Importance A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes. Objective To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units. Design, Setting, and Participants This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024. Intervention Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up. Main Outcomes and Measures The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA. Results A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups. Conclusions and Relevance In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

ImportanceA multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes.ObjectiveTo examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units.Design, Setting, and ParticipantsThis was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks’ gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024.InterventionInfants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up.Main Outcomes and MeasuresThe primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA.ResultsA total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups.Conclusions and RelevanceIn this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

BackgroundHypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants.MethodsThis is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system.ResultsA total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069–2.117).ConclusionsInfants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

Introduction: The umbilical venous catheter is a vital access device in neonatal intensive care units for preterm and critically ill infants. Correct positioning is crucial, as malpositioning can lead to severe complications. According to international guidelines, the position of the umbilical venous catheter tip must be assessed in real time; traditionally, the catheter is visualized with a thoracoabdominal X-ray, but one of the most effective and safest methods is therefore real-time ultrasound. Methods: This study compares real-time ultrasound and traditional X-ray methods for assessing umbilical venous catheter tip location in 461 cases. The rate of tip malposition was analyzed retrospectively. The secondary aim was to assess indwelling time of umbilical venous catheters and reasons of removal. Results: Real-time ultrasound tip location, found to be more reliable and efficient, demonstrated a significantly lower incidence of primary malpositioning compared to X-ray assessments (9.6 vs. 75.9%). The study also highlighted the association of real-time ultrasound with reduced catheter manipulation, fewer radiographs, and higher indwelling times of umbilical venous catheter. The multiple logistic regression showed a high probability of the central safe position of the umbilical venous catheter tip using real-time ultrasound tip location (odds ratio 29.5, 95% confidence interval: 17.4-49.4). Conclusion: The findings support the adoption of real-time ultrasound in clinical settings to enhance umbilical venous catheter placement accuracy and minimize associated risks. A minimal training investment is needed to attain the proficiency to visualize the umbilical venous catheters, offering a substantial advantage in terms of both cost-effectiveness for the procedure and enhanced patient safety.

The interesting comments by Fusagawa et al focus our attention on 2 relevant issues regarding the management of the umbilical venous catheter (UVC). First, there is a difference between the migration of the tip of an UVC and the dislodgement of its external tract. These 2 phenomena may occur independently or simultaneously, but they have different causes. Tip migration may occur even without any apparent dislodgment of the external tract of the UVC, and migration may be caused by variations in abdominal pressure, lung volume, or level of sedation; periodic postural changes; any manipulation of the infant; progressive desiccation of the Wharton jelly; or many other factors. In other words, appropriate external securement of the UVC can prevent catheter dislodgement but will have no influence on the actual position of the tip. Such is the reason why even when securing the UVC with the most effective strategies (which in our opinion should include cyanoacrylate glue), the position of the tip of the UVC should be assessed by bedside ultrasound on a daily basis or at least every other day. Second, regards the indication for a UVC, we agree that this should be carefully defined by local policies, avoiding unnecessary insertion of catheters that may be associated with severe complications. In our neonatal intensive care unit, we follow the very strict indications suggested by the GAVeCeLT consensus (so-called neonatal "DAV-Expert" algorithm) published by Barone et al.1Barone G. D'Andrea V. Ancora G. Cresi F. Maggio L. Capasso A. et al.The neonatal DAV-expert algorithm: a GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access in newborns.Eur J Pediatr. 2023; 182: 3385-3395https://doi.org/10.1007/s00431-023-04984-4Crossref PubMed Scopus (7) Google Scholar According to this consensus, appropriate indications for UVC include not only infants born preterm at or less than 28 weeks of gestation but also neonates with severe respiratory distress (intubated or on noninvasive ventilation with fraction of inspired oxygen >40%), hemodynamic instability, difficult peripheral venous access at the time of birth, asphyxia requiring therapeutic hypothermia, and so on. In our neonatal intensive care unit, we have not only infants born preterm but also infants born at term with acute illness, asphyxia, malformations, and other clinical conditions that are regarded as indication to UVC insertion. Obviously, cyanoacrylate glue is not going to reduce all complications associated with umbilical catheters, but it seems to be a quite effective strategy in reducing one specific complication of UVC, ie, catheter dislodgment.2D'Andrea V. Prontera G. Pinna G. Cota F. Fattore S. Costa S. et al.Securement of umbilical venous catheter using cyanoacrylate glue: a randomized controlled trial.J Pediatr. 2023; 260113517https://doi.org/10.1016/j.jpeds.2023.113517Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Vito D'Andrea: Conceptualization, Writing – original draft, Data curation, Investigation. Giorgia Prontera: Data curation, Investigation, Methodology, Writing – original draft. Giovanni Pinna: Data curation, Investigation. Francesco Cota: Data curation, Formal analysis. Simona Fattore: Data curation, Formal analysis. Simonetta Costa: Methodology, Supervision. Martina Migliorato: Data curation, Methodology. Giovanni Barone: Supervision, Writing – review & editing. Mauro Pittiruti: Supervision, Writing – review & editing. Giovanni Vento: Supervision, Validation, Visualization. The authors declare no conflicts of interest. Causes of outward movement of umbilical venous catheters and the external validity of a studyThe Journal of PediatricsVol. 266PreviewWe read with interest the article "Securement of Umbilical Venous Catheter Using Cyanoacrylate Glue: A Randomized Controlled Trial" by D'Andrea et al.1 Because umbilical venous catheter (UVC) dislodgement can cause various complications, preventive measures should be considered. The authors' study of cyanoacrylate glue is novel and clinically important. The study concludes that cyanoacrylate glue was safe and effective for securing UVCs and particularly effective in decreasing early catheter dislodgement. Full-Text PDF

Objective Epicutaneo-caval catheters (ECCs) are essential for the care of sick infants who require long-term medical and nutritional management. The aim of this study was to investigate the use of real-time ultrasound as an alternative to X-rays to reduce the incidence of primary malpositions during catheter insertion. Study Design Data on ECCs were retrospectively collected in a tertiary neonatal intensive care unit. Catheter were analyzed considering the tip location technique (standard chest–abdominal radiograph vs real-time ultrasound) Results A total of 248 ECCs were analyzed. Of these, 118 catheters had primary malposition (47.6%). The tip of 165 catheters was assessed using standard chest–abdominal X-rays and 107 (64.8%) were found to be in an inappropriate location. In the group of 83 catheters that were placed using real-time ultrasound for tip location, only 11 catheters (13.2%) had primary malposition. The rate of malposition among the two groups showed a statistically significant difference (p < 0.001). Hypothetically, 300 chest X-rays could have been saved if real-time ultrasound had been used to locate the tip, reducing radiation exposure to infants. Conclusion The use of a real-time ultrasound may be beneficial in reducing primary catheter malpositions compared with conventional radiography. In addition, secondary malpositions and catheter-related complications can be monitored over time. Key Points

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.

BACKGROUND:Few studies in the literature have analyzed the long-term neurodevelopmental outcomes of the administration of a multicomponent versus a soybean-based lipid emulsion (LE) in preterm infants receiving parenteral nutrition (PN). A recent randomized controlled trial conducted in our unit provided evidence of better growth in head circumference during the hospital stay in those who received a multicomponent LE.METHODS:This is a 24 month follow-up study of preterm infants, previously enrolled in a randomized trial, who received a multicomponent LE (SMOFlipid®) or a standard soybean-based one (Intralipid®). We evaluated neurodevelopmental outcomes at 24 months of corrected age (CA) in the two groups.RESULTS:Ninety-three children were followed up to the age of 24 months CA. Due to the peculiar time frame of the SARS-CoV-2 pandemic, neurodevelopmental outcomes were evaluated only in 77 children: 37 in the SMOFlipid® group and 40 in the Intralipid® group. No differences in major disability rates or in Griffith's evaluation were found between the two groups.CONCLUSIONS:In our population study, the administration of a multicomponent LE containing fish oil, compared to a soybean-based LE, had no significant effects on neurodevelopmental outcomes in preterm infants at 24 months CA.

OBJECTIVE:To evaluate the role of cyanoacrylate glue in reducing dislodgement of umbilical venous catheters (UVCs). STUDY DESIGN:This was a single-center, randomized, controlled, nonblinded trial. All infants requiring an UVC according to our local policy were included in the study. Infants with a UVC with a centrally located tip as verified by real-time ultrasound examination were eligible for the study. Primary outcome was the safety and efficacy of securement by cyanoacrylate glue plus cord-anchored suture (SG group) vs securement by suture alone (S group), as measured by reduction in dislodgment of the external tract of the catheter. Secondary outcomes were tip migration, catheter-related bloodstream infection, and catheter-related thrombosis. RESULTS:In the first 48 hours after UVC insertion, dislodgement was significantly higher in the S group than in the SG group (23.1% vs 1.5%; P < .001). The overall dislodgement rate was 24.6% in the S group vs 7.7% in the SG group (P = .016). No differences were found in catheter-related bloodstream infection and catheter-related thrombosis. The incidence of tip migration was similar in both groups (S group 12.2% vs SG group 11.7%). CONCLUSIONS:In our single-center study, cyanoacrylate glue was safe and effective for securement of UVCs, and particularly effective in decreasing early catheter dislodgments. TRIAL REGISTRATION:UMIN-CTR Clinical Trial; Registration number: R000045844.

The incidence of sensorineural hearing loss (SNHL) is still high in very low birth weight (VLBW) infants. The purpose of our study was to provide the prevalence rates of SNHL and to analyze the risk factors of hearing impairment and changes in hearing thresholds in a cohort of VLBW infants. A retrospective observational study was conducted in our neonatal intensive care unit (NICU) from 2012 to 2016. All VLBW infants included were screened by transient evoked otoacoustic emissions (TEOAEs) and diagnostic auditory brainstem response (ABR). In total, we enrolled 316 infants and SNHL was diagnosed in 68, leading to an early incidence of 21.5% as 36 infants out of 68 improved. Finally, SNHL was confirmed in 20 patients (6.3%) who needed hearing aids. They were significantly smaller, sicker, had longer hospitalizations, and received more ototoxic therapies. Logistic regression analysis showed that gestational age (GA) influenced the association between drugs and SNHL. The results underlined how the total exposure to antibiotics is significantly associated with SNHL, even after GA correction. In conclusion, GA, birth weight and, above all, the length and complexity of NICU stay quantify the risk of SNHL and should be considered at the individual level for parent counseling.

Background: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP. Objective: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates. Study design: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates <= 32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP. Result: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial.

To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. The HINE was performed at 3, 6, 9, and 12 months’ corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23–31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.

IntroductionUreaplasma (U.) and Mycoplasma (M.) species have been related to pregnancy complications (including preterm birth) and worse neonatal outcomes. The aim of our work is to evaluate neurodevelopmental outcomes in preterm infants born to mothers with Ureaplasma/Mycoplasma colonization during pregnancy.MethodsPreterm infants with gestational age (GA) of ≤ 30 weeks were included in a retrospective follow-up study. To evaluate the effects of maternal vaginal colonization, we divided preterm infants into two groups: exposed and unexposed infants. All infants were assessed at 24 ± 3 months of age using Griffith’s Mental Developmental Scales (GMDS).ResultsAmong 254 preterm infants, only 32 infants (12.6%) were exposed to U. /M. colonization during pregnancy. Exposed infants and unexposed ones had a similar Griffith′s Developmental Quotient (106 ± 27.2 vs. 108.9 ± 19.5, respectively), without significant differences (p = 0.46). However, exposed infants had a significantly poorer outcome than their unexposed peers in terms of locomotor abilities (100.7 ± 28.3 exposed vs. 111.5 ± 26.1 unexposed, p = 0.03).ConclusionFor visual and hearing impairment, exposed and unexposed infants had similar incidences of cognitive and motor impairment. However, exposed infants had significantly lower locomotor scores than unexposed peers.

Aim To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. Method The HINE was performed at 3, 6, 9, and 12 months' corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. Results A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23-31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. Interpretation Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.

Background Mechanical ventilation is still needed in most preterm newborns, even in the non-invasive ventilation era. Ventilator-induced lung injury is one of the known pathogenetic factors of bronchopulmonary dysplasia (BPD) in preterm newborns. Lung injury has several patterns including surfactant dysfunction. Some recent trials have showed that a late surfactant administration can improve respiratory outcome in preterm babies still on invasive ventilation after the first week of life. Unfortunately, these results are still not conclusive. Moreover, giving surfactant after a recruitment manoeuvre in High Frequency Oscillatory Ventilation (HFOV) was shown to be safe and to reduce mortality in extremely preterm infants in a recent RCT. Our aim is to test the hypothesis that endotracheal administration of poractant-alfa preceded by a recruitment manoeuvre in HFOV in preterm infants still requiring mechanical ventilation at 7-10 days of life could facilitate extubation. Methods/Design: This will be an unblinded monocentric pilot trial that will be conducted in a III level Neonatal Intensive Care Unit at Fondazione Policlinico Agostino Gemelli IRCCS in Rome - Italy. Preterm newborns with a gestational age < 28 weeks still requiring invasive mechanical ventilation at 7-10 days of life with a fraction of inspired oxygen (FiO 2 ) of more than 0.30 and/or an oxygenation index of 8 or more for at least 6 hours will be eligible for the study. Patients will be randomly assigned to intervention or to standard care. Intervention group infants will receive up to 4 doses of Poractant-alfa every 12 hours, each dose preceded by a recruitment manoeuvre in HFOV, until extubation. Primary endpoint will be the first successful extubation. Discussion Surfactant therapy is nowadays recommended in case of RDS in the first days of life but little is known about its effects in ventilator-dependant preterm newborns. Late administration of surfactant could help healing the lung of preterm babies in which RDS is evolving in a chronic pulmonary insufficiency of prematurity. The findings of this pilot trial will permit evaluation of the study design for a full-scale RCT. Trial registration: Clinicaltrials.gov – ID NCT04825197. Registered 12 April 2021, https://clinicaltrials.gov/ct2/home

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

AIM:Extra-uterine Growth Restriction (EUGR) is common among preterm infants. Two types of EUGR definitions are still now available: cross-sectional definitions and longitudinal ones. In a cohort of very preterm infants, we aimed to evaluate which definition could better predict neurodevelopmental outcomes at 2 years of corrected age. We used Italian Neonatal Study Charts (INeS) growth charts and INTERGROWTH-21st (IG-21) standard charts and compared results. METHOD:We restrospectively collected data from clinical charts of 324 preterm newborns with a gestational age ≤30 weeks born from 2012 to 2017. Then we compared forty-eight definitions (24 cross-sectional and 24 longitudinal) of EUGR, in term of neurodevelopmental outcomes at 2 years of corrected age. RESULTS:We included in the study 254 preterm infants, whose clinical information met the enrolment criteria. Nineteen out of 48 definitions of EUGR were significantly predictive both for Griffith's Development Quotient (GDQ) and Neurodevelopment Impairment (NDI). Among these, longitudinal definitions appeared to have a higher negative predictive value for NDI than cross-sectional ones. Furthermore, infants with EUGR appeared to have a lower cognitive score than their peers without EUGR. INTERPRETATION:A loss of Zs > 1 SDS in weight and head circumference, calculated from when physiological weight loss is over and identified as soon as possible rather than at discharge, better predicts neurodevelopmental outcomes of preterm infants.

Objective To evaluate the efficacy of a strict glycaemic control protocol using a continuous glucose monitoring (CGM) in infants at high risk of dysglycaemia with the aim of reducing the number of dysglycaemic episodes. Design Randomised controlled trial. Setting Neonatal intensive care unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome. Patients All infants <1500 g fed on parental nutrition (PN) since birth were eligible. A total of 63 infants were eligible and 48 were randomised. Intervention All participants wore a CGM sensor and were randomised in two arms with alarms set at different cut-off values (2.61-10 mmol/L (47-180 mg/dL) vs 3.44-7.78 mmol/L (62-140 mg/dL)), representing the operative threshold requiring modulation of glucose infusion rate according to an innovative protocol. Main outcome measures The primary outcome was the number of severe dysglycaemic episodes (<2.61 mmol/L (47 mg/dL) or >10 mmol/L (180 mg/dL)) in the intervention group versus the control group, during the monitoring time. Results We enrolled 47 infants, with similar characteristics between the two arms. The number of dysglycaemic episodes and of infants with at least one episode of dysglycaemia was significantly lower in the intervention group (strict group): respectively, 1 (IQR 0-2) vs 3 (IQR 1-7); (p=0.005) and 12 (52%) vs 20 (83%); p=0.047. Infants managed using the strict protocol had a higher probability of having normal glycaemic values: relative risk 2.87 (95% CI 1.1 to 7.3). They spent more time in euglycaemia: 100% (IQR 97-100) vs 98% (IQR 94-99), p=0.036. The number needed to treat to avoid dysglycaemia episodes is 3.2 (95% CI 1.8 to 16.6). Conclusion We provide evidence that CGM, combined with a protocol for adjusting glucose infusion, can effectively reduce the episodes of dysglycaemia and increase the percentage of time spent in euglycaemia in very low birthweight infants receiving PN in the first week of life.