Late Fetal Loss Research Articles

Bicornuate Uterus and Pregnancy a Propos One Case and Review of the Litterature

Frequency of uterine malformations having an impact on reproduction is difficult to assess. Their detection requires specific exams (hysterosalpingography, hysteroscopy, laparoscopy). Spontaneous fertility can be altered depending on the type of uterine anomaly. All these anomalies can affect the evolution of the pregnancy: early fetal loss and late fetal loss, ectopic pregnancy, premature delivry, premature birth,vascular pathologies in pregnancy and fetal growth restriction. Ovarian function is not changed. Bicornuate uterus is the most common uterine malformations representing about half of the anomalies of the uterus. Surgery, including endoscopic allows precise diagnosis, assessment of prognosis and treatment improving the chances of conception and evolution of pregnancies. The occurrence of such a pregnancy is a dangerous situation that can lead to maternal death, but early diagnosis and good following can carry pregnancies to term. Ultrasound screening should allowed the identification of such cases in order to take preventive measures. We report a case of a bicornualunicervical uterus in a pregnancy at 38 weeks of gestation diagnosed during ultrasound first trimester of pregnancy.

Group B streptococcal infection in the first 90 days of life in North Queensland.

Group B Streptococcus (GBS) infection is recognised as an important cause for neonatal sepsis. To describe the incidence and risk factors for invasive GBS under 90 days of age in North Queensland from January 2002 to December 2011. Patients were identified with positive blood and cerebrospinal fluid cultures to obtain incidence figures. The Townsville district cohort was further investigated for the presence of maternal and fetal risk factors in a retrospective case-controlled study. Early onset GBS continues to occur at 0.43/1000 live births, and late onset disease at 0.38/1000 live births. Early onset GBS and late onset GBS are shown to be two distinct diseases. Early onset disease is significantly different from the control group for these risk factors: previous late fetal loss, prolonged rupture of membranes, inadequate intrapartum antibiotics, abnormal cardiotocography, delivery by emergency caesarean section, lower one minute Apgar scores and need for resuscitation at delivery. Significant variables for late onset disease are earlier gestation and need for resuscitation at birth, first born babies, multiple pregnancy and birth by emergency caesarean section. The incidence of early or late onset GBS in Aboriginal or Torres Strait Islanders was not significantly different. Group B Streptococcus continues to occur in North Queensland at higher than expected rates, and a new approach to its prevention should be considered. Previous fetal loss may be a risk factor which is under recognised. Babies with late onset infection appear to be significantly more preterm.

Effects of early pregnancy diagnosis by per rectal palpation of the amniotic sac on pregnancy loss in dairy cattle

To determine effects of per rectal amniotic sac palpation (ASP) for pregnancy diagnosis during early gestation on pregnancy loss in lactating cows. Controlled, randomized block design. 368 pregnant dairy cows. Pregnancy was detected via transrectal ultrasonography (TRUS) at day 29 (day of estrus = day 0), and cows were allocated into a control group (n = 167 cows) and ASP group (180). Control cows were not subjected to pregnancy diagnosis via palpation per rectum. Per rectal ASP was performed between days 34 and 43 by only 1 experienced veterinarian. All cows were reevaluated with TRUS on days 45, 60, and 90. 21 cows were removed because of illness. Pregnancy loss between days 29 and 90 occurred in 44 of 347 (12.7%) cows. Pregnancy loss for the control and ASP groups from days 29 to 90 occurred in 22 of 167 (13.2%) and 22 of 180 (12.2%) cows, respectively. Late embryonic pregnancy loss (days 29 to 45) for the control and ASP groups occurred in 18 (10.8%) and 15 (8.3%) cows, respectively. Early fetal pregnancy loss (days 46 to 60) for the control and ASP groups occurred in 2 of 149 (1.3%) and 6 of 165 (3.6%) cows, respectively, and late fetal pregnancy loss (days 61 to 90) for the same groups occurred in 2 of 147 (1.4%) and 1 of 159 (0.6%) cows, respectively. Pregnancy diagnosis via per rectal ASP during early gestation did not increase pregnancy loss in dairy cattle.

Hospital based prospective longitudinal clinical and immunologic study of 179 patients of primary anti-phospholipid syndrome

To study the clinical and immunological features of primary antiphospholipid syndrome (APS), and to analyze the differences between primary APS and APS associated with autoimmune rheumatic disease (ARD/APS). This prospective, longitudinal study, carried out from December 2004 to July 2011 included 179 patients with primary APS and 52 patients of ARD/APS diagnosed as per modified 2006 Sapporo's Criteria. Out of 179 patients of primary APS, 12 were male and 167 were female. The mean age at the time of study entry was 27 ± 4.33 years. Venous thrombosis was noted in 33 (18.43%) patients. Seventeen patients had deep vein thrombosis and 11 (7.19%) had cortical vein and/or cortical sinus thrombosis. Arterial thrombosis was noted in 19 (10.61%) patients, out of which nine had intracranial arterial thrombosis. Thirty-two (17.85%) had recurrent early fetal losses (< 10 weeks) and 97 (54.18%) had late fetal loss (> 10 weeks). Immunoglobulin G (IgG) and IgM aCLA were present in 141 (78.77%) and 32 (17.87%) patients respectively, whereas lupus anticoagulant was present in 99 (55.3%) patients. In patients with bad obstetric outcome, lupus anticoagulant positivity was significantly more prevalent (P < 0.05) than aCLA positivity. Both venous and arterial thrombosis were significantly more common (P < 0.05) in ARD/APS. However, late fetal loss was significantly more prevalent (P < 0.001) in primary APS. Primary APS may lead to a variety of clinical manifestations due to venous and/or arterial thrombosis, which at times may be lethal. It is also an important cause of early and late pregnancy loss(es) and other pregnancy morbidities.

Role of sulphate in development

Sulphate contributes to numerous processes in mammalian physiology, particularly during development. Sulphotransferases mediate the sulphate conjugation (sulphonation) of numerous compounds, including steroids, glycosaminoglycans, proteins, neurotransmitters and xenobiotics, transforming their biological activities. Importantly, the ratio of sulphonated to unconjugated molecules plays a significant physiological role in many of the molecular events that regulate mammalian growth and development. In humans, the fetus is unable to generate its own sulphate and therefore relies on sulphate being supplied from maternal circulation via the placenta. To meet the gestational needs of the growing fetus, maternal blood sulphate concentrations double from mid-gestation. Maternal hyposulphataemia has been linked to fetal sulphate deficiency and late gestational fetal loss in mice. Disorders of sulphonation have also been linked to a number of developmental disorders in humans, including skeletal dysplasias and premature adrenarche. While recognised as an important nutrient in mammalian physiology, sulphate is largely unappreciated in clinical settings. In part, this may be due to technical challenges in measuring sulphate with standard pathology equipment and hence the limited findings of perturbed sulphate homoeostasis affecting human health. This review article is aimed at highlighting the importance of sulphate in mammalian development, with basic science research being translated through animal models and linkage to human disorders.

Viral Infections: Contributions to Late Fetal Death, Stillbirth, and Infant Death

To determine the role of viral infections in causing fetal and infant death. We assessed a well-validated population database of fetal (≥20 weeks gestation) and infant death for infective deaths and deaths from viruses over a 21-year period (1988-2008). We analyzed by specific viral cause, timing (late fetal loss [20-23 weeks], stillbirth [≥24 weeks], neonatal death [0-27 days], and post-neonatal infant death [28-364 days]) and across time. Of the 989 total infective deaths, 108 were attributable to viral causes (6.5% of late fetal losses, 14.5% of stillbirths, 6.5% of neonatal deaths, and 19.4% of postneonatal infant deaths). Global loss (combined fetal and infant losses per 100,000 registerable births) was 139.6 (95% CI, 130.9-148.3) for any infective cause and 15.2 (95% CI, 12.3-18.1) for viral infections. More than one-third (37%) of viral-attributed deaths were before live birth, from parvovirus (63%) or cytomegalovirus (33%). Parvovirus accounted for 26% (28 of 108) of all viral deaths. Cytomegalovirus was associated with a global loss rate of 3.1 (95% CI, 1.8-4.4) and an infant mortality rate of 1.3 (95% CI, 0.4-2.1) per 100,000 live births; 91% of cases were congenital infections. Herpes simplex virus caused death only after live births (infant mortality rate, 1.4; 95% CI, 0.5-2.3). No changes in rates were seen over time. We have identified a substantial contribution of viral infections to global fetal and infant losses. More than one-third of these losses occurred before live births. Considering our methodology, our estimates represent the minimum contribution of viral illness. Strategies to reduce this burden are needed.

Mid-Trimester Maternal Serum hCG and AFP Levels: Clinical Significance and Prediction of Adverse Pregnancy Outcome

ContextMaternal serum human Chorionic Gonadotropin (hCG) and Alpha Fetal Protein (AFP) were originally introduced to detect trisomy 21 and neural tube defects. However, in the absence of aneuploidy or neural tube defects, mid-trimester maternal serum hCG and/or maternal serum AFP associated with adverse pregnancy outcomes. Pregnancies with unexplained mid-trimester elevation in maternal serum hCG and/or maternal serum AFP, are at increased risk for pregnancy complications resulting from placental insufficiency.Evidence AcquisitionMid-trimester maternal serum hCG>2.5 MoM associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, intrauterine growth restriction (IUGR), preterm delivery and intrauterine fetal death(IUFD). Mid-trimester maternal serum AFP levels >2.5 MoM are thought to reflect a defect in placentation and associated with an increased risk for pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD.ResultsCombined mid-trimester elevation in maternal serum hCG and AFP levels suggest a more complex type of placental pathology. They have stronger association with pregnancy complications including: late fetal loss, gestational hypertension, preeclampsia, IUGR, preterm delivery and IUFD.ConclusionsMid-trimester maternal serum hCG or AFP levels alone cannot detect all pregnant women with increased risk to develop pregnancy complications. Multiparameter testing of placental function in mid-trimester (maternal serum hCG and AFP screening, uterine artery Doppler and placental morphology) may allow us to identify women with increased risk to develop severe placental insufficiency and pregnancy complications. However, future prospective studies are needed to confirm the prognostic significance of multiparameter testing of placental function in mid-trimester.

Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study

Please cite this paper as: Korteweg F, Folkeringa N, Brouwer J, Erwich J, Holm J, van der Meer J, Veeger N. Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study. BJOG 2012;119:422–430. Objective To assess the absolute risk of fetal loss associated with hereditary deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), and the contribution of additional thrombophilic defects to this risk. Design A retrospective family cohort study. Setting A tertiary referral teaching hospital. Population Women from families with hereditary deficiencies of AT, PC and PS, and their non-deficient relatives. Methods We assessed the absolute risk of fetal loss, comparing deficient women with non-deficient female relatives. Main outcome measures Early, late and total fetal loss rates; odds ratios of fetal loss. Results We evaluated 289 women, who had 860 pregnancies. The total fetal loss rates were 23% (AT deficient), 26% (PC deficient), 11% (type-I PS deficient) and 15% (type-III PS deficient), compared with 11, 18, 12 and 13% in non-deficient women, respectively. Odds ratios were 2.3 (95% CI 0.9–6.1), 2.1 (95% CI 0.9–4.7), 0.7 (95% CI 0.2–1.8) and 1.1 (95% CI 0.6–2.0), none of which reached statistical significance. Differences were mainly the result of higher late fetal loss rates in women deficient in AT (OR 11.3, 95% CI 3.0–42.0) and PC (OR 4.7, 95% CI 1.3–17.4). The concomitance of factor-V Leiden and prothrombin G20210A was observed in 19% of women, and did not increase the risk of fetal loss. Conclusions Although absolute risks of fetal loss were high, odds ratios of total fetal loss were not statistically significant in deficient versus non-deficient women. However the higher absolute risks appeared to reflect higher late fetal loss rates as opposed to early fetal loss rates. An additional effect of concomitance of factor-V Leiden and prothrombin G20210A was not demonstrated, which may result from the exclusion of women at highest risk of venous thromboembolism, or from the small numbers sampled in the study.

Management of Obstetric Antiphospholipid Syndrome

Recurrent early miscarriages (excluding chromosomal anomalies), late fetal loss, and maternal thrombosis are characteristic of obstetric antiphospholipid syndrome (APS). Obstetric complications such as preeclampsia, fetal growth restriction, premature delivery, and fetal death also occur in higher frequency in APS patients than in the general population. A high-risk obstetric center is needed for proper evaluation of and intervention with pregnant women with APS. Association with lupus carries additional risk of thrombosis when antiphospholipid antibodies (aPLs) are present. Gestational results with live births are improved to about 80% when antithrombotic therapy is used, but failure in 20% to 30% of the cases despite correct treatment with low-dose aspirin with or without heparin reveals new pathways for pregnancy loss in APS and unmet needs. At the moment, there is no recommendation to investigate patients with infertility for the presence of aPLs.

Occupational carrying of loads during pregnancy and the risk of fetal loss

ObjectivesLifting heavy loads is generally discouraged in pregnancy. Older studies, mainly based on retrospectively collected data, have suggested an increased risk of early fetal loss among women with occupational heavy...

Comparative evaluation of Tissue factor and Thrombomodulin activity changes during normal and idiopathic early and late foetal loss: The cause of hypercoagulability?

Various components of the coagulation and fibrinolytic pathways are involved in normal embryonic implantation, trophoblast invasion, placentation, and recurrent miscarriages are characterized by defective placentation and microthrombi in the placental vasculature. Although recurrent miscarriage is a heterogeneous condition the relationship between abnormalities in the haemostatic pathways and pregnancy outcome is increasingly recognized. The challenge we face is how to discriminate between women who are destined to miscarry from those whose pregnancy will be successful. Considering the crucial role of thrombomodulin and tissue factor in coagulation and in embryonic development, we have performed a study using specific assays for thrombomodulin, tissue factor activity and procoagulant phospholipids in association with other parameters in 30 early (under 12weeks) and 32 late (over 22weeks) pregnancy loss women and compared them with 62 normal pregnancy women and 35 non-pregnant women. Plasma levels of tissue factor activity, thrombomodulin activity, and procoagulant phospholipids were significantly higher in patients than in control subjects. In addition the tissue factor activity/free tissue factor pathway inhibitor ratio was higher in patients than in controls. Interestingly, patients with late pregnancy loss had higher tissue factor activity/free tissue factor pathway inhibitor ratios than patients with early pregnancy loss. The combinations of these different parameters reveal an increase in procoagulant activity which could be secondary to endothelial damage or coagulation activation and then are involved in the pathogenesis of pregnancy loss. Their simultaneous measurement of these activities might provide a new tool to assess the prognosis of pregnancy loss.

Parental care pathway after late fetal loss and stillbirth: an audit of cases in sunderland royal hospital over a 2-year period

BackgroundRecently the RCOG published Green-Top Guideline ‘Late Intrauterine Fetal Death & Stillbirth’.1 The North East has the highest adjusted mortality for stillbirth,2 therefore an audit of the parental care pathway...

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.

Pregnancy with prosthetic heart valves — 30 years’ nationwide experience in Denmark☆☆☆

Pregnancy in women with prosthetic heart valves remains a risk factor for both mother and fetus, but unselected and unbiased outcome and complication data remain scarce. We analyzed nationwide outcome data from 1977 to 2007 for all pregnancies in women with prosthetic valves. Cardiac, obstetric, and neonatal data were obtained from obligatory databases and compared with general female population data. Questionnaires were used to corroborate important information. Outcome data were analyzed according to type of anticoagulation used. The data were compared between the two first and the last decades of the study period. In the last decade, patients were compared to an age-adjusted selected population of healthy, pregnant women. Of 356 women between 15 and 40 years of age, 79 women had 155 pregnancies after valve replacement. Two women died during pregnancy, one from heart failure and one from post-partum bleeding. There were four thrombo-embolic episodes in the early study period in women with mitral prosthesis on unfractionated heparin. Important cardiac complications were otherwise almost absent. There were significantly more early miscarriages and terminations in patients compared with controls (last decade 34%, vs 20% (p=0.0036) and 26% vs 13% (p=0.000019)). Post-partum bleeding was more common in the patient group (p=0.0021). Two late fetal losses (one from intracerebral bleeding) were seen. The remaining pregnancies resulted in 60 live births. Cesarean section was the predominant method of delivery in patients as opposed to controls (55% vs 16%, p=0.000000000097). Premature births were more frequent in patients (49% vs 5.5%, p=0.00000000039) as were congenital malformations (14% vs 5.7%, p=0.044). Two of the six malformations were warfarin embryopathy (8% of all first-trimester warfarin exposures), both seen in high-risk patients on high warfarin dosing. Small for gestational age did not differ significantly from the general population (9.3% vs 6.0%, p=0.39). Data acquired over 30 years confirm that women with prosthetic heart valves, especially aortic prostheses for congenital lesions, generally tolerate pregnancy well, although cardiac mortality, mortality related to anticoagulation and thrombo-embolic risks are raised. Our data provide further documentation on the significance and importance of the risks associated with predominantly warfarin-based treatment regimens, which still remains optional for a number of patients. Finally, the data also serve as a comparison for recently published series based on low-molecular-weight heparin (LMWH) regimens.

P.26 Evaluation of risk factors in women with breast carcinoma who developed venous thromboembolism

P.26 Evaluation of risk factors in women with breast carcinoma who developed venous thromboembolism

Detection of Lupus Anticoagulant In Women with Obstetric complications

AbstractAbstract 3185 Introduction:Lupus anticoagulant (LA) is one of the laboratory criteria for the diagnosis of antiphospholipid syndrome. To detect the presence of LA, ISTH recommends performing two assays based on different principles. Our LA profile includes dilute Russell viper venom time (dRVVT) and two different activated partial thromboplastin time (aPTT) reagents.The aim of the study was to evaluate sensitivity and specificity of aPTT and dRVVT in women with a history of pre-eclampsia, intra-uterine growth restriction, early recurrent abortion, late fetal loss and placental abruption collectively termed “placenta mediated complications”. Materials and Methods:We studied a total of 247 patients and 287 samples in a 10 months period. Based on consensus criteria, samples were retested within a period of three months. 62/247 plasmas samples were collected during pregnancy.Laboratory studies: Screening tests: aPTT was performed using PTT-LA (Stago) and an aPTT home made reagent with diluted cephalin. dRVVT was performed using Russel viper venom RVV (Stago) and diluted cephalin. Negative control plasma was prepared according to ISTH LA recommendations for the mixing tests. Confirmatory tests: We performed a home made reagent for platelet neutralization procedure (PNP)-aPTT and dRVVT; Rosner Index and % of Correction as criteria for mixing and confirmatory tests interpretation.Statistical evaluation was performed by ROC method using EP Evaluator 9.9 software. Results:172/287 samples (59.9%) were negative, while 115/287 samples (40.1%) were positive for LA. 44/115 samples (38.26%) were positive for both tests (aPTT and dRVVT), 60/115 samples (52.17 %) were positive only for dRVVT and 11/115 samples (9.57%) were positive only for aPTT.LA was confirmed in 9/62 pregnant women samples (14.5 %). 7 (11.3%) had abnormal dRVVT, the remaining 2 samples were positive for both tests.Table for PP–Assay(UCA)/Cut offSensitivity (SE)Specificity (SP)aPTT (Cephalin)0.812/43 seg57.494.8aPTT (PTT–LA, Stago)0.813/42 seg58.391.9dRVVT (Cephalin)0.964/45 seg87.0100 Conclusions:Our results demonstrated: 1- High prevalence of dRVVT positive plasmas 104/115 (90.43%); 2- Despite showing a low performance regarding sensitivity when compared to dRVVT, both aPTT tests were able to detect LA in 47.83% of the positive studies. 3- According to our experience, considering this initial cohort of selected patients, the use of dRVVT as the first and aPTT as the second screening test may help improve the performance for the diagnosis of LA. Disclosures:No relevant conflicts of interest to declare.

Prevalence of allo‐immunization anti‐HLA and anti‐integrin αIIbβ3 in Glanzmann Thromboasthenia patients

Platelet transfusions, main therapy of Glanzmann Thromboasthenia (GT), can induce an allo-immunization against human leucocyte antigen and integrin alphaIIbbeta3. We have investigated in our GT patients the rate of allo-immunization and of refractoriness to platelet transfusions. From 1975 until December 2005, we have followed 17 GT patients: 14 type 1, 3 variant type; nine females, eight males; median age at diagnosis 9.8 years (range 1-44.5); median age at the time of the study 35.5 years (range 23.6-68.5). In our patients, 121 bleeding episodes occurred (24 severe, 37 moderate, and 60 mild). Ten major and 22 minor surgical procedures have been performed. Two spontaneous deliveries and three caesarian sections with five live births were performed; moreover, one late foetal loss occurred, and one voluntary abortion was performed. Sixteen of 17 patients have been transfused at least once in life with platelets and/or red blood cells (RBC). All transfused patients have been investigated for the presence of anti-HLA and anti-integrin alphaIIbbeta3 allo-antibodies. The positiveness of allo-antibodies has been demonstrated in 4/16 transfused patients (25%): isolated for anti-HLA in two; isolated for anti-integrin alphaIIbbeta3 in one; and combined in one. In spite of the presence of allo-antibodies, platelet transfusions have always been effective and the haemostasis was not compromised.

Use of therapeutic dose low molecular weight heparin during pregnancy in women with mechanical heart valves

Management of anticoagulation in women with mechanical heart valves (MHV) is one of the most challenging issues faced by obstetric physicians who manage pregnant women with cardiac problems. The already high risk of valve thrombosis is increased further during pregnancy because of the prothrombotic changes of pregnancy. The safest option for the mother, to reduce the risk of valve thrombosis leading to valve failure or systemic thromboembolism, is to remain on oral anticoagulants such as warfarin. However, warfarin crosses the placenta with a 5–6% risk of warfarin embryopathy if taken between six and nine weeks gestation.1 In addition, warfarin anticoagulates the fetus and there is a high rate of late fetal loss, up to 40% in some studies,2 which further increases women's reluctance to continue taking this form of anticoagulation. Heparin, which does not cross the placenta, is an effective alternative to warfarin for treatment and prevention of venous thrombosis during pregnancy, but there are concerns relating to its efficacy as an anticoagulant in women with MHV. Subcutaneous unfractionated heparin, even when given in high and monitored doses, is associated with an unacceptably high rate of maternal thrombosis. The more predicable anticoagulant effect of low molecular weight heparin (LMWH) makes it is an attractive agent for use in this clinical situation but there are limited data relating to its safety and efficacy. In 2004, Oran and co-workers3 reviewed published case reports and case series of LMWH use in pregnant women with MHV. The overall rate of thromboembolic complications in 81 pregnancies was 11.1% but four of these events were reported in single case studies. Monitoring of anti-Xa levels was not carried out in all centres and women received LMWH for variable periods during pregnancy. Such discrepancies make it difficult to extrapolate these data to other situations.

Factor V Leiden Homozygous Genotype and Pregnancy Outcomes

To assess the rate of early (first trimester) and late (second and third trimester) fetal loss in women who are factor V Leiden homozygous. Between December 1995 and February 2007, consecutive, unrelated white women who were factor V Leiden homozygous and who had been pregnant at least once were recruited from 10 French hemostasis units. For reasons of comparison, we included women who were factor V Leiden heterozygous and a group of noncarriers. The frequency of early and late fetal loss was assessed retrospectively and compared among the three groups. The effect of concomitant thrombophilic abnormalities was evaluated. The overall pregnancy outcome was reported. We analyzed 240 thromboprophylaxis-free pregnancies in 95 women who were factor V Leiden homozygous, 425 in 195 women who were factor V Leiden heterozygous, and 182 in 73 women who were noncarriers. The risk of late fetal loss was higher in women who were homozygous (13/95, 13.7%) compared with those who were noncarriers (1/73, 1.4%, odds ratio 11.41, 95% confidence interval 1.46-89.46, P=.002), whereas it was similar in women who were heterozygous and in noncarriers (6/195, 3.1% compared with 1/73, 1.4%, P=.68). The percentage of women with early fetal loss was similar in the three groups (P=.81). The live-birth rate was 80%, 84%, and 85%, respectively, for women who where homozygous, heterozygous, and noncarriers (P=.88). The factor V Leiden homozygous genotype increases the risk of late fetal loss. However, the overall likelihood of a positive outcome is high in our series of women who were homozygous. III.

The Association Between Anti-beta2 Glycoprotein 1 Antibodies and Adverse Pregnancy Outcomes.

Abstract 4003Poster Board III-939 BACKGROUNDThe Sapporo criteria include anti-β2 glycoprotein1 (anti-B2GP1) antibodies among antiphospholipid antibodies used to diagnose the antiphospholipid syndrome (APS). 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, strong evidence to support their association with anti-B2GP1 antibodies is lacking. OBJECTIVEThis study aims to assess the association between anti-B2GP1 antibodies and placenta mediated complications. METHODSWe performed a nested case-control study from a prospective cohort of 7000 mother baby pairs whereby women and their fetuses were recruited between 12-20 weeks gestation. Five hundred cases were randomly selected amongst women who experienced one of the following adjudicated adverse pregnancy outcomes: pre-eclampsia (BP ≥140/90 with proteinuria), placental abruption (antepartum bleeding with objective evidence of placental thrombus), late pregnancy loss (≥ 12 weeks gestation) and IUGR (birth weight less than the 10th percentile of normal population). Random selection of 500 controls was performed amongst women who did not experience the above mentioned adverse pregnancy outcomes. Stored blood samples were analyzed for the presence of anti-B2GP1 IgG and IgM antibodies by enzyme-linked immunosorbent assay. Titers ≥ than 20 G or M units were considered positive. This study has an 80% power to detect an odds ratio of 2.25 at the 5% level of significance based on an estimated 4 % prevalence of anti-B2GP1 IgG and/or IgM antibodies in titers ≥ 20 G/M units in our cohort of pregnant women. RESULTSAnti-B2GP1 IgG and/or IgM antibodies in titers ≥ 20 G/M units were present in 24/497 (4.8%) controls and 33/503 (6.6%) cases. The presence of anti-B2GP1 IgG and/or IgM in titers ' 20 G/M units was not significantly associated with a composite outcome of pre-eclampsia, IUGR, late fetal loss and placental abruption (OR 1.38; 95%CI 0.8-2.37 p=0.18). This combination of antibodies and titers only demonstrated a weak association with IUGR (OR 1.86; 95%CI 1.09-3.18 p=0.02). The presence of anti-B2GP1 IgG and/or IgM antibodies in titers ≥ 40 G/M units also failed to show an association with a composite outcome of pre-eclampsia, IUGR, late fetal loss and placental abruption (OR 2.65; 95%CI 0.7-10.04 p=0.15). However, stronger associations were observed with placental abruption (OR 4.87; 95%CI 1.02-23.25 p=0.047) and IUGR (OR 3.53; 95%CI 1.03-12.15 p=0.045). CONCLUSIONThe presence of anti-B2GP1 IgG and/or IgM antibodies in titers 20 ≥ G/M units during pregnancy is only associated with an increased risk of IUGR. Anti-B2GP1 antibodies in titers ' 40 G/M units, as suggested in the Sapporo diagnostic criteria for the APS, are associated with IUGR and placental abruption and possibly other placenta mediated complications. Larger adequately powered studies will be required to provide definitive answers. Disclosures:No relevant conflicts of interest to declare.