Non-invasive cell-free DNA prenatal screening for trisomy 21 as part of primary screening strategy in twin pregnancies.

OBJECTIVES: The performance of non-invasive prenatal screening using cell-free DNA testing in maternal blood in twin pregnancies is still under-evaluated, while serum marker-based strategies yield poor results. This study aims at assessing the performance of non-invasive prenatal screening for trisomy 21 in twin pregnancies as a first-tier test. The secondary objectives were to assess the failure rate and associated factors. METHODS: This retrospective cohort study included twin pregnancies for which non-invasive prenatal screening using cell-free DNA was performed as the primary screening strategy between May 2017 and October 2019. We used the NIPT VeriSeq® test for in vitro diagnosis and set a fetal fraction cut-off of 4% for monochorionic pregnancies and 8% for dichorionic ones. Clinical data and pregnancy outcome was collected from either physicians or midwives through a questionnaire or were retrieved directly on site. We calculated the performance of non-invasive cell free DNA screening for trisomy 21 and analyzed failure rate and factors. RESULTS: We included 2577 multiple pregnancies among which 1885 (84.8%) were retained after excluding vanishing twins and pregnancies without follow-up. Overall, there were six confirmed trisomy 21 cases (0.32%). For trisomy 21, sensitivity was 100% (95% CI, 61-100%) and the false-positive rate 0.2% (95% CI, 0.07-0.6%). The primary failure rate was 4.6% with 4% due to insufficient fetal fraction. After a new blood draw (59.8% of failed cases), failure rate was only 1.5%. Body mass index and chorionicity were significantly correlated with the risk of failure. CONCLUSION: This study adds further evidence on the high performance of NIPS in twins, as part of the primary screening strategy for trisomy 21, at an extremely low false-positive rate. This article is protected by copyright. All rights reserved.

Impact of variants of SARS-CoV-2 on obstetrical and neonatal outcomes.

BACKGROUND: SARS-CoV-2 can lead to several types of complications during pregnancy. Variant surges are associated with different severities of disease. Few studies have compared the clinical consequences of specific variants on obstetrical and neonatal outcomes. Our goal was to evaluate and compare disease severity in pregnant women and obstetrical or neonatal complications between variants of SARS-CoV-2 that have circulated in France over a two-year period (2020-2022). METHOD: This retrospective cohort study included all pregnant women with a confirmed SARS-CoV-2 infection (positive naso-pharyngeal RT-PCR test) from March 12, 2020 to January 31, 2022, in three tertiary maternal referral obstetric units in the Paris metropolitan area, France. We collected clinical and laboratory data for mothers and newborns from patients' medical records. Variant identification was either available following sequencing or extrapolated from epidemiological data. RESULTS: There were 234/501 (47%) Wild Type (WT), 127/501 (25%) Alpha, 98/501 (20%) Delta, and 42/501 (8%) Omicron. No significative difference was found regarding two composite adverse outcomes. There were significantly more hospitalizations for severe pneumopathy in Delta variant than WT, Alpha and Omicron respectively (63% vs 26%, 35% and 6%, p<0.001), more frequent oxygen administration (23% vs 12%, 10% and 5%, p = 0,001) and more symptomatic patients at the time of testing with Delta and WT (75% and 71%) versus Alpha and Omicron variants (55% and 66% respectively, p<0.01). Stillbirth tended to be associated with variants (p = 0.06): WT 1/231 (<1%) vs 4/126 (3%), 3/94 (3%), and 1/35 (3%) in Alpha, Delta and Omicron cases respectively. No other difference was found. CONCLUSION: Although the Delta variant was associated with more severe disease in pregnant women, we found no difference regarding neonatal and obstetrical outcomes. Neonatal and obstetrical specific severity may be due to mechanisms other than maternal ventilatory and general infection.

New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection. METHODS: This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score. RESULTS: In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases. CONCLUSION: Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

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

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

[Reprint of: Severe pre-eclampsia: guidelines for clinical practice from the French Society of anesthesiology and intensive care (SFAR) and the French College of gynaecologists and obstetricians (CNGOF)]. / Republication de : recommandations formalisées d'experts. Prise en charge de la patiente avec une pré-éclampsie sévère­RFE communes Société française d'anesthésie-réanimation (SFAR)­Collège national des gynécologues et obstétriciens français (CGNOF).

OBJECTIVE: To provide national guidelines for the management of women with severe preeclampsia. DESIGN: A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology. RESULTS: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. CONCLUSIONS: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia.

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

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

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

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

Successful use of a Bakri Tamponade Balloon in the treatment of puerperal uterine inversion during caesarean section.

Acute puerperal inversion of the uterus is a rare life-threatening obstetric emergency, especially during caesarean section. We present the case of a 30-year-old patient with acute puerperal inversion of the uterus that occurred during placental removal. After a quick reversion of the uterus, an immediate postpartum haemorrhage (PPH) due to massive uterine atony was observed. This atony impacted the whole uterus, with a very thin uterine myometrium. The use of a Bakri Tamponade Balloon use allowed treating extreme uterine atony, immediately stop haemorrhage, and prevent a possible risk of immediate recurrence.