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.

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.

Assessment of All-Cause Cancer Incidence Among Individuals With Preeclampsia or Eclampsia During First Pregnancy.

Importance: Preeclampsia or eclampsia (preeclampsia/eclampsia) during pregnancy induces major physiological changes and may be associated with specific cancer occurrences in later life. The current data regarding the association between preeclampsia/eclampsia and cancer are heterogeneous, and cancer risk after preeclampsia/eclampsia could be different depending on the organ. These uncertainties warrant reexamination of the association between preeclampsia/eclampsia and the risk of cancer overall and by specific cancer type. Objective: To evaluate the risk of cancer, overall and by type, after preeclampsia/eclampsia during a first pregnancy. Design, Setting, and Participants: This retrospective cohort study used data from the French hospital discharge database to identify all female individuals who had a pregnancy-associated hospitalization between January 1, 2010, and December 31, 2019. To allow a minimum of 2 years for the detection of medical history, individuals with a first detected pregnancy before January 1, 2012, were excluded, as were those with a cancer-associated hospitalization before or during their first detected pregnancy. Exposures, comorbidities, and occurrences of cancer were evaluated using data from the medico-administrative registers of hospitalizations in private and public French hospitals. Cox proportional hazards models were used to analyze cancer risk according to the occurrence of preeclampsia/eclampsia during first pregnancy. Exposures: Preeclampsia/eclampsia-associated hospitalization during the first detected pregnancy. Main Outcomes and Measures: The primary outcome was the incidence of cancer, including myelodysplastic or myeloproliferative diseases, after a first pregnancy with and without preeclampsia/eclampsia. Results: After exclusions, a total of 4 322 970 female individuals (mean [SD] age at first detected pregnancy, 29.6 [6.2] years) with and without preeclampsia/eclampsia during their first pregnancy were included. Of those, 45 523 individuals (1.1%) were diagnosed with preeclampsia/eclampsia during their first detected pregnancy. The maximum follow-up was 8 years, during which 29 173 individuals (0.7%) were diagnosed with cancer. No significant difference in overall cancer incidence was found between those with and without preeclampsia/eclampsia during their first pregnancy (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.84-1.05). Preeclampsia/eclampsia was associated with an increase in the risk of myelodysplastic syndromes or myeloproliferative diseases (AHR, 2.43; 95% CI, 1.46-4.06) and kidney cancer (AHR, 2.19; 95% CI, 1.09-4.42) and a decrease in the risk of breast cancer (AHR, 0.79; 95% CI, 0.62-0.99) and cervical cancer (AHR, 0.75; 95% CI, 0.58-0.96). Conclusions and Relevance: In this study, a history of preeclampsia/eclampsia during first pregnancy was associated with an increase in the incidence of myelodysplastic or myeloproliferative diseases and kidney cancer and a decrease in the incidence of cervical and breast cancers. These associations might reflect an underlying common factor among preeclampsia/eclampsia and these pathologies and/or an association between preeclampsia/eclampsia and the development of these cancers.

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 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).

Screening for placenta accreta at 11-14 weeks of gestation.

OBJECTIVE: We sought to describe the potential value of 11-14 weeks' screening for placenta accreta (PA). STUDY DESIGN: Patients with a history of lower segment cesarean section were prospectively included between 11-13+6 weeks over a 1.5-year period. The first 258 were offered standard screening whereas the following 105 underwent screening for PA. Women were considered high-risk when the trophoblast overlapped the scar visualized by transvaginal ultrasound and low-risk otherwise. RESULTS: The group screened for PA did not differ from the nonscreened group for demographic characteristics. In all, 6 of 105 (5.8%) women were considered high-risk. In the nonscreened group, 1 case of PA was discovered during an elective repeat cesarean. In the screened population, 1 case of PA occurred in a high-risk patient allowing a conservative planned management at 35 weeks. CONCLUSION: At 11-14 weeks, ultrasound may help risk stratification for PA with a specific follow-up. Early recognition of patients at risk might improve the perinatal outcome of PA.