Neonatal Respiratory Distress Research Articles

Knee-to-chest flexion manoeuvre to reduce respiratory distress after planned caesarean birth: a feasibility study

BackgroundPlanned caesarean section (CS) is a risk factor for neonatal respiratory distress caused by a greater volume of airway liquid in the absence of uterine contractions.Performing a newly conceptualised knee-to-chest...

Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare, genetic disease characterized by dysfunctional motile cilia and abnormal mucociliary clearance, resulting in chronic sino-oto-pulmonary disease, neonatal respiratory distress, subfertility, and organ laterality defects. Over the past 2 decades, research and international collaborations have led to an improved understanding of disease prevalence, classic and variable phenotypes, novel diagnostics, genotype-phenotype correlations, long term morbidity, and innovative therapeutics. However, PCD is often underrecognized in clinical settings and the recent analyses of genetic databases suggest that only a fraction of these patients are being accurately diagnosed. Knowledge of significant advancements, from pathophysiology to the expanded range of clinical manifestations, will have important clinical impacts. These may include increasing disease recognition, improving diagnostic testing and management, and establishing an adequate pool of affected patients to enroll in upcoming clinical therapeutic trials. The objective of this state-of-the-art review is for readers to gain a greater understanding of the clinical spectrum of motile ciliopathies, cutting-edge diagnostic practices, emerging genotype-phenotype associations, and currently accepted management of people with PCD.

Life-saving effect of pulmonary surfactant in premature babies.

The discovery and replacement of lung surfactant have helped increase survival rates for neonatal respiratory distress syndrome in extremely premature infants.

Radiographic Evaluation of Neonatal Respiratory Distress: Cross-Sectional Study on Chest X-ray Findings in the Neonatal Intensive Care Unit

Introduction: Neonatal Respiratory distress (NRD) is a common reason for admission to the Neonatal Intensive Care Unit (NICU). While clinical diagnosis is essential, imaging evaluation can help confirm lung lesions, their extent, and associated abnormalities. However, radiation exposure from imaging modalities such as Computed Tomography (CT) and Chest X-ray (CXR) is a concern, particularly for neonates. This study aims to identify the various CXR findings in neonates with respiratory distress in the NICU. Methods: A quantitative cross-sectional study was conducted on 59 neonates with respiratory distress in the NICU from November 2019 to November 2020. Ethical clearance was obtained, and data were collected through portable CXR. The collected data were analyzed using Microsoft Excel 2016 and Statistical Package of Social Services (SPSS) IBM version 23. Results: CXR findings of 59 neonates with a mean age of 15.9 ± 7.4 days were evaluated. The majority were premature neonates, and the most common clinical diagnosis was respiratory distress syndrome (RDS). Hypoaeration was the most common finding in lung fields, followed by normal aeration. Parenchymal changes were observed in most cases, with reticulations/haziness being the most common, followed by consolidation. Pleural effusion was seen in a few cases, predominantly in preterm neonates with RDS. Conclusions: The study underscores the prevalence of hypoaeration, reticulations, and consolidations in NICU patients with RDS, emphasizing the importance of early diagnosis and future research in neonatal chest imaging for respiratory distress.

Anti-infectious and anti-inflammatory effect of amniopatch in the treatment of spontaneous previable rupture of membranes.

Spontaneous previable rupture of membranes complicates approximately 0.4-0.7% of pregnancies and is associated with severe maternal and neonatal morbidity and mortality. Intra-amniotic inflammation is present in up to 94.4% of cases, most often caused by a bacterial infection. In comparison, the effectiveness of antibiotic therapy in its eradication reaches less than 17%. Inflammatory activity in the amniotic cavity disrupts the physiological development of the fetus with an increase in maternal, fetal, and neonatal inflammatory morbidity through the development of fetal inflammatory response syndrome, maternal chorioamnionitis, and neonatal sepsis. Amniopatch is an invasive therapeutic technique based on intra-amniotic administration of maternal hemoderivates in the form of thromboconcentrate and plasma cryoprecipitate to provide the temporary closure of the fetal membranes defect and secondary restitution of normohydramnios with correction of pressure-volume ratios. The supposed basis of this physical-mechanical action is the aggregation of coagulant components of amniopatch in the area of the defect with the formation of a valve cap. The background for the formulation of the hypothesis on the potential anti-infectious and anti-inflammatory action of non-coagulant components of amniopatch involved: i) clinical-academic and publishing outputs of the authors based on their many years' experience with amniopatch application in the treatment of spontaneous previable rupture of membranes (2008-2019), ii) the documented absence of clinically manifested chorioamnionitis in patients treated this way with a simultaneously reduced incidence of neonatal respiratory distress syndrome compared to expectant management (tocolysis, corticotherapy, antibiotic therapy). The non-coagulant components of plasma cryoprecipitate include mainly naturally occurring isohemagglutinins, albumin, and soluble plasma fibrinogen. Although these components of the amniopatch have not been attributed a significant therapeutic role, the authors assume that due to their opsonizing and aggregative properties, they can significantly participate in optimizing the intrauterine environment through the reduction in bacterial and cytokine charge in the amniotic fluid. The authors think these facts constitute a vital stimulus to future research-academic activity and, at the same time, an idea for reconsidering the therapeutic role of amniopatch as a tool for improving perinatal results of spontaneous previable ruptures of membranes.

Fungal microbiota in newborn infants with and without respiratory distress syndrome.

Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in the bacterial microbiota of the airways have also been described in infants with bronchopulmonary dysplasia. However, until now there has been no information on the airway mycobiota in newborns. The purpose of this study was to describe the airway mycobiota in term and preterm newborns and its possible association with respiratory distress syndrome. Twenty-six matched preterm newborns with and without respiratory distress syndrome were studied, as well as 13 term babies. The identification of the fungal microbiota was carried out using molecular procedures in aspirated nasal samples at birth. The ascomycota phylum was identified in 89.7% of newborns, while the basidiomycota phylum was found in 33.3%. Cladosporium was the predominant genus in both term and preterm infants 38.4% vs. 73% without statistical differences. Candida sake and Pneumocystis jirovecii were only found in preterm infants, suggesting a potential relationship with the risk of prematurity. This is the first report to describe the fungal microbiota of the airways in term and preterm infants with and without respiratory distress syndrome. Although no differences have been observed, the number of cases analyzed could be small to obtain conclusive results, and more studies are needed to understand the role of the fungal microbiota of the airways in neonatal respiratory pathology.

The Outcomes of Preterm Infants with Neonatal Respiratory Distress Syndrome Treated by Minimally Invasive Surfactant Therapy and Non-Invasive Ventilation.

In recent years, the utilization of minimally invasive surfactant therapy (MIST) and Non-invasive ventilation (NIV) as the primary respiratory assistance has become increasingly prevalent among preterm infants with neonatal respiratory distress syndrome (RDS). This study aims to compare the outcomes between MIST administered with nasal continuous positive airway pressure (NCPAP) versus nasal intermittent positive pressure ventilation (NIPPV), with the objective of exploring the respiratory therapeutic benefits of these two approaches. This retrospective study collected data from the neonatal intensive care unit of Kaohsiung Medical University Hospital spanning from January 2016 to June 2021. Infants were divided into two groups based on the type of NIV utilized. The NCPAP group comprised 32 infants, while the NIPPV group comprised 22 infants. Statistical analysis revealed significant differences: the NIPPV group had a smaller gestational age, lower birth weight, higher proportion of female infants, and earlier initiation of MIST. Additionally, the NIPPV group exhibited higher incidence rates of retinopathy of prematurity, longer respiratory support duration, prolonged hospitalization, and mortality. However, upon adjustment, these differences were not statistically significant. Analysis of venous blood gas and respiratory parameter changes indicated that both the NCPAP and NIPPV groups experienced improvements in oxygenation and ventilation following MIST.

The association of LPCAT1-rs9728 polymorphism with cord blood IL-10, MIF, and VEGF levels in neonatal respiratory distress syndrome: a case–control study

BackgroundLysophospholipid acyltransferase (LPCAT) is crucial for surfactant biosynthesis. It is encoded by LPCAT genes. We investigated the LPCAT1-rs9728 genotypes in neonatal respiratory distress syndrome (NRDS) cases and their possible association with the cord arterial serum interleukin-10 (IL-10), macrophage migration inhibitory factor (MIF), and vascular endothelial growth factor (VEGF) levels.MethodsThe study included 160 neonates grouped into G1: 60 healthy neonates and G2: 100 NRDS cases. IL-10, MIF, and VEGF levels were measured by their corresponding kits. The Gene JETTM Whole Blood Genomic DNA Purification Mini Kit was used to extract the DNA from the newborn venous blood. The quantitative real-time polymerase chain reaction was carried out for LPCAT1-rs9728 genotyping.ResultsThe IL-10 and MIF levels were significantly higher, while VEGF levels were significantly lower in G2 than in G1. The percentages of LPCAT1-rs9728 AA and LPCAT1-rs9728 AG genotypes were significantly higher in G2 than in G1. The IL-10 and MIF levels were significantly higher, while the VEGF levels, birth weight, and APGAR score at 1 and 5 min were significantly lower in neonates with LPCAT1-rs9728 AA genotype than in neonates with LPCAT1-rs9728 AG and LPCAT1-rs9728 GG genotypes and in neonates with LPCAT1-rs9728 AG genotype than in neonates with LPCAT1-rs9728 GG genotype.ConclusionThere is an association between the LPCAT1-rs9728 AA genotype and its A allele and the NRDS development and severity. Further research may provide a better understanding of this association to help future management.

Meconium aspiration syndrome: from pathophysiology to treatment.

Meconium aspiration syndrome (MAS) is a clinical condition characterized by respiratory distress in neonates born through meconium-stained amniotic fluid (MSAF). Despite advances in obstetric practices and perinatal care, MAS remains an important cause of morbidity and mortality in term and post-term newborns. Since the 1960s, there have been significant changes in the perinatal and postnatal management of infants born through MSAF. Routine endotracheal suctioning is no longer recommended in both vigorous and non-vigorous neonates with MSAF. Supportive care along with new treatments such as surfactant, inhaled nitric oxide, and high-frequency ventilation has significantly improved the outcome of MAS patients. However, determining the most appropriate approach for this condition continues to be a topic of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management, and prognosis of infants with MAS.

Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns

With the widespread use of immune checkpoint inhibitors (ICIs), concerns about their pregnancy outcomes through maternal exposure have emerged, and clinical comparative data are lacking. To assess the risk of pregnancy-, fetal-, and/or newborn-related adverse outcomes associated with exposure to ICIs compared with exposure to other anticancer agents. In this cohort study, all reports mentioning a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) used for a cancer indication registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. Anticancer agents, including ICIs, used during pregnancy for a cancer indication. Immune checkpoint inhibitors included blockers of programmed cell death 1 (PD1) or its ligand (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA4). The main outcome was the reporting odds ratio (ROR) for maternal, fetal, or newborn complications in patients treated with ICIs vs any other anticancer drug. Adverse events, categorized into 45 individual maternofetal adverse outcomes, were directly mapped to Medical Dictionary for Regulatory Activities preferred terms in VigiBase. A total of 3558 reports (ICI: 91 [2.6%]; other anticancer drugs: 3467 [97.4%]) were included in the analysis. In the ICI group, most reports were from the US (60 [65.9%]), and the mean (SD) patient age was 28.9 (10.2) years; in 24 of 55 reports with data on cancer type (43.6%), patients were treated for melanoma. The molecules involved in the ICI group were anti-PD1 (58 reports [63.7%]), anti-PD1 plus anti-CTLA4 (15 [16.5%]), anti-CTLA4 (13 [14.3%]), anti-PD-L1 (4 [4.4%]), and anti-PD1 plus anti-lymphocyte activation gene 3 (1 [1.1%]). An ICI was used in combination with a non-ICI anticancer agent in 10 participants (11.0%). Compared with other anticancer drugs, none of the 45 adverse outcomes identified were overreported in the group exposed to ICIs. However, preterm birth was significantly overreported for the anti-PD1 plus anti-CTLA4 combination compared with other anticancer drugs (12 of 15 [80.0%] vs 793 of 3452 [23.0%]; ROR, 13.87; 95% CI, 3.90-49.28; P < .001) but not for anti-PD-L1 or anti-CTLA4 monotherapy. Three reports of possibly immune-related maternofetal events were identified: 1 case of maternal antiphospholipid syndrome leading to spontaneous abortion, 1 case of pneumonitis leading to neonatal respiratory distress syndrome and death, and 1 case of transient congenital hypothyroidism. In this cohort study of 91 individuals exposed to ICIs during pregnancy, ICI exposure was not associated with overreporting of specific adverse pregnancy, fetal, and/or newborn outcomes compared with other anticancer treatments. However, due to possible rare immune-related neonatal adverse events, ICI use in pregnant women should be avoided when possible, especially the anti-PD1 plus anti-CTLA4 combination.

Towards quantifying biomarkers for respiratory distress in preterm infants: Machine learning on mid infrared spectroscopy of lipid mixtures

Neonatal respiratory distress syndrome (nRDS) is a challenging condition to diagnose which can lead to delays in receiving appropriate treatment. Mid infrared (IR) spectroscopy is capable of measuring the concentrations of two diagnostic nRDS biomarkers, lecithin (L) and sphingomyelin (S) with the potential for point of care (POC) diagnosis and monitoring. The effects of varying other lipid species present in lung surfactant on the mid IR spectra used to train machine learning models are explored. This study presents a lung lipid model of five lipids present in lung surfactant and varies each in a systematic approach to evaluate the ability of machine learning models to predict the lipid concentrations, the L/S ratio and to quantify the uncertainty in the predictions using the jackknife + -after-bootstrap and variant bootstrap methods. We establish the L/S ratio can be determined with an uncertainty of approximately ±0.3 mol/mol and we further identify the 5 most prominent wavenumbers associated with each machine learning model.

Cardiovascular outcomes 50 years after antenatal exposure to betamethasone: Follow-up of a randomised double-blind, placebo-controlled trial.

Antenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids. We assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159/229 [69.4%] versus 131/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments. There is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease.

Exploring the diagnostic value of ultrasound radiomics for neonatal respiratory distress syndrome

BackgroundNeonatal respiratory distress syndrome (NRDS) is a prevalent cause of respiratory failure and death among newborns, and prompt diagnosis is imperative. Historically, diagnosis of NRDS relied mostly on typical clinical manifestations, chest X-rays, and CT scans. However, recently, ultrasound has emerged as a valuable and preferred tool for aiding NRDS diagnosis. Nevertheless, evaluating lung ultrasound imagery necessitates rigorous training and may be subject to operator-dependent bias, limiting its widespread use. As a result, it is essential to investigate a new, reliable, and operator-independent diagnostic approach that does not require subjective factors or operator expertise. This article aims to explore the diagnostic potential of ultrasound-based radiomics in differentiating NRDS from other non-NRDS lung disease.MethodsA total of 150 neonatal lung disease cases were consecutively collected from the department of neonatal intensive care unit of the Quanzhou Maternity and Children’s Hospital, Fujian Province, from September 2021 to October 2022. Of these patients, 60 were diagnosed with NRDS, whereas 30 were diagnosed with neonatal pneumonia, meconium aspiration syndrome (MAS), and transient tachypnea (TTN). Two ultrasound images with characteristic manifestations of each lung disease were acquired and divided into training (n = 120) and validation cohorts (n = 30) based on the examination date using an 8:2 ratio. The imaging texture features were extracted using PyRadiomics and, after the screening, machine learning models such as random forest (RF), logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), and multilayer perceptron (MLP) were developed to construct an imaging-based diagnostic model. The diagnostic efficacy of each model was analyzed. Lastly, we randomly selected 282 lung ultrasound images and evaluated the diagnostic efficacy disparities between the optimal model and doctors across differing levels of expertise.ResultsTwenty-two imaging-based features with the highest weights were selected to construct a predictive model for neonatal respiratory distress syndrome. All models exhibited favorable diagnostic performances. Analysis of the Youden index demonstrated that the RF model had the highest score in both the training (0.99) and validation (0.90) cohorts. Additionally, the calibration curve indicated that the RF model had the best calibration (P = 0.98). When compared to the diagnostic performance of experienced and junior physicians, the RF model had an area under the curve (AUC) of 0.99; however, the values for experienced and junior physicians were 0.98 and 0.85, respectively. The difference in diagnostic efficacy between the RF model and experienced physicians was not statistically significant (P = 0.24), whereas that between the RF model and junior physicians was statistically significant (P < 0.0001).ConclusionThe RF model exhibited excellent diagnostic performance in the analysis of texture features based on ultrasound radiomics for diagnosing NRDS.

Prediction of neonatal respiratory distress syndrome by Quantitative ultrasound texture analysis of fetal lung Observational cross section study

Prediction of neonatal respiratory distress syndrome by Quantitative ultrasound texture analysis of fetal lung Observational cross section study

Analysis and risk factors of deep vein catheterization-related bloodstream infections in neonates.

To investigate the incidence, risk factors, and pathogenic characteristics of catheter-related bloodstream infection caused by peripherally inserted central venous catheter in neonates, and to provide references for reducing the infection rate of peripherally inserted central venous catheter. The clinical data of 680 neonates who underwent peripherally inserted central catheter (PICC) in the neonatal intensive care unit from June 2020 to June 2023 were retrospectively analyzed. The risk factors and independent risk factors of catheter-related bloodstream infection caused by PICC were determined by univariate and multivariate analysis, respectively. Catheter-related bloodstream infection occurred in 38 of 680 neonates who underwent PICC. The infection rate was 4.74%. The proportions of fungi, gram-positive bacteria, and gram-negative bacteria were 42.11%, 36.84%, and 21.05%, respectively. Candida parapsilosis was the main fungus (18.42%), coagulase negative Staphylococcus was the main gram-positive bacteria (23.68%), and Klebsiella pneumoniae and Escherichia coli were the main gram-negative bacteria (7.89%). Univariate analysis showed that gestational age ≤32 weeks, birth weight ≤1500 g, congenital diseases, nutritional support, catheterization time, 5-minute APGAR score ≤7, and neonatal respiratory distress syndrome were associated with catheter-related bloodstream infection caused by PICC. Multivariate analysis showed that premature delivery, low birth weight, parenteral nutrition, long catheterization time, and 5-minute APGAR score ≤7 were associated with catheter-related bloodstream infection caused by PICC. Among the pathogens detected, there were 6 cases of K pneumoniae, 5 cases of coagulase negative staphylococci, and 2 cases of fungi. Low birth weight, premature delivery, off-site nutrition, long catheterization time, and 5-minute APGAR score ≤7 are independent risk factors for catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters. The pathogenic bacteria are fungi and multidrug-resistant bacteria.

Cannabis exposure during pregnancy and perinatal outcomes: A cohort study.

Cannabis potency and its use during pregnancy have increased in the last decade. The aim of this study was to investigate the impact of antenatal cannabis use on fetal growth, preterm birth and other perinatal outcomes. A propensity score-matched analysis was performed in women with singleton pregnancies attending a tertiary care site in Barcelona. Women in the cannabis group were selected based on the results of a detection test. Primary outcomes were small for gestational age at birth (SGA), low birthweight and preterm birth. Secondary outcomes were other biometric parameters (neonatal length and head circumference), respiratory distress, admission to the neonatal intensive care unit and breastfeeding at discharge. A second propensity score-matched analysis excluding other confounders (use of other recreational drugs and discontinuation of cannabis use during pregnancy) was performed. Antenatal cannabis was associated with a higher odds ratio of SGA (OR 3.60, 95% CI: 1.68-7.69), low birthweight (OR 3.94, 95% CI: 2.17-7.13), preterm birth at 37 weeks (OR 2.07, 95% CI: 1.12-3.84) and 32 weeks of gestation (OR 4.13, 95% CI: 1.06-16.11), admission to the neonatal intensive care unit (OR 1.95, 95% CI: 1.03-3.71), respiratory distress (OR 2.77, 95% CI: 1.26-6.34), and lower breastfeeding rates at discharge (OR 0.10, 95% CI: 0.05-0.18). When excluding other confounders, no significant association between antenatal cannabis use and SGA was found. Antenatal cannabis use increases the risk of SGA, low birthweight, preterm birth and other adverse perinatal outcomes. However, when isolating the impact of cannabis use by excluding women who use other recreational drugs and those who discontinue cannabis during pregnancy, no significant association between antenatal cannabis use and SGA birth was found.

An adaptive network model for AI-assisted monitoring and management of neonatal respiratory distress

This article presents the use of second-order adaptive network models of hospital teams consisting of doctors and nurses, interacting together. A variety of scenarios are modelled and simulated, in relation with respiratory distress of a neonate, along with the integration of an AI-Coach for monitoring and support of such teams and of organizational learning. The research highlights the benefits of introducing a virtual AI-Coach in a hospital setting. The practical application setting revolves around a medical team responsible for managing neonates with respiratory distress. In this setting an AI-Coach act as an additional team member, to ensure correct execution of medical procedure. Through simulation experiments, the adaptive network models demonstrate that the AI-Coach not only aids in maintaining correct medical procedure execution but also facilitates organizational learning, leading to significant improvements in procedure adherence and error reduction during neonatal care.

Association Between Intrapartum Nitrous Oxide for Labor Analgesia and Short-Term Neonatal Outcomes.

To evaluate the association between intrapartum nitrous oxide use and adverse short-term neonatal outcomes. This was a retrospective cohort study of individuals with singleton gestations at 35 or more weeks who attempted labor and delivered at an academic hospital between June 1, 2015, and February 28, 2020. Data were extracted from the electronic medical record using billing and diagnostic codes. Patients were classified based on whether they received no intrapartum analgesia or received nitrous oxide only. Those who received other analgesia types were excluded. The primary outcome was neonatal intensive care unit (NICU) admission. Secondary outcomes included Apgar score less than 7 at 1 minute and 5 minutes, respiratory composite outcome (including meconium aspiration syndrome, neonatal bronchopulmonary disorders, neonatal transient tachypnea, and other neonatal respiratory distress that required NICU admission), hypoglycemia, and hyperbilirubinemia. Univariable and multivariable analyses were used to estimate the association between nitrous oxide exposure intrapartum and the selected outcomes. Of 6,047 included, 4,153 (68.7%) received no analgesia, and 1,894 (31.3%) received nitrous oxide only. In comparison with individuals who received no analgesia, those who received nitrous oxide were more likely to be nulliparous, be of Black racial identity, have noncommercial insurance, and be less likely to deliver by intrapartum cesarean. The reception of nitrous oxide, compared with the reception of no analgesia, was associated with a lower likelihood of NICU admission (6.4% vs 8.1%; adjusted odds ratio [aOR] 0.77, 95% CI, 0.62-0.96) and an increased likelihood of neonatal hyperbilirubinemia (aOR 1.23, 95% CI, 1.08-1.41). Inhaled nitrous oxide exposure, in comparison with the reception of no analgesia, was not associated with the other secondary outcomes, including Apgar score less than 7 at 1 minute (odds ratio [OR] 0.74, 95% CI, 0.50-1.10) or 5 minutes (OR 0.91, 95% CI, 0.32-2.60), respiratory composite outcome (OR 0.91, 95% CI, 0.70-1.17), and hypoglycemia (OR 0.82, 95% CI, 0.64-1.05). In this single-center retrospective cohort of low-risk patients, intrapartum inhaled nitrous oxide, compared with the reception of no analgesia, was associated with a decreased risk for NICU admission but with an increased risk for hyperbilirubinemia; other outcomes did not differ. These findings may be used to counsel patients when considering nitrous oxide for labor analgesia.

Inspired oxygen fraction thresholds to accurately predict surfactant administration in neonatal RDS is gestational age strata: A pragmatic, multi‐center study

AbstractObjectiveCurrent international guidelines on neonatal respiratory distress syndrome (RDS) recommend continuous positive airway pressure (CPAP) stabilization as primary treatment. Some guidelines recommend surfactant replacement for babies requiring FiO2 &gt; 0.3 regardless of gestational age (GA). We explore the accuracy of alternative inspired oxygen fraction (FiO2) thresholds as early predictors of surfactant replacement in babies stratified by GA.Study DesignPragmatic, observational study in 12 Italian and Spanish neonatal intensive care units. This is a secondary analysis of data from two cohorts of preterm babies with RDS, stratified by GA (25°− 276; 28°−306; 31°−336) and stabilized on CPAP. FiO2 was collected soon after stabilization and its accuracy to predict subsequent surfactant administration by a rigorously masked physician was assessed.ResultsWe enrolled 412 preterm infants. FiO2 was collected within 2 h of life of life. A cut off of FiO2 &gt; 0.30 failed to identify 50.3% of infants who were later given surfactant by a masked physician. A FiO2 = 0.29 threshold improved sensitivity values to 0.85, 0.79, and 0.61 for the three GA ranges while maintaining specificity of ≥85%. A FiO2 = 0.26 threshold gave sensitivity = 0.83 specificity = 0.79 with GA dependent differences (250−276 sensitivity = 0.90 specificity = 0.80; 280−306 sensitivity = 0.84 specificity = 0.78; 310−336 sensitivity = 0.73 specificity = 0.80).ConclusionsFiO2 is a GA dependent predictor of early surfactant administration. Its accuracy increases when used at lower levels than currently recommended by international guidelines (236 words).

New insights into the clinical and molecular spectrum of the MADD-related neurodevelopmental disorder.

Biallelic pathogenic variants in MADD lead to a very rare neurodevelopmental disorder which is phenotypically pleiotropic grossly ranging from severe neonatal hypotonia, failure to thrive, multiple organ dysfunction, and early lethality to a similar but milder phenotype with better survival. Here, we report 5 patients from 3 unrelated Egyptian families in whom 4 patients showed the severe end of the spectrum displaying neonatal respiratory distress, hypotonia and chronic diarrhea while one patient presented with the mild form displaying moderate intellectual disability and myopathy. In addition, we observed distal arthrogryposis and nonspecific structural brain anomalies in all our patients. Interestingly, cerebellar and brainstem hypoplasia were noted in one patient. Whole exome sequencing identified three novel homozygous variants in the MADD gene: two likely pathogenic [c.4321delC p.(Gln1441ArgfsTer46) and c.2620 C > T p.(Arg874Ter)] and one variant of uncertain significance (c.4307 G > A, p.Arg1436Gln). The variants segregated with the disease in all available family members. Our findings confirm that arthrogryposis, genital, cardiac and structural brain anomalies are manifestations of MADD which expand the spectrum of MADD-related neurodevelopmental disorder. Moreover, they further highlight the convergence of MADD variants on different organ systems leading to complex phenotypes.