Publications

Abstract

Objective: To study perinatal outcomes for newborns with early, isolated, severe FGR, for whom initial active management was considered unreasonable or impossible at an obstetric-pediatric assessment and to identify the determinants associated with a course that made active management reasonable.

Material and methods: This retrospective observational single-center study occurred in a level-3 university hospital maternity unit. It included all pregnancies with a singleton fetus presenting isolated FGR <3rd percentile at 23 weeks or more of gestation with an obstetric-pediatric assessment (OPA) initially unfavorable to active management. The main outcome measure was perinatal mortality. Characteristics of the women and pregnancies were compared between the groups « OPA became favorable » versus « OPA remained unfavorable ».

Results: Among the 80 cases included, 48 (60%) of the children died, 38 (47.5%) before birth, 2 (2.5%) in the delivery room, and 8 (10%) in the NICU. Overall, the OPA for 32 (40%) became favorable. There were 44 (91.7%) perinatal deaths when the OPA remained unfavorable versus 4 (12.5%) when it became favorable (P<0.001). The median gestational age at the first OPA (25 weeks) did not differ between the groups. The patients in the OPA became favorable group had initially abnormal uterine Doppler findings less often (56.2% vs 85.4%, P=0.001), absent diastole or reverse flow umbilical artery less often (9.4% vs 33.3%, P=0.0016), less preeclampsia (6.2% vs 31.2%, P=0.009) and a higher estimated fetal weight (520 [491-546] g vs 487 [449-523] g, P=0.005).

Conclusion: In fetuses with early severe FGR, the risk of perinatal death was very high when the initial OPA was unfavorable. Initial OPA without preeclampsia and umbilical reverse diastolic flow were associated with higher probability that the OPA became favorable.

Abstract

Aim: Healthcare givers are exposed to stress and therefore are at risk of the development of pathologies. We aimed to provide recommendations regarding psychosocial risks such as stress, moral distress, burnout syndrome or secondary stress syndrome in neonatal care units to best support neonatal healthcare givers.

Methods: We searched PubMed for articles published from 1 January 2017 to 1 December 2023 by using the keywords burnout OR (moral and distress) AND neonatal unit. Recommendations were developed after internal and external review by a multidisciplinary group including 15 professionals and parent representatives.

Results: We identified 207 studies and developed 15 recommendations based on 118 eligible studies. Recommendations to support neonatology healthcare givers were developed for the individual level, the collective or department level to organise the environment, the training of the team with communication sessions and team cohesion; and the institutional level to respect and organise working time.

Conclusion: Psychosocial risks have consequences for the neonatal healthcare givers themselves and possibly those being cared for. To date, prevention, screening and treatment have been insufficiently developed and explored. In this context, an overall institutional review of the chosen care model is needed.

Abstract

The short-term respiratory consequences of small for gestational (SGA) are only partially known. Our aim was to compare the early respiratory features between SGA and appropriate for gestational age (AGA) in very preterm infants. We conducted a secondary analysis of the French prospective EPIPAGE-2 cohort. Eligible children were those born alive before 32 weeks’ gestation. The exposed group consisted of children with SGA. The unexposed group consisted of AGA children. SGA and AGA children were randomly matched in a ratio of 1:1 on the same gestational age and sex. Primary outcomes were age at final extubation and age at weaning from any respiratory support. Among 3.964 very preterm from the EPIPAGE2 cohort, 1123 SGA and 1123 AGA very preterm children were included in the study. The median gestational age was 30.0 weeks (interquartile range 28.0-31.0) in both groups. The median birthweight was 1440 g (1138-1680) in the AGA group and 1000 g (780-1184) in the SGA group. Invasive mechanical ventilation was less common in the SGA than in the AGA group: 68.6% (770/1123) versus 72.0% (808/1062), odds ratio 0.85 (95% CI [0.72-1.00]). In cases of mechanical ventilation, median age at final extubation was 4 days (1-23) and 2 days (1-9) in the SGA and AGA groups. Median postmenstrual age at weaning from any respiratory support was 33.4 weeks (31.7-35.9) in the SGA group and 32.4 weeks (31.4-34.3) in the AGA group.

Conclusion: SGA is associated with delayed extubation and respiratory support weaning.

What is known: • Small for gestational age concerns more than 30% of very preterm children. • The condition is strongly associated with increased neonatal mortality and morbidity, including bronchopulmonary dysplasia.

What is new: • Small for gestational age is associated with delayed extubation and respiratory support weaning in very preterm children. • Shortening invasive mechanical ventilation as much as possible is a crucial issue in this population to try to reduce the risk of bronchopulmonary dysplasia.

Abstract

Prophylactic administration of low-dose hydrocortisone, at replacement dosage, targets inability of extremely low gestational age neonates (ELGANs) to respond to postnatal stress due to adrenal glands immaturity and is intended to prevent serious complications such as death and bronchopulmonary dysplasia (BPD). Increasing evidence from systematic reviews shows that prophylactic hydrocortisone reduces pre-discharge mortality, improves survival without BPD, favors patent ductus arteriosus (PDA) closure, and may have beneficial effects on cardiovascular stability and urine output. In contrast, an increased risk of spontaneous intestinal perforation when prophylactic hydrocortisone is combined with indomethacin and late-onset sepsis, particularly in infants of 24-25 weeks of gestation, have been reported as major adverse events. No significant negative impact on long-term neurodevelopmental outcomes following prophylactic hydrocortisone exposure was observed. Recent real-world data, despite their intrinsic methodological limitations, generally confirm the benefits observed in clinical trials, even with additional potential benefits and without increased adverse events. Ongoing challenges and questions discussed in this invited review relate to the best population to treat, optimal timing and duration of treatment, and potential barriers to implementation due to evolving knowledge and guidelines. IMPACT STATEMENT: Prophylactic low-dose hydrocortisone improves survival without BPD in infants born extremely preterm. Recent real-world data generally confirm the benefits observed in clinical trials, even with additional potential benefits and without increased adverse events. Unanswered questions remain about optimal timing and duration of treatment, and potential barriers to implementation due to evolving knowledge and guidelines.

Abstract

Aim: Infants born very preterm spend their early postnatal life in a neonatal intensive care unit, where irregular and unpredictable sounds replace the structured and familiar intrauterine auditory environment. Music interventions may contribute to alleviate these deleterious effects by reducing stress and providing a form of environmental enrichment.

Material and methods: This was an ancillary study as part of a blinded randomised controlled clinical trial entitled the effect of music on preterm infant’s brain development. It measured the impact of music listening on the autonomic nervous system (ANS), we assessed heart rate variability (HRV) through high-resolution recordings of heart rate monitoring, at three specific postmenstrual ages in premature infants.

Results: From 29 included subjects, 18 were assessed for complete HRV dataset, including nine assigned to the music intervention and nine to the control group. Postmenstrual age appeared to be the main factor influencing HRV from 33 weeks to term equivalent age. Further analyses did not reveal any detectable effect of music intervention on ANS response.

Conclusion: This study found that ANS responses were not modified by recorded music intervention in very preterm infants during wakefulness or sleep onset. Further research is warranted to explore other factors influencing ANS development in this population.

Keywords: autonomic nervous system; heart rate variability; music intervention; neonatal intensive care unit; preterm infants.

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.