Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis.

Importance: Modulation of intestinal microbiome by administering probiotics, prebiotics, or both may prevent morbidity and mortality in premature infants. Objective: To assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials. Data Sources: MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023. Study Selection: Eligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants. Data Extraction and Synthesis: A frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach. Main Outcomes and Measures: All-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization. Results: A total of 106 trials involving 25 840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, -3.7%; 95% CI, -4.1% to -2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, -5.1%; 95% CI, -5.6% to -3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, -10.7%; 95% CI, -13.7% to -3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, -10.0%; 95% CI, -13.9% to -5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, -14.1%; 95% CI, -18.3% to -8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, -10.0%; 95% CI, -12.6% to -7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, -1.94 days; 95% CI, -2.96 to -0.92) and multistrain probiotics (MD, -2.03 days; 95% CI, -3.04 to -1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, -3.31 days; 95% CI, -5.05 to -1.58; and MD, -2.20 days; 95% CI, -4.08 to -0.31, respectively). Conclusions and Relevance: In this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.

C-reactive protein as a predictor of meningitis in early onset neonatal sepsis: a single unit experience.

Objectives To determine whether there is a cut off value of serum C-reactive protein (CRP) associated with a higher risk of meningitis in suspected early onset sepsis (EOS) (onset birth to 7 days of life). Methods A retrospective cohort study on neonates admitted in neonatal intensive care unit at McMaster Children's Hospital from January 2010 to 2017 and had lumbar puncture (LP) and CRP for workup of EOS. Included subjects had either (a) non-traumatic LP or (b) traumatic LP with cerebral spinal fluid (CSF) polymerase chain reaction or gram stain or culture-positive or had received antimicrobials for 21 days. Excluded were CSF done for metabolic errors, before cytomegalovirus (CMV) treatment; from ventriculo-peritoneal (VP) shunts; missing data and contamination. Neonates were classified into definite and probable meningitis and on the range of CRP. We calculated sensitivity, specificity, and likelihood ratios for CRP values; and area under the receiver operating characteristic (AUROC) curve. Results Out of 609 CSF samples, 184 were eligible (28 cases of definite or probable meningitis and 156 controls). Sensitivity, specificity, predictive values, likelihood ratios, and AUROC were too low to be of clinical significance to predict meningitis in EOS. Conclusions Serum CRP values have poor discriminatory power to distinguish between subjects with and without meningitis, in symptomatic EOS.

Comparative Effectiveness of Prophylactic Therapies for Necrotizing Enterocolitis in Preterm Infants: Protocol for a Network Meta-analysis of Randomized Trials.

Necrotizing enterocolitis (NEC) is a common and devastating disease with high morbidity and mortality in premature infants. Current literature on the prevention of NEC has limitations including lack of direct and indirect comparisons of available therapies. We will search MEDLINE, EMBASE, Science Citation Index Expanded, Social Sciences Citation Index, CINAHL, Scopus, ProQuest Dissertations and Theses database, and grey literature sources to identify eligible trials evaluating NEC preventive therapies. Eligible studies will (1) enroll preterm (gestational age <37 weeks) and/or low birth weight (birth weight <2500 g) infants, (2) randomize infants to any preventive intervention or a placebo, or alternative active or nonactive intervention. Our outcomes of interest are severe NEC (stage II or more, based on Bell's criteria), all-cause mortality, NEC-related mortality, late-onset sepsis, duration of hospitalization, weight gain, time to establish full enteral feeds, and treatment-related adverse events. Two reviewers will independently screen trials for eligibility, assess risk of bias, and extract data. All discrepancies will be resolved by discussion. We will specify a priori explanations for heterogeneity between studies. For available comparisons between treatment and no treatment, and direct comparisons of treatments, we will conduct conventional meta-analysis using a random effects model. We will conduct a network meta-analysis using a random effects model within the Bayesian framework using Markov chain Monte Carlo methods to assess relative effects of eligible interventions. We will assess the certainty in direct, indirect, and network estimates using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: We will disseminate our findings through a peer-reviewed publication and conference presentations.

Video recording of neonatal resuscitation: A feasibility study to inform widespread adoption.

AIM: To determine the feasibility of introducing video recording (VR) of neonatal resuscitation (NR) in a perinatal centre. METHODS: This was a prospective cohort quality improvement study on preterm infants and their caregivers. Based on evidence and experience of other centers using VR intervention, a contextually relevant implementation and evaluation strategy was designed in the planning phase. The components of intervention were pre-resuscitation team huddle, VR of NR and video debriefing (VD), all occurring on the same day. Various domains of feasibility and sustainability as well as feasibility criteria were predefined. Data for analysis was collected using quantitative and qualitative methods. RESULTS: Seventy-one caregivers participated in VD of 14 NRs facilitated by six trained instructors. Ninety-one percent of caregivers perceived enhanced learning and patient safety and, 48 issues were identified related to policy, caregiver roles, and latent safety threats. Ninety percent of caregivers expressed their willingness to participate in VD activity and supported the idea of integrating it into a resuscitation team routine. Eighty-three percent and 50% of instructors expressed satisfaction with video review software and quality of audio VR. No issues about maintenance of infant or caregivers' confidentiality and erasure of videos were reported. Criteria for feasibility were met (refusal rate of < 10%, VR performed on > 50% of occasions, and < 20% caregivers' perceiving a negative impact on team performance). Necessary adaptations to enhance sustainability were identified. CONCLUSION: VR of NR as a standard of care quality assurance activity to enhance caregivers' learning and create opportunities that improve patient safety is feasible. Despite its complexity with inherent challenges in implementation, the intervention was acceptable, implementable, and potentially sustainable with adaptations.

Introduction of microsystems in a level 3 neonatal intensive care unit-an interprofessional approach.

BACKGROUND: Growth of neonatal intensive care units in number and size has raised questions towards ability to maintain continuity and quality of care. Structural organization of intensive care units is known as a key element for maintaining the quality of care of these fragile patients. The reconstruction of megaunits of intensive care to smaller care units within a single operational service might help with provision of safe and effective care. METHODS/DESIGN: The clinical team and patient distribution lay out, admission and discharge criteria and interdisciplinary round model was reorganized to follow the microstructure philosophy. A working group met weekly to formulate the implementation planning, to review the adaptation and adjustment process and to ascertain the quality of implementation following the initiation of the microsystem model. DISCUSSION: In depth examination of microsystem model of care in this study, provides systematic evaluation of this model on variable aspects of health care. The individual projects of this trial can be source of solid evidence for guidance of future decisions on optimized model of care for the critically ill newborns. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02912780 . Retrospectively registered on 22 September 2016.

High-flow nasal cannulae are associated with increased diaphragm activation compared with nasal continuous positive airway pressure in preterm infants.

AIM: High-flow nasal cannulae (HFNC) are increasingly used for respiratory management of preterm infants. However, their ability to provide support compared to nasal continuous positive airway pressure (CPAP) has been questioned. We compared the effect of HFNC versus nasal CPAP on diaphragm electrical activity (EAdi) in preterm infants. METHODS: Preterm infants ≤1500 g were randomised in a crossover design to receive 2 hours of either Infant Flow(®) CPAP (IF-CPAP) at 5-6 cmH2 O or HFNC with the flow rate adjusted to achieve an equivalent pharyngeal pressure. A feeding catheter with miniaturised sensors was inserted for continuous EAdi measurement. RESULTS: The study comprised ten infants. Physiologic parameters and oxygen requirements were not different between the two modes. However, seven infants demonstrated a higher EAdi peak and six showed a higher EAdi tonic on HFNC, even though the mean group data showed no difference between HFNC and IF-CPAP. Neural inspiratory time was significantly longer with HFNC than IF-CPAP (0.55 ± 0.11 versus 0.48 ± 0.06 seconds, p = 0.018). CONCLUSION: In this cohort of preterm infants, the majority exhibited greater diaphragm activation, as assessed by neural breathing patterns, when supported with HFNC than IF-CPAP, suggesting that nasal CPAP may provide more effective respiratory support.