Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study.

BACKGROUND: Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti-ß2 glycoprotein-I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well-established. OBJECTIVE: The purpose of this study was to assess the risk of obstetric complications in women with primary antiphospholipid syndrome that is associated with specific antibody profile. STUDY DESIGN: The Pregnancy In Women With Antiphospholipid Syndrome study is a multicenter, retrospective, cohort study. Diagnosis and classification of antiphospholipid syndrome were based on the 2006 International revised criteria. All women included in the study had at least 1 clinical criteria for antiphospholipid syndrome, were positive for at least 1 antiphospholipid antibody (anticardiolipin antibodies, anti-ß2 glycoprotein-I, and/or lupus anticoagulant), and were treated with low-dose aspirin and prophylactic low molecular weight heparin from the first trimester. Only singleton pregnancies with primary antiphospholipid syndrome were included. The primary outcome was live birth, defined as any delivery of a live infant after 22 weeks gestation. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction, and stillbirth. We planned to assess the outcomes that are associated with the various antibody profile (test result for lupus anticoagulant, anticardiolipin antibodies, and anti-ß2 glycoprotein-I). RESULTS: There were 750 singleton pregnancies with primary antiphospholipid syndrome in the study cohort: 54 (7.2%) were positive for lupus anticoagulant only; 458 (61.0%) were positive for anticardiolipin antibodies only; 128 (17.1%) were positive for anti-ß2 glycoprotein-I only; 90 (12.0%) were double positive and lupus anticoagulant negative, and 20 (2.7%) were triple positive. The incidence of live birth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared with women with only 1 antibody positive test results, women with multiple antibody positive results had a significantly lower live birth rate (40.9% vs 56.6%; adjusted odds ratio, 0.71; 95% confidence interval, 0.51-0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; adjusted odds ratio, 1.56; 95% confidence interval, 1.22-1.95) and with severe features (22.7% vs 13.8%, adjusted odds ratio, 1.66; 95% confidence interval, 1.19-2.49), of intrauterine growth restriction (53.6% vs 40.8%; adjusted odds ratio, 2.31; 95% confidence interval, 1.17-2.61) and of stillbirth (36.4% vs 21.7%; adjusted odds ratio, 2.67; 95% confidence interval, 1.22-2.94). In women with only 1 positive test result, women with anti-ß2 glycoprotein-I positivity present alone had a significantly lower live birth rate (47.7% vs 56.3% vs 79.6%; P<.01) and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; P<.01) and with severe features (17.2% vs 14.4% vs 0%; P=.02), intrauterine growth restriction (48.4% vs 40.1% vs 25.9%; P<.01), and stillbirth (29.7% vs 21.2% vs 7.4%; P<.01) compared with women with anticardiolipin antibodies and with women with lupus anticoagulant present alone, respectively. In the group of women with >1 antibody positivity, triple-positive women had a lower live birth rate (30% vs 43.3%; adjusted odds ratio,0.69; 95% confidence interval, 0.22-0.91) and a higher incidence of intrauterine growth restriction (70.0% vs 50.0%; adjusted odds ratio,2.40; 95% confidence interval, 1.15-2.99) compared with double positive and lupus anticoagulant negative women. CONCLUSION: In singleton pregnancies with primary antiphospholipid syndrome, anticardiolipin antibody is the most common sole antiphospholipid antibody present, but anti-ß2 glycoprotein-I is the one associated with the lowest live birth rate and highest incidence of preeclampsia, intrauterine growth restriction, and stillbirth, compared with the presence of anticardiolipin antibodies or lupus anticoagulant alone. Women with primary antiphospholipid syndrome have an increased risk of obstetric complications and lower live birth rate when <1 antiphospholipid antibody is present. Despite therapy with low-dose aspirin and prophylactic low molecular weight heparin, the chance of a liveborn neonate is only 30% for triple-positive women.

Cell-Free Fetal DNA for the Prediction of Pre-Eclampsia at the First and Second Trimesters: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and pooled analysis was carried out to estimate whether the increase in the quantity of cell-free fetal DNA (cffDNA) before the onset of pre-eclampsia (PE) can predict the disease using real-time polymerase chain reaction (PCR). METHOD: A comprehensive literature search of the PubMed, Scopus, and Web of Knowledge databases was conducted to identify relevant studies that included evaluated cffDNA levels in pregnant women before the clinical onset of PE. A simulation model was generated to calculate the detection rate (DR) of cffDNA for PE, and a random variable was generated using the same number of cases and same statistical measurements of central tendency and dispersion as those reported in the papers considered for the analysis. Simulation of the receiver operating characteristic (ROC) curves was also carried out. RESULTS: Four studies (82 cases and 1315 controls) evaluated cffDNA in early-onset PE, with DRs of 18 and 68.8% at 11-13 and 17-28 weeks, respectively, at a false positive rate of 10%. Nine studies (including two considered for early-onset PE) encompassing 376 cases and 1270 controls were available for the evaluation of 'any PE'. At 11-14 weeks no significant DR was found, while at 15-28 weeks the DR was 37%. CONCLUSION: CffDNA quantification is a marker for predicting the development of both early-onset PE and 'any PE'; however, it can probably only be used from the beginning of the second trimester, otherwise its predictive value is burdened with a DR that is too low or not significant. Due to the heterogeneity and difficulty in interpreting the published data, no conclusion regarding the statistical and clinical relevance, especially for screening 'any PE', can be made at present.

Elevated maternal placental protein 13 serum levels at term of pregnancy in postpartum major hemorrhage (>1000 mLs). A prospective cohort study.

PROBLEM: To compare placental protein 13 (PP13) levels in the serum of women with primary postpartum hemorrhage (PPH) with a control population. METHODS: A prospective cohort study was conducted between May 2014 and May 2016 and included 435 pregnant women at term (38 weeks gestation) without any known risk factor and with normal labor. Multiples of median (MoM) were used to evaluate differences of the PP13 values between cases and controls. PP13 concentrations were adjusted for maternal and neonatal weight. Multivariable analysis was used to detect independent contribution of predictors of PPH. RESULTS: Fifteen had a major PPH >1000 mLs and represented the cases of the study. They were matched with 399 controls. Twenty-one patients who had a minor PPH (500-1000 mLs) were excluded. The mean observed rank in the PPH group was higher than that of controls (28.5 vs 13.5, P-value=.01). PP13 MoM values adjusted for maternal weight were higher than expected being 1.44±0.45 in PPH cases and 1.00±0.59 in controls (P-value .008). This difference was still significant even after adjustment for neonatal weight that represented a confounding variable. CONCLUSION: Higher PP13 levels are independently associated with major PPH >1000 mLs.

A First-Trimester Biomarker Panel for Predicting the Development of Gestational Diabetes.

OBJECTIVE: Serum markers measured early in pregnancy have been associated with the later diagnosis of gestational diabetes mellitus (GDM). This study aims to explore the performance of a panel of first-trimester biochemical markers for the prediction of GDM. METHODS: A case-control study was performed that included 12 women who developed GDM and 60 controls matched for maternal and gestational age at blood collection. Levels of pregnancy-associated plasma protein A (PAPP-A), soluble endoglin, pregnancy protein 13, and adiponectin (Adipo) were measured on residual sera used in first-trimester screening for Down syndrome. Data were analyzed by nonparametric methods. A receiver operating characteristic curve was used to calculate the detection rate (DR) obtained with a panel of significant predictors for GDM. RESULTS: Multiples of the median values for Adipo and PAPP-A were significantly reduced in GDM cases versus matched controls. Combination of Adipo and PAPP-A yielded a DR of 63.6% at a false-positive rate of 10%. Addition of body mass index (BMI) to this panel increased DR to 72.7%. CONCLUSION: This study suggests that first-trimester screening with Adipo, PAPP-A, and BMI may effectively identify women at high risk for the development of GDM.

Fetal cerebellar damage in fetuses with severe anemia undergoing intrauterine transfusions.

OBJECTIVE: To evaluate radiologic findings and outcomes of cerebellar injuries in fetuses with severe anemia due to RhD alloimmunization undergoing intrauterine transfusions. METHODS: Imaging of multiplanar neurosonography and magnetic resonance imaging (MRI) were reviewed. Pregnancy outcomes were recorded. RESULTS: Cerebellar injuries were identified after the first intravascular transfusion in four fetuses. Two of these cases were previously reported. The median hemoglobin concentration was 2.1 g/dL. Prenatal neurosonography identified an echogenic collection involving the cerebellum suggestive for hemorrhage in three cases. A progressive hypoplasia of a hemisphere was demonstrated at follow-up examination in one of these cases. Hypoplasia of a cerebellar hemisphere was seen in the fourth fetus. Ultrasound diagnosis was confirmed by prenatal MRI in two cases. In the third case, the postnatal MRI showed as additional finding vermian involvement. One pregnancy was terminated and autopsy confirmed the presence of infratentorial hemorrhage. The remaining infants were delivered alive. At time of writing, a truncal ataxia was diagnosed in the child with vermian hypoplasia, while the other children have met all age-appropriate milestones. CONCLUSIONS: A severe anemia seems to put the fetus at risk of cerebellar damage, despite successful intravascular transfusion.