Placenta-mediated Pregnancy Complications Research Articles

Thromboprophylaxie pendant la grossesse et le post-partum

The incidence of venous thromboembolism (VTE) during pregnancy is about one event per 1000 pregnancies and placenta-mediated pregnancy complications (PC) occurred in 15%. Knowing the biological combined with clinical risk factors would help to prevent problems during the pregnancy. Several antithrombotic therapies exist, including very recent ones but LMWH and aspirin are still molecules of choice. The women should be assessed for VTE and PC risk in order to improve the outcome.

PM.06 Low Molecular Heparin Within the Uteroplacental Unit

BackgroundPerturbation of the uteroplacental haemostasis has been implicated in placenta mediated pregnancy complications in thrombophilic women. LMWH may be effective in altering local thrombin production in the uteroplacental compartment.AimWe determined...

Heparin rescues factor V Leiden–associated placental failure independent of anticoagulation in a murine high-risk pregnancy model

AbstractLow molecular weight heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven, and the issue of antithrombotic prophylaxis is intensely debated. Using a murine model of factor V Leiden–associated placental failure, we show that treatment of the mother with LMWH allows placental development to proceed and affords significant protection from fetal loss. Nonetheless, the therapeutic effect of LMWH is not replicated by anticoagulation; fondaparinux and a direct Xa inhibitor, C921-78, achieve anticoagulation similar to LMWH but produce little or no improvement in pregnancy outcome. Genetic attenuation of maternal platelet aggregation is similarly ineffective. In contrast, even a partial loss of thrombin sensitivity of maternal platelets protects pregnancies. Neonates born from these pregnancies are growth retarded, suggesting that placental function is only partially restored. The placentae are smaller but do not reveal any evidence of thrombosis. Our data demonstrate an anticoagulation-independent role of LMWH in protecting pregnancies and provide evidence against the involvement of thrombotic processes in thrombophilia-associated placental failure. Importantly, thrombin-mediated maternal platelet activation remains central in the mechanism of placental failure.

An update on thrombophilia and placenta mediated pregnancy complications: What should we tell our patients?

The placenta mediated pregnancy complications, including pre-eclampsia, birth of a small for gestational age child, placental abruption or late pregnancy loss, are common and often devastating pregnancy complications leading to important maternal/fetal/neonatal morbidity and mortality. In this narrative review I examine two common questions related to women with prior placenta mediated pregnancy complications. Do thrombophilias cause placenta mediated pregnancy complications? Does low molecular weight heparin prevent recurrent placenta mediated pregnancy complications?

Association of fetal-derived hypermethylated RASSF1A concentration in placenta-mediated pregnancy complications

ObjectivesTo assess whether fetal-derived hypermethylated RASSF1A concentrations in maternal plasma during pregnancy are altered in pregnancies associated with placental dysfunction manifested by intrauterine growth restriction (IUGR), preeclampsia (PE), or placental previa (PP) and whether this alteration can be detected in susceptible subjects before the onset of clinical disease. MethodsWe performed a real-time quantitative polymerase chain reaction to quantify RASSF1A concentrations before and after methylation-sensitive restriction digestion in maternal plasma at 7–41 gestational weeks of normal pregnancies (n = 161), IUGR (n = 43), PE (n = 22), PP (n = 14) and non-pregnant women (n = 20). ResultsA positive correlation was observed between fetal-derived hypermethylated RASSF1A concentration and gestational age for all study groups (r = 0.624, p < 0.001 for IUGR; r = 0.381, p = 0.042 for PE; r = 0.697, p < 0.001 for PP; r = 0.560, p < 0.001 for controls). The concentration of hypermethylated RASSF1A was relatively high at 7–14 gestational weeks in all patient groups. Hypermethylated RASSF1A concentration at 15–28 weeks was significantly higher in patients who subsequently developed IUGR (p = 0.002), PE (p < 0.001) or PP (p < 0.001) than in controls. ConclusionWe first demonstrated increased concentration of fetal-derived hypermethylated RASSF1A sequences according to advancing gestation and before the onset of the clinical manifestation of pregnancy complications secondary to placental dysfunction, such as IUGR, PE and PP. Hypermethylated RASSF1A in maternal plasma may be useful as a potential biomarker to detect placental-mediated pregnancy complications, regardless of fetal gender and polymorphism.

Risk of placenta‐mediated pregnancy complications or pregnancy‐related VTE in VTE‐asymptomatic families of probands with VTE and heterozygosity for factor V Leiden or G20210 prothrombin mutation

Few studies have evaluated the risk of pregnancy-related adverse events in asymptomatic relatives of probands for VTE and factor V Leiden or the G20210A variant. The antepartum management of this population ranges from antepartum anticoagulation therapy to clinical surveillance. To evaluate the risk of placenta-mediated pregnancy complications and pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and who are heterozygous carriers of either factor V Leiden or PT-G20210A mutation. One hundred and fifty-eight relatives, who had 415 pregnancies, were retrospectively evaluated. Odds ratios and 95% confidence intervals were calculated to compare pregnancy outcomes between women with and without thrombophilia. In the factor V Leiden group, 22 placenta-mediated pregnancy events of 152 pregnancies (14.4%) were reported, compared with 25 adverse events of 172 pregnancies in the G20210A prothrombin group (14.5%) and 13 adverse events of 91 pregnancies in the non-carrier group (14.2%). Carriers of factor V Leiden or G20210A prothrombin were not associated with a higher risk of pregnancy-adverse outcomes compared with non-carriers: OR 1.02 (95% CI, 0.40-2.25) and 1.25 (95% CI, 0.48-3.24), respectively. Four episodes of pregnancy-associated VTE of 415 pregnancies (0.96%) were recorded. Two episodes of VTE in the G20210A group, one in the factor V Leiden group, and one episode in the non-carrier group were noted. In VTE-asymptomatic relatives of probands with VTE, the presence of factor V Leiden or the G20210A prothrombin mutation in heterozygosis should not lead to a decision to instigate antepartum prophylaxis.

Is thrombophilia a risk factor for placenta-mediated pregnancy complications?

To determine if thrombophilia is a risk factor for placenta-mediated pregnancy complications (PMPC) (i.e., preeclampsia, intrauterine growth restriction (IUGR), placental abruption, intrauterine fetal death and recurrent pregnancy loss). A 5-year retrospective cohort study. Ongoing pregnancies in women with an antecedent PMPC with thrombophilia were compared with the pregnancies in similar women without thrombophilia. The main outcome measures were mean birth weight deviations, corrected for gestational age, and recurrence of PMPC. Low-molecular-weight heparin (LMWH) was employed for thromboprophylaxis only. Mann-Whitney's, Fisher's and Chi-square tests were employed for comparison. PMPC recurred in 10/43 (23%) in the thrombophilia group and in 7/41 (17%) in the non-thrombophilia group, P<0.059. The mean birth weight deviations were not significantly different either: -7.2 versus -3.0%, respectively. LMWH, as could be expected, was used more often in thrombophilia patients (39/43 vs. 10/41, P<0.001). Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH.

Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial

AbstractTo assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; −1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco.it as EudraCT 2006-004205-26.

The association of antiphospholipid antibodies with intrauterine fetal death: A case–control study

IntroductionOver the past few decades it has been recognized that antiphospholipid antibodies are associated with pregnancy loss. Other placenta-mediated pregnancy complications have also been associated with the presence of antiphospholipid antibodies. Most studies have measured antiphospholipid antibodies near the time of the event investigated. ObjectivesTo investigate the association of antiphospholipid antibodies and a history of intrauterine fetal death (IUFD) in a case–control design. Materials and methodsA case–control study of 105 women with a history of IUFD after 22 gestational weeks and 262 controls with live births. The prevalence of lupus anticoagulant, anticardiolipin- and anti-β2-glycoprotein 1 antibodies were measured 3–18years after the event of IUFD. ResultsTotal 9.5% of women with a history of IUFD and 5.0% of controls had at least one positive test for antiphospholipid antibodies (OR 2.0; 95% confidence interval (CI) 0.9-4.8). Women with a history of IUFD were significantly more often positive for lupus anticoagulant compared to controls (OR 4.3; 95% CI 1.0-18.4). The association of lupus anticoagulant with a history of IUFD was confined to women positive for other antiphospholipid antibodies in addition to lupus anticoagulant. Being positive for anti-β2-glycoprotein 1 or anticardiolipin antibodies alone was not significantly associated with a history of IUFD. ConclusionsWomen with a history of IUFD after 22 gestational weeks were more often lupus anticoagulant positive. The association was confined to women with multiple positivity for antiphospholipid antibodies, although firm conclusions on the importance of multiple positivity cannot be made from this study.

The association of inherited thrombophilia and intrauterine fetal death

Inherited thrombophilias are probably associated with placenta-mediated pregnancy complications, but the strength of the association between inherited thrombophilias and intrauterine fetal death after 22 gestational weeks varies due to small sample size and different methodologies used across studies. The objective of the present study was to investigate the association of inherited thrombophilia and intrauterine fetal death in a case-control design. We studied 105 women with a history of intrauterine fetal death after 22 gestational weeks and 262 controls with live births. We investigated the prevalence of the factor V Leiden (F5 rs6025) and prothrombin gene G20210A (F2 rs1799963) polymorphisms, and antithrombin, protein C and protein S deficiencies, and their association with intrauterine fetal death. Results were presented as percentages and odds ratios (ORs) with 95% confidence intervals (CIs). A total of 18.4% of cases and 11.8% of controls were positive for at least one inherited thrombophilia (OR 1.7; 95% CI 0.9-3.1). The prothrombin gene G20210A polymorphism (OR 4.0; 95% CI 1.1-14.4), but not the factor V Leiden polymorphism, or antithrombin, protein C or protein S deficiencies, was associated with intrauterine fetal death after 22 weeks of gestation. Compared with women with live births only, women with a history of intrauterine fetal death after 22 gestational weeks were significantly more often carriers of the prothrombin gene G20210A polymorphism.

The association between antiphospholipid antibodies and placenta mediated complications: A systematic review and meta-analysis

BackgroundThe association between antiphospholipid antibodies (APLA) and placenta mediated pregnancy complications (pre-eclampsia, intrauterine growth restriction (IUGR), late fetal loss and placental abruption) remains controversial. MethodsWe 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. ResultsOur 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. ConclusionAPLAs 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.

Anticoagulant prophylaxis for placenta mediated pregnancy complications

Thrombophilias are not yet established as a cause of the placenta-mediated pregnancy complications (pregnancy loss, pre-eclampsia, small for gestational age and placental abruption). A thrombophilia may be only one of many factors that lead to development of these complications. Our recent large systematic review of prospective cohort studies highlight that the association between thrombophilia and placenta mediated pregnancy complications is far from proven. The small step of previously describing an association in case control studies has led a large number of clinicians and opinion leaders to take the large leap of accepting this relationship as being causal and potentially treatable with anticoagulant interventions. Furthermore, while data in women with prior severe pre-eclpamsia, abruption and small for gestational age births without thrombophilia suggests some promise for anticoagulant prophylaxis to prevent complications in subsequent pregnancies in these women, in the absence of large well done and generalisable “no intervention” controlled studies adopting anticoagulant prophylaxis to prevent these complications is premature. The absence of strong evidence, coupled with the small potential for harm from anticoagulant prophylaxis suggests that these drugs should be considered experimental in thrombophilic and non-thrombophilic women with prior placenta mediated pregnancy complications.

The Association of Factor V Leiden and Prothrombin Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review and Meta-analysis of Prospective Cohort Studies

Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications. A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR = 1.52, 95% confidence interval [CI] 1.06-2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89-1.70) or between FVL and SGA (OR = 1.0, 95% CI 0.80-1.25). PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79-1.99) or SGA (OR 1.25, 95% CI 0.92-1.70). Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants. Please see later in the article for the Editors' Summary.

Therapeutic Effects of Anticoagulant Agents on Preeclampsia in a Murine Model Induced by Phosphatidylserine/Phosphatidylcholine Microvesicles

Preeclampsia (PE) is a placenta-mediated pregnancy complication that results in high maternal and neonatal mortality and morbidity worldwide. Currently, there is no satisfactory pharmacotherapeutic treatment to stop the PE progression. In this study, we investigated the therapeutic effects of anticoagulant agents, including annexin V, heparin, and a fusion protein of annexin V and hirudin (AND), in a murine PE model induced by intravenous injection of phosphatidylserine/phosphatidylcholine (PS/PC) microvesicles. Compared with the control pregnant animals, the pregnant mice injected with PS/PC presented PE-like symptoms, including elevated systolic blood pressure, proteinuria, and reduction of antithrombin III and blood platelets. However, the PE-like symptoms were significantly alleviated after the PS/PC-injected mice were treated with annexin V, AND, or heparin. Furthermore, fibrin deposition in the placentas in the anticoagulant treated mice was remarkably improved, compared with that in the mice injected with PS/PC alone. The data demonstrate that anticoagulants are effective to prevent the occurrence of PE in the murine model and also suggest that hypercoagulation in the placenta is a contributing factor in the pathogenesis of PE.

Assisted Reproductive Technology and Placenta-Mediated Adverse Pregnancy Outcomes

To estimate whether the use of specific types of assisted reproductive technology (ART) is associated with an increased risk of placenta-mediated pregnancy complications, which include preeclampsia, stillbirth, small for gestational age at birth, and placental abruption. A population-based retrospective cohort study was conducted on singleton pregnancies conceived by different types of ART based on the 2004-2007 Ontario Niday Perinatal Database. Patients with fetal anomalies and maternal health problems were excluded as important confounders. Three exposed groups were created by the subtype of ART, including in vitro fertilization with or without intracytoplasmic sperm injection, intrauterine insemination, and ovulation induction. The nonexposed groups were the singleton pregnancies conceived naturally. For each exposed woman, four women from the nonexposed group were randomly matched by maternal age and parity. There were 2,118 exposed participants and 8,420 matched nonexposed participants in the study. The sample size provided 80% power for a relative risk of 2.0 of placenta-mediated adverse pregnancy outcomes with ART. After adjustment of potential confounders, including smoking, delivery hospital level, initiating time of prenatal care, average neighborhood income, fetal sex, and previous cesarean delivery, there was no association observed between different types of ART groups and the composite of placenta-mediated pregnancy complications. Intrauterine insemination was associated with a significantly increased risk of preeclampsia (12 [2.67%] odds ratio 2.2, 95% confidence interval 1.04-5.04) compared with the corresponding control group (23 [1.29%]). Assisted reproductive technology is not associated with an increased risk of the composite outcome of placenta-mediated pregnancy complications among singleton pregnancies. II.

Anticoagulants to prevent placenta-mediated pregnancy complications: a review of current evidence

Placenta-mediated pregnancy complications are relatively common and are associated with significant morbidity and mortality. Although anticoagulants are increasingly being used to prevent these complications, the evidence supporting their use is limited. This article will focus on reviewing the current evidence base for the use of anticoagulants to prevent placenta-mediated pregnancy complications in women with or without identifiable thrombophilia. Controversy exists whether inherited or acquired thrombophilias cause placenta-mediated complications. Small randomized studies with methodological limitations suggest that antepartum anticoagulant prophylaxis will reduce pregnancy loss in women with both acquired and inherited thrombophilia and prior pregnancy loss. There are no published randomized controlled trials examining anticoagulant prophylaxis in thrombophilic women with prior preeclampsia, intrauterine growth restriction or placental abruption. More recently, the benefit of antepartum anticoagulant prophylaxis in women without thrombophilia with prior placenta-mediated pregnancy complications has been suggested in a small pilot randomized trial. Overall, although antepartum anticoagulant prophylaxis has the potential to reduce placenta-mediated pregnancy complications in women with and without identifiable thrombophilia, the data generated by these trials are methodologically limited and inadequate. Hence, we conclude that further trials are required prior to adopting the use of antepartum anticoagulant prophylaxis to prevent placenta-mediated pregnancy complications in routine clinical practice.

Thrombophilia and placenta-mediated pregnancy complications: from the bench to bedside to policy

While it is well known that thrombin plays a central role in the coagulation component of hemostasis [1] a developing story is emerging that demonstrates thrombin’s central role in placental development. Tissue Factor (TF), the most important initiator of coagulation, is constitutively expressed on almost all cells other than endothelial cells [2]. Endothelial cells line the inner layer of blood vessels and provide a physical barrier between TF laden sub-endothelial tissues and coagulation ready blood. When the endothelial barrier is disrupted (e.g. vascular injury) coagulation ensues. FVIIa circulates in minute quantities in normal plasma at the ready to encounter TF. Coagulation activation is initiated through interaction of Tissue Factor, calcium and circulating FVIIa which then convert factor X to Xa and factor IX to IXa. Xa then complexes with Va and calcium on a phospholipids surface to form the Tenase complex. The Tenase complex then converts prothrombin to thrombin. Next, coagulation activation is maintained by thrombin activating factors XI, V and VIII to generate a positive feedback cycle that leads to a thrombin burst which then cleaves sufficient fibrinogen to form adequate fibrin for a hemostatic plug. Thrombin also activates platelets via binding to the PAR-4 receptor on platelets. Without an adequate anticoagulant mechanism unchecked thrombin generation would lead to disseminated coagulation throughout the vascular system. The

Inherited Thrombophilia and Pregnancy Complications Revisited

Inherited thrombophilias are not yet established as a cause of placenta-mediated pregnancy complications, such as fetal growth restriction, preeclampsia, abruption, and pregnancy loss. An inherited thrombophilia is only one of many factors that lead to development of these diseases and is unlikely to be the unique factor that should drive management in subsequent pregnancies. The paucity of evidence for benefit, coupled with a small potential for harm, suggests that low molecular weight heparin should be considered an experimental drug for these indications until data from controlled trials are published. At present, women with a history of placenta-mediated pregnancy complications, with or without a thrombophilia, should be followed closely without routine prophylactic low molecular weight heparin other than for prevention of venous thromboembolism in limited circumstances.

Do Thrombophilias Cause Placenta-Mediated Pregnancy Complications?

There has been an sudden increase of knowledge about thrombophilias in the last decade as new thrombophilias are discovered and new associations are explored. It is now evident that thrombophilias are common and that the clinical consequences of having a thrombophilia do not appear to be limited to venous thromboembolism. The placenta-mediated pregnancy complications are also common (more than one in six pregnancies are affected) and include pregnancy loss, preeclampsia, placental abruption, and intrauterine growth restriction. These complications as a whole are the leading causes of maternal and neonatal morbidity in the developed world. Evidence has emerged to suggest that thrombophilic women may be at higher risk of developing these placenta-mediated pregnancy complications. However, is this evidence mature enough to claim that a causal association is proven? Is the evidence strong enough to recommend anticoagulant prophylaxis? We suggest that causality is not yet proven and that the data to support management with anticoagulant prophylaxis in thrombophilic pregnancies is too immature to consider this an established intervention.

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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.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.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.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.