Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Safety and efficacy of smart tracheal occlusion device in diaphragmatic hernia lamb model.

OBJECTIVE: To investigate the efficacy and safety of the 'smart' tracheal occlusion (Smart-TO) device in fetal lambs with diaphragmatic hernia (DH). METHODS: DH was created in fetal lambs on gestational day 70 (term, 145 days). Fetuses were allocated to either pregnancy continuation until term (DH group) or fetoscopic endoluminal tracheal occlusion (TO), performed using the Smart-TO balloon on gestational day 97 (DH + TO group). On gestational day 116, the presence of the balloon was confirmed on ultrasound, then the ewe was walked around a 3.0-Tesla magnetic resonance scanner for balloon deflation, which was confirmed by ultrasound immediately afterwards. At term, euthanasia was performed and the fetus retrieved. Efficacy of occlusion was assessed by the lung-to-body-weight ratio (LBWR) and lung morphometry. Safety parameters included tracheal side effects assessed by morphometry and balloon location after deflation. The unoccluded DH lambs served as a comparator. RESULTS: Six fetuses were included in the DH group and seven in the DH + TO group. All balloons deflated successfully and were expelled spontaneously from the airways. In the DH + TO group, in comparison to controls, the LBWR at birth was significantly higher (1.90 (interquartile range (IQR), 1.43-2.55) vs 1.07 (IQR, 0.93-1.46); P = 0.005), while on lung morphometry, the alveolar size was significantly increased (mean linear intercept, 47.5 (IQR, 45.6-48.1) vs 41.9 (IQR, 38.8-46.1) µm; P = 0.03); whereas airway complexity was lower (mean terminal bronchiolar density, 1.56 (IQR, 1.0-1.81) vs 2.23 (IQR, 2.14-2.40) br/mm2 ; P = 0.005). Tracheal changes on histology were minimal in both groups, but more noticeable in fetal lambs that underwent TO than in unoccluded lambs (tracheal score, 2 (IQR, 1-3) vs 0 (0-1); P = 0.03). CONCLUSIONS: In fetal lambs with DH, TO using the Smart-TO balloon is effective and safe. Occlusion can be reversed non-invasively and the deflated intact balloon expelled spontaneously from the fetal upper airways. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal risk factors of neurodevelopmental impairment after fetoscopic laser photocoagulation for twin-twin transfusion syndrome: systematic review and meta-analysis.

OBJECTIVE: Monochorionic twins with twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) are at increased risk of neurodevelopmental impairment (NDI). This meta-analysis aimed to identify the prevalence of and perinatal risk factors for NDI in TTTS survivors treated with FLP. METHODS: We performed a search in PubMed, EMBASE, Scopus and Web of Science, from inception to 13 February 2021, for studies evaluating perinatal risk factors for NDI in children diagnosed prenatally with TTTS managed by FLP. Data on severity of TTTS at the time of diagnosis, defined according to the Quintero staging system, FLP-related complications and perinatal outcomes were compared between children with a history of TTTS treated with FLP with and those without NDI, which was defined as performance on a cognitive or developmental assessment tool ≥ 2 SD below the mean or a defined motor or sensory disability. A random-effects model was used to pool the mean differences or odds ratios (OR) with the corresponding 95% CIs. Heterogeneity was assessed using the I2 statistic. RESULTS: Nine studies with a total of 1499 TTTS survivors were included. The overall incidence of NDI was 14.0% (95% CI, 9.0-18.0%). The occurrence of NDI in TTTS survivors was associated with later gestational age (GA) at FLP (mean difference, 0.94 weeks (95% CI, 0.50-1.38 weeks); P < 0.0001, I2 = 0%), earlier GA at delivery (mean difference, -1.44 weeks (95% CI, -2.28 to -0.61 weeks); P = 0.0007, I2 = 49%) and lower birth weight (mean difference, -343.26 g (95% CI, -470.59 to -215.92 g); P < 0.00001, I2 = 27%). Evaluation of different GA cut-offs showed that preterm birth before 32 weeks was associated with higher risk for NDI later in childhood (OR, 2.25 (95% CI, 1.02-4.94); P = 0.04, I2 = 35%). No statistically significant difference was found between cases with and those without NDI with respect to Quintero stage of TTTS, recipient or donor status, development of postlaser twin anemia-polycythemia sequence, recurrence of TTTS and incidence of small- for-gestational age or cotwin fetal demise. CONCLUSIONS: TTTS survivors with later GA at the time of FLP, earlier GA at delivery and lower birth weight are at higher risk of developing NDI. No significant association was found between Quintero stage of TTTS and risk of NDI. Our findings may be helpful for parental counseling and highlight the need for future studies to understand better the risk factors for NDI in TTTS survivors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

New device permitting non-invasive reversal of fetal endoscopic tracheal occlusion: ex-vivo and in-vivo study.

OBJECTIVE: One of the drawbacks of fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to re-establish airway patency. The 'Smart-TO' device is a new balloon for FETO that deflates spontaneously when placed in a strong magnetic field, therefore overcoming the need for a second procedure. The safety and efficacy of this device have not yet been demonstrated. The aim of this study was to investigate the reversibility, local side effects and occlusiveness of the Smart-TO balloon, both in a simulated in-utero environment and in the fetal lamb model. METHODS: First, the reversibility of tracheal occlusion by the Smart-TO balloon was tested in a high-fidelity simulator. Following videoscopic tracheoscopic balloon insertion, the fetal mannequin was placed within a 1-L water-filled balloon to mimic the amniotic cavity. This was held by an operator in front of their abdomen, and different fetal and maternal positions were simulated to mimic the most common clinical scenarios. Following exposure to the magnetic field generated by a 1.5-T magnetic resonance (MR) machine, deflation of the Smart-TO balloon was assessed by tracheoscopy. In cases of failed deflation, the mannequin was reinserted into a water-filled balloon for additional MR exposure, up to a maximum of three times. Secondly, reversibility, occlusiveness and local effects of the Smart-TO balloon were tested in vivo in fetal lambs. Tracheal occlusion was performed in fetal lambs on gestational day 95 (term, 145 days), either using the balloon currently used in clinical practice (Goldbal2) (n = 5) or the Smart-TO balloon (n = 5). On gestational day 116, the presence of the balloon was assessed by tracheoscopy. Deflation was performed by puncture (Goldbal2) or MR exposure (Smart-TO). Six unoccluded fetal lambs served as controls. Following euthanasia, the lung-to-body-weight ratio (LBWR), lung morphometry and tracheal circumference were assessed. Local tracheal changes were measured using a hierarchical histologic scoring system. RESULTS: Ex vivo, Smart-TO balloon deflation occurred after a single MR exposure in 100% of cases in a maternal standing position with the mannequin at a height of 95 cm (n = 32), 55 cm (n = 8) or 125 cm (n = 8), as well as when the maternal position was 'lying on a stretcher' (n = 8). Three out of eight (37.5%) balloons failed to deflate at first exposure when the maternal position was 'sitting in a wheelchair'. Of these, two balloons deflated after a second MR exposure, but one balloon remained inflated after a third exposure. In vivo, all Smart-TO balloons deflated successfully. The LBWR in fetal lambs with tracheal occlusion by a Smart-TO balloon was significantly higher than that in unoccluded controls, and was comparable with that in the Goldbal2 group. There were no differences in lung morphometry and tracheal circumference between the two balloon types. Tracheal histology showed minimal changes for both balloons. CONCLUSIONS: In a simulated in-utero environment, the Smart-TO balloon was effectively deflated by exposure of the fetus in different positions to the magnetic field of a 1.5-T MR system. There was only one failure, which occurred when the mother was sitting in a wheelchair. In healthy fetal lambs, the Smart-TO balloon is as occlusive as the clinical standard Goldbal2 system and has only limited local side effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Technical aspects and effectiveness of percutaneous fetal therapies for large sacrococcygeal teratomas: cohort study and literature review.

OBJECTIVES: The objectives of this study were to evaluate the efficacy of minimally invasive ablation of high-risk large sacrococcygeal teratomas (SCT) and to compare the efficacy of vascular and interstitial tumor ablation. METHODS: This was a retrospective multicenter study including a cohort of fetuses with high-risk large SCTs between 2004 and 2010. In addition, we performed a systematic literature review of all cases that underwent tumor ablation in order to compare the survival rates after 'vascular' and 'interstitial' ablation. Statistical analysis was conducted using Bayesian methods. RESULTS: In our cohort, a total of 13 fetuses had high-risk large SCT and five of them underwent tumor ablation. The estimated difference in hydrops resolution rate between the fetal intervention and the no fetal intervention groups was 44.6% (95% credibility interval, 1.5 to 81.0%; Pdiff> 0 = 97.9%). The estimated difference in survival rate between the fetal intervention and the no fetal intervention groups was 31.0% (13.9 to 48.1%; Pdiff> 0 = 99.9%). We analyzed our five cases together with 28 cases from the literature and estimated the difference in survival rate between the vascular and interstitial ablation groups as 19.8% (-13.1 to 50.1%; Pdiff> 0 = 88.3%). The estimated difference in hydrops resolution rate between the vascular and the interstitial ablation groups was 36.7% (-5.7 to 72.7%; Pdiff> 0 = 95.5%). CONCLUSION: Minimally invasive surgery seems to improve perinatal outcome in cases of high-risk large fetal SCT. Our findings suggest that 'vascular' ablation may improve outcome and may be more effective than 'interstitial' tumor ablation, but this hypothesis needs further investigation in a larger multicenter prospective study. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal lower urinary tract obstruction: proposal for standardized multidisciplinary prenatal management based on disease severity.

OBJECTIVE: To present a single center experience of a standardized prenatal multidisciplinary management protocol for fetal lower urinary tract obstruction (LUTO) and to propose a classification of fetal LUTO based on disease severity. METHODS: This was a retrospective cohort study of 25 consecutive fetal patients with prenatal diagnosis of primary LUTO. Fetal intervention was offered after evaluation by a multidisciplinary team. Analyses were conducted using Bayesian methodology to determine predictors of survival at 6 months postpartum. Odds ratios (ORs) with 95% credibility intervals are reported. RESULTS: Fifteen (60.0%) of the 25 patients referred for assessment survived to postnatal evaluation. Fetal vesicoamniotic shunt was placed in 14 (56.0%) patients with 12 survivors. Multivariable analysis suggested that fetal intervention (OR, 6.97 (0.88-70.16), Pr(OR > 1) = 96.7%), anhydramnios (OR, 0.12 (0.04-0.35), Pr(OR < 1) = 99.9%), favorable fetal urine analysis (OR, 3.98 (0.63-25.15), Pr(OR > 1) = 92.7%) and absence of renal cortical cysts (OR, 3.9 (0.66-24.2), Pr(OR > 1) = 93.3%) were predictors of survival. CONCLUSIONS: Fetal intervention and fetal renal function were independently associated with postnatal survival of fetuses with LUTO. A classification based on the severity of disease is proposed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting.

OBJECTIVE: To evaluate the efficacy of fetal intervention using fetal cystoscopy or vesicoamniotic shunting in the treatment of severe lower urinary obstruction (LUTO). METHODS: A cohort of 111 fetuses with severe LUTO attending two centers between January 1990 and August 2013 were included retrospectively. Fetuses were categorized into three groups based on the method of intervention: (1) fetal cystoscopy, (2) vesicoamniotic shunting or (3) no intervention. Multivariate analyses were performed to determine the probability of survival and normal renal function until 6 months of age by comparing fetal cystoscopy and vesicoamniotic shunting to no fetal intervention. RESULTS: Of the 111 fetuses with severe LUTO that were included in the analysis, fetal cystoscopy was performed in 34, vesicoamniotic shunting was performed in 16 and there was no fetal intervention in 61. Gestational age at diagnosis, method of fetal intervention and cause of bladder obstruction were associated with prognosis. In multivariate analysis and after adjustment for potential confounders (considering all causes of LUTO) the overall probability of survival was significantly higher with fetal cystoscopy and vesicoamniotic shunting when compared to no intervention (adjusted relative risk (ARR), 1.86 (95% CI, 1.01-3.42; P = 0.048) and ARR, 1.73 (95% CI, 1.01-3.08; P = 0.04) respectively). A clear trend for normal renal function was present in the fetal cystoscopy group (ARR, 1.73 (95% CI, 0.97-3.08; P = 0.06)) but was not observed in the vesicoamniotic shunt group (ARR, 1.16 (95% CI, 0.86-1.55; P = 0.33)). In cases in which there was a postnatal diagnosis of posterior urethral valves, fetal cystoscopy was effective in improving both the 6-month survival rate and renal function (ARR, 4.10 (95% CI, 1.75-9.62; P < 0.01) and 2.66 (95% CI, 1.25-5.70; P = 0.01) respectively) while vesicoamniotic shunting was associated only with an improvement in the 6-month survival rate (ARR, 3.76 (95% CI, 1.42-9.97; P < 0.01)) with no effect on renal function (ARR, 1.03 (95% CI, 0.49-2.17, P = 0.93)). CONCLUSION: Fetal cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO. However, only fetal cystoscopy may prevent impairment of renal function in fetuses with posterior urethral valves. Our data support the idea of performing a subsequent randomized controlled trial to compare the effectiveness of fetal cystoscopy vs vesicoamniotic shunting for severe fetal LUTO.

Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects.

OBJECTIVE: To describe the surgical technical aspects associated with the development of urological fistulas after fetal antegrade cystoscopic laser fulguration of the posterior urethral valves (PUV). METHODS: The perioperative data for all fetal cystoscopies performed between January 2004 and August 2013 at three institutions in the USA, France and Brazil were reviewed, with particular emphasis on surgical technical aspects of the procedure and the complications encountered. RESULTS: A total of 40 fetal cystoscopies were performed at the three institutions. Laser fulguration of the PUV was performed in 23 of these cases, with a survival rate of 60.9% (14/23) and normal renal function in 85.7% (12/14) of these infants. Urological fistulas were diagnosed postnatally in four (10%) newborns. The presence of fistulas was associated with a higher gestational age at diagnosis of PUV (P < 0.01) and with the use of semi-curved rather than curved sheaths (P < 0.01), the use of a diode laser (P < 0.01) and the use of higher laser power and energy (P < 0.01 and P < 0.01, respectively), as well as with less operator experience (P < 0.01) and with absence of fetal anesthesia/immobilization (P = 0.02). CONCLUSION: Urological fistulas are a severe complication of fetal cystoscopic laser fulguration of PUV and are associated with type, energy and power settings of the laser and instrumentation. The use of appropriate technique and proper training of the operator are necessary to perform this fetal intervention safely.

Fetoscopic laser coagulation for twin-twin transfusion syndrome before 17 weeks' gestation: laser data, complications and neonatal outcome.

OBJECTIVE: To compare laser data, complications and neonatal outcome in pregnancies that undergo 'early' (≤ 17 weeks' gestation) fetoscopic laser ablation of placental vascular anastomoses for twin-twin transfusion syndrome (TTTS) with those from 'conventional' cases treated after 17 weeks. METHODS: This was a cohort study of data collected prospectively between January 2004 and December 2012. We included monochorionic diamniotic twin pregnancies complicated by TTTS and treated by fetoscopic laser coagulation. Pregnancies were grouped according to laser treatment ≤ 17 gestational weeks or > 17 weeks and obstetric and neonatal outcomes were compared between groups. RESULTS: A total of 178 pregnancies with TTTS underwent laser therapy: 40 at or before 17 weeks and 138 after 17 weeks. There was no statistically significant difference between these two groups with respect to the rate of preterm prelabor rupture of membranes (PPROM), gestational age at PPROM and rate of PPROM occurring in the 7 days following fetoscopic laser coagulation. In the early group, the interval between performing fetoscopic laser coagulation and the time of delivery was significantly longer (104 days vs 74 days, P=0.0002) and the delivery rate within 7 days of laser treatment was significantly lower (2.5% vs 15.9%, P=0.026). There was no significant difference between the two groups with regard to the rates of pregnancy without live birth (15.4% vs 15.4%, P=0.993), with one live birth (84.6% vs 84.6%, P=0.993) and with two live births (64.1% vs 58.1%, P=0.500). CONCLUSION: In the event of early TTTS, fetoscopic laser coagulation is technically feasible before 17 gestational weeks and obstetric and neonatal outcomes are comparable with those in cases of laser treatment performed after 17 weeks.

Predictive value of cardiovascular parameters in twin-to-twin transfusion syndrome.

OBJECTIVE: To evaluate the prognostic value of the Children's Hospital Of Philadelphia (CHOP) cardiovascular score and the modified myocardial performance index (MPI), in determining the risk of recipient fetal loss in twin-to-twin transfusion syndrome (TTTS). METHODS: This cohort study was based on data collected prospectively from 105 pregnancies complicated by TTTS (Quintero stages I-IV) and treated with laser photocoagulation between May 2008 and February 2013. Fetuses underwent detailed anatomical and Doppler ultrasonography with cardiac assessment as part of routine care. CHOP score and right MPI were calculated and cut-offs selected using receiver-operating characteristics curve analysis. These were compared according to loss of recipient fetus, using univariate and multivariate logistic regression. The correlation between CHOP score, MPI and Quintero stage was determined and we investigated differences in MPI before and after laser coagulation in a cohort of 90 recipient fetuses. RESULTS: Rates of recipient fetal loss were significantly higher when the CHOP score was ≥ 3 (39.5% vs 12.9%, P = 0.002) and when MPI z-score was > 1.645 (34.5% vs 10.6%, P = 0.004). After adjustment for Quintero stage, the risk of recipient fetal loss remained significantly higher when the CHOP score was ≥ 3 (odds ratio, 3.09; 95% CI, 1.035-9.21). There was a positive correlation between CHOP score, MPI and Quintero stage. MPI was significantly lower after compared with before laser coagulation. CONCLUSION: CHOP score and MPI are predictors of recipient fetal loss in TTTS and may be used to supplement Quintero's classification.

Efficacy and safety of labour induction in patients with a single previous caesarean section: a proposal for a clinical protocol.

PURPOSE: To evaluate the efficacy and safety of induction in women with a single prior Caesarean section. METHODS: This was a cohort study in which we included all singleton pregnancies in patients with a single prior Caesarean who delivered between 2007 and 2012. Methods of induction were ocytocic infusion plus amniotomy (if Bishop score ≥6) or insertion of a Foley catheter (Bishop <6). RESULTS: Of the 2,075 patients included, 806 (38.8 %) had an elective repeat Caesarean, 1,045 (50.4 %) went into spontaneous labour, 89 (4.3 %) were induced by artificial rupture of the membranes and infusion of ocytocics and 135 (6.5 %) were induced using a Foley catheter. Rates of vaginal delivery were 79.2, 79.8 and 43.7 %, respectively. Six cases of uterine rupture were reported in the group of patients who went into spontaneous labour. There was no difference between groups with regard to neonatal morbidity. On multivariate analysis, risk factors for Caesarean delivery were macrosomia (OR 2.04, 95 % CI 1.31-3.18) and induction by Foley catheter (OR 3.73, 95 % CI 2.47-5.62); protective factors were previous vaginal delivery (OR 0.41, 95 % CI 0.29-0.57) and cervical dilatation (OR 0.84, 95 % CI 0.78-0.91). CONCLUSIONS: Uterine induction after a single Caesarean section with ocytocic infusion and amniotomy where the cervix is favourable does not appear to entail any significant added risk in terms of maternal or foetal morbidity. Foley catheter induction is a reasonable option if the cervix is not ripe.

Prediction of spontaneous preterm delivery in singleton pregnancies: where are we and where are we going? A review of literature.

Prematurity is the chief cause of neonatal morbidity and mortality. The objective of this study is to review the different methods for predicting preterm delivery in asymptomatic pregnant women and in situations of threatened preterm delivery. A search of the PubMed/Medline database was carried out for the years 1980-2012. We included studies for predicting preterm birth in asymptomatic and symptomatic patients. Models for predicting preterm delivery based on maternal factors, cervical length and obstetric history in first trimester of pregnancy is a valuable avenue of research. Nevertheless, prediction accuracy still needs to be improved. In the second and third trimesters, routine digital vaginal examination is of no value in asymptomatic women. Echography of the cervix is not useful except in patients with a history of late miscarriage or preterm delivery in order to offer them a preventive treatment. In symptomatic women, the combination of digital vaginal examination, cervical echography and fibronectin gives the best predictive results. Electromyography of the uterus and elastography of the cervix are interesting avenues for future research. Identifying patients at risk of preterm delivery should be considered differently at each stage of pregnancy.

Postnatal phenotype according to prenatal ultrasound features of Noonan syndrome: a retrospective study of 28 cases.

OBJECTIVE: Noonan syndrome is a frequent genetic disorder with autosomal dominant transmission. Classically, it combines postnatal growth restriction with dysmorphic and malformation syndromes that vary widely in expressivity. Lymphatic dysplasia induced during the embryonic stage might interfere with tissue migration. Our hypothesis is that the earlier the edema, the more severe postnatal phenotype. METHOD: This retrospective study analyzed data from all 32 cases of Noonan syndrome diagnosed in the Medical Genetics Department of Hautepierre Hospital in Strasbourg, France, between 1995 and 2011. The postnatal evolution of Noonan syndrome was compared according to the presence of at least one prenatal ultrasound feature of lymphatic dysplasia. RESULTS: The most frequent prenatal ultrasound features found were increased nuchal translucency, cystic hygroma and polyhydramnios; their global prevalence was 46.4%. The presence of these features was not significantly associated with the postnatal phenotype of Noonan syndrome. CONCLUSION: The results of our study indicate that prenatal ultrasound features of lymphatic dysplasia do not predict an unfavorable postnatal prognosis for Noonan syndrome.

[Intrahepatic cholestasis of pregnancy: French College of Obstetricians and Gynecologists guidelines for clinical practice]. / La cholestase gravidique : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies for reducing neonatal and maternal morbidity associated with intrahepatic cholestasis pregnancy (ICP). MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 14 questions (from 12 PICO questions and one definition question outside the PICO format), there was agreement between the working group and the external reviewers on 14 (100%). The level of evidence of the literature was insufficient to provide a recommendation on two questions. ICP is defined by the occurrence of suggestive pruritus (palmoplantar, nocturnal) associated with a total bile acid level>10µmol/L or an alanine transaminase level above 2N after ruling out differential diagnoses. In the absence of suggestive symptoms of a differential diagnosis, it is recommended not to carry out additional biological or ultrasound tests. In women with CIP, ursodeoxycholic acid is recommended to reduce the intensity of maternal pruritus (Strong recommendation. Quality of the evidence moderate) and to decrease the level of total bile acids and alanine transaminases. (Strong recommendation. Quality of the evidence moderate). S-adenosyl-methionine, dexamethasone, guar gum or activated charcoal should not be used to reduce the intensity of maternal pruritus (Strong recommendation. Quality of evidence low), and there is insufficient data to recommend the use of antihistamines (No recommendation. Quality of evidence low). Rifampicin (Weak recommendation. Very low quality of evidence) or plasma exchange (Strong recommendation. Very low quality of evidence) should not be used to reduce maternal pruritus and perinatal morbidity. Serum monitoring of bile acids is recommended to reduce perinatal morbidity and mortality (stillbirth, prematurity) (Low recommendation. Quality of the evidence low). The level of evidence is insufficient to determine whether fetal heart rate or fetal ultrasound monitoring are useful to reduce perinatal morbidity (No recommendation). Birth is recommended when bile acid level is above 99µmol/L from 36 weeks gestation to reduce perinatal morbidity, in particular stillbirth. When bile acid level is above 99µmol/L is below 100µmol/L, women should be informed that induction of labor could be considered 37 and 39 weeks gestation to reduce perinatal morbidity. (Strong recommendation. Quality of evidence low). In postpartum, total bile acids and alanine transaminases level should be checked and normalized before prescribing estrogen-progestin contraception, ideally with a low estrogen dose (risk of recurrence of pruritus and cytolysis) (Low recommendation. Quality of evidence very low). CONCLUSION: Although the quality of evidence regarding ICP gestational cholestasis remains low, there is a strong consensus in France, as shown by our Delphi study, on how to manage women with ICP. The reference first-line treatment is ursodeoxycholic acid.

[The cesarean procedure: Guidelines for clinical practice from the French College of Obstetricians and Gynecologists]. / La technique de la césarienne : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify procedures to reduce maternal morbidity during cesarean. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane and EMBASE databases. The quality of the evidence was assessed (high, moderate, low, very low) and a (i) strong or (ii) weak recommendations or (iii) no recommendation were formulated. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Of the 27 questions, there was agreement between the working group and the external reviewers on 26. The level of evidence of the literature was insufficient to provide a recommendation on 15 questions. Preventing hypothermia is recommended to increase maternal satisfaction and comfort (weak recommendation) and to reduce neonatal hypothermia (strong recommendation). The quality of the evidence of the literature did not allow to recommend the skin disinfectant to be used nor the relevance of a preoperative vaginal disinfection nor the choice between the use or nonuse of an indwelling bladder catheterization (if micturition takes place 1 hour before the cesarean section). The Misgav-Ladach technique or its analogues should be considered rather than the Pfannenstiel technique to reduce maternal morbidity (weak recommendation) bladder flap before uterine incision should not be performed routinely (weak recommendation), but a blunt (weak recommendation) and cephalad-caudad extension of uterine incision (weak recommendation) should be considered to reduce maternal morbidity. Antibiotic prophylaxis is recommended to reduce maternal infectious morbidity (strong recommendation) without recommendation on its type or the timing of administration (before incision or after cord clamping). The administration of carbetocin after cord clamping does not significantly decrease the incidence of blood loss>1000 ml, anemia, or blood transfusion compared with the administration of oxytocin. Thus, it is not recommended to use carbetocin rather than oxytocin in cesarean. It is recommended that systematic manual removal of the placenta not to be performed (weak recommendation). An antiemetic should be administered after cord clamping in women having a planned cesarean under locoregional anaesthesia to reduce intraoperative and postoperative nausea and vomiting (strong recommendation) with no recommendation regarding choice of use one or two antiemetics. The level of evidence of the literature was insufficient to provide any recommendation concerning single or double-layer closure of the uterine incision, or the uterine exteriorization. Closing the peritoneum (visceral or parietal) should not be considered (weak recommendation). The quality of the evidence of the literature was not sufficient to provide recommendation on systematic subcutaneous closure, including in obese or overweight patients, or the use of subcuticular suture in obese or overweight patients. The use of subcuticular suture in comparison with skin closure by staples was not considered as a recommendation due to the absence of a consensus in the external review rounds. CONCLUSION: In case of cesarean, preventing hypothermia, administering antiemetic and antibiotic prophylaxis after cord clamping are the only strong recommendations. The Misgav-Ladach technique, the way of performing uterine incision (no systematic bladder flap, blunt cephalad-caudad extension), not performing routine manual removal of the placenta nor closure of the peritoneum are weak recommendations and may reduce maternal morbidity.

3D-printed simulator for nasopharyngeal swab collection for COVID-19.

OBJECTIVES: Diagnosis of COVID-19 is essential to prevent the spread of SARS-CoV-2. Nasopharyngeal swabs (NPS) remain the gold standard in screening, although associated with false negative results (up to 30%). We developed a 3D simulator of the nasal and pharyngeal cavities for the learning and improvement of NPS collection. PATIENTS AND METHODS: Simulator training sessions were carried out in 11 centers in France. A questionnaire assessing the simulator was administered at the end of the sessions. The study population included both healthcare workers (HCW) and volunteers from the general population. RESULTS: Out of 589 participants, overall satisfaction was scored 9.0 [8.9-9.1] on a scale of 0 to 10 with excellent results in the 16 evaluation items of each category (HCWs and general population, NPS novices and experienced). The simulator was considered very realistic (95%), easy to use (97%), useful to understand the anatomy (89%) and NPS sampling technique (93%). This educational tool was considered essential (93%). Participants felt their future NPS would be more reliable (72%), less painful (70%), easier to perform (88%) and that they would be carried out more serenely (90%). The mean number of NPS conducted on the simulator to feel at ease was two; technical fluency with the simulator can thus be acquired quickly. CONCLUSION: Our simulator, whose 3D printing can be reproduced freely using a permanent open access link, is an essential educational tool to standardize the learning and improvement of NPS collection. It should enhance virus detection and thus contribute to better pandemic control.

Nuchal translucency and cystic hygroma colli in screening for fetal major congenital heart defects in a series of 12,910 euploid pregnancies.

OBJECTIVE: Many studies have shown that an increased nuchal translucency (NT) may be a good marker of fetal heart malformation, but the extent to which NT is suitable for identifying the population at risk remains unclear. We aimed to determine the value of NT measurement and of the presence of cystic hygroma colli in the screening of euploid fetuses for congenital heart defects (CHD). METHODS: We carried out a retrospective analysis of 12 910 euploid pregnancies examined between January 1995 and August 2007 at our institution. The screening performance of NT measurements in identifying fetuses with CHD was assessed, with comparison between the use of cut-offs defined as absolute values, multiples of the median (MoM) and percentiles. The presence of cystic hygroma colli was also assessed in the prediction of CHD. RESULTS: The incidence of major CHD was 3.4 per thousand (44/12 910). The sensitivity of NT measurement in screening for major CHD was 54.5% if the threshold was set at the 95(th) percentile, 45.4% if it was set at 3 mm, 27.3% for 3.5 mm, 50.0% for 1.5 MoM and 45.5% for 1.75 MoM. The false-positive rates for these thresholds were 8.4, 6.6, 1.7, 8.9 and 6.3%, respectively. The incidence of major CHD was 1.2% (10/813) in cases of thick NT (> 95(th) centile) and 4.3% (13/304) in cases of hygroma colli. CONCLUSIONS: NT measurement during the first trimester is potentially useful for screening for fetal major CHD. Screening performance is consistent whether NT values are expressed as MoMs, percentiles or absolute values. The incidence of major CHD seems to be higher in cases of cystic hygroma colli.

[Breech Presentation: CNGOF Guidelines for Clinical Practice - Benefits and Risks for the Neonate and Child of Planned Vaginal Delivery versus Elective Cesarean Section]. / Présentation du siège. Recommandations pour la pratique clinique du CNGOF ­ Bénéfices et risques pour l'enfant de la tentative de voie basse en comparaison de la césarienne programmée.

OBJECTIVE: To provide guidelines regarding the benefits and risks for the neonate and the child of planning vaginal delivery versus planning elective cesarean section in case of term breech presentation. METHODS: MedLine and Cochrane Library databases search and review of the main foreign guidelines. RESULTS: In case of term breech presentation, planned vaginal delivery might be associated with an increased composite risk of perinatal mortality or occurrence of a combined outcome of serious neonatal morbidity in comparison to elective cesarean section (LE2). In case of planned vaginal delivery of term breech presentation, the risk of perinatal mortality is around 1‰ (LE3). It is potentially less but still exists in case of elective cesarean section (LE2). Risks of neonatal trauma - especially fracture of clavicle and breech hematoma -, Apgar score lower than 7 at 5minutes, and need for neonatal intubation and ventilation, are increased in case of planned vaginal delivery (LE2) and are around 1% (LE3). However, no difference has been demonstrated between planned vaginal and planned cesarean delivery regarding neurodevelopmental outcomes at 2 years (LE2), cognitive and psychomotor outcomes between 5 and 8 years (LE3), and adult intellectual performances (LE4). CONCLUSIONS: In case of term breech presentation, risks of severe complications for neonate and child are low in case of planned vaginal delivery or elective cesarean section. Short-term benefit/risk balance for the neonate might favor elective cesarean section but long-term morbidity seems to be similar whatever the delivery route (Professional consensus).

Vanishing Gastroschisis with a Favorable Outcome after a 3-Year Follow-Up: A Case Report and Literature Review.

Vanishing gastroschisis (VG) is a severe complication of gastroschisis with a high mortality rate. We report here a case of VG with a favorable outcome after a 3-year follow-up. A 26-year-old primigravida woman was referred to Strasbourg University Hospital because her fetus was diagnosed with an isolated gastroschisis at 13-week gestation. The ultrasound evolution was marked by a progressive closure of the abdominal wall defect from 19-week gestation and the appearance of dilated intra-abdominal loops. The child was born with a closed abdominal wall except a small remnant at the level of the former gastroschisis orifice. Explorative laparotomy revealed extensive midgut atresia with only 50 cm of remaining midgut. A jejunocolic anastomosis was performed. The child is now 3 years old and has a favorable outcome with only 2 nights a week of parenteral nutrition. A total of 39 cases of VG type D from Perrone et al. classification are described in the literature from 1991 to 2019, among which 19 (48.7%) are alive at the time of publication but only 4 cases are described with a long-term follow-up of 3 years or more. This is the fifth case described with a favorable evolution after 3-year follow-up.