treatment group; no data was provided for 205 controls and 264 women from the treatment group (no details provided). In the control group 649 women gave birth to Rh-positive infants (398 infants were Rh-negative; unknown for 21 infants). One additional woman was excluded from the control group after she was found to have immune anti-D at randomisation with a history of threatened abortion. Therefore, only 648 women were included in the analysis. In the treatment group 532 women and infants were included in the analysis (393 infants were Rh-negative, and 52 women did not receive both doses of anti-D and these women were excluded from further analyses - unknown whether infants were Rh-positive/negative). Not an intention-to-treat analysis.

Selective reporting (reporting bias)Unclear riskTrial reported only presence of anti-D at birth and 6 months postpartum; a number of outcomes that may have been expected, such as positive Kleihauer during pregnancy/delivery/postpartum, or neonatal morbidity were not reported.

Other biasLow riskNo other obvious sources of bias identified.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Ismail 2002This is only the plan for a trial. Trial not proceeding at this stage (Z Alfirevic, personal communication March 2004).

 
Characteristics of ongoing studies [ordered by study ID]
Manjunath 2008

Trial name or titleA clinical trial to study the effect of injection of anti-D administered during pregnancy for Rh-negative mothers

MethodsRandomised controlled trial.

Participants100 women.

Setting: Dr TMA Pai Rotary Hospital, Karkala, India.

Inclusion criteria: all Rh-negative and indirect agglutinin test negative primigravida and un-sensitised multigravida who are willing to participate in the study.

Exclusion criteria: all Rh-negative mothers with Rh-negative husbands. Indirect agglutinination test positive.

InterventionsTreatment group (n = ?) antenatal administration of 300 micrograms (1500 IU) of Rh-D immunoglobulin.

Control group (n = ?) no intervention.

OutcomesPrimary outcomes: incidence of immunisation during pregnancy at term, at delivery and at 6 months.

Secondary outcomes: incidence of neonatal hyperbilirubinaemia, need for exchange transfusion, and need for phototherapy.

Starting date1/12/2008 (on the trial registry however, the trial is listed as "not yet recruiting").

Contact informationScientific queries:

Dr A P Manjunath

Associate Professor

Department of Obstetrics and Gynaecology

576104, India

Phone: 09845913140

Fax: 080257061

Email: manjunanth.ap@manipal.edu

Notes

 
Comparison 1. Anti-D administration in pregnancy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Immunisation in pregnancy23902Risk Ratio (M-H, Fixed, 95% CI)0.42 [0.15, 1.17]

    1.1 100 micrograms at 28 and 34 weeks
11882Risk Ratio (M-H, Fixed, 95% CI)0.17 [0.02, 1.42]

    1.2 50 micrograms at 28 and 34 weeks
12020Risk Ratio (M-H, Fixed, 95% CI)0.64 [0.19, 2.18]

 2 Immunisation after birth of a Rhesus-positive infant22297Risk Ratio (M-H, Fixed, 95% CI)0.42 [0.15, 1.17]

    2.1 100 micrograms at 28 and 34 weeks
11189Risk Ratio (M-H, Fixed, 95% CI)0.16 [0.02, 1.36]

    2.2 50 micrograms at 28 and 34 weeks
11108Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.20, 2.25]

 3 Immunisation at 2-12 months22048Risk Ratio (M-H, Random, 95% CI)0.39 [0.10, 1.62]

    3.1 100 micrograms at 28 and 34 weeks
1940Risk Ratio (M-H, Random, 95% CI)0.14 [0.02, 1.15]

    3.2 50 micrograms at 28 and 34 weeks
11108Risk Ratio (M-H, Random, 95% CI)0.64 [0.22, 1.91]

 4 Immunisation at 2-12 months - primigravidae alone1722Risk Ratio (M-H, Fixed, 95% CI)0.11 [0.01, 2.04]

 5 Positive Kleihauer at 32-35 weeks11884Risk Ratio (M-H, Fixed, 95% CI)0.60 [0.41, 0.88]

 6 Positive Kleihauer at birth of a Rhesus-positive infant11189Risk Ratio (M-H, Fixed, 95% CI)0.60 [0.46, 0.79]

 7 Kleihauer > 1/10,000 - Rhesus-positive infant11189Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.59, 1.54]

 8 Neonatal jaundice11882Risk Ratio (M-H, Fixed, 95% CI)0.26 [0.03, 2.30]