BACKGROUND: The Sapporo criteria for the diagnosis of the antiphospholipid syndrome (APS) are based on the presence of antiphospholipid antibodies (APLA) and clinical criteria. Although pre-eclampsia, intra-uterine growth restriction (IUGR), late fetal loss and placental abruption, collectively termed “placenta mediated complications”, are recognized as clinical criteria for the APS, their association with APLA remains controversial.

OBJECTIVE: This review was conducted to evaluate the association between APLA (anticardiolipin antibodies, lupus anticoagulant, anti B2 glycoprotein 1 antibodies) and placenta mediated complications in untreated women without autoimmune diseases.

METHODS: We performed a systematic review of published case-control, cohort and cross sectional studies using MEDLINE (1975 to October week 2 2007), EMBASE 16 (1980 to 2007 week 42) and all EBM Reviews (3rd quarter of 2007). For eligible studies, the rates of adverse pregnancy outcomes were compared between patients with and without specific APLA. Pooled odds ratios with 95% CI were generated using random-effects models.

RESULTS: Our search strategy identified 1204 potentially relevant studies. Twenty five were included in the final analysis. Results are outlined in table 1.

CONCLUSION: The association between various APLA and pregnancy complications is for the most part weak and inconsistent. There is currently insufficient data to support a significant link between anti-B2 glycoprotein 1 antibodies and pregnancy morbidity. Caution should be used when establishing a diagnosis of APS based on the presence of any APLA, particularly anti-B2 glycoprotein 1 antibodies, in the setting of late pregnancy complications. Table 1 Association Between APLA and Adverse Pregnancy Outcomes

Pre-eclampsia OR (95%CI) # studies / participantsIUGR OR (95%CI) # studies / participantsPlacental abruption OR (95%CI) # studies / participantsLate fetal loss OR (95%CI) # studies / participants
LA: Lupus anticoagulant; aCL: Anticardiolipin antibodies; Anti-B2 GP1 antibodies: Anti-B2 glycoprotein 1 antibodies 
italic characters indicate statistically significant associations 
LA 2.88 (1.42, 5.87)
 11 / 6085 3.51 (1.38, 8.93)
 4 / 3232 0.78 (0.13, 4.80)
 2 / 226 3.56 (0.12, 106.05)
 3 / 3870 
aCL (IgG/IgM) 1.71 (1.09, 2.70)
 21 / 9722 2.31 (0.74, 7.17)
 6 / 5753 1.35 (0.45, 4.02)
 4 / 1274 3.86 (1.14, 13.07)
 7 / 5963 
aCL IgG 1.65 (0.84, 3.22)
 15 / 3627 6.16 (2.50, 15.18)
 2 / 1006 1.87 (0.21, 16.83)
 2 / 500 10.06 (0.88, 114.96)
 2 / 1006 
aCL IgM 1.36 (0.93, 1.97)
 13 / 5397 0.75 (0.19, 2.93)
 2 / 3002 0.96 (0.24, 3.85)
 2 / 500 1.37 (0.42, 4.46)
 3 / 3212 
anti- B2GP1 (IgG/IgM) 2.97 (0.47, 18.69)
 4 / 2225 20.03 (4.59, 87.43)
 1 / 1108 2.64 (0.14, 50.63)
 1 / 510 6.74 (0.24, 191.23)
 3 / 1828 
anti- B2GP1 IgG 0.87 (0.38, 2.01)
 2 / 607 N/A
 0 / 0 N/A
 0 / 0 0.52 (0.02, 11.02)
 1 / 212 
anti- B2GP1 IgM 0.37 (0.16, 0.85)
 1 / 400 N/A
 0 / 0 N/A
 0 / 0 1.32 (0.24, 7.42)
 1 / 210 
Pre-eclampsia OR (95%CI) # studies / participantsIUGR OR (95%CI) # studies / participantsPlacental abruption OR (95%CI) # studies / participantsLate fetal loss OR (95%CI) # studies / participants
LA: Lupus anticoagulant; aCL: Anticardiolipin antibodies; Anti-B2 GP1 antibodies: Anti-B2 glycoprotein 1 antibodies 
italic characters indicate statistically significant associations 
LA 2.88 (1.42, 5.87)
 11 / 6085 3.51 (1.38, 8.93)
 4 / 3232 0.78 (0.13, 4.80)
 2 / 226 3.56 (0.12, 106.05)
 3 / 3870 
aCL (IgG/IgM) 1.71 (1.09, 2.70)
 21 / 9722 2.31 (0.74, 7.17)
 6 / 5753 1.35 (0.45, 4.02)
 4 / 1274 3.86 (1.14, 13.07)
 7 / 5963 
aCL IgG 1.65 (0.84, 3.22)
 15 / 3627 6.16 (2.50, 15.18)
 2 / 1006 1.87 (0.21, 16.83)
 2 / 500 10.06 (0.88, 114.96)
 2 / 1006 
aCL IgM 1.36 (0.93, 1.97)
 13 / 5397 0.75 (0.19, 2.93)
 2 / 3002 0.96 (0.24, 3.85)
 2 / 500 1.37 (0.42, 4.46)
 3 / 3212 
anti- B2GP1 (IgG/IgM) 2.97 (0.47, 18.69)
 4 / 2225 20.03 (4.59, 87.43)
 1 / 1108 2.64 (0.14, 50.63)
 1 / 510 6.74 (0.24, 191.23)
 3 / 1828 
anti- B2GP1 IgG 0.87 (0.38, 2.01)
 2 / 607 N/A
 0 / 0 N/A
 0 / 0 0.52 (0.02, 11.02)
 1 / 212 
anti- B2GP1 IgM 0.37 (0.16, 0.85)
 1 / 400 N/A
 0 / 0 N/A
 0 / 0 1.32 (0.24, 7.42)
 1 / 210 
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Topics:
adverse pregnancy outcome, antiphospholipid antibodies, meta-analysis, fetal death, antibodies, glycoprotein, immunoglobulin g, immunoglobulin m, antiphospholipid syndrome, beta 2-glycoprotein i

Disclosures: Carrier:Pfizer: Honoraria; Leo Pharma: Honoraria. Rodger:Leo Pharma: Research Funding; Biomerieux: Membership on an entity’s Board of Directors or advisory committees, Research Funding; GTC Therapeutics: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Pfizer: Research Funding; Canadian Medical Protective Association: Consultancy.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
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