Publications

Abstract

Perinatal brain injury (PBI) is a major predictor of neurological disability. Commonly associated with prematurity, infection, stroke, hypoxia-ischemia, hemorrhage, and/or toxin exposure, PBI triggers acute and persistent systemic inflammation. There are many stages of vulnerability to PBI during development including pregnancy, birth – term and preterm, and neonatal age. The vulnerable stages can compound inflammation through injury to the placental-fetal-brain axis, adaptive and innate immune system development, neural-immune communication, and central nervous system maturation. Neonates exhibit unique inflammatory signatures and lasting neural-immune responses to various etiologies. Chronic immune dysregulation and priming to a secondary, later-in-life immune challenge defines different forms of PBI while shaping the neonatal and adult immune response with long-term changes. Immunomodulated changes impact regulatory, helper and innate T cells, neutrophils, natural killer cells and immune responsiveness. The major routes of persistent and compounding inflammation in PBI are perinatal neural-immune interactions, cytokine influx, and glial crosstalk. Most treatments are not administered long enough or in the optimal time window to combat sustained inflammation in tertiary and quaternary phases of PBI pathophysiology and are ineffective in reducing neonatal mortality and morbidity and promoting functional recovery. Indeed, persistent systemic and central inflammation is a likely explanation for failed recovery of PBI after the resolution of acute insults. We propose attenuating persistent inflammation and normalizing systemic immune reactivity as key to reducing the functional impact of PBI throughout the lifespan through various avenues including therapeutic treatment, gut microbiome modulation, and novel immunomodulation from preclinical research.

Keywords: Immunology; Inflammation; Neonatology; Neurology; Neuroscience; Pediatrics.

Abstract

Random-effects meta-analysis typically assumes a normal distribution for the underlying effects of the studies. However, under certain conditions, this assumption may not be the most appropriate. Simulation studies comparing several alternative random-effects models have found small differences in bias but larger differences in coverage probabilities and precision. To investigate the impact of using different meta-analysis models, we used a meta-analysis of 58 cohort studies comparing the cognitive functioning between preterm- and term-born children. We compared the results between seven different random-effects models based on: asymmetric distributions, mixtures of distributions and Dirichlet process (DP) prior. Sensitivity analysis using variations of the seven main models was also performed. While estimates for mean treatment effect were similar across models, the between-study variance estimates were identical. Asymmetric distribution models indicated studies with extreme effects and a left-shifted random-effects distribution while mixture models were less informative. DP models revealed clusters of studies with similar characteristics, suggesting that the observed heterogeneity may be partially explained by certain methodological and clinical characteristics of the studies. Overall, our study highlights that applying various meta-analysis models might not affect materially the summary estimates but may provide better insights into the underlying effects’ distribution and the explanation of between-study variance.

Keywords: Bayesian meta-analysis; heterogeneous treatment effects; semi-parametric models; synthesis of observational data.

Abstract

Precise regulation of uterine immunity is required to support fundamental processes including reproduction and pathogen protection. How the local milieu and constitutive stressors, including the cervicovaginal microbiota, shape the delicate balance underlying uterine immunity is poorly understood. Here, we found that the cervicovaginal microbiota promotes both local immunity and the immunoregulatory activity of interferon lambdas (IFN-λ) in the uterus. Using murine models, we found a keystone role for IFN-λ in constraining the immune tone of this compartment, more specifically of innate lymphoid cells and Th17 cells. Conversely, in the context of pregnancy, IFN-λ promotes antibacterial responses at maternal-fetal barriers, and as a result controlling fetal and neonatal transmission. Collectively, this work demonstrates how IFN-λ integrates microbial signals under both steady state and pregnancy conditions thereby orchestrating key functions of the uterine immune system, namely immunoregulation and antibacterial protection

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

Inequalities in severe maternal morbidity (SMM) and mortality in high-income countries are persistent, socially patterned, and evident across multiple dimensions, including socioeconomic deprivation, race and ethnicity, and migration status. These inequalities are not fully explained by individual clinical risk factors but arise from the interaction of structural disadvantage, intermediate social conditions, and health systems. Many determinants of risk are established before pregnancy; however, variation in access to care, quality of care, and responsiveness to symptoms during pregnancy and childbirth can either mitigate or exacerbate vulnerability. Identifying social and structural determinants, ensuring equitable access to care, providing culturally responsive care, and promoting timely, unbiased clinical decision making are essential components of clinician efforts to reduce inequalities in SMM and mortality.

Abstract

Introduction: Parenting an infant in the neonatal intensive care unit (NICU) can be highly stressful, undermine parental confidence and minimise involvement in infant care. Enhancing parental self-efficacy is therefore crucial to promoting active engagement and supporting positive child outcomes. This study aims to identify the psychosocial needs (emotion regulation and stress management) of NICU parents and examine the factors that influence their engagement in infant care. It also seeks to determine whether higher levels of parental self-efficacy are associated with greater engagement and collaboration with healthcare providers (HCPs) and a shorter NICU stay.

Methods and analysis: A mixed-methods study will be conducted at the Montreal Children’s Hospital’s Level III NICU located in Quebec, Canada. Parents (ie, mothers and, when available, their partners) will be recruited during their infant’s hospitalisation. Participants will complete a set of self-report questionnaires measuring parental engagement, self-efficacy, parent-infant attachment, mental health, perceived stress and social support. Additionally, one parent per family will be invited to participate in a qualitative interview to discuss their experience in the NICU. Qualitative data will be analysed thematically using NVivo 12 to identify key themes, and statistical analyses will be conducted using RStudio to determine which factors are most strongly associated with parental engagement and their interactions with the clinical team. Finally, HCPs will be invited to assist and participate in a qualitative interview regarding their perspectives on the NICU environment and the study’s impact on the unit (ie, reduction in HCP burden due to increased parental engagement). Findings from this study will offer valuable insights to inform future clinical strategies aimed at enhancing parental engagement and self-efficacy in the NICU. These outcomes may contribute to improved neonatal outcomes, parental mental health and the advancement of evidence-based, family-centred care policies.

Ethics and dissemination: The protocol was approved by the Montreal University Health Centre’s (MUHC) Research Ethics Board (2025-9392). Findings derived from this study have the potential to optimise parental engagement in the NICU to promote family resilience and child well-being.

Implications of findings: Our study protocol aims to underscore the critical role of self-efficacy and other key psychosocial factors, such as lower parental stress and higher emotion regulation, in promoting parental engagement and collaboration within the NICU. We anticipate that higher levels of self-efficacy will correlate with parental well-being, increased caregiving engagement (ie, basic baby care, improved communication with NICU staff) and enhanced parent-infant bonding. These findings may support the development of structured interventions that empower parents and streamline provider-parent collaboration. In clinical practice, these insights can guide the integration of tailored parental support programmes to optimise discharge preparation and reduce provider burden by promoting shared caregiving responsibilities. Future initiatives could build further on this model to guide institutional policies that aim to prioritise parental empowerment (ie, greater self-efficacy and engagement) as a fundamental pillar of neonatal care.

Keywords: Health; MENTAL HEALTH; Neonatal intensive & critical care; Parents.

Abstract

Background: Variation in the uptake of evidence-based practices and adoption of unproven therapies by neonatal intensive care units might contribute to clinical variability. Objective was to survey current oxygen saturation targets (SpO2), the use of automatic adjustment of inspired oxygen in infants on respiratory support, the criteria for routine retinal examinations for ROP and the use of anti-vascular endothelial growth factor (VEGF) agents to treat ROP in the International Network for Evaluating Outcomes for Neonates (iNeo).

Methods: Online pre-piloted anonymous questionnaires on care practices in 2023 for extremely preterm (<29 weeks) infants were sent to the Directors of 608 NICUs in the iNeo. Four questions concerned ROP management and results were compared with a similar 2015 survey.

Results: There were 11 participating networks from 12 high-income countries and one from a middle-income country. The overall NICU response rate was 63% (382 units). Despite variability between NICUs, within networks there was limited change in SpO2 targets between 2015 and 2023. The median upper and lower SpO2 targets were 95% and 89%; in 18% of NICUs the upper target was ≥96%, in 13% the lower target was ≤85%. Automated loop systems for controlled oxygen delivery were used in 24% of NICUs. Most NICUs (78%) used a combination of birthweight and gestation as ROP screening criteria. Intravitreal anti-VEGF agents were used to treat ROP in all networks and by 76% of NICUs.

Conclusions: There was considerable variation in care practices between NICUs and the relationship of this to clinical outcomes should be explored.

Abstract

Introduction: Preeclampsia is a hypertensive disorder of pregnancy associated with placental dysfunction. Optoacoustic imaging enables non-invasive, real-time assessment of placental oxygen saturation. This study aimed to evaluate placental oxygenation and its response to hypoxia in the STOX1A mouse model of preeclampsia.

Methods: Two groups were studied: STOX1A pregnancies (wild-type females crossed with transgenic STOX1A males) and controls (wild-type crosses). Blood pressure and urinary albumin-to-creatinine ratio were monitored during gestation. Placental oxygen saturation was assessed by multispectral optoacoustic imaging between embryonic days 15.5 and 17.5 under normoxia and hypoxia. Delta oxygen saturation and desaturation kinetics were analyzed using sigmoid curve fitting.

Results: Thirty-one placentas from seventeen control pregnancies and twenty-nine placentas from twenty STOX1A pregnancies were analyzed. The STOX1A group showed increased blood pressure and albuminuria compared to controls (mean systolic blood pressure change at embryonic day 17.5: +21.2 ± 11 mmHg versus -8.4 ± 3.7 mmHg, p = 0.006; albumin-to-creatinine ratio fold-change: 3.91 [2.52-17.14] versus 0.86 [0.43-2.49], p = 0.033). Placental baseline oxygen saturation was similar between groups (70.1 ± 5.3 percent versus 70.0 ± 6.9 percent, p = 0.96). No significant differences were observed in delta oxygen saturation (17.0 ± 6.9 percent versus 16.1 ± 7.1 percent, p = 0.61) or desaturation rate (8.6 ± 6.0 versus 7.9 ± 6.1, p = 0.43) during hypoxia.

Discussion: Despite a confirmed preeclamptic phenotype, placental oxygenation and adaptation to maternal hypoxia were preserved in the STOX1A model, suggesting maintained placental resilience in late gestation.

Keywords: Mouse model; Optoacoustic imaging; Placental oxygenation; Preeclampsia.

Abstract

Objective: To assess whether procalcitonin-guided decision making can safely reduce the duration of antibiotic treatment in neonatal late onset sepsis.

Design: Prospective multicentre, randomised open label trial.

Setting: 33 level 3 and level 2B neonatology departments in France.

Participants: Newborn babies born after 24 weeks’ gestation, of postconceptional age 24-45 weeks and after 4 days of life, weighing more than 700 g, with suspected or proven late onset sepsis, requiring antibiotics for more than 48 hours, and without meningitis, septic shock, and deep-seated infection.

Interventions: Participants were randomly assigned to procalcitonin-guided or usual care antibiotic treatment. In the procalcitonin-guided group, procalcitonin concentration was measured at randomisation and then every two days. A non-binding recommendation to discontinue antibiotics was given if the procalcitonin concentration was 0.5 µg/L or lower. In the usual care group, treatment was provided according to local protocols.

Main outcome measures: The primary outcome was the duration of antibiotic treatment (under the superiority hypothesis). The key secondary outcome was non-inferiority for mortality (margin 3%) at day 28 after randomisation.

Results: Between February 2019 and February 2023, 248 newborns were randomised to the procalcitonin-guided group and 256 to the usual care group. In the intention-to-treat analysis, the median duration of antibiotic treatment was eight days (interquartile range (IQR) 5.0-12.0) in the procalcitonin-guided group versus 10 days (8.0-13.0) in the usual care group (absolute difference between groups -2.0 (IQR -3.8 to -1.0), P<0.001). At day 28, the proportion of death was six of 248 newborns (2.4%) in the procalcitonin-guided group versus 10 of 256 (3.9%) in the usual care group (absolute difference between groups -1.5% (95% confidence interval (CI) -5.0 to 1.8). The proportion of recurrence was seven of 248 (2.8%) newborns in the procalcitonin-guided group versus 10 (3.9%) of 256 in the usual care group (absolute difference between groups -1.1% (95% CI -4.6 to 2.3).

Conclusion: In this study population, the use of procalcitonin significantly reduced the duration of antibiotic treatment in neonatal late onset sepsis, without increasing mortality or serious adverse events.

Trial registration: NCT03730636.

Keywords: Intensive care units, neonatal; Neonatology.

Abstract

Objective: Preterm birth is the leading cause of neonatal mortality and remains a major public health concern. Antenatal corticosteroids (ACS) significantly reduce the complications associated with prematurity, particularly when administered between 24h and 7 days before delivery. The objective of this study was to assess the proportion of women receiving ACS within the optimal window according to clinical indication, and to identify factors that may influence timing for each indication.

Material and methods: We conducted a retrospective, single center observational study at Armand Trousseau Hospital (APHP, Paris) throughout 2022. Singleton pregnancies at risk of preterm birth and treated with ACS were included. The primary outcome was delivery within the optimal ACS-to-birth interval (24h-7 days), adjusted for indication. The secondary outcome was the proportion of patients who delivered at term.

Results: Among the 185 women included, only 19% delivered within the optimal window. The mean ACS-to-delivery interval was 31.2 days. Optimal timing varied by indication: preeclampsia (40%), preterm premature rupture of membranes (31%), threatened preterm labor (6%), isolated fetal growth restriction (13%), and vaginal bleeding without cervical change (0%). No clinical factor was significantly associated with optimal timing, except for severe hypertension in the context of preeclampsia. Notably, 29% of patients delivered at term.

Conclusion: Most women received ACS outside the optimal therapeutic window. These findings highlight the need for predictive tools tailored to each indication to improve ACS targeting and reduce unnecessary exposure.

Keywords: Antenatal corticosteroids; Corticothérapie anténatale; Délai optimal; Naissance prématurée; Optimal timing; Preterm delivery.