Point-of-Care Serum Amyloid A as a Diagnostic Marker for Neonatal Sepsis.

OBJECTIVES: To evaluate diagnostic accuracy of point-of-care Serum Amyloid A (POC-SAA) and its comparison with procalcitonin for diagnosis of neonatal sepsis. METHODS: The present diagnostic accuracy study consecutively recruited neonates with suspected sepsis. Blood samples for sepsis screen, culture, high sensitivity C-reactive protein (CRP) (hs-CRP, as a part of sepsis screen), procalcitonin and POC-SAA were collected before starting antibiotics. The optimum cut-off level of biomarkers (POC-SAA and procalcitonin) was determined by receiver-operating-characteristics curve (ROC) analysis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of POC-SAA and procalcitonin were derived for 'clinical sepsis (neonates with suspected sepsis and either positive sepsis screen and/or blood culture)' and 'culture positive sepsis' (neonates with suspected sepsis and positive blood culture). RESULTS: Seventy-four neonates with mean±SD gestational age of 32.8±3.7 wk were evaluated for suspected sepsis, of which the proportion of 'clinical sepsis' and 'culture positive sepsis' was 37.8% had 16.2%, respectively. At a cut-off of 25.4 mg/L, POC-SAA had sensitivity, specificity, PPV and NPV of 53.6%, 80.4%, 62.5% and 74.0%, respectively for diagnosis of clinical sepsis. The sensitivity, specificity, PPV and NPV of POC-SAA for detection of culture positive sepsis were 83.3%, 61.3%, 29.4% and 95.0%, respectively at a cut-off of 10.3 mg/L. There was no significant difference in the diagnostic accuracy of biomarkers for detection of culture positive sepsis (area under the curve, AUC of POC-SAA vs. procalcitonin vs. hs-CRP: 0.72 vs. 0.85 vs. 0.85; p = 0.21). CONCLUSIONS: POC-SAA is comparable to procalcitonin and hs-CRP for diagnosis of neonatal sepsis.

Delivery Room Respiratory Stabilization of Preterm Neonates: A Randomized, Controlled Trial.

OBJECTIVE: To determine whether heated humidified high-flow nasal cannula (HHHFNC) is noninferior to NCPAP to provide DR respiratory support to preterm neonates of gestational age (GA) 28-36 wk. METHODS: This randomized, controlled, noninferiority trial included 124 spontaneously breathing preterm neonates who developed respiratory distress soon after birth and/or had a FiO2 requirement > 0.3. Primary outcome measure was treatment failure within 24 h. The absolute risk difference with 95% confidence interval (CI) were calculated with a noninferiority margin of 10%. Secondary outcome variables were temperature at admission, time to treatment failure, treatment failure at 72 h, need for surfactant, intubation, duration of respiratory support, and incidences of adverse events including mortality. Intention-to-treat analysis was done in Stata software. RESULTS: Both the groups were similar in baseline characteristics. There was no statistically significant difference between the treatment failure rates with HHHFNC (13.1%, n = 61) and NCPAP (11.1%, n = 63) (risk difference 2.0%, 95% CI - 9.9% to 14.07%, p = 0.73). However, noninferiority of HHHFNC to NCPAP could not be conclusively proved as the 95% CI crossed both 0 and the noninferiority margin of 10%. There were no significant differences in secondary outcomes. CONCLUSIONS: HHHFNC showed similar efficacy and safety as NCPAP irrespective of gestational age, though its noninferiority to NCPAP remained inconclusive. TRIAL REGISTRATION: Clinical Trial Registry of India, Registration no: CTRI/2019/10/021633, https://ctri.icmr.org.in/.

Developmentally Supportive Positioning Policy for Preterm Low Birth Weight Infants in a Tertiary Care Neonatal Unit: A Quality Improvement Initiative.

OBJECTIVES: To improve developmentally supportive positioning practices by 50% in neonates weighing <1800 g, admitted in a neonatal intensive care unit over 6 months. METHODS: Infant Position Assessment Tool (IPAT) scores were used for assessment of the ideal position. Proportion of neonates with IPAT score ≥8 and improvement of average IPAT score were the process and the outcome measures, respectively. At baseline, 16.6% of infants had optimum position. After root cause analysis, interventions were done in multiple Plan-Do-Study-Act (PDSA) cycles of educational sessions, positioning audits, use of low-cost nesting aids, and training of mothers. RESULTS: Over 21 weeks, 74 neonates were observed at 714 opportunities. Over 6 months, mean (SD) IPAT score improved from 3.4 (1.4) to 9.2 (2.8). Optimum positioning was maintained in 83.3% neonates during sustenance phase. CONCLUSIONS: Low-cost interventions, awareness regarding standards of optimum positioning and involvement of primary caregiver can effectively improve infant positioning practices.

Agitated saline contrast to delineate central venous catheter position in neonates.

OBJECTIVE: Central venous catheter (CVC) insertion is required for the management of sick neonates. Ultrasonography/targeted neonatal echocardiography (TNE) with/without normal saline (NS) flush is used to identify CVC position. The present study compared the visibility and safety of agitated saline (AS) with normal saline (NS) flush. STUDY DESIGN: This prospective interventional study included 110 CVC insertions, both umbilical venous catheterization (UVC) and peripherally inserted central catheterization (PICC). Catheter position was monitored by real-time TNE. RESULTS: Overall visibility of catheter tip (combined UVC and PICC) was significantly better in AS (n = 55) compared with NS group (n = 55) [48/55 (87.2%) vs. 28/55 (50.9%); p < 0.0001]. Time to detect catheter tip by AS push was significantly less than that of NS push. There was no difference in the amount of saline flush required with either method. No major adverse effect was observed. CONCLUSIONS: AS push can be used as a safe method to delineate CVC position in neonates.

Oral Care with Mother's Own Milk in Sick and Preterm Neonates: A Quality Improvement Initiative.

OBJECTIVE: Oral care with mother's own milk (OC-MOM) in sick and preterm neonates provides immune protection, improves feed tolerance and helps in earlier achievement of full enteral nutrition. This quality improvement (QI) initiative was undertaken when authors documented scanty awareness regarding neonatal oral care practices among care-givers in their neonatal unit. The project aimed to improve the proportion of OC-MOM in sick and preterm neonates from the baseline of 5.9% to 80%. METHODS: The QI project was designed as per Point of Care Quality Improvement (POCQI) model and conducted over 6 mo (January 14, 2019 to July 12, 2019). Preterm and sick term neonates on enteral fasting or gavage feeding were included. Neonates with major congenital malformation and whose MOM was not available were excluded. An OC-MOM team was formed and baseline data were collected. Flow charts and fish-bone diagrams were used to analyse the problem and identify the key issues. Mouth assessment tool (MAT) was customized and adapted as one of the outcome measures. An OC-MOM protocol was designed and implemented as a part of routine neonatal care. RESULTS: Four Plan-Do-Study-Act (PDSA) cycles were conducted to achieve the target. After successful implementation of OC-MOM protocol, proportion of neonates receiving OC-MOM increased to 83.3% from a baseline of 5.9% and proportion of neonates having MAT score "0" improved to 94.4% from a baseline of 24.4%. CONCLUSIONS: This QI initiative using POCQI model resulted in a significant and sustained improvement in the proportion of neonatal oral care with MOM using locally available resources.

Effects of Cellular Methylation on Transgene Expression and Site-Specific Integration of Adeno-Associated Virus.

DNA methylation is a major epigenetic event that affects not only cellular gene expression but that also has the potential to influence bacterial and viral DNA in their host-dependent functions. Adeno-associated virus (AAV) genome contains a high degree of CpG sequences capable of methylation in its terminal repeat sequences, which are the sole elements retained in AAV-based vectors used in gene therapy. The present study determined the influence of methylation status of the host cell on wild type (wt) AAV integration and recombinant (r) AAV transgene expression in HeLa cells. Results of the study indicated that hypo-methylation significantly enhanced both wtAAV chromosomal integration and transgene expression of rAAV. A direct influence of methylation on AAV integration was further confirmed by methylating the AAVS1 integration sites prior to viral infection with DNA trans-complementation assay. These results signify the importance of epigenetic status of target cells as one of the key factors in long-term transgene expression in AAV gene therapy.