Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan.

BACKGROUND: Antenatal corticosteroids (ACS) are administered to prevent neonatal complications and death in women at risk of imminent preterm birth. Internationally, the optimal interval from ACS to delivery (ACS-to-delivery interval) is within seven days; however, evidence in Asian populations specifically is limited. This study aimed to investigate the association between ACS-to-delivery interval and the incidence of neonatal complications in Japan. METHODS: This retrospective observational study enrolled singleton neonates born preterm at < 32 weeks of gestational age between 2012 and 2020 at two tertiary centers. A total of 625 neonates were divided into the following four groups according to the timing of ACS (measured in days): no ACS (n = 145), partial ACS (n = 85), ACS 1-7 (n = 307), and ACS ≥ 8 (n = 88). The following outcomes were compared between the groups: treated respiratory distress syndrome (RDS), severe intraventricular hemorrhage (IVH), treated patent ductus arteriosus (PDA), necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity (ROP), periventricular leukomalacia, and death discharge. RESULTS: The ACS 1-7 group had significantly decreased adjusted odds ratios (ORs) for treated RDS (0.37 [95% confidence interval: 0.23, 0.57]), severe IVH (0.21 [0.07, 0.63]), treated PDA (0.47 [0.29, 0.75]), and treated ROP (0.50 [0.25, 0.99]) compared with the no ACS group. The ACS ≥ 8 group also showed significantly reduced adjusted ORs for RDS (0.37 [0.20, 0.66]) and treated PDA (0.48 [0.25, 0.91]) compared with the no ACS group. However, the adjusted ORs for BPD significantly increased in both the ACS 1-7 (1.86 [1.06, 3.28]) and ACS ≥ 8 groups (2.94 [1.43, 6.05]) compared to the no ACS group. CONCLUSIONS: An ACS-to-delivery interval of 1-7 days achieved the lowest incidence of several complications in preterm neonates born at < 32 weeks of gestational age. Some of the favorable effects of ACS seem to continue even beyond ≥ 8 days from administration. In contrast, ACS might be associated with an increased incidence of BPD, which was most likely to be prominent in neonates delivered ≥ 8 days after receiving ACS. Based on these findings, the duration of the effect of ACS on neonatal complications should be studied further.

A nationwide survey on the management of neonatal respiratory distress syndrome: insights from the MUNICH survey in 394 Chinese hospitals.

BACKGROUND: At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. METHODS: A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. RESULTS: Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at < 34 weeks of gestation (90·0% inborn vs. 50·0% outborn, p < 0·001). The median fraction of inspired oxygen (FiO2) for initial resuscitation was 0·30 for babies born at ≤ 32 weeks of gestation and 0·25 for those born at > 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p < 0·001). Surfactant was used in 51·6% of the DRs. Less invasive surfactant administration (LISA) was used in 49·7% of the hospitals (tertiary hospitals: 55·3% vs. secondary hospitals: 31·5%, p < 0·001). Primary non-invasive ventilation was initiated in approximately 80·0% of the patients. High-frequency oscillation ventilation was primarily reserved for rescue after conventional mechanical ventilation (MV) failure. Caffeine was routinely used during MV in 59·1% of the hospitals. Bedside lung ultrasonography was performed in 54·3% of the health facilities (tertiary hospitals: 61·6% vs. secondary hospitals: 30·4%, p < 0·001). Qualified breast milk banks and Family Integrated Care (FICare) were present in 30·2% and 63·7% of the hospitals, respectively. CONCLUSIONS: Significant disparities in resource availability and guidelines adherence were evident across hospitals. Future strategies should address DR facilities and medication access, technical training, staff allocation, and ancillary facility development for a better management of RDS patients in China.

Delayed sustained lung inflation for preterm neonates in neonatal intensive care unit: a randomized controlled trial.

INTRODUCTION: Sustained lung inflation (SLI) right after birth to decrease the use of mechanical ventilation of preterm infants is controversial because of potential harm. This randomized controlled trial was conducted to evaluate the effectiveness and safety of delayed SLI in neonatal intensive care unit (NICU). METHODS: Preterm neonates requiring continuous positive airway pressure after birth were eligible for enrollment. In the experimental group, SLI with 20 cm H2O for 15 s was conducted by experienced staff in the NICU between 30 min and 24 h after birth. RESULTS: A total of 45 neonates were enrolled into this study, including 24 in the experimental group and 21 in the control group. There was no significant difference in the birth condition between the experimental and control groups, including gestational age (p = 0.151), birth weight (p = 0.692), and Apgar score at 1 min (p = 0.410) and 5 min (p = 0.518). The results showed the duration of respiratory support was shorter in the experimental group than the control group (p = 0.044). In addition, there was no significant difference in the other outcomes, such as pneumothorax, patent ductus arteriosus, and bronchopulmonary dysplasia. CONCLUSION: Our findings indicate that sustained inflation conducted by experienced staff in the NICU is safe. The data suggest that SLI conducted by experienced staff in the NICU after stabilization could serve as an alternative management for preterm infants with respiratory distress. However, the reduction in use of respiratory support should be interpreted cautiously as a result of limited sample size. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000052797 (retrospectively registered).

Impact of implementation of 2019 European respiratory distress syndrome guidelines on bronchopulmonary dysplasia in very preterm infants.

BACKGROUND: To evaluate the impact of implementation of 2019 European respiratory distress syndrome (RDS) guidelines on the incidence of bronchopulmonary dysplasia (BPD). METHOD: We retrospectively collected the clinical data of very preterm infants (VPIs) born before 32 gestational weeks from January 1st 2018 to December 31st 2021. VPIs were divided into group A and group B according to their birth date which was before or at/after January 1st 2020, when the 2019 European RDS guidelines were introduced. BPD is considered as primary outcome. We statistically analyzed all the data, and we compared the general characteristics, ventilation support, medication, nutrition and the outcomes between the two groups. RESULTS: A total of 593 VPIs were enrolled, including 380 cases in group A and 213 cases in group B. There were no statistic differences regarding to gender ratio, gestational age, birth weight and delivery mode between the two groups. Compared with group A, group B showed higher rate of antenatal corticosteroid therapy (75.1% vs. 65.5%). The improvement of ventilation management in these latter patients included lower rate of invasive ventilation (40.4% vs. 50.0%), higher rate of volume guarantee (69.8% vs. 15.3%), higher positive end expiratory pressure (PEEP) [6 (5, 6) vs. 5 (5, 5) cmH2O] and higher rate of synchronized nasal intermittent positive pressure ventilation (sNIPPV) (36.2% vs. 5.6%). Compared with group A, group B received higher initial dose of pulmonary surfactant [200 (160, 200) vs. 170 (130, 200) mg/Kg], shorter antibiotic exposure time [13 (7, 23) vs. 17 (9, 33) days], more breast milk (86.4% vs. 70.3%) and earlier medication for hemodynamically significant patent ductus arteriosus (hsPDA) treatment [3 (3, 4) vs. 8 (4, 11) days] (p < 0.05). As the primary outcome, the incidence of BPD was significantly decreased (16.9% vs. 24.2%) (p < 0.05), along with lower extrauterine growth retardation (EUGR) rate (39.0% vs. 59.7%), while there were no statistic differences regarding to other secondary outcomes, including mortality, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of preterm (ROP) and necrotizing enterocolitis (NEC). However, in the subgroups of infants less than 28 gestational weeks or infants less than 1,000 g, the incidence of BPD was not significantly decreased (p > 0.05). CONCLUSIONS: After implementation of 2019 European RDS guidelines, the overall incidence of BPD was significantly decreased in VPIs. Continuous quality improvement is still needed in order to decrease the incidence of BPD in smaller infants who are less than 28 gestational weeks or less than 1,000 g.

[Risk factors for initial non-invasive ventilation failure in very low birth weight infants with gestational age <32 weeks: a multicenter retrospective study]. / 胎龄<32å‘¨æžä½Žå‡ºç”Ÿä½“é‡å„¿åˆå§‹æ— åˆ›é€šæ°”å¤±è´¥çš„å½±å“å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the risk factors and adverse prognosis associated with initial non-invasive ventilation (NIV) failure in very low birth weight infants (VLBWI) with gestational age <32 weeks. METHODS: A retrospective collection of clinical data from preterm infants admitted to the neonatal intensive care unit (NICU) in 28 tertiary hospitals in Jiangsu Province from January 2019 to December 2021 was conducted. Based on the outcomes of initial NIV, the infants were divided into a successful group and a failure group to analyze the risk factors for NIV failure and adverse prognosis. RESULTS: A total of 817 infants were included, with 453 males (55.4%) and 139 failures (17.0%). The failure group had lower gestational age, birth weight, and 1-minute and 5-minute Apgar scores compared to the successful group (P<0.05). The failure group also had a higher proportion of respiratory distress syndrome (RDS) diagnosed upon NICU admission, higher maximum positive end-expiratory pressure during NIV, and higher percentages of reaching the required maximum fraction of inspired oxygen (FiO2) ≥30%, ≥35%, and ≥40% throughout the initial NIV process compared to the successful group (P<0.05). Gestational age (OR=0.671, 95%CI: 0.581-0.772), RDS (OR=1.955, 95%CI: 1.181-3.366), and FiO2 ≥30% (OR=2.053, 95%CI: 1.106-4.044) were identified as risk factors for initial NIV failure in these infants with gestational age <32 weeks (P<0.05). The failure group had higher incidences of complications such as pulmonary infections, pneumothorax, retinopathy of prematurity, moderate to severe bronchopulmonary dysplasia, and severe intraventricular hemorrhage during hospitalization, as well as longer hospital stays and higher total costs compared to the successful group (P<0.05). CONCLUSIONS: Smaller gestational age, a diagnosis of RDS in the NICU, and achieving a maximum FiO2 ≥30% during the initial NIV process are risk factors for initial NIV failure in infants with gestational age <32 weeks. Initial NIV failure significantly increases the risk of adverse outcomes in this population.

The molecular mechanisms that underlie IGHMBP2-related diseases.

Immunoglobulin Mu-binding protein 2 (IGHMBP2) pathogenic variants result in the fatal, neurodegenerative disease spinal muscular atrophy with respiratory distress type 1 (SMARD1) and the milder, Charcot-Marie-Tooth (CMT) type 2S (CMT2S) neuropathy. More than 20 years after the link between IGHMBP2 and SMARD1 was revealed, and 10 years after the discovery of the association between IGHMBP2 and CMT2S, the pathogenic mechanism of these diseases is still not well defined. The discovery that IGHMBP2 functions as an RNA/DNA helicase was an important step, but it did not reveal the pathogenic mechanism. Helicases are enzymes that use ATP hydrolysis to catalyse the separation of nucleic acid strands. They are involved in numerous cellular processes, including DNA repair and transcription; RNA splicing, transport, editing and degradation; ribosome biogenesis; translation; telomere maintenance; and homologous recombination. IGHMBP2 appears to be a multifunctional factor involved in several cellular processes that regulate gene expression. It is difficult to determine which processes, when dysregulated, lead to pathology. Here, we summarise our current knowledge of the clinical presentation of IGHMBP2-related diseases. We also overview the available models, including yeast, mice and cells, which are used to study the function of IGHMBP2 and the pathogenesis of the related diseases. Further, we discuss the structure of the IGHMBP2 protein and its postulated roles in cellular functioning. Finally, we present potential anomalies that may result in the neurodegeneration observed in IGHMBP2-related disease and highlight the most prominent ones.

Recombinant fragment of human surfactant protein D to prevent neonatal chronic lung disease (RESPONSE): a protocol for a phase I safety trial in a tertiary neonatal unit.

INTRODUCTION: Chronic respiratory morbidity from bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth and has consequences for later respiratory, cardiovascular and neurodevelopmental outcomes. The early phases of respiratory illness are characterised by rapid consumption of endogenous surfactant and slow replenishment. Exogenous surfactant is routinely administered to infants born before 28 weeks of gestation as prophylaxis. Endogenous surfactant includes four proteins, known as surfactant proteins (SPs) A, B, C and D. Current bovine-derived and porcine-derived surfactant preparations only contain SPs B and C. SP-D has a key role in lung immune homeostasis as part of the innate immune system. Laboratory studies using recombinant SP-D have demonstrated reduced inflammation, which may be a pathway to reducing the associated morbidity from BPD. RESPONSE uses a recombinant fragment of human SP D (rfhSP-D), in a phase I safety and dose-escalation trial as the first stage in determining its effect in humans. METHODS AND ANALYSIS: This is a single-centre, dose-escalation, phase I safety study aiming to recruit 24 infants born before 30 weeks gestation with respiratory distress syndrome. In addition to routine surfactant replacement therapy, participants will receive three doses of rfhSP-D via endotracheal route at either 1 mg/kg, 2 mg/kg or 4 mg/kg. The study uses a Bayesian continual reassessment method to make dose escalation decisions. Dose-limiting events (DLE) in this trial will be graded according to the published Neonatal Adverse Event Severity Score. The primary outcome of this study is to evaluate the safety profile of rfhSP-D across each dose level based on the profile of DLE to establish the recommended phase 2 dose (RP2D) of rfhSP-D. ETHICS AND DISSEMINATION: The RESPONSE study has received ethical approval from London-Brent NHS Research Health Authority ethics committee. Results from the study will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBERS: ISRCTN17083028, NCT05898633. PROTOCOL VERSION: RESPONSE Protocol V.4.0 24th July 2024.

Unveiling collodion baby: confronting ectropion and respiratory drama in neonatal care.

A neonate presented to us with respiratory distress with diffuse involvement of skin with thickening, cracking and peeling since birth with severe ectropion and eclabium. The hospital course was complicated by polymicrobial sepsis requiring prolonged antibiotics and antifungals. The skin lesions were treated with acitretin, humidification and topical emollients. With the improvement of pneumonia and clearing of nasal debris, the neonate could be gradually weaned off respiratory support. Despite a stormy course, there was marked improvement in all skin lesions including ectropion and eclabium at discharge. This case highlights and discusses the challenges in diagnosis and underscores the need for multidisciplinary involvement of neonatology, dermatology and ophthalmology for a neonate with collodion baby syndrome.

The Clinical Heterogeneity of Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1)-A Report of Three Cases, Including Twins.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1; OMIM #604320, ORPHA:98920) is a rare autosomal recessive congenital motor neuron disease. It is caused by variants in the IGHMBP2 gene. Clinically, it presents with respiratory failure due to diaphragmatic paralysis, progressive muscle weakness starting in the distal parts of the limbs, dysphagia, and damage to sensory and autonomic nerves. Unlike spinal muscular atrophy (SMA), SMARD1 has a distinct genetic etiology and is not detected in the population newborn screening programs. Most children with SMARD1 do not survive beyond the first year of life due to progressive respiratory failure. Artificial ventilation can prolong survival, but no specific treatment is available. Therapy focuses on mechanical ventilation and improving the patient's quality of life. Research into gene therapy is ongoing. We report three female patients with SMARD1, including twins from a triplet pregnancy. In twin sisters (patient no. 1 and patient no. 2), two heterozygous variants in the IGHMBP2 gene were identified: c.595G>C/p.Ala199Pro and c.1615_1623del/p.Ser539_Tyr541del. In patient no. 3, a variant c.1478C>T/p.Thr493Ile and a variant c.439C>T/p.Arg147* in the IGHMBP2 gene were detected. Our findings underscore the variability of clinical presentations, even among patients sharing the same pathogenic variants in the IGHMBP2 gene, and emphasize the importance of early genetic diagnosis in patients presenting with respiratory failure, with or without associated diaphragmatic muscle paralysis.

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part I: In Vitro Testing and Characterization.

PURPOSE: Improving the deep lung delivery of aerosol surfactant therapy (AST) with a dry powder formulation may enable significant reductions in dose while providing improved efficacy. The objective of Part I of this two-part study was to present the development of a new dry powder aerosol synthetic lung surfactant (SLS) product and to characterize performance based on aerosol formation and realistic in vitro airway testing leading to aerosol delivery recommendations for subsequent in vivo animal model experiments. METHODS: A new micrometer-sized SLS excipient enhanced growth (EEG) dry powder formulation was produced via spray drying and aerosolized using a positive-pressure air-jet dry powder inhaler (DPI) intended for aerosol delivery directly to intubated infants with respiratory distress syndrome (RDS) or infant-size test animals. RESULTS: The best-case design (D2) of the air-jet DPI was capable of high emitted dose (> 80% of loaded) and formed a < 2 µm mass median aerodynamic diameter (MMAD) aerosol, but was limited to ≤ 20 mg mass loadings. Testing with a realistic in vitro rabbit model indicated that over half of the loaded dose could penetrate into the lower lung regions. Using the characterization data, a dose delivery protocol was designed in which a 60 mg total loaded dose would be administered and deliver an approximate lung dose of 14.7-17.7 mg phospholipids/kg with a total aerosol delivery period < 5 min. CONCLUSIONS: A high-efficiency aerosol SLS product was designed and tested that may enable an order of magnitude reduction in administered phospholipid dose, and provide rapid aerosol administration to infants with RDS.

Lung Ultrasound Score for Prediction of Surfactant Administration in Preterm Infants with Respiratory Failure.

OBJECTIVE: We investigated the predictive value of a lung ultrasound score (LUS) for surfactant administration in a United States Level 4 Neonatal Intensive Care Unit. STUDY DESIGN: Thirty infants born at <37 weeks gestational age with respiratory distress syndrome associated respiratory failure requiring continuous positive airway pressure were included. A LUS was obtained within six hours of life. Surfactant administration in the first five days of life was recorded. Receiver operating characteristic (ROC) analysis for LUS and surfactant administration was performed. RESULTS: Median completed gestational age was 33 weeks (31-34 weeks interquartile range) and median birth weight was 2.0 kg (1.5-2.3 kg). LUS for predicting an initial surfactant dose had an area under the ROC curve of 0.97. A score > 9 provided 100% sensitivity and 91% specificity for predicting administration of an initial surfactant dose. CONCLUSION: A LUS > 9 provided excellent sensitivity and specificity for predicting which infants will receive surfactant for associated respiratory failure.

Impact of early caffeine administration on respiratory outcomes in very preterm infants initially receiving invasive mechanical ventilation.

OBJECTIVE: The guidelines recommend early caffeine administration for preterm infants requiring non-invasive mechanical ventilation since earlier treatment is associated with better outcomes. The objective was to evaluate the impact of early caffeine therapy (within 24 hours after birth) on respiratory outcomes in very preterm infants who were initially receiving invasive mechanical ventilation. METHODS: This was an observation cohort study from 1 January 2018 to 31 December 2022 based on a database that was prospectively collected and maintained. Infants who initially received invasive mechanical ventilation were divided into two groups based on the timing of caffeine initiation: within the first 24 hours after birth (early) and within 48 hours of birth or later (late). Generalised linear mixed models with a random effect model for the centre were used to assess the impact of different caffeine initiation times on neonatal outcomes. RESULTS: Among the cohort of 9880 infants born at <32 weeks gestation, 2381 were eligible for this study (early initiation: 1758 (73.8%) and late initiation: 623 (26.2%)). For infants born at more than 28 weeks of gestation, the adjusted generalised linear mixed model showed that the duration of invasive mechanical ventilation was 1.34 (95% CI -2.40 to -0.27) days shorter and the incidence of moderate-to-severe bronchopulmonary dysplasia (BPD) was lower (adjusted OR 0.63; 95% CI 0.41 to 0.96) in the early caffeine group compared with the late caffeine group. CONCLUSION: In very preterm infants who initially receive invasive mechanical ventilation, early administration of caffeine within 24 hours after birth can shorten the duration of invasive mechanical ventilation, reduce the incidence of moderate-to-severe BPD and improve respiratory outcomes. The very early initiation of caffeine treatment does not appear to be associated with any adverse outcomes. TRIAL REGISTRATION NUMBER: ChiCTR1900025234.

[Analysis of clinical characteristics and variant of NKX2-1 gene in a Chinese boy with Brain-Lung-Thyroid syndrome].

OBJECTIVE: To carry out clinical and genetic analysis for a child featuring Brain-Lung-Thyroid syndrome (BLTS). METHODS: A child who had presented at the Children's Hospital Affiliated to Shandong University on May 27, 2022 was selected as the study subject. Clinical data was collected. Trio-whole exome sequencing (Trio-WES) was carried out for the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The child was given individualized treatment following the diagnosis. RESULTS: The child, a two-year-and-seven-month-old boy, had presented with global developmental delay, ataxia and hypothyroidism. WES revealed that he has harbored a heterozygous c.674C>T variant of the NKX2-1 gene, based on which he was diagnosed with BLTS. CT scan revealed interstitial and parenchymal inflammation in his lungs, which was reduced by budesonide aerosol inhalation. CONCLUSION: Discovery of the novel c.674C>T variant has enriched the mutational spectrum of the NKX2-1 gene. Budesonide aerosol may be used to treat lung inflammation associated with BLTS.

Incidence of neonatal respiratory morbidity after vaginal and caesarean delivery in the late-preterm and term period - a retrospective cohort study.

BACKGROUND: Respiratory distress syndrome is a leading cause of neonatal intensive care unit admissions for late preterm (34-36 weeks gestational age) and term infants (37-41 weeks). The risk for respiratory morbidity appears to increase after an elective caesarean delivery and might be reduced after antenatal corticosteroids. However, before considering antenatal corticosteroids for women at high risk of preterm birth after 34 weeks, the incidence of respiratory distress syndrome and the effect of delivery mode on this incidence requires further evaluation. Therefore, this study aimed to investigate the relationship between respiratory distress syndrome incidence and delivery mode in late preterm and term infants. METHODS: In this retrospective cohort study, the clinical databases of the University Hospitals of Zurich and Basel were queried regarding all live births between 34 + 0 and 41 + 6 weeks. Neonatal intensive care unit admissions due to respiratory distress syndrome were determined and analysed in regard to the following delivery modes: spontaneous vaginal, operative vaginal, elective caesarean, secondary caesarean and emergency caesarean. RESULTS: After excluding malformations (n = 889) and incomplete or inconclusive data (n = 383), 37,110 infants out of 38,382 were evaluated. Of these, 5.34% (n = 1980) were admitted to a neonatal intensive care unit for respiratory distress syndrome. Regardless of gestational age, respiratory distress syndrome in infants after spontaneous vaginal delivery was 2.92%; for operative vaginal delivery, it was 4.02%; after elective caesarean delivery it was 8.98%; following secondary caesarean delivery, it was 8.45%, and after an emergency caesarean it was 13.3%. The risk of respiratory distress syndrome was higher after an elective caesarean compared to spontaneous vaginal delivery, with an odds ratio (OR), adjusted for gestational age, of 2.31 (95% CI 1.49-3.56) at 34 weeks, OR 5.61 (95% CI 3.39-9.3) at 35 weeks, OR 1.5 (95% CI 0.95-2.38) at 36 weeks, OR 3.28 (95% CI 1.95-5.54) at 37 weeks and OR 2.51 (95% CI 1.65-3.81) at 38 weeks. At 39 weeks, there was no significant difference between the risk of respiratory distress syndrome after an elective caesarean vs. spontaneous vaginal delivery. Over the study period, gestational age at elective caesarean delivery remained stable at 39.3 ± 1.65 weeks. CONCLUSION: The incidence of respiratory distress syndrome following an elective caesarean is up to threefold higher in infants born with less than 39 weeks gestational age compared to those born by spontaneous vaginal delivery. Therefore - and whenever possible - an elective caesarean delivery should be planned after 38 completed weeks to minimise the risk of respiratory morbidity in neonates.

Maternal prenatal systemic inflammation indexes predicts premature neonatal respiratory distress syndrome.

Neonatal respiratory distress syndrome (NRDS) is one of the leading causes of neonatal mortality in low-income countries. It is caused by a lack of surface-active substances in the lungs, and the maternal inflammatory response plays an important role in the formation of surface-active substances in the fetal lungs. We aimed to investigate the correlation between maternal prenatal systemic inflammatory indices and respiratory distress syndrome in preterm neonates. This is a retrospective case-control study that collected data from all patients who delivered between 28 and 36 weeks of gestation at Longhua District People's Hospital in Shenzhen City and whose infants were admitted to the neonatal unit, newborns with respiratory distress syndrome were in the experimental group (NRDS group), and newborns without NRDS were in the control group (non-NRDS group). To minimize the effect of confounders on the results, propensity score matching was performed on baseline characteristics. Totally, 524 patients were included (93 in the NRDS group and 431 in the non-NRDS group), and 71 matched pairs (142 patients). The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI) and neutrophil lymphocyte to platelet ratio (NLPR) were higher in the NRDS group than in the non-NRDS group (p < 0.05). The ROC curves of NLR, dNLR, SII, SIRI, AISI and NLPR for the diagnosis of NRDS were plotted, and it was found that the combined diagnostic efficacy of these six systemic inflammatory markers was better (AUC: 0.643, P = 0.003). Patients were divided into two groups based on the cut-off values determined from the ROC curves, and analysis using binary regression models revealed that SII ≥ 1199.94 (OR, 2.554; 95% CI 1.245-5.239, P = 0.011) and NLPR ≥ 0.0239 (OR, 2.175; 95% CI 1.061-4.459, P = 0.034) were independent risk factors predicting NRDS. Maternal prenatal SII ≥ 1199.94 and NLPR ≥ 0.0239 are independent risk factors for NRDS, and clinicians may be used to prevent neonatal respiratory distress in advance to reduce the incidence of NRDS.

Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) in the neonatal intensive care unit (NICU): an Australian NICU experience.

BACKGROUND: Preterm infants often require non-invasive breathing support while their lungs and control of respiration are still developing. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is an emerging technology that allows infants to breathe spontaneously while receiving support breaths proportional to their effort. This study describes the first Australian Neonatal Intensive Care Unit (NICU) experience of NIV-NAVA. METHODS: Retrospective cohort study of infants admitted to a major tertiary NICU between October 2017 and April 2021 supported with NIV-NAVA. Infants were divided into three groups based on the indication to initiate NIV-NAVA (post-extubation; apnoea; escalation). Successful application of NIV-NAVA was based on the need for re-intubation within 48 h of application. RESULTS: There were 169 NIV-NAVA episodes in 122 infants (82 post-extubation; 21 apnoea; 66 escalation). The median (range) gestational age at birth was 25 + 5 weeks (23 + 1 to 43 + 3 weeks) and median (range) birthweight was 963 g (365-4320 g). At NIV-NAVA application, mean (SD) age was 17 days (18.2), and median (range) weight was 850 g (501-4310 g). Infants did not require intubation within 48 h in 145/169 (85.2%) episodes [72/82 (87.8%) extubation; 21/21 (100%) apnoea; 52/66 (78.8%) escalation). CONCLUSION: NIV-NAVA was successfully integrated for the three main indications (escalation; post-extubation; apnoea). Prospective clinical trials are still required to establish its effectiveness versus other modes of non-invasive support.

Hemodynamically significant patent ductus arteriosus profile in preterm neonates (26-34 weeks' gestation) undergoing surfactant replacement therapy in India: a prospective observational study.

Surfactant administration significantly improves respiratory outcomes in preterm infants with respiratory distress syndrome (RDS). However, surfactant administration may lead to hemodynamic alterations, particularly in the heart, affecting the patent ductus arteriosus (PDA), the consequences of which are not fully understood. This prospective observational study took place in an Indian neonatal care unit from July 2019 to November 2020, enrolling preterm neonates (26-34 weeks' gestation) with RDS needing non-invasive positive pressure ventilation. They were divided into two groups: those who received surfactant while on respiratory support and those who did not. All newborns in the study had an initial echocardiogram within 24 h to detect PDA flow. Subsequent echocardiograms were conducted between 48 and 72 h or earlier based on symptoms. Of 220 infants requiring respiratory support, 84 were enrolled, with 42 in each group. While demographic variables were similar, the surfactant group had a lower median gestational age (29.0 vs. 31.0 weeks). In the surfactant group, a significantly higher percentage of neonates had hemodynamically significant PDA (hsPDA) compared to the non-surfactant group (54.76% vs. 26.19%, P-value = .008). Multiple logistic regression found no significant association between gestation, birth weight, or shock and hsPDA occurrence. Pulmonary hemorrhage occurred more often in the surfactant group. Bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) > grade 2, and necrotizing enterocolitis (NEC) ≥ grade 2 did not differ significantly between the groups. Surfactant therapy via the less invasive surfactant administration technique was associated with a higher incidence of hsPDA. While surfactant is crucial for neonatal respiratory care, its potential hemodynamic effects, including hsPDA, should be considered.

Risk factors for neonatal hypoglycemia: a meta-analysis.

OBJECTIVE: This Study aims to investigate the risk factors of hypoglycemia in neonates through meta-analysis. METHOD: PubMed, Embase, Cochrane library, and Web of science databases were searched for case-control studies on risk factors for neonatal hypoglycemia. The search was done up to 1st October 2023 and Stata 15.0 was used for data analysis. RESULTS: A total of 12 published studies were included, including 991 neonates in the hypoglycemic group and 4388 neonates in the non-hypoglycemic group. Meta-analysis results suggested caesarean section [OR = 1.90 95%CI (1.23, 2.92)], small gestational age[OR = 2.88, 95%CI (1.59, 5.20)], gestational diabetes [OR = 1.65, 95%CI (1.11, 2.46)], gestational hypertension[OR = 2,79, 95%CI (1.78, 4.35)] and respiratory distress syndrome[OR = 5.33, 95%CI (2.22, 12.84)] were risk factors for neonatal hypoglycemia. CONCLUSION: Based on the current study, we found that caesarean section, small gestational age, gestational diabetes, gestational hypertension, respiratory distress syndrome are risk factors for neonatal hypoglycemia. PROSPERO REGISTRATION NUMBER: CRD42023472974.

Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: 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. METHODS: 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). DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Metabolic and Microbial Dysregulation in Preterm Infants with Neonatal Respiratory Distress Syndrome: An Early Developmental Perspective.

Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.