Publications by authors named "Yves Ville"

224 Publications

The randomized TOTAL-trials on fetal surgery for congenital diaphragmatic hernia: re-analysis using pooled data.

Am J Obstet Gynecol 2021 Nov 19. Epub 2021 Nov 19.

Department of Development and Regeneration, Cluster Woman and Child, KU Leuven, Leuven, Belgium; Clinical Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.

Background: Two randomized controlled trials compared the neonatal and infant outcomes after fetoscopic endoluminal tracheal occlusion (FETO) with expectant prenatal management in fetuses with moderate and severe isolated congenital diaphragmatic hernia (CDH), respectively. FETO was carried out at 27 to 29 weeks' gestation (referred to as "early") for severe and at 30 to 31 weeks ("late") for moderate hypoplasia. Reported absolute increase in survival to discharge were 13% (95% confidence interval, -1-28; P=.059), and 25% (95% confidence interval, 6-46; P=.0091) for moderate and hypoplasia CDH, respectively.

Objectives: Data from the two trials were pooled to study the heterogeneity of the treatment effect by observed over expected lung-to-head ratio and explore the effect of the gestational age at balloon insertion.

Study Design: Individual participant data from the two trials were reanalyzed. Women were assessed between 2008 and 2020 at 14 experienced FETO centers, and were randomized in a 1:1 ratio to either expectant management or FETO. All received standardized postnatal management. The combined data involved 287 patients (196 moderate and 91 severe hypoplasia). The primary endpoint was survival to discharge from the neonatal intensive care unit. Secondary endpoints were survival to 6 months of age, survival to 6 months without oxygen supplementation, and gestational age at live birth. Penalized regression was used with the following covariates: intervention (FETO vs. expectant), early balloon insertion (yes vs. no), observed over expected lung-to-head ratio, liver herniation (yes vs. no), and trial (severe vs moderate). The interaction between intervention and observed over expected lung-to-head ratio was evaluated to study treatment effect heterogeneity.

Results: For survival to discharge, the adjusted odds ratio of FETO was 1.78 (95% confidence interval, 1.05-3.01; P=.031). The additional effect of early balloon insertion was positive but highly uncertain (adjusted odds ratio, 1.53; 95% confidence interval, 0.60-3.91; P=.370). When combining these two effects, the adjusted odds ratio of FETO with early balloon insertion was 2.73 (95% confidence interval, 1.15-6.49). Results for survival to 6 months and survival to 6 months without oxygen dependence were comparable. The gestational age at delivery was on average 1.7 weeks earlier (95% CI, 1.1-2.3) following FETO with late insertion and 3.2 weeks earlier (95% CI, 2.3-4.1) following FETO with early insertion, as compared to expectant management. There was no evidence that the effect of FETO depended on the observed over expected lung-to-head ratio for any of the endpoints.

Conclusions: This analysis suggests that FETO increases survival both for moderate and severe lung hypoplasia. The difference between the results for the TOTAL trials, when considered apart, may be due to the difference in the time point of balloon insertion. However, the effect of time point of balloon insertion could not be robustly assessed due to small sample size and the confounding effect of disease severity. FETO, in particular with early balloon insertion, strongly increases the risk for preterm delivery.
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http://dx.doi.org/10.1016/j.ajog.2021.11.1351DOI Listing
November 2021

Long-term Indomethacin therapy after Laser surgery for TTTS. Worth the effort?

Authors:
Yves Ville

BJOG 2021 Nov 15. Epub 2021 Nov 15.

Universite paris descartes - fetal medicine, 149 rue de sevres, paris, 75015, France.

Fetal endoscopic surgery is a life-saving procedure for severe cases of TTTS. Over 25,000 cases of laser surgery for TTTS have been published since 1991, achieving survival rates of over 75% overall and 90% for at least one twin. However, preterm premature rupture of the membranes (PPROM) and birth before 32 weeks follow laser surgery in 20-50% of cases. This is due to the insult to the membranes caused by the trocar and the surgical procedure. Considerable efforts have been made for secondary prevention of PPROM, but despite more than 15 years of work in this field, clinical validation is lacking.
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http://dx.doi.org/10.1111/1471-0528.17015DOI Listing
November 2021

Predicting factors of protracted intestinal failure in children with gastroschisis.

J Pediatr 2021 Nov 5. Epub 2021 Nov 5.

Department of Pediatric Surgery and Transplantation, Necker-Enfants Malades Hospital, APHP, Paris, France; Paris Descartes School of Medicine, Paris Center University, Paris, France.

Objective: To identify prenatal and neonatal predictors of short-bowel-syndrome related intestinal failure (SBS-IF) in gastroschisis.

Study Design: This retrospective study included all patients with gastroschisis born between 2000 and 2017 who were enrolled in our home parenteral nutrition (PN) program, and all patients with gastroschisis born in our institution who survived two weeks, during the same time period. Prenatal ultrasound features, neonatal status, anatomic features, oral feeding and PN dependency were analyzed.

Results: Among 180 patients, 35 required long-term PN (SBS-IF group) and 145 acquired full oral feeding within 6 months (OF group). The mean follow-up was 7.9 years [1.6-17.5] and 5.0 years [0.1-18.2], respectively. Both bowel-matting (OR=14.23 [1.07-16.7] (P = .039)) and secondarily diagnosed atresia or stenosis (OR=17.78 [3.13-100.98] (p=0.001)) were independent postnatal predictors of SBS-IF. Eighteen children (51% of the SBS-IF group) were still dependent on artificial nutrition at last follow-up. SBS-IF patients who achieved full oral feeding had a median residual small-bowel length of 74 cm [51-160] vs. 44 cm [10-105] for those still dependent on artificial nutrition (p=0.02). Initial residual small bowel length of > 50 centimeters was the best predictive cut-off for nutritional autonomy with a sensitivity of 67% and a specificity of 100%.

Conclusion: Bowel-matting, complex gastroschisis and secondary intestinal obstruction were associated with SBS-IF in gastroschisis. For SBS-IF patients, small bowel length > 50 cm was predictive of secondary nutritional autonomy.
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http://dx.doi.org/10.1016/j.jpeds.2021.11.004DOI Listing
November 2021

MRI based morphological examination of the placenta.

Placenta 2021 Nov 24;115:20-26. Epub 2021 Aug 24.

EA fetus 7328 and LUMIERE Platform, Université de Paris, Paris, France; Radiology Department, Assistance Publique - Hôpitaux de Paris, Hôpital Necker - Enfants Malades, 149 rue de Sèvres, 75015, Paris, France.

Ultrasound is widely used as the initial diagnostic imaging modality during pregnancy with both high spatial and temporal resolution. Although MRI in pregnancy has long focused on the fetus, its use in placental imaging has greatly increased over recent years. In addition to the possibilities of evaluating function, MRI with a wide field of view and high contrast resolution allows characterization of placental anatomy, particularly in situations that are difficult to specify with ultrasound, especially for suspected placenta accreta. MRI also appears to be a particularly useful examination for the anatomical evaluation of the placenta independent of maternal body habitus or fetal position. Indeed, surprisingly little attention is paid to the placenta in MRI when the indication for the examination is fetal. Thus, some aspects of the placenta seem to us to be important to be recognized by the radiologist and to be described on the MRI report. In this review, we will describe MRI sequences used for, and common features seen in, imaging of i) the normal placenta, ii) abnormal aspects of the placenta that should be identified on MRI performed for fetal reason, and iii) placental anomalies for which placental MRI may be indicated.
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http://dx.doi.org/10.1016/j.placenta.2021.08.056DOI Listing
November 2021

Dynamic contrast enhanced magnetic resonance imaging: A review of its application in the assessment of placental function.

Placenta 2021 Oct 24;114:90-99. Epub 2021 Aug 24.

Obstetrics and Gynecology Department, Assistance Publique - Hôpitaux de Paris, Hôpital Necker - Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France; EA FETUS 7328 and LUMIERE Unit, Université de Paris, France. Electronic address:

It is important to develop a better understanding of placental insufficiency given its role in common maternofetal complications such as preeclampsia and fetal growth restriction. Functional magnetic resonance imaging offers unprecedented techniques for exploring the placenta under both normal and pathological physiological conditions. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is an established and very robust method to investigate the microcirculatory parameters of an organ and more specifically its perfusion. It is currently a gold standard in the physiological and circulatory evaluation of an organ. Its application to the human placenta could enable to access many microcirculatory parameters relevant to the placental function such as organ blood flow, fractional blood volume, and permeability surface area, by the acquisition of serial images, before, during, and after administration of an intravenous contrast agent. Widely used in animal models with gadolinium-based contrast agents, its application to the human placenta could be possible if the safety of contrast agents in pregnancy is established or they are confirmed to not cross the placenta.
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http://dx.doi.org/10.1016/j.placenta.2021.08.055DOI Listing
October 2021

Prenatal-onset of congenital neuronal ceroid lipofuscinosis with a novel CTSD mutation.

Birth Defects Res 2021 Nov 7;113(18):1324-1332. Epub 2021 Sep 7.

Unité d'Embryofœtopathologie, Hôpital Necker-Enfants Malades, AP-HP.Centre, Paris, France.

Background: Neuronal ceroid lipofuscinoses (NCLs) form a clinically and genetically heterogeneous group of inherited neurodegenerative disorders that share common neuropathological features. Although they are the first cause of neurodegenerative disorders in children, their congenital forms are rarely documented. They are classically due to mutations in the CTSD gene (the CLN10 disease). Affected newborns usually present severe microcephaly, seizures and respiratory failure leading to death within the first postnatal days or weeks.

Cases: We report on two siblings, in which exome sequencing identified a novel homozygous CTSD variant. The first sib presented at birth with seizures, rapidly progressive postnatal microcephaly and visual deficiency related to retinal dysfunction. Progressive neurological deterioration leads to death at the age of 24 months. Cathepsin D activity was reduced in the cultured fibroblasts of this patient. The second sib, a fetus of 36 weeks of gestation, was delivered after pregnancy termination for brain abnormalities (in accordance with French Legislation) suggesting a recurrence of the disease. Fetal postmortem examination disclosed neuropathological features consistent with NCL.

Conclusions: Congenital NCL related to CTSD mutations is a neuronal storage disorder that produces in the developing brain diffuse neurodegeneration and white matter atrophy resulting in a progressive and rapidly lethal microcephaly.
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http://dx.doi.org/10.1002/bdr2.1950DOI Listing
November 2021

Human placental perfusion measured using dynamic contrast enhancement MRI.

PLoS One 2021 2;16(9):e0256769. Epub 2021 Sep 2.

Service de Gynécologie-Obstétrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Objectives: To evaluate the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) and measure values of in vivo placental perfusion in women.

Methods: This study was part of the Placentimage trial (NCT01092949). Gadolinium-chelate (Gd) enhanced dynamic MRI was performed two days before termination of pregnancies at 16 to 34 weeks gestational age (GA). Quantitative analysis was performed using one-compartment intravascular modeling. DCE perfusion parameters were analyzed across GA and were compared in IUGR and AGA fetuses.

Results: 134 patients were enrolled. After quality control check, 62 DCE MRI were analyzed including 48 and 14 pregnancies with normal and abnormal karyotypes, respectively. Mean placental blood flow was 129±61 mL/min/100ml in cases with normal karyotypes. Fetuses affected by IUGR (n = 13) showed significantly lower total placental blood flow values than AGA fetuses (n = 35) (F total = 122±88 mL/min versus 259±34 mL/min, p = 0.002). DCE perfusion parameters showed a linear correlation with GA.

Conclusions: Measuring placental perfusion in vivo is possible using DCE MRI. Although this study has many limitations it gives us the first DCE MRI values that provide a potential standard for future research into placental perfusion methods and suggests that placental functional parameters are altered in IUGR pregnancies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256769PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412340PMC
November 2021

Ultrasound and Fetal MRI Complementary Contributions to Appropriate Counseling in Small Bowel Obstruction.

Fetal Diagn Ther 2021 30;48(8):567-574. Epub 2021 Aug 30.

AP-HP, Hôpital Necker Enfants Malades, Service de Radiologie Pédiatrique, Paris, France.

Objective: Bowel obstructions beyond the duodenum represent a heterogeneous group of congenital anomalies with a highly variable prognosis, the main issue being postnatal short bowel syndrome (SBS). The objective of our study was to evaluate the contributions of fetal MRI in cases of bowel obstruction.

Materials And Methods: A retrospective analysis of all newborns, for whom both ante-natal ultrasound and fetal MRI were available, referred to our center for suspected bowel obstruction was performed. Examinations were reviewed blinded to the postnatal outcome. Key outcome measures included exact diagnosis and the existence of postoperative SBS. We evaluated the contribution of MRI in determining precise location and etiology of the bowel obstruction, dilatation of the proximal bowel loops, and assessment of the quality of the remaining distal bowel loops.

Results: Twenty-five newborns were included. There were 19 single obstructions and 6 complex forms (4 apple peel syndromes and 2 multiple atresias). MRI correctly identified the affected segment of the small bowel in 59.1% of the cases. MRI identified the mechanism of obstruction in 72% of cases. MRI reliably predicted an abnormal appearance of the bowel distal to the obstruction in 100% of the severe cases (3/3) and in 66.7% of complex forms (4/6).

Conclusion: Our study suggests that fetal MRI, when done in addition to prenatal ultrasound, is contributory in the management of fetuses with suspected bowel obstruction. MRI may be particularly useful in determining the location and origin of the bowel obstruction and in assessing the quality of the bowel distal to the obstruction, which might assist in the prediction of SBS and more detailed prenatal counseling.
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http://dx.doi.org/10.1159/000517728DOI Listing
November 2021

Evaluation of the usefulness of ultrasound measurement of the lower uterine segment before delivery of women with a prior cesarean delivery: a randomized trial.

Am J Obstet Gynecol 2021 Aug 9. Epub 2021 Aug 9.

Centre of Research Epidemiology and Statistics, Institut National de la Santé et de la Recherche Médical U1153, Université de Paris, Paris, France; Centre of Clinical Epidemiology, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: The main reason to avoid trial of labor after cesarean delivery is the possibility of uterine rupture. Identifying women at risk is thus an important aim, for it would enable women at low risk to proceed with a secure planned vaginal birth.

Objective: To evaluate the impact of proposing mode of delivery based on the ultrasound measurement of the lower uterine segment thickness on a composite outcome of maternal-fetal mortality and morbidity, compared with usual management, among pregnant women with a previous cesarean delivery.

Study Design: This multicenter, randomized, controlled, parallel-group, unmasked trial was conducted at 8 referral university hospitals with a neonatal intensive care unit and enrolled 2948 women at 36 weeks 0 days to 38 weeks 6 days of gestation with 1 previous low transverse cesarean delivery and no contraindication to trial of labor. Women in the study group had their lower uterine segment thickness measured by ultrasound. Those with measurements >3.5 mm, were encouraged to choose a planned vaginal delivery, and those with measurements ≤3.5 mm, were encouraged to choose a planned repeat cesarean delivery. This measurement was not taken in the control group; their mode of delivery was decided according to standard management. The primary outcome was a composite criterion comprising maternal mortality, uterine rupture, uterine dehiscence, hysterectomy, thromboembolic disease, transfusion, endometritis, perinatal death, or neonatal encephalopathy. Prespecified secondary outcomes were repeat cesarean deliveries, elective or after trial of labor.

Results: The study group included 1472 women, and the control group included 1476 women. These groups were similar at baseline. The primary outcome occurred in 3.4% of the study group and 4.3% of the control group (relative risk, 0.78; 95% confidence interval, 0.54-1.13: risk difference, -1.0%; 95% confidence interval, -2.4 to 0.5). The uterine rupture rate in the study group was 0.4% and in the control group 0.9% (relative risk, 0.43; 95% confidence interval, 0.15-1.19). The planned cesarean delivery rate was 16.4% in the study group and 13.7% in the control group (relative risk, 1.21; 95% confidence interval, 1.00-1.47), whereas the rates of cesarean delivery during labor were 25.1% and 25.0% (relative risk, 1.01; 95% confidence interval, 0.89-1.14) in the study and control groups, respectively.

Conclusion: Ultrasound measurements of lower uterine segment thickness did not result in a statistically significant lower frequency of maternal and perinatal adverse outcomes than standard management. However, because this study was underpowered, further research should be encouraged.
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http://dx.doi.org/10.1016/j.ajog.2021.08.005DOI Listing
August 2021

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Sci Rep 2021 07 6;11(1):13898. Epub 2021 Jul 6.

Department of Obstetrics & Gynecology, University of Campinas, Campinas, Brazil.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease.
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http://dx.doi.org/10.1038/s41598-021-92357-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260739PMC
July 2021

Biplane mode for more precise intrauterine procedures.

Am J Obstet Gynecol 2021 Jun 8. Epub 2021 Jun 8.

Department of Obstetrics and Fetal Medicine, Necker Enfants-Malades Hospital, Paris Descartes University, Paris, France; Université de Paris, Paris, France.

The evolution of ultrasound and the introduction of 3- and 4-dimensional ultrasound techniques led to a shift in the perception and usage of ultrasound in fetal medicine. The biplane mode might help in multiple fetal procedures, including but not limited to basic intrauterine thoracocentesis, thoracoamniotic shunting, amnioreduction, amnioinfusion, cordocentesis, intraumbilical infusion, and umbilical cord coagulation, with a possible reduction in the complication rate. Despite its theoretical usefulness, more studies are required to assess the clinical importance of this technique.
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http://dx.doi.org/10.1016/j.ajog.2021.06.005DOI Listing
June 2021

Outcomes of sustained fetal tachyarrhythmias after transplacental treatment.

Heart Rhythm O2 2021 Apr 9;2(2):160-167. Epub 2021 Mar 9.

Obstetric and Maternal Fetal Medicine and EA7328.

Background: Fetal tachyarrhythmia is a condition that may lead to cardiac dysfunction, hydrops, and death. Despite a transplacental treatment, failure to obtain or maintain sinus rhythm may occur.

Objective: We aimed to analyze the perinatal outcomes of sustained fetal tachyarrhythmias after in utero treatment.

Methods: We performed a retrospective evaluation of 69 cases with sustained fetal tachyarrhythmia. We compared the perinatal and long-term outcomes of prenatally converted and drug-resistant fetuses. Tachyarrhythmia subtypes were also evaluated.

Results: Conversion to sinus rhythm was obtained in 74% of cases; 26% of cases were drug-resistant and delivered arrhythmic. Three perinatal deaths occurred in both groups (6.7% vs 17%, = .34). Neonates delivered arrhythmic were more frequently admitted to neonatal intensive care units (75% vs 31%, < .01), and their hospital stay was longer (20.9 vs 6.64 days, < .001). Multiple neonatal recurrences (81% vs 11%, < .001), temporary hemodynamic dysfunction or heart failure (50% vs 6.7%, < .001), and postnatal use of a combination treatment (44% vs 13%,  = .028) were also more frequent in this population. Beyond the neonatal period, rates of recurrences within the first 16 months were higher in drug-resistant fetuses (HR = 16.14, CI 95% [4.485; 193.8], < .001). In this population, postnatal electrocardiogram revealed an overrepresentation of rare mechanisms, especially permanent junctional reciprocating tachycardia (PJRT) (31%).

Conclusion: Prenatal conversion to stable sinus rhythm is a major determinant of perinatal and long-term outcomes in fetal tachyarrhythmias. The underlying electrophysiological mechanisms have a major role in predicting these differential outcomes with an overrepresentation of PJRT in the drug-resistant population.
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http://dx.doi.org/10.1016/j.hroo.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183966PMC
April 2021

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia.

N Engl J Med 2021 07 8;385(2):119-129. Epub 2021 Jun 8.

From the Department of Obstetrics and Gynecology, University Hospitals KU Leuven (J.A.D., P.L.J.D.) and Academic Department of Development and Regeneration, Biomedical Sciences, KU Leuven, Leuven, Belgium (J.A.D., B.V.C., P.L.J.D.); Hospital Antoine-Béclère, Université Paris-Saclay, Clamart (A.B.), and Necker-Enfants Malades Hospital, Paris (Y.V.) - both in France; Hospital Clinic and Sant Joan de Déu, Barcelona (E.G.); Institute for Women's Health, University College London Hospital (J.A.D.) and King's College Hospital(K.H.N.) - both in London; the University Hospital Bonn, Bonn, Germany (C.B.); Hospital Maggiore Policlinico, Milan (N.P.), and Bambino Gesù Children's Hospital, Rome (F.M.) - both in Italy; Baylor College of Medicine and Texas Children's Hospital (M.B.) and Children's Memorial Hermann Hospital (A.J.) - all in Houston; Mater Mothers' Hospital, Brisbane, QLD, Australia (G.J.G.); the Medical University of Warsaw, Warsaw, Poland (M.W.); and Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands (P.L.J.D.).

Background: Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease.

Methods: In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age.

Results: In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal.

Conclusions: This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).
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http://dx.doi.org/10.1056/NEJMoa2026983DOI Listing
July 2021

Prevalence and incidence of postpartum depression and environmental factors: The IGEDEPP cohort.

J Psychiatr Res 2021 06 16;138:366-374. Epub 2021 Apr 16.

Université de Paris, INSERM UMR1266, Institute of Psychiatry and Neurosciences, Team 1, Paris, France; Department of Psychiatry, AP-HP, Louis Mourier Hospital, F-92700, Colombes, France.

Background: IGEDEPP (Interaction of Gene and Environment of Depression during PostPartum) is a prospective multicenter cohort study of 3310 Caucasian women who gave birth between 2011 and 2016, with follow-up until one year postpartum. The aim of the current study is to describe the cohort and estimate the prevalence and cumulative incidence of early and late-onset postpartum depression (PPD).

Methods: Socio-demographic data, personal and family psychiatric history, as well as stressful life events during childhood and pregnancy were evaluated at baseline. Early and late-onset PPD were assessed at 8 weeks and 1 year postpartum respectively, using DSM-5 criteria.

Results: The prevalence of early-onset PPD was 8.3% (95%CI 7.3-9.3), and late PPD 12.9% (95%CI 11.5-14.2), resulting in an 8-week cumulative incidence of 8.5% (95%CI 7.4-9.6) and a one-year cumulative incidence of PPD of 18.1% (95%CI: 17.1-19.2). Nearly half of the cohort (N = 1571, 47.5%) had a history of at least one psychiatric or addictive disorder, primarily depressive disorder (35%). Almost 300 women in the cohort (9.0%) reported childhood trauma. During pregnancy, 47.7% women experienced a stressful event, 30.2% in the first 8 weeks and 43.9% between 8 weeks and one year postpartum. Nearly one in five women reported at least one stressful postpartum event at 8 weeks.

Conclusion: Incident depressive episodes affected nearly one in five women during the first year postpartum. Most women had stressful perinatal events. Further IGEDEPP studies will aim to disentangle the impact of childhood and pregnancy-related stressful events on postpartum mental disorders.
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http://dx.doi.org/10.1016/j.jpsychires.2021.04.004DOI Listing
June 2021

Advocating for cytomegalovirus maternal serologic screening in the first trimester of pregnancy: if you do not know where you are going, you will wind up somewhere else.

Authors:
Yves Ville

Am J Obstet Gynecol MFM 2021 07 21;3(4):100356. Epub 2021 Mar 21.

Department of Obstetrics, Fetal Medicine and Surgery, Hôpital Necker-Enfants malades, University of Paris, Paris, France. Electronic address:

Congenital cytomegalovirus infection is an important health problem for the individual and the community. Although it could derive from both primary and nonprimary maternal infection, the prospective risk of congenital infection in seronegative pregnant women is 4 times than that of immune women. Maternal serology is the only reliable screening tool in pregnancy that would identify up to 50% of all congenital cytomegalovirus infections, by yielding positive immunoglobulin M and immunoglobulin G and low immunoglobulin G avidity in approximately 0.5% of the population at 11 to 14 weeks. The exceptionally high risk for young parous seronegative women planning a second pregnancy makes a compelling case for offering serologic screening as soon as pregnancy is planned or diagnosed and by the end of the first trimester. The 11- to 14-week consultation has become an unmissable one worldwide and would represent the most practical compromise if only 1 sample can be taken. Valaciclovir that can be safely used in the early fetal period decreases vertical transmission by 70% and should be implemented as early as possible after maternal infection. Facilities for diagnosis and treatment are available in high- and middle-income countries through laboratory and fetal medicine networks. Amniocentesis with amplification of the viral DNA by polymerase chain reaction in the amniotic fluid is a reliable diagnostic test but chorionic villi sampled by chorionic villus sampling could achieve the same performance 2 months earlier. Fetal imaging of a known infected fetus yields a negative predictive value on symptoms at birth and congenital handicap of between 95% and 99%, and prenatal treatment of infected fetuses decreases the occurrence of symptoms at birth and at 2 years of age.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100356DOI Listing
July 2021

Cystic kidney diseases associated with mutations in phosphomannomutase 2 promotor: a large spectrum of phenotypes.

Pediatr Nephrol 2021 08 13;36(8):2361-2369. Epub 2021 Feb 13.

Laboratory of Hereditary Kidney Diseases, Université de Paris, Imagine Institute, INSERM UMR 1163, F-75015, Paris, France.

Background: Co-occurrence of polycystic kidney disease and hyperinsulinemic hypoglycemia has been reported in children in a few families associated with a variant in the promotor of the PMM2 gene, at position -167 upstream of the coding sequence. PMM2 encodes phosphomannomutase 2, a key enzyme in N-glycosylation. While biallelic coding PMM2 mutations are involved in congenital disorder of glycosylation CDG1A, that particular variant in the promoter of the gene, either in the homozygous state or associated with a mutation in the coding exons of the gene, is thought to restrict the N-glycosylation defect to the kidney and the pancreas.

Methods: Targeted exome sequencing of a panel of genes involved in monogenic kidney diseases.

Results: We identified a PMM2 variant at position -167 associated with a pathogenic PMM2 variant in the coding exons in 3 families, comprising 6 cases affected with a cystic kidney disease. The spectrum of phenotypes was very broad, from extremely enlarged fetal cystic kidneys in the context of a COACH-like syndrome, to isolated cystic kidney disease with small kidneys, slowly progressing toward kidney failure in adulthood. Hypoglycemia was reported only in one case.

Conclusion: These data show that the PMM2 promotor variation, in trans of a PMM2 coding mutation, is associated with a wide spectrum of kidney phenotypes, and is not always associated with extra-renal symptoms. When present, extra-renal defects may include COACH-like syndrome. These data prompt screening of PMM2 in unresolved cases of fetal hyperechogenic/cystic kidneys as well as in cystic kidney disease in children and adults. Graphical Abstract.
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http://dx.doi.org/10.1007/s00467-021-04953-9DOI Listing
August 2021

Announcing fetal pathology: Challenges encountered by physicians and potential role of simulation in training for breaking bad news.

J Gynecol Obstet Hum Reprod 2021 Apr 17;50(4):102044. Epub 2020 Dec 17.

Simechole, Simulation School for Education and Training of Obstetrical and Gynecological Ultrasound, Paris, France; Department of Obstetrics and Fetal Medicine, Necker-Enfants-Malades Hospital, APHP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Department of Obstetrics and Gynecology, American University of Beirut Medical Center, American University of Beirut, Beirut, Lebanon.

Background: Informing couples about the diagnosis of severe fetal pathologies is part of the daily routine in fetal medicine. This situation is usually complex and can put untrained professionals in an uncomfortable position. The aim of this study was to assess the perception of health care professionals when faced with the need to announce a fetal pathology in order to target their training gaps in this domain.

Materials And Methods: A questionnaire was created and disseminated on a national level among physicians practicing or collaborating with the multidisciplinary centers of prenatal diagnosis in France. The questionnaire focused on the difficulties encountered by practitioners when announcing fetal pathologies, and their potential interest in simulation sessions regarding the delivery of bad news.

Results: 193 participants filled the questionnaire. 65 % report not receiving any theoretical courses in this field during their initial training, 49 % admit feeling uncomfortable when a fetal anomaly needs to be announced, 79.5 % think that role-play could help them, 87.5 % believe that training sessions in communication skills would help improve their methods and 73.1 % support teaching the delivery of bad news by simulation sessions.

Conclusion: This survey illustrates the significance of announcing a fetal pathology for fetal medicine professionals. Many of them report not being properly trained to cope with this situation and would like to improve with a more practical way of teaching. Simulation would be the ideal educational tool to meet this demand.
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http://dx.doi.org/10.1016/j.jogoh.2020.102044DOI Listing
April 2021

SARS-COV-2 IgG antibody response in pregnant women at delivery.

J Gynecol Obstet Hum Reprod 2021 Sep 10;50(7):102041. Epub 2020 Dec 10.

Université Paris-Saclay, 94804 Villejuif, France; Laboratoire de Virologie, AP-HP, Hôpital Paul-Brousse, F-94804 Villejuif, France.

Background: The prevalence of COVID-19 infection during pregnancy is not known. COVIPREG is a prospective French multicenter study to assess the seroprevalence at the time of delivery and the maternal and neonatal impact of COVID-19 infection during pregnancy. In order to study factors associated with poor outcomes after COVID-19 Infection during pregnancy and adapt the sample size of the study, a preliminary assessment of the prevalence of SARS-CoV-2 IgG was planned after 500 inclusions in a one perinatal center of Paris area.

Objectives: To assess the prevalence of SARS-CoV-2 IgG antibody response in pregnant women at the time of delivery during the COVID-19 pandemia.

Study Design: A prospective observational study at Cochin hospital (Level III maternity). Patients admitted for delivery were offered to participate to the study. Each patient participating to the study was tested for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA.

Results: Among the 529 patients included in the COVIPREG study between April 29 and June 26, 529 were assessed for SARS-CoV-2 IgG antibody response and 25 had a positive test, ie 4.7 % with a confidence interval at 95 % [3.0 %-6.9 %]).

Conclusions: Four months after the beginning of the infection in Paris, the seroprevalence of SARS-CoV-2 IgG in pregnant women at the time of delivery is low. Studies evaluating the impact of COVID-19 infection during pregnancy should take this information in account in order to adapt the sample size.
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http://dx.doi.org/10.1016/j.jogoh.2020.102041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831450PMC
September 2021

A retrospective study on the efficacy of prenatal diagnosis for pregnancies at risk of mitochondrial DNA disorders.

Genet Med 2021 04 11;23(4):720-731. Epub 2020 Dec 11.

Université de Paris-Sorbonne Paris Cité, Imagine Institute, INSERM UMR1163, Paris, France.

Purpose: Prenatal diagnosis of mitochondrial DNA (mtDNA) disorders is challenging due to potential instability of fetal mutant loads and paucity of data connecting prenatal mutant loads to postnatal observations. Retrospective study of our prenatal cohort aims to examine the efficacy of prenatal diagnosis to improve counseling and reproductive options for those with pregnancies at risk of mtDNA disorders.

Methods: We report on a retrospective review of 20 years of prenatal diagnosis of pathogenic mtDNA variants in 80 pregnant women and 120 fetuses.

Results: Patients with undetectable pathogenic variants (n = 29) consistently had fetuses free of variants, while heteroplasmic women (n = 51) were very likely to transmit their variant (57/78 fetuses, 73%). In the latter case, 26 pregnancies were terminated because fetal mutant loads were >40%. Of the 84 children born, 27 were heteroplasmic (mutant load <65%). To date, no medical problems related to mitochondrial dysfunction have been reported.

Conclusion: Placental heterogeneity of mutant loads questioned the reliability of chorionic villous testing. Fetal mutant load stability, however, suggests the reliability of a single analysis of amniotic fluid at any stage of pregnancy for prenatal diagnosis of mtDNA disorders. Mutant loads under 40% reliably predict lack of symptoms in the progeny of heteroplasmic women.
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http://dx.doi.org/10.1038/s41436-020-01043-3DOI Listing
April 2021

Longitudinal Analysis of Fetal Ventricular Rate for Risk Stratification in Immune Congenital Heart Block.

Fetal Diagn Ther 2021 9;48(1):1-8. Epub 2020 Dec 9.

Obstetrics, Fetal Medicine and Surgery, Hôpital Necker Enfants Malades, Paris, France,

Objectives: To assess the perinatal risks of immune complete congenital heart block (iCCHB) based on the longitudinal analysis of fetal heart rate.

Methods: Retrospective analysis of a cohort of grade III congenital heart block diagnosed in utero, in the absence of associated cardiac defect, with positive maternal serum antibodies. Longitudinal measurements of the fetal heart rate were used to estimate the average slope of ventricular rate as a function of gestational age. We then defined the following prognostic stratification based on longitudinal follow-up observations: the high-rate (HR) group included cases for which all prenatal ventricular rate measurements were above the age-specific mean of our population of iCCHB and the low-rate (LR) group included those with at least one observation below the mean during follow-up. The 2 groups were compared to analyze the potential relationship between prenatal ventricular rate and adverse neonatal outcome defined by in utero or perinatal death, neonatal heart rate <50 bpm, or hemodynamic failure requiring emergency pacing.

Results: Forty-four cases were studied. Overall, the average heart rate significantly decreased during gestation from 65 bpm at 20 weeks to 55 bpm at 38 weeks. The HR and LR groups included 18 (41%) and 26 (59%) cases, respectively. Adverse perinatal outcome occurred in 1/18 (6%) and 22/26 (85%) cases in the HR and LR groups, respectively (p < 0.001). In the HR group, 33% of cases remained nonpaced at >6 months. The positive predictive values and negative predictive values for adverse perinatal outcome in the LR group were 85% (22/26) and 94% (17/18), respectively (100 and 80% <30 weeks and 88 and 78% at ≥30 weeks).

Conclusions: The prognostic classification we developed based on longitudinal heart rate assessment may be used in the late 2nd or early 3rd trimester to identify iCCHB cases at high risk of adverse perinatal outcome. This prognostic stratification should help refine counseling and perinatal management earlier in pregnancy instead of waiting for late gestation or predelivery assessment.
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http://dx.doi.org/10.1159/000507811DOI Listing
November 2021

Intrauterine fetoscopic laser surgery versus expectant management in stage 1 twin-to-twin transfusion syndrome: an international randomized trial.

Am J Obstet Gynecol 2021 05 26;224(5):528.e1-528.e12. Epub 2020 Nov 26.

Department of Obstetrics and Maternal-Fetal Medicine, Hôpital Necker-Enfants Malades, AP-HP and EA7328, Université de Paris, Paris, France.

Background: Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition.

Objective: This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome.

Study Design: We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks' gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes.

Results: The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively).

Conclusion: It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.
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http://dx.doi.org/10.1016/j.ajog.2020.11.031DOI Listing
May 2021

Ultrasound detected prenatal hyperechoic lung lesions and concordance with postnatal findings: A common aspect for multiple diagnoses.

Prenat Diagn 2021 02 5;41(3):323-331. Epub 2020 Nov 5.

Department of Pediatric Surgery, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.

Objective: Hyperechoic lung lesions are largely detected prenatally but their underlying etiology is still poorly defined. The aim of the study was to determine the concordance between pre and postnatal diagnosis of hyperechoic lung lesions.

Methods: Prenatal ultrasound (US) evaluation was performed by a fetal medicine specialist. Postnatal diagnosis was based on CT-scan. Pre- and postnatal features were retrieved from medical charts.

Results: Seventy five patients were included from January 2009 to December 2018. Main prenatal diagnoses were bronchopulmonary sequestrations (BPS) (n = 24%-32%), pulmonary cystic malformations (PCM) (n = 19%-25%), congenital lobar emphysemas (CLE) (n = 15%-20%). Mediastinal shift was observed in 18 cases (24%). The prenatal detection of a systemic arterial supply had a diagnostic accuracy of 90%, while the prenatal detection of a cystic component had a diagnostic accuracy of 76.5%. All 16 neonates with prenatal isolated mediastinal shift were asymptomatic at birth. Seven neonates showed respiratory distress that was not predicted prenatally.

Conclusions: Hyperechoic lung malformations reflect a heterogeneous group of lesions with a good concordance for bronchopulmonary sequestration, but not a satisfying prediction for cystic lesions.
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http://dx.doi.org/10.1002/pd.5854DOI Listing
February 2021

Comparison of crown-rump length discordance and abnormal cord insertions as first-trimester predictors of poor outcome in monochorionic diamniotic twin pregnancies.

J Matern Fetal Neonatal Med 2020 Sep 15:1-5. Epub 2020 Sep 15.

Department of Obstetrics, Fetal Medicine and Surgery, Hôpital Necker Enfants Malades, AP-HP, Université de Paris, Paris, France.

Objectives: This is a retrospective study to determine the predictive value and comparison of first trimester (1) crown-rump length discordance and (2) abnormal cord insertion as screening tests for poor outcome in monochorionic diamniotic twin pregnancies.

Results: Retrospective data were collected over last 10 years from a single center (2009-2018). A total of 261 patients were a part of this study. CRL discordance or abnormal cord insertions are not accurate predictors of twin-to-twin transfusion syndrome, which corresponds to previously published data on the same subject. Both CRL discordance and abnormal cord insertions are strongly associated with selective fetal growth restriction (sFGR) as defined according to conventional criteria or the newer consensus criteria. A combination of these two markers substantially improves the screening rates, with a positive likelihood ratio of 10.33 for sFGR. However, this combination fails to distinguish the type 1 sFGR cases from the type 2/3, which typically have poorer outcomes.

Conclusion: CRL discordance and abnormal cord insertions are strongly associated with the development sFGR in monochorionic pregnancies. A combination of these two markers shows promising potential as a screening test to identify pregnancies at a high risk for development of sFGR. Earlier diagnosis can help plan timely fetal intervention and improve the overall outcomes of these pregnancies. These markers need to be validated in larger studies before being adopted for screening of monochorionic pregnancies.
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http://dx.doi.org/10.1080/14767058.2020.1818199DOI Listing
September 2020

Secondary prevention of congenital cytomegalovirus infection.

Lancet 2020 09;396(10253):739-741

Fetal Medecine and Obstetrics, AP-HP, Hospital Necker Enfants-Malade, Paris 75015, France; EA 7328, Paris Descartes Université, Université de Paris, Paris, France.

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http://dx.doi.org/10.1016/S0140-6736(20)31903-6DOI Listing
September 2020

Reply.

Authors:
Yves Ville

Am J Obstet Gynecol 2020 11 13;223(5):776. Epub 2020 Aug 13.

Department of Obstetrics and Fetal Medicine, Necker-Enfants Malades Hospital, University of Paris Descartes, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2020.08.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423533PMC
November 2020

Maternal type of CMV infection and sequelae in infants with congenital CMV: Systematic review and meta-analysis.

J Clin Virol 2020 08 27;129:104518. Epub 2020 Jun 27.

Third Department of Pediatrics, National and Kapodistrian University of Athens, School of Health Sciences, University General Hospital ATTIKON, Rimini 1, Chaidari 12462, Athens, Greece. Electronic address:

Cytomegalovirus (CMV) is the most common congenital infection. Intrauterine transmission may occur following primary (PI) or non-primary (NPI) maternal infection and result in both neonatal symptomaticdisease and long-term complications.The aim of the present systematic review and meta-analysis was the qualitative and quantitative comparison of neonatal symptomatic disease and long-term sequelae of congenitally CMV infected children born following maternal PI or NPI. Articles from MEDLINE and SCOPUS databases were systematically reviewed. Articles describing neonatal symptoms and/or long-term sequelae in infants and children with cCMV born to mothers following PI and NPI were eligible.From eligible articles, data on the prevalence of neonatal symptoms, sensorineural hearing loss (SNHL) or neurologic sequelae in children born following PI and NPI were extracted and statistically analyzed. Maternal infection status did not influence neonatal symptomatic disease (pooled Odds Ratio (OR) 0.83, 95 % CI [0.55; 1.27], p=0.397). Additionally, the two groups of cCMV infected children had similar risk of developing SNHL, bilateral SNHL or other neurologic outcomes. Importantly, these findings remained as such, when newborns identified through universal screening were separately analyzed. Finally, when data on symptomatic and/or asymptomatic newborns were evaluated alone, maternal type was not associated with outcomes examined. Considering available data, the universal screening of all newborns for CMV infection may be discussed as a perspective. The systematic review and meta-analysis were registered in PROSPERO (Prospero registration number: CRD42019125179).
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http://dx.doi.org/10.1016/j.jcv.2020.104518DOI Listing
August 2020

Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene.

Clin Genet 2020 09 4;98(3):261-273. Epub 2020 Aug 4.

Service de génétique, Hôpital Nord CHU Saint-Etienne, Saint Etienne, France.

Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a severe congenital visceral myopathy characterized by an abdominal distension due to a large non-obstructed urinary bladder, a microcolon and intestinal hypo- or aperistalsis. Most of the patients described to date carry a sporadic heterozygous variant in ACTG2. More recently, recessive forms have been reported and mutations in MYH11, LMOD1, MYLK and MYL9 have been described at the molecular level. In the present report, we describe five patients carrying a recurrent heterozygous variant in ACTG2. Exome sequencing performed in four families allowed us to identify the genetic cause in three. In two families, we identified variants in MMIHS causal genes, respectively a nonsense homozygous variant in MYH11 and a previously described homozygous deletion in MYL9. Finally, we identified compound heterozygous variants in a novel candidate gene, PDCL3, c.[143_144del];[380G>A], p.[(Tyr48Ter)];[(Cys127Tyr)]. After cDNA analysis, a complete absence of PDLC3 expression was observed in affected individuals, indicating that both mutated transcripts were unstable and prone to mediated mRNA decay. PDCL3 encodes a protein involved in the folding of actin, a key step in thin filament formation. Presumably, loss-of-function of this protein affects the contractility of smooth muscle tissues, making PDCL3 an excellent candidate gene for autosomal recessive forms of MMIHS.
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http://dx.doi.org/10.1111/cge.13801DOI Listing
September 2020

Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases.

J Clin Med 2020 Jun 5;9(6). Epub 2020 Jun 5.

Fetal Medicine Centre, Birmingham Women's and Children's Foundation Trust, University of Birmingham, Birmingham B4 6NH, UK.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7-28, range: 1-119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6-33.7; range: 19.0-41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients ( < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1-8.3, < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7-0.9, = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3-1.7, < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.
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http://dx.doi.org/10.3390/jcm9061759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355738PMC
June 2020

Ultrasound features of fetal toxoplasmosis: A contemporary multicenter survey in 88 fetuses.

Prenat Diagn 2020 12 30;40(13):1741-1752. Epub 2020 Jun 30.

Assistance Publique-Hôpitaux de Paris, Service de Gynécologie-Obstétrique, Hôpital Louis Mourier, APHP Nord Université de Paris, Colombes, France.

Objective: To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT).

Methods: We retrospectively analyzed all cases of fetal infection with Toxoplasma gondii with ultrasound anomalies described by fetal medicine experts in 2009 to 2019 in 30 French centers.

Results: Eighty-eight cases of CT were included. Forty-five (51.1%) had one or more cerebral signs only, 35 (39.8%) had cerebral plus extracerebral signs and 8 (9.1%) had extracerebral signs only. The main cerebral signs were intracranial hyperechogenic nodular foci (n = 60) of which 20 were isolated, ventriculomegalies (n = 44) which generally increased during follow-up, and periventricular abscesses (n = 12). The main extracerebral signs were hepatomegaly and/or splenomegaly (n = 14), small for gestational age (n = 14), ascites (n = 14, including 2 with hydrops), and hyperechogenic bowel (n = 11). Maternal infection occurred mostly in the first or second trimester (81 cases), periconceptionally in one and in the third trimester in six cases. The first ultrasound signs were detected after a median of 7 weeks (range: 1.4; 24.0) following maternal toxoplasmosis seroconversion.

Conclusion: While no sign was specific of CT, there were typical associations of cerebral signs with or without extracerebral signs. Detailed ultrasound examination could improve prognostic evaluation, as well as diagnosis of CT in settings lacking serological screening.
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http://dx.doi.org/10.1002/pd.5756DOI Listing
December 2020
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