Effect of cannula insertion site during fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm prelabor rupture of membranes.

OBJECTIVE: To assess whether the cannula insertion site on the maternal abdomen during fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) was associated with preterm prelabor rupture of membranes (PPROM) before balloon removal. METHODS: This was a multicenter retrospective study of consecutive pregnancies with isolated left- or right-sided CDH that underwent FETO in four centers between January 2009 and January 2021. The site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups to calculate an average treatment effect (ATE) by inverse probability of treatment weighting. Logistic regression and Cox proportional hazard regression including the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM before balloon removal. RESULTS: A total of 294 patients were included. The mean ± SD gestational age at PPROM was 33.45 ± 2.01 weeks and the mean rate of PPROM before balloon removal was 25.9% (76/294). Gestational age at FETO was later in the below-umbilicus group (mean ± SD, 29.47 ± 1.29 weeks vs 29.00 ± 1.25 weeks; P = 0.002) and the duration of FETO was longer in the above-umbilicus group (median, 14.49 min (interquartile range (IQR), 8.00-21.00 min) vs 11.00 min (IQR, 7.00-14.49 min); P = 0.002). After balancing for possible confounding factors, trocar entry point below the umbilicus did not increase the risk of PPROM before balloon removal (adjusted odds ratio, 1.56 (95% CI, 0.89-2.74); P = 0.120) and had no effect on the timing of PPROM before balloon removal (adjusted hazard ratio, 1.56 (95% CI, 0.95-2.55); P = 0.080). CONCLUSION: There was no evidence that uterine entry site for FETO was correlated with the risk of PPROM before balloon removal. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

[SARS-Cov-2 vaccine's acceptance among pregnant women-A cross-sectional survey]. / Acceptabilité du vaccin-Sars CoV-2 chez les femmes enceintes, une enquête transversale par questionnaire.

OBJECTIVE: SARS-CoV-2 is more likely to cause severe cases in pregnant women. They were part of the priority groups since April 2021 to benefit from SARS-CoV-2 vaccination before its extent to general population. This contribution aims to evaluate, in the postpartum period, the achievement of COVID-19 vaccination and factors associated in women during their pregnancy. MATERIAL AND METHOD: Multicenter cross-sectional survey study conducted from September to December 2021 with online self-questionnaire. All postpartum patients hospitalized in one of the 6 participating maternity hospitals were invited to answer. The questionnaire asked patients about their demographic characteristics, vaccination modalities, vaccine tolerance, and their general perception of vaccination. RESULTS: Of the 371 women who responded, the vaccination rate was 65.7% (IC95% [60.8-70.4]), whom 98.8% entirely during pregnancy. Associated factors with vaccination during pregnancy were older age, higher socio-professional category, and prior information provided by health professionals. Factors that appear to motivate vaccination were personal protection and protection of the newborn. Finally, main factors negatively influencing the vaccination process were the fear of vaccine side effects and the negative perception of vaccines in general. DISCUSSION: Acceptability and information about the vaccine by health professionals is in constant improvement. Information campaigns should be continued to improve the acceptability of vaccination, in light of the accumulating data.

Universal newborn screening for congenital cytomegalovirus infection: feasibility and relevance in a French type-III maternity cohort.

OBJECTIVE: Evaluation of relevance and feasibility of universal newborn congenital cytomegalovirus infection (cCMVI) screening in saliva. DESIGN: Retrospective, population-based cohort study. SETTING: Clamart, France, 2016-2020. POPULATION: All neonates born consecutively in our level III maternity unit. METHODS: CMV PCR in saliva for all neonates at birth, and, if positive, CMV PCR in urine to confirm or exclude cCMVI. Prospective and retrospective characterisation of maternal infections. ROC curve analysis to assess saliva PCR performances. Acceptability of screening among staff members evaluated by a survey. MAIN OUTCOME MEASURES: Number of cCMVI neonates; number of expected and unexpected cCMVI. RESULTS: Among 15 341 tested neonates, 63 had cCMVI (birth prevalence of 0.4%, 95% CI 0.3-0.5). In 50% of cases, maternal infection was a non-primary infection (NPI) during pregnancy. cCMVI was expected or suspected (maternal primary infection [PI], antenatal or neonatal signs) in 24/63 neonates (38%), and unexpected in 39/63 neonates (62%). The best CMV saliva threshold to predict cCMVI was 356 (2.55 log) copies/ml [95% CI 2.52 log-3.18 log], with an area under the ROC curve of 0.97. Over 90% of the 72 surveyed staff members reported that the screening was easy and quick. No parent refused the screening. CONCLUSIONS: Universal screening for cCMVI with CMV PCR on saliva samples is feasible and highly acceptable to parents and healthcare providers. Over half (62%) of the cases had no prenatal/neonatal signs of cCMVI or a maternal history of CMV infection during pregnancy and would probably not have been diagnosed without universal screening. TWEETABLE ABSTRACT: In 62% of congenital cytomegalovirus infection cases, only universal neonatal screening in saliva can detect infection.

Prenatal stomach position predicts gastrointestinal morbidity at 2 years in fetuses with left-sided congenital diaphragmatic hernia.

OBJECTIVE: The long-term morbidity associated with isolated left-sided congenital diaphragmatic hernia (CDH) has been described previously. However, antenatal criteria impacting gastrointestinal morbidity (GIM) are not yet defined. The objective of this study was to evaluate the effect of fetal stomach position on the risk of GIM at 2 years of age in children with left-sided CDH. METHODS: This was a retrospective, observational multicenter cohort study of data obtained from January 2010 to January 2014, that included patients whose fetus had isolated left-sided CDH, with or without fetal endoscopic tracheal occlusion (FETO). Prenatal maternal, fetal and pediatric data were collected. Fetal stomach position was evaluated a posteriori by two observers, using ultrasound images at the level of the four-chamber view of the heart that had been obtained to calculate the observed-to-expected lung-area-to-head-circumference ratio (O/E-LHR). Fetal stomach position was graded as follows: Grade 1, stomach not visualized; Grade 2, stomach visualized anteriorly, next to the apex of the heart, with no structure in between the stomach and the sternum; Grade 3, stomach visualized alongside the left ventricle of the heart, and abdominal structures anteriorly; or Grade 4, as Grade 3 but with stomach posterior to the level of the atrioventricular heart valves. The primary outcome was GIM at 2 years of age, assessed in a composite manner, including the occurrence of gastroesophageal reflux disease, need for gastrostomy, duration of parenteral and enteral nutrition and persistence of oral aversion. Regression analysis was performed in order to investigate the effect of O/E-LHR, stomach position and FETO on various GIM outcome variables. RESULTS: Forty-seven patients with fetal left-sided CDH were included in the analysis. Thirteen (27.7%) infants did not meet the criterion of exclusive oral feeding at 2 years of age. Fetal stomach position grade was associated significantly and independently with the duration of parenteral nutrition (odds ratio (OR), 19.86; P = 0.031) and persistence of oral aversion at 2 years (OR, 3.40; P = 0.006). On multivariate analysis, O/E-LHR was predictive of the need for prosthetic patch repair, but not for GIM. FETO did not seem to affect the risk of GIM at 2 years. CONCLUSION: In isolated left-sided CDH, fetal stomach position is the only factor that is predictive of GIM at 2 years of age. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal endoscopic tracheal occlusion reverses the natural history of right-sided congenital diaphragmatic hernia: European multicenter experience.

OBJECTIVE: To evaluate the neonatal outcome of fetuses with isolated right-sided congenital diaphragmatic hernia (iRCDH) based on prenatal severity indicators and antenatal management. METHODS: This was a retrospective review of prospectively collected data on consecutive cases diagnosed with iRCDH before 30 weeks' gestation in four fetal therapy centers, between January 2008 and December 2018. Data on prenatal severity assessment, antenatal management and perinatal outcome were retrieved. Univariate and multivariate logistic regression analysis were used to identify predictors of survival at discharge and early neonatal morbidity. RESULTS: Of 265 patients assessed during the study period, we excluded 40 (15%) who underwent termination of pregnancy, two cases of unexplained fetal death, two that were lost to follow-up, one for which antenatal assessment of lung hypoplasia was not available and six cases which were found to have major associated anomalies or syndromes after birth. Of the 214 fetuses with iRCDH included in the neonatal outcome analysis, 86 were managed expectantly during pregnancy and 128 underwent fetal endoscopic tracheal occlusion (FETO) with a balloon. In the expectant-management group, lung size measured by ultrasound or by magnetic resonance imaging was the only independent predictor of survival (observed-to-expected lung-to-head ratio (o/e-LHR) odds ratio (OR), 1.06 (95% CI, 1.02-1.11); P = 0.003). Until now, stratification for severe lung hypoplasia has been based on an o/e-LHR cut-off of 45%. In cases managed expectantly, the survival rate was 15% (4/27) in those with o/e-LHR ≤ 45% and 61% (36/59) for o/e-LHR > 45% (P = 0.001). However, the best o/e-LHR cut-off for the prediction of survival at discharge was 50%, with a sensitivity of 78% and specificity of 72%. In the expectantly managed group, survivors with severe pulmonary hypoplasia stayed longer in the neonatal intensive care unit than did those with mildly hypoplastic lungs. In fetuses with an o/e-LHR ≤ 45% treated with FETO, survival rate was higher than in those with similar lung size managed expectantly (49/120 (41%) vs 4/27 (15%); P = 0.014), despite higher prematurity rates (gestational age at birth: 34.4 ± 2.7 weeks vs 36.8 ± 3.0 weeks; P < 0.0001). In fetuses treated with FETO, gestational age at birth was the only predictor of survival (OR, 1.25 (95% CI, 1.04-1.50); P = 0.02). CONCLUSIONS: Antenatal measurement of lung size can predict survival in iRCDH. In fetuses with severe lung hypoplasia, FETO was associated with a significant increase in survival without an associated increase in neonatal morbidity. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Optimal gestational age at delivery in isolated left-sided congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the morbidity and mortality of neonates with left-sided isolated congenital diaphragmatic hernia (CDH) according to gestational age at delivery. METHODS: This was a retrospective study of fetuses diagnosed prenatally with isolated left-sided CDH that were delivered in the University Hospitals of Antoine Béclère-Bicêtre and Leuven between 1 January 2010 and 31 December 2018. The Kaplan-Meier method was used to calculate cumulative survival at 28 days after birth according to gestational age at delivery. The association between gestational age at delivery, as a continuous variable, and survival at 28 days was modeled using a fractional polynomial. Adjustment for position of the liver, management center and mode of delivery was performed. The association was also evaluated according to the severity of CDH, as defined by the observed-to-expected lung-to-head ratio (o/e-LHR), which was classified as severe (o/e-LHR < 25%), moderate (o/e-LHR between 25% and 45%) or mild (o/e-LHR > 45%). RESULTS: We included 213 fetuses with isolated left-sided CDH, with a median gestational age at delivery of 38 + 2 weeks (interquartile range, 37 + 0 to 39 + 1 weeks). The survival rates at 28 days and at 6 months were 66.7% (142/213) and 64.3% (137/213), respectively. Kaplan-Meier analysis showed a higher survival rate at 28 days for babies delivered between 37 + 0 and 38 + 6 weeks than for those delivered at or after 39 + 0 weeks (log-rank test, P < 0.001). In the subgroup of moderate CDH, the 28-day survival rate was significantly higher in newborns delivered between 37 + 0 and 38 + 6 weeks than in those delivered at or after 39 + 0 weeks (81.5% vs 61.5%; P = 0.03), and this was also the case for survival rate at 6 months. In the subgroup with moderate CDH, 28-day survival significantly increased with advancing gestational age at birth up to about 38-39 weeks (P = 0.005), and significantly decreased from 39 weeks onwards. CONCLUSION: Delivery between 37 + 0 and 38 + 6 weeks' gestation is associated with a higher survival rate at 28 days in neonates with isolated left-sided CDH and moderate lung hypoplasia, independently of intrathoracic liver, management center and mode of delivery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Evolution of awareness and knowledge of congenital cytomegalovirus infection among health care providers in France between 2011 and 2018.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection. Approximately 1 % of newborns are congenitally infected and in up to 10 % of them the consequences are severe. Antenatal and postnatal treatments, although promising, are still under evaluation. Hygiene counseling to prevent CMV infection is important and should be systematic. OBJECTIVE: To evaluate health care providers' awareness of CMV maternal and congenital infection in France. STUDY DESIGN: A questionnaire on CMV infection was sent in 2018 by e-mail to obstetricians, pediatricians, midwives and laboratory physicians, and members of medical or midwifery associations. We evaluated their knowledge concerning CMV epidemiology, transmission, symptoms in adults, newborns and long-term effects (scores from 0 to 30) and compared the results with those of our 2012 published study. RESULTS: Of the 597 respondents who completed the questionnaire, 91 % were unaware of the precise transmission route of CMV, 33 % wrongly thought thatin utero therapy for congenital CMV infection was a current standard of care in France, and less than half were familiar with the HAS (Haute Autorité de Santé) and CNGOF (Collège National des Gynécologues et Obstétriciens Français) recommendations. When respondents' knowledge of CMV was greater, patients were given more hygiene counseling. Between 2011 and 2018, knowledge improved among doctors and midwives concerning the route of transmission, the symptoms in adults, and the long-term effects of CMV infection. CONCLUSIONS: Knowledge is improving among healthcare providers, but gaps remain. To bridge these gaps, health care providers should improve their knowledge about congenital CMV by various means: medical reviews, continuing medical education, meetings, conferences, the Internet. Moreover, greater knowledge will allow for more effective counseling of pregnant women, as recommended by HCSP and CNGOF in France.

Determination of rubella virus-specific humoral and cell-mediated immunity in pregnant women with negative or equivocal rubella-specific IgG in routine screening.

BACKGROUND: Immunity to rubella-virus (RV) is commonly determined by measuring specific IgG (RV-IgG). However, RV-IgG results may be different and even discordant, depending on the assay used. Cell-mediated immunity is not routinely investigated for diagnostic purposes. OBJECTIVES: Our aim was to investigate humoral and cellular immunity of women with negative or equivocal RV-IgG before, and after post-partum vaccination. STUDY DESIGN: A total of 186 pregnant women were included in the study. During pregnancy, humoral immunity was investigated with two RV-IgG immunoassays, an immunoblot and a T-cell mediated immunity test. In the post-partum vaccination period, measuring RV-IgM and RV-IgG avidity allowed us to determine whether women raised a primary or a secondary immune response. RESULTS: Before vaccination, 52.2% women, supposed to be susceptible, had positive anti-E1 RV-IgG indicating strong evidence of previous exposure to RV. All (100%) pregant women who had a positive immunoblot before immunization raised a secondary immune response to vaccination, and 96.8% who had a negative immunoblot before immunization, raised a primary immune response to vaccination. All women who raised a primary immune response after vaccination had negative anti-E1 RV-IgG and negative cell-mediated immunity. DISCUSSION: These results indicate that individuals can have evidence of protective immunity against rubella despite negative RV-IgG.

Optimal non-invasive diagnosis of fetal achondroplasia combining ultrasonography with circulating cell-free fetal DNA analysis.

OBJECTIVES: To assess the performance of non-invasive prenatal testing (NIPT) for achondroplasia using high-resolution melting (HRM) analysis, and to propose an optimal diagnostic strategy combining ultrasound examination and cell-free fetal DNA (cffDNA) analysis. METHODS: In this prospective multicenter study, cffDNA was extracted from blood of pregnant women at risk for fetal achondroplasia (owing to paternal achondroplasia, previous affected child or suspected rhizomelic shortening) and of pregnant low-risk controls. The presence of either one of the two main fibroblast growth factor receptor 3 gene (FGFR3) mutations was determined using HRM combined with confirmation by SNaPshot minisequencing. Results were compared with phenotypes obtained using three-dimensional computed tomography or postnatal examination, and/or molecular diagnosis by an invasive procedure. Fetal biometry (head circumference and femur length) was analyzed in order to develop a strategy in which cffDNA analysis for diagnosis of achondroplasia is offered only in selected cases. RESULTS: Eighty-six blood samples from women at risk for fetal achondroplasia and 65 from controls were collected. The overall sensitivity and specificity of NIPT were 1.00 (95% CI, 0.87-1.00) and 1.00 (95% CI, 0.96-1.00), respectively. Critical reduction in femur length of affected fetuses could be observed from 26 weeks' gestation. CONCLUSIONS: HRM combined with SNaPshot minisequencing is a reliable method for NIPT for achondroplasia. Its implementation in routine clinical care combined with ultrasonography is an efficient strategy for the non-invasive diagnosis of achondroplasia. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

[Neonatal arterial ischemic stroke in term or near-term newborns: prevalence and risk factors]. / Accident vasculaire cérébral ischémique artériel chez le nouveau-né à terme ou proche du terme : prévalence et facteurs de risque.

The general designation ischemic perinatal stroke includes several disease states that differ in pathophysiology, timing of occurrence and presentation. While it seems logical to assume that their prevalence and their risk factors depend primarily on the considered type of stroke, most studies used inconsistent definitions or included heterogeneous populations, which limits their accuracy. Given these biases, the French Society of Neonatology and the French Centre for Paediatric Stroke wished to update the knowledge in this domain, focusing on a specific form of perinatal stroke, i.e neonatal arterial ischemic stroke (NAIS) in term or near term newborns. A comprehensive analysis of published epidemiological data was dedicated to the following issues: Is the prevalence of NAIS well defined from epidemiological studies? What are the best recognized risk factors and is it possible to delineate a maternal and fetal population at risk for this condition? On July 31, 2015 a total of four hospitalized-based and five population-based studies, and six case-control studies were found. The conclusions are the following: The prevalence of NAIS in term or near term newborns varies from 6 to 17/100,000 live births (level of evidence 2). NAIS represents a half of total ischemic perinatal strokes (i.e. including those with delayed presentation as well) and one fourth of perinatal strokes (i.e. including cerebral haemorrhage stroke as well). Four sets of risk factors are consistent across different studies (level of evidence 3): (1) male sex, (2) obstetrical determinants (first pregnancy, caesarean section), and two peripartum complications: (3) intrapartum hypoxia and (4) materno-fetal/neonatal infection. Bacterial meningitis, cardiac disorders/procedures and invasive care such as extra-corporeal circulation carry a risk of NAIS as well. A registry could help refining epidemiological descriptive data. It could also be used to develop etiological studies focusing on pathophysiological hypotheses derived from the identified aforementioned risk factors.

Relevance of routine Doppler sampling at the two umbilical arteries in the follow-up of dichorionic twin pregnancies with intrauterine growth-restricted fetuses.

OBJECTIVE: The aim of this study is to assess if the presence of bilateral absent or reverse end-diastolic velocity (AREDV) indicates a poorer prognosis than unilateral AREDV in dichorionic-diamniotic twin pregnancies complicated by intrauterine growth restriction. METHODS: A prospective observational study of 36 dichorionic-diamniotic twin pregnancies complicated by intrauterine growth restriction. One hundred and fifty seven ultrasound (US) examinations were performed. The pulsatility indexes (PI) of the two umbilical arteries (UA-perivesical site), the middle cerebral artery (MCA) and the ductus venosus (DV) were recorded. The fetal hemodynamic status was represented by the existence of a bilateral positive end-diastolic velocity (PEDV), a unilateral AREDV or a bilateral AREDV in the umbilical arteries. RESULTS: Bilateral PEDV, unilateral AREDV and bilateral AREDV represented respectively 66.0%, 10.6% and 23.4% of the US examinations. Intervals between Doppler examinations and delivery were significantly longer (P<0.005) in the bilateral PEDV group (26.5 days±19.7) than in the unilateral AREDV group (11.8 days±11.7) and in the bilateral AREDV group (11.0 days±8.6). MCA-PI, DV-PI, IFI and early neonatal outcomes did not differ between the unilateral and bilateral AREDV groups. CONCLUSION: The routine measurement of the Doppler indices of the two umbilical arteries seems to be no more relevant than unilateral measurement in fetuses of dichorionic-diamniotic twin pregnancies complicated by intrauterine growth restriction.

[Neonatal arterial ischemic stroke: Review of the current guidelines]. / Accidents vasculaires cérébraux ischémiques artériels néonatals : synthèse des recommandations.

Neonatal arterial ischemic stroke (NAIS) is a rare event that occurs in approximately one in 5000 term or close-to-term infants. Most affected infants will present with seizures. Although a well-recognized clinical entity, many questions remain regarding diagnosis, risk factors, treatment, and follow-up modalities. In the absence of a known pathophysiological mechanism and lack of evidence-based guidelines, only supportive care is currently provided. To address these issues, a French national committee set up by the French Neonatal Society (Société française de néonatologie) and the national referral center (Centre national de référence) for arterial ischemic stroke in children drew up guidelines based on an HAS (Haute Autorité de santé [HAS]; French national authority for health) methodology. The main findings and recommendations established by the study group are: (1) among the risk factors, male sex, primiparity, caesarean section, perinatal hypoxia, and fetal/neonatal infection (mainly bacterial meningitis) seem to be the most frequent. As for guidelines, the study group recommends the following: (1) the transfer of neonates with suspected NAIS to a neonatal intensive care unit with available equipment to establish a reliable diagnosis with MRI imaging and neurophysiological monitoring, preferably by continuous video EEG; (2) acute treatment of suspected infection or other life-threatening processes should be addressed immediately by the primary medical team. Persistent seizures should be treated with a loading dose of phenobarbital 20mg/kg i.v.; (3) MRI of the brain is considered optimal for the diagnosis of NAIS. Diffusion-weighted imaging with apparent diffusion coefficient is considered the most sensitive measure for identifying infarct in the neonatal brain. The location and extent of the lesions are best assessed between 2 and 4 days after the onset of stroke; (4) routine testing for thrombophilia (AT, PC PS deficiency, FV Leiden or FII20210A) or for detecting other biological risk factors such as antiphospholipid antibodies, high FVIII, homocysteinemia, the Lp(a) test, the MTHFR thermolabile variant should not be considered in neonates with NAIS. Testing for FV Leiden can be performed only in case of a documented family history of venous thromboembolic disease. Testing neonates for the presence of antiphospholipid antibodies should be considered only in case of clinical events arguing in favor of antiphospholipid syndrome in the mother; (5) unlike childhood arterial ischemic stroke, NAIS has a low 5-year recurrence rate (approximately 1 %), except in those children with congenital heart disease or multiple genetic thrombophilia. Therefore, initiation of anticoagulation or antithrombotic agents, including heparin products, is not recommended in the newborn without identifiable risk factors; (6) the study group recommends that in case of delayed motor milestones or early handedness, multidisciplinary rehabilitation is recommended as early as possible. Newborns should have physical therapy evaluation and ongoing outpatient follow-up. Given the risk of later-onset cognitive, language, and behavioral disabilities, neuropsychological testing in preschool and at school age is highly recommended.

[Detailed in utero ultrasound description of 34 cases of congenital cytomegalovirus infection]. / Étude descriptive de signes échographiques anténataux de 34 cas d'infections congénitales à cytomégalovirus.

OBJECTIVES: To describe precisely prenatal ultrasound features in congenital cytomegalovirus (CMV) infection. MATERIAL AND METHODS: We retrospectively evaluated the ultrasound descriptions of cases of congenital CMV infection between 2004 and 2013. RESULTS: In 74 congenital CMV infections, related ultrasound abnormalities were reported in 34 cases (45.9%). Abnormalities reported were either cerebral (11 cases), either extracerebral (6 cases), or associated (17 cases). A total of 22/34 cases presented extracerebral features of 11 different sorts of abnormalities, mainly intra-uterine growth retardation (11 cases) and hyperechogenic bowel (10 cases) and 26/34 cases presented cerebral features of 14 different sorts, mainly brain calcifications (12 cases) and occipital horn cavity (12 cases). MRI was performed in 25 cases and have found additional abnormalities in 8 cases. These abnormalities are not specific to CMV infection. However, a frequent finding attracted our attention: the anechogenic cavity located on the extremity of the occipital horn. CONCLUSION: A potentially specific sign, inexistent in other fetal pathologies, is an anechogenic cavity located on the extremity of the occipital and/or temporal horn, a germinal region which contains numerous proliferating and differentiating germinal cells. A better understanding of these signs could increase the sensitivity of ultrasound, and clarify the pathophysiology of congenital CMV infection.

[Contribution of ultrasound signs for the prenatal diagnosis of posterior urethral valves: Experience of 3years at the maternity of the Bicêtre Hospital]. / Apport des signes d'appel échographiques dans le diagnostic anténatal des valves de l'urètre postérieur : expérience de 3ans à la maternité de l'hôpital Bicêtre.

OBJECTIVES: Posterior urethral valves (PUV) are the most common cause of renal impairment in boys during early childhood. The aim of this study was to evaluate the value of ultrasound (US) criteria currently used to diagnose PUV. MATERIALS AND METHODS: From 2009 to 2012, 31 patients were referred to the Bicêtre Hospital after detection of fetal bilateral hydronephrosis in male fetus. The ultrasound criteria were bladder dilation, thick-walled bladder, urethral dilation ("keyhole sign"), and amniotic fluid volume. Patients were divided in two groups: suspected or not to have PUV. RESULTS: US diagnosis of PUV was done in 18 fetuses and confirmed in 14 new borns, one of them without prenatal diagnosis. Sensitivity and specificity of US scan were 92.8 and 66.7%. The likelihood ratio (LHR) was 4.8 for a thick-walled bladder, 4.2 for oligohydramnios, 3.6 for the "keyhole sign", 2.4 for bladder dilation and 1.6 for ureteral dilation. The first four signs were combined in four fetuses, all of them with PUV. CONCLUSION: US scan is a very sensitive exam for the diagnosis of PUV but with a low specificity. A thick-walled bladder seems to have a better diagnostic performance than the "keyhole sign".

Integrated pharmacokinetic, pharmacodynamic and immunogenicity profiling of an anti-CCL21 monoclonal antibody in cynomolgus monkeys.

QBP359 is an IgG1 human monoclonal antibody that binds with high affinity to human CCL21, a chemokine hypothesized to play a role in inflammatory disease conditions through activation of resident CCR7-expressing fibroblasts/myofibroblasts. The pharmacokinetics (PK) and pharmacodynamics (PD) of QBP359 in non-human primates were characterized through an integrated approach, combining PK, PD, immunogenicity, immunohistochemistry (IHC) and tissue profiling data from single- and multiple-dose experiments in cynomolgus monkeys. When compared with regular immunoglobulin typical kinetics, faster drug clearance was observed in serum following intravenous administration of 10 mg/kg and 50 mg/kg of QBP359. We have shown by means of PK/PD modeling that clearance of mAb-ligand complex is the most likely explanation for the rapid clearance of QBP359 in cynomolgus monkey. IHC and liquid chromatography mass spectrometry data suggested a high turnover and synthesis rate of CCL21 in tissues. Although lymphoid tissue was expected to accumulate drug due to the high levels of CCL21 present, bioavailability following subcutaneous administration in monkeys was 52%. In human disease states, where CCL21 expression is believed to be expressed at 10-fold higher concentrations compared with cynomolgus monkeys, the PK/PD model of QBP359 and its binding to CCL21 suggested that very large doses requiring frequent administration of mAb would be required to maintain suppression of CCL21 in the clinical setting. This highlights the difficulty in targeting soluble proteins with high synthesis rates.

Stomach position in prediction of survival in left-sided congenital diaphragmatic hernia with or without fetoscopic endoluminal tracheal occlusion.

OBJECTIVE: To investigate the value of fetal stomach position in predicting postnatal outcome in left-sided congenital diaphragmatic hernia (CDH) with and without fetoscopic endoluminal tracheal occlusion (FETO). METHODS: This was a retrospective review of CDH cases that were expectantly managed or treated with FETO, assessed from May 2008 to October 2013, in which we graded, on a scale of 1-4, stomach position on the four-chamber view of the heart with respect to thoracic structures. Logistic regression analysis was used to investigate the effect of management center (Paris, Brussels, Barcelona, Milan), stomach grading, observed-to-expected lung area-to-head circumference ratio (O/E-LHR), gestational age at delivery, birth weight in expectantly managed CDH, gestational ages at FETO and at removal and period of tracheal occlusion, on postnatal survival in CDH cases treated with FETO. RESULTS: We identified 67 expectantly managed CDH cases and 47 CDH cases that were treated with FETO. In expectantly managed CDH, stomach position and O/E-LHR predicted postnatal survival independently. In CDH treated with FETO, stomach position and gestational age at delivery predicted postnatal survival independently. CONCLUSION: In left-sided CDH with or without FETO, stomach position is predictive of postnatal survival.

Annual diagnosis rate of superficial vein thrombosis of the lower limbs: the STEPH community-based study.

BACKGROUND: The incidence of superficial vein thrombosis (SVT) in the general adult population remains unknown. OBJECTIVES: To assess the annual diagnosis rate of symptomatic, objectively confirmed lower limb SVT, associated or not with concomitant deep vein thrombosis and/or symptomatic pulmonary embolism. METHODS/PATIENTS: We conducted, from November 14, 2011, to November 13, 2012, a multicenter, community-based study in the Saint-Etienne urban area, France, representing a population of 265 687 adult residents (according to the 2009 census). All 248 general practitioners located within the area were asked to refer any patient with clinically suspected lower limb acute SVT to a vascular physician for systematic compression ultrasonography. All 28 vascular physicians located within the area participated in the study. The annual diagnosis rate, with the corresponding 95% confidence interval (CI), was calculated as the number of patients with symptomatic, objectively confirmed SVT divided by the number of person-years at risk defined by population data of the area. All venous thromboembolic events were validated by an independent central adjudication committee. RESULTS: Overall, 171 patients with symptomatic, confirmed SVT were reported. The annual diagnosis rate was 0.64& (95% CI, 0.55%-0.74&), was higher in women, and increased with advancing age regardless of gender [corrected]. Concomitant deep vein thrombosis (20 proximal) was observed in 42 patients (24.6% [95% CI, 18.3%-31.7%]), and concomitant symptomatic pulmonary embolism was observed in eight patients (4.7% [95% CI, 2.0%-9.0%]). CONCLUSIONS: This first community-based study showed that symptomatic SVT with confirmed diagnosis is a relatively common disease frequently associated with thromboembolic events in the deep venous system.

Detailed in utero ultrasound description of 30 cases of congenital cytomegalovirus infection.

OBJECTIVES: The aim of this research was to describe precisely prenatal ultrasound (US) features in congenital cytomegalovirus (CMV) infection. METHODS: We retrospectively evaluated the US descriptions of cases of congenital CMV infection between 2004 and 2013. RESULTS: In 69 congenital CMV infections, related US abnormalities were reported in 30 cases (43.5%). There were both extracerebral and cerebral abnormalities in 16 cases, purely abnormal brain features in ten, and purely extracerebral features in two. About 19/30 cases presented extracerebral features of 11 different sorts of abnormalities, mainly hyperechogenic bowel (ten cases) and intrauterine growth retardation (nine cases). About 24/30 cases presented cerebral features of 13 different sorts, mainly brain calcifications (12 cases) and occipital horn cavity (11 cases). The main US findings in our series are not specific to CMV infection. However, a frequent finding attracted our attention: the anechogenic cavity located on the extremity of the occipital horn, a region which contains numerous proliferating and differentiating germinal cells. CONCLUSIONS: By improving knowledge of US findings linked to CMV infection, US sensitivity may be improved. Understanding why CMV leads to lesions of the occipital horn may help clarify the pathophysiology of congenital infection.