Association between bronchopulmonary dysplasia severity and its risk factors and long-term outcomes in three definitions: a historical cohort study.

OBJECTIVE: To compare the association of the severity categories of the 2001-National Institutes of Health (NIH), the 2018-NIH and the 2019-Jensen bronchopulmonary dysplasia (BPD) definitions with neurodevelopmental and respiratory outcomes at 2 and 5 years' corrected age (CA), and several BPD risk factors. DESIGN: Single-centre historical cohort study with retrospective data collection. SETTING: Infants born between 2009 and 2015 at the Amsterdam University Medical Centers, location Amsterdam Medical Center. PATIENTS: Preterm infants born at gestational age (GA) <30 weeks and surviving up to 36 weeks' postmenstrual age. INTERVENTIONS: Perinatal characteristics, (social) demographics and comorbidities were collected from the electronic patient records. MAIN OUTCOME MEASURES: The primary outcomes were neurodevelopmental impairment (NDI) or late death, and respiratory morbidity at 2 and 5 years' CA. Using logistic regression and Brier scores, we investigated if the ordinal grade severity is associated with incremental increase of adverse long-term outcomes. RESULTS: 584 preterm infants (median GA: 28.1 weeks) were included and classified according to the three BPD definitions. None of the definitions showed a clear ordinal incremental increase of risk for any of the outcomes with increasing severity classification. No significant differences were found between the three BPD definitions (Brier scores 0.169-0.230). Respiratory interventions, but not GA, birth weight or small for GA, showed an ordinal relationship with BPD severity in all three BPD definitions. CONCLUSION: The severity classification of three BPD definitions showed low accuracy of the probability forecast on NDI or late death and respiratory morbidity at 2 and 5 years' CA, with no differences between the definitions.

Heart Rate Characteristics Monitoring for Late-Onset Sepsis in Preterm Infants: A Systematic Review.

BACKGROUND: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) by monitoring heart rate characteristics (HRC) of preterm infants might reduce the risk of death and morbidities. We aimed to systematically assess the effects of HRC monitoring on death, LOS, and NEC. METHODS: A systematic search was performed in MEDLINE, Embase, Cochrane Library, and Web of Science. RESULTS: Fifteen papers were included in this review. Three of these papers reported results from the only identified randomized controlled trial (RCT). This RCT showed that HRC monitoring resulted in a small but significant reduction in mortality (absolute risk reduction 2.1% [95% confidence interval 0.01-4.14]) without any differences in neurodevelopmental impairment. The risk of bias was rated high due to performance and detection bias and failure to correct for multiple testing. Most diagnostic cohort studies showed high discriminating accuracy in predicting LOS but lacked sufficient quality and generalizability. No studies for the detection of NEC were identified. CONCLUSION: Supported by multiple observational cohort studies, the RCT identified in this systematic review showed that HRC monitoring as an early warning system for LOS might reduce the risk of death in preterm infants. However, methodological weaknesses and limited generalizability do not justify implementation of HRC in clinical care. A large international RCT is warranted.

Can Presepsin Be Valuable in Reducing Unnecessary Antibiotic Exposure after Birth?

BACKGROUND: Due to a lack of rapid, accurate diagnostic tools for early-onset neonatal sepsis (EOS) at the initial suspicion, infants are often unnecessarily given antibiotics directly after birth. We aimed to determine the diagnostic accuracy of presepsin for EOS before antibiotic initiation and to investigate whether presepsin can be used to guide clinicians' decisions on whether to start antibiotics. METHODS: In this multicenter prospective observational cohort study, all infants who started on antibiotics for EOS suspicion were consecutively included. Presepsin concentrations were determined in blood samples collected at the initial EOS suspicion (t = 0). In addition to this, samples were collected at 3, 6, 12 and 24 h after the initial EOS suspicion and from the umbilical cord directly after birth. The diagnostic accuracy of presepsin was calculated. RESULTS: A total of 333 infants were included, of whom 169 were born preterm. We included 65 term and 15 preterm EOS cases. At the initial EOS suspicion, the area under the curve (AUC) was 0.60 (95% confidence interval (CI) 0.50-0.70) in the term-born infants compared to 0.84 (95% CI 0.73-0.95) in the preterm infants. A cut-off value of 645 pg/mL resulted in a sensitivity of 100% and a specificity of 54% in the preterm infants. The presepsin concentrations in cord blood and at other time points did not differ significantly from the concentrations at the initial EOS suspicion. CONCLUSIONS: Presepsin is a biomarker with an acceptable diagnostic accuracy for EOS (culture-proven and clinical EOS) in preterm infants and might be of value in reducing antibiotic exposure after birth when appended to current EOS guidelines. However, the small number of EOS cases prevents us from drawing firm conclusions. Further research should be performed to evaluate whether appending a presepsin-guided step to current EOS guidelines leads to a safe decrease in antibiotic overtreatment and antibiotic-related morbidity.