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

Abstract

Objectives: The performance of non-invasive prenatal screening using cell-free DNA testing of maternal blood in twin pregnancy is underevaluated, while serum marker-based strategies yield poor results. This study aimed to assess the performance of non-invasive prenatal screening for trisomy 21 in twin pregnancy as a first-tier test. Secondary objectives were to assess its failure rate and factors associated with failure.

Methods: This retrospective cohort study included twin pregnancies in 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 were collected from physicians or midwives via a questionnaire or were retrieved directly on-site. We calculated the performance of non-invasive cell-free DNA screening for trisomy 21, analyzed its failure rate and assessed potentially associated factors.

Results: Among 1885 twin pregnancies with follow-up, there were six (0.32%) confirmed cases of trisomy 21. The sensitivity of non-invasive prenatal screening for trisomy 21 was 100% (95% CI, 54.1-100%) and the false-positive rate was 0.23% (95% CI, 0.06-0.59%). The primary failure rate was 4.6%, with 4.0% being due to insufficient fetal fraction. A successful result was obtained for 65.4% of women who underwent a new blood draw, reducing the overall failure rate to 2.8%. Maternal body mass index, gestational age at screening as well as chorionicity were significantly associated with the risk of failure.

Conclusion: This study provides further evidence of the high performance, at an extremely low false-positive rate, of non-invasive prenatal screening in twins as part of a primary screening strategy for trisomy 21. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Performances of two rapid LAMP-based techniques for the intrapartum detection of Group B Streptococcus vaginal colonization

Abstract

Purpose: Group B Streptococcus (GBS) is the leading cause of invasive infections in newborns. The prevention of GBS neonatal disease relies on the administration of an intrapartum antibiotic prophylaxis to GBS-colonized women. In recent years, rapid intrapartum detection of GBS vaginal colonization using real-time nucleic acid amplification tests (NAATs) emerged as an alternative to antenatal culture screening methods.

Methods: We compared the performances of two loop-mediated isothermal amplification (LAMP) tests, the Ampliflash® GBS and the PlusLife® GBS tests, to standard culture for GBS detection in vaginal specimens from pregnant women. The study was conducted from April to July 2023 in a French hospital of the Paris area.

Results: A total of 303 samples were analyzed, including 85 culture-positive samples (28.1%). The Ampliflash® GBS test and the PlusLife® GBS tests gave a result for 100% and 96.3% tests, respectively. The performances of the tests were as follows: sensitivity 87.1% (95% confidence interval (CI) 78.3-92.6) and 98.7% (95% CI 93.0-99.8), specificity 99.1% (95% CI 96.7-99.8), and 91.9% (95% CI 87.3-95.0), respectively. False negative results of the Ampliflash® GBS test correlated with low-density GBS cultures. Time-to-results correlated with GBS culture density only for the PlusLife® GBS test (p < 0.001).

Conclusion: Both techniques provide excellent analytical performances with high sensitivity and specificity together with a short turnaround time and results available in 10 to 35 min. Their potential to further reduce the burden of GBS neonatal disease compared with antenatal culture screening needs to be assessed in future clinical studies.

Comparison of pregnancy outcomes after bariatric surgery by sleeve gastrectomy versus gastric bypass

Abstract

Objective: Bariatric surgery has an impact on subsequent pregnancies, in particular an association between gastric bypass and small for gestational age. Knowledge is lacking on whether sleeve gastrectomy is associated with more favorable pregnancy outcomes. This study aimed to compare the impact of sleeve gastrectomy and Roux-en-Y gastric bypass on the incidence of small for gestational age (SGA), and of adverse pregnancy outcomes.

Study design: We conducted a retrospective study in a single reference center, including all patients with a history of sleeve or bypass who delivered between 2004 and 2021 after their first pregnancy following bariatric surgery. We compared the incidence of SGA, intrauterine growth retardation, preterm delivery and adverse maternal outcomes between patients who had sleeve versus bypass.

Results: Of 244 patients, 145 had a sleeve and 99 had a bypass. The proportion of SGA < 10th percentile did not differ between the two groups (38/145 (26.2 %) vs 22/99 (22.22 %), respectively, p = 0.48). Preterm birth < 37 WG was lower in the sleeve group (5/145 (3.45%) vs 12/99 (12.12 %) in the bypass group (p = 0.01), as well as NICU hospitalizations (3 (2.07%) vs 12/99 (12.12%), p < 0.01). There was no difference regarding adverse maternal outcomes such as gestational diabetes and hypertensive complications. The proportion of SGA was not lower in patients with bypass when adjusting for other risk factors (BMI, smoking, geographic origin, diabetes and hypertension) (aOR 0.70; 95%CI 0.01 – 2.85).

Conclusion: sleeve was associated with an incidence of SGA which was as high as after bypass, however the incidence of preterm birth was lower.

Glucocorticosteroids and bronchopulmonary dysplasia : is epigenetics the missing link?

No abstract available

Systematic culture of central catheters and infections related to catheters in a neonatal intensive care unit: an observational study

Abstract

Systematic culture of the tip of central lines is performed in many neonatal intensive care units (NICUs) to guide any subsequent antibiotic therapy. The clinical relevance of this procedure is debated, given the significant bacterial contamination during its removal. We aimed to describe infections related to catheters and assess the usefulness of central catheter systematic cultures for probabilistic antibiotic therapy in cases of suspicion of catheter-related infections in a NICU. A retrospective study in a NICU included all newborn patients hospitalized with a central catheter, between January 2018, and June 2019. The main outcome measures were bacterial catheter colonization, catheter-related infection rate, and simulation-based approach to antibiotic prescription. Three hundred and seventy-five newborns, with 634 central catheters were included. There were 273 (43%) catheters that were colonized by at least one microorganism. There were 183 cases of suspected sepsis, with 31 infections definitively related to the catheter. In our simulation antibiotic prescription approach, there was no significant difference in terms of the efficacy toward the microorganism(s) involved between the probabilistic antibiotic therapies proposed by the experts and those ultimately prescribed. Performing a catheter culture only if catheter-related infection is suspected could be an alternative to routine screening

Mise au point sur les modalités de gestion des efforts expulsifs lors de l’accouchement. Update on the management modalities of expulsive efforts during childbirth

Abstract

The second stage of labour includes both the passive and active stages, involving expulsive efforts. The management of this phase of labour aims to minimise the maternal and neonatal complications that could be associated with a prolonged active2nd stage, but also to limit medical interventions. On the maternal side, prolonged duration of expulsive effort appears to be correlated with increased postpartum haemorrhage, perineal injury and, in the long term, urinary and anal incontinence. From a neonatal viewpoint, expulsive efforts carry risks of neonatal acidosis, asphyxia, admission to the neonatal intensive care unit and trauma. Optimal management of expulsive efforts involves several strategies. Various aspects need to be addressed in order to optimise this management, including the timing of the start of expulsive efforts, comparing immediate pushing with delayed pushing, and the duration of expulsive efforts. In addition, it is important to examine the different pushing modalities, whether intense or moderate, using open or closed-glottis pushing, as well as the maternal position during pushing. According to the current literature, no specific technique or predefined duration appears to reduce the risk of neonatal or maternal complications. It therefore seems essential to adopt an individualised approach for each woman, placing her at the centre of the care and decision-making process, in order to take account of her preferences during childbirth.

A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections.

Abstract

Preterm birth is currently the leading cause of neonatal morbidity and mortality. Genetic, immunological and infectious causes are suspected. Preterm infants have a higher risk of severe bacterial neonatal infections, most of which are caused by Escherichia coli an in particular E. coli K1strains. Women with history of preterm delivery have a high risk of recurrence and therefore constitute a target population for the development of vaccine against E. coli neonatal infections. Here, we characterize the immunological, microbiological and protective properties of a live attenuated vaccine candidate in adult female mice and their pups against after a challenge by K1 and non-K1 strains of E. coli. Our results show that the E. coli K1 E11 ∆aroA vaccine induces strong immunity, driven by polyclonal bactericidal antibodies. In our model of meningitis, mothers immunized prior to mating transfer maternal antibodies to pups, which protect newborn mice against various K1 and non-K1 strains of E. coli. Given the very high mortality rate and the neurological sequalae associated with neonatal E. coli K1 meningitis, our results constitute preclinical proof of concept for the development of a live attenuated vaccine against severe E. coli infections in women at risk of preterm delivery.

Intra-individual variability of serum progesterone levels on the day of frozen blastocyst transfer in hormonal replacement therapy cycles.

Abstract

Study question: Is there a significant intra-individual variability of serum progesterone levels on the day of single blastocyst Hormone Replacement Therapy-Frozen Embryo Transfer (HRT-FET) between two consecutive cycles?

Summary answer: No significant intra-individual variability of serum progesterone (P) levels was noted between two consecutive HRT-FET cycles.

What is known already: In HRT-FET cycles, a minimum P level on the day of embryo transfer is necessary to optimise reproductive outcomes. In a previous study by our team, a threshold of 9.8 ng/ml serum P was identified as significantly associated with the live birth rates in single autologous blastocyst transfers under HRT using micronized vaginal progesterone (MVP). Such patients may benefit from an intensive luteal phase support (LPS) using other routes of P administration in addition to MVP. A crucial question in the way towards individualising LPS is whether serum P measurements are reproducible for a given patient in consecutive HRT-FET cycles, using the same LPS.

Study design, size, duration: We conducted an observational cohort study at the university-based reproductive medicine centre of our institution focusing on women who underwent at least two consecutive single autologous blastocyst HRT-FET cycles between January 2019 and March 2020.

Participants/materials, setting, methods: Patients undergoing two consecutive single autologous blastocyst HRT-FET cycles using exogenous oestradiol and vaginal micronized progesterone for endometrial preparation were included. Serum progesterone levels were measured on the morning of the Frozen Embryo Transfer (FET), by a single laboratory. The two measurements of progesterone levels performed on the day of the first (FET1) and the second FET (FET2) were compared to evaluate the intra-individual variability of serum P levels. Paired statistical analyses were performed, as appropriate.

Main results and the role of chance: Two hundred and sixty-four patients undergoing two consecutive single autologous blastocyst HRT-FET were included. The mean age of the included women was 35.0 ± 4.2 years. No significant intra-individual variability was observed between FET1 and FET2 (mean progesterone level after FET1: 13.4 ± 5.1 ng/ml vs after FET2: 13.9 ± 5.0; P = 0.08). The characteristics of the embryo transfers were similar between the first and the second FET. Forty-nine patients (18.6%) had discordant progesterone levels (defined as one progesterone measurement > and one ≤ to the threshold of 9.8 ng/ml) between FET1 and FET2. There were 37/264 women (14.0%) who had high intra-individual variability (defined as a difference in serum progesterone values >75th percentile (6.0 ng/ml)) between FET1 and FET2. No specific clinical parameter was associated with a high intra-individual variability nor a discordant P measurement.

Limitations, reasons for caution: This study is limited by its retrospective design. Moreover, only women undergoing autologous blastocyst HRT-FET with MVP were included, thereby limiting the extrapolation of the study findings to other routes of P administration and other kinds of endometrial preparation for FET.

Wider implications of the findings: No significant intra-individual variability was noted. The serum progesterone level appeared to be reproducible in >80% of cases. These findings suggest that the serum progesterone level measured on the day of the first transfer can be used to individualize luteal phase support in subsequent cycles.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study.

Abstract

Background: Because selective termination (ST) for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal.

Objective: To determine whether perinatal outcomes were more favorable following deferred rather than immediate ST.

Study design: A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with ST for fetal conditions which were diagnosed before 24 WG. Pregnancies with additional risk factors for late miscarriage were excluded. We defined two groups according to the intention to perform ST within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate ST) or to wait until the third trimester (deferred ST). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 WG and preterm delivery.

Results: Of 390 pregnancies, 258 were in the immediate ST group and 132 in deferred ST group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate ST group vs 100% (132/132) in the deferred ST group (p<0.01). Preterm birth < 37 weeks’ gestation was lower in the immediate than in the deferred ST group (66.7% vs 20.2%, p<0.01); preterm birth < 28 WG and < 32 WG did not differ significantly (respectively 1.7% vs 0.8%, p=0.66 and 8.26% vs 11.4%, p=0.36). In the deferred ST group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery.

Conclusion: Overall survival after ST was high regardless of the gestational age at which the procedure was performed. Postponing ST until the third trimester seems to improve survival, while immediate ST reduces the risk of preterm delivery. Furthermore, deferred ST requires an expert center capable of performing the ST procedure on an emergency basis if required.

Early Mortality, Cardiovascular, and Renal Diseases in Women’s Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION

Abstract

Background: We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France.

Methods and results: CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2 819 655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining International Classification of Diseases, Tenth Revision (ICD-10) coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes.

Conclusions: Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.