Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis.

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.

The pros, cons, and many unknowns of probiotics.

Consumption of over-the-counter probiotics for promotion of health and well-being has increased worldwide in recent years. However, although probiotic use has been greatly popularized among the general public, there are conflicting clinical results for many probiotic strains and formulations. Emerging insights from microbiome research enable an assessment of gut colonization by probiotics, strain-level activity, interactions with the indigenous microbiome, safety and impacts on the host, and allow the association of probiotics with physiological effects and potentially useful medical indications. In this Perspective, we highlight key advances, challenges and limitations in striving toward an unbiased interpretation of the large amount of data regarding over-the-counter probiotics, and propose avenues to improve the quality of evidence, transparency, public awareness and regulation of their use.

A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis.

Importance: Current algorithms for management of neonatal early-onset sepsis (EOS) result in medical intervention for large numbers of uninfected infants. We developed multivariable prediction models for estimating the risk of EOS among late preterm and term infants based on objective data available at birth and the newborn's clinical status. Objectives: To examine the effect of neonatal EOS risk prediction models on sepsis evaluations and antibiotic use and assess their safety in a large integrated health care system. Design, Setting, and Participants: The study cohort includes 204 485 infants born at 35 weeks' gestation or later at a Kaiser Permanente Northern California hospital from January 1, 2010, through December 31, 2015. The study compared 3 periods when EOS management was based on (1) national recommended guidelines (baseline period [January 1, 2010, through November 31, 2012]), (2) multivariable estimates of sepsis risk at birth (learning period [December 1, 2012, through June 30, 2014]), and (3) the multivariable risk estimate combined with the infant's clinical condition in the first 24 hours after birth (EOS calculator period [July 1, 2014, through December 31, 2015]). Main Outcomes and Measures: The primary outcome was antibiotic administration in the first 24 hours. Secondary outcomes included blood culture use, antibiotic administration between 24 and 72 hours, clinical outcomes, and readmissions for EOS. Results: The study cohort included 204 485 infants born at 35 weeks' gestation or later: 95 343 in the baseline period (mean [SD] age, 39.4 [1.3] weeks; 46 651 male [51.0%]; 37 007 white, non-Hispanic [38.8%]), 52 881 in the learning period (mean [SD] age, 39.3 [1.3] weeks; 27 067 male [51.2%]; 20 175 white, non-Hispanic [38.2%]), and 56 261 in the EOS calculator period (mean [SD] age, 39.4 [1.3] weeks; 28 575 male [50.8%]; 20 484 white, non-Hispanic [36.4%]). In a comparison of the baseline period with the EOS calculator period, blood culture use decreased from 14.5% to 4.9% (adjusted difference, -7.7%; 95% CI, -13.1% to -2.4%). Empirical antibiotic administration in the first 24 hours decreased from 5.0% to 2.6% (adjusted difference, -1.8; 95% CI, -2.4% to -1.3%). No increase in antibiotic use occurred between 24 and 72 hours after birth; use decreased from 0.5% to 0.4% (adjusted difference, 0.0%; 95% CI, -0.1% to 0.2%). The incidence of culture-confirmed EOS was similar during the 3 periods (0.03% in the baseline period, 0.03% in the learning period, and 0.02% in the EOS calculator period). Readmissions for EOS (within 7 days of birth) were rare in all periods (5.2 per 100 000 births in the baseline period, 1.9 per 100 000 births in the learning period, and 5.3 per 100 000 births in the EOS calculator period) and did not differ statistically (P = .70). Incidence of adverse clinical outcomes, including need for inotropes, mechanical ventilation, meningitis, and death, was unchanged after introduction of the EOS calculator. Conclusions and Relevance: Clinical care algorithms based on individual infant estimates of EOS risk derived from a multivariable risk prediction model reduced the proportion of newborns undergoing laboratory testing and receiving empirical antibiotic treatment without apparent adverse effects.