Estimating Preterm Lung Volume: A Comparison of Lung Ultrasound, Chest Radiography, and Oxygenation.

OBJECTIVE: To determine the relationship between lung ultrasound (LUS) examination, chest radiograph (CXR), and radiographic and clinical evaluations in the assessment of lung volume in preterm infants. STUDY DESIGN: In this prospective cohort study LUS was performed before CXR on 70 preterm infants and graded using (1) a LUS score, (2) an atelectasis score, and (3) measurement of atelectasis depth. Radiographic diaphragm position and radio-opacification were used to determine global and regional radiographic atelectasis. The relationship between LUS, CXR, and oxygenation was assessed using receiver operator characteristic and correlation analysis. RESULTS: LUS scores, atelectasis scores, and atelectasis depth did not correspond with radiographic global atelectasis (area under receiver operator characteristics curves, 0.54 [95% CI, 0.36-0.71], 0.49 [95% CI, 0.34-0.64], and 0.47 [95% CI, 0.31-0.64], respectively). Radiographic atelectasis of the right upper, right lower, left upper, and left lower quadrants was predicted by LUS scores (0.75 [95% CI, 0.59-0.92], 0.75 [95% CI, 0.62-0.89], 0.69 [95% CI, 0.56-0.82], and 0.63 [95% CI, 0.508-0.751]) and atelectasis depth (0.66 [95% CI, 0.54-0.78], 0.65 [95% CI, 0.53-0.77], 0.63 [95% CI, 0.50-0.76], and 0.56 [95% CI, 0.44-0.70]). LUS findings were moderately correlated with oxygen saturation index (ρ = 0.52 [95% CI, 0.30-0.70]) and saturation to fraction of inspired oxygen ratio (ρ = -0.63 [95% CI, -0.76 to -0.46]). The correlation between radiographic diaphragm position, the oxygenation saturation index, and peripheral oxygen saturation to fraction of inspired oxygen ratio was very weak (ρ = 0.36 [95% CI, 0.11-0.59] and ρ = -0.32 [95% CI, -0.53 to -0.07], respectively). CONCLUSIONS: LUS assessment of lung volume does not correspond with radiographic diaphragm position preterm infants. However, LUS predicted radiographic regional atelectasis and correlated with oxygenation. The relationship between radiographic diaphragm position and oxygenation was very weak. Although LUS may not replace all radiographic measures of lung volume, LUS more accurately reflects respiratory status in preterm infants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12621001119886.

Lung ultrasound of the dependent lung detects real-time changes in lung volume in the preterm lamb.

BACKGROUND: Effective lung protective ventilation requires reliable, real-time estimation of lung volume at the bedside. Neonatal clinicians lack a readily available imaging tool for this purpose. OBJECTIVE: To determine the ability of lung ultrasound (LUS) of the dependent region to detect real-time changes in lung volume, identify opening and closing pressures of the lung, and detect pulmonary hysteresis. METHODS: LUS was performed on preterm lambs (n=20) during in vivo mapping of the pressure-volume relationship of the respiratory system using the super-syringe method. Electrical impedance tomography was used to derive regional lung volumes. Images were blindly graded using an expanded scoring system. The scores were compared with total and regional lung volumes, and differences in LUS scores between pressure increments were calculated. RESULTS: Changes in LUS scores correlated moderately with changes in total lung volume (r=0.56, 95% CI 0.47-0.64, p<0.0001) and fairly with right whole (r=0.41, CI 0.30-0.51, p<0.0001), ventral (r=0.39, CI 0.28-0.49, p<0.0001), central (r=0.41, CI 0.31-0.52, p<0.0001) and dorsal (r=0.38, CI 0.27-0.49, p<0.0001) regional lung volumes. The pressure-volume relationship of the lung exhibited hysteresis in all lambs. LUS was able to detect hysteresis in 17 (85%) lambs. The greatest changes in LUS scores occurred at the opening and closing pressures. CONCLUSION: LUS was able to detect large changes in total and regional lung volume in real time and correctly identified opening and closing pressures but lacked the precision to detect small changes in lung volume. Further work is needed to improve precision prior to translation to clinical practice.

Quantitative lung ultrasound detects dynamic changes in lung recruitment in the preterm lamb.

BACKGROUND: Lung ultrasound (LUS) may not detect small, dynamic changes in lung volume. Mean greyscale measurement using computer-assisted image analysis (Q-LUSMGV) may improve the precision of these measurements. METHODS: Preterm lambs (n = 40) underwent LUS of the dependent or non-dependent lung during static pressure-volume curve mapping. Total and regional lung volumes were determined using the super-syringe technique and electrical impedance tomography. Q-LUSMGV and gold standard measurements of lung volume were compared in 520 images. RESULTS: Dependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.60, 95% CI 0.51-0.67) and fairly with right whole (rho = 0.39, 0.27-0.49), central (rho = 0.38, 0.27-0.48), ventral (rho = 0.41, 0.31-0.51) and dorsal regional lung volumes (rho = 0.32, 0.21-0.43). Non-dependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.57, 0.48-0.65) and fairly with right whole (rho = 0.43, 0.32-0.52), central (rho = 0.46, 0.35-0.55), ventral (rho = 0.36, 0.25-0.47) and dorsal lung volumes (rho = 0.36, 0.25-0.47). All correlation coefficients were statistically significant. Distinct inflation and deflation limbs, and sonographic pulmonary hysteresis occurred in 95% of lambs. The greatest changes in Q-LUSMGV occurred at the opening and closing pressures. CONCLUSION: Q-LUSMGV detected changes in total and regional lung volume and offers objective quantification of LUS images, and may improve bedside discrimination of real-time changes in lung volume. IMPACT: Lung ultrasound (LUS) offers continuous, radiation-free imaging that may play a role in assessing lung recruitment but may not detect small changes in lung volume. Mean greyscale image analysis using computer-assisted quantitative LUS (Q-LUSMGV) moderately correlated with changes in total and regional lung volume. Q-LUSMGV identified opening and closing pressure and pulmonary hysteresis in 95% of lambs. Computer-assisted image analysis may enhance LUS estimation of lung recruitment at the bedside. Future research should focus on improving precision prior to clinical translation.

Relationships between early postnatal cranial ultrasonography linear measures and neurobehaviour at term-equivalent age in infants born <30 weeks' gestational age.

BACKGROUND: The relationship between early postnatal brain development and neurobehaviour at term-equivalent age (TEA) remains uncertain. AIM: We aimed to explore relationships between early postnatal cranial ultrasonography (cUS) linear measures of brain size and brain growth with neurobehaviour at TEA in infants born <30 weeks' gestational age (GA). STUDY DESIGN: Prospective observational cohort study. SUBJECTS: 137 infants born <30 weeks' GA without major brain injury on neonatal cUS. OUTCOME MEASURES: Neurobehaviour at TEA assessed using the General Movements Assessment (GMA) and Hammersmith Neonatal Neurological Examination (HNNE). RESULTS: The GMA was administered in 115/137 (84%) infants; 80 (70%) presented with abnormal general movements (GMs) (79 poor repertoire, 1 cramped synchronised). The HNNE was assessed in 106/137 (77%) infants; 52 (49%) had a suboptimal total score. With respect to brain size, larger measures of the corpus callosum length (CCL) and right anterior horn width (AHW) at 1-month were related to lower risk of abnormal GMs, and larger measures of the biparietal diameter at 1-week and 2-months were related to lower risk of a suboptimal HNNE. As for brain growth, increases of the CCL and transcerebellar diameter between birth and 1-month, and left and right AHWs between 1- and 2-months, were related to lower risk of abnormal GMs. CONCLUSION: Early postnatal brain size and brain growth were related to neurobehaviour at TEA in infants born <30 weeks' GA. This study provides preliminary evidence for the prognostic utility of early postnatal cUS linear measures as potential markers of neurodevelopment in later childhood.

Lung ultrasound during newborn resuscitation predicts the need for surfactant therapy in very- and extremely preterm infants.

INTRODUCTION: Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants. METHODS: Infants born at <320/7 weeks were prospectively enrolled at 2 centres. LUS videos of both sides of the chest were obtained 5-10 min, 11-20 min, and 1-3 h after birth. Clinicians were masked to the results of the LUS assessment and surfactant therapy was provided according to local guidelines. LUS videos were graded blinded to clinical data. Presence of unilateral type 1 ('whiteout') LUS or worse was considered test positive. Receiver Operating Characteristic (ROC) analysis compared the accuracy of LUS and an FiO2 threshold of 0.3 to predict subsequent surfactant therapy. RESULTS: Fifty-two infants with a median age of 276/7 weeks (IQR 260/7-286/7) were studied. Thirty infants (58%) received surfactant. Area under the ROC curve (AUC) for LUS at 5-10 min, 11-20 min and 1-3 h was 0.78 (95% CI, 0.66-0.90), 0.76 (95% CI, 0.65-0.88) and 0.86 (95% CI, 0.75-0.97) respectively, outperforming FiO2 at the 5-10 min timepoint (AUC 0.45, 95% CI 0.29-0.62, p = 0.001). At 11-20 min, LUS had a specificity of 95% (95% CI 77-100%) and sensitivity of 59% (95% CI, 39-77%) to predict surfactant therapy. All infants born at 23-276/7 weeks with LUS test positive received surfactant. Twenty-six infants (50%) had worsening of LUS grades on serial assessment. CONCLUSIONS: LUS in the delivery room and accurately predicts surfactant therapy in infants <320/7 weeks.

Lung ultrasound immediately after birth to describe normal neonatal transition: an observational study.

OBJECTIVE: Lung ultrasound (LUS) has shown promise as a diagnostic tool for the evaluation of the newborn with respiratory distress. No study has described LUS during 'normal' transition. Our goal was to characterise the appearance of serial LUS in healthy newborns from the first minutes after birth until airway liquid clearance is achieved. STUDY DESIGN: Prospective observational study. SETTING: Single-centre tertiary perinatal centre in Australia. PATIENTS: Of 115 infants born at ≥35 weeks gestational age, mean (SD) gestational age of 386/7 weeks±11 days, mean birth weight of 3380±555 g, 51 were delivered vaginally, 14 via caesarean section (CS) after labour and 50 infants via elective CS. INTERVENTIONS: We obtained serial LUS videos via the right and left axillae at 1-10 min, 11-20 min and 1, 2, 4 and 24 hours after birth. MAIN OUTCOME MEASURES: LUS videos were graded for aeration and liquid clearance according to a previously validated system. RESULTS: We analysed 1168 LUS video recordings. As assessed by LUS, lung aeration and airway liquid clearance occurred quickly. All infants had an established pleural line at the first examination (median=2 (1-4) min). Only 14% of infants had substantial liquid retention at 10 min after birth. 49%, 78% and 100% of infants had completed airway liquid clearance at 2, 4 and 24 hours, respectively. CONCLUSIONS: In healthy transitioning newborn infants, lung aeration and partial liquid clearance are achieved on the first minutes after birth with complete liquid clearance typically achieved within the first 4 hours of birth. TRIAL REGISTRATION NUMBER: ANZCT 12615000380594.

Lung ultrasound during the initiation of breathing in healthy term and late preterm infants immediately after birth, a prospective, observational study.

INTRODUCTION: Lung ultrasound (LUS) has shown promise for evaluation of newborns with respiratory distress. However, no study has described the appearance of LUS during the initiation of breathing. We used LUS to describe the appearance of the lungs in healthy infants immediately after birth, starting with the infant's first breath, through the first 20min after birth. METHODS: This was a single-center observational study enrolling neonates born at ≥35 weeks. We obtained LUS video recordings with the initiation of breathing. Recordings that captured one of the 1st four breaths after birth were included. We also obtained recordings at 1-10 and 11-20min after birth. Recordings were graded using a modified version of a previously published system, with additional grades to describe the appearance of the lungs prior to establishment of the pleural line. RESULTS: We studied 63 infants, mean gestational age=391/7±2 days, mean weight=3473g±422, 33 infants were delivered vaginally and 30 via cesarean section. We captured the first breath after birth in 28 infants and within the first four breaths from the remaining 35 infants. The pleural line was established by a median of 4 breaths (3-6). At the 1-10min examination, all infants had an established pleural line and 89% demonstrated substantial liquid clearance. At the 11-20min examination, all infants had substantial liquid clearance. CONCLUSION: Establishment of the pleural line, indicating lung aeration and substantial liquid clearance is achieved with the first few breaths after birth in term and near term infants.

Hemodynamic effects of nasal continuous positive airway pressure in preterm infants with evolving chronic lung disease, a crossover randomized trial.

Previous studies suggest that high airway pressure may compromise cardiac output. We investigated the effect of 3 nasal continuous positive airway pressure levels on cardiac output in preterm infants with evolving chronic lung disease. We found that brief changes in continuous positive airway pressure did not affect cardiac output.

The relationship between ventricular size at 1 month and outcome at 2 years in infants less than 30 weeks' gestation.

BACKGROUND: Cranial ultrasound cerebral biometric measurements have been used in preterm neonates, particularly in cases of ventriculomegaly. While cerebral biometric measures using MRI have been found to correlate with long-term outcome, the relationship between cranial ultrasound biometric measures and neurodevelopmental outcome has not been established. OBJECTIVE: To assess the relationship between ventricular size at 1 month of age using cranial ultrasound and neurodevelopmental outcome at 2 years in very preterm infants. METHOD: Digital cranial ultrasound images taken between 25 and 35 days of age of 44 infants born at less than 30 weeks' gestation were analysed independently by two observers. Infants with significant ultrasound abnormalities were excluded. A range of ultrasound linear measures were correlated with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) motor, language and cognitive composite scores at 2 years using linear regression. RESULTS: Larger lateral ventricular sizes (anterior horn width, ventricular height, midbody ventricular height) and larger ventricular-brain biparietal ratios were related to poorer motor composite score at 2 years. A ventricular-brain ratio of less than 0.3 was reassuring with regard to motor outcome. Poorer language composite scores at 2 years were associated with larger midbody ventricular heights. There was little evidence of a relationship with the cognitive composite score. CONCLUSIONS: Larger lateral ventricles in the parietal region at a month of age were related to poorer motor development at 2 years. Larger ventricular measurements were also related to slower early language development. The role of cranial ultrasound biometric measures as biomarkers of later outcome in very preterm infants warrants further investigation.

The effects of nasal continuous positive airway pressure on cardiac function in premature infants with minimal lung disease: a crossover randomized trial.

OBJECTIVE: To assess the effects of different nasal continuous positive airway pressure (nCPAP) pressures on cardiac performance in preterm infants with minimal lung disease, we conducted a randomized, blinded crossover study. STUDY DESIGN: We studied infants between 28 and 34 weeks' corrected gestational age, treated with nCPAP of 5 cm H2O, in air. Infants with significant cardiac shunts were excluded. Infants were randomly assigned to nCPAP levels of 4, 6, and 8 cm H2O for 15 minutes each. Right and left ventricular outputs and left pulmonary artery and superior vena cava flows were measured 15 minutes after each change. RESULTS: Thirty-four infants born at a mean gestational age of 29 weeks with a birth weight of 1.3 kg were studied. There were no significant differences in right and left ventricular outputs and left pulmonary artery and superior vena cava flows at different levels of nCPAP. CONCLUSION: We investigated the effect of increasing nCPAP levels on cardiac output. We conclude that nCPAP levels between 4 and 8 cm H2O did not have an effect on cardiac output in stable preterm infants with minimal lung disease.

HIV infection among paediatric in-patients in Blantyre, Malawi.

To investigate the impact of HIV infection on hospital admission and death we studied children admitted to paediatric medical and surgical wards in Blantyre, Malawi, in March 2000. Unselected children whose parents or guardians consented to HIV testing of the child were recruited and HIV infection was determined by serology, with confirmation in children aged 15 months or less by PCR. We assessed the prevalence of HIV infection by age, clinical diagnosis and outcome of admission. Of 1064 admissions, 991 were tested for HIV infection, and 187 (18.9%) were infected. HIV was most common in children aged less than six months, 53 of 166 (32%). Parents of HIV-infected children were better educated, and more likely to have died, than those of uninfected children. Clinical symptoms and signs were not adequately sensitive or specific to be used for diagnosis of HIV. HIV was common in children with malnutrition (prevalence 40%), lower respiratory tract infection (29%) and sepsis (28%), and less prevalent among children with malaria (11%) or surgical admissions (11%). Almost 30% of HIV-infected children died, compared with 8.9% of uninfected children, and HIV-infected children constituted over 40% of in-patient deaths.