Publications

Abstract

Proteins play a crucial role in determining disease states in humans, making them prime targets for the development of diagnostic sensors. The developed sensor array is used to investigate global proteomic changes by fingerprinting multifactorial disease states in model urine simulating phenylketonuria and in serum from preeclamptic pregnant women. Here, we report a fluorescence-based chemical sensing array that exploits the host-guest interaction between cucurbit[7]uril (CB[7]) and fluorescent triphenylamine derivatives (TPA) to detect a range of proteins. Using linear discriminant analysis, we identify fluorescence fingerprints of 14 proteins with over 98% accuracy in buffer and human serum. The array is optimized on an automated droplet microfluidic-based platform, for high-throughput sensing with controlled composition and lower sample volumes. This sensor enables the discrimination of proteins in physiological buffer and human serum, with promising applications in disease diagnosis.

Abstract

Background: Pertussis vaccination in young mothers aims to protect neonates through cocooning. We estimated pertussis vaccination coverage (VC) in women at two months postpartum in France in 2021, and the proportion of women who got vaccinated in the first two months postpartum; associated determinants were studied.

Methods: We used data from the 2021 National Perinatal Surveys conducted in metropolitan France (ENP 2021) and French overseas territories (ENP-DROM 2021). Multivariate poisson regressions were employed to study the following determinants: age, educational level, monthly household income, socio-professional situation, birth country, parity, health professional who monitored pregnancy, influenza vaccination during pregnancy, region of residence, prenatal care consultations, having health insurance, having a partner, and having a chronic pathology. Results were weighted.

Results: The study sample comprised 7999 women. Estimated pertussis VC at two months postpartum was 66.8 % (95 %CI [65.5-68.0]). VC was significantly lower in i) unemployed women (vs. executives/managers, intermediate and higher intellectual professionals), ii) those on low income (vs. high), and iii) those with two or more children (vs. primiparous). It was significantly higher in i) women born in France, ii) those vaccinated against influenza during pregnancy, iii) those who received pre-natal care from a private midwife, and iv) those with more prenatal consultations. The proportion of women vaccinated against pertussis in the two-month postpartum period (33.4 % [31.7-35.9]) was significantly lower in i) women on low incomes, ii) unemployed women, iii) women with health insurance, and iv) multiparous women. It was significantly higher in those vaccinated against influenza during pregnancy.

Discussion – conclusion: Pertussis VC in women at two months postpartum in 2021 was insufficient and was marked by social and territorial inequalities in health. Vaccination for pregnant women has been recommended in France since 2022. A study monitoring the impact of this new recommendation is essential.

Abstract

Introduction: This study aimed to evaluate the agreement between the proteinuria/creatinuria (P/C) ratio and the traditional 24-hour proteinuria measurement for proteinuria levels above 3 g/24h in pregnant patients with preeclampsia. Additionally, we assessed whether high levels of each measurement are predictive of adverse maternal and neonatal outcomes.

Material and methods: We conducted a monocentric retrospective study of pregnant patients hospitalized for preeclampsia between January 1, 2019, and November 11, 2020. The primary outcome was a composite measure of adverse maternal outcomes associated with preeclampsia, and the secondary outcome focused on adverse neonatal outcomes. Agreement between high levels of 24-hour proteinuria and the P/C ratio was evaluated using Cohen’s Kappa. Maternal and neonatal outcomes were compared across three groups: those with neither, one, or both high proteinuria levels (24-hour proteinuria ≥ 3 g/24h and/or P/C ratio ≥ 300 mg/mmol). Logistic regression, adjusted for confounders, analyzed associations between measures and outcomes, with ROC curves and AUC calculated for predictive models.

Results: We found a strong correlation between 24-hour proteinuria and P/C ratio, with 95.1% agreement at the threshold of 3 g/24h and 300 mg/mmol, respectively (Kappa = 0.87, p < 0.01). Both measurements were associated with an increased risk of adverse maternal (aOR 6.78 [2.47-18.63]) and neonatal (aOR 7.00 [1.56-31.31]) outcomes.

Discussion: This study demonstrated a strong agreement between the P/C ratio ≥ 300 mg/mmol and 24-hour proteinuria ≥ 3 g/24h, both associated with an increased risk of adverse perinatal outcomes, with the P/C ratio offering a quicker, simpler alternative for managing preeclampsia.

Abstract

Introduction: Preeclampsia, a hypertensive disorder of pregnancy triggered by placental dysfunction, is reproduced in the murine STOX1A model, with hypertension, proteinuria, and abnormalities in umbilical and uterine Dopplers. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an innovative technique that provides insights into tissue perfusion. The present study aims at analyzing placental perfusion using DCE-MRI to further characterize placental defects in the STOX1A model.

Methods: Two study groups were formed: the « TgSTOX13 pregnancy group » from mating TgSTOX13 genotype males with wild-type females, and the « wild-type pregnancy group » from mating wild-type males with wild-type females. Blood pressure, urinary albumin to creatinine ratio, and fetal weights were measured and compared between the groups, while perfusion parameters were analyzed using both conventional compartmental (1C) and free-time point-Hermite (FTPH) models in the DCE analysis.

Results: Seventeen pregnant mice in the « TgSTOX13 pregnancy group » and thirteen in the « wild-type pregnant group » were included in the analysis. During late gestation, the TgSTOX13 pregnancy group exhibited higher blood pressure, elevated albumin/creatinine ratio, and decreased fetal weights compared to the wild-type pregnancy group. In the DCE analysis utilizing the 1C model, blood flow (Fb) was significantly reduced by approximately 31.8 % in the TgSTOX13 pregnancy group compared to the wild-type pregnancy group (p < 0.01), a finding corroborated by the FTPH model with a reduction estimated at 31.5 % (p < 0.01).

Discussion: Our investigation successfully utilized DCE MRI to assess placental perfusion in a mouse model of preeclampsia, revealing a significant reduction of approximately 30 % in the preeclamptic mice, mirroring human pathophysiology.

Abstract

The fitness cost associated with antimicrobial resistance has an important influence on evolutionary dynamics. We compared the genomes of three Klebsiella aerogenes isolates recovered from blood samples or deep abscess cultures from the same patient: the wild-type strain (CT_WT), a piperacillin-tazobactam-resistant strain (CT_PENI), and an extended-spectrum-cephalosporin (ESC)-resistant strain (CT_R). Whole-genome sequencing revealed that CT_PENI had acquired a TEM-1 β-lactamase with a mutated promoter, accounting for overproduction. CT_PENI then acquired an E240G substitution in the TEM-1 β-lactamase (resulting in TEM-207) and lost the porin-encoding ompK36 gene to give CT_R. All three strains showed the same virulence in a mouse model of intraperitoneal infection. The results of recombination and transformation assays indicated that when present separately, the TEM-207 overproduction and the ompK36 gene deletion had only small effects on susceptibility to ESCs. However, the combination of the two changes led to a much lower susceptibility to ESCs. Moreover, the levels of fitness in vitro and in vivo in a murine model of gut colonization were significantly lower after TEM-1 β-lactamase overproduction and lower still after E240G substitution and OmpK36 loss. We hypothesize that the chosen courses of antibiotics led to the stepwise emergence of a clone with resistance to penicillins and ESCs and no loss of virulence. However, acquired resistance may have a fitness cost that limits evolutionary success. Our results might explain why the overproduction of extended-spectrum β-lactamases (which should confer a high level of piperacillin-tazobactam resistance) is not observed in clinical practice and why TEM-207 has rarely been detected in clinical isolates.

Abstract

Background: Maternal exposure to unfavourable social conditions is associated with a higher rate of perinatal complications, such as placental vascular pathologies. A higher risk of preterm birth (PTB) has also been reported, and variations across studies and settings suggest that different patterns may be involved in this association.

Objective: To assess the association between maternal social deprivation and PTB (overall and by phenotype).

Methods: We analysed 9365 patients included in the PreCARE cohort study. Four dimensions (social isolation, insecure housing, no income from work and absence of standard health insurance) defined maternal social deprivation (exposure). They were considered separately and combined into a social deprivation index (SDI). The associations between social deprivation and PTB <37 weeks (primary outcome) were analysed with univariable and multivariable log-binomial models (adjusted for maternal age, parity, education level and birthplace). Then we used multinomial analysis to examine the association with preterm birth phenotypes (secondary outcome): spontaneous labour, preterm prelabour rupture of membranes (PPROM) and placental vascular pathologies.

Results: In all, 66.3%, 17.8%, 8.9% and 7.0% of patients had an SDI of 0, 1, 2 and 3, respectively. Social isolation affected 4.5% of the patients, insecure housing 15.5%, no income from work 15.6% and no standard health insurance 22.4%. Preterm birth complicated 7.0% of pregnancies (39.8% spontaneous labour, 28.3% PPROM, 21.8% placental vascular pathologies and 10.1% other phenotypes). Neither the univariable nor multivariable analyses found any association between social deprivation and the risk of preterm birth overall (SDI 1 versus 0: aRR 1.02, 95% confidence interval [CI] 0.83, 1.26; 2 versus 0: aRR 1.05, 95% CI 0.80, 1.38; 3 versus 0: aRR 0.92, 95% CI 0.66, 1.29) or its different phenotypes.

Conclusions: In the French PreCARE cohort, we observed no association between markers of social deprivation and the risk of preterm birth, regardless of phenotype.

Abstract

The patent ductus arteriosus is a very common condition in preterm infants, and a hemodynamically significant patent ductus arteriosus increases morbidity and mortality in these vulnerable patients. However, despite numerous randomized controlled trials, there is no consensus regarding management. Medical therapy is typically offered as first-line treatment, although it yields limited success and carries the potential for severe adverse events. In recent years, there has been rapid development in transcatheter patent ductus arteriosus closure primary with the use of the Amplatzer Piccolo Occluder, and this has gained widespread acceptance as a safe and effective alternative to surgical ligation in extremely low-birth-weight infants weighing over 700 g. This article aims to provide an appraisal of the patient selection process, a step-by-step procedural guide, and a comprehensive review of the outcomes associated with this approach.

Abstract

Objective: To report neurodevelopment at age 5.5 years according to developmental delay screening with the Ages & Stages Questionnaire (ASQ) in late infancy in preterm-born children.

Design: Population-based cohort study, EPIPAGE-2.

Setting: France, 2011-2017.

Participants: 2504 children born at 24-26, 27-31 and 32-34 weeks, free of cerebral palsy, deafness or blindness at 2 years’ corrected age.

Main outcome measures: Moderate/severe, mild or no disability at age 5.5 years using gross and fine motor, sensory, cognitive and behavioural evaluations. Results of the ASQ completed between 22 and 26 months’ corrected age described as positive screening or not.

Results: Among 2504 participants, 38.3% had ASQ positive screening. The probability of having moderate/severe or mild disability was higher for children with ASQ positive versus negative screening: 14.2% vs 7.0%, adjusted OR 2.5 (95% CI 1.8 to 3.4), and 37.6% vs 29.7%, adjusted OR 1.5 (1.2 to 1.9). For children with ASQ positive screening, the probability of having neurodevelopmental disabilities at age 5.5 years was associated with the number of domain scores below threshold, very low gestational age and severe neonatal morbidities. For children with ASQ negative screening, this probability was increased for boys and children born small-for-gestational age. For both groups, maternal level of education was strongly associated with outcomes.

Conclusion: In preterm-born children, ASQ screening at 2 years’ corrected age was associated with neurodevelopmental disabilities at age 5.5 years. However, other factors should be considered when interpreting the ASQ data to draw further follow-up.

Abstract

Thrombocytopenia is common in preterm neonates and can be associated with hemorrhage. Most platelet transfusions are prophylactic. Previously, higher platelet-count thresholds were recommended for neonates, but this recommendation has been questioned in recent studies. In the PlaNeT2 trial, mortality and serious bleeding were more frequent in neonates with the highest platelet-count threshold than in others. Following this trial, we changed our platelet transfusion practice by lowering the platelet-count threshold for prophylactic transfusion from 50,000 to 25,000/mm³. We conducted a before-after retrospective cohort study to quantify the frequency of platelet transfusions and assess the new protocol by analyzing death and serious hemorrhage events. This retrospective monocentric study included neonates born before 37 weeks of gestation with platelet count < 150,000/mm³ during the 2 years preceding the new platelet transfusion protocol (high prophylactic transfusion threshold, 50,000/mm³) and during the 2 years after the new platelet transfusion protocol (low prophylactic transfusion threshold, 25,000/mm³). The primary outcome was the proportion of neonates receiving at least one platelet transfusion in both groups. We also compared the proportion of deaths and severe hemorrhage events. A total of 707 neonates with thrombocytopenia were identified. In the high-threshold group, 99/360 (27.5%) received at least one platelet transfusion as compared with 56/347 (16.1%) in the low-threshold group (p < 0.001). The groups did not differ in proportion of deaths or severe hemorrhage events.

Conclusions: A reduced platelet-count threshold for transfusion allowed for a significant reduction in the number of platelet transfusions without increasing severe hemorrhage events.

No abstract available