Spatiotemporal changes of pelagic food webs investigated by environmental DNA metabarcoding and connectivity analysis.

Environmental DNA metabarcoding (eDNA metaB) is fundamental for monitoring marine biodiversity and its spread in coastal ecosystems. We applied eDNA metaB to seawater samples to investigate the spatiotemporal variability of plankton and small pelagic fish, comparing sites with different environmental conditions across a coast-to-offshore gradient at river mouths along the Campania coast (Italy) over 2 years (2020-2021). We found a marked seasonality in the planktonic community at the regional scale, likely owing to the hydrodynamic connection among sampling sites, which was derived from numerical simulations. Nonetheless, spatial variability among plankton communities was detected during summer. Overall, slight changes in plankton and fish composition resulted in the potential reorganization of the pelagic food web at the local scale. This work supports the utility of eDNA metaB in combination with hydrodynamic modelling to study marine biodiversity in the water column of coastal systems. This article is part of the theme issue 'Connected interactions: enriching food web research by spatial and social interactions'.

Lung Ultrasonography Scores in Preterm Infants and Respiratory Outcomes at Age 2 Years.

This cohort study examines the role of lung ultrasonography score in estimating respiratory episodes needing drugs or hospitalization in premature infants.

Blinding Assessments in Neonatal Ventilation Meta-Analyses: A Systematic Meta-Epidemiological Review.

INTRODUCTION: Randomization and blinding are generally important in randomized trials. In neonatology, blinding of ventilation strategies is unfeasible if not impossible and we hypothesized that its importance has been overestimated, while the peculiarities of the neonatal patient and the specific outcomes have not been considered. METHODS: For this meta-epidemiological review, we searched PubMed and Scopus databases in November 2023. We included all meta-analyses focusing on ventilation, published in past 5 years, and reporting either mortality or bronchopulmonary dysplasia (BPD) as an outcome. We extracted the information about how the authors had analyzed risk of bias and evidence certainty. RESULTS: We screened 494 abstracts and included 40 meta-analyses. Overall, 13 of the 40 reviews assessed blinding properly. Australian and European authors were most likely to perform correct assessment of the blinding (p = 0.03) and the use of RoB 2.0 tool was also associated with proper assessment (p < 0.001). In multivariate regression, the use of RoB 2.0 was the only factor associated with a proper assessment (Beta 0.57 [95% confidence interval: 0.29-0.99]). GRADE ratings were performed in 25 reviews, and the authors downgraded the evidence certainty due to risk of bias in 19 of these and none of these reviews performed the blinding assessment correctly. CONCLUSION: In past neonatal evidence syntheses, the role of blinding has been mostly overestimated, which has led to downgrading of evidence certainty. Objective outcomes (such as mortality and BPD) do not need to be downgraded due to lack of blinding, as the knowledge of the received intervention does not influence the outcome assessment.

The Multifaceted Burden of Respiratory Syncytial Virus (RSV) Infections in Young Children on the Family: A European Study.

INTRODUCTION: Since the majority of hospitalisations due to RSV occur in young children, the illness profoundly influences the entire family. However, comprehensive evidence regarding its overall effects remains limited. The ResQ Family study aims to investigate the burden of RSV-induced pediatric hospitalisation on affected families. METHODS: Spanning the 2022-2023 RSV season, an interdisciplinary, observational study was conducted in Germany, France, Italy and Sweden. Using an online questionnaire, parents and caregivers of children (< 24 months of age) with an RSV-induced hospitalisation were recruited. Information was gathered on topics related to RSV and parental health-related quality of life (HRQoL) during the acute infection phase (t0) and 6 weeks later (t1). Descriptive evaluations of the data set were performed during t0 and regarding a potential change over the observation period (t0 vs. t1). Subgroup analysis aimed to further identify differences across the countries. RESULTS: A total set of 138 affected parents/caregivers were included in the study, with 59 participants responding to the follow-up survey (t1). Particularly during the acute infection phase, parental HRQoL was shown to be negatively influenced by the child's RSV infection [total score (p < 0.001, d = 0.54), parent HRQoL summary score (p < 0.001, d = 0.67) and family functioning summary score (p = 0.007, d = 0.33)]. Significant disparities in disease awareness and support structures were observed across Europe, with France and Sweden showing notably higher levels. CONCLUSION: The ResQ Family study provides convincing evidence that RSV-associated hospitalisations in young children across Europe generate a multifaced burden for the entire family, partly even beyond the acute infection phase. Standardised approaches for disease prevention at societal, educational and policy levels are needed to guarantee every newborn the best possible start into life. TRIAL REGISTRATION: ClinicalTrials.gov, identifier, NCT05550545.

Quantitative Lung Ultrasonography to Guide Surfactant Therapy in Neonates Born Late Preterm and Later.

Importance: Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of early preterm neonates. The lung ultrasonography score (LUS) is accurate to guide surfactant replacement in early preterm neonates, but to our knowledge, it has not yet been studied in the late preterm through full-term neonatal population. Objective: To assess whether LUS is equally accurate to predict surfactant need in late preterm through full-term neonates as in early preterm neonates. Design, Setting, and Participants: This prospective, international, multicenter diagnostic study was performed between December 2022 and November 2023 in tertiary academic neonatal intensive care units in France, Italy, Spain, and the US. Late preterm through full-term neonates (≥34 weeks' gestation) with respiratory failure early after birth were enrolled. Exposure: Point-of-care lung ultrasonography to calculate the neonatal LUS (range, 0-18, with higher scores indicating worse aeration), which was registered in dedicated research databases and unavailable for clinical decision-making. Main Outcomes and Measures: The main outcomes were the area under the curve (AUC) in receiver operating characteristic analysis and derived accuracy variables, considering LUS as a replacement for other tests (ie, highest global accuracy) and as a triage test (ie, highest sensitivity). Sample size was calculated to assess noninferiority of LUS to predict surfactant need in the study population compared with neonates born more prematurely. Correlations of LUS with the ratio of hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) and with the oxygen saturation index (OSI) were assessed. Results: A total of 157 neonates (96 [61.1%] male) were enrolled and underwent lung ultrasonography at a median of 3 hours (IQR, 2-7 hours) of life; 32 (20.4%) needed surfactant administration (pretest probability, 20%). The AUC was 0.87 (95% CI, 0.81-0.92). The highest global accuracy and sensitivity were reached for LUS values higher than 8 or 4 or lower, respectively. Subgroup analysis gave similar diagnostic accuracy in neonates born late preterm (AUC, 0.89; 95% CI, 0.81-0.97; n = 111) and early term and later (AUC, 0.84; 95% CI, 0.73-0.96; n = 46). After adjusting for gestational age, LUS was significantly correlated with SpO2:FiO2 (adjusted ß, -10.4; 95% CI, -14.0 to -6.7; P < .001) and OSI (adjusted ß, 0.2; 95% CI, 0.1-0.3; P < .001). Conclusions and Relevance: In this diagnostic study of late preterm through full-term neonates with respiratory failure early after birth, LUS accuracy to predict surfactant need was not inferior to that observed in earlier preterm neonates. An LUS higher than 8 was associated with highest global accuracy (replacement test), suggesting that it can be used to guide surfactant administration. An LUS value of 4 or lower was associated with the highest sensitivity (triage test), suggesting it is unlikely for this population to need surfactant.

Skin thickness in preterm neonates: relationship with skin bilirubin and predicted mortality.

This study investigates the relationship between the thickness of skin in preterm infants and its link with bilirubin and mortality, as this may help understanding the potential deleterious effects of phototherapy. Observational, prospective cohort study enrolling preterm neonates needing phototherapy and admitted to a neonatal intensive care unit. Transcutaneous bilirubin (TcB) and blood bilirubin were simultaneously measured before the onset of phototherapy, if any. The skin depth was measured by high-frequency point-of-care ultrasound. Mortality risk was estimated using the critical risk index for babies-II. Correlations and multivariate regressions (adjusting for several confounders) were applied to study the relationship between skin depth, TcB, and predicted mortality. One hundred fifty-nine neonates were studied. There was a positive and steady correlation between skin depth and TcB (r = 0.402 (95%CI: 0.206; 0.568), p < 0.001) and inverse correlation between skin depth and predicted mortality (r = -0.503 (95%CI: -0.61; -0.37), p < 0.001) as well as between TcB and predicted mortality (r = -0.303 (95%CI: -0.49; -0.09), p = 0.005). Multivariate analyses showed skin depth to be the strongest risk factors associated with both increasing TcB (ß = 198 (59;338), p < 0.001) and decreasing risk of death (ß = -24 (-46;2), p = 0.049). Blood bilirubin and gestational age were also associated with TcB and predicted mortality, respectively.   Conclusion: In NICU-admitted preterm infants, thicker skin is associated with higher TcB levels irrespective of gestational age. Greater skin depth is also associated with lower predicted mortality irrespective of blood bilirubin. What is Known: • In preterm infants, phototherapy may improve neuro-developmental outcomes but, particularly in the smallest and sickest ones, may increase mortality. • Mechanisms behind this effect are unclear but could involve the small thickness of preterm skin. This however has never been studied in relationship with bilirubin and mortality. What is New: • In NICU-admitted preterm infants, thicker skin is associated with higher levels of transcutaneous bilirubin, irrespective of gestational age and with lower predicted mortality, irrespective of blood bilirubin. • These data suggest that a thinner skin may contain less bilirubin to be photoisomerised and protect internal tissues less efficiently.

Global and regional heterogeneity of lung aeration in neonates with different respiratory disorders: a physiological, observational study.

BACKGROUND.: Aeration heterogeneity affects lung stress and influences outcomes in adults with acute respiratory distress syndrome (ARDS). We hypothesize that aeration heterogeneity may differ between neonatal respiratory disorders and is associated with oxygenation, so its evaluation may be relevant in managing respiratory support. METHODS.: Observational, prospective study. Neonates with respiratory distress syndrome (RDS), transient tachypnea (TTN), evolving bronchopulmonary dysplasia (BPD) and neonatal ARDS (NARDS) were enrolled. Quantitative lung ultrasound and transcutaneous blood gas measurements were simultaneously performed. Global aeration heterogeneity (with its intra- and inter-patient components) and regional aeration heterogeneity were primary outcomes; oxygenation metrics were the secondary outcomes. RESULTS.: 230 (50 RDS, TTN or evolving BPD and 80 NARDS) patients were studied. Intra-patient aeration heterogeneity was higher in TTN (mean: 61% [standard deviation: 33%]) and evolving BPD (mean: 57% [standard deviation: 20%], p<0.001), with distinctive aeration distributions. Inter-patient aeration heterogeneity was high for all disorders (Gini-Simpson index: between 0.6 and 0.72) except RDS (Gini-Simpson index: 0.5) whose heterogeneity was significantly lower than all others (p<0.001). NARDS and evolving BPD had the most diffuse injury and worst gas exchange metrics. Regional aeration heterogeneity was mostly localized in upper anterior and posterior zones. Aeration heterogeneity and total lung aeration had an exponential relationship (p<0.001; adj-R 2=0.62). Aeration heterogeneity is associated with greater total lung aeration (i.e., higher heterogeneity means a relatively higher proportion of normally aerated lung zones, thus greater aeration; p<0.001; adj-R 2=0.83) and better oxygenation metrics upon multivariable analyses. CONCLUSIONS.: Global aeration heterogeneity and regional aeration heterogeneity differ amongst neonatal respiratory disorders. TTN and evolving BPD have the highest intra-patient aeration heterogeneity. TTN, evolving BPD and NARDS have the highest inter-patient aeration heterogeneity, but the latter two have the most diffuse injury and worst gas exchange. Higher aeration heterogeneity is associated with better total lung aeration and oxygenation.

NIV-NAVA versus non-invasive respiratory support in preterm neonates: a meta-analysis of randomized controlled trials.

OBJECTIVE: To analyze the clinical and physiological outcomes of NIV-NAVA in preterm infants compared with other non-invasive respiratory support. STUDY DESIGN: We conducted a meta-analysis of RCTs and randomized crossover studies comparing NIV-NAVA to other non-invasive strategies in preterm neonates. RESULTS: NIV-NAVA was superior to other non-invasive support in maximum EAdi (MD - 0.66 µV; 95% CI - 1.17 to -0.15; p = 0.01), asynchrony index (MD - 49.8%; 95% CI - 63.1 to -36.5; p < 0.01), and peak inspiratory pressure (MD - 2.2 cmH2O; 95% CI - 2.7 to -1.7; p < 0.01). However, there were no significant differences in the incidences of intubation (RR 0.91; 95% CI 0.56-1.48; p = 0.71), reintubation (RR 0.72; 95% CI 0.45-1.16; p = 0.18), or bronchopulmonary dysplasia (RR 0.77; 95% CI 0.37-1.60; p = 0.48). CONCLUSION: NIV-NAVA was associated with improvements in maximum Edi, asynchrony index, and peak inspiratory pressure relative to other non-invasive respiratory strategies, without significant differences in clinical outcomes between groups.

Maternal and neonatal outcomes of French prospective multicenter cohort study COVIPREG during the first two COVID-19 waves.

BACKGROUND: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic. METHODS: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13]). CONCLUSIONS: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines. TRIAL REGISTRATION: NCT04355234 (registration date: 21/04/2020).

Critical care of severe bronchiolitis during shortage of ICU resources.

Large seasonal outbreaks of bronchiolitis put pressure on healthcare systems and particularly on intensive care units (ICUs). ICU admission is necessary to provide respiratory support to the severest cases, otherwise bronchiolitis can result in substantial mortality. ICU resources are often insufficient and there is scant evidence to guide the ICU clinical management. Most available studies do not cover the ICU-admitted cases and do not consider the associated public health issues. We review this topic through a multidisciplinary approach from both the clinical and public health perspectives, with an analysis based on pathophysiology and cost-effectiveness. We suggest ways to optimise respiratory care, minimise ICU stay, "protect" ICU beds and, whenever possible, make them available for other critically ill children. We also provide guidance on how to prepare ICUs to work under stressful conditions due to outbreaks and to reduce the risk of nosocomial cross-contamination, particularly in ICUs caring for high-risk children. Funding: None.

Inspiratory-expiratory variation of pleural line thickness in neonates with and without acute respiratory failure.

BACKGROUND: There are relatively few data about the ultrasound evaluation of pleural line in patients with respiratory failure. We measured the pleural line thickness during different phases of the respiratory cycle in neonates with and without acute respiratory failure as we hypothesized that this can significantly change. METHODS: Prospective, observational, cohort study performed in an academic tertiary neonatal intensive care unit recruiting neonates with transient tachypnoea of the neonate (TTN), respiratory distress syndrome (RDS) or neonatal acute respiratory distress syndrome (NARDS). Neonates with no lung disease (NLD) were also recruited as controls. Pleural line thickness was measured with high-frequency ultrasound at end-inspiration and end-expiration by two different raters. RESULTS: Pleural line thickness was slightly but significantly higher at end-expiration (0.53 [0.43-0.63] mm) than at end-inspiration (0.5 [0.4-0.6] mm; p = 0.001) for the whole population. End-inspiratory (NLD: 0.45 [0.38-0.53], TTN: 0.49 [0.43-0.59], RDS: 0.53 [0.41-0.62], NARDS: 0.6 [0.5-0.7] mm) and -expiratory (NLD: 0.47 [0.42-0.56], TTN: 0.48 [0.43-0.61], RDS: 0.53 [0.46-0.65], NARDS: 0.61 [0.54-0.72] mm) thickness were significantly different (overall p = 0.021 for both), between the groups although the absolute differences were small. The inter-rater agreement was optimal (ICC: 0.95 (0.94-0.96)). Coefficient of variation was 2.8% and 2.5% for end-inspiratory and end-expiratory measurements, respectively. These findings provide normative data of pleural line thickness for the most common forms of neonatal acute respiratory failure and are useful to design future studies to investigate possible clinical applications.

Hydrocortisone in very preterm neonates for BPD prevention: meta-analysis and effect size modifiers.

OBJECTIVES: To clarify if systemic hydrocortisone, in protocols allowing to start it before the 15th day of life, prevents bronchopulmonary dysplasia (BPD) or other adverse outcomes in very preterm neonates, and to identify any possible effect size modifiers. STUDY DESIGN: Systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Additional analyses included meta-regressions and review of biological plausibility. RESULTS: Seven trials were included, they were of general good quality and accounted for a total of 2193 infants. Hydrocortisone treatment did not reduce BPD (risk ratio (RR) 0.84 (95% CI 0.64 to 1.04)), but heterogeneity was evident (I2=51.6%). The effect size for BPD is greatest for 10-12 days duration of treatment (ß=0.032 (0.01), p=0.007) and tended to be greater in patients with chorioamnionitis (ß=-1.5 (0.841), p=0.07). Hydrocortisone treatment may significantly reduce mortality (RR 0.75 (95% CI 0.59 to 0.91)), there is no heterogeneity (I2=0) and the reduction tended to be greater in males (ß=-0.06 (0.03), p=0.07). Hydrocortisone may significantly reduce necrotising enterocolitis (NEC; RR 0.72 (95% CI 0.53 to 0.92)); there is neither heterogeneity (I2=0%) nor any effect size modifiers. Hydrocortisone did not affect other adverse outcomes of prematurity. CONCLUSIONS: Systemic hydrocortisone may be considered, on a case-by-case evaluation, to reduce mortality and NEC, while it does not affect BPD. There are some potential effect size modifiers for mortality and BPD which should be addressed in future explanatory trials. PROSPERO REGISTRATION NUMBER: CRD42023400520.

International Online Survey on the Management of Patent Ductus Arteriosus.

INTRODUCTION: There is uncertainty and lack of consensus regarding optimal management of patent ductus arteriosus (PDA). We aimed to determine current clinical practice in PDA management across a range of different regions internationally. MATERIALS AND METHODS: We surveyed PDA management practices in neonatal intensive care units using a pre-piloted web-based survey, which was distributed to perinatal societies in 31 countries. The survey was available online from March 2018 to March 2019. RESULTS: There were 812 responses. The majority of clinicians (54%) did not have institutional protocols for PDA treatment, and 42% reported variable management within their own unit. Among infants <28 weeks (or <1,000 g), most clinicians (60%) treat symptomatically. Respondents in Australasia were more likely to treat PDA pre-symptomatically (44% vs. 18% all countries [OR 4.1; 95% CI 2.6-6.5; p < 0.001]), and respondents from North America were more likely to treat symptomatic PDA (67% vs. 60% all countries [OR 2.0; 95% CI 1.5-2.6; p < 0.001]). In infants ≥28 weeks (or ≥1,000 g), most clinicians (54%) treat symptomatically. Respondents in North America were more likely to treat PDAs in this group of infants conservatively (47% vs. 38% all countries [OR 2.3; 95% CI 1.7-3.2; p < 0.001]), and respondents from Asia were more likely to treat the PDA pre-symptomatically (21% vs. 7% all countries [OR 5.5; 95% CI 3.2-9.8; p < 0.001]). DISCUSSION/CONCLUSION: There were marked international differences in clinical practice, highlighting ongoing uncertainty and a lack of consensus regarding PDA management. An international conglomeration to coordinate research that prioritises and addresses these areas of contention is indicated.

Efficacy and Safety of Palivizumab as a Prophylaxis for Respiratory Syncytial Virus (RSV) Disease: An Updated Systemic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to summarize the current evidence regarding the efficacy and safety of palivizumab as a prophylaxis for respiratory syncytial virus (RSV) disease. We searched MEDLINE via PubMed, Scopus, Cochrane, Web of Science, Embase, and Science Direct from inception till November 2023. Studies that assessed the efficacy and safety of palivizumab in infants aged between 28 days and three months of age were included. We analyzed the data using Review Manager 5.4 software, with results pooled across studies and expressed as risk ratios (RR) with 95% confidence intervals (CI). A total of 10 studies were included. The effect estimates favored palivizumab over placebo regarding the hospitalization for RSV infection (RR=0.51, 95% CI: 0.40 to 0.65; P<0.00001) and ICU admission (RR=0.49, 95% CI: 0.30 to 0.81; P=0.005). On the other hand, the effect estimate showed no significant difference between palivizumab and placebo regarding all-cause mortality (RR=0.69, 95% CI: 0.42 to 1.15; P=0.16), lower respiratory tract infection (RR=0.42, 95% CI: 0.11 to 1.69; P=0.22), and need for mechanical ventilation (RR=0.75, 95% CI: 0.34 to 1.67; P=0.48). Palivizumab can be considered a prophylaxis for RSV disease in young children as it is safe, well-tolerated, and effective in reducing RSV hospitalizations. However, further research through high-quality randomized controlled trials is required to determine its efficacy as a therapeutic agent for established RSV infections.