Andrea Dall’Asta

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‐&bgr;2 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‐&bgr;2 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‐&bgr;2 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‐&bgr;2 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‐&bgr;2 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‐&bgr;2 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.

An Update on Maternal Hydration Strategies for Amniotic Fluid Improvement in Isolated Oligohydramnios and Normohydramnios: Evidence from a Systematic Review of Literature and Meta-Analysis.

Objective Several trials aimed at evaluating the efficacy of maternal hydration (MH) in increasing amniotic-fluid-volume (AFV) in pregnancies with isolated oligohydramnios or normohydramnos have been conducted. Unfortunately, no evidences support this intervention in routine-clinical-practice. The aim of this systematic-literature-review and meta-analysis was to collect all data regarding proposed strategies and their efficacy in relation to each clinical condition for which MH-therapy was performed with the aim of increasing amniotic-fluid (AF) and improving perinatal outcomes. Materials and Methods A systematic literature search was conducted in electronic-database MEDLINE, EMBASE, ScienceDirect and the Cochrane-Library in the time interval between 1991 and 2014. Following the identification of eligible trials, we estimated the methodological quality of each study (using QADAS-2) and clustered patients according to the following outcome measures: route of administration (oral versus intravenous versus combined), total daily dose of fluids administered (<2000 versus >2000), duration of hydration therapy: (1 day, >1 day but <1 week, >1 week), type of fluid administered (isotonic versus hypotonic versus combination). Results In isolated-oligohydramnios (IO), maternal oral hydration is more effective than intravenous hydration and hypotonic solutions superior to isotonic solutions. The improvement in AFV appears to be time-dependent rather than daily-dose dependent. Regarding normohydramnios pregnancies, all strategies seem equivalent though the administration of hypotonic-fluid appears to have a slightly greater effect than isotonic-fluid. Regarding perinatal outcomes, data is fragmentary and heterogeneous and does not allow us to define the real clinical utility of MH. Conclusions Available data suggests that MH may be a safe, well-tolerated and useful strategy to improve AFV especially in cases of IO. In view of the numerous obstetric situations in which a reduced AFV may pose a threat, particularly to the fetus, the possibility of increasing AFV with a simple and inexpensive practice like MH-therapy may have potential clinical applications. Considering the various strategies of maternal hydration implemented in the treatment of IO, better results were observed when treatment was based on a combination of intravenous (for a period of 1 day) and oral (for a period of at least 14 days) hypotonic fluids (≥2000ml).

Does vacuum delivery carry a higher risk of shoulder dystocia? Review and meta-analysis of the literature.

INTRODUCTION Vacuum extractor has been increasingly used over the last decades and is acknowledged as a risk factor for shoulder dystocia (SD). In this meta-analysis we assess the actual risk of SD following a vacuum delivery compared to spontaneous vaginal delivery (SVD) and forceps. MATERIALS AND METHODS Systematic literature search (English literature only) on MEDLINE, EMBASE, ScienceDirect, the Cochrane library and ClinicalTrials.gov conducted up to May 2015. Key search terms included: Operative/Vacuum/Forceps delivery [Mesh] and shoulder dystocia and subheadings. 2 stage-process study selection. We included only studies where data concerning the occurrence of SD following operative vaginal delivery were reported as adjusted odds ratio (AOR) and no significant difference in confounding factors for SD was recorded. Included trials clustered according to the delivery mode (1) vacuum vs. SVD, (2) forceps vs. vacuum. Methodological quality of each study evaluated with the Newcastle-Ottawa System (NOS). RESULTS 87 potentially relevant papers. After applying inclusion and exclusion criteria only 7 were selected for the meta-analysis. Vacuum delivery appeared associated with a higher risk of SD than SVD in both fixed and random model (OR 2.87 and 2.98 respectively). No difference in the rate of SD was found between vacuum and forceps (p>0.05). CONCLUSION Vacuum extractor carries an increased risk of SD compared with spontaneous vaginal delivery whereas the occurrence of SD does not seem to vary following vacuum or forceps.

Female Stress Urinary Incontinence Clinical Efficacy and Satisfaction After Transobturator Adjustable Tape Sling. An Observational Longitudinal Cohort Study

We performed an observational longitudinal cohort study on patients affected by stress urinary incontinence (SUI) and surgically treated with a transobturator adjustable tape sling (TOA) in order to evaluate this surgical procedure in terms of efficacy, safety, quality of life (QoL) improvement, and patient satisfaction. For all patients, we recorded: general features, preoperative SUI risk factors, obstetrics history, preoperative urodynamic tests, intraoperative/postoperative complications, number of postoperative sling regulations, postmicturition residue, and hospital stay. All patients were asked to complete the validated short version of the Urogenital Distress Inventory (UDI-6) questionnaire 18 months after discharge to evaluate the efficacy of the TOA system. We added 2 adjunctive items to the UDI-6 in order to evaluate patient satisfaction and QoL. All 77 surgical procedures were performed under locoregional anesthesia without complications. Postoperative TOA regulations were performed in 46.8% of patients immediately after the procedure and in 14.3% during hospitalization. Before discharge, postmicturition residue was negative in 67 cases and less than 50 cc in 10 cases. Mean hospital stay was 2.18 days. From the questionnaire evaluation, we found that after the procedure, 90.9% of patients showed a complete regression of urinary symptoms, 1.3% obtained considerable relief from preoperative symptoms, and 6.6% reported poor or absent symptom improvements; 75.3% of patients were totally satisfied and 5.2% totally disappointed. The possibility of modulating postoperative sling tension and reusing the surgical materials in association with short hospitalization as well as high patient satisfaction render TOA a safe, effective, and low-cost technique for the treatment of female SUI.

Reduced short-term variation following antenatal administration of betamethasone: Is reduced fetal size a predisposing factor?

OBJECTIVE To assess the association between fetal size and the incidence of reduced short-term variability (STV) following bethametasone administration for fetal lung maturity. STUDY DESIGN This was a retrospective, multicenter, cohort study conducted in two Tertiary University Units. Only uncomplicated singleton pregnancies admitted for threatened preterm labor between 26 and 34 weeks and submitted to betamethasone for fetal lung maturity were included. Delivery occurring within 72h from betamethasone administration represented criteria for exclusion. Computerized cardiotocography was carried out on a daily basis. Cases were identified by persistently reduced STV, defined as <5th percentile for gestational age and lasting for at least 72h after the first dose of betamethasone. The primary outcome was estimated fetal weight (EFW) at ultrasound in fetuses with normal and in those with persistently reduced STV. Pregnancy outcomes were also evaluated. RESULTS Persistently reduced STV occurred in 33/405 of the included patients (8.1%). Compared to women with normal STV, those with persistently reduced STV had significantly lower EFW (1472±435 vs 1812±532g, p 0.04), lower birthweight (2353±635 vs 2857±796g, p<0.01) and earlier gestational age at delivery (35.1±4.2 vs 37.3±2.4weeks, p<0.01), whereas all the other variables including gestational age on admission were comparable. CONCLUSIONS Reduced STV following maternal betamethasone administration among appropriately grown fetuses seems to correlate with lower fetal size. Furthermore, fetuses with such abnormal response to steroids seem to carry a higher risk of perinatal complications, including lower birthweight and earlier gestational age at delivery.

Quantitative analysis of fetal facial morphology using 3D ultrasound and statistical shape modeling: a feasibility study

BACKGROUND: The antenatal detection of facial dysmorphism using 3‐dimensional ultrasound may raise the suspicion of an underlying genetic condition but infrequently leads to a definitive antenatal diagnosis. Despite advances in array and noninvasive prenatal testing, not all genetic conditions can be ascertained from such testing. OBJECTIVES: The aim of this study was to investigate the feasibility of quantitative assessment of fetal face features using prenatal 3‐dimensional ultrasound volumes and statistical shape modeling. STUDY DESIGN: Thirteen normal and 7 abnormal stored 3‐dimensional ultrasound fetal face volumes were analyzed, at a median gestation of 29+4 weeks (25+0 to 36+1). The 20 3‐dimensional surface meshes generated were aligned and served as input for a statistical shape model, which computed the mean 3‐dimensional face shape and 3‐dimensional shape variations using principal component analysis. RESULTS: Ten shape modes explained more than 90% of the total shape variability in the population. While the first mode accounted for overall size differences, the second highlighted shape feature changes from an overall proportionate toward a more asymmetric face shape with a wide prominent forehead and an undersized, posteriorly positioned chin. Analysis of the Mahalanobis distance in principal component analysis shape space suggested differences between normal and abnormal fetuses (median and interquartile range distance values, 7.31 ± 5.54 for the normal group vs 13.27 ± 9.82 for the abnormal group) (P = .056). CONCLUSION: This feasibility study demonstrates that objective characterization and quantification of fetal facial morphology is possible from 3‐dimensional ultrasound. This technique has the potential to assist in utero diagnosis, particularly of rare conditions in which facial dysmorphology is a feature.

Early labor cerebroplacental ratio assessment in uncomplicated term pregnancies and prediction of adverse perinatal outcomes: a prospective, multicentre study

It has been suggested that the use of Doppler ultrasound in term pregnancies with normal‐sized fetuses is able to identify those at high risk of subclinical placental function impairment. The objective of this study was to evaluate the relationship between cerebroplacental ratio (CPR) measured in early labor and perinatal and delivery outcomes in a cohort of uncomplicated singleton term pregnancies.

Etiology and Prognosis of Severe Ventriculomegaly Diagnosed at Late Gestation

OBJECTIVES  We sought to assess the causes and outcomes of severe VM diagnosed de novo after 24 weeks of gestation where a mid-trimester anomaly scan was described as normal. METHODS  Multicenter retrospective study of five European fetal medicine centers. The inclusion criteria were normal anatomy at the mid-trimester scan, uni/bilateral finding of posterior ventricle measuring ≥ 15 mm after 24 weeks with neonatal and postnatal pediatric and/or neurological assessment data. RESULTS  Of 74 potentially eligible cases, 10 underwent termination, the outcome was missing in 19 cases and there was 1 neonatal death. Therefore, 44 formed the study cohort with a median gestation at diagnosis of 32 + 0 weeks (25 + 6 - 40 + 5). VM was unilateral in five cases. Agenesis of the corpus callosum (ACC) and grade III/IV intraventricular hemorrhage (IVH) accounted for 14 cases each. ACC was isolated in 9 fetuses. Obstructive abnormalities included 5 arachnoid and 1 cavum velum interpositum cyst. Four fetuses had an associated suspected or confirmed genetic condition, 2 congenital infections, 1 abnormal cortical development and the etiology was unknown in 3/44. Postnatal assessment at median 20 months (3 - 96) showed 22/44 (50 %) normal, 7 (16 %) mildly abnormal and 15 (34 %) severely abnormal neurodevelopmental outcomes. CONCLUSION  One half of babies with severe VM diagnosed after 24 weeks have normal infant outcome with ACC and IVH representing the most common causes. Etiology is the most important factor affecting the prognosis of fetuses with severe VM diagnosed at late gestation.

How often an isolated cardiac disproportion predicts a coarctation of the aorta? Single center experience and systematic review of the literature

Abstract Background: Cardiac disproportion is considered as an indirect sign of coarctation of the aorta (CoA). In this review, we have reassessed the positive predictive value (PPV) of such finding for a postnatal confirmation of CoA. Data sources: All cases of isolated cardiac disproportion diagnosed in the four-chamber and/or three-vessel/three-vessel and trachea views (right/left sections >1.5) were included. Postnatal cardiac findings were recorded. Additionally, a systematic literature search (PubMed, EMBASE, Cochrane library, and the reference lists of identified articles) regarding the association between antenatally detected cardiac disproportion and postnatal confirmation of CoA was performed. Data from our center were pooled with those derived from the literature. Results: Ten fetuses with isolated cardiac disproportion were selected from our center and 259 from the literature review. CoA was postnatally confirmed in 101/269 (PPV 38%). PPV of antenatal cardiac findings was significantly higher in earlier gestation (23/27, 85% <26+0 weeks versus 11/39, 28%≥26+0 weeks, p < .001). No significant difference was noticed comparing ventricular disproportion with combined ventricular and great vessels disproportion (86/230 versus 15/39, p  .89). Discussion: Isolated cardiac disproportion has an overall chance of one in three of heralding a CoA in the neonate. The specificity of these findings is significantly higher in the second trimester.

Antenatal Care of Preeclampsia: From the Inverted Pyramid to the Arrow Model?

The recent demonstration of the effectiveness of low-dose aspirin administered from the first trimester in the prevention of preeclampsia will probably lead to establishing and radicating the “inverted pyramid” screening model for preeclampsia. Such a multiparametric approach for the screening of preeclampsia in the first trimester, albeit highly sensitive in identifying early-onset disease, is poor at screening the forms of preeclampsia occurring close to term. Late-onset preeclampsia is 3 to 6 times more common than early-onset preeclampsia and currently represents the major determinant of maternal morbidity related to hypertensive disorders of the pregnancy. On this ground, we discuss our idea to construct a second “screening checkpoint” in the third trimester with the aim of reassessing the risk of preeclampsia of those women who screened negative in the first trimester. If implemented, the sequential screening model we propose would convert the “inverted pyramid model” into an “arrow model” for the antenatal care of preeclampsia.