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Patients in neonatal intensive care units (NICUs) are at high risk of adverse events. The effects of medical and paramedical education programmes to reduce these have not yet been assessed.In this multicentre, stepped-wedge, cluster-randomised controlled trial done in France, we randomly assigned 12 NICUs to three clusters of four units. Eligible neonates were inpatients in a participating unit for at least 2 days, with a postmenstrual age of 42 weeks or less on admission. Each cluster followed a 4-month multifaceted programme including education about root-cause analysis and care bundles. The primary outcome was the rate of adverse events per 1000 patient-days, measured with a retrospective trigger-tool based chart review masked to allocation of randomly selected files. Analyses used mixed-effects Poisson modelling that adjusted for time. This trial is registered with ClinicalTrials.gov, NCT02598609.Between Nov 23, 2015, and Nov 2, 2017, event rates were analysed for 3454 patients of these 12 NICUs for 65 830 patient-days. The event rate per 1000 patient-days reduced significantly from the control to the intervention period (33·9 vs 22·6; incidence rate ratio 0·67; 95% CI 0·50-0·88; p=0·0048).A multiprofessional safety-promoting programme in NICUs reduced the rate of adverse events and severe and preventable adverse events in highly vulnerable patients. This programme could significantly improve care offered to critically ill neonates.Solidarity and Health Ministry, France.

Background Training and assessment of operator competence for the less invasive surfactant administration (LISA) procedure vary. This study aimed to obtain international expert consensus on LISA training (LISA curriculum (LISA-CUR)) and assessment (LISA assessment tool (LISA-AT)). Methods From February to July 2022, an international three-round Delphi process gathered opinions from LISA experts (researchers, curriculum developers, and clinical educators) on a list of items to be included in a LISA-CUR and LISA-AT (Round 1). The experts rated the importance of each item (Round 2). Items supported by more than 80% consensus were included. All experts were asked to approve or reject the final LISA-CUR and LISA-AT (Round 3). Results A total of 153 experts from 14 countries participated in Round 1, and the response rate for Rounds 2 and 3 was >80%. Round 1 identified 44 items for LISA-CUR and 22 for LISA-AT. Round 2 excluded 15 items for the LISA-CUR and 7 items for the LISA-AT. Round 3 resulted in a strong consensus (99–100%) for the final 29 items for the LISA-CUR and 15 items for the LISA-AT. Conclusions This Delphi process established an international consensus on a training curriculum and content evidence for the assessment of LISA competence. Impact This international consensus-based expert statement provides content on a curriculum for the less invasive surfactant administration procedure (LISA-CUR) that may be partnered with existing evidence-based strategies to optimize and standardize LISA training in the future. This international consensus-based expert statement also provides content on an assessment tool for the LISA procedure (LISA-AT) that can help to evaluate competence in LISA operators. The proposed LISA-AT enables standardized, continuous feedback and assessment until achieving proficiency.

International audience; Background: Inappropriate humidification of inspired gas during mechanical ventilation can impair lung development in extremely low birthweight (ELBW) infants. Humidification depends on multiple factors, such as the heater-humidifier device used, type of ventilation, and environmental factors. Few studies have examined inspired gas humidification in these infants, especially during high-frequency oscillatory ventilation (HFOV). Our objective was to compare humidity during HFOV and intermittent positive pressure ventilation (IPPV), in vitro and in vivo.Methods: In vitro and in vivo studies used the same ventilator during both HFOV and IPPV. The bench study used a neonatal test lung and two heater-humidifiers with their specific circuits; the in vivo study prospectively included preterm infants born before 28 weeks of gestation.Results: On bench testing, mean absolute (AH) and relative (RH) humidity values were significantly lower during HFOV than IPPV (RH = 79.4 ± 8.1% vs. 89.0 ± 6.2%, p < 0.001). Regardless of the ventilatory mode, mean RH significantly differed between the two heater-humidifiers (89.6 ± 6.7% vs 78.7 ± 6.8%, p = 0.003). The in vivo study included 10 neonates (mean ± SD gestational age: 25.7 ± 0.9 weeks and birthweight: 624.4 ± 96.1 g). Mean RH during HFOV was significantly lower than during IPPV (74.6 ± 5.7% vs. 83.0 ± 6.7%, p = 0.004).Conclusion: RH was significantly lower during HFOV than IPPV, both in vitro and in vivo. The type of heater-humidifier also influenced humidification. More systematic measurements of humidity of inspired gas, especially during HFOV, should be considered to optimize humidification and consequently lung protection in ELBW infants.

Introduction: Synchronization of non-invasive ventilation is challenging in extremely premature infants. We compared patient-ventilator synchrony between non-invasive neurally adjusted ventilatory assist (NIV-NAVA) using transdiaphragmatic (Edi) catheter and synchronized intermittent positive airway pressure (SiPAP) using an abdominal trigger. Methods: This study was a monocentric, randomized, crossover trial in premature infants born before 28 weeks of gestation, aged 3 days or more, and below 32 weeks postmenstrual age. NIV-NAVA and SiPAP were applied in a random order for 2 h with analysis of data from the second hour. The primary outcome was the asynchrony index. Results: Fourteen patients were included (median [IQR] gestational age at birth 25.6 (25.3–26.4) weeks, median [IQR] birth weight 755 [680–824] g, median [IQR] postnatal age 26.5 [19.8–33.8] days). The median (IQR) asynchrony index was significantly lower in NIV-NAVA versus SiPAP (49.9% [44.1–52.6] vs. 85.8% [74.2–90.9], p < 0.001). Ineffective efforts and auto-triggering were significantly less frequent in NIV-NAVA versus SiPAP (3.0% vs. 32.0% p < 0.001 and 10.0% vs. 26.6%, p = 0.004, respectively). Double triggering was significantly less frequent in SiPAP versus NIV-NAVA (0.0% vs. 9.0%, p < 0.001). No significant difference was observed for premature cycling and late cycling. Peak Edi and swing Edi were significantly lower in NIV-NAVA as compared to SiPAP (7.7 [6.1–9.9] vs. 11.0 [6.7–14.5] μV, p = 0.006; 5.4 [4.2–7.6] vs. 7.6 [4.3–10.8] μV, p = 0.007, respectively). No significant difference was observed between NIV-NAVA and SiPAP for heart rate, respiratory rate, COMFORTneo scores, apnoea, desaturations, or bradycardias. Discussion/Conclusion: NIV-NAVA markedly improves patient-ventilator synchrony as compared to SiPAP in extremely premature infants.

Key Points Question Is early amino acid intake among very preterm infants associated with cognitive performance at age 5 years? Findings In this cohort study of 1789 infants born at less than 30 weeks’ gestation, exposure vs nonexposure to amino acid intake between 3.51 and 4.50 g/kg/d at 7 days after birth was significantly and independently associated with a higher likelihood (61% vs 54%, respectively) of surviving with a full-scale IQ score greater than −1 SD at age 5 years. Meaning The results of this study suggest that high early amino acid intake among very preterm infants is safe and significantly associated with improved cognitive outcomes at age 5 years., Importance An international expert committee recently revised its recommendations on amino acid intake for very preterm infants, suggesting that more than 3.50 g/kg/d should be administered only to preterm infants in clinical trials. However, the optimal amino acid intake during the first week after birth in these infants is unknown. Objective To evaluate the association between early amino acid intake and cognitive outcomes at age 5 years. Design, Setting, and Participants Using the EPIPAGE-2 (Epidemiologic Study on Small-for-Gestational-Age Children—Follow-up at Five and a Half Years) cohort, a nationwide prospective population-based cohort study conducted at 63 neonatal intensive care units in France, a propensity score–matched analysis was performed comparing infants born at less than 30 weeks’ gestation who had high amino acid intake (3.51-4.50 g/kg/d) at 7 days after birth with infants who did not. Participants were recruited between April 1 and December 31, 2011, and followed up from September 1, 2016, to December 31, 2017. Full-scale IQ (FSIQ) was assessed at age 5 years. A confirmatory analysis used neonatal intensive care unit preference for high early amino acid intake as an instrumental variable to account for unmeasured confounding. Statistical analysis was performed from January 15 to May 15, 2021. Exposures Amino acid intake at 7 days after birth. Main Outcomes and Measures The primary outcome was an FSIQ score greater than −1 SD (ie, ≥93 points) at age 5 years. A complementary analysis was performed to explore the association between amino acid intake at day 7 as a continuous variable and FSIQ score at age 5 years. Data from cerebral magnetic resonance imaging at term were available for a subgroup of preterm infants who participated in the EPIRMEX (Cerebral Abnormalities Detected by MRI, Realized at the Age of Term and the Emergence of Executive Functions) ancillary study. Results Among 1789 preterm infants (929 boys [51.9%]; mean [SD] gestational age, 27.17 [1.50] weeks) with data available to determine exposure to amino acid intake of 3.51 to 4.50 g/kg/d at 7 days after birth, 938 infants were exposed, and 851 infants were not; 717 infants from each group could be paired. The primary outcome was known in 396 of 646 exposed infants and 379 of 644 nonexposed infants who were alive at age 5 years and was observed more frequently among exposed vs nonexposed infants (243 infants [61.4%] vs 206 infants [54.4%], respectively; odds ratio [OR], 1.33 [95% CI, 1.00-1.71]; absolute risk increase in events [ie, the likelihood of having an FSIQ score >−1 SD at age 5 years] per 100 infants, 7.01 [95% CI, 0.06-13.87]; P = .048). In the matched cohort, correlation was found between amino acid intake per 1.00 g/kg/d at day 7 and FSIQ score at age 5 years (n = 775; β = 2.43 per 1-point increase in FSIQ; 95% CI, 0.27-4.59; P = .03), white matter area (n = 134; β = 144 per mm2; 95% CI, 3-285 per mm2; P = .045), anisotropy of the corpus callosum (n = 50; β = 0.018; 95% CI, 0.016-0.021; P, This cohort study assesses the association between high amino acid intake among very preterm infants at 7 days after birth and cognitive performance at age 5 years.

ObjectiveThis study aimed to describe how parents and physicians experienced the informed consent interview and to investigate the aspects of the relationship that influenced parents’ decision during the consent process for a randomised clinical trial in a tertiary neonatal intensive care unit (NICU). The secondary objective was to describe the perspectives of parents and physicians in the specific situation of prenatal informed consent.SettingSingle centre study in NICU of the Centre Hospitalier Intercommunal de Créteil, France, using a convenience period from February to May 2016.DesignAncillary study to a randomised clinical trial: Prettineo. Records of interviews for consent. Population: parents and physicians. Mixed study including qualitative and quantitative interview data about participants’ recall and feelings about the consent process. Interviews were reviewed using thematic discourse analysis.ResultsParents’ recall and understanding of the study’s main goal and design was good. Parents and physicians had a positive experience, and trust was one of the main reasons for parents to consent. Misunderstanding (bad comprehension) was the main reason for refusal.Before birth, three situations can compromise parents’ consent: the mother already consented to participate in other studies, the absence of the father during the interview and the feeling that the baby’s birth is not an imminent possibility.ConclusionsConfronting parents and physicians’ perspectives in research can help us reach answers to sensitive issues such as content and timing of information. Each different types of study raises different ethical dilemmas for consent that might be discussed in a more individual way.

International audience; Objective: To evaluate the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age 2 years in very premature infants who were ventilated.Study: design This national observational study included premature infants born before 32 weeks of gestation intubated within 1 hour after birth and still intubated at 24 hours from the French EPIPAGE 2 cohort. Infants only treated with bolus were excluded. Treated infants received continuous opioid and/or midazolam infusion started before 7 days of life and before the first extubation. Naive infants did not receive these treatments before the first extubation, or received them after the first week of life, or never received them. This study compared treated (n = 450) vs naive (n = 472) infants by using inverse probability of treatment weighting after multiple imputation in chained equations. The primary outcomes were survival and survival without moderate or severe neuromotor or sensory impairment at age 2 years.Results: Survival at age 2 years was significantly higher in the treated group (92.5% vs 87.9%, risk difference, 4.7%; 95% CI, 0.3-9.1; P =.037), but treated and naive infants did not significantly differ for survival without moderate or severe neuromotor or sensory impairment (86.6% vs 81.3%; risk difference, 5.3%; 95% CI -0.3 to 11.0; P =.063). These results were confirmed by sensitivity analyses using 5 alternative models.Conclusions: Continuous opioid and/or midazolam infusions in very premature infants during initial mechanical ventilation that continued past 24 hours of life were associated with improved survival without any difference in moderate or severe sensorimotor impairments at age 2 years.

Background An increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days. Goal To examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants Study Design Predefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial. Results Among 307 infants who survived >14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58–5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated n = 307): infants intubated ≥10 days: OR (95% CI) = 2.41 (1.47–3.95)); infants intubated Conclusions Moderate-to-large PDAs were associated with increased risks of BPD and BPD/death—but only when infants required intubation ≥10 days. Impact Infants with a moderate-to-large hsPDA that persist beyond 14 days are only at risk for developing BPD if they also receive prolonged tracheal ventilation for ≥10 days. Infants who receive less ventilatory support (intubation for Early PDA closure may be unnecessary in infants who require short durations of intubation since the PDA does not seem to alter the incidence of BPD in infants who require intubation for

To describe the frequency and nature of premedication practices for neonatal tracheal intubation (TI) in 2011; to identify independent risk factors for the absence of premedication; to compare data with those from 2005 and to confront observed practices with current recommendations. Data concerning TI performed in neonates during the first 14 days of their admission to participating neonatal/pediatric intensive care units were prospectively collected at the bedside. This study was part of the Epidemiology of Procedural Pain in Neonates study (EPIPPAIN 2) conducted in 16 tertiary care units in the region of Paris, France, in 2011. Multivariate analysis was used to identify factors associated with premedication use and multilevel analysis to identify center effect. Results were compared with those of the EPIPPAIN 1 study, conducted in 2005 with a similar design, and to a current guidance for the clinician for this procedure. One hundred and twenty-one intubations carried out in 121 patients were analyzed. The specific premedication rate was 47% and drugs used included mainly propofol (26%), sufentanil (24%), and ketamine (12%). Three factors were associated with the use of a specific premedication: nonemergent TI (Odds ratio (OR) [95% CI]: 5.3 [1.49-20.80]), existence of a specific written protocol in the ward (OR [95% CI]:4.80 [2.12-11.57]), and the absence of a nonspecific concurrent analgesia infusion before TI (OR [95% CI]: 3.41 [1.46-8.45]). No center effect was observed. The specific premedication rate was lower than the 56% rate observed in 2005. The drugs used were more homogenous and consistent with the current recommendations than in 2005, especially in centers with a specific written protocol. Premedication use prior to neonatal TI was low, even for nonemergent procedures. Scientific consensus, implementation of international or national recommendations, and local written protocols are urgently needed to improve premedication practices for neonatal intubation.

International audience; Objective: To examine the effects of early echocardiography-targeted ibuprofen treatment of large patent ductus arteriosus (PDA) on survival without cerebral palsy at 24 months of corrected age.Study design: We enrolled infants born at

Aim Less invasive surfactant administration (LISA) can avoid tracheal intubation for neonatal respiratory distress syndrome, but can be painful because it requires laryngoscopy. The aim of this study was to assess the efficacy and tolerance of intravenous atropine plus ketamine administration before LISA. Methods We conducted a prospective observational study of all premature infants hospitalised in our French neonatal intensive care unit treated with LISA between March 2015 and March 2016. Ketamine was titrated by 0.5 mg/kg increments. The technical conditions, pain scores, emergent intubations and vital signs were collected and analysed. Results Values are reported as medians (interquartile ranges). We included 29 patients with a gestational age of 29.6 (28.6-30.9) weeks and birth weight of 1290 (945-1600) grams. Technical conditions were satisfying for 24 infants (83%). The Faceless Acute Neonatal Pain Scale score was 2 (2-4); seven infants (24%) required tracheal intubation before LISA could be performed; 17 (59%) had a pulse oxymetry value under 80% that lasted more than 60 seconds. Heart rate and mean arterial blood pressure transiently increased. Conclusion Atropine plus ketamine before LISA resulted in low pain scores and stable haemodynamic parameters, but prolonged desaturations or apnoea leading to tracheal intubation were frequently observed.

Non-invasive ventilation is currently the preferred respiratory support for premature infants with respiratory distress. The lung-protective effects of non-invasive ventilation should however not prompt disregard for the possible pain and discomfort it can generate. Non-pharmacological interventions should be used in all premature infants, regardless of their respiratory support, and are not detailed in this review. This review includes currently available evidence and gaps in knowledge regarding three aspects of pain management in premature infants receiving non-invasive ventilation: optimisation of non-invasive ventilation especially through the choice of positive pressure source, appropriate interface and synchronisation; sedative or analgesic drug use for strategies aiming at administering surfactant with reduction or avoidance of tracheal ventilation; risks and benefits of some analgesic and/or sedative drugs used to treat or prevent prolonged pain and discomfort during non-invasive ventilation. In spite of limited robust evidence, this overview should trigger caregivers' reflections on their daily practice.

Continuous intravenous (IV) morphine is commonly used in ventilated neonates. Oral route is theoretically feasible but data on oral morphine in ventilated premature infants are lacking.To assess the efficacy, efficiency, and tolerability of a continuous intravenous to oral morphine switch protocol.Retrospective study.Single level III center's neonatal intensive care unit.Ventilated premature infants hospitalized in the NICU in 2016 and 2017, receiving continuous IV morphine with an expected ventilation course of at least 72 more hours. We excluded patients treated for withdrawal syndrome or palliative care.Continuous IV to oral morphine switch with the same initial cumulated daily dose.Pain scores (ComfortNeo scale) and morphine doses were analyzed over time using Friedman's test in the 24 hours preceding and the 48 hours following the oral switch. Adverse effects attributable to opioids were collected.Seventeen infants were included with a median [IQR] gestational age at birth of 25.9 [24.6-26.9] weeks and a median postnatal age at oral switch of 30 [22-36] days. One patient's intravenous treatment had to be resumed because of a high ComfortNeo score. All others remained on oral morphine. No significant change over time was observed for ComfortNeo scores (Oral morphine might be useful in ventilated neonates in the NICU but deserves further studies and additional safety assessment.

This study followed 173 newborn infants in the PREmedication Trial for Tracheal Intubation of the NEOnate multicenter, double-blind, randomized controlled trial of atropine-propofol vs atropine-atracurium-sufentanil for premedication before nonemergency intubation. At 2 years of corrected age, there was no significant difference between the groups in death or risk of neurodevelopmental delay assessed with the Ages and Stages Questionnaire. Trial registration Clinicaltrials.gov : NCT01490580 .

Background Heelstick is the most frequently performed skin-breaking procedure in the neonatal intensive care units (NICUs). There are no large multicenter studies describing the frequency and analgesic approaches used for heelsticks performed in NICUs. Objectives To describe the frequency of heelsticks and their analgesic management in newborns in the NICU. To determine the factors associated with the lack of specific preprocedural analgesia for this procedure. Design EPIPPAIN 2 (Epidemiology of Procedural PAin In Neonates) is a descriptive prospective epidemiologic study. Setting All 16 NICUs in the Paris region in France. Participants All newborns in the NICU with a maximum corrected age of 44 weeks +6 days of gestation on admission who had at least one heelstick during the study period were eligible for the study. The study included 562 newborns. Methods Data on all heelsticks and their corresponding analgesic therapies were prospectively collected. The inclusion period lasted six weeks, from June 2, 2011 to July 12, 2011. Newborns were followed from their admission to the 14th day of their NICU stay or discharge, whichever occurred first. Results The mean (SD) gestational age was 33.3 (4.4) weeks and duration of participation was 7.5 (4.4) days. The mean (SD; range) of heelsticks per neonate was 16.0 (14.4; 1–86) during the study period. Of the 8995 heelsticks studied, 2379 (26.4%) were performed with continuous analgesia, 5236 (58.2%) with specific preprocedural analgesia. Overall, 6764 (75.2%) heelsticks were performed with analgesia (continuous and/or specific). In a multivariate model, the increased lack of preprocedural analgesia was associated with female sex, term birth, high illness severity, tracheal or noninvasive ventilation, parental absence and use of continuous sedation/analgesia. Conclusions Heelstick was very frequently performed in NICUs. Although, most heelsticks were performed with analgesia, this was not systematic. The high frequency of this procedure and the known adverse effects of repetitive pain in neonates should encourage the search of safe and effective strategies to reduce their number.

International audience; Background Parents of preterm neonates wish greater involvement in pain management; little is known about factors associated with this involvement. We aim to describe perceived maternal information on infants’ pain during hospitalization (PMIP), to study associations between PMIP and mothers’ attitudes during painful procedures, and to identify individual and contextual factors associated with PMIP. Methods Analyses of questionnaires from the French national cohort study of preterm neonates, EPIPAGE-2. PMIP was derived from mothers’ answers to questions about information perceived on both pain assessment and management. Results Among 3056 eligible neonates born before 32 weeks, 1974, with available maternal reports, were included in the study. PMIP was classified as “sufficient,” “little, not sufficient,” or “insufficient, or none” for 22.7, 45.9, and 31.3% of neonates, respectively. Mothers reporting PMIP as “sufficient” were more frequently present and more likely comforting their child during painful procedures. Factors independently associated with “sufficient” PMIP were high maternal education, gestational age

International audience; Among 831 cases of neonatal bacterial meningitis occurring from 2001 to 2013, Neisseria meningitidis was the third most frequent bacterial species found. All cases occurred only in term neonates and were mainly late onset. Serogroup B accounted for 78% of cases. At diagnosis, 27% of cases had at least one sign of disease severity. All strains were susceptible to cefotaxime, but 12% showed intermediate susceptibility to penicillin G and to aminopenicillin.

OBJECTIVES The objective of the study was to assess the efficacy of reduced sufentanil doses for postoperative analgesia following surgical ductal closure in extremely premature infants. METHODS This was a retrospective, single-center, cohort study comparing 2 sufentanil dosing regimens used between 2001 and 2010 and included all infants born at

Place: England; OBJECTIVE: Many extremely preterm neonates die in the delivery room (DR) after decisions to withhold or withdraw life-sustaining treatments or after failed resuscitation. Specific palliative care is then recommended but sparse data exist about the actual management of these dying babies. The objective of this study was to describe the clinical course and management of neonates born between 22 and 26 weeks of gestation who died in the DR in France. DESIGN, SETTING, PATIENTS: Prospective study including neonates, who were liveborn between 22(+0) and 26(+6) weeks of gestation and died in the DR in 2011, among infants included in the EPIPAGE-2 study at the 18 centres participating in this substudy of extremely preterm neonates. Data were collected by a questionnaire completed by the professional caring for each baby. RESULTS: The study included 73 children, with a median (IQR) gestational age of 24 (23-24) weeks. Median (IQR) duration of life was 53 (20-82) min. All but one were both wrapped and warmed. Pain was assessed for 72%, although without using any scale. Gasping was described for 66%. Comfort medications were administered to 35 children (50%), significantly more frequently to babies with gasping (p=0.001). Mother-child contact was reported for 78%, and psychological support offered to parents of 92%. CONCLUSIONS: Non-pharmacological comfort care and parental support were routinely given. Comfort medication was given much more frequently than previously reported in other DRs. These data should encourage work on the indications for comfort medication and the interpretation of gasping.

To compare outcomes at hospital discharge for preterm infants born before 29 weeks of gestation who had at least one episode of isolated hypotension during their first 72 hours of life for which they did or did not receive antihypotensive treatment.Etude Epidémiologique sur les Petits Ages Gestationnels 2 (EPIPAGE 2) French national prospective population-based cohort study in 2011.60 neonatal intensive care units.All infants with a minimum mean arterial blood pressure less than gestational age (in weeks) (minMAPGA) within 72 hours of birth. Infants whose reason for receiving antihypotensive treatments was isolated hypotension only were compared with untreated hypotensive infants by propensity score matching.Fluid bolus and/or inotropes and/or corticosteroids.The primary outcome was survival at hospital discharge without major morbidity, defined as any of necrotising enterocolitis, severe cerebral abnormalities, severe bronchopulmonary dysplasia or severe retinopathy of prematurity.Among the 1532 infants with available data, 662 had a minMAPGA; 206 were treated for unknown or other reasons than isolated hypotension, 131 were treated for isolated hypotension only and 325 were untreated; 119 infants from each of these last two groups were matched. Treated infants had a significantly higher survival rate without major morbidity (61.3% vs 48.7%; OR, 1.67, 95% CI 1.00 to 2.78, p=0.049) and a lower rate of severe cerebral abnormalities (10.1% vs 26.5%, p=0.002).In this population, antihypotensive treatment was associated with improved short-term outcomes. Therapeutic abstention should be cautiously considered for early isolated hypotension in extremely premature infants.

Resume L’evolution des meningites neonatales a E. coli, precoces et tardives, est marquee par une mortalite elevee, 12 % a terme et 18 % chez le premature, des complications precoces – abces cerebral, ventriculite, infarctus ischemo-hemorragiques- et des sequelles frequentes, neurosensorielles (14–17 %) et neuro-developpementales (10–17 %). Ces complications, bien qu’observees meme apres un traitement precoce et efficace, sont plus frequentes apres un retard au traitement ou une antibiotherapie initiale inadaptee. Les autres principaux facteurs de mauvais pronostic sont des troubles hemodynamiques, des apnees, des convulsions, une hypoglycorachie et un EEG anormal. Le traitement antibiotique doit donc etre le plus precoce possible et repose sur l’utilisation d’une cephalosporine de 3e generation (C3G) – en particulier le cefotaxime – en raison de ses caracteres pharmacocinetiques-pharmacodynamiques (Pk-Pd) les mieux adaptes. Des molecules neuroprotectrices ont ete recemment proposees de facon experimentale pour ameliorer le pronostic, inhibiteurs des mediateurs de l’inflammation ou du relargage de composants bacteriens, inhibiteurs de l’apoptose. L’effet protecteur des corticoides est discute. La ciprofloxacine presente une activite anti-inflammatoire intrinseque et peut etre utilisee en association avec le cefotaxime les premiers jours du traitement. Recemment la prevalence des souches d’E. coli resistantes aux C3G a augmente, impliquant le recours au meropeneme en cas de meningite confirmee a bacille a Gram negatif dans l’attente de l’antibiogramme et en cas de souche resistante au C3G.

An extreme attentiveness is mandatory when caring about extremely-low-gestational-age neonates at birth because of their innate vulnerability. The interventions performed during resuscitation of these infants may have direct influence on the immediate survival and also on long-term morbidity. Although stressfull, each resuscitation step is crucial and needs to be precise, fast and harmless. In order to determine our compliance to the international guidelines and to assess our neonatal performances in delivery room, we used a Mobotix camera to record all resuscitations of extremely-low-gestational-age neonates during the decisive first minutes of life. Neonatal medical and nursing staff agreed to be recorded. Our local ethics committee approved that videotaping neonatal resuscitation is an audit of clinical practice and thus does not require informed consent. During debriefing sessions, we reviewed the videotaped recordings, which allowed us to identify frequent deviations from the international guidelines and to re-educate and improve performance. The most frequent errors we recognized were errors of hygiene, not re-evaluating oxygen titration and airway obstruction during mask ventilation. We observed team behaviour and coordination during resuscitation and focused on quality of care. We believe that this method may be very effective as a teaching tool.

Summary Background In animal models, inhaled nitric oxide improved gas exchange and lung structural development, but its use in premature infants at risk of developing bronchopulmonary dysplasia remains controversial. We therefore tested the hypothesis that inhaled nitric oxide at a low concentration, started early and maintained for an extended period in babies with mild respiratory failure, might reduce the incidence of bronchopulmonary dysplasia. Methods 800 preterm infants with a gestational age at birth of between 24 weeks and 28 weeks plus 6 days (inclusive), weighing at least 500 g, requiring surfactant or continuous positive airway pressure for respiratory distress syndrome within 24 h of birth were randomly assigned in a one-to-one ratio to inhaled nitric oxide (5 parts per million) or placebo gas (nitrogen gas) for a minimum of 7 days and a maximum of 21 days in a double-blind study done at 36 centres in nine countries in the European Union. Care providers and investigators were masked to the computer-generated treatment assignment. The primary outcome was survival without development of bronchopulmonary dysplasia at postmenstrual age 36 weeks. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551642. Findings 399 infants were assigned to inhaled nitric oxide, and 401 to placebo. 395 and 400, respectively, were analysed. Treatment with inhaled nitric oxide and placebo did not result in significant differences in survival of infants without development of bronchopulmonary dysplasia (258 [65%] of 395 vs 262 [66%] of 400, respectively; relative risk 1·05, 95% CI 0·78–1·43); in survival at 36 weeks' postmenstrual age (343 [86%) of 399 vs 359 [90%] of 401, respectively; 0·74, 0·48–1·15); and in development of bronchopulmonary dysplasia (81 [24%] of 339 vs 96 [27%] of 358, respectively; 0·83, 0·58–1·17). Interpretation Early use of low-dose inhaled nitric oxide in very premature babies did not improve survival without bronchopulmonary dysplasia or brain injury, suggesting that such a preventive treatment strategy is unsuccessful. Funding INO Therapeutics.

Resume Les progres recents de la medecine perinatale permettent la survie d’enfants extremement prematures. Le devenir psychomoteur et socio-affectif de ces enfants et de leur famille est un enjeu central des soins qui leur sont prodigues. Notre service a mis en place un systeme de consultations pluri-disciplinaires communes associant pediatre et psychomotricien(ne) ou kinesitherapeute et dont l’objectif est d’evaluer le devenir de l’enfant en accompagnant sa famille apres l’hospitalisation.

AIM We assessed the outcomes of ventilated extremely premature infants treated with late postnatal corticosteroids from 2005-2008, according to permissive or restrictive policies in two centres. METHODS This retrospective study included inborn infants below 27 weeks of gestational age who were ventilator dependent after 14 days. Centre P permitted postnatal corticosteroids but centre R restricted their use. The effects on infants were assessed in hospital and after two years using multivariable analysis. RESULTS We compared 62 infants from centre P, including 92% who received hydrocortisone, and 48 infants from centre R, including 13% who received betamethasone. Infants from both centres had comparable baseline characteristics and perinatal management, but bronchopulmonary dysplasia (BPD) rates were significantly lower in centre P (30% versus 71%, p < 0.001) and this centre was significantly associated with a younger post-conceptional age at oxygen weaning, with an adjusted hazard ratio (aHR) of 0.45 and an aHR of 0.51at discharge. At two years of corrected age, 18% of centre P infants and 30% of centre R infants showed poor neurodevelopmental outcome (p = 0.18). CONCLUSION Using hydrocortisone after 14 days on ventilated extremely preterm infants was associated with decreased BPD, with no apparent effects on neurodevelopment at two years of corrected age.

Summary. Objective: To compare immediate extubation versus delayed extubation after 36 hr in extremely low-birth weight infants receiving gentle mechanical ventilation and perinatal lung protective interventions. Our hypothesis was that a delayed extubation in this setting would decrease the rate of reintubation. Study design/Methodology: A prospective, unmasked, randomized, controlled trial to compare immediate extubation and delayed extubation after 36 hr. Optimized ventilation in both groups included continuous tracheal gas insufflation (CTGI), prophylactic surfactant administration, low oxygen saturation target and moderate permissive hypercapnia. Successful extubation for at least 7 days was the primary criterion and ventilatory support requirements until 36 weeks gestational age the main secondary criteria. Patient selection: Eighty-six infants under 28 weeks gestational age in a single neonatal intensive tertiary careunit.Results:Delayedextubation(1.9! 0.8daysvs.0.5! 0.7days)didnotimprovetherateof successfulextubation but hadno long-term adverseeffects. CTGI andthe lungprotective strategy we describe resulted in a very gentle ventilation. The rate of survival without bronchopulmonary dysplasia(BPD,definedas anyrespiratorysupportat36 weeksgestationalage)wassimilarinthe two groups and remarkably high for the global population (78%) and for the subgroup of infants

International audience; IMPORTANCE:There is currently no consensus for the screening and treatment of patent ductus arteriosus (PDA) in extremely preterm infants. Less pharmacological closure and more supportive management have been observed without evidence to support these changes.OBJECTIVE:To evaluate the association between early screening echocardiography for PDA and in-hospital mortality.DESIGN, SETTING, AND PARTICIPANTS:Comparison of screened and not screened preterm infants enrolled in the EPIPAGE 2 national prospective population-based cohort study that included all preterm infants born at less than 29 weeks of gestation and hospitalized in 68 neonatal intensive care units in France from April through December 2011. Two main analyses were performed to adjust for potential selection bias, one using propensity score matching and one using neonatal unit preference for early screening echocardiography as an instrumental variable.EXPOSURES:Early screening echocardiography before day 3 of life.MAIN OUTCOMES AND MEASURES:The primary outcome was death between day 3 and discharge. The secondary outcomes were major neonatal morbidities (pulmonary hemorrhage, severe bronchopulmonary dysplasia, severe cerebral lesions, and necrotizing enterocolitis).RESULTS:Among the 1513 preterm infants with data available to determine exposure, 847 were screened for PDA and 666 were not; 605 infants from each group could be paired. Exposed infants were treated for PDA more frequently during their hospitalization than nonexposed infants (55.1% vs 43.1%; odds ratio [OR], 1.62 [95% CI, 1.31 to 2.00]; absolute risk reduction [ARR] in events per 100 infants, -12.0 [95% CI, -17.3 to -6.7). Exposed infants had a lower hospital death rate (14.2% vs 18.5% ; OR, 0.73 [95% CI, 0.54 to 0.98]; ARR, 4.3 [95% CI, 0.3 to 8.3]) and a lower rate of pulmonary hemorrhage (5.6% vs 8.9%; OR, 0.60 [95% CI, 0.38 to 0.95]; ARR, 3.3 [95% CI, 0.4 to 6.3]). No differences in rates of necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions were observed. In the overall cohort, instrumental variable analysis yielded an adjusted OR for in-hospital mortality of 0.62 [95% CI, 0.37 to 1.04].CONCLUSIONS AND RELEVANCE:In this national population-based cohort of extremely preterm infants, screening echocardiography before day 3 of life was associated with lower in-hospital mortality and likelihood of pulmonary hemorrhage but not with differences in necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions. However, results of the instrumental variable analysis leave some ambiguity in the interpretation, and longer-term evaluation is needed to provide clarity.

Critical care physicians facing patients that require invasive mechanical ventilation are confronted with the questions what type of ventilator and what ventilator strategy is most appropriate for this particular patient. Mechanical ventilation is initiated to bridge a gap to recovery or to supply chronic support. Failure of mechanical ventilation can arise through inability to deliver adequate gas exchange or through resulting complications, like pneumothorax. Although mechanical ventilation is meant to support respiratory function, mechanical ventilation can also result in pulmonary damage and contribute to increased risk of mortality. Therefore, the selection of the ventilator type and strategy should be guided by the capacity to achieve adequate gas exchange and, in the meanwhile, to prevent lung injury.

High-frequency oscillatory ventilation (HFOV) is now a mainstay of respiratory care for the neonatal patient. In this chapter, we will define HFOV as those ventilators with a “true” active expiratory phase created by a piston or diaphragm. Jet ventilation and flow interrupters are discussed elsewhere in this book.

Although first described in animals in mythologies and ancient civilizations (Raju 1999), neonatal endotracheal intubation was first recommended as resuscitation practice at birth in Parisian maternities at the beginning of the nineteenth century (Obladen 2009). Techniques and opinions relative to this practice dramatically evolved in the next years until it was finally considered as a life-saving practice for compromised newborns in the late 1920s and early 1930s. This procedure requires specific skills due to potentially life-threatening situation, small size of babies, and particular physiological status of newborns. This chapter will cover the specificities of neonatal intubation regarding its physiological effects, possible adverse effects, and recommended practice.