Late Pregnancy Loss Research Articles

Methyl donor supplementation of gestating sow diets improves pregnancy outcomes and litter size

Maternal intake of B-vitamin and methyl donors can affect sow prolificacy. A total of 1079 Large White/Landrace sows (parities 2–9 at mating) were used in a 2 by 2 by 2 factorial design to determine the effects of two levels of betaine supplementation (0 versus 3 g added betaine/kg feed), two levels of folic acid plus vitamin B12 supplementation (0 versus 20 mg/kg folic acid plus 150 µg/kg vitamin B12) during gestation, and two parity groups (parity 2 and 3 versus parity 4 and greater) on litter size and pregnancy outcomes. The number of sows returning to oestrus post-insemination, as well as the number of early (<Day 30) and late (>Day 30) pregnancy losses were recorded. At farrowing, the total number of piglets born, the number of piglets born alive and dead, as well as the number of mummified fetuses were recorded. Pre-prandial blood samples were collected from a subset of 20 sows/treatment on Days 3, 30 and 107 of gestation to analyse homocysteine. The incidence of early pregnancy loss was reduced (P < 0.001) by folic acid plus vitamin B12 supplementation (0.03 versus 0.07). There was a significant interaction between parity at mating (parities 2 and 3 versus parity 4 and greater) and the addition of betaine or folic acid plus vitamin B12 to the gestation diet on litter size. Litter size was higher (0.5 piglets; P < 0.05) for betaine supplemented, compared with unsupplemented, parity 4 plus sows. Folic acid plus vitamin B12-supplemented parity 2 and 3 sows gave birth to more (P < 0.05) piglets than all other treatment groups. Folic acid plus vitamin B12 supplementation decreased (P < 0.001) plasma homocysteine concentration by 2.2 and 2.8 μM, respectively, on Days 3 and 107 of gestation. However, betaine supplementation decreased (P < 0.05) homocysteine on Day 3 only. Overall, folic acid plus vitamin B12 supplementation decreased incidences of early pregnancy failure and increased litter size in early parity sows, while betaine increased litter size in older parity sows.

Study on clinical risk of maternal underlying medical conditions and onset of preeclampsia

To investigate the effect of clinical risk factors including maternal underlying medical conditions on the development of preeclampsia (PE) in order to improve and strengthen the early assessment of high clinical risk population of PE. Clinical observational data of patients with PE in Peking University Third Hospital from November 2008 to January 2011 were analyzed. Comparative analysis was made among medical conditions with PE (M-PE) sub-group and isolated PE (I-PE) sub-group and non-PE pregnancy with or without medical conditions (control group). Totally 159 cases, 43.09% (159/369) of total cases of PE had high clinical risk factors (multiple pregnancy and medical conditions) and 32.3% (97/300) of singleton PE accompanied with medical conditions. The incidence of PE in singleton pregnancies with medical conditions was significantly higher than those without medical conditions [15.0% (97/646) versus 4.45% (210/4719), P < 0.05]. In M-PE sub-group, the average age [(31.7 ± 4.5) versus (29.3 ± 5.2) year-old] and body mass index (BMI) in first trimester [(26.0 ± 5.6) versus (23.3 ± 3.7) kg/m(2)], the proportion with previous preeclampsia [11% (11/97) versus 4.9% (10/203)] and pregnancy loss in third trimester [11% (11/97) versus 3.0% (6/203)], were higher than those of I-PE sub-group (all P < 0.05). The onset of preeclampsia in M-PE sub-group was earlier than I-PE (32.9 versus 34.4 gestation weeks, P < 0.05). The proportion serious cases of PE occurring before 32 gestational weeks were higher in M-PE than that of I-PE sub-group [45% (44/97) versus 34.0% (69/203), P < 0.05]. Multivariate regression analysis showed that previous history of late pregnancy loss and irregular prenatal care were clinical risk factors for early-onset PE whether early-onset was defined as < 34 or < 32 gestational weeks respectively (all P < 0.05); medical conditions were risk factors for PE if early-onset was defined as < 32 gestational weeks (OR = 1.718, 95%CI: 1.005 - 2.937, P = 0.048). Multiple pregnancies and pregnancies with medical conditions exceed one-third of total subjects of PE. The onset of PE in subjects with maternal underlying medical conditions was earlier which is the subgroup should not be ignored. The difference of early pregnancy BMI may show the maternal heterogeneity in early onset and late onset of preeclampsia. Assessment of clinical risk factors including the underlying medical disorders for preeclampsia in early trimester should be strengthened.

Candidate gene study of genetic thrombophilic polymorphisms in pre‐eclampsia and recurrent pregnancy loss in Sinhalese women

Genetic thrombophilias are known to contribute to adverse pregnancy outcomes. Studies in Western populations show that 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and Factor V (F5) 1691G>A (Leiden) polymorphisms are commonly associated with pre-eclampsia and recurrent spontaneous pregnancy loss. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133); 1298A>C (rs1801131) and F5 1691G>A (rs6025); 4070A>G (rs1800595) polymorphisms with pre-eclampsia and recurrent pregnancy loss among Sinhalese women in Sri Lanka. Genotype and allele frequencies at each polymorphic site in the MTHFR and F5 genes and the haplotypes defined by them were determined in 175 Sinhalese women with pre-eclampsia, 171 normotensive controls, 200 Sinhalese women with two or more recurrent pregnancy losses and 200 controls with two or more living children and no pregnancy losses. Genotyping was done by polymerase chain reaction/restriction fragment length polymorphism. Odds ratios and χ(2) -testing were performed to compare genotype/haplotype frequencies at each polymorphic site for both cases and controls. The genotype frequencies at each polymorphic site in the MTHFR 677C>T; 1298A>C; F5 1691G>A and 4070A>G genes and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss. There was no significant association of genetic thrombophilia with either early or late pregnancy losses. The MTHFR and F5 polymorphisms and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss in this group of Sinhalese women.

Guidelines on the investigation and management of antiphospholipid syndrome

This guidance updates and replaces the previous guideline on the investigation and management of antiphospholipid syndrome (APS) published in 2000 (Greaves et al, 2000), though where there have not been changes we refer back to them when appropriate. The guidance is updated with reference to relevant publications since 2000. Publications known to the writing group were supplemented with additional papers identified by searching PubMed for publications in the last 11 years using the key words: lupus anticoagulant, anticardiolipin, antiphospholipid, b2–glycoprotein I, antiprothrombin and limits (clinical trial, randomized control trial, meta-analysis, humans, core clinical journals, English language). The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the Royal College of Obstetricians and Gynaecologists (RCOG), and the British Committee for Standards in Haematology (BCSH) Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMEN DATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with antiphospholipid syndrome though individual patient circumstances may dictate an alternative approach.

‘She was a person, she was here’: The experience of late pregnancy loss in Australia

Objective: To describe Australian women’s experience of late pregnancy loss, with a particular emphasis on their experiences with the health care system. Background: Stillbirth occurs in 1 of every 200 births, yet little research attention has been paid to women’s experiences of stillbirth or the role of heath care providers in helping them cope with this profoundly distressing experience. Methods: Qualitative analysis of 14 Australian women’s descriptions of their recent stillbirth experiences, collected via an online survey. Results: Women generally described the experience of pregnancy loss as exceptionally distressing, but health care providers as positive and supportive. They were more negative about hospital policies and procedures, and about ambiguities and misunderstandings which increased their distress. Conclusion: Most women interpreted the experience as the birth and death of a baby, and as a major family tragedy, while at least some health care professionals appeared to view it primarily as a medical problem. This mismatch in perceptions appeared on occasions to exacerbate levels of distress and to result in care that was focused on medical rather than personal concerns.

Seasonal variation in the ovarian function of sows

The modern domestic sow exhibits a period of impaired reproductive performance known as seasonal infertility during the late summer and early autumn months. A reduction in farrowing rate due to pregnancy loss is the most economically significant manifestation of this phenomenon. Presently, little is known of the aetiology of seasonal pregnancy loss in the pig. Recent findings represent a major advancement in the understanding of sow reproductive physiology and implicate poor oocyte developmental competence as a contributing factor to pregnancy loss during the seasonal infertility period. It has also been demonstrated that ovarian activity is depressed during the seasonal infertility period. The reduction in oocyte quality is associated with decreased levels of progesterone in follicular fluid during final oocyte maturation in vivo. The recent identification of sow-specific risk factors, such as parity for late pregnancy loss, should improve breeding herd efficiency by allowing producers to tailor management interventions and/or culling protocols that target animals identified as having a greater risk of late pregnancy loss during the seasonal infertility period.

Association of elevated soluble P-selectin levels with fetal loss in women with a history of venous thromboembolism

IntroductionAn association between pregnancy complications such as fetal loss with inherited and acquired thrombophilic defects has frequently been reported. Recently, the cell adhesion molecule P-selectin has been identified to be a strong risk factor for venous thromboembolism (VTE). Patients and MethodsThe aim of our study was to investigate whether soluble P-selectin (sP-selectin) is also associated with fetal loss (e.g. miscarriage or stillbirth) in 304 women (median age [25th-75th percentile]: 45 [37–54] years) with a history of VTE, in whom data on pregnancy-associated complications had been evaluated. At the time of sP-selectin measurement none of the women was pregnant or had an acute VTE. ResultsThe prevalence of miscarriage was 21.4% and that of stillbirth was 4.6%. The median sP-selectin level of the total study population was 38.0 [31.7-44.4] ng/mL. In subjects with elevated sP-selectin levels (defined as sP-selectin ≥44.4ng/mL, representing the 75th percentile of levels in the study population) the prevalence of stillbirth was significantly higher compared to those with lower levels (10.5% vs. 2.6%, p=0.008), whereas no statistically significant difference in the prevalence of miscarriage was observed between women with and without elevated sP-selectin (17.1% vs. 22.9%, p=0.303). The odds ratio [95% CI] of elevated sP-selectin was 4.2 [1.5-12.7] for stillbirth and 0.7 [0.4-1.3] for miscarriage. ConclusionsElevated sP-selectin plasma levels were associated with a 4.2-fold risk for stillbirth in women with a history of VTE. Our data support a possible role of P-selectin in late pregnancy loss.

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.

Religiosity is an Important Part of Coping with Grief in Pregnancy After a Traumatic Second Trimester Loss

Women (n=15) who were pregnant after a traumatic late pregnancy loss (termination because of fetal death or serious anomalies) completed psychometric screening tests and scales, including the Perinatal Grief Scale (PGS), the Impact of Event Scale (IES), the Duke Depression Inventory (DDI), the Generalized Anxiety Disorder-7 (GAD), and the Hoge Scale for Intrinsic Religiosity (IR). Despite a mean elapsed time since the prior loss of 27 (range, 7-47) months, half (7/15, 47%) of the combined groups had high levels of grief on the PGS. Multiple positive scores on psychometric tests were frequent: Sixty percent (9/15) had high scores on the PGS Active Grief subscale or on the IES. Forty percent (6/15) had a high score on the DDI, and 17% (3/15) on the GAD. IR scores significantly and negatively correlated with scores on the Despair subscale of the PGS. The results from this pilot study suggest that high levels of grief and PTS symptoms are significant problems for pregnant women who have suffered late loss of a wanted pregnancy. Religiosity may play an important part in maternal coping during these stressful pregnancies.

Seasonal effects on oocyte developmental competence in sows experiencing pregnancy loss

Recently, oocyte quality in sows culled for reasons unrelated to fertility was found to decline during the period of seasonal infertility. Wean-to-service interval (WSI) has also been associated with pregnancy loss in sows mated during the period of seasonal infertility. The aims of this study were to determine whether WSI and season are associated with changes in oocyte developmental competence in sows experiencing early (before Day 35 of gestation) and late (after Day 35 of gestation) pregnancy loss. Ovaries were collected in pairs from sows sourced from commercial piggeries that were culled for reasons related to infertility after being mated in summer and winter/spring. Sows were grouped according to their pregnancy loss type, their previous WSI and the presence or absence of corpora lutea (CL) on their ovaries. Oocyte developmental competence was assessed following in vitro maturation, artificial activation and parthenote development in vitro. In sows culled for early-pregnancy loss, there was a greater number of CL present on ovaries collected in spring compared to those collected in summer (11.57 ± 3.3 vs. 9.26 ± 0.99; P < 0.05). Also, the proportion of oocytes developing to the blastocyst stage was greater in summer than in spring (55.9 ± 5.2% vs. 31.2 ± 6.4%; P < 0.05). In sows culled for late-pregnancy loss, a greater proportion of oocytes developed to the blastocyst stage in winter compared with late-spring (64.3 ± 7.0% vs. 34.1 ± 6.6%; P < 0.05). In addition, the blastocyst formation rate of oocytes was lower in sows that displayed a WSI ≤ 6 days than in sows that displayed a WSI > 6 days (37.8 ± 7.3% vs. 62.2 ± 6.9%; P < 0.05). The results of the present study indicate that sows culled for pregnancy loss exhibit seasonal changes in oocyte developmental competence. The mechanism which causes WSI to be prolonged does not appear to result in reduced oocyte developmental competence. While poor oocyte quality and the mechanism that increases WSI may contribute to pregnancy loss during the seasonal infertility period, the findings suggest that these factors are not the main drivers of early and late pregnancy loss throughout the year.

622: Late pregnancy loss after A(H1N1) vaccination

622: Late pregnancy loss after A(H1N1) vaccination

Treatment of adverse perinatal outcome in inherited thrombophilias: a clinical study

Inherited thrombophilia may cause important complications in pregnancies including maternal death, early and late pregnancy loss, preeclampsia, intrauterine growth restriction and placental abruption. This study was developed to investigate the fetal loss and successful birth rates in hereditary thrombophilic patients treated with low-dose acetylsalicylic acid and low molecular weight heparin to determine the necessity and effectiveness of this treatment. Ninety-three patients with the history of recurrent pregnancy loss or thromboembolism were included in this study. Eighty milligram acetylsalicylic acid treatment was started just after the diagnosis for the patients with hereditary thrombophilia, continued throughout pregnancy and ceased 3 days before the delivery. Low molecular weight heparin (LMWH) was started for the patients with the unsuccessful in-vitro fertilization (IVF) history, just after finishing the egg collection. For the other patients, LMWH was started after the positive result of the pregnancy test. Treatment was started for 67 (72%) of patients. Among the treated 67 patients, 38 had MTHFR C677T gene mutation, 25 had protein S deficiency, 19 had FV Leiden mutation, four had protein C deficiency, two had Prothrombin 20210A gene abnormality, two had antiphospholipid anticore syndrome and two had AT III deficiency. Fifty-seven (85.1%) of 67 patients under treatment had pregnancy. Forty-one (61.2%) of those 57 patients had a live birth, whereas 16 (23.9%) of them had abortus under treatment. In regression analysis, only protein C and S deficiencies were found to be independent risk factors. In conclusion, inherited thrombophilia should always be kept in mind as an etiological factor of recurrent abortus. With treatment, success rates are between 60 and 80%. Severe side effects due to treatment are rare. But randomized, double-blind, placebo-controlled studies are still necessary to evaluate the benefit of heparin and acetylsalicylic acid treatment in women with the history of inherited thrombophilia.

The obstetric outcome following treatment in a cohort of patients with antiphospholipid antibody syndrome in a tertiary care center

Antiphospholipid antibody syndrome (APAS) is regarded as the most frequently acquired risk factor for thrombophilia. The obstetric manifestations of APAS include early or late pregnancy losses and complications like preeclampsia and fetal growth restriction. Its timely diagnosis and treatment can improve maternal and neonatal outcome. To study the pregnancy outcome of patients with APAS treated with heparin and aspirin. This was a retrospective study of pregnancy outcome in 42 consecutive women with APAS, treated with heparin and aspirin. The case records of 42 diagnosed cases of APAS with pregnancy, over a 3-year period, were studied. The pregnancy outcome in this group was compared before and after treatment with heparin and low-dose aspirin in terms of abortions, intrauterine deaths and live birth rate. The outcome of the present pregnancy in terms of fetal and maternal complications was analyzed. The mean age and average parity of women with APAS were 30.1±4.1 years and 3.2±1.2, respectively. Among the treated patients of APAS, 13 (30.9%) had preeclampsia and 9 (21.4%) had intrauterine growth restriction (IUGR). There were 2 (4.7%) intrauterine deaths, 4 (9.5%) missed abortions and 3 (7.1%) abruptio placentae. Women with APAS had a live birth rate of 4.6% before treatment and 85.7% in the index pregnancy after treatment. Treatment of pregnant women with APAS results in marked improvement in the live birth rate (4.6-85.7%). However, complications like preeclampsia and IUGR occur even after treatment, requiring strict monitoring and timely delivery.

Increased thrombin generation measured in the presence of thrombomodulin in women with early pregnancy loss

Compared with 537 parous controls with no history of pregnancy loss, a lower thrombomodulin-related inhibition of the endogenous thrombin potential was measured in 264 cases with previous unexplained pregnancy loss, especially when losses occurred between 9 and 12 weeks of gestation. Adjusting age, protein S, factor VIII, factor V Leiden, and prothrombin G20210A did not change the results.

Prolactin’s role in the pathogenesis of the antiphospholipid syndrome

Increased levels of serum prolactin have been reported in patients with various autoimmune diseases and have been associated with lupus disease activity. Currently, there is a lack of data regarding hyperprolactinaemia in patients with the antiphospholipid syndrome. Hence, this study was carried out in order to evaluate the prevalence and clinical significance of hyperprolactinaemia in antiphospholipid syndrome. A total of 172 European patients with antiphospholipid syndrome and 100 geographically and sex-matched healthy controls were included in the study; none had obvious causes of hyperprolactinaemia. All patients underwent clinical assessment for disease manifestations, in addition to laboratory assessment for serum prolactin, antiphospholipid antibodies and some other biomarkers of autoimmune diseases. The tests were performed utilizing the LIAISON® Analyzer (DiaSorin, Sallugia Italy). Hyperprolactinaemia was detected in 21/172 patients with antiphospholipid syndrome and 0/100 controls (p < 0.001). This significant difference was present in both genders and was obvious even after subgrouping the patients into primary and secondary antiphospholipid syndrome. When clinical features were compared, hyperprolactinaemia was associated with reproductive failure, including early and late pregnancy loss (p < 0.05), as well as intrauterine growth retardation (p < 0.05). Hyperprolactinaemia was negatively related to arthralgias, venous thrombosis, pulmonary microthrombosis, pulmonary hypertension in both primary antiphospholipid syndrome and antiphospholipid syndrome secondary to other diseases, and to neurological manifestations in primary antiphospholipid syndrome (p<0.05). The data indirectly imply that prolactin may play a role in the pathogenesis of antiphospholipid syndrome, especially antiphospholipid syndrome-related reproductive failure.

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.

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.

Low Molecular Weight Heparin to Achieve Live Birth Following Unexplained Pregnancy Loss: A Meta-Analysis.

Abstract 489 The management of recurrent pregnancy loss is uncertain. Some cohort studies have identified an association between inherited thrombophilias and recurrent or late-nonrecurrent pregnancy loss which has prompted investigators to evaluate the benefit of low molecular weight heparin to achieve live birth. A similar benefit for low molecular weight heparin has also been proposed independent of thrombophilia status. A recent Cochrane Review on this topic included the results of a single randomized trial in their analysis. As there are several recent randomized trials using low molecular weight heparin in women with recurrent pregnancy loss published in the obstetrical literature, we performed a meta-analysis to evaluate the benefit of low molecular weight heparin in women who experienced unexplained recurrent or late-nonrecurrent pregnancy loss. Methods: We conducted a meta-analysis of randomized controlled trials investigating the benefit of low molecular weight heparin versus a non-anticoagulant control arm in women with a history of ≥2 early pregnancy losses or ≥1 late pregnancy loss; we excluded women with antiphospholipid antibodies and those with an underlying cause of recurrent fetal loss, except for the hereditary thrombophilias. We planned to use random-effects analysis as the primary summary model due to the anticipated variations in enrollment criteria and interventions between the studies. Results: A total of 757 women were enrolled in five studies that satisfied the eligibility criteria. Using the random effects model, the risk ratio of fetal loss for low molecular weight heparin versus control was 0.49 (0.25-0.97 95% CI, P=0.04). There was significant heterogeneity observed between studies (Q-value was 15.59, P=0.004, and I2=74.33%). A priori, we identified the presence or absence of a hereditary thrombophilia as a potential source of heterogeneity. However, subgroup analysis of the studies according to the inclusion or exclusion of women with hereditary thrombophilia did not resolve the observed heterogeneity between studies. Exclusion of the only trial that enrolled women following a non-recurrent pregnancy loss improved the observed heterogeneity but diminished the apparent benefit of low molecular weight heparin (0.63, 95% CI 0.34-1.16, P=0.14). In this trial, the observed birth rate in the control arm was significantly lower than in the other two trials included in this meta-analysis with aspirin-only controls (29% versus 84% or 87% in aspirin-only arms, P&lt;0.001). Conclusion: There is a trend for increased live births when using low molecular weight heparin for the prevention of recurrent pregnancy loss. However, considering the observed heterogeneity across studies, there is insufficient evidence to support the routine use of low molecular weight heparin to improve pregnancy outcomes in women with a history of pregnancy loss. Disclosures: Off Label Use: low molecular weight heparin to prevent pregnancy loss. Bauer:Bayer Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Speakers Bureau; GTC Biotherapeutics: Membership on an entity's Board of Directors or advisory committees. Zwicker:Sanofi-Aventis: Research Funding.

Low molecular weight heparin to achieve live birth following unexplained pregnancy loss: a systematic review.

The management of recurrent pregnancy loss is uncertain. Some cohort studies have identified an association between inherited thrombophilias and recurrent or late non-recurrent pregnancy loss, which has prompted investigators to evaluate the benefit of low molecular weight heparin (LWMH) to achieve live birth. A similar benefit for LMWH has also been proposed independent of thrombophilia status. We conducted a systematic review of randomized controlled trials to assess the benefit of LMWH in achieving live birth for women with a history of recurrent or late non-recurrent pregnancy loss in the absence of antiphospholipid antibodies. For the five studies that satisfied the eligibility criteria, the risk ratio of live birth for women with a history of pregnancy loss treated with LWMH compared with control ranged from 0.95 to 3.00. There was considerable heterogeneity among studies in terms of treatment effect (Q-value was 41.7, P=0.000, and I2=90.4%) independent of thrombophilia status. There was also a wide variation among all studies in terms of definition of early or late pregnancy loss, thrombophilic risk factors, and number of prior pregnancy losses. There is a trend for increased live births when using LWMH for the prevention of recurrent pregnancy loss. Currently, there is insufficient evidence to support the routine use of LWMH to improve pregnancy outcomes in women with a history of pregnancy loss. Not only are additional studies necessary but standardized criteria for trials evaluating the benefit of an intervention in recurrent pregnancy loss should be established.

Array‐based comparative genomic hybridization (aCGH) in the genetic evaluation of stillbirth

This study examined the utility of array-based comparative genomic hybridization (aCGH) in detecting genetic abnormalities associated with late pregnancy loss. Comparisons were made with classic cytogenetics to test whether aCGH represents a superior methodology for the clinical evaluation of stillbirth. Stillborn infants were selected for aCGH testing from the Wisconsin Stillbirth Service Program (WiSSP) database and tissue bank, based on abnormal clinical findings (presence of at least two abnormalities of two different organs or parts of the body). aCGH analysis was successfully completed in 15 cases which met the clinical criteria and for which sufficient amount of high quality DNA was recovered from archival material. The testing was performed using commercially available 1 Mb BAC arrays. Among 15 tested stillborns, aCGH detected two abnormalities (trisomy 21 and an unbalanced translocation between chromosomes 3 and 10), for an overall detection rate of 13% in stillborns with malformations who had normal or unobtainable cytogenetic results. This preliminary study supports the clinical value of aCGH testing in diagnostic evaluation of stillborns with congenital anomalies.