Correlation between early postnatal body weight changes and lung ultrasound scores as predictors of bronchopulmonary dysplasia in preterm infants: A secondary analysis of a prospective study.

Recent research links early weight changes (EWC) with bronchopulmonary dysplasia (BPD) in preterm neonates, while lung ultrasound score (LUS) has shown promise in predicting BPD. We aimed to explore the correlation between LUS and EWC as markers of extravascular lung edema and to investigate the correlation between LUS and EWC in preterm infants with respiratory distress syndrome regarding future BPD development. This secondary analysis of a prospective study involved infants ≤ 28 weeks gestation. Enrolled infants underwent lung ultrasound assessment on postnatal days 3, 7 and 14, measuring LUS. EWC was computed on the same time points. Infants were classified as either having BPD or not. Descriptive statistics, correlation coefficient, and area under the receiver operating characteristic (AUROC) curve analysis were utilized. Of 132 infants, 70 (53%) had BPD. Univariate analysis revealed statistically significant differences in LUS and EWC at days 3, 7, and 14 between BPD and no-BPD groups (p < 0.001). A statistically significant but weak positive correlation existed between LUS and EWC (r0.37, r0.29, r0.24, and p < 0.01) at postnatal days 3, 7, and 14, respectively. AUROC analysis indicated LUS having superior predictive capacity for the need for invasive mechanical ventilation at day 14 as well as the later BPD development compared to EWC (p < 0.0001). CONCLUSION: In a cohort of extreme preterm infants, our study revealed a positive yet weak correlation between LUS and EWC, suggesting that EWC was not the major contributing to the evolving chronic lung disease. WHAT IS KNOWN: • Recent evidence links Early Weight-Changes with bronchopulmonary dysplasia in preterm neonates. • Lung ultrasound score has shown promise in early prediction of the subsequent development of bronchopulmonary dysplasia in preterm infants. No studies have examined the correlation between Early Weight-Changes and Lung ultrasound score in preterm infants during first 2 weeks after birth. WHAT IS NEW: • Our study demonstrated a positive and statistically significant correlation between early LUS and EWC, indicating their potential role as early predictors for the subsequent development of BPD in extreme preterm infants. • The weak correlation between the two parameters may stem from the possible restricted influence of EWC, given that it may not be the primary factor contributing to the evolving chronic lung disease.

Current perception and barriers to implementing lung ultrasound in Canadian neonatal intensive care units: a national survey.

Despite the growing body of literature supporting the use of point-of-care lung ultrasound (POC-LU) in neonates, its adoption in Canadian neonatal intensive care units (NICUs) remains limited. This study aimed to identify healthcare providers' perceptions and barriers to implementing POC-LU in Canadian NICUs. We conducted an electronic survey targeting neonatologists, neonatal fellows, neonatal nurse practitioners, and registered respiratory therapists in 20 Canadian NICUs. The survey comprised a 28-item questionnaire divided into four sections: (1) participants' demographics and availability of POC-LU equipment, (2) experience and interest in POC-LU learning, (3) perception of POC-LU as a diagnostic tool, and (4) barriers to POC-LU implementation in NICUs. A total of 194 participants completed the survey, with neonatologists comprising the majority (45%). Nearly half of the participants (48%) reported prior experience with POC-LU. The most prevalent indications for POC-LU use were diagnosis of pleural effusion (90%), pneumothorax (87%), and respiratory distress syndrome (76%). Participants identified the primary barrier to POC-LU adoption as the lack of trained providers available for both training and clinical integration. Notably, most respondents (87%) expressed keen interest in learning neonatal POC-LU. A subgroup analysis based on the responses collected from NICU-directors of 12 institutions yielded results consistent with those of the overall participant pool.     Conclusion: This survey underscores the perceived importance of POC-LU among NICU healthcare providers. A Canadian consensus is required to facilitate the development of widespread training programs as well as standardized clinical practice guideline for its implementation. What is Known: • In recent years, point-of-care lung ultrasound (POC-LU) has emerged as an important tool in neonatology, revolutionizing the assessment and management of critically ill infants. However, its adoption in Canadian Neonatal Intensive Care Units remains limited. What is New: • Most Canadian healthcare providers showed high level of interest in learning POC-LU techniques. Additionally, POC-LU was perceived as a useful tool for diagnosis and guiding intervention in various neonatal respiratory diseases. Nonetheless, the lack of expertise emerged as the primary barrier to its adoption and practice across different groups of participants regardless of their clinical experience level.

Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study.

OBJECTIVES: To evaluate the diagnostic and predictive ability of lung ultrasound at 3 time points in the first 2 weeks after birth for predicting bronchopulmonary dysplasia (BPD) among infants <29 weeks of gestational age. STUDY DESIGN: This was a prospective, diagnostic cohort study. Lung ultrasound was performed on days 3, 7, and 14 after birth and lung ultrasound scores (LUS) were calculated in blinded fashion. Diagnostic test characteristics and area under receiver operating characteristic (AUROC) curves were calculated. RESULTS: A total of 152 infants were enrolled with mean (SD) gestational age of 25.8 (1.5) weeks gestation. Of them, 87 (57%) infants were diagnosed with BPD. The LUS were significantly higher in infants diagnosed with BPD compared with those without BPD at all scan time points (P < .01). The score of >10 at all 3 time points had higher sensitivity (0.89, 0.89, and 0.77), specificity (0.87, 0.90, and 0.92), and corresponding clinically important positive and negative likelihood ratios. The AUROC for LUS at the 3 time points were 0.96, 0.97, and 0.95 on day 3, 7, and 14, respectively. Compared with the model using clinical characteristics, LUS alone had higher AUROC (P < .05 for all 3 time points). CONCLUSIONS: In this cohort, LUS in the first 2 weeks after birth had a very high predictive value for the diagnosis of BPD among infants of <29 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.govNCT04756297.

Challenges in clinical identification of right ventricular dysfunction in preterm infants with persistent pulmonary hypertension of the newborn.

BACKGROUND: Right ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. METHODS: Forty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as "low" or "normal" using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. RESULTS: Mean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41±7 vs. 47±9 mmHg, p = 0.02) and higher shock index (4.02±0.80 vs. 3.44±0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32-0.77). CONCLUSIONS: The non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants.

Lung and diaphragm ultrasound as predictors of successful weaning from nasal continuous positive airway pressure in preterm infants.

OBJECTIVE: Assessment of the utility of lung and diaphragm ultrasound in the prediction of successful weaning from nasal continuous positive airway pressure (NCPAP) in preterm infants. STUDY DESIGN: This prospective cohort study was conducted on preterm infants who were considered ready for weaning off NCPAP. Lung and diaphragm ultrasound were performed just before and 3 h after weaning off NCPAP. The primary outcome was to evaluate the accuracy of lung ultrasound (LUS) in predicting successful weaning from NCPAP. RESULTS: Out of 65 enrolled preterm infants, 30 (46.2%) were successfully weaned from NCPAP to room air. The successful weaning group had higher gestational ages, lower incidences of previous invasive mechanical ventilation, and treated hemodynamically significant patent ductus arteriosus before the trial weaning. A LUS score of ≤6, measured before discontinuation of NCPAP, exhibited a predictive sensitivity of 80% and specificity of 75% for successful weaning (Area under the curve (AUC) = 0.865, ≤.001). When the LUS score was assessed 3 h after weaning from NCPAP, a cutoff point of ≤7 predicted successful weaning with a sensitivity and specificity of 90% and 60% respectively (AUC = 0.838, p ≤ .001). The diaphragmatic thickness fraction (DTF) was significantly lower in the successful weaning group. After adjustment for various factors, LUS score remained the only independent predictor of successful weaning. CONCLUSION: LUS score before weaning from NCPAP has a good sensitivity and specificity for predicting successful weaning from NCPAP in preterm infants. Diaphragmatic excursion and DTF were not good predictors.

Accuracy of lung ultrasound in predicting extubation failure in neonates: A systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyze the diagnostic accuracy of lung ultrasound score (LUS) in predicting extubation failure in neonates. STUDY DESIGN: MEDLINE, COCHRANE, EMBASE, CINAHL, and clinicaltrials.gov were searched up to 30 November 2022, for studies evaluating the diagnostic accuracy of LUS in predicting extubation outcome in mechanically ventilated neonates. METHODOLOGY: Two investigators independently assessed study eligibility, extracted data, and assessed study quality using the Quality Assessment for Studies of Diagnostic Accuracy 2 tool. We conducted a meta-analysis of pooled diagnostic accuracy data using random-effect models. Data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We calculated pooled sensitivity and specificity, pooled diagnostic odds ratios with 95% confidence intervals (CI), and area under the curve (AUC). RESULTS: Eight observational studies involving 564 neonates were included, and the risk of bias was low in seven studies. The pooled sensitivity and specificity for LUS in predicting extubation failure in neonates were 0.82 (95% CI: 0.75-0.88) and 0.83 (95% CI: 0.78-0.86), respectively. The pooled diagnostic odds ratio was 21.24 (95% CI: 10.45-43.19), and the AUC for LUS predicting extubation failure was 0.87 (95% CI: 0.80-0.95). Heterogeneity among included studies was low, both graphically and by statistical criteria (I2 = 7.35%, p = 0.37). CONCLUSIONS: The predictive value of LUS in neonatal extubation failure may hold promise. However, given the current level of evidence and the methodological heterogeneity observed, there is a clear need for large-scale, well-designed prospective studies that establish standardized protocols for lung ultrasound performance and scoring. REGISTRATION: The protocol was registered in OSF (https://doi.org/10.17605/OSF.IO/ZXQUT).

Accuracy of lung and diaphragm ultrasound in predicting successful extubation in extremely preterm infants: A prospective observational study.

OBJECTIVE: Chest ultrasound has emerged as a promising tool in predicting extubation readiness in adults and children, yet its utility in preterm infants is lacking. Our aim was to assess the utility of lung ultrasound severity score (LUSS) and diaphragmatic function in predicting extubation readiness in extremely preterm infants. STUDY DESIGN: In this prospective cohort study, preterm infants < 28 weeks gestational age (GA) who received invasive mechanical ventilation for ≥12 h were enrolled. Chest ultrasound was performed before extubation. The primary outcome was lung ultrasound accuracy for predicting successful extubation at 3 days. Descriptive statistics and logistic regression were done using SPSS version 22. RESULTS: We enrolled 45 infants, of whom 36 (80%) were successfully extubated. GA and postmenstrual age (PMA) at extubation were significantly higher in the successful group. The LUSS was significantly lower in the successful group compared to failed group (11.9 ± 3.2 vs. 19.1 ± 3.1 p < 0.001). The two groups had no statistically significant difference in diaphragmatic excursion or diaphragmatic thickness fraction. Logistic regression analysis controlling for GA and PMA at extubation showed LUSS was an independent predictor for successful extubation (odd ratio 0.46, 95% confidence interval [0.23-0.9], p = 0.02). The area under the receiver operating characteristic curve was 0.95 (p ˂ 0.001) for LUSS, and a cut-off value of ≥15 had 95% sensitivity and 85% specificity in detecting extubation failure. CONCLUSION: In extremely preterm infants, lung ultrasound has good accuracy for predicting successful extubation. However, diaphragmatic measurements were not reliable predictors.

Diaphragmatic Thickness and Excursion in Preterm Infants With Bronchopulmonary Dysplasia Compared With Term or Near Term Infants: A Prospective Observational Study.

BACKGROUND: Diaphragmatic atrophy associated with mechanical ventilation is reported in pediatric and adult patients, but a similar association has not been described in preterm infants with bronchopulmonary dysplasia (BPD). RESEARCH QUESTION: Does BPD impact the diaphragm thickness (DT) and diaphragm excursion (DE) in infants born before 32 weeks' gestation compared with healthy late preterm or term infants? STUDY DESIGN AND METHODS: In this prospective observational case-control study, DT at end of expiration (DTexp), DT at end of inspiration (DTins), DT fraction (DTF), and DE (DE) were assessed using bedside ultrasound. Two groups were compared: infants with BPD (patients) and healthy, postmenstrual age-matched infants (control participants). To account for variations in body size between groups, diaphragmatic measurements were expressed as a ratio of body surface area (BSA). Statistical analyses were conducted using SAS software version 9.4 (SAS Institute, Inc.). RESULTS: We enrolled 111 infants, including 56 preterm infants with BPD (mean ± SD study age, 37.7 ± 1.7 weeks) and 55 healthy control participants (mean ± SD study age, 38.1 ± 1.5 weeks). DTexp and DTexp to BSA ratio were significantly lower in the BPD group compared with the healthy control group (mean ± SD, 1.3 ± 0.4 mm vs 1.5 ± 0.4 mm [P = .01] and 7.1 ± 1.4 mm/m2 vs 7.8 ± 1.8 mm/m2 [P = .03]). DTF and DE were significantly higher in the BPD group vs the healthy control group (mean ± SD, 61.8 ± 26.0 vs 43.3 ± 19.7 [P < .01] and 6.0 ± 1.7 mm vs 4.4 ± 1.6 mm [P < .01], respectively). INTERPRETATION: In infants with BPD, DTexp was significantly lower, whereas DTF and DE were significantly higher, compared with healthy, age-matched control participants. Future studies are required and should focus on describing the evolution of diaphragmatic dimensions in preterm infants with and without BPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04941963; URL: www. CLINICALTRIALS: gov.

Prophylactic versus therapeutic caffeine for apnea of prematurity: a randomized controlled trial.

BACKGROUND: Therapeutic initiation of methyxanthines for treatment of apnea in preterm infants was the standard policy. Caffeine therapy is beneficial for various outcomes of preterm infants. AIM: To evaluate the efficacy of early prophylactic compared to routine therapeutic caffeine therapy on duration of oxygen support and other outcomes of preterm infants. METHODS: In a randomized controlled trial including preterm infants < 32 weeks' gestation, prophylactic (in the first 72 h of life) versus therapeutic (only if apnea exists or infant requires mechanical ventilation) decision of caffeine was compared. The primary outcome was the duration of oxygen therapy. Secondary outcomes included duration of respiratory support modalities; bronchoplumonary dysplasia (BPD); necrotizing enterocolitis; intra-ventricular hemorrhage; retinopathy of prematurity; length of hospital stay (LOS); neonatal mortality; and caffeine side effects. RESULTS: We enrolled 90 infants in the prophylactic and 91 infants in therapeutic groups respectively. Prophylactic caffeine decreased the duration of oxygen therapy [median and IQR of 28 (18-36) days versus 34 (23-51) days, p = .005 respectively]. Prophylactic caffeine significantly decreased the durations of respiratory support modalities, LOS, and incidences of mild to moderate BPD without reported effects on the incidence of severe BPD or other clinical outcomes compared to therapeutic caffeine. A significantly higher proportion of infants in the prophylactic caffeine group did not require mechanical ventilation during their NICU admission and a significant lower proportion required late mechanical ventilation compared to the prophylactic caffeine group. CONCLUSION: Prophylactic caffeine decreased the duration of oxygen therapy, invasive and noninvasive ventilation, incidences of mild to moderate BPD, and LOS in preterm infants.

Investigation of the effect of verapamil on the regional absorption of sofosbuvir from rabbit intestine in situ.

PURPOSE: Sofosbuvir, a nucleotide antiviral drug, is a Biopharmaceutics Classification System (BCS) class III prodrug suffering from limited intestinal absorption due to its high hydrophilicity and low intestinal permeability. This research aims to investigate the luminal stability of Sofosbuvir, the influence of anatomical site on its intestinal absorption and the effects of verapamil on such absorption. METHOD: The study utilized in situ rabbit intestinal perfusion technique to examine absorption of Sofosbuvir from duodenum, jejunum, ileum and ascending colon. This was conducted both with and without verapamil. RESULTS: The luminal stability study showed that Sofosbuvir was subjected to premature degradation with varying fractions degraded from the different intestinal segments. The in situ perfusion data showed incomplete absorption of Sofosbuvir from small and large intestinal segments. The recorded values of the absorptive clearance per unit length (Pe.A/L) of Sofosbuvir were 0.026, 0.0075, 0.0026, & 0.054 ml/min.cm for duodenum, jejunum, ileum, and ascending colon, respectively. The Pe.A/L values were ordered as colon > duodenum > jejunum > ileum. This is the opposite rank of P-gp content in the different intestinal segments. The recorded values of the length required for complete Sofosbuvir absorption (L95%) were 29.58, 128.47, 949.2 and, 13.63 cm for duodenum, jejunum, ileum, and ascending colon, respectively. Co-perfusion with verapamil significantly increased Pe.A/L and reduced the L95% of Sofosbuvir from both jejunum and ileum (P-value < 0.05). CONCLUSION: The results indicated that the absorptive clearance of Sofosbuvir was site dependent and associated with the content of P-glycoprotein, in addition to the expected drug interactions that can occur in polymedicated hepatitis C virus (HCV) infected patients.

Predictors of successful trial off continuous positive airway pressure and high flow nasal cannula in preterm infants <30 weeks' gestation: A retrospective study.

OBJECTIVES: To identify the predictors of successful first trial off nasal continuous positive airway pressure (nCPAP). METHODS: A retrospective cohort study of infants ≤29 weeks' gestation who required nCPAP for >24 h was conducted. Logistic regression was used to detect predictors for successful trial off nCPAP. Statistical analysis was performed using the SAS software. RESULTS: A total of 727 infants were included in the analysis. Infants who were successful in their first trial off nCPAP (n = 313) were of higher gestational age (GA) and birth weight (BW), as well as a higher proportion of female infants, compared with those who were not successful (p < 0.01). When stratified by GA, a negative correlation was noted between GA and postmenstrual age at successful trial off nCPAP or high flow nasal cannula (HFNC) (r = 0.45, p < 0.01). Logistic regression analysis showed that GA (odds ratio [OR] 1.13, 95% confidence interval [CI] [1.03-1.24], p = 0.01) and percentage of time spent with an oxygen saturation over 89% in the 24 h preceding the trial off nCPAP (OR 1.08, 95% CI [1.05-1.11], p = 0.00) were independent predictors for successful trial off nCPAP. CONCLUSION: Successful trial off nCPAP or HFNC in preterm infants is significantly associated with higher GA, BW, female gender, and the specific oxygen saturation histogram in the preceding 24-h period.