Use of neonatal lung ultrasound in European neonatal units: a survey by the European Society of Paediatric Research.

OBJECTIVE: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved. DESIGN AND INTERVENTION: International online survey. RESULTS: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique. CONCLUSIONS: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline.

Association between patent ductus arteriosus flow and home oxygen therapy in extremely preterm infants.

BACKGROUND: Central blood flow measurements include the estimation of right and left ventricular output (RVO, LVO), superior vena cava (SVC) flow, and calculated patent ductus arteriosus (PDA) flow. We aimed to provide an overview of the maturation patterns of these values and the relationship between PDA flow and the need for home oxygen therapy. METHODS: This prospective single-center study was conducted in infants born at <26 weeks of gestation. We performed echocardiographic measurements five times during their life (from the 4th post-natal day to the 36th postmenstrual week). RESULTS: Sixty patients with a mean birth weight of 680 (590, 760) g were included. Postnatal development of LVO and PDA flow peaked at the end of the second postnatal week (427 and 66 mL/kg/min, respectively). The RVO increased between days 4 and 7-8. The SVCF was most stable. The development curves of PDA flow differed between the groups with (n = 28; 47%) and without home oxygen therapy. CONCLUSION: We present the central blood flow values and their postnatal development in infants <26 weeks of gestation. This study demonstrates the association between PDA flow and the future need for home oxygen therapy. IMPACT: This study enriches our knowledge of the long-term development of central blood flow parameters and derived patent ductus arteriosus (PDA) flow in extremely preterm infants (<26 weeks). While pulmonary resistance decreased, PDA flow continued to increase from day 4 to the end of the second week of life. Similarly, left ventricular output increased as a marker of preload. The superior vena cava flow remained stable. The observed association between PDA flow and an unfavorable respiratory outcome is important for future studies focusing on the prevention of chronic lung disease.

Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial.

Importance: Preterm newborns at risk of respiratory distress syndrome are supported with continuous positive airway pressure (CPAP). Many newborns worsen despite CPAP and are intubated for surfactant administration, an effective therapy for treatment of respiratory distress syndrome. Endotracheal intubation is associated with adverse effects. Pharyngeal administration of surfactant to preterm animals and humans has been reported as an alternative. Objective: To assess whether giving prophylactic oropharyngeal surfactant to preterm newborns at birth would reduce the rate of intubation for respiratory failure. Design, Setting, and Participants: This unblinded, parallel-group randomized clinical trial (Prophylactic Oropharyngeal Surfactant for Preterm Infants [POPART]) was conducted from December 17, 2017, to September 11, 2020, at 9 tertiary neonatal intensive care units in 6 European countries. Newborns born before 29 weeks of gestation without severe congenital anomalies, for whom intensive care was planned, were eligible for inclusion. The data were analyzed from July 27, 2022, to June 20, 2023. Intervention: Newborns were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. Randomization was stratified by center and gestational age (GA). Main Outcomes and Measures: The primary outcome was intubation in the delivery room for bradycardia and/or apnea or in the neonatal intensive care unit for prespecified respiratory failure criteria within 120 hours of birth. Caregivers were not masked to group assignment. Results: Among 251 participants (mean [SD] GA, 26 [1.5] weeks) who were well matched at study entry, 126 (69 [54.8%] male) with a mean (SD) birth weight of 858 (261) grams were assigned to the oropharyngeal surfactant group, and 125 (63 [50.4%] male) with a mean (SD) birth weight of 829 (253) grams were assigned to the control group. The proportion of newborns intubated within 120 hours was not different between the groups (80 [63.5%) in the oropharyngeal surfactant group and 81 [64.8%] in the control group; relative risk, 0.98 [95% CI, 0.81-1.18]). More newborns assigned to the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax (21 [16.6%] vs 8 [6.4%]; P = .04). Conclusions and Relevance: This randomized clinical trial found that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks' GA did not reduce the rate of intubation in the first 120 hours of life. These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used. Trial Registration: EudraCT: 2016-004198-41.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update.

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of "European Guidelines for the Management of RDS" by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome.

OBJECTIVE: To investigate the efficacy and safety of nebulized poractant alfa (at 200 and 400 mg/kg doses) delivered in combination with nasal continuous positive airway pressure compared with nasal continuous positive airway pressure alone in premature infants with diagnosed respiratory distress syndrome. STUDY DESIGN: This randomized, controlled, multinational study was conducted in infants at 280/7 to 326/7 weeks of gestation. The primary outcome was the incidence of respiratory failure in the first 72 hours of life, defined as needing endotracheal surfactant and/or mechanical ventilation owing to prespecified criteria. Secondary outcomes included the time to respiratory failure in the first 72 hours, duration of ventilation, mortality, incidence of bronchopulmonary dysplasia, and major associated neonatal comorbidities. In addition, the safety and tolerability of the treatments were assessed reporting the number and percentage of infants with treatment-emergent adverse events and adverse drug reactions during nebulization. RESULTS: In total, 129 infants were randomized. No significant differences were observed for the primary outcome: 24 (57%), 20 (49%), and 25 (58%) infants received endotracheal surfactant and/or mechanical ventilation within 72 hours in the poractant alfa 200 mg/kg, poractant alfa 400 mg/kg, and nasal continuous positive airway pressure groups, respectively. Similarly, secondary respiratory outcomes did not differ among groups. Enrollment was halted early owing to a change in the benefit-risk balance of the intervention. Nebulized poractant alfa was well-tolerated and safe, and no serious adverse events were related to the study treatment. CONCLUSIONS: The intervention did not decrease the likelihood of respiratory failure within the first 72 hours of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03235986.

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome: two-year outcomes.

OBJECTIVE: To assess at 24 months corrected age (CA) the neurological, respiratory, and general health status of children born prematurely from 27+0 to 33+6 weeks' gestation who were treated in a first-in-human study with a new fully synthetic surfactant (CHF5633) enriched with SP-B and SP-C proteins. OUTCOME MEASURES: Children were assessed using Bayley Scales of Infant Development (BSID), with a score below normal defined as BSID-II Mental Development Index score <70, or BSID-III cognitive composite score <85. In addition, a health status questionnaire was used to check for functional disability including respiratory problems and related treatments, sensory and neurodevelopment assessments, communication skills as well as the number of hospitalizations. RESULTS: 35 of 39 survivors had a neurodevelopmental assessment, 24 infants being evaluated by Bayley's Scales and 11 by health status questionnaires only. 23 children had scores within normal limits and one had BSID-III <85. The remaining 11 were judged clinically to have normal development. Health status questionnaires detected only issues that would normally be expected in preterm-born children. CONCLUSIONS: This assessment offers reassurance that treatment with CHF5633 surfactant was not associated with adverse neurodevelopmental, respiratory, or health outcomes by two years corrected age.

Comparing the effect of two different interfaces on breathing of preterm infants at birth: A matched-pairs analysis.

OBJECTIVE: Applying a face mask could provoke a trigeminocardiac reflex. We compared the effect of applying bi-nasal prongs with a face mask on breathing and heart rate of preterm infants at birth. METHODS: In a retrospective matched-pairs study of infants <32 weeks of gestation, the use of bi-nasal prongs for respiratory support at birth was compared to the use of a face mask. Infants who were initially breathing at birth and subsequently received respiratory support were matched for gestational age (±4 days), birth weight (±300 g), general anaesthesia and gender. Breathing, heart rate and other parameters were collected before and after interface application and in the first 5 min thereafter. RESULTS: In total, 130 infants were included (n = 65 bi-nasal prongs, n = 65 face mask) with a median (IQR) gestational age of 27+2 (25+3-28+4) vs 26+6 (25+3-28+5) weeks. The proportion of infants who stopped breathing after applying the interface was not different between the groups (bi-nasal prongs 43/65 (66%) vs face mask 46/65 (71%), p = 0.70). Positive pressure ventilation was given more often when bi-nasal prongs were used (55/65 (85%) vs 40/65 (62%), p < 0.001). Heart rate (101 (75-145) vs 110 (68-149) bpm, p = 0.496) and oxygen saturation (59% (48-87) vs 56% (35-84), p = 0.178) were similar in the first 5 min after an interface was applied in the infants who stopped breathing. CONCLUSION: Apnoea and bradycardia occurred often after applying either bi-nasal prongs or a face mask on the face for respiratory support in preterm infants at birth.

Early inhaled budesonide in extremely preterm infants decreases long-term respiratory morbidity.

BACKGROUND: There is no strict correlation between early bronchopulmonary dysplasia and long-term respiratory disease. Early inhaled corticosteroids seem to reduce the incidence of bronchopulmonary dysplasia, but the long-term outcome remains unknown. RESEARCH QUESTION: The aim of this study was to evaluate the effect of early inhaled corticosteroids on chronic respiratory morbidity. METHODS: Fifty-nine survivors from the Prague cohort included in Neonatal European Study of Inhaled Steroids underwent further follow-up comprising of respiratory morbidity monitoring during the first 2 years of life followed by objective lung function testing performed at the age of 5.9 years (range 5-7 years). Both outcomes were pursued and finalized before the unblinding of budesonide subgroups. RESULTS: Fifty randomized (budesonide vs placebo group, 56% vs 44%) survivors were included in the study. Spirometry was successfully performed in 48 children. No statistically significant differences were found in the lung function test (forced expiratory flow [FEF] - FEF75 , FEF50, FEF25 , and FEF25-75; FEV1 , forced vital capacity [FVC], FEV1 /FVC) although mild trend to the improvement of expiratory flow pattern was observed in the budesonide group (median z-score of FEV1 /FVC -0.376 vs -0.983, P = .13; median z-score of FEF25-75 -1.004 vs -1.458, P = .13; median z-score of FEF75 -0.527 vs -0.996, P = .17). Children assigned to budesonide had a significantly lower rate of symptoms of chronic lung disease (34.6% vs 68.2%; P = .04) than children assigned to placebo. INTERPRETATION: Our study suggests that early inhaled budesonide was associated with the trend to the improvement of functional lung parameters and with a lower rate of symptoms of chronic lung disease within the first 2 years of life.

A novel accurate LC-MS/MS method for quantitative determination of Z-lumirubin.

Although phototherapy (PT) is a standard treatment for neonatal jaundice, no validated clinical methods for determination of bilirubin phototherapy products are available. Thus, the aim of our study was to establish a such method for clinical use. To achieve this aim, a LC-MS/MS assay for simultaneous determination of Z-lumirubin (LR) and unconjugated bilirubin (UCB) was conducted. LR was purified after irradiation of UCB at 460 nm. The assay was tested on human sera from PT-treated neonates. Samples were separated on a HPLC system with a triple quadrupole mass spectrometer detector. The instrument response was linear up to 5.8 and 23.4 mg/dL for LR and UCB, respectively, with submicromolar limits of detection and validity parameters relevant for use in clinical medicine. Exposure of newborns to PT raised serum LR concentrations three-fold (p < 0.01), but the absolute concentrations were low (0.37 ± 0.16 mg/dL), despite a dramatic decrease of serum UCB concentrations (13.6 ± 2.2 vs. 10.3 ± 3.3 mg/dL, p < 0.01). A LC-MS/MS method for the simultaneous determination of LR and UCB in human serum was established and validated for clinical use. This method should help to monitor neonates on PT, as well as to improve our understanding of both the kinetics and biology of bilirubin phototherapy products.

Analysis of (O-acyl) alpha- and omega-hydroxy fatty acids in vernix caseosa by high-performance liquid chromatography-Orbitrap mass spectrometry.

Fatty acid esters of long-chain hydroxy fatty acids or (O-acyl)-hydroxy fatty acids (OAHFAs) were identified for the first time in vernix caseosa and characterized using chromatography and mass spectrometry. OAHFAs were isolated from the total lipid extract by a two-step semipreparative TLC. The general structure of OAHFAs was established using high-resolution and tandem mass spectrometry of intact lipids and their transesterification and derivatization products. Two isomeric lipid classes were identified: O-acyl esters of ω-hydroxy fatty acids (ωOAHFA) and O-acyl esters of α-hydroxy fatty acids (αOAHFAs). To the best of our knowledge, αOAHFAs have never been detected in any biological sample before. Chromatographic separation and identification of OAHFAs species were achieved using non-aqueous reversed-phase HPLC coupled to electrospray ionization hybrid linear ion trap-Orbitrap mass spectrometry. The lipid species were detected as deprotonated molecules, and their structures were elucidated using data-dependent fragmentation in the negative ion mode. More than 400 OAHFAs were identified in this way. The most abundant ωOAHFAs species were 28:0/ω-18:2, 29:0/ω-18:2, 30:0/ω-18:2, 32:0/ω-18:2, and 30:0/ω-18:3, while αOAHFAs comprised saturated species 21:0/α-24:0, 22:0/α-24:0, 23:0/α-24:0, 24:0/α-24:0, and 26:0/α-24:0. OAHFAs were estimated to account for approximately 0.04% of vernix caseosa lipids. Graphical Abstract.

The effect of a face mask for respiratory support on breathing in preterm infants at birth.

OBJECTIVE: Applying a mask on the face for respiratory support could induce a trigeminocardiac reflex leading to apnoea and bradycardia. We have examined the effect of applying a face mask on breathing and heart rate in preterm infants at birth. METHODS: Resuscitation videos of infants ≤ 32 weeks gestation recorded from 2010 until 2018 at the Leiden University Medical Centre and the General University Hospital in Prague were reviewed. All infants received respiratory support via face mask. Breathing and heart rate were noted before and after application of the face mask and over the first 5 min. RESULTS: Recordings of 429 infants were included (median (IQR) gestational age of 28+6 (27+1-30+4) weeks). In 368/429 (86%) infants breathing was observed before application of the face mask and 197/368 (54%) of these infants stopped breathing following application of the face mask. Apnoea occurred at a median of 5 (3-17) seconds after application of the face mask with a duration of 28 (22-34) seconds of the first minute. In a logistic regression model, the occurrence of apnoea after face mask application was inversely associated with gestational age (OR = 1.424 (1.281-1.583), p < 0.001). Infants who stopped breathing had a significantly lower heart rate 82 (66-123) vs 134 (97-151) bpm, p < 0.001) and oxygen saturation (49% (33-59) vs 66% (50-82), p < 0.001) over the first minute after face mask application, compared to infants who continued breathing. CONCLUSION: Applying a face mask for respiratory support affects breathing in a large proportion (54%) of preterm infants and this effect is gestational age dependent.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update.

As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of "European Guidelines for the Management of RDS" by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

Nonhydroxylated 1-O-acylceramides in vernix caseosa.

Vernix caseosa, the waxy substance that coats the skin of newborn babies, has an extremely complex lipid composition. We have explored these lipids and identified nonhydroxylated 1-O-acylceramides (1-O-ENSs) as a new class of lipids in vernix caseosa. These ceramides mostly contain saturated C11-C38 ester-linked (1-O) acyls, saturated C12-C39 amide-linked acyls, and C16-C24 sphingoid bases. Because their fatty acyl chains are frequently branched, numerous molecular species were separable and detectable by HPLC/MS: we found more than 2,300 molecular species, 972 of which were structurally characterized. The most abundant 1-O-ENSs contained straight-chain and branched fatty acyls with 20, 22, 24, or 26 carbons in the 1-O position, 24 or 26 carbons in the N position, and sphingosine. The 1-O-ENSs were isolated using multistep TLC and HPLC and they accounted for 1% of the total lipid extract. The molecular species of 1-O-ENSs were separated on a C18 HPLC column using an acetonitrile/propan-2-ol gradient and detected by APCI-MS, and the structures were elucidated by high-resolution and tandem MS. Medium-polarity 1-O-ENSs likely contribute to the cohesiveness and to the waterproofing and moisturizing properties of vernix caseosa.

Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia.

BACKGROUND: The long-term effects on neurodevelopment of the use of inhaled glucocorticoids in extremely preterm infants for the prevention or treatment of bronchopulmonary dysplasia are uncertain. METHODS: We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to receive early (within 24 hours after birth) inhaled budesonide or placebo. The prespecified secondary long-term outcome was neurodevelopmental disability among survivors, defined as a composite of cerebral palsy, cognitive delay (a Mental Development Index score of <85 [1 SD below the mean of 100] on the Bayley Scales of Infant Development, Second Edition, with higher scores on the scale indicating better performance), deafness, or blindness at a corrected age of 18 to 22 months. RESULTS: Adequate data on the prespecified composite long-term outcome were available for 629 infants. Of these infants, 148 (48.1%) of 308 infants assigned to budesonide had neurodevelopmental disability, as compared with 165 (51.4%) of 321 infants assigned to placebo (relative risk, adjusted for gestational age, 0.93; 95% confidence interval [CI], 0.80 to 1.09; P=0.40). There was no significant difference in any of the individual components of the prespecified outcome. There were more deaths in the budesonide group than in the placebo group (82 [19.9%] of 413 infants vs. 58 [14.5%] of 400 infants for whom vital status was available; relative risk, 1.37; 95% CI, 1.01 to 1.86; P=0.04). CONCLUSIONS: Among surviving extremely preterm infants, the rate of neurodevelopmental disability at 2 years did not differ significantly between infants who received early inhaled budesonide for the prevention of bronchopulmonary dysplasia and those who received placebo, but the mortality rate was higher among those who received budesonide. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190 .).

Proactive approach at the limits of viability improves the short-term outcome of neonates born after 23 weeks' gestation.

OBJECTIVE: The aim of this single-center study was to identify factors that affect the short-term outcome of newborns delivered around the limits of viability. METHODS: A group of 137 pregnant women who gave birth between 22+0/7 and 25+6/7 weeks of gestation was retrospectively studied. The center supports a proactive approach to infants around the limits of viability. Perinatal and neonatal characteristics were obtained and statistically evaluated. RESULTS: A total of 166 live-born infants were enrolled during a 6-year period; 162 (97.6%) of them were admitted to the neonatal intensive care unit (ICU) and 119 (73.5%) survived until discharge. The decrease in neonatal mortality was associated with an advanced gestational age (P<0.001) and a completed course of corticosteroids (P=0.002). Neonatal morbidities were common among infants of all gestational ages. The incidence of severe intraventricular hemorrhage significantly depended on gestational age (P<0.001) and a completed course of corticosteroids (P=0.002). Survival without severe neonatal morbidities was 39.5% and occurred mostly after 24+0/7 weeks of gestation. CONCLUSION: The short-term outcome of newborns delivered around the limits of viability is mostly affected by gestational age and antenatal corticosteroid treatment. A consistently proactive approach improves the survival of infants at the limits of viability. This is most pronounced in cases where the delivery is delayed beyond 24 completed gestational weeks.

Oropharyngeal surfactant can improve initial stabilisation and reduce rescue intubation in infants born below 25 weeks of gestation.

AIM: Minimally aggressive and easily performed techniques that facilitate spontaneous respiratory stabilisation are required to reduce rescue intubation in extremely premature infants. This study evaluated the feasibility and safety of administering surfactant into the pharynx of infants born at <25 weeks immediately after birth. METHODS: This study of 19 infants was conducted from January 2013 to June 2014 in a tertiary perinatal centre in Prague. We administered 1.5 mL of Curosurf as a bolus into the pharynx and simultaneously performed a sustained inflation manoeuvre (SIM). The extent of the interventions, death and severe neonatal morbidity in the study group were compared with 20 controls born before the study period and 20 born after it. RESULTS: All infants received oropharyngeal surfactant within the median (interquartile range) time of 40 seconds (25-75) after cord camping. The surfactant had to be suctioned in one infant because of upper airway obstruction. Although more subsequent surfactant was administered in the study group, significantly fewer study period infants required intubation than the before and after controls (16% versus 75% and 58%, respectively, p < 0.01). CONCLUSION: Oropharyngeal surfactant with simultaneous SIM was feasible and safe and reduced the need for delivery room intubation in these fragile infants.

Cholesteryl esters of ω-(O-acyl)-hydroxy fatty acids in vernix caseosa.

Cholesteryl esters of ω-(O-acyl)-hydroxy FAs (Chl-ωOAHFAs) were identified for the first time in vernix caseosa and characterized using chromatography and MS. Chl-ωOAHFAs were isolated using adsorption chromatography on silica gel and magnesium hydroxide. Their general structure was established using high-resolution and tandem MS of intact lipids, and products of their transesterification and derivatizations. Individual molecular species were characterized using nonaqueous reversed-phase HPLC coupled to atmospheric pressure chemical ionization. The analytes were detected as protonated molecules, and their structures were elucidated in the negative ion mode using controlled thermal decomposition and data-dependent fragmentation. About three hundred molecular species of Chl-ωOAHFAs were identified in this way. The most abundant Chl-ωOAHFAs contained 32:1 ω-hydroxy FA (ω-HFA) and 14:0, 15:0, 16:0, 16:1, and 18:1 FAs. The double bond in the 32:1 ω-HFA was in the n-7 and n-9 positions. Chl-ωOAHFAs are estimated to account for approximately 1-2% of vernix caseosa lipids.

A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome.

OBJECTIVE: CHF5633 (Chiesi Farmaceutici S.p.A., Parma, Italy) is the first fully synthetic surfactant enriched by peptide analogues of two human surfactant proteins. We planned to assess safety and tolerability of CHF5633 and explore preliminary efficacy. DESIGN: Multicentre cohort study. PATIENTS: Forty infants from 27+0 to 33+6 weeks gestation with respiratory distress syndrome requiring fraction of inspired oxygen (FiO2) ≥0.35 were treated with a single dose of CHF5633 within 48 hours after birth. The first 20 received 100 mg/kg and the second 20 received 200 mg/kg. OUTCOME MEASURES: Adverse events (AEs) and adverse drug reactions (ADRs) were monitored with complications of prematurity considered AEs if occurring after dosing. Systemic absorption and immunogenicity were assessed. Efficacy was assessed by change in FiO2 after dosing and need for poractant-alfa rescue. RESULTS: Rapid and sustained improvements in FiO2 were observed in 39 (98%) infants. One responded neither to CHF5633 nor two poractant-alfa doses. A total of 79 AEs were experienced by 19 infants in the 100 mg/kg cohort and 53 AEs by 20 infants in the 200 mg/kg cohort. Most AEs were expected complications of prematurity. Two unrelated serious AEs occurred in the second cohort. One infant died of necrotising enterocolitis and another developed viral bronchiolitis after discharge. The single ADR was an episode of transient endotracheal tube obstruction following a 200 mg/kg dose. Neither systemic absorption, nor antibody development to either peptide was detected. CONCLUSIONS: Both CHF5633 doses were well tolerated and showed promising clinical efficacy profile. These encouraging data provide a basis for ongoing randomised controlled trials. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01651637.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update.

Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.