Postnatal outcome of children with antenatal colonic hyperechogenicity.

OBJECTIVE: To evaluate the postnatal outcome of children with antenatal colonic hyperechogenicity, currently considered as a sign of lysinuria-cystinuria, but which may also be a sign of other disorders with a more severe prognosis. METHOD: We carried out a French multi-centric retrospective study via 15 Multidisciplinary Center for Prenatal Diagnosis from January 2011 to January 2021. We included pregnancies for which fetal colonic hyperechogenicity had been demonstrated. We collected the investigations performed during pregnancy and at birth as well as the main clinical features of the mother and the child. We then established the prevalence of pathologies such as lysinuria-cystinuria (LC), hypotonia-cystinuria syndrome (HC), or lysinuric protein intolerance (LPI). RESULTS: Among the 33 cases of colonic hyperechogenicity collected, and after exclusion of those lost to follow-up, we identified 63% of children with lysinuria-cystinuria, 8% with lysinuric rotein intolerance, and 4% with hypotonia-cystinuria syndrome. CONCLUSION: Management of prenatal hyperechoic colon should include a specialized consultation with a clinical geneticist to discuss further investigations, which could include invasive amniotic fluid sampling for molecular diagnosis. A better understanding of diagnoses and prognosis should improve medical counseling and guide parental decision making.

Micro-CT and high-field MRI for studying very early post-mortem human fetal anatomy at 8 weeks of gestation.

OBJECTIVE: This study involved very early post-mortem (PM) examination of human fetal anatomy at 8 weeks of gestation (WG) using whole-body multimodal micro-imaging: micro-CT and high-field MRI (HF-MRI). We discuss the potential place of this imaging in early first-trimester virtual autopsy. METHODS: We performed micro-CT after different contrast-bath protocols including diffusible iodine-based contrast-enhanced (dice) and HF-MRI with a 9.4 T machine with qualitative and quantitative evaluation and obtained histological sections. RESULTS: Nine fetuses were included: the crown-rump length was 10-24 mm and corresponded to 7 and 9 WG according to the Robinson formula. The Carnegie stages were 17-21. Dice micro-CT and HF-MRI presented high signal to noise ratio, >5, according to the Rose criterion, and for allowed anatomical phenotyping in these specimens. Imaging did not alter the histology, allowing immunostaining and pathological examination. CONCLUSION: PM non-destructive whole-body multimodal micro-imaging: dice micro-CT and HF-MRI allows for PM human fetal anatomy study as early as 8 WG. It paves the way to virtual autopsy in the very early first trimester. Obtaining a precision phenotype, even regarding miscarriage products, allows a reverse phenotyping to select variants of interest in genome-wide analysis, offering potential genetic counseling for bereaved parents.

Fetal intestinal loop dilatation: Follow-up and outcome of a series of 133 consecutive cases (the DILDIG study).

OBJECTIVES: To define the prognostic markers of fetal dilated bowel loops. METHODS: National non-interventional study of 133 consecutive prenatal observations of dilated loops including ultrasound examinations, complementary laboratory tests, magnetic resonance imaging (MRI), outcomes, and postnatal diagnosis. RESULTS: One hundred twenty seven cases were classified according to outcome: Group 1, very severe (n = 43), Group 2, children needing specific care (n = 39), and Group 3, healthy children (n = 45). Prenatal ultrasound scan suggested duodenal obstruction in 30 cases, small bowel obstruction in 81, colonic obstruction in 11, and diffuse dilatation in 5. Diameter of dilated loops did not significantly differ between the groups. A poor prognosis was significantly associated with duodenal obstruction, genetic anomalies (53% vs. 21.8%), including aneuploidies or CFTR gene mutations and abnormal amniotic fluid biochemistry (86.4% vs. 38.7%). A good prognosis was associated with regression of dilatation and normal MRI. CONCLUSION: In this study, postnatal outcomes for fetuses with intestinal dilatation were best predicted by assessing the level of obstruction with prenatal ultrasound and MRI, determining the presence of associated malformations, amniotic fluid biochemical and genetic testing, and monitoring for regression of bowel dilatation. These results should help inform future guidelines on the prenatal and neonatal management of congenital intestinal obstruction.

Extending the prenatal Noonan's phenotype by review of ultrasound and autopsy data.

OBJECTIVES: The antenatal phenotypic spectrum of Noonan Syndrome (NS) requires better characterization. METHODS: This multicenter retrospective observational included 16 fetuses with molecularly confirmed NS admitted for fetopathological examination between 2009 and 2016. RESULTS: Among 12 pathogenic variants (PV) in PTPN11 (80%), 5 (42%) fell between position c.179 and c.182. Ultrasound showed increased nuchal translucency (n = 13/16, 93%), increased nuchal fold after 15 weeks of gestation (n = 12/16, 75%), pleural effusions (n = 11/16, 69%), polyhydramnios (n = 9/16, 56%), hydrops (n = 7/16, 44%), cardiovascular (n = 6/16, 38%) and cerebral (n = 4/16, 25%) anomalies. Fetopathological examination found dysmorphic features in all cases, cardiovascular anomalies (n = 12/15, 80%), pulmonary hypoplasia (n = 10/15, 67%), effusions (n = 7/15, 47%) and neuropathological anomalies (n = 5/15, 33%). Hydrops was significantly (p = 0.02) more frequent in the four fetuses with RIT1, NRAS and RAF1 PV versus the 12 fetuses with PTPN11 PV. CONCLUSIONS: Increased nuchal translucency and nuchal fold is common in NS. Noonan Syndrome antenatal phenotype showed high in utero fetal death, hydrops, prenatal pleural effusion and pulmonary hypoplasia, although the inclusion of only deceased fetuses will have selected more severe phenotypes. Non-specific cardiovascular and neurological abnormalities should be added to NS antenatal phenotype. Next generation sequencing will help detect more genotypes, clarifying the prenatal phenotype and identifying genotype-phenotype correlations.

Terminal 6q deletions cause brain malformations, a phenotype mimicking heterozygous DLL1 pathogenic variants: A multicenter retrospective case series.

OBJECTIVE: Terminal 6q deletion is a rare genetic condition associated with a neurodevelopmental disorder characterized by intellectual disability and structural brain anomalies. Interestingly, a similar phenotype is observed in patients harboring pathogenic variants in the DLL1 gene. Our study aimed to further characterize the prenatal phenotype of this syndrome as well as to attempt to establish phenotype-genotype correlations. METHOD: We collected ultrasound findings from 22 fetuses diagnosed with a pure 6qter deletion. We reviewed the literature and compared our 22 cases with 14 fetuses previously reported as well as with patients with heterozygous DLL1 pathogenic variants. RESULTS: Brain structural alterations were observed in all fetuses. The most common findings (>70%) were cerebellar hypoplasia, ventriculomegaly, and corpus callosum abnormalities. Gyration abnormalities were observed in 46% of cases. Occasional findings included cerebral heterotopia, aqueductal stenosis, vertebral malformations, dysmorphic features, and kidney abnormalities. CONCLUSION: This is the first series of fetuses diagnosed with pure terminal 6q deletion. Based on our findings, we emphasize the prenatal sonographic anomalies, which may suggest the syndrome. Furthermore, this study highlights the importance of chromosomal microarray analysis to search for submicroscopic deletions of the 6q27 region involving the DLL1 gene in fetuses with these malformations.

Should prenatal chromosomal microarray analysis be offered for isolated fetal growth restriction? A French multicenter study.

BACKGROUND: Compared with standard karyotype, chromosomal microarray analysis improves the detection of genetic anomalies and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of chromosomal microarray analysis in cases of isolated fetal growth restriction. OBJECTIVE: This study aimed to estimate the proportion of copy number variants detected by chromosomal microarray analysis and the incremental yield of chromosomal microarray analysis compared with karyotype in the detection of genetic abnormalities in fetuses with isolated fetal growth restriction. STUDY DESIGN: This retrospective study included all singleton fetuses diagnosed with fetal growth restriction and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over 1 year in 2016. Fetal growth restriction was defined as an estimated fetal weight of

Use of Remifentanil Associated with Lidocaine for Feticides in Late Terminations of Pregnancy: A Randomized Clinical Trial.

INTRODUCTION: In France, performance of a termination of pregnancy is legally possible without any gestational age limit. After 22 weeks of gestation, a feticide is ethically performed using usually sufentanil and lidocaine. The aim of this study was to compare the use of remifentanil, a fast-acting morphine-derivating product, instead of sufentanil. METHODS: This 2-center randomized, controlled, single-blinded phase-III treatment trial had 2 parallel arms: an experimental group using remifentanil with lidocaine versus a control group receiving sufentanil associated with lidocaine. This trial took place over a 40-month period. The primary outcome was time to fetal asystole after lidocaine injection. The secondary outcome measures were the procedure's success rate, the rate of serious maternal side effects, and the presence of cellular or tissue modifications. RESULTS: The study included 66 women, randomized into 2 groups of similar size and characteristics. Time to fetal asystole did not differ significantly between the groups, with a delay of 4 min (Q1-Q3, 2-11) in the sufentanil group and 4 min (Q1-Q3, 1-10) in the remifentanil group (p = 0.84). Similarly, the success rate of the procedure did not differ significantly. Fetal asystole was procured in <2 min and persisted >1 min for 16 (25.8%) women in our total population: 7 (22.5%) in the sufentanil group and 9 (29.0%) in the remifentanil group, p = 0.77. No severe maternal side effects were observed. Among the 49 fetopathological examinations performed, the few tissue and cell modifications observed did not cause any interpretation difficulties in either group. DISCUSSION/CONCLUSION: Use of remifentanil instead of sufentanil for feticide procedure did not improve time to fetal asystole. No harmful effect was observed for either maternal tolerance or interpretation of the histologic slides.

Increased incidence of cancer in the follow-up of obstetric antiphospholipid syndrome within the NOH-APS cohort.

Malignancies can be associated with positive antiphospholipid antibodies but the incidence of cancer among women with the purely obstetric form of antiphospholipid syndrome (APS) is currently unknown. Our aim was to investigate the comparative incidence of cancers in women with a history of obstetric APS within a referral university hospital-based cohort (NOH-APS cohort). We performed a 17-year observational study of 1,592 non-thrombotic women with three consecutive spontaneous abortions before the 10th week of gestation or one fetal death at or beyond the 10th week of gestation. We compared the incidence of cancer diagnosis during follow-up among the cohort of women positive for antiphospholipid antibodies (n=517), the cohort of women carrying the F5 rs6025 or F2 rs1799963 polymorphism (n=279) and a cohort of women with negative thrombophilia screening results (n=796). The annualized rate of cancer was 0.300% (0.20%-0.44%) for women with obstetric APS and their cancer risk was substantially higher than that of women with negative thrombophilia screening [adjusted hazard ratio (aHR) 2.483; 95% confidence interval (CI) 1.27-4.85]. The computed standardized incidence ratio for women with obstetric APS was 2.89; 95% CI: 1.89-4.23. Among antiphospholipid antibodies, lupus anticoagulant was associated with incident cancers (aHR 2.608; 95% CI: 1.091-6.236). Our cohort study shows that the risk of cancer is substantially higher in women with a history of obstetric APS than in the general population, and in women with a similar initial clinical history but negative for antiphospholipid antibodies.

Prenatal ultrasound diagnosis of cleft palate without cleft lip, the new ultrasound semiology.

OBJECTIVES: The aim of this study was to define the prenatal ultrasound semiology of cleft palate without cleft lip using 3D visualization of the fetal palate. METHODS: A prospective longitudinal study was performed in our University Hospital Center from 2011 to 2018. The fetal secondary palate was studied in 3D, starting with 2D axial transverse ultrasound view. We defined a cleft palate as a disruption of the horizontal plate of the palatine bone of the secondary palate. Prenatal findings were correlated to anatomic postnatal examinations performed by a paediatric plastic surgeon. RESULTS: Forty-three cases of cleft palate without cleft lip were prenatally diagnosed, of whom 34 were associated with malformations. We defined four types of disruptive appearances: isolated nonvisualization of the posterior nasal spine; partial-disruption or cleft velum; complete disappearance or V-shaped cleft palate; and complete disappearance or U-shaped cleft palate. The adjusted kappa coefficient, between prenatal and postnatal evaluation, was 0.88 (95% CI: 0.79-0.97), corresponding to an excellent agreement. CONCLUSIONS: Using a strictly axial transverse ultrasound view, visualization of the secondary fetal palate enables to diagnose a cleft palate without cleft lip. This method offers a prenatal anatomic classification of cleft palate with a high level of concordance to postnatal findings.

Balloon catheter vs oxytocin alone for induction of labor in women with a previous cesarean section: A randomized controlled trial.

INTRODUCTION: The aim of this study was to compare the efficacy and maternal-neonatal morbidity between balloon catheter and oxytocin for induction of labor in women with a previous cesarean section and an unfavorable cervix. MATERIAL AND METHODS: This open-label randomized controlled trial took place in seven French hospitals. Inclusion criteria were medical indication for labor induction in pregnant women, ≥37 weeks, with lower segment cesarean section, Bishop score ≤4, no pre-labor rupture of membranes, singleton fetus in cephalic presentation. Women were allocated randomly to induction with a 50-mL balloon catheter for 12 hours or a low-dose oxytocin infusion. Primary outcome was the rate of vaginal birth. Secondary outcomes were maternal and neonatal complications. RESULTS: The study enrolled 204 women from 26 December 2010 to 31 December 2013: 101 were allocated to receive balloon catheter and 103 to oxytocin. Vaginal birth rate was 50% (n = 51) in the balloon catheter group vs 37% (n = 38) in the oxytocin group (P = 0.050). Maternal and neonatal morbidity did not differ between balloon catheter and oxytocin groups: two uterine dehiscences vs one, one vs four maternal infections, five vs two hemorrhages and 11 vs five neonatal transfers, respectively. Heterogeneity of treatment effect for vaginal delivery was observed across initial Bishop scores. Balloon catheter was more effective for low values of bishop score. CONCLUSIONS: Balloon catheter tended to be associated with a higher probability of vaginal delivery as compared with low-dose intravenous oxytocin when used for induction of labor in women with a previous cesarean section and low Bishop score at induction.

Prenatal and postnatal evolution of isolated fetal splenic cysts.

OBJECTIVES: The aim of this study was to evaluate the prevalence, the prenatal, and postnatal evolution of isolated fetal splenic cysts. METHODS: All cases of suspected fetal splenic cyst or abdominal unidentified cyst discovered during routine ultrasound scan, from 2007 to 2017, and referred to a French tertiary care center, were retrospectively collected. For each case, several prenatal parameters and postnatal evolution were reported. RESULTS: Among 5450 cases of fetal anomalies, 14 patients (0.3%) had a prenatal diagnosis of fetal splenic cysts. Median gestational age at diagnosis was 30.1 weeks. A unique cyst was present in 78.6%, whereas 2 cysts were observed in 14.3% and 3 cysts in 7.1%. During the pregnancy, cysts remained the same (78.6%) or disappeared (21.4%). Ultrasound scans at 6 months of age found total disappearance of the cysts (36.4%), spontaneous reduction from 2 to 1 cyst (18.2%) or persistence of the cysts (45.4%). CONCLUSION: Fetal splenic cysts are rare images, always isolated, usually unique and mainly found during third trimester of pregnancy. Their evolution is to disappear spontaneously during pregnancy or at 6 months of age leaving only half of them to remain beyond that age but without any symptoms.

Obstetric antiphospholipid syndrome: early variations of angiogenic factors are associated with adverse outcomes.

The prognostic value of angiogenic factors in newly pregnant women with obstetric antiphospholipid syndrome (oAPS) has not been documented. We observed 513 oAPS who experienced three consecutive spontaneous abortions before the 10th week of gestation or one fetal loss at or beyond the 10th week. We assessed the plasma concentrations of the proangiogenic factor placenta growth factor (PIGF) and of the antiangiogenic factor soluble fms-like tyrosine kinase-1 on the eve and on the 4th day of the low-molecular weight heparin-low-dose aspirin treatment. Placenta growth factor and fms-like tyrosine kinase-1 plasma concentrations showed marked increases. Treatment-associated variations of PIGF and of soluble fms-like tyrosine kinase-1 were antagonist risk factors for placenta-mediated complications (PMC) and for severe PMC, for fetal death, stillbirth and neonatal death. The ratio between PIGF increase and soluble fms-like tyrosine kinase-1 was a summary variable whose best cut-off values (1.944.10-2) had high negative predictive values for PMC (0.918) and may be used to help rule out the development of PMC in evolutive pregnancies after 19 completed weeks. The early variations of PIGF and soluble fms-like tyrosine kinase-1 concentrations in newly pregnant oAPS may help to detect patients at low risk of PMC. (clinicaltrials.gov identifier: 02855047).

Success factors for Bakri™ balloon usage secondary to uterine atony: a retrospective, multicentre study.

BACKGROUND: Post-partum haemorrhage (PPH) is one of the major obstetric complications and remains a cause of avoidable maternal mortality and morbidity. AIMS: The aims of this study were to assess the success and practicability of a Bakri™ balloon intrauterine tamponade for PPH and evaluate the predictive factors for success. MATERIALS AND METHODS: Women who received the Bakri™ balloon secondary to uterine atony and subsequent failure of routine drug treatment were identified at 6 hospital sites. Demographic, obstetric and specific factors in regard to the Bakri™ balloon use were recorded. Factors predictive of Bakri™ balloon success were evaluated. RESULTS: Intrauterine Bakri™ balloon tamponade was used in 36 women with uterine atony of which 28 received the balloon treatment after vaginal delivery: more than 50% of women (16/28) presented with PPH with blood loss > 1000 mL (mean blood loss: 1130 mL). Two balloon insertions failures were identified. Bakri balloon success was 100% for women with bleeding < 1000 mL. Twenty-five women (69%) did not require invasive treatment; seven (19%) required arterial embolisation and four (11%) surgical management. No short-term complication was observed after balloon insertion. CONCLUSION: The use of the Bakri™ balloon method, if undertaken early, is effective for the management of PPH with uterine atony (100% success compared to 69% overall success rate). Intrauterine balloon tamponade should included in PPH management guidelines.

Successful pregnancy after 10 consecutive failures in a liver transplant patient with advanced kidney failure.

We report a successful, albeit complicated pregnancy with a live-born healthy baby at 28 weeks' gestation, after 10 pregnancy failures, in a 39-year-old patient with a history of liver transplantation and chronic kidney disease with hypertension and proteinuria. Multidisciplinary management (obstetrician, nephrologist and hepatology transplant specialist) allowed close monitoring, adaptation of immunosuppressive treatments and strict control of fetal growth. The onset of preeclampsia at 28 weeks' gestation led to a cesarean section, resulting in the birth of a healthy 830 g boy, with subsequent normal development. Following pregnancy, the patient experienced liver transplant rejection, which resolved after adapting immunosuppressive drugs. No deterioration in kidney function was observed in the year following delivery.

Intimate partner violence as a risk factor for venous thromboembolism in women on combined oral contraceptives: An international matched case-control study.

BACKGROUND: Intimate partner violence (IPV) targeting women is probably underestimated during a woman's lifetime. Venous thromboembolism (VTE) is a multifactorial disease associated with haemostasis-activating conditions. Minor injuries can trigger VTE. OBJECTIVES: We aimed to look for an association between VTE and IPV in women taking combined oral contraceptives (COCs) METHODS: We performed a multicentric, international, matched case-control study. Patients were women with a first VTE associated with COC intake. Controls were women taking COCs undergoing regular gynaecological check-ups. Patients and Controls were matched for country, age, length of COC intake and type (997 pairs). IPV was evaluated using the WAST self-administrated questionnaire. RESULTS: IPV, defined as a WAST score value at least 5, was diagnosed in 33 Controls (3.3 %) and 109 patients (10.9 %), conditional odds ratio (OR): 3.586, 95 % confidence interval (2.404-5.549), p < 0.0001. After multivariate analysis, the adjusted OR was 3.720 (2.438-5.677), p < 0.0001. Sensitivity analysis using increasing WAST score thresholds confirmed the association. CONCLUSIONS: A first VTE in women taking COCs is associated with IPV. This association can have strong human consequences but also raises significant medical issues, for instance on the haemorrhagic risk of anticoagulant treatments in abused women. Pathophysiological studies are warranted.

Vital NETosis vs. suicidal NETosis during normal pregnancy and preeclampsia.

Background: NETosis occurs in the context of infection or inflammation and results in the expulsion of decondensed DNA filaments called NETs (Neutrophil Extracellular Traps) into the extracellular environment. NETosis activates coagulation and contributes to the thrombotic risk of inflammatory diseases. To date, two mechanisms of NETosis have been identified: suicidal NETosis, in which neutrophils die after expelling the filaments; and vital NETosis, in which expulsion appears without altering the membrane. Human pregnancy is associated with a mild pro-inflammatory state, which is increased in the event of complications such as preeclampsia (PE). NETosis has been observed in these situations, but the mechanism of its production has not yet been studied. The aim of our study was to evaluate the balance of vital vs. suicidal NETosis in normal pregnancy and in PE. Patients/Methods: Neutrophils from healthy volunteers were stimulated with plasma from normal pregnancies (n = 13) and from women developing preeclampsia (n = 13). Immunofluorescent labelling was performed to determine the percentages and origin of NETs in both groups. Inhibition with suicidal or vital NETosis inhibitors was also performed to validate our results. Results: We found a significant increase in NETs in women with PE compared to women with normal pregnancies. We showed that vital and non-vital NETosis are present in normal and preeclamptic pregnancies. We demonstrated that the higher proportion of NETs observed in PE was due to non-vital NETosis whose main component is represented by suicidal NETosis. Discussion: These results suggest the important part of non-vital NETosis in the pathophysiology of PE.

Pregnancy after Combined Oral Contraceptive-Associated Venous Thromboembolism: An International Retrospective Study of Outcomes.

BACKGROUND: Few data are available on thrombotic outcomes during pregnancy and puerperium occurring after an initial provoked venous thromboembolic (VTE) event. OBJECTIVES: To describe thrombotic outcomes during pregnancy after a first combined oral contraceptive (COC)-associated VTE and the factors associated with recurrence. METHODS: This was an international multicentric retrospective study on patients referred for thrombophilia screening from January 1, 2010 to January 1, 2021 following a first COC-associated VTE, including women with neither inherited thrombophilia nor antiphospholipid antibodies and focusing on those who had a subsequent pregnancy under the same thromboprophylaxis treatment. Thrombotic recurrences during pregnancy and puerperium as well as risk factors for recurrence were analyzed. RESULTS: We included 2,145 pregnant women. A total of 88 thrombotic events, 58 antenatal and 29 postnatal, occurred, mostly during the first trimester of pregnancy and the first 2 weeks of puerperium. Incidence rates were 49.6 (37-62) per 1,000 patient-years during pregnancy and 118.7 (78-159) per 1,000 patient-years during puerperium. Focusing on pulmonary embolism, incidence rates were 1.68 (1-4) per 1,000 patient-years during pregnancy and 65.5 (35-97) per 1,000 patient-years during puerperium.Risk factors for antenatal recurrences were maternal hypercholesterolemia and birth of a very small-for-gestational-age neonate. A risk factor for postnatal recurrence was the incidence of preeclampsia. CONCLUSION: Our multicentric retrospective data show significant rates of VTE recurrence during pregnancy and puerperium in women with a previous VTE event associated with COC, despite a unique low-molecular-weight heparin-based thromboprophylaxis. These results may provide benchmarks and valuable information for designing future randomized controlled trials.

Combined oral contraceptive-associated venous thromboembolism revealing an antiphospholipid syndrome: International retrospective study of outcomes.

INTRODUCTION: Limitations in the data used to define thromboprophylaxis for patients with antiphospholipid antibodies (aPLAbs) and thrombosis include uncertainties after an initial provoked venous thromboembolic event (VTE). We aimed to study such cases associated with combined oral contraceptive (COC) intake. METHODS: We retrospectively analysed thrombotic outcomes after a first COC-associated VTE and positive aPLAbs, with a low risk HERDOO2 score, on low-dose aspirin (LDA) secondary thromboprophylaxis, seen from 2010 to 2021 in 3 tertiary referral centres, one in France and 2 in Russia. Data from 264 patients (distal deep vein thrombosis DVT: 62.9 %), cumulating in 1327.7 patient-years of observation, were collected. RESULTS: There were 22 cases of thrombosis: 16 distal DVTs, 3 proximal, 1 pulmonary embolism (PE) and 2 transient ischemic attacks. Recurrence rate was 1.66 per 100 patient-years (p-y; 95 % CI: 0.96-2.33). No major bleeding occurred. Risk factors affecting recurrence-free survival were the time between first COC intake and VTE (p < 0.0001; the shortest, the lower), proximal DVT (p = 0.021), active smoking (p = 0.039), an associated systemic disease (p = 0.043) and circulating monocyte counts (p = 0.001). CONCLUSIONS: We observed a low risk of recurrence which was modulated by classical risk factors for VTE. These observational data may provide clues for future randomized controlled trials.

Soluble CD146 is increased in preeclampsia and interacts with galectin-1 to regulate trophoblast migration through VEGFR2 receptor.

OBJECTIVE: To explore the regulatory role of soluble CD146 (sCD146) and its interaction with galectin-1 (Gal1) in placenta-mediated complications of pregnancy. DESIGN: Prospective pilot and experimental studies. SETTING: University-affiliated hospital and academic research laboratory. PATIENT(S): One hundred fifteen women divided into three groups: 30 healthy, nonpregnant women, 50 women with normal pregnancies, and 35 with placenta-mediated pregnancy complications. INTERVENTION(S): Wound-healing experiments were conducted to study trophoblast migration. MAIN OUTCOME MEASURE(S): Quantification of sCD146 and Gal1 by enzyme-linked immunosorbent assay. Analysis of trophoblast migration by wound closure. RESULT(S): Concomitant detection of sCD146 and Gal1 showed lower sCD146 and higher Gal1 concentrations in women with normal pregnancies compared with nonpregnant women. In addition, follow-up of these women revealed a decrease in sCD146 associated with an increase in Gal1 throughout pregnancy. In contrast, in women with preeclampsia, we found significantly higher sCD146 concentrations compared with women with normal pregnancies and no modification of Gal1. We emphasize the opposing effects of sCD146 and Gal, since, unlike Gal1, sCD146 inhibits trophoblast migration. Moreover, the migratory effect of Gal1 was abrogated with the use of an anti-CD146 blocking antibody or the use of small interfering RNA to silence VEGFR2 expression. This suggests that trophoblast migration is mediated though the interaction of Gal1 with CD146, further activating the VEGFR2 signaling pathway. Significantly, sCD146 blocked the migratory effects of Gal1 on trophoblasts and inhibited its secretion, suggesting that sCD146 acts as a ligand trap. CONCLUSION(S): Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01736826.