Antenatal ultrasound features of isolated recurrent copy number variation in 7q11.23 (Williams syndrome and 7q11.23 duplication syndrome).

OBJECTIVE: We aimed to gather fetal cases carrying a 7q11.23 copy number variation (CNV) and collect precise clinical data to broaden knowledge of antenatal features in these syndromes. METHODS: We retrospectively recruited unrelated cases with 7q11.23 deletion, known as Williams-Beuren syndrome (WBS), or 7q11.23 duplication who had prenatal ultrasound findings. We collected laboratory and clinical data, fetal ultrasound, cardiac ultrasound and fetal autopsy reports from 18 prenatal diagnostic centers throughout France. RESULTS: 40 fetuses with WBS were collected and the most common features were intra-uterine growth retardation (IUGR) (70.0%, 28/40), cardiovascular defects (30.0%, 12/40), polyhydramnios (17.5%, 7/40) and protruding tongue (15.0%, 6/40). Fetal autopsy reports were available for 11 cases and were compared with ultrasound prenatal features. Four cases of fetuses with 7q11.23 microduplication were collected and prenatal ultrasound signs were variable and often isolated. CONCLUSION: This work strengthens the fact that 7q11.23 CNVs are associated with a broad spectrum of antenatal presentations. IUGR and cardiovascular defects were the most frequent ultrasound signs. By reporting the biggest series of antenatal WBS, we aim to better delineate distinctive signs in fetuses with 7q11.23 CNVs.

Arabin pessary to prevent adverse perinatal outcomes in twin pregnancies with a short cervix: a multicenter randomized controlled trial (PESSARONE).

BACKGROUND: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial. OBJECTIVE: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix. STUDY DESIGN: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of <35 mm compared pessary placement at 16+0 to 24+0 weeks' gestation with standard care alone. The primary endpoint was a composite of adverse neonatal outcomes, namely peripartum or neonatal death or significant neonatal morbidity before hospital discharge, defined as at least 1 of the following complications: bronchopulmonary dysplasia, intraventricular hemorrhage grade III to IV, periventricular leukomalacia, necrotizing enterocolitis grade II or higher, culture-proven sepsis, and retinopathy requiring treatment. A sample size of 308 pregnancies was planned to ensure 80% power to compare the proportions of women with at least 1 infant with an adverse neonatal outcome. The intention-to-treat analysis after multiple imputation of missing data, was supplemented with a secondary analysis that controlled for gestational age and cervical length, both at inclusion. The primary endpoint was also compared between randomization groups in the per-protocol population, which excluded patients with prespecified major protocol violations (mostly cervical cerclage and/or progesterone after inclusion). Secondary endpoints included preterm birth, spontaneous preterm birth, and pessary side effects. RESULTS: In total, 315 women were randomized to either receive a pessary (n=157) or standard management (n=158). Overall, 10.8% (34 women) of participants had a missing value for the primary endpoint, mostly (79%) because of the lack of paternal consent for neonatal data collection. In the intention-to-treat analysis, the adverse neonatal outcome occurred in 16.8% of the pessary group vs in 22.5% of the control group (risk ratio, 0.69; 95% confidence interval, 0.39-1.23; P=.210). The per-protocol analysis did not show any significant difference between groups (risk ratio, 0.78; 95% confidence interval, 0.47-1.28; P=.320). The occurrence of preterm birth or spontaneous preterm birth did not differ significantly between groups. No serious side effects were associated with pessary use. CONCLUSION: Pessary use in our study did not significantly reduce adverse neonatal outcomes in twin pregnancies with a short cervix.

Who needs prenatal counselling with a pediatric surgeon? Experience from a large tertiary care university hospital.

OBJECTIVES: To describe our experience with prenatal counselling for surgical anomalies in a large volume center. The secondary aim is to suggest a list of prenatal abnormalities warranting counselling by a pediatric surgeon. METHODS: We reviewed all prenatal counselling consultations performed by the pediatric surgery team between January 1st, 2015 and December 31st, 2016. RESULTS: A total of 169 patients or couples had a prenatal consultation with a pediatric surgeon. Prenatal work-up included a fetal MRI in 26% of cases, mainly for digestive and thoracic pathologies (56.1% of cases). Consultation with the pediatric surgeon led mainly to recommendations concerning the place of delivery. Induction for reasons related to the fetal anomaly occurred in 22.2% of cases. Most children were surgically treated within the first year of life (63.5%). Correlation between predicted prognosis and actual status at four years of life was 96.9%. Correlation between prenatal and postnatal diagnosis was 87.4%. CONCLUSIONS: Prenatal counselling by a pediatric surgeon allows couples to obtain clear information on the pathology of their unborn child, giving them greater autonomy in their decision to continue the pregnancy.

Interest of chromosomal microarray analysis in the prenatal diagnosis of fetal intrauterine growth restriction.

OBJECTIVE: The aim of this study is to evaluate the diagnostic utility of prenatal diagnosis using the chromosomal microarray analysis (CMA) for fetuses presenting with isolated or associated intrauterine growth restriction (IUGR). METHOD: We retrospectively included all fetuses with IUGR referred for prenatal testing and studied by rapid fluorescence in situ hybridization (FISH), karyotype, and CMA. RESULTS: Among the 162 IUGR fetuses (78 associated and 84 isolated IUGR) included, 15 had an abnormal FISH result: 10 associated and five isolated fetal IUGRs. Among the 143 fetuses studied by CMA, 10 (7%) presented pathogenic copy number variations (CNVs). All 10 were in the associated fetal IUGR group (10/65 or 15.4%; 95% confidence interval [CI]: 8.4%-26.2%) versus 0/78 in the isolated fetal IUGR group (95% CI: 0%-5.6%). Six fetuses (4.2%) carried variants of unknown significance (VOUS) (three associated and three isolated fetal IUGRs). CONCLUSION: Our study highlights the added value of CMA in the case of associated fetal IUGR with an incremental yield of 6.1% (4/65) over karyotyping. No pathogenic CNVs were reported in the isolated fetal IUGR group. More studies must be conducted to determine when and whether CMA would be wisely indicated in this population.

The diagnosis of rupture of fetal membranes (ROM): a meta-analysis.

AIM: The aim of this study was to compare the performance of tests based on the detection of insulin-like growth factor binding protein 1 (IGFBP-1) and placental α-microglobulin-1 (PAMG-1) in diagnosing rupture of fetal membranes (ROM) across different patient populations. METHODS: A meta-analysis was conducted on prospective observational or cohort studies investigating ROM tests based on the detection of IGFBP-1 and PAMG-1 meeting the following criteria: (1) performance metrics calculated by comparing results to an adequate reference method; (2) sensitivity thresholds of the investigated tests matching those of the currently available tests; (3) study population, as a minimum, included patients between 25 and 37 weeks of gestation. Sensitivities, specificities, and diagnostic odds ratios were calculated. RESULTS: Across all patient populations, the analyzed performance measures of the PAMG-1 test were significantly superior compared with those of the IGFBP-1 test. Of particular clinical relevance, PAMG-1 outperformed IGFBP-1 in the equivocal group, which comprised patients with uncertain rupture of membranes (sensitivity, 96.0% vs. 73.9%; specificity, 98.9% vs. 77.8%; PAMG-1 vs. IGFBP-1 tests, respectively). CONCLUSIONS: Compared with its performance in women with known membrane status, the accuracy of the IGFBP-1 test decreases significantly when used on patients whose membrane status is unknown. In this latter clinically relevant population, the PAMG-1 test has higher accuracy than the IGFBP-1 test.

[Management of isolated increased nuchal translucency: survey among the Pluridisciplinary Centers for Prenatal Diagnosis]. / Prise en charge de l'hyperclarté nucale isolée : enquête auprès des Centres pluridisciplinaires de diagnostic prénatal.

OBJECTIVES: The management for isolated increased nuchal translucency (NT) in the first trimester with a normal karyotype and normal Chromosomal Microarray Analysis (CMA) is not consensual. The aim was to perform a survey among the Pluridisciplinary Centers for Prenatal Diagnosis (CPDPN) in France regarding their management of increased NT in the first trimester. METHODS: We conducted a multicenter descriptive survey between September 2021 and October 2021 among the 46 CPDPNs of France. RESULTS: The response rate was 56.5% (n = 26/46). The NT thickness threshold for which invasive diagnosis testing is performed is 3.0mm in 23.1% of centers (n = 6/26) and 3.5mm in 76.9% of centers (n = 20/26). A CMA was performed alone in 26.9% of centers (n = 7/26) while 7.7% of centers (n = 2/26) did not perform a CMA. The gestational age for the first reference ultrasound scan was 16 to 18 WG in 88.5% of centers (n = 23/26), while it was not performed before 22 WG in 11.5% of centers (n = 3/26). Fetal echocardiography is proposed systematically in 73.1% of centers (n = 19/26). CONCLUSION: There is heterogeneity in the management of increased NT in the first trimester among the CPDPNs in France. In case of increased NT on first trimester ultrasound scan, the NT thickness threshold for which invasive diagnosis testing is performed varies from 3.0 mm or 3.5mm depending on the center. Moreover, CMA and early reference morphological ultrasound scan between 16 and 18 WG were not systematically performed, despite the current data suggesting their interest.

Mothers' perception of prenatal counseling following diagnosis of congenital anomalies of the urinary tract.

Congenital abnormalities of the genitourinary tract are the most common sonographically identified malformations. Although prenatal diagnosis seldom modifies perinatal management, it can cause significant anxiety in parents. We aimed to assess how parents perceived the prenatal counseling they had received in our institution. Using a questionnaire, we evaluated by phone the mothers of 78 children diagnosed prenatally with urological tract anomalies between January 2018 and May 2019. Overall, mothers were satisfied and reassured by the prenatal counseling they received, although 19% of the mothers found the time from diagnosis to specialist consultation to be too long. Forty percent of the responders stated that the most important information they needed to hear during the specialist consultation was management and not diagnosis. Specialist counseling should focus on explaining postnatal management, should be offered as soon as possible, and should include practical aspects, especially concerning outpatient care.

Chronic Stress protection for postnatal dEpREssioN prEvention (SERENE): a protocol for an exploratory study.

INTRODUCTION: The prevalence of postnatal depression (PND) is significant: reaching up to 20% in the general population. In mechanistic terms, the risk of PND lies in an interaction between a maternal psychophysiological vulnerability and a chronic environmental context of stress. On the one hand, repetition of stressor during pregnancy mimics a chronic stress model that is relevant to the study of the allostatic load and the adaptive mechanisms. On the other hand, vulnerability factors reflect a psychological profile mirroring mindfulness functioning (psychological quality that involves bringing one's complete and non-judgemental attention to the present experience on a moment-to-moment basis). This psychological resource is linked to protective and resilient psychic functioning. Thus, PND appears to be a relevant model for studying the mechanisms of chronic stress and vulnerability to psychopathologies.In this article, we present the protocol of an ongoing study (started in May 2017). METHODS AND ANALYSIS: The study is being carried out in five maternities and will involve 260 women. We aim to determine the predictive psychobiological factors for PND emergence and to provide a better insight into the mechanisms involved in chronic stress during pregnancy. We use a multidisciplinary approach that encompasses psychological resources and biophysiological and genetic profiles in order to detect relevant vulnerability biomarkers for chronic stress and the development of PND. To do so, each woman will be involved in the study from her first trimester of pregnancy until 12 months postdelivery. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ile de France III Ethics Committee, France (2016-A00887-44). We aim to disseminate the findings through international conferences and international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03088319; Pre-results.

Vascular uterine abnormalities: Comparison of imaging findings and clinical outcomes.

OBJECTIVE: To retrospectively compare the imaging findings and the outcomes for patients with vascular uterine abnormalities (VUA) and to identify prognostic factors. MATERIAL AND METHODS: Between 2007 and 2012, 38 patients with vaginal bleeding and abnormal ultrasonographic (US) findings consistent with acquired VUA were consecutively included (mean age 31.6 years, range 19-62). Follow-up was 32 months in mean (1-78 months). Seventeen women (44.7%) started bleeding immediately after curettage, spontaneous miscarriage, trophoblastic disease, or section scars, with the remainder starting bleeding after 8 days to 2 years. All US, CT (n=2), MR (n=5) and angiographic (n=26) images were reviewed and compared to medical reports in order to identify severe VUA requiring treatment, and predictive factors. RESULTS: No information about severity was provided by US, MRI or CT. Twelve patients were successfully managed conservatively. Angiography identified 6 non-severe VUA, corresponding to an isolated uterine hyperemia, and 20 severe VUA, corresponding to an association of a nidus and early venous drainage. Recurrences were more often observed for severe VUA (p=0.001). The hemoglobin level was significantly lower (below 11 g/L) in these cases (p=0.004). Recurrences were significantly more frequently observed for patients with history of dilatation and curettage (p=0.02). Hysterectomy was performed for three patients only (8%). Among the women who wished to have children, 14 (77.8%) were pregnant after 9 months in mean (range 2-23). CONCLUSIONS: Recurrence happens more frequently after curettage and in case of anemia or severe VUA findings on angiography, justifying adequate embolization for these patients.

Prolonged and post-term pregnancies: guidelines for clinical practice from the French College of Gynecologists and Obstetricians (CNGOF).

The duration of pregnancy varies between 40(+0) and 41(+3) weeks. Conventionally, and essentially arbitrarily, a pregnancy is considered to be "prolonged" after 41(+0) weeks, but the infant is not considered "post-term" until 42(+0) weeks (Professional consensus). A term birth thus occurs during the period from 37(+0) to 41(+6) weeks. In France, prolonged pregnancies (≥41(+0)weeks) involve 15-20% of pregnant women, and post-term pregnancies (≥42(+0) weeks) approximately 1%. The frequency of post-term pregnancies is very heterogeneous: in Europe and the United States, it ranges from 0.5% to 10% according to country. In prolonged pregnancies, the cesarean section rate-especially the emergency cesarean rate-is multiplied by approximately 1.5 (grade B). From 37(0-6) to 43(0-6) weeks, the risk of perinatal mortality increases regularly, from 0.7‰ to 5.8‰. Meconium aspiration syndrome is responsible for substantial morbidity and mortality, and its incidence increases regularly between 38(+0) and 42(+6) weeks, from 0.24‰ to 1.42‰ (grade B). Similarly, the risks of neonatal acidosis (grade B), 5-min Apgar scores less than 7 (grade B) and admissions to neonatal intensive care (grade B) increase progressively between 38(+0) and 42(+6) weeks. These risks appear to double for post-term growth-restricted newborns (grade C). Ultrasound dating of the pregnancy makes it possible to reduce the risk that it will be incorrectly considered prolonged and that labor will therefore be induced unnecessarily. To harmonize practices, if the crown-rump length (CRL) is correctly measured (this measurement should be taken between 11(+0) and 13(+6) weeks, when CRL should measure from 45 to 84mm), ultrasound dating based on it should be used to determine the official date pregnancy began, regardless of its difference from the date assumed by the patient or estimated based on the date of the last menstrual period. This rule does not apply to pregnancies by IVF, for which the date pregnancy began is defined by the date of oocyte retrieval (Professional consensus). From 37(0-6) to 43(0-6) weeks, the risk of perinatal mortality increases regularly and there is no threshold at which a clear increase in perinatal mortality becomes visible. Fetal monitoring by cardiotocography (CTG) that begins at 41(+0) weeks would cover approximately 20% of women and reduce perinatal morbidity compared with monitoring that begins at 42(+0) weeks (grade C). The frequency recommended for this monitoring ranges between two and three times a week (Professional consensus). For ultrasonography assessment, measurement of the largest fluid pocket is recommended, because measurement of the amniotic fluid index (that is, the sum of the four quadrants) is accompanied by more diagnoses of oligohydramnios, inductions of labor, and cesareans for fetal distress without any improvement in neonatal prognosis (grade A). The practice of assessing the Manning biophysical score increases the number of diagnoses of oligohydramnios and fetal heart rage (FHR) abnormalities and generates an increase in the rates of inductions and cesareans without improving neonatal prognosis. The use of this biophysical score in monitoring prolonged pregnancies is therefore not recommended (grade B). In the absence of a specific disorder, induction of labor can be proposed in patients between 41(+0) and 42(+6) weeks (grade B). Nonetheless, the choice of prolongation beyond above 42(+0) weeks appears to involve an increase in fetal risk, which must be explained to the patient and balanced against the potential disadvantages of induction (Professional consensus). Stripping the membranes can reduce the duration of pregnancy by increasing the number of patients going into labor spontaneously during the week afterward (grade B). Compared to an expectant approach, it does not increase the cesarean section rate (grade A). It reduces recourse to induction by 41% at 41(+0) weeks and by 72% at 42(+0) weeks (grade B), without increasing the risk of either membrane rupture or maternal or neonatal infection (grade B). Used as a tampon or vaginal gel, prostaglandins E2 (PGE2) are an effective method of inducing labor (grade A). They can be used to induce labor successfully, regardless of cervical ripeness (grade A). If misoprostol is chosen, the lowest dose is to be preferred, starting with a vaginal dose of 25µg every 3-6h (grade A). For misoprostol, more powerful studies remain necessary for better defining the doses, routes of administration, tolerance and indications. Misoprostol at any dose is contraindicated in women with uterine scars (grade B). Placement of an intracervical Foley catheter is an effective mechanical means of inducing labor, with less uterine hyperstimulation than prostaglandins and no increase in the cesarean section rate (grade A). Nonetheless, as the risk of infection might be increased, this technique requires more robust evaluation before entering general practice (grade B). In cases of meconium-stained amniotic fluid, pharyngeal aspiration before delivery of the shoulders is not recommended (grade A). The team managing a post-term newborn with meconium-stained amniotic fluid at birth must know how to perform intubation and, if the intubation is not helpful, endotracheal aspiration (grade C) and ventilation with a mask. Routine endotracheal intubation of a vigorous newborn is not recommended (grade A).

Multicentric infantile myofibromatosis: two perinatal cases.

Infantile myofibromatosis, the most common fibrous tumor of infancy, occurs in solitary, multiple, and generalized forms, with similar histology but different clinicopathologic and prognostic implications. This entity is a mesenchymal disorder characterized by the proliferation of fibrous tumors in the skin, muscles, viscera, bones, and subcutaneous tissues. Visceral lesions are associated with significant morbidity and mortality, generally within the first few months of life. They lead to failure to thrive, to infection, hemorrhage, or to the obstruction of vital organs. We describe two cases of multicentric myofibromatosis with significant in utero lesional growth, resulting in one fetal demise and one post-natal demise. To the best of our knowledge, this is the first report of a fetal death secondary to infantile myofibromatosis.