Publications by authors named "Julien Stirnemann"

41 Publications

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
December 2020

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

Am J Obstet Gynecol 2020 Nov 26. 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
November 2020

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

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.

Department of Obstetrics, Division of Fetal therapy, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

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

Management of monochorionic twins discordant for structural fetal anomalies.

Prenat Diagn 2020 10 19;40(11):1375-1382. Epub 2020 Aug 19.

Department of Obstetrics and Fetal Therapy, AP-HP, Necker-Enfants Malades Hospital, Paris, France.

Objective: To review the perinatal management and outcomes of monochorionic twin pregnancies (MC) discordant for congenital anomalies (DCA).

Methods: Retrospective, study of all MC DCA cases referred to our tertiary referral center from 1997 to 2018. We excluded cases complicated with twin-to-twin transfusion syndrome, twin anemia-polycythemia sequence, twin reversed arterial perfusion sequence or selective intra-uterine growth restriction. Patients were counseled about the possibility of expectant (EM) or interventional management (selective feticide [SF] or termination of the entire pregnancy [TOP]).

Results: One hundred eight of 4157 (2.6%) MC pregnancies were discordant for anomaly. Fifty two of 108 n(48.1%) underwent SF at a mean gestational age of 31.4 ± 5.9 weeks while 52/108(48.1%) opted for EM. Livebirth rate of the healthy co-twin was similar between the two groups (SF: 88.5% vs EM: 82.7%, P = .87). In the SF group, six healthy co-twins (6/52, 11.5%) died 5.3 ± 3.1 days after SF of the abnormal co-twin. In the EM group, in-utero demise of the abnormal twin occurred in 9 of 52 (17.3%) of the cases and was followed by the spontaneous demise of the healthy co-twin in 4 of 9 (44.4%) of these cases.

Conclusion: Selective feticide does not seem to significantly alter survival of the healthy co-twin compared to EM.
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http://dx.doi.org/10.1002/pd.5734DOI Listing
October 2020

Placental transfer of Letermovir & Maribavir in the ex vivo human cotyledon perfusion model. New perspectives for in utero treatment of congenital cytomegalovirus infection.

PLoS One 2020 30;15(4):e0232140. Epub 2020 Apr 30.

APHP, Fetal Medicine and Obstetric Department, Necker-Enfants Malades Hospital, Paris, France.

Background: Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment. Letermovir (LMV) and Maribavir (MBV) are new CMV antivirals, and potential candidates for fetal treatment.

Methods: The objective was to investigate the placental transfer of LMV and MBV in the ex vivo method of the human perfused cotyledon. Term placentas were perfused, in an open-circuit model, with LMV or MBV at concentrations in the range of clinical peak plasma concentrations. Concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Mean fetal transfer rate (FTR) (fetal (FC) /maternal concentration), clearance index (CLI), accumulation index (AI) (retention of each drug in the cotyledon tissue) were measured. Mean FC were compared with half maximal effective concentrations of the drugs (EC50(LMV) and EC50(MBV)).

Results: For LMV, the mean FC was (± standard deviation) 1.1 ± 0.2 mg/L, 1,000-fold above the EC50(LMV). Mean FTR, CLI and AI were 9 ± 1%, 35 ± 6% and 4 ± 2% respectively. For MBV, the mean FC was 1.4 ± 0.2 mg/L, 28-fold above the EC50(MBV). Mean FTR, CLI and AI were 10 ± 1%, 50 ± 7% and 2 ± 1% respectively.

Conclusions: Drugs' concentrations in the fetal side should be in the range for in utero treatment of fetuses infected with CMV as the mean FC was superior to the EC50 for both molecules.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232140PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192425PMC
July 2020

Severe and progressive neuronal loss in myelomeningocele begins before 16 weeks of pregnancy.

Am J Obstet Gynecol 2020 08 10;223(2):256.e1-256.e9. Epub 2020 Apr 10.

Department of Obstetrics and Maternal-Fetal Medicine, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University; EHU FETUS, Université de Paris and IMAGINE Institute. Electronic address:

Background: Despite undisputable benefits, midtrimester prenatal surgery is not a cure for myelomeningocele (MMC): residual intracranial and motor deficits leading to lifelong handicap question the timing of prenatal surgery. Indeed, the timing and intensity of intrauterine spinal cord injury remains ill defined.

Objective: We aimed to describe the natural history of neuronal loss in MMC in utero based on postmortem pathology.

Study Design: Pathology findings were analyzed in 186 cases of myelomeningocele with lesion level between S1 and T1. Using a case-control, cross-sectional design, we investigated the timewise progression and topographic extension of neuronal loss between 13 and 39 weeks. Motor neurons were counted on histology at several spinal levels in 54 isolated MMC meeting quality criteria for cell counting. These were expressed as observed-to-expected ratios, after matching for gestational age and spinal level with 41 controls.

Results: Chiari II malformation increased from 30.7% to 91.6% after 16 weeks. The exposed spinal cord displayed early, severe, and progressive neuronal loss: the observed-to-expected count dropped from 17% to ≤2% after 16 weeks. Neuronal loss extended beyond the lesion to the upper levels: in cases <16 weeks, the observed-to-expected motor neuron count was 60% in the adjacent spinal cord, decreasing at a rate of 16% per week. Progressive loss was also found in the upper thoracic cord, but in much smaller proportions. The observed-over-expected ratio of motor neurons was not correlated with the level of myelomeningocele.

Conclusions: Significant neuronal loss is present ≤16 weeks in the exposed cord and progressively extends cranially. Earlier prenatal repair (<16 weeks) could prevent Chiari II malformation in 69.3% of cases, rescue the 17% remaining motor neurons in the exposed cord, and prevent the extension to the upper spinal cord.
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http://dx.doi.org/10.1016/j.ajog.2020.02.052DOI Listing
August 2020

Is laterality of congenital diaphragmatic hernia a reliable prognostic factor? French national cohort study.

Prenat Diagn 2020 07 8;40(8):949-957. Epub 2020 May 8.

Department of Obstetrics and Gynecology, Hôpitaux universitaires de Strasbourg, Strasbourg, France.

Objectives: The objective of this study was to assess whether the laterality of congenital diaphragmatic hernia (CDH) was a prognostic factor for neonatal survival.

Methods: This was a cohort study using the French national database of the Reference Center for Diaphragmatic Hernias. The principal endpoint was survival after hospitalization in intensive care. We made a comparative study between right CDH and left CDH by univariate and multivariate analysis. Terminations and stillbirths were excluded from analyses of neonatal outcomes.

Results: A total of 506 CDH were included with 67 (13%) right CDH and 439 left CDH (87%). Rate of survival was 49% for right CDH and 74% for left CDH (P < .01). Multivariate analysis showed two factors significantly associated with mortality: thoracic herniation of liver (OR 2.27; IC 95% [1.07-4.76]; P = .03) and lung-to-head-ratio over under expected (OR 2.99; IC 95% [1.41-6.36]; P < .01). Side of CDH was not significantly associated with mortality (OR 1.87; IC 95% [0.61-5.51], P = .26).

Conclusion: Rate of right CDH mortality is more important than left CDH. Nevertheless after adjusting for lung-to-head-ratio and thoracic herniation of liver, right CDH does not have a higher risk of mortality than left CDH.
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http://dx.doi.org/10.1002/pd.5706DOI Listing
July 2020

Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains.

Microorganisms 2020 Jan 25;8(2). Epub 2020 Jan 25.

EHU 7328 PACT, 75015 Paris, France.

Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage.

Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected ( = 13) and moderately affected ( = 8), and 5 were uninfected controls. The respective magnitude of infected cells, immune cells (CD8, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified by quantitative imaging analysis.

Results: Quantities of CD8, plasma cells, NK cells, macrophages, and HCMV cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all values < 0.05). A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis.

Conclusions: The higher expression of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells. These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions. The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis.
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http://dx.doi.org/10.3390/microorganisms8020176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074756PMC
January 2020

Quantifying the Burden of Congenital Cytomegalovirus Infection With Long-term Sequelae in Subsequent Pregnancies of Women Seronegative at Their First Pregnancy.

Clin Infect Dis 2020 Oct;71(7):1598-1603

Paris Descartes University, Paris, France.

Background: In women seronegative before pregnancy, congenital cytomegalovirus (cCMV)-related sequelae are exclusively seen in those infected in the first trimester of pregnancy. Following a maternal primary infection in the first trimester, up to 30% of infected neonates suffer long-term sequelae. Maternal parity is an established risk factor of cCMV in previously seronegative women. Our objective was to quantify, in a population of women seronegative at their first pregnancy, the risk of cCMV and related sequelae following primary infections in the first trimester in subsequent pregnancies.

Methods: There were 739 women seronegative at their first pregnancy who had at least 1 of 971 subsequent pregnancies and deliveries managed at our institution. All women had CMV immunoglobin (Ig) G and IgM testing at 11-14 weeks of each pregnancy.

Results: Between 2 consecutive pregnancies, 15.6% (115/739) of women seroconverted. Of these seroconversions, 29% (33/115) occurred in the periconceptional period or in the first trimester. The risks for cCMV and related sequelae (neurologic and/or hearing loss) following a maternal infection in the first trimester were, respectively, 24- and 6-fold higher (risk ratios, 24 [95% confidence interval {CI}, 10.8-62.3] and 6 [95% CI 1.5-24], respectively) than in the general pregnant population. Of all primary maternal infections and fetal infections in the first trimester, 88% (29/33) and 92% (11/12), respectively, occurred when the inter-pregnancy interval was ≤2 years.

Conclusions: Women seronegative at their first pregnancy with a subsequent pregnancy within 2 years have the highest risk of delivering a child with cCMV-related sequelae. These women should be made aware of the risk and given the opportunity of serology screening in the first trimester.
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http://dx.doi.org/10.1093/cid/ciz1067DOI Listing
October 2020

Fetal Cystoscopy and Vesicoamniotic Shunting in Lower Urinary Tract Obstruction: Long-Term Outcome and Current Technical Limitations.

Fetal Diagn Ther 2020 9;47(1):74-83. Epub 2019 Aug 9.

Department of Obstetrics, Fetal Medicine and Surgery, Necker-Enfants Malades Hospital, APHP, Paris, France,

Background: In utero therapeutic approaches for lower urinary tract obstruction (LUTO) have been developed to salvage the fetal kidney function.

Objective: The aim of this work was to report the long-term survival, nephrological, and urological outcome of children treated prenatally for LUTO using operative fetal cystoscopy (FC) and vesicoamniotic shunting (VAS) or both.

Methods: A retrospective study of 48 procedures (23 FC, 25 VAS) was performed on 33 patients (between 2008 and 2018). Reviewed data included prenatal management and clinical follow-up by a pediatric nephrologist and a pediatric urologist. Both intention-to-treat and per-protocol analyses were conducted.

Results: The median follow-up was 3.6 years (0.5-7) for FC and 2.5 years (1.1-5.1) for VAS. There was no difference between FC and VAS in terms of survival (92 vs. 83%, p = 1), complication rate (74 vs. 92%, p = 0.88), or chronic kidney disease (58 vs. 50%, p = 1). The number of procedures was higher in the VAS group: 1.7 (1-3) versus 1.1 (1-2), p = 0.01. With a 30% rate of technical failure, FC added diagnostic value in 3 out of 21 cases.

Conclusions: No difference was found between FC and VAS regarding survival, long-term kidney function, or urological outcome. Despite overly optimistic reports on FC, it lacks reproducibility due to posterior-urethra inadequate visualization and inappropriate instrumentation.
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http://dx.doi.org/10.1159/000500569DOI Listing
November 2020

SOX3 duplication: A genetic cause to investigate in fetuses with neural tube defects.

Prenat Diagn 2019 10 9;39(11):1026-1034. Epub 2019 Aug 9.

Department of Histology Embryology and Cytogenetics, Necker-Enfants Malades Hospital, APHP, Paris, France.

Objective: Neural tube defects (NTDs) are one of the most common congenital anomalies caused by a complex interaction of many genetic and environmental factors. In about 10% of cases, NTDs are associated with genetic syndromes or chromosomal anomalies. Among these, SOX3 duplication has been reported in some isolated cases. The phenotype associated with this microduplication is variable and includes myelomeningocele (MMC) in both sexes as well as hypopituitarism and cognitive impairment in males. In order to determine the prevalence of this anomaly in fetuses with MMC, a retrospective cohort of fetuses with MMC was analyzed by quantitative PCR (qPCR) targeting SOX3 locus.

Methods: The detection of an SOX3 microduplication by chromosomal microarray analysis (CMA) in two female fetuses with MMC prompted us to analyze retrospectively by qPCR this gene in a cohort of 53 fetuses with MMC.

Results: In addition to our two initial cases, one fetus harboring an Xq27.1q28 duplication that encompasses the SOX3 gene was detected.

Conclusion: Our data demonstrate that SOX3 duplication is a genomic imbalance involved in the pathogenesis of NTDs. In addition, our survey highlights the importance of CMA testing in fetuses with NTDs to enable genetic counseling upstream of any considerations of in utero fetal surgery.
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http://dx.doi.org/10.1002/pd.5523DOI Listing
October 2019

Fetoscopic Release of Amniotic Bands Causing Limb Constriction: Case Series and Review of the Literature.

Fetal Diagn Ther 2019 6;46(4):246-256. Epub 2019 Feb 6.

Fetal Medicine Unit, Department of Obstetrics and Fetal Medicine, Necker-Enfants Malades Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

The aim of this study was to review the perioperative complication rates and neonatal outcomes after fetoscopic release of amniotic bands that caused bilateral limb constrictions. We present 5 cases of limb constriction by amniotic bands occurring spontaneously or following fetoscopic surgery and also include a review of 21 previously published cases. The cases were analyzed for indication, surgical technique, and postoperative follow-up. In our population and the literature, the majority of the children acquired a functional limb (75%), with few perioperative complications (15%). Fetal morbidity was mainly linked to the consequences of preterm premature rupture of the membranes (38.4%) and preterm birth (34.7 GW). The mortality rate was low (7.7%). This review only describes amniotic bands causing limb constriction, and illustrates that fetoscopic surgery for their release is technically feasible with an acceptable perioperative complication rate. However, the 75% success rate is very likely to be an overestimation of the true success rate. In view of these observations we cannot recommend treatment for cases where the fetus has been extensively affected by the bands. We believe, however, that we could consider this technique for a fraction of amniotic band syndrome cases isolated to the limb constrictions. This kind of surgery should be proposed as a potential treatment for amniotic band syndrome.
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http://dx.doi.org/10.1159/000495505DOI Listing
March 2020

Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy.

Clin Infect Dis 2019 10;69(9):1526-1532

Equipe d'Accueil, Paris Descartes University, Sorbonne Paris CitéArchet, France.

Background: The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools.

Methods: We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months.

Results: We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72-42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0-6.49) after an infection in the second trimester, and 0 (95% CI 0-11.95) after an infection in the third trimester (P < .0001).

Conclusions: These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.
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http://dx.doi.org/10.1093/cid/ciy1128DOI Listing
October 2019

Successful in utero transesophageal pacing for severe drug-resistant tachyarrhythmia.

Am J Obstet Gynecol 2018 10 25;219(4):320-325. Epub 2018 Jul 25.

Obstetrics and Maternal Fetal Medicine, Hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France.

Sustained fetal tachyarrhythmia can evolve into a life-threatening condition in 40% of cases when hydrops develops, with a 27% risk of perinatal death. Several antiarrhythmic drugs can be given solely or in combination to the mother to achieve therapeutic transplacental concentrations. Therapeutic failure could lead to progressive cardiac insufficiency and restrict therapeutic options to either elective delivery or direct fetal administration of antiarrhythmic drugs, which may increase the risk of death. We report for the first time successful fetal transesophageal pacing to treat a hydropic fetus with drug-resistant tachyarrhythmia.
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http://dx.doi.org/10.1016/j.ajog.2018.07.018DOI Listing
October 2018

Clarification of INTERGROWTH-21st newborn birthweight standards - Authors' reply.

Lancet 2018 05 17;391(10134):1996. Epub 2018 May 17.

Nuffield Department of Women's & Reproductive Health and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford OX2 6HG, UK.

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http://dx.doi.org/10.1016/S0140-6736(18)31067-5DOI Listing
May 2018

Comparison of biochemical analysis of fetal serum and fetal urine in the prediction of postnatal renal outcome in lower urinary tract obstruction.

Prenat Diagn 2018 Apr 12. Epub 2018 Apr 12.

Department of Biochemistry and Hormonology, Robert Debré Hospital, AP-HP, Paris, France.

Objectives: To compare the prognostic value of fetal serum biochemistry and fetal urine biochemistry in predicting renal outcome in lower urinary tract obstruction (LUTO).

Methods: We retrospectively studied renal outcome following a prenatal diagnosis of LUTO in cases for which both fetal blood and fetal urine were sampled. We classified the renal outcome as either "favorable," when postnatal renal function was normal, or "adverse," in the case of postnatal chronic renal failure or when renal histological lesions were present at autopsy in the case of termination of pregnancy. A prognostic model was constructed for urine and serum separately. β2-Microglobulin was the only remaining independent predictor in fetal urine. β2-Microglobulin in serum and urine were compared by using receiver operating characteristic curves.

Results: In the 50 cases included, the rate of adverse outcome was 34 of 50(68%): autopsy confirmed severity of renal disease in all 27 cases who underwent termination of pregnancy, and among the 23 live born children, 7 developed renal failure. Fetal serum and urine markers were all significantly associated with renal outcome (P < .01). The receiver operating characteristic curves for fetal serum and fetal urinary β2-microglobulin were similar (area under the curve = 0.908 versus 0.909, P = .96).

Conclusion: Fetal serum biochemistry and fetal urine biochemistry are of similar prognostic value in predicting postnatal renal outcome in fetuses with LUTO.
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http://dx.doi.org/10.1002/pd.5263DOI Listing
April 2018

Bronchopulmonary sequestrations in a paediatric centre: ongoing practices and debated management.

Eur J Cardiothorac Surg 2018 08;54(2):246-251

Deparmtent of Pediatric Surgery, AP-HP, Hopital Necker-Enfants malades, Paris, France.

Objectives: Bronchopulmonary sequestration (BPS) is the second most common congenital lung malformation, with an estimated incidence ranging from 0.15% to 1.8%. Surgical treatment is elective in patients with symptoms, but the management of asymptomatic patients remains controversial.

Methods: We retrospectively reviewed the medical records of 99 patients treated for BPS in our institution from January 2000 to December 2015. BPS was diagnosed prenatally in 86 (87%) cases. Management throughout this 16-year period was based on 3 interventions: resection by open surgery, resection by thoracoscopy and embolization.

Results: Among the 86 patients with a prenatal diagnosis of BPS, 14% had symptoms at birth and 10% had delayed symptoms at a median delay of 8 months (4.5-42 months). For the other 13 patients, symptoms occurred at a median age of 34 months (range 3-96 months). Embolization of the feeding vessel was performed in 46 patients with 6 secondary surgical resections (13%). A total of 59 patients were operated on: 23 cases by open surgery and 36 cases by thoracoscopy. The mean hospitalization stay was significantly longer for open surgery: 4.8 ± 1.3 days vs 4.1 ±1.5 days, respectively (P = 0.03). Differences in hospitalization stay were also found between asymptomatic and symptomatic patients: 3.5 ± 1.2 vs 5.1 ±1.6 days, respectively (P = 0.002). Two of the operated patients died.

Conclusions: When surgery is chosen, thoracoscopy appears to be a valuable procedure. A better understanding of the natural history of BPS is still needed to define the optimal management and the respective roles of surgery, embolization or non-interventional follow-up.
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http://dx.doi.org/10.1093/ejcts/ezy049DOI Listing
August 2018

Twin-twin transfusion syndrome - What we have learned from clinical trials.

Semin Fetal Neonatal Med 2017 12 6;22(6):367-375. Epub 2017 Nov 6.

Obstetrics and Maternal-Fetal Medicine, Hôpital Necker Enfants Malades, AP-HP, Paris, France; EA7328, Faculté de Medicine Paris Descartes, Paris, France. Electronic address:

Monochorionic twin pregnancies are at increased risk for adverse outcome compared to dichorionic twin pregnancies and singletons. Monochorionic-specific complications include twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence, single intrauterine fetal demise and its consequences on the co-twin, and selective intrauterine growth restriction. Whereas the natural history of monochorionic-specific complications carries a high risk of fetal death or severe neurologic disability, a framework now exists, based on well-designed clinical trials, for optimal treatment of these entities. Fetoscopic selective laser coagulation of anastomotic vessels on the chorionic plate has been clearly demonstrated to improve survival and neurologic outcomes for Quintero stage ≥2 TTTS. However, many challenges remain unsolved, the most important of which is preterm premature rupture of membranes. Further improvement in the outcomes of monochorionic pregnancies will require improvements in the rate of premature delivery, and improved diagnosis and treatment strategies for early and late onset TTTS.
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http://dx.doi.org/10.1016/j.siny.2017.08.005DOI Listing
December 2017

Impact on spina bifida screening of shifting prenatal Down syndrome maternal serum screening from the second trimester to the first.

Prenat Diagn 2017 Jul 7;37(7):673-679. Epub 2017 Jun 7.

Department of Biochemistry-Hormonology, Robert Debré Hospital, AP-HP, Paris, France.

Objectives: Shifting screening for trisomy 21 to the first trimester has resulted in the loss of maternal serum alpha-fetoprotein screening for spina bifida. The aim of this study was to study the impact on open spina bifida prenatal screening.

Study Design: We reviewed prenatally diagnosed cases of spina bifida over three years: 2009 (only second-trimester screening, MSM2T), 2010 (transient period) and 2011 (majority first-trimester screening, MSM1T). Cases were assigned to three groups based on maternal serum markers (MSM2T, MSM1T and 'not performed'). Gestational age at diagnosis of spina bifida was compared between these three groups and between the years 2009 and 2011.

Results: Median gestational ages at diagnosis of the 742 spina bifida cases between the three groups were 22 weeks [18 -23], 22  weeks [21 -23] and 21  weeks [14 -23], respectively (P < 0.005). The diagnosis was made at 14-20 weeks in 34.7% for MSM2T group versus 8.5% for MSM1T (P < 0.001). Spina bifida diagnosis at 14-20 weeks declined from 38.8% in 2009 to 13.3% in 2011 (P < 0.001).

Conclusion: Loss of maternal serum alpha-fetoprotein had a tangible effect on the gestational age at diagnosis of spina bifida and resulted in a decrease of 25% of cases of spina bifida detected before 20 weeks. © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.5064DOI Listing
July 2017

Discordances Between Pre-Natal and Post-Natal Diagnoses of Congenital Heart Diseases and Impact on Care Strategies.

J Am Coll Cardiol 2016 08;68(9):921-30

Unité Médico-Chirurgicale de Cardiologie Congénitale et Pédiatrique, Centre de Référence Malformations Cardiaques Congénitales Complexes, M3C, Hôpital Necker Enfants Malades, Assistance publique hôpitaux de Paris, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Background: Pre-natal diagnosis of congenital heart disease (CHD) allows anticipation of urgent neonatal treatment and provides adequate information to the parents on cardiac outcomes.

Objectives: This study sought to analyze the discordances between expert fetal cardiac diagnosis and final diagnosis of CHD and their impact on neonatal and long-term care strategies.

Methods: We included 1,258 neonates with a pre-natally diagnosed CHD and 189 fetopsies following termination of pregnancy at our tertiary center over a 10-year period. Pre-natal echocardiographic and final diagnoses were compared.

Results: For live births, we identified 368 (29.3%) discordances between pre- and post-natal diagnoses. The pre-natal diagnosis was different from the post-natal diagnosis in 36 cases (2.9%) and partially different with a major impact on neonatal treatment of the CHD in 97 cases (7.7%). In 235 cases (18.7%), the diagnosis was partially different with no impact on neonatal planned treatment. The discordances had a negative impact on late care strategy in 62 cases (4.9%): more complex CHD that was unsuitable for biventricular repair, leading to unplanned compassionate care, additional surgery or increase of the complexity level of the Aristotle score. A positive impact was found in 31 cases (2.5%): less complex CHD that allowed biventricular repair, fewer surgical procedures, or decrease of the complexity of the Aristotle score. For 275 patients (21.9%), there was no impact on late care strategy. Of the 872 terminations of pregnancy and intrauterine fetal deaths, 189 fetopsies were available: 16 (8.5%) different diagnoses, 27 (14.3%) major differences, and 60 (31.7%) minor differences.

Conclusions: Correcting fetal cardiac diagnosis after birth can lead to significant changes in neonatal (10.6%) and late (7.4%) care strategies. Tools should be developed to try to improve the accuracy of pre-natal diagnosis of CHD. Clinicians should be cautious when predicting required treatment and outcomes during pre-natal counseling.
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http://dx.doi.org/10.1016/j.jacc.2016.05.087DOI Listing
August 2016

In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study.

Am J Obstet Gynecol 2016 Oct 13;215(4):462.e1-462.e10. Epub 2016 Apr 13.

Equipe d'Accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Maternité, Unité de Médecine Fœtale, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France. Electronic address:

Background: Congenital infection with human cytomegalovirus is a major cause of morbidity and mortality. A randomized controlled trial showed that high-dosage valacyclovir prevents cytomegalovirus disease in transplant recipients. Fetuses showing ultrasound features of infection are at high risk of being symptomatic at or before birth. In a pilot study, oral administration of high-dosage valacyclovir to mothers significantly decreased viral load and produced therapeutic concentrations in the blood of infected fetuses. A randomized controlled trial comparing prenatal treatment with valacyclovir against placebo in infected fetuses failed to recruit because women declined randomization. Randomized controlled trials in fetal medicine have often proven unacceptable by women who decline termination of pregnancy and are not prepared to resign themselves to the odds of the natural history of the disease.

Objective: We evaluated the efficacy of oral valacyclovir, 8 g daily, for pregnant women carrying a symptomatic cytomegalovirus-infected fetus, targeting a high-risk group for developing both neurosensory and neurological impairment.

Study Design: We designed a multicenter, open-label, phase II study with 1 arm, using one of Simon's optimal 2-stage designs. Symptomatic fetuses were defined by the presence of measurable extracerebral or mild cerebral ultrasound symptoms. They were treated in utero from prenatal diagnosis at a median of 25.9 weeks' gestation until delivery or termination of pregnancy. Fetuses with severe brain anomalies on ultrasound were not included as were cases completely asymptomatic at presentation, because treatment was unlikely to modify either outcome. The primary endpoint was the proportion of asymptomatic neonates born to treated mothers.

Results: At the interim analysis, 8 of 11 women delivered an asymptomatic neonate (required: ≥7). In step 2, 32 additional cases were included for a total of 43; the final number of asymptomatic neonates was 34, more than the 31 required to indicate efficacy according to the Simon 2-stage design. They remained asymptomatic at 12 months. High-dosage valacyclovir given for a median of 89 days to pregnant women carrying a moderately infected fetus was efficient at giving birth to asymptomatic neonates. Fetal blood viral loads decreased and platelet counts increased, both significantly (P = .01 and P < .001, respectively), between treatment initiation and birth after treatment completion, regardless of duration of fetal infection. Compared with a historical cohort obtained by a metaanalysis of the literature, the use of valacyclovir (8 g daily) significantly increased the proportion of asymptomatic neonates from 43% without treatment to 82% with treatment. Although the pill burden was high (16 pills a day) adherence to treatment was >90%. Finally, valacyclovir at this high dosage was extremely well tolerated.

Conclusion: Our results indicate that high-dosage valacyclovir given in pregnancy is effective for improving the outcome of moderately symptomatic infected fetuses. Although this study is not a randomized controlled trial, this is the first study reporting the efficacy of an antiviral drug to treat cytomegalovirus-infected fetuses. Moreover, this first study will allow new trials to be conducted, using valacyclovir as a baseline safe and effective treatment in pregnancy, to be compared to the new emerging and more potent anticytomegalovirus drugs that have not currently been tested in pregnancy.
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http://dx.doi.org/10.1016/j.ajog.2016.04.003DOI Listing
October 2016

Twin-to-Twin Transfusion Syndrome: From Observational Evidence to Randomized Controlled Trials.

Twin Res Hum Genet 2016 06 14;19(3):268-75. Epub 2016 Apr 14.

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

Fetoscopic surgery is widely accepted as the preferred first-line treatment for twin-twin transfusion syndrome (TTTS). Nonetheless, the broad diffusion of this technique relies on a single multicentric-randomized trial. We hereby question this trial in a post-hoc Bayesian analysis, submitting its results to several scenarios comprising the alternative published non-randomized literature and pessimistic opinions regarding this surgery. Furthermore, we also discuss further refinements in indications, questioning potential alternatives in early stages of the disease.
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http://dx.doi.org/10.1017/thg.2016.22DOI Listing
June 2016

The Impact of Entry Technique and Access Diameter on Prelabour Rupture of Membranes Following Primary Fetoscopic Laser Treatment for Twin-Twin Transfusion Syndrome.

Fetal Diagn Ther 2016 14;40(2):100-9. Epub 2016 Apr 14.

Mater Mothers' Hospital, University of Western Australia, Perth, Australia.

Objective: To evaluate the impact of entry method and access diameter at fetoscopic surgery for twin-twin transfusion syndrome in twin pregnancies with at least one survivor. The outcomes evaluated were prelabour rupture of membranes (PROM) and birth <4 weeks, preterm birth (PTB) <28 weeks, and latency to birth.

Methods: A retrospective analysis of prospectively collected data of consecutive laser procedures from 6 centers was performed. Three entry methods (sheath + trocar; cannula + trocar; cannula + Seldinger) and 6 access diameters (2.3, 3.0, 3.3, 3.5, 3.8, 4.0 mm) were used. Exclusion criteria were subsequent invasive interventions, termination of pregnancy or double fetal death after laser. Multivariate analysis was performed to determine risk factors for the study outcomes.

Results: Six hundred seventy three fetoscopic laser cases were analyzed. The use of different entry methods and access diameters did not affect PROM or birth <4 weeks, or latency from laser to birth. Access diameter was associated with PTB <28 weeks. Cervical length was associated with PROM and birth <4 weeks, and latency from laser to birth.

Conclusion: Instrument choice at fetoscopic laser procedures did not affect outcomes <4 weeks. Access diameter may affect the likelihood for PTB <28 weeks. Cervical length is critically associated with obstetrical outcomes following laser surgery.
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http://dx.doi.org/10.1159/000441915DOI Listing
February 2017

Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis.

Am J Obstet Gynecol 2016 09 8;215(3):342.e1-9. Epub 2016 Apr 8.

Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Maternité, Unité de Médecine Fœtale, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.

Background: Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy.

Objective: We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection.

Study Design: We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination.

Results: In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of 23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm(3), and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis (P < .001, P = .001, and P = .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive value for symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively.

Conclusion: Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling.
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http://dx.doi.org/10.1016/j.ajog.2016.03.052DOI Listing
September 2016

A French Approach to Test Fetuses with Ultrasound Abnormalities Using a Customized Microarray as First-Tier Genetic Test.

Cytogenet Genome Res 2015 7;147(2-3):103-10. Epub 2016 Jan 7.

Service d'Histologie-Embryologie-Cytogx00E9;nx00E9;tique, Hx00F4;pital Necker-Enfants Malades, AP-HP, Paris, France.

Cytogenetic microarray analysis is now the first-tier genetic test used in a postnatal clinical setting to explore genomic imbalances in individuals with developmental disability and/or birth defects. However, in a prenatal setting, this technique is not widely implemented, largely because the clinical impact of some copy number variants (CNVs) remains difficult to assess. This limitation is especially true in France where termination of pregnancy for medical reasons may be performed at any stage of gestation. During a period of 15 months, we investigated 382 fetuses presenting with ultrasound anomalies, using a customized microarray designed to avoid the detection of CNVs raising challenges for genetic counseling. After excluding common aneuploidies, 20/374 (5.3%) fetuses had a pathogenic CNV, among which 12/374 (3.2%) could have been detected by karyotyping, whereas 8/374 (2.1%) were cryptic. Within these 374 cases, 300 were ongoing pregnancies at the time of array comparative genomic hybridization (aCGH) testing. For these pregnancies, we detected 18/300 (6%) pathogenic CNVs, among which 6/300 (2%) were cryptic. Using this approach, only 2/300 (0.6%) of the detected CNVs raised difficulties for genetic counseling. This study confirms the added value of this strategy in a prenatal clinical setting to minimize ethical issues for genetic counseling while enhancing the detection of genomic imbalances.
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http://dx.doi.org/10.1159/000442904DOI Listing
August 2016

Evaluation of trainees' ability to perform obstetrical ultrasound using simulation: challenges and opportunities.

Am J Obstet Gynecol 2016 Apr 10;214(4):525.e1-525.e8. Epub 2015 Nov 10.

Department of Obstetrics and Fetal Medicine, Necker-Enfants-Malades Hospital, APHP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; SimECHOle, Ecole de simulation pour l'enseignement et le perfectionnement en échographie, Paris, France.

Background: Evaluation of trainee's ability in obstetrical ultrasound is a time-consuming process, which requires involving patients as volunteers. With the use of obstetrical ultrasound simulators, virtual reality could help in assessing competency and evaluating trainees in this field.

Objective: The objective of the study was to test the validity of an obstetrical ultrasound simulator as a tool for evaluating trainees following structured training by comparing scores obtained on obstetrical ultrasound simulator with those obtained on volunteers and by assessing correlations between scores of images and of dexterity given by 2 blinded examiners.

Study Design: Trainees, taking the 2013 French national examination for the practice of obstetrical ultrasound were asked to obtain standardized ultrasound planes both on volunteer pregnant women and on an obstetrical ultrasound simulator. These planes included measurements of biparietal diameter, abdominal circumference, and femur length as well as reference planes for cardiac 4-chamber and outflow tracts, kidneys, stomach/diaphragm, spine, and face. Images were stored and evaluated subsequently by 2 national examiners who scored each picture according to previously established quality criteria. Dexterity was also evaluated and subjectively scored between 0 and 10. The Raghunathan's modification of Pearson, Filon's z, Spearman's rank correlation, and analysis of variance tests were used to assess correlations between the scores by the 2 examiners and scores of dexterity and also to compare the final scores between the 2 different methods.

Results: We evaluated 29 trainees. The mean dexterity scores in simulation (6.5 ± 2.0) and real examination (5.9 ± 2.3) were comparable (P = .31). Scores with an obstetrical ultrasound simulator were significantly higher than those obtained on volunteers (P = .027). Nevertheless, there was a good correlation between the scores of the 2 examiners judging on simulation (R = 0.888) and on volunteers (R = 0.873) (P = .81).

Conclusion: An obstetrical ultrasound simulator is as good a method as volunteer-based examination for evaluating practical skills in trainees following structured training in obstetrical ultrasound. The threshold for success/failure should, however, be adapted as candidates obtain higher scores on the simulator. Advantages of the obstetrical ultrasound simulator include the absence of location and time constraints without the need to involve volunteers or to interfere with the running of ultrasound clinics. However, an obstetrical ultrasound simulator still lacks the ability to evaluate the trainees' ability to interact with patients.
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http://dx.doi.org/10.1016/j.ajog.2015.10.932DOI Listing
April 2016

First fetal case of the 8q24.3 contiguous genes syndrome.

Am J Med Genet A 2016 Jan 5;170A(1):239-42. Epub 2015 Oct 5.

Department of Histology-Embryology and Cytogenetics, Necker-Enfants Malades Hospital, AP-HP, Paris, France.

Molecular cytogenetics, particularly array-CGH, opened the way to the « genotype first approach » and for the discovery of new micro rearrangement syndromes. This was the case for the 8q24.3 microdeletion syndrome. Here, we describe the phenotype of a fetus with a 8q24.3 deletion. This rare condition has to be considered as a contiguous genes syndrome because its phenotype is generated by the SCRIB and PUF60 adjacent gene endophenotypes. The fetus presented atrioventricular septal defect and hypoplastic aortic arch, facial dysmorphism, microretrognathia, dysmorphic ears, clinodactyly of the 5th digit on both hands, mild rocker bottom feet and abnormal third sacral vertebra. This fetus is the first case where the endophenotype produced by SCRIB gene is absent. This case is compared with the previous published cases.
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http://dx.doi.org/10.1002/ajmg.a.37411DOI Listing
January 2016

Prenatal diagnosis of intra-abdominal cystic lesions by fetal ultrasonography: diagnostic agreement between prenatal and postnatal diagnosis.

Prenat Diagn 2015 Sep 24;35(9):848-52. Epub 2015 Jun 24.

Department of Obstetrics and Fetal Medicine, Hôpital Necker Enfants Malades, Université René Descartes, Paris, France.

Objective: The aim of this study was to assess the diagnostic agreement between the prenatal diagnosis of intra-abdominal cystic lesions made by ultrasound examination and the postnatal diagnosis.

Methods: We reviewed all consecutive cases referred for an anechoic abdominal cyst from 2009 to 2013. Prenatal ultrasound diagnosis was compared with postnatal diagnosis. Prenatal diagnosis was defined as 'correct' if a specific prenatal diagnosis or one of the possible diagnoses was confirmed postnatally, as 'not confirmed' if the postnatal examination revealed no abnormalities and as 'incorrect' if the postnatal diagnosis was different from those suggested prenatally.

Results: Seventy-three cases were included, and prenatal diagnoses were made at a median gestational age of 27 weeks (range: 13-36). Correct diagnoses were made in 66 cases (90.4%), including four in which the lesion resolved spontaneously in utero; two diagnoses were 'not confirmed' postnatally, and one was incorrect (a prenatal diagnosis of intestinal duplication was in fact an anorectal malformation). Postnatal diagnosis was not achieved in four cases: None of them required surgery, and clinical follow-up was favorable. The abdominal cysts were isolated in 52 cases (71%) and associated with other anomalies in 21 cases (29%). Aneuploidies were diagnosed in three cases (all trisomy 21). Eight cases underwent termination of pregnancy; there were no fetal deaths and one neonatal death. Postnatal surgery was performed in 30 out of 65 liveborn infants (46.1%).

Conclusion: Overall diagnostic agreement between prenatal and postnatal diagnosis of fetal intra-abdominal cystic lesions is high.
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http://dx.doi.org/10.1002/pd.4614DOI Listing
September 2015