OBJECTIVE: To measure within-subject changes in ventilation/perfusion (V'/Q') mismatch in response to a protocol of individualised nasal continuous positive airway pressure (CPAP) level selection.

DESIGN: Single-arm, non-randomised, feasibility trial.

SETTING: Three centres in the Children's Hospital of Philadelphia neonatal care network.

PATIENTS: Twelve preterm infants of postmenstrual age 27-35 weeks, postnatal age >24 hours, and receiving a fraction of inspired oxygen (FiO) >0.25 on CPAP of 4-7 cm HO.

INTERVENTIONS: We applied a protocol of stepwise CPAP level changes, with the overall direction and magnitude guided by individual responses in V'/Q' mismatch, as determined by the degree of right shift (kilopascals, kPa) in a non-invasive gas exchange model. Best CPAP level was defined as the final pressure level at which V'/Q' improved by more than 5%.

MAIN OUTCOME MEASURES: Within-subject change in V'/Q' mismatch between baseline and best CPAP levels.

RESULTS: There was a median (IQR) within-subject reduction in V'/Q' mismatch of 1.2 (0-3.2) kPa between baseline and best CPAP levels, p=0.02. Best CPAP was observed at a median (range) absolute level of 7 (5-8) cm HO.

CONCLUSIONS: Non-invasive measures of V'/Q' mismatch may be a useful approach for identifying individualised CPAP levels in preterm infants. The results of our feasibility study should be interpreted cautiously and replication in larger studies evaluating the impact of this approach on clinical outcomes is needed.

TRIAL REGISTRATION NUMBER: NCT02983825.

OBJECTIVE: To measure within-subject changes in ventilation/perfusion (V'/Q') mismatch in response to a protocol of individualised nasal continuous positive airway pressure (CPAP) level selection.

DESIGN: Single-arm, non-randomised, feasibility trial.

SETTING: Three centres in the Children's Hospital of Philadelphia neonatal care network.

PATIENTS: Twelve preterm infants of postmenstrual age 27-35 weeks, postnatal age >24 hours, and receiving a fraction of inspired oxygen (FiO) >0.25 on CPAP of 4-7 cm HO.

INTERVENTIONS: We applied a protocol of stepwise CPAP level changes, with the overall direction and magnitude guided by individual responses in V'/Q' mismatch, as determined by the degree of right shift (kilopascals, kPa) in a non-invasive gas exchange model. Best CPAP level was defined as the final pressure level at which V'/Q' improved by more than 5%.

MAIN OUTCOME MEASURES: Within-subject change in V'/Q' mismatch between baseline and best CPAP levels.

RESULTS: There was a median (IQR) within-subject reduction in V'/Q' mismatch of 1.2 (0-3.2) kPa between baseline and best CPAP levels, p=0.02. Best CPAP was observed at a median (range) absolute level of 7 (5-8) cm HO.

CONCLUSIONS: Non-invasive measures of V'/Q' mismatch may be a useful approach for identifying individualised CPAP levels in preterm infants. The results of our feasibility study should be interpreted cautiously and replication in larger studies evaluating the impact of this approach on clinical outcomes is needed.

TRIAL REGISTRATION NUMBER: NCT02983825.

<p><strong>OBJECTIVE: </strong>To determine the prevalence of limited health literacy in parents of infants born ≤32 and 0/7 weeks and if health literacy changes during hospitalization.</p>

<p><strong>STUDY DESIGN: </strong>Multi-site, prospective cohort study measuring health literacy using the Parent Health Literacy Activities Test, which estimates caregivers' ability to complete tasks such as reading prescription labels and preparing bottles. Data were analyzed using parametric and nonparametric comparison tests and multivariable regression to control for confounders.</p>

<p><strong>RESULT: </strong>Of the 137 participants, 31% missed ≥3 questions of 8. Scores were not associated with admission characteristics or NICU complications. Lower scores were associated with lower nurses' (rho 0.20, p = 0.04) but not parents' (rho -0.12, p = 0.22) ratings of discharge readiness. Scores improved slightly from admission to discharge (p = 0.049).</p>

<p><strong>CONCLUSION: </strong>Many parents have difficulty answering questions related to basic infant care tasks. NICUs should ensure that communication and discharge planning are mindful of health literacy.</p>

<p><strong>BACKGROUND: </strong>Diagnosis of bacterial meningitis (BM) is challenging in newborn infants. Presently, biomarkers of BM have limited diagnostic accuracy. Analysis of cerebrospinal fluid (CSF) metabolites may be a useful diagnostic tool in BM.</p>

<p><strong>METHODS: </strong>In a nested case-control study, we examined &gt;400 metabolites in CSF of uninfected infants and infants with culture-confirmed BM using gas and liquid chromatography mass spectrometry. Preterm and full-term infants in a Level III or IV Neonatal Intensive Care Unit were prospectively enrolled when evaluated for serious bacterial infection.</p>

<p><strong>RESULTS: </strong>Over 200 CSF metabolites significantly differed in uninfected infants and infants with BM. Using machine learning, we found that as few as 6 metabolites distinguished infants with BM from uninfected infants in this pilot cohort. Further analysis demonstrated three metabolites associated with Group B Streptococcal meningitis.</p>

<p><strong>CONCLUSIONS: </strong>We report the first comprehensive metabolic analysis of CSF in infants with BM. In our pilot cohort, we derived a metabolic signature that predicted the presence or absence of BM, irrespective of gestational age, postnatal age, sex, race and ethnicity, presence of neurosurgical hardware, white blood cell count in CSF, and red blood cell contamination in CSF. Metabolic analysis may aid diagnosis of BM and facilitate clinical decision-making in infants.</p>

<p><strong>IMPACT: </strong>In a pilot cohort, metabolites in cerebrospinal fluid distinguished infants with bacterial meningitis from uninfected infants. We report the first comprehensive metabolic analysis of cerebrospinal fluid in infants with bacterial meningitis. Our findings may be used to improve diagnosis of bacterial meningitis and to offer mechanistic insights into the pathophysiology of bacterial meningitis in infants.</p>