Serial measurements and use of combinations of markers have been reported to improve sensitivity and negative predictive value of these tests. Current markers are not infallible, however, and do not permit neonatologists to withhold antibiotics in sick infants with suspected infection. Thus, many have emerged as useful indicators for early discontinuation of unnecessary antimicrobial therapy. Some infection markers are also useful for identifying infants with severe infection and adverse prognosis. Advances in flow cytometry have allowed simultaneous measurement of key markers using only minimal blood volume. Judicious selection of a panel of markers with complementary properties could greatly increase the ability of neonatologists to diagnose infection and discern valuable prognostic information.

Preterm infants are highly susceptible to life-threatening infections that are clinically difficult to detect, such as late-onset septicemia and necrotizing enterocolitis (NEC). Here, we used a proteomic approach to identify biomarkers for diagnosis of these devastating conditions. In a case-control study comprising 77 sepsis/NEC and 77 nonsepsis cases (10 in each group being monitored longitudinally), plasma samples collected at clinical presentation were assessed in the biomarker discovery and independent validation phases. We validated the discovered biomarkers in a prospective cohort study with 104 consecutively suspected sepsis/NEC episodes. Proapolipoprotein CII (Pro-apoC2) and a des-arginine variant of serum amyloid A (SAA) were identified as the most promising biomarkers. The ApoSAA score computed from plasma apoC2 and SAA concentrations was effective in identifying sepsis/NEC cases in the case-control and cohort studies. Stratification of infants into different risk categories by the ApoSAA score enabled neonatologists to withhold treatment in 45% and enact early stoppage of antibiotics in 16% of nonsepsis infants. The negative predictive value of this antibiotic policy was 100%. The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC. Upon confirmation by further multicenter trials, the score would facilitate rational prescription of antibiotics and target infants who require urgent treatment.

Acute phase reactants, pro and antiinflammatory mediators including chemokines and cytokines, and cell-surface antigens are nonspecific biomarkers that have been extensively studied for the diagnosis and management of late-onset neonatal sepsis (LONS) and necrotizing enterocolitis. It is expected that the next generation of biomarkers and tests will be more specific, will pinpoint the precise disease entity, and will provide crucial information on the exact pathogen or category of microorganism and its antibiotic profile within hours of clinical presentation. Research on molecular pathogen detection and proteomic profiling has shown promising results. Academic-industry partnerships are vital for successful development of new diagnostic biomarkers for LONS, which are sensitive, inexpensive, fully automated, and easy to measure, allowing a quick turnaround time for clinical decision making.

Background: Infants receiving prolonged parenteral nutrition (PN) are at risk of PN-associated cholestasis (PNAC). This can progress to hepatic failure and death if PN cannot be discontinued. Fish oil-based parenteral lipid preparation (FOLP) has been shown to be beneficial in case studies. Objectives: (1) To evaluate whether FOLP could halt or reverse the progression of PNAC compared with soy-based parenteral lipid preparation (SLP) and (2) to assess the effects of FOLP on liver function and physical growth. Methods: Design: double-blind randomised controlled trial. Setting: level III neonatal intensive care unit. Participants: infants with PNAC (plasma-conjugated bilirubin concentration ≥34 µmol/l or 2 mg/dl) expected to be PN-dependent for >2 weeks. Intervention: to receive either FOLP or SLP at 1.5 g/kg/day. Primary outcome measure: reversal of PNAC within 4 months after commencement of lipid treatment; secondary outcomes: rate of change of weekly liver function tests, infant growth parameters, blood lipid profile and episodes of late-onset sepsis. Results: A total of 9 infants were randomised to the FOLP group and 7 to the SLP group. There was no significant difference in reversal of PNAC at 4 months between groups. Rates of increase of plasma-conjugated bilirubin and alanine aminotransferase in the SLP group were significantly greater than the FOLP group (13.5 vs. 0.6 µmol/l per week and 9.1 vs. 1.1 IU/l per week, respectively, p = 0.03). Increased enteral nutrition was associated with significant improvement of PNAC in infants receiving FOLP compared with SLP (-8.5 vs. -1.6 µmol/l per 10% increase in enteral nutrition, respectively). The study was terminated prematurely. Conclusions: progression of PNAC in PN-dependent infants can be halted by replacing SLP with FOLP and reversed by increasing the proportion of enteral nutrition in infants receiving FOLP. Replacement of SLP with FOLP in PN-dependent infants who develop PNAC may be considered.

BackgroundAlthough the serological antibody responses induced by SARS-CoV-2 vaccines are well characterized, little is known about their ability to elicit mucosal immunity.ObjectivesThis study aims to examine and compare the mucosal and systemic responses of recipients of two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac).MethodsSerial blood and nasal epithelial lining fluid (NELF) samples were collected from the recipients of either Comirnaty or CoronaVac. The plasma and NELF immunoglobulins A and G (IgA and IgG) specific to SARS-CoV-2 S1 protein (S1) and their neutralization effects were quantified.ResultsComirnaty induced nasal S1-specific immunoglobulin responses, which were evident as early as 14 ± 2 days after the first dose. In 64% of the subjects, the neutralizing effects of NELF persisted for at least 50 days. Moreover, 85% of Comirnaty recipients exhibited S1-specific IgA and IgG responses in plasma by 14 ± 2 days after the first dose. By 7 ± 2 days after the booster, all plasma samples possessed S1-specific IgA and IgG responses and were neutralizing. The induction of S1-specific plasma antibodies by CoronaVac was IgG dominant, and 83% of the subjects possessed S1-specific IgG by 7 ± 2 days after the booster, with neutralizing effects.ConclusionComirnaty induces S1-specific IgA and IgG responses with neutralizing activity in the nasal mucosa; a similar response is not seen with CoronaVac.Clinical ImplicationThe presence of a nasal response with mRNA vaccine may provide additional protection compared with inactivated virus vaccine. However, whether such widespread immunological response may produce inadvertent adverse effects in other tissues warrants further investigation.

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High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition and in whom anatomically obstructive pathologies of the gastrointestinal tract have been excluded.

Our findings suggest that parents of preterm infants as a group were most likely to save the infant at all costs and prepared to tolerate more severe disability health states. However, personal characteristics, in particular religious belief and severity of neonatal complications, have overriding influence on these attitudes. We suggest inclusion of experienced parents of preterm infants for more effective counseling of parents in making life-and-death decisions.