Publications

Abstract

Objectives: The primary objective was to describe probiotic exposure in a nationwide cohort of very preterm infants cared for in neonatal intensive care units (NICUs) in France. Secondary outcomes were to describe prescription practices across centers and associated clinical outcomes.

Methods: This retrospective multicentre study included 18,146 infants born at less than 32 weeks of gestation and admitted to NICUs using the same Computer Prescribing Order Entry-Clinical Decision Support system, Logipren®, between January 2019 and December 2023. Linear and logistic regression assessed the association between probiotic exposure and several outcomes, adjusted for sex, gestational age, intrauterine growth restriction, and center-specific effects.

Results: The rate of probiotic exposure in the study cohort was 14.3%, and significantly decreased from 16.2% to 12.7% over the study period. Prescribing practices were highly heterogeneous in terms of: choice of probiotic strains, timing of initiation, duration of treatment, dosing regimens, and pharmaceutical formulations. Limosilactobacillus reuteri DSM 17938 (65.6%) was most frequently used, followed by Lacticaseibacillus (L.) rhamnosus lcr35 (30.0%) and L. rhamnosus GG ATCC 53103 (4.5%). Only one center prescribed the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)-recommended combination (Bifidobacterium (B.) infantis Bb-02, B. lactis Bb-12, and Streptococcus thermophilus TH-4). After multivariate analysis, mortality was significantly lower in the probiotic group (5.2% vs. 7.4%; adjusted odds ratio: 0.20, 95% confidence interval [0.15-0.26]).

Conclusions: Probiotic use in French NICUs remains limited and practice patterns are heterogeneous, with minimal adherence to ESPGHAN recommendations. These results underscore the need for standardized national guidelines and prospective trials.

Keywords: critical care; enteral nutrition; mortality; prescription; supplemental food.

Abstract

As part of the ADVANCE-VAC4PM project, the European Vaccine Initiative (EVI) and La Fondation pour la Recherche Scientifique (FORS) co-hosted a hybrid workshop titled « Strategies for using malaria vaccines to prevent malaria in pregnancy (MiP) ». The event brought together researchers, regulators, civil society, global health experts, and policymakers to discuss the need for MiP vaccines and strategies for their development, evaluation, and implementation. Malaria remains a major global health threat, with sub-Saharan Africa bearing the highest burden. Pregnant women (PW) are highly vulnerable, with an estimated 12.4 million affected in 2023. Beyond maternal health effects, a major cause of the MiP-related disease burden is placental malaria (PM), which can cause significant morbidity in newborns. PM risk is greatest in primigravidae and secundigravidae, as immunity develops over successive pregnancies. As existing malaria control strategies remain insufficient, MiP vaccines have the potential to complement them by eliciting immunity comparable to that seen in multigravidae. To be effective, such a vaccine should provide long-lasting immunity and target adolescent girls and women before their first pregnancy. PM vaccine candidates targeting the VAR2CSA antigen (PRIMVAC and PAMVAC) are in development, and existing malaria vaccines preventing infection are being repurposed to prevent MiP. However, limited awareness of MiP-specific burden, weak pharmacovigilance systems, and vaccine hesitancy may hinder future vaccine implementation. Key recommendations highlighted during the workshop included strengthening communication and community engagement strategies, defining relevant efficacy endpoints for pivotal clinical trials, reinforcing pharmacovigilance systems to support safety and real-world effectiveness studies, and planning for early regulatory alignment. Panel discussions emphasized the importance of stakeholder coordination and reduced-dose schedules to support future MiP vaccine programmatic feasibility. The workshop concluded with a call for sustained collaboration and national investment to ensure that MiP vaccines become a viable and effective component of global malaria prevention efforts.

Keywords: Malaria in pregnancy; Placental malaria; Vaccine development; Vaccine implementation.

Abstract

Background: Preeclampsia (PE) affects 2 8% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality. In high risk pregnant women, low dose aspirin (LDA 100 160 mg/day) started before 16 WG reduces the incidence of PE, prematurity, perinatal mortality and low birth weight. First trimester screening of PE allows the identification of a population of pregnant women at high risk of early onset PE and perinatal mortality. It remains unclear whether, on a population scale, the systematic implementation of first trimester screening of PE with treatment of high risk patients by LDA leads to an improvement of maternal and perinatal health.
Methods: This multicenter open randomized controlled trial with two parallel groups will include 14500 pregnant women between 11 14 WG. Eligible women agreeing to participate in the trial will be randomized either to the experimental group with management including screening of PE, or to the control group with usual care without screening of PE. For women in the screening group, the risk of PE will be calculated according to an algorithm combining clinical characteristics, uterine arteries Doppler profile and PlGF concentration. Women with a positive screening test (i.e. predicted risk >1/100) will receive aspirin at 160 mg/day. For women with negative screening, usual pregnancy monitoring without aspirin will be offered. The primary outcome is a composite of severe perinatal morbidity including at least one of the following: perinatal mortality, birth before 34 WG and birth weight < 3rd centile. Secondary endpoints include maternal morbidity and mental health outcomes, and a cost effectiveness evaluation. This study will have a 90% power to show a 50% reduction of the primary outcome in at risk women, expected to represent 10% of the total population in each group, i.e an overall expected 3% frequency of the primary outcome in the intervention group as a whole versus 4% in the control group.
Discussion: This large multicenter randomized trial aims to determine with adequate power if the implementation of first trimester PE screening in all pregnant women would decrease the incidence of perinatal mortality, prematurity before 34 WG and birth weight < 3rd centile.

Abstract

The µ-opioid receptor (MOP) is a critical pharmaceutical target that mediates both the therapeutic benefits and adverse effects of opioid drugs. However, the large-scale neural circuit dynamics underlying key opioid effects, such as analgesia and respiratory depression, remain poorly understood, hindering the development of safer analgesics. Here, we present a multimodal experimental framework that integrates functional ultrasound imaging through the intact skull with behavioral and molecular analyses to investigate opioid-induced large-scale functional responses and their physiological relevance in awake, behaving male mice. Administration of major opioids-morphine, fentanyl, methadone, and buprenorphine-elicited robust, dose- and time-dependent reorganization of functional brain connectivity (FC) patterns, with magnitude scaling according to MOP agonist efficacy. This opioid-specific functional fingerprint is marked by decreased FC between the somatosensory cortex and hippocampal/thalamic regions and increased bilateral FC within the somatosensory cortex. Notably, this fingerprint was attenuated following tolerance induction and abolished by pharmacological or genetic MOP inactivation. Through power Doppler spectral analysis and lagged correlation measurements, we show that morphine perturbs temporal FC dynamics and the propagation of brain-wide oscillatory activity, disrupting critical-state dynamics. Importantly, we identify a dissociation between fast, transient processes-such as cerebral blood volume changes, locomotion, and respiratory depression-and slower processes driving FC reorganization, analgesia, and sustained MOP activation. This study provides mechanistic insights into opioid-induced network reorganization, establishes FC alterations as a reliable biomarker of opioid efficacy, and offers a framework for advancing the development of analgesic compounds with improved therapeutic windows and reduced side effects.

Keywords: brain imaging; functional connectivity; opioids; pain.

Abstract

Introduction: Availability and expertise of healthcare professional are essential for the quality of care of preterm infants. Objective was to survey different healthcare professionals’ availability for management of preterm neonates <29 weeks’ gestation among neonatal intensive care units (NICU) of 12 population-based neonatal networks.

Methods: Questionnaires were distributed to 608 NICU participating in the International Network for Evaluating Outcomes in Neonates (iNeo). Networks included: Australia/New-Zealand (n= 30), Brazil (n=20), Canada (n=32), Finland (n=5), France (n=70), Israel (n=26), Japan (n=292), Poland (n=56), Spain (n=55), Sweden (n=9), Switzerland (n=9) and Tuscany (n=4). Questions focused on availability of physicians, nurses and additional healthcare professionals in 2023.

Results: A total of 382 (63%) NICU responded. The 24/7 availability of healthcare professionals varied within and between networks and overall was reported to be 66% for neonatologists, 55% for neonatal fellows, 62% for pediatric residents and 55% for nurse practitioners. Nurse-to-patient ratios were most commonly 1:1 for complex critical care infants (53%) and 1:2 for intensive care infants (48%). Low 24/7 availability was reported for respiratory therapists and pharmacists.

Conclusions: Marked variations exist in health care professionals’ availability, which might be associated with NICU organization and management of infants <29 weeks’ gestation. While majority of NICU have reported 24/7 availability of neonatologists, the availability of other healthcare professionals was inconsistent. Nurse-to-patient ratio has improved. Further evaluation is needed to understand how these variations are associated with outcomes of extremely preterm infants and to optimize resource utilization.

Abstract

Objectives: To describe the process for the translation and validation of the Postpartum Specific Anxiety Scale-Preterm Birth [PSAS-PTB] and the Postpartum Specific Anxiety Scale-Neonatal Intensive Care Unit [PSAS-NICU].

Methods: We outline a four-stage process for translation and validation of the 10-item PSAS-PTB and the 16-item PSAS-NICU.

Results: The protocol outlines a multi-stage translation and validation process, including (1) independent forward translation, (2) independent back translation, (3) final approval following review, and (4) validity and reliability study.

Conclusions: Culturally and contextually relevant assessment of postpartum anxiety is vital, particularly in vulnerable populations. Following standardised procedures will support broader applicability across diverse populations, providing a reliable self-report tool for both research and clinical use.

Keywords: NICU; cross‐cultural validity; postpartum anxiety; preterm birth; psychometrics; translation.

Abstract

Preterm birth is known to severely impact the neurological development of newborns with long-lasting complications and higher risks of neurological disorders. Sheep (Ovis aries) is well known as a pre-clinical model in therapeutic studies, such as extra-uterine support. The aim of our study was to investigate the relevance of the lamb as a pre-clinical model for preterm birth when cortical maturation of preterm and term lamb is addressed. Cesarean sections were performed on time-dated pregnant ewes to obtain 13 lambs at 100 days and 140 days of pregnancy each (corresponding to 24 and 36 weeks of pregnancy in humans, respectively). Brains were collected and separated in frontal lobe, temporo-parietal lobe, occipital lobe, and cerebellum. Immunohistochemistry staining was used for each brain area by targeting neurons, interneurons, synaptic vesicles, oligodendrocytes, myelin, astrocytes, and microglia. Quantifications were normalized by the surface area of analysis. Overall, 140-days late preterm lambs have significantly higher mean positivity for interneurons, synaptic vesicles, oligodendrocytes, astrocytes, and myelin than 100-days extremely preterm lambs. Similarly, significantly higher mean positivity for neurons was found in the cerebellum of 140-days term lambs. No significant difference was observed regarding microglia. Based on the cellular and structural markers used in this study, brain development in lamb seems to follow an antero-posterior direction similarly to what was reported in humans. Further studies with more specific markers and in-depth analysis will allow for a more accurate and exhaustive description of brain development in lamb.

Keywords: brain development; immunohistochemical comparison

Abstract

Aim: Eye movements have rarely been explored in preterm born children. The aim of this study was to compare horizontal eye movements in children born preterm and full term when they reached 8 years of age.

Methods: Eye movements were recorded in 24 preterm born children (18 boys) and 26 matched controls (19 boys), recruited by a French hospital, using an eye tracker. This identified different types of visually guided saccades, namely step, gap, overlap and antisaccades and pursuit eye movements. The saccades task measured the latency and the percentage of anticipatory and express saccades and errors. The pursuit task measured the gain and percentage of intrusive saccades.

Results: This study confirmed that children born at 24-28 weeks of gestation demonstrated a global deficit in inhibitory processes compared to children born full term. The saccades were less precise in the preterm group, anticipatory and express saccades were elevated and there was a high occurrence of intrusive saccades during pursuit movements.

Conclusion: These findings suggest that preterm born children have immature brain structures, particularly the parietal and frontal cortexes that are responsible for both saccade and pursuit performance. These could have been the cause of the abnormal inhibitory control measured in this study.

Abstract

In France, the rate of twin deliveries is estimated at 1.6% of all births. These recommendations address the gestational age at delivery and the mode of delivery for twin pregnancies. They were developed using the GRADE methodology, with questions formulated according to the PICO framework. Regarding gestational age at delivery, in cases of uncomplicated dichorionic diamniotic pregnancies, it is recommended to plan delivery between 37 weeks and 0 days and 38 weeks and 6 days of gestation (weak recommendation, very low-quality evidence). In cases of uncomplicated monochorionic diamniotic pregnancies, it is recommended to plan delivery between 36 weeks and 0 day and 37 weeks and 6 days of gestation (weak recommendation, very low-quality evidence). Finally, in cases of uncomplicated monochorionic monoamniotic pregnancies, it is recommended to plan delivery between 33 weeks and 0 day and 34 weeks and 6 days of gestation (weak recommendation, very low-quality evidence). Regarding the mode of delivery for diamniotic twin pregnancies, when the first twin is in cephalic presentation and the gestational age is 32 weeks or more, a planned vaginal birth is recommended (strong recommendation, high-quality evidence). When the first twin is in breech presentation and the gestational age is 32 weeks or more, it is recommended to offer either a trial of vaginal birth or a scheduled cesarean section; the expert group suggests favoring a trial of vaginal birth when all eligibility criteria are met (weak recommendation, low-quality evidence). In monoamniotic twin pregnancies, the available data are insufficient in both quantity and quality to issue a recommendation regarding a trial of vaginal birth compared with a scheduled cesarean section (no recommendation, very low-quality evidence). It is recommended to offer labor induction rather than a scheduled cesarean section when delivery is indicated at 32 weeks or more and the first twin is in cephalic presentation (weak recommendation, very low-quality evidence). Regarding the delivery of the second twin, in vaginal births at 32 weeks or more with the second twin in cephalic presentation, it is recommended to perform either internal version or resumption of pushing efforts, with artificial rupture of membranes with or without oxytocin (weak recommendation, low-quality evidence). When the second twin is in breech presentation, total breech extraction is recommended rather than resumption of pushing efforts (weak recommendation, very low-quality evidence). In diamniotic twin pregnancies with spontaneous labor before 32 weeks and with the first twin in cephalic presentation, it is recommended to offer a trial of vaginal birth rather than systematic cesarean section (weak recommendation, low-quality evidence). The available data are insufficient in both quantity and quality to issue a recommendation regarding a trial of vaginal birth compared with systematic cesarean section in cases of spontaneous labor before 32 weeks with the first twin in breech presentation (no recommendation, very low-quality evidence). It is recommended not to take growth discordance into account when choosing the mode of delivery (weak recommendation, very low-quality evidence). The available data are insufficient in both quantity and quality to issue a recommendation regarding the usefulness of pelvimetry when the first twin is in cephalic presentation (no recommendation, very low-quality evidence).

Abstract

Preterm neonates present multiple challenges due to organ immaturity.Cardiovascular:Patent ductus arteriosus (PDA) is common in lower gestational ages and may cause respiratory and circulatory complications. Treatment includes medical (ibuprofen, para-cetamol), surgical, or percutaneous approaches. Bradycardia is frequent and requires continuous monitoring.Digestive/Metabolic:Early enteral nutrition with fortified breast milk is preferred; parenteral nutrition is often required. Gastroesophageal reflux is usually benign. Preventing metabolic bone disease necessitates adequate calcium and phosphate intake. Jaundice is common; cholestasis often relates to parenteral nutrition.Infectious:Immune immaturity and invasive devices increase risks of early-onset (E.coli), nosocomial (CoNS), and fungal (Candida) infections. Diagnosis relies on blood cultures; treatment is empirical then targeted.Neurological:Common lesions include periventricular leukomalacia and intraventricular hemorrhage, with potential sequelae. Monitoring includes cranial ultrasound, EEG, MRI, and routine screening for hearing loss and retinopathy of prematurity.