Background: Over the last few years, probiotics have been one of the most studied interventions in neonatal medicine. Objectives: The aim of this work was to analyse all studies (randomized controlled trials, RCTs, and observational studies) assessing the use of probiotics in very low birth weight (VLBW) preterm infants. Search Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane Library, and Web of Science. The data from RCTs and observational studies were pooled and analysed separately. Selection Criteria: RCTs and observational studies that enrolled VLBW infants with enteral administration of probiotics were considered. Extracted study data included probiotic characteristics and at least 1 clinical outcome (necrotizing enterocolitis [NEC], late-onset sepsis or all-cause mortality). Data Collection and Analysis: Forty-four studies were eligible for our review: 30 RCTs and 14 observational studies. Severe NEC rates (stage II or more) and all-cause mortality were reduced among the probiotic groups in both the RCTs (RR 0.57, 95% CI 0.47-0.70, and RR 0.77, 95% CI 0.65-0.92, respectively) and the observational studies (RR 0.51, 95% CI 0.37-0.70, and RR 0.71, 95% CI 0.62-0.81, respectively). Furthermore, there was a 12% reduction in the risk of sepsis in RCTs and a 19% reduction in observational studies. The meta-analysis of observational studies showed a reduction in the risk of NEC in extremely low birth weight infants. However, this was not statistically significant. Conclusions: This meta-analysis of RCT and observational studies found that the use of probiotics was beneficial for the prevention of severe NEC, late-onset sepsis, and all-cause mortality in VLBW infants.

ObjectiveTo compare necrotising enterocolitis (NEC), late-onset sepsis (LOS), focal intestinal perforation (FIP) and mortality in infants from a single neonatal unit before and after probiotic introduction.DesignRetrospective review of infants <32 weeks admitted January 2009–December 2012 (no probiotic) and January 2013–December 2017 (routine probiotics). Infants included were admitted before day 3, and not transferred out before day 3. NEC, LOS and FIP were defined with standard definitions.Patients1061 infants were included, 509 preprobiotic and 552 postprobiotic. Median gestation, birth weight and antenatal steroid use did not differ, and proportions of extremely low birthweight infants were similar (37% and 41%).ResultsOverall unadjusted risk of NEC (9.2% (95% CI 7.1 to 12.1) vs 10.6% (95% CI 8.2 to 13.4), p=0.48), LOS (16.3% (95% CI 13.2 to 19.6) vs 14.1% (95% CI 11.5 to 17.4), p=0.37) and mortality (9.2% (95% CI 7.1 to 12.1) vs 9.7% (95% CI 7.6 to 12.6), p=0.76) did not differ, nor proportion of surgical NEC. In multiple logistic regression, accounting for gestation, birth weight, antenatal steroid, maternal milk, chorioamnionitis and sex, probiotic receipt was not significantly associated with NEC (adjusted OR (aOR) 1.08 (95% CI 0.71 to 1.68), p=0.73), LOS or mortality. In subgroup (645 infants) >28 weeks, aOR for NEC in the probiotic cohort was 0.42 (95% CI 0.2 to 0.99, p=0.047). FIP was more common in the probiotic cohort (OR 2.3 (95% CI 1.0 to 5.4), p=0.04), not significant in regression analysis (2.11 (95% CI 0.97 to 4.95), p=0.05).ConclusionsProbiotic use in this centre did not reduce overall mortality or rates of NEC, LOS or FIP but subgroup analysis identified NEC risk reduction in infants >28 weeks, and LOS reduction <28 weeks.

Flexible bronchoscopy (FB), developed in the 1960s, is widely used in the clinical practice of pediatrics and has demonstrated fundamental value in clinical diagnoses and treatment. However, as an invasive procedure, the use of FB is limited due to concerns regarding the tolerance of the procedure and the possible complications in neonatal units. Thus, the present study aimed to investigate the clinical safety and efficacy of flexible bronchoscopy (FB) in a neonatal intensive care unit (NICU). Neonates (n=54) who received FB in the NICU of Shanghai Children's Hospital between January 2012 and December 2016 were enrolled as the experimental group and another 54 neonates who required nebulization and tracheal secretion suction treatments were the control group. Indicators including blood gas, complete blood count, C-reactive protein (CRP), X-ray, patient breathing rate, temperature and blood pressure were monitored prior to and following the procedure. No significant differences in sex, gestational age, birth weight or postnatal age were observed between the experimental group and the control group (P>0.05). Among the 54 FB patients, several cases with side effect were identified, including 18 (33.3%) with respiratory tract stenosis, nine (16.7%) with malacia and stenosis and six (11.1%) with esophagotracheal fistula. Among the 54 members of the control group, 44 neonates (81.4%) were discharged with improved condition, five (9.3%) succumbed and five patients (9.3%) abandoned the treatment and left the hospital. Bronchoalveolar lavage demonstrated consistent results with respiratory secretion culture or tracheal tube culture. In comparison between the experimental and the control groups, no significant difference in pH, partial pressure of carbon dioxide (PCO 2 ), partial pressure of oxygen (PO 2 ) and HCO 3 was observed, while there were no statistical differences in the values of pH, PCO 2 and HCO 3 -(P>0.05). However, PO 2 was significantly increased, and CRP was significantly reduced, following FB procedure compared with prior to FB (P<0.05). No pneumothorax, shock, other severe complications, fever or diffused pneumonia were observed during or after FB. The data from the present study demonstrated that FB is a safe and effective strategy for the diagnosis and differentiation of neonatal respiratory diseases in NICU.

BackgroundGastro-oesophageal reflux is prevalent in preterm infants. Despite widespread use in clinical practice, there is still much controversy over the efficacy and safety of drug interventions, particularly antacid therapy.ObjectiveTo systematically review the effects of antacid therapy on preterm infants with symptoms of gastro-oesophageal reflux, and to assess the safety of these interventions.MethodsWe carried out an electronic search of the Cochrane central register of controlled trials (CENTRAL, The Cochrane Library), MEDLINE (1966–present), EMBASE (1980–present) and CINAHL (1982–present) as well as other online sources. Participants were preterm infants (<37 weeks gestation) with gastro-oesophageal reflux disease who were receiving care on a neonatal unit. We assessed the effects of histamine-2 receptor antagonists, proton pump inhibitors and alginates against placebo, primarily to see if they reduced the symptoms of reflux.ResultsSix studies were included in this review. Meta-analysis could not be carried out due to a lack of studies assessing the same intervention with the same outcomes. Omeprazole therapy significantly reduced the oesophageal acid exposure percentage time with pH<4 (p<0.01) and sodium alginate significantly decreased gastro-oesophageal reflux episodes (p=0.024). Metoclopramide and ranitidine showed a significant increase in gastro-oesophageal reflux disease symptoms versus placebo (p<0.04). No significant results were found for the use of esomeprazole or lansoprazole versus placebo.ConclusionsThere is insufficient evidence available to conclude whether antacid therapy is effective or safe when treating gastro-oesophageal reflux disease in preterm infants. Further research is needed into this topic and caution should be taken when administering antacids to preterm infants.Trial registration numberCRD42017078778

ObjectiveReview of age of onset of necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in very preterm (≤32 weeks) and/or very low birthweight (VLBW, ≤1500 g) infants.DesignPreregistered review undertaken according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses in July 2021 and updated October 2021.Data sourcesMEDLINE/ PubMed, Embase, CINAHL and Cochrane Central Register of Controlled Trials.EligibilityEligible studies reported age of onset of NEC and/or FIP in randomised controlled trials of >200 or observational studies of >500 infants.Data extraction and synthesisTitles/abstracts were screened; eligible articles underwent data extraction. Age of onset as day of life (DOL) and/or corrected gestational age (CGA) were extracted alongside study information, such as NEC definition, included population, intervention, location and dates studied. Weighted means were used to compare onset by birth gestation, study type, NEC definition, trial intervention, location and dates studied. Comparison was done by Mann-Whitney U test or one-way analysis of variance.ResultsOf the 747 screened studies 188 were eligible. Removal of duplicates, studies without onset data and ineligible populations left 10 RCTs and 14 observational studies contributing 51 NEC cohorts; 49 reported onset DOL and 14 CGA. 2984 cases of NEC had average DOL onset of 16.7 (15.5 in RCTs, 16.9 in observational studies), and CGA onset of 30.1 weeks. Gestation did not impact DOL onset. No other demographic feature impacted NEC onset. Few studies included data on FIP.ConclusionsAverage onset of NEC in exclusively very preterm/very low birthweight infants is in the third week of life and unlike in cohorts including more mature or heavier infants is not impacted by birth gestation.

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