Publications

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.

Abstract

Background & aims: Body mass index (BMI) is used to identify high-risk groups in childhood and to target early interventions to prevent later metabolic disorders. This is a priority area for research among children born very preterm (VPT) given growing concern with their long-term risks of adverse metabolic outcomes. Two principal international BMI classifications exist for underweight, overweight and obesity (OWOB) in children (International Obesity Task Force (IOTF) and World Health Organization (WHO)), but how the choice of reference affects results of research in children born VPT is unknown. Our objective was to compare the prevalence and risk factors for underweight and OWOB using these two references among five-year-old children born VPT.

Methods: Data comes from a population-based cohort of children born VPT in 11 European countries in 2011-12 with information from medical records during the neonatal hospitalization and parental questionnaires at age five. BMI at five years of age was classified into underweight and OWOB using IOTF and WHO references (n=2,654 children). Conversion algorithms were also applied to prevalence estimates. Associations with sociodemographic, perinatal and neonatal characteristics were assessed using multinomial logistic regression with multiple imputation and inverse probability weighting to account for missing data and attrition.

Results: After applying a cutoff of -1SD to define mild underweight for WHO – since this category exists only for IOTF – the estimated prevalence of total underweight was similar between IOTF and WHO references (27.8% vs 27.0%, respectively). IOTF classified a higher proportion of children as having severe underweight (4.1% vs 1.6%). For OWOB, prevalence estimates were lower using IOTF, particularly among boys (8.6% vs 14.1%). The algorithms provided good conversion (1-2% absolute difference) of prevalence between references for underweight and obesity overall, and overweight for girls, but had a larger error for overweight in boys. Risk factors were similar for underweight and OWOB for both references, with the exception of sex and maternal country of birth (OWOB significantly associated using IOTF but not WHO references).

Conclusion: Clinicians and researchers should be aware of the difference in prevalence of suboptimal BMI when interpreting findings from studies using different classifications and IOTF should be used with caution for investigating sex differences. Given the high prevalence of mild underweight in children born VPT, the cutoff of -1SD should be used with the WHO references in studies of BMI in this population.

Keywords: Body mass index; IOTF growth charts; Overweight and obesity; Underweight; Very preterm; WHO growth charts.

Abstract

Background & aims: Body mass index (BMI) is used to identify high-risk groups in childhood and to target early interventions to prevent later metabolic disorders. This is a priority area for research among children born very preterm (VPT) given growing concern with their long-term risks of adverse metabolic outcomes. Two principal international BMI classifications exist for underweight, overweight and obesity (OWOB) in children (International Obesity Task Force (IOTF) and World Health Organization (WHO)), but how the choice of reference affects results of research in children born VPT is unknown. Our objective was to compare the prevalence and risk factors for underweight and OWOB using these two references among five-year-old children born VPT.

Methods: Data comes from a population-based cohort of children born VPT in 11 European countries in 2011-12 with information from medical records during the neonatal hospitalization and parental questionnaires at age five. BMI at five years of age was classified into underweight and OWOB using IOTF and WHO references (n=2,654 children). Conversion algorithms were also applied to prevalence estimates. Associations with sociodemographic, perinatal and neonatal characteristics were assessed using multinomial logistic regression with multiple imputation and inverse probability weighting to account for missing data and attrition.

Results: After applying a cutoff of -1SD to define mild underweight for WHO – since this category exists only for IOTF – the estimated prevalence of total underweight was similar between IOTF and WHO references (27.8% vs 27.0%, respectively). IOTF classified a higher proportion of children as having severe underweight (4.1% vs 1.6%). For OWOB, prevalence estimates were lower using IOTF, particularly among boys (8.6% vs 14.1%). The algorithms provided good conversion (1-2% absolute difference) of prevalence between references for underweight and obesity overall, and overweight for girls, but had a larger error for overweight in boys. Risk factors were similar for underweight and OWOB for both references, with the exception of sex and maternal country of birth (OWOB significantly associated using IOTF but not WHO references).

Conclusion: Clinicians and researchers should be aware of the difference in prevalence of suboptimal BMI when interpreting findings from studies using different classifications and IOTF should be used with caution for investigating sex differences. Given the high prevalence of mild underweight in children born VPT, the cutoff of -1SD should be used with the WHO references in studies of BMI in this population.

Keywords: Body mass index; IOTF growth charts; Overweight and obesity; Underweight; Very preterm; WHO growth charts.

Abstract

Background: Hypertensive disorders of pregnancy represent a major cause of maternal and fetal morbidity and mortality. Despite primary aldosteronism (PA) being the most common cause of secondary hypertension, there is limited data on pregnancy complications in patients with PA.

Methods: We conducted an international survey across 5 Hypertension Centers in Europe to gather data on maternal and neonatal complications in women diagnosed with PA from 2000 to 2022. We included 102 women aged 18 to 45 years at PA diagnosis who were pregnant either after or <1-year before the diagnosis of PA. The first eligible pregnancy for each patient was included.

Results: Overall, 56% of pregnancies were complicated, with the most frequent complications being maternal preeclampsia (36%), preterm birth (30%), low birth weight (30%), and neonatal intensive care admission (22%). Hypokalemia occurred in 31% of pregnancies. Pregnancies occurring before PA diagnosis presented a poorer blood pressure control and were associated with higher rates of overall, maternal, and fetal/neonatal complications compared with pregnancies in patients with an established PA diagnosis. Independent predictors of complications included uncontrolled blood pressure values during pregnancy (odds ratio [OR], 7.05), undiagnosed PA (OR, 4.37), North/Black African ethnicity (OR, 3.69), a higher body mass index (OR, 1.09), and treatment with a higher number of antihypertensive drugs at PA diagnosis (OR, 2.18).

Conclusions: PA is associated with a high rate of pregnancy-related complications, predominantly preeclampsia. Undiagnosed PA during gestation significantly increases the risk of adverse outcomes. Early identification and optimized hypertension control in women with PA are critical to improve maternal and fetal outcomes.

Keywords: aldosterone; blood pressure; body mass index; hypokalemia; pregnancy.

Abstract

Genome-wide Association Studies (GWAS) have played a crucial role in uncovering the genetics underlying complex human traits. Recently, there has been considerable interest in adapting GWAS-like methodologies to investigate pathogenic bacteria. Despite the variety of methods proposed, there remains a lack of clarity on how to effectively model the intricate population structures found in bacterial cohorts. In this study, we analyze the genetic architecture of whole-genome sequencing data from three distinct bacterial species, showing that the standard models used in human genetics, typically employed by existing bacterial GWAS methods, fall short when applied to organisms with highly structured genomes. Building on these findings, we introduce ChoruMM, a robust and powerful multi-component linear mixed model. This model infers components through hierarchical clustering of the bacterial genetic relatedness matrix. Extensive simulations show that our approach reduces false positives while maintaining, or even improving, detection rates compared to current pipelines. The ChoruMM package includes post-processing and visualization tools designed to address the prevalent issue of long-range correlations in bacterial genomes, enabling accurate assessment and calibration of type I error rates.

Abstract

Background and objective: Extremely preterm infants are at very high risk of neonatal death and disabilities. Their survival rate is much variable in developed countries and in France is much lower than other countries. Our objective is to evaluate the impact of an intervention to standardize the perinatal management of extremely preterm infants.

Population: Women hospitalized between 22 and 26 weeks for risk of preterm delivery with a alive fetus or a stillbirth at admission and with a delivery between 22 and 26 completed weeks.

Intervention: Our complex intervention aimed at standardizing the organization of care based on the following principles: A collective obstetric-pediatric prognostic assessment, in a non-emergency setting, with a consensus decision about the obstetric and neonatal management proposed-either active or palliative care; An interview with the parents to inform them, answer their questions, propose either active or palliative care and then ask their opinion.

Methods: A Stepped-wedge cluster-randomized trial. Perinatal networks will be randomly allocated to the intervention in 5 waves every 3 months, with a total recruitment period of 21 months (including 3-month transition periods). All perinatal networks will have a period with and without the intervention. After the allocation of clusters to the intervention period, the teams will be trained in the intervention protocol and then will undergo a 3-month transition period to learn the protocol thoroughly.

Sample size: We hypothesis hypothesized is that survival without severe morbidity will could rise from 20 to 35% after the intervention, but envisaged different scenarios with varying survival without severe morbidity in the control and intervention periods. The intraclass correlation coefficients was set to 0.07. With an average number of 60 to 70 extremely preterm infants recruited per year, a number of 20 clusters (perinatal networks) were was sufficient to provide at least 80% power in most scenarios, and 25 clusters would provide at least 80% power in all scenarios envisaged.

Setting: Twenty-five perinatal networks including 34 neonatal level-3 hospital, and 285 maternity units overall.

Outcome: Child’s survival without severe morbidity at hospital discharge.

Expected results: Improvement of the health of extremely preterm infants and, if the intervention shows that it is effective, equitable access to care according to place of birth in France.

Ethics: The protocol was approved by the Committee for Protection of Persons Involved in Biomedical Research (CPP Ile de France V PARIS), and the French Data Protection Authority (30/12/2021, N°21.03700000050-MS02).

Trial registration: The trial was registered before the beginning of the study at ClinicalTrials.gov (December 20, 2021-NCT05248477).

Keywords: Extremely preterm infants; Organization of care; Perinatal management; Perinatal network.