Regular Article The association between antiphospholipid antibodies and placenta mediated complications: A systematic review and meta-analysis Karim Abou-Nassar a , Marc Carrier a,b , Tim Ramsay b , Marc A. Rodger a,b, ⁎ a Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada b Clinical Epidemiology Program, The Ottawa Health Research Institute, Ottawa, Ontario, Canada abstract article info Article history: Received 6 October 2010 Received in revised form 21 January 2011 Accepted 10 February 2011 Available online 21 March 2011 Background: The association between antiphospholipid antibodies (APLA) and placenta mediated pregnancy complications (pre-eclampsia, intrauterine growth restriction (IUGR), late fetal loss and placental abruption) remains controversial. Methods: We performed a systematic review of published case-control, cohort and cross sectional studies (MEDLINE (1975 to 2009), EMBASE 16 (1980 to 2009) and all EBM Reviews (2009)) to evaluate the association between APLA and placenta mediated complications in untreated women without autoimmune diseases. Results: Our search strategy identified 1207 potentially relevant studies. Twenty eight were included in the final analysis. LA was associated with pre-eclampsia (OR 2.34; 95%CI 1.18-4.64), IUGR (OR 4.65 95% CI 1.29- 16.71) and late fetal loss (OR 4.73; 95%CI 1.08-20.81) amongst case-control studies and only with late fetal loss (OR 10.59 95% CI 1.87-59.88) amongst cohort studies. ACA were associated with pre-eclampsia (OR 1.52; 95%CI 1.05-2.20) and late fetal loss (OR 4.29; 95% CI 1.34-13.68) amongst case-control studies and only late fetal loss (OR 8.85 95% CI 1.84-42.50) amongst cohort studies. Finally, anti-B2 GP1 antibodies showed associations with pre-eclampsia (OR 19.14, 95% CI 6.34-57.77), IUGR (OR 20.03; 95%CI 4.59-87.43) and late fetal loss (OR 23.46, 95% CI 1.21-455.01) in two cohort studies. Conclusion: APLAs appear to be associated with late fetal losses. However, the association between APLAs and other placenta mediated complications is inconsistent. LA is most strongly and consistently associated with placenta mediated complications. There are currently insufficient data to support a significant link between anti-B2 GP1 antibodies and pregnancy morbidity. © 2011 Elsevier Ltd. All rights reserved. Introduction Antiphospholipid antibodies (APLA) are a group of auto-antibodies that have the ability to bind to cardiolipin alone, to cardiolipin complexed to a cofactor or to a cofactor alone. APLA are found in up to 5% of healthy subjects [1] in the general population and in 35% of patients with SLE [2,3]. The prevalence of APLA in the low risk obstetrical population ranges from 1-9% [4–8]. The concept of antiphospholipid syndrome (APS) was first introduced when the association between APLA and hypercoagulability became evident [9,10]. In addition to an increased risk of vascular thrombosis in women with APLA, some studies have suggested an association with pregnancy complications including recurrent pregnancy losses (RPL) and placenta mediated pregnancy complications such as late fetal losses, pre-eclampsia, placental abruption and intrauterine growth restriction (IUGR) [11]. The international preliminary classification criteria for APS (Sapporo criteria) were first introduced in 1998 [12] and were revised in 2005 [13]. The current definition requires at least one clinical and one laboratory criterion to make a diagnosis of APS. Clinical criteria include the presence of vascular thrombosis and/or pregnancy complications. As described by the revised Sapporo criteria, pregnancy morbidity includes ≥1 unexplained deaths of morphologically normal fetus at ≥10 weeks gestation; ≥1 premature birth of morphologically normal neonate before 34 weeks gestation because of preeclampsia, eclampsia or features of placental insuffi- ciency (non-reassuring fetal surveillance test, abnormal Doppler flow velocimetry suggestive of fetal hypoxiemia, oligohydramnios, intra- uterine growth restriction (IUGR)); ≥3 unexplained spontaneous abortions at b 10 weeks gestation not due to anatomic or hormonal abnormalities in the mother or chromosomal abnormalities on maternal or paternal side. Laboratory criteria require one of the following detected in patient's serum or plasma on two separate Thrombosis Research 128 (2011) 77–85 ⁎ Corresponding author at: Division of Hematology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa Hospital, General Campus, 501 Smyth Road, Room W6116, Eye Institute, Ottawa, ON, Canada K1H 8L6. Tel.: +1 613 737 8899x74641; fax: +1 613 739 6102. E-mail address: mrodger@ohri.ca (M.A. Rodger). 0049-3848/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2011.02.006 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres