Chrono-proteomics of human saliva: variations of the salivary proteome during human development.

An important contribution to the variability of any proteome is given by the time dimension that should be carefully considered to define physiological modifications. To this purpose, whole saliva proteome was investigated in a wide age range. Whole saliva was collected from 17 preterm newborns with a postconceptional age at birth of 178-217 days. In these subjects sample collection was performed serially starting immediately after birth and within about 1 year follow-up, gathering a total of 111 specimens. Furthermore, whole saliva was collected from 182 subjects aged between 0 and 17 years and from 23 adults aged between 27 and 57 years. The naturally occurring intact salivary proteome of the 316 samples was analyzed by low- and high-resolution HPLC-ESI-MS platforms. Proteins peculiar of the adults appeared in saliva with different time courses during human development. Acidic proline-rich proteins encoded by PRH2 locus and glycosylated basic proline-rich proteins encoded by PRB3 locus appeared following 180 days of postconceptional age, followed at 7 months (±2 weeks) by histatin 1, statherin, and P-B peptide. The other histatins and acidic proline-rich proteins encoded by PRH1 locus appeared in whole saliva of babies from 1 to 3 weeks after the normal term of delivery, S-type cystatins appeared at 1 year (±3 months), and basic proline-rich proteins appeared at 4 years (±1 year) of age. All of the proteinases involved in the maturation of salivary proteins were more active in preterm than in at-term newborns, on the basis of the truncated forms detected. The activity of the Fam20C kinase, involved in the phosphorylation of various proteins, started around 180 days of postconceptional age, slowly increased reaching values comparable to adults at about 2 years (±6 months) of age. Instead, MAPK14 involved in the phosphorylation of S100A9 was fully active since birth also in preterm newborns.

Determination of Lung Volume and Hemodynamic Changes During High-Frequency Ventilation Recruitment in Preterm Neonates With Respiratory Distress Syndrome.

OBJECTIVES: To evaluate the changes in end-expiratory lung volume during an oxygenation-guided stepwise recruitment procedure in elective high-frequency ventilation. We hypothesized that high continuous distending pressure impedes pulmonary blood flow as evidenced by reduced lung volume measurements using respiratory inductive plethysmography. Changes in oxygenation, ventilation, and peripheral perfusion were evaluated as secondary outcomes. DESIGN: A prospective, single center, observational, nonrandomized study. SETTING: The study was conducted in a neonatal ICU in Italy. PATIENTS: High-frequency ventilated preterm infants with respiratory distress syndrome. INTERVENTIONS: During the recruitment procedure, end-expiratory lung volume measured by respiratory inductive plethysmography, oxygen saturation, perfusion index, regional cerebral and perirenal tissue oxygenation, heart rate, transcutaneous PCO2, and tidal volume were simultaneously recorded at each airway pressure step. MEASUREMENTS AND MAIN RESULTS: In 12 preterm newborns (gestational age, 27.4 ± 0.2 wk; birth weight, 979 ± 198 g), high-frequency ventilation was initiated at a continuous distending pressure of 10 cm H2O and incrementally increased by 1-2 cm H2O every 2-5 minutes until FIO2 was less than or equal to 0.25. End-expiratory lung volume progressively increased during the initial recruitment, but decreased at the maximum airway pressure in nine patients, indicative of a reduction in pulmonary perfusion. At the end of recruitment, tidal volume was significantly higher (p = 0.002) and oxygenation was significantly improved (p = 0.002); however, mean perfusion index, postductal saturation, and mean renal tissue oxygenation values were significantly reduced (p < 0.05) compared with baseline. Mean cerebral tissue oxygenation and mean transcutaneous PCO2 values were reduced but failed to reach significance. CONCLUSIONS: High distending lung pressures increased oxygenation but decreased peripheral perfusion with no adverse cerebral side effects. Coupled with the reduction in respiratory inductive plethysmography-derived lung volume, high continuous distending pressure had adverse cardiopulmonary effects. Incorporation of lung volume and hemodynamic and oxygenation variables may guide optimum lung volume determination during high-frequency ventilation recruitment procedure while preventing adverse effects on the pulmonary circulation.

Association of high levels of α-defensins and S100A proteins with Candida mannan detection in bronchoalveolar lavage fluid of preterm neonates.

BACKGROUND: Candida mannan (Mn) detection in bronchoalveolar lavage fluid (BALF) was shown to be useful for earlier identification and preemptive therapy targeting in preterm infants at high risk of invasive Candida infection. We investigated whether early detection of Candida Mn in BALF is associated with the presence of some neutrophilic products, as markers of prenatal infection/inflammation. METHODS: BALF specimens were collected during the first 48 h of life from mechanically ventilated preterm newborns. Samples were analyzed by high-performance liquid chromatography-electrospray ionization-mass spectrometry. The relative amounts of α-defensins 1-4 and S100A proteins were measured by extracted ion current peak area. Absolute and differential white cell counts in BALF were obtained. Mn antigen concentrations were determined by the Platelia Candida antigen kit. RESULTS: Twenty-five studied neonates were divided into two groups: Mn-positive group and Mn-negative group. Levels of α-defensins 1-4 and S100A12 were significantly higher in the Mn-positive group than in the Mn-negative group. Moreover, positive significant correlations between the absolute number of neutrophils and the levels of α-defensins 1-4 and S100A8 were observed. CONCLUSION: The detection of Mn antigen in BALF of preterm infants is consistent with evidence of an innate immune response in their lungs as demonstrated by higher levels of α-defensins and S100A proteins.

Efficacy of exogenous surfactant during conventional and high-frequency oscillatory ventilation in preterm infants with RDS.

INTRODUCTION: The immediate effects of exogenous surfactant on lung volume and hemodynamics in preterm infants have been poorly studied. MATERIALS AND METHODS: Lung volume, SpO2, perfusion index, regional SO2, transcutaneous partial pressure of CO2 were simultaneously monitored and recorded ten minutes after surfactant tracheal instillation in elective HFOV ventilated preterm infants with RDS. OUTCOMES: Despite a reduction in gas exchange during the first 5 minutes post surfactant instillation, most likely dependent on airway obstruction, lung volume increases rapidly in HFOV preterm infants with RDS. After 5 minutes from administration of surfactant, lung volume, gas exchange and PI reach stable values and CDP can be safely reduced.

Respiratory Management of the Preterm Infant: Supporting Evidence-Based Practice at the Bedside.

Extremely preterm infants frequently require some form of respiratory assistance to facilitate the cardiopulmonary transition that occurs in the first hours of life. Current resuscitation guidelines identify as a primary determinant of overall newborn survival the establishment, immediately after birth, of adequate lung inflation and ventilation to ensure an adequate functional residual capacity. Any respiratory support provided, however, is an important contributing factor to the development of bronchopulmonary dysplasia. The risks correlated to invasive ventilatory techniques increase inversely with gestational age. Preterm infants are born at an early stage of lung development and are more susceptible to lung injury deriving from mechanical ventilation. Any approach aiming to reduce the global burden of preterm lung disease must implement lung-protective ventilation strategies that begin from the newborn's first breaths in the delivery room. Neonatologists today must be able to manage both invasive and noninvasive forms of respiratory assistance to treat a spectrum of lung diseases ranging from acute to chronic conditions. We searched PubMed for articles on preterm infant respiratory assistance. Our narrative review provides an evidence-based overview on the respiratory management of preterm infants, especially in the acute phase of neonatal respiratory distress syndrome, starting from the delivery room and continuing in the neonatal intensive care unit, including a section regarding exogenous surfactant therapy.

Early Respiratory Physiotherapy versus an Individualized Postural Care Program for Reducing Mechanical Ventilation in Preterm Infants: A Randomised Controlled Trial.

BACKGROUND: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure. METHODS: This is a monocentric, randomised controlled trial. Preterm infants (gestational age ≤ 30 weeks) not intubated in the delivery room and requiring non-invasive respiratory support at birth were eligible for the study. The intervention group received early respiratory physiotherapy, while the control group received only a daily physiotherapy program (i.e., modifying the infant's posture in accordance with the patient's needs). RESULTS: between October 2019 and March 2021, 133 preterm infants were studied, 68 infants in the study group and 65 in routine care. The study group showed a reduction in the need for mechanical ventilation (not statistically significant) and a statistically significant reduction in hemodynamically significant patent ductus arteriosus with respect to the control group (19/68 (28%) vs. 35/65 (54%), respectively, p = 0.03). CONCLUSIONS: early respiratory physiotherapy in preterm infants requiring non-invasive respiratory support at birth is safe and has proven to be protective against haemodynamically significant PDA.

Renal failure of the surviving fetus after intrauterine death of the co-twin.

Twin pregnancies are considered at a higher risk for fetal mortality than singleton pregnancies. The antenatal death of one of the twins is associated with an increasing rate of cerebral impairment and lesions in other organs in the surviving fetus, especially if the pregnancy is monochorionic. We describe a case of isolate renal failure becoming evident gradually after birth in a surviving twin after the antenatal death of the co-twin. Considering the deleterious effects of vascular disruption in a surviving twin, our findings suggest careful investigation of renal function, even if no intrauterine signs of diminished renal function were previously detected.

The Relationship Between Maternal and Neonatal Microbiota in Spontaneous Preterm Birth: A Pilot Study.

The newborn's microbiota composition at birth seems to be influenced by maternal microbiota. Maternal vaginal microbiota can be a determining factor of spontaneous Preterm Birth (SPPTB), the leading cause of perinatal mortality. The aim of the study is to investigate the likelihood of a causal relationship between the maternal vaginal microbiota composition and neonatal lung and intestinal microbiota profile at birth, in cases of SPPTB. The association between the lung and/or meconium microbiota with the subsequent development of bronchopulmonary dysplasia (BPD) was also investigated. Maternal vaginal swabs, newborns' bronchoalveolar lavage fluid (BALF) (1st, 3rd, 7th day of life) and first meconium samples were collected from 20 women and 23 preterm newborns with gestational age ≤ 30 weeks (12 = SPPTB; 11 = Medically Indicated Preterm Birth-MIPTB). All the samples were analyzed for culture examination and for microbiota profiling using metagenomic analysis based on the Next Generation Sequencing (NGS) technique of the bacterial 16S rRNA gene amplicons. No significant differences in alpha e beta diversity were found between the neonatal BALF samples of SPPTB group and the MIPTB group. The vaginal microbiota of mothers with SPPTB showed a significant difference in alpha diversity with a decrease in Lactobacillus and an increase in Proteobacteria abundance. No association was found between BALF and meconium microbiota with the development of BPD. Vaginal colonization by Ureaplasma bacteria was associated with increased risk of both SPPTB and newborns' BPD occurrence. In conclusion, an increase in α-diversity values and a consequent fall in Lactobacillus in vaginal environment could be associated to a higher risk of SPPTB. We could identify neither a specific neonatal lung or meconium microbiota profiles in preterm infants born by SPPTB nor a microbiota at birth suggestive of subsequent BPD development. Although a strict match has not been revealed between microbiota of SPPTB mother-infant couples, a relationship cannot be excluded. To figure out the reciprocal influence of the maternal-neonatal microbiota and its potential role in the pathogenesis of SPPTB and BPD further research is needed.

Weaning from the Ventilator in Bronchopulmonary Dysplasia.

For the newborns needing respiratory support at 36 weeks postmenstrual age, regardless of the type of ventilation used, it is critical to take into account the mechanics properties of both airways and lungs affected by severe bronchopulmonary dysplasia (sBPD). Ventilator strategies, settings, and weaning must change dramatically after sBPD is established, but to date there is almost no high-quality evidence base supporting a specific approach to guide the optimal ventilator management and weaning in patients with sBPD. Weaning from invasive mechanical ventilation, management of the immediately postextubation period, and weaning from noninvasive ventilation in patients with sBPD are the topics covered in this chapter.

Effects of High-Frequency Oscillatory Ventilation With Volume Guarantee During Surfactant Treatment in Extremely Low Gestational Age Newborns With Respiratory Distress Syndrome: An Observational Study.

Objective: To evaluate the effect of volume guarantee (VG) combined with high-frequency oscillatory ventilation (HFOV) on respiratory and other physiological parameters immediately after lung recruitment and surfactant administration in HFOV elective ventilated extremely low gestational age newborns (ELGAN) with respiratory distress syndrome (RDS). Design: Observational study. Setting: Tertiary neonatal intensive care unit. Patients: Twenty-two ELGANs of 25.5 ± 1.1 weeks of gestational age requiring invasive mechanical ventilation and surfactant administration for RDS during the first 6 h of life. Interventions: All infants intubated in delivery room, were managed with elective HFOV and received surfactant after a lung recruitment manoeuver. Eleven infants received HFOV + VG and were compared with a control group of 11 infants receiving HFOV alone. HFOV was delivered in both groups by Dräger Babylog VN500 ventilator (Dräger, Lubeck, Germany). Main Outcome Measures: Variations and fluctuations of delivered high-frequency tidal volume (VThf), fluctuation of pressure amplitude (ΔP) and partial pressure of CO2 (pCO2) levels after recruitment manoeuver and immediately after surfactant administration, in HFOV + VG vs. HFOV ventilated infants. Results: There were no significant differences in the two groups at starting ventilation with or without VG. The mean applied VThf per kg was 1.7 ± 0.3 ml/kg in the HFOV group and 1.7 ± 0.1 ml/kg in the HFOV + VG group. Thirty minutes after surfactant administration, HFOV group had a significant higher VThf/Kg than HFOV + VG (2.1 ± 0.3 vs. 1.6 ± 0.1 ml/kg, p < 0.0001) with significantly lower pCO2 levels (43.1 ± 3.8 vs. 46.8 ± 1.5 mmHg, p = 0.01), 54.4% of patients having pCO2 below 45 mmHg. Measured post-surfactant ΔP values were higher in HFOV group (17 ± 3 cmH2O) than in HFOV + VG group (13 ± 3 cmH2O, p = 0.01). Conclusion: HFOV + VG maintains pCO2 levels within target range and reduces VThf delivered variations more consistently than HFOV alone after surfactant administration.

Oxidative and Proteolytic Inactivation of Alpha-1 Antitrypsin in Bronchopulmonary Dysplasia Pathogenesis: A Top-Down Proteomic Bronchoalveolar Lavage Fluid Analysis.

The study investigates the role of the oxidative and proteolytic inactivation of alpha-1 antitrypsin (AAT) in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature infants. Bronchoalveolar lavage fluid (BALF) samples were collected on the 3rd day of life from mechanically ventilated neonates with gestational age ≤ 30 weeks and analyzed without previous treatment (top-down proteomics) by reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. AAT fragments were identified by high-resolution LTQ Orbitrap XL experiments and the relative abundances determined by considering the extracted ion current (XIC) peak area. Forty preterm neonates were studied: 20 (50%) did not develop BPD (no-BPD group), 17 (42.5%) developed mild or moderate new-BPD (mild + moderate BPD group), and 3 (7.5%) developed severe new-BPD (severe BPD group). Eighteen fragments of AAT and a fragment of AAT oxidized at a methionine residue were identified: significantly higher values of AAT fragments 25-57, 375-418, 397-418, 144-171, and 397-418 with oxidized methionine were found in the severe BPD group. The significantly higher levels of several AAT fragments and of the fragment 397-418, oxidized in BALF of preterm infants developing BPD, underlie the central role of an imbalance between proteases and protease inhibitors in exacerbating lung injury and inducing most severe forms of BPD. The study has some limitations, and between them, the small sample size implies the need for further confirmation by larger studies.

Effects of early respiratory physiotherapy on spontaneous respiratory activity of preterm infants: study protocol for a randomized controlled trial.

BACKGROUND: Tactile maneuvers stimulating spontaneous respiratory activity in preterm infants are recommended since birth, but data on how and how often these maneuvers are applied in clinical practice are unknown. In the last years, most preterm newborns with respiratory failure are preferentially managed with non-invasive respiratory support and by stimulating spontaneous respiratory activity from the delivery room and in neonatal intensive care unit (NICU), in order to avoid the risks of intubation and prolonged mechanical ventilation. METHODS: Preterm infants with gestational age < 31 weeks not intubated in the delivery room and requiring non-invasive respiratory support at birth will be eligible for the study. They will be randomized and allocated to one of two treatment groups: (1) the study group infants will be subject to the technique of respiratory facilitation within the first 24 h of life, according to the reflex stimulations, by the physiotherapist. The newborn is placed in supine decubitus and a slight digital pressure is exerted on a hemithorax. The respiratory facilitation technique will be performed for about three minutes and repeated for a total of 4/6 times in sequence, three times a day until spontaneous respiratory activity is achieved; thus, no respiratory support is required; (2) the control group infants will take part exclusively in the individualized postural care program. They will perform the technique of respiratory facilitation and autogenous drainage. OBJECTIVE: To evaluate the efficacy of early respiratory physiotherapy in reducing the incidence of intubation and mechanical ventilation in the first week of life (primary outcome). DISCUSSION: The technique of respiratory facilitation is based on reflex stimulations, applied early to preterm infant. Slight digital pressure is exerted on a "trigger point" of each hemithorax, to stimulate the respiratory activity with subsequent increase of the ipsilateral pulmonary minute ventilation and to facilitate the contralateral pulmonary expansion. This mechanism will determine the concatenation of input to all anatomical structures in relation to the area being treated, to promote spontaneous respiratory activity and reducing work of breathing, avoiding or minimizing the use of invasive respiratory support. TRIAL REGISTRATION: UMIN-CTR Clinical Trial UMIN000036066. Registered on March 1, 2019. Protocol 1. https://www.umin.ac.jp/ctr.

Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial.

BACKGROUND: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). METHODS: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. FINDINGS: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). INTERPRETATION: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. FUNDING: None.

Effect of Different Milk Diet on the Level of Fecal Calprotectin in Very Preterm Infants.

Objective: To evaluate the course of fecal calprotectin (FC) in very preterm infants over the first 15 days of life in relation to the type of milk diet. Methods: This study was part of a randomized controlled trial comparing two different ways of integrating the own mother's milk (OMM) for the evaluation of feeding tolerance in very preterm infants. In infants with gestational age of ≤ 32 weeks randomized to receive preterm formula (PF group) or pasteurized donor human milk (PDHM group) as a supplement to the OMM insufficient or unavailable, FC level was planned to be measured at the first meconium passage and at days 8 and 15 of life (T0, T1, and T2, respectively). Results: FC data were available for all the 70 infants randomized, 35 in the PF group, and 35 in the PDHM group. The mean FC levels were similar in the two study groups at T0 and T1, whereas they were significantly higher in the PF group than the PDHM group at T2. FC values decreased over the first week of life in both groups and significantly increased over the second week of life only in the PF group. Conclusions: Our study demonstrates a significant increase in FC levels when PF is used as a supplement to the OMM compared to the use of PDHM. Further studies are needed to establish if the higher FC levels in infants receiving PF are the expression of a normal immunological maturation rather than an initial inflammatory process.

Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes.

In recent years, an aberrant gastrointestinal colonization has been found to be associated with an higher risk for postnatal sepsis, necrotizing enterocolitis (NEC) and growth impairment in preterm infants. As a consequence, the reasons of intestinal dysbiosis in this population of newborns have increasingly become an object of interest. The presence of a link between the gut and lung microbiome's development (gut-lung axis) is emerging, and more data show as a gut-brain cross talking mediated by an inflammatory milieu, may affect the immunity system and influence neonatal outcomes. A revision of the studies which examined gut and lung microbiota in preterm infants and a qualitative analysis of data about characteristic patterns and related outcomes in terms of risk of growing impairment, Necrotizing Enterocolitis (NEC), Bronchopulmonary Dysplasia (BPD), and sepsis have been performed. Microbiota take part in the establishment of the gut barrier and many data suggest its immune-modulator role. Furthermore, the development of the gut and lung microbiome (gut-lung axis) appear to be connected and able to lead to abnormal inflammatory responses which have a key role in the pathogenesis of BPD. Dysbiosis and the gut predominance of facultative anaerobes appear to be crucial to the pathogenesis and subsequently to the prevention of such diseases.

A modified physiologic test for bronchopulmonary dysplasia: a clinical tool for weaning from CPAP and/or oxygen-therapy the premature babies?

BACKGROUND: A physiologic test for estimating BPD rate has been developed by Walsh and collaborators. Actually there are not standard criteria for weaning from CPAP and/or oxygen therapy the premature babies. Aim of this study was to verify if a physiologic test, modified respect to that developed by Walsh and collaborators for estimating BPD rate, can be used as a clinical tool for weaning the premature babies from CPAP and/or oxygen therapy. METHODS: Neonates with BW 500-1250 g and GA ≤ 32 weeks, receiving FiO2 ≤ 0.30 by hood or CPAP, were prospectively studied at 28 days of life and at 36 weeks of postmestrual age. The test was performed in 3 steps: baseline, challenge (FiO2 and CPAP reduction to room air) and post test (room air). Monitoring of transcutaneous CO2 was added to SpO2 and the newborns passing the test were left in room air. RESULTS: Six of 23 tested babies (26%) passed the challenge at 28 days of life, 4 of 10 tested babies (40%) passed the challenge at 36 weeks. Median values of SpO2 were significantly higher in the neonates passing the test, respect to the failing patients. At the same time median values of TcPCO2 were significantly higher in the latter babies. CONCLUSION: TcPCO2 monitoring appeared to be a new useful parameter for failure prediction of weaning. The test represented a clinical guide because the newborns passing it were left in room air.

Extubation from high-frequency oscillatory ventilation in extremely low birth weight infants: a prospective observational study.

OBJECTIVE: To evaluate if weaning from high-frequency oscillatory ventilation (HFOV) directly to a non-invasive mode of respiratory support is feasible and results in successful extubation in extremely low birth weight (ELBW) infants. DESIGN: Prospective observational study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: One hundred and eight ELBW infants of 26.2±1.4 weeks of gestational age (GA) directly extubated from HFOV. INTERVENTIONS: All infants were managed with elective HFOV and received surfactant after a recruitment HFOV manoeuvre. Extubation was attempted at mean airways pressure (MAP) ≤6 cm H2O with FiO2 ≤0.25. After extubation, all infants were supported by nasal continuous positive airway pressure (6-8 cm H2O). MAIN OUTCOME MEASURES: Extubation failure (clinical deterioration requiring reintubation) was defined as shorter than 7 days. RESULTS: Ninety patients (83%) were successfully extubated and 18 (17%) required reintubation. No significant differences were found between the two groups in terms of birth weight, day of life and weight at the time of extubation. Multivariable analysis showed that GA (OR 1.71; 95% CI 1.04, 2.08) and higher MAP prior to surfactant (OR 1.51; 95% CI 1.06, 2.15) were associated with successful extubation. CONCLUSIONS: In ELBW infants, direct extubation from HFOV at MAP ≤6 cm H2O with FiO2 ≤0.25 is feasible. Our extubation success rate (83%) is higher than conventional mechanical ventilation in this very vulnerable class of infants.

Ventilation Prior to Umbilical Cord Clamping Improves Cardiovascular Stability and Oxygenation in Preterm Lambs After Exposure to Intrauterine Inflammation.

Background: Delaying umbilical cord clamping until after aeration of the lung (physiological-based cord clamping; PBCC) maintains cardiac output and oxygenation in preterm lambs at birth, however, its efficacy after intrauterine inflammation is not known. Given the high incidence of chorioamnionitis in preterm infants, we investigated whether PBCC conferred any benefits compared to immediate cord clamping (ICC) in preterm lambs exposed antenatally to 7 days of intrauterine inflammation. Methods: Ultrasound guided intraamniotic injection of 20 mg Lipopolysaccharide (from E. coli:055:B5) was administered to pregnant ewes at 0.8 gestation. Seven days later, ewes were anesthetized, preterm fetuses exteriorised via cesarean section, and instrumented for continuous measurement of pulmonary, systemic and cerebral pressures and flows, and systemic, and cerebral oxygenation. Lambs were then randomized to either PBCC, whereupon ventilation was initiated and maintained for 3 min prior to umbilical cord clamping, or ICC where the umbilical cord was cut and ventilation initiated 30 s later. Ventilation was maintained for 30 min. Results: ICC caused a rapid fall in systemic (by 25%) and cerebral (by 11%) oxygen saturation in ICC lambs, concurrent with a rapid increase in carotid arterial pressure and heart rate. The overshoot in carotid arterial pressure was sustained in ICC lambs for the first 20 min of the study. PBCC maintained cardiac output and prevented the fall in cerebral oxygen delivery at birth. PBCC lambs had lower respiratory compliance and higher respiratory requirements throughout the study. Conclusion: PBCC mitigated the adverse effects of ICC on oxygenation and cardiac output, and therefore could be more beneficial in preterm babies exposed to antenatal inflammation as it maintains cardiac output and oxygen delivery. The increased respiratory requirements require further investigation in this sub-group of preterm infants.

Nasal high-frequency oscillatory ventilation and CO2 removal: A randomized controlled crossover trial.

OBJECTIVE: To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP). WORKING HYPOTHESIS: nHFOV improves CO2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life. STUDY DESIGN: Multicenter non-blinded prospective randomized crossover study. PATIENT SELECTION: Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight. METHODOLOGY: Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO2 (TcCO2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP. RESULTS: Significantly lower TcCO2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13). CONCLUSIONS: nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO2 .