Search

Abstract Background Current evidence indicates that probiotic supplementation significantly reduces all-cause mortality and definite necrotising enterocolitis without significant adverse effects in preterm neonates. As the debate about the pros and cons of routine probiotic supplementation continues, many institutions are satisfied with the current evidence and wish to use probiotics routinely. Because of the lack of detail on many practical aspects of probiotic supplementation, clinician-friendly guidelines are urgently needed to optimise use of probiotics in preterm neonates. Aim To develop evidence-based guidelines for probiotic supplementation in preterm neonates. Methods To develop core guidelines on use of probiotics, including strain selection, dose and duration of supplementation, we primarily used the data from our recent updated systematic review of randomised controlled trials. For equally important issues including strain identification, monitoring for adverse effects, product format, storage and transport, and regulatory hurdles, a comprehensive literature search, covering the period 1966-2010 without restriction on the study design, was conducted, using the databases PubMed and EMBASE, and the proceedings of scientific conferences; these data were used in our updated systematic review. Results In this review, we present guidelines, including level of evidence, for the practical aspects (for example, strain selection, dose, duration, clinical and laboratory surveillance) of probiotic supplementation, and for dealing with non-clinical but important issues (for example, regulatory requirements, product format). Evidence was inadequate in some areas, and these should be a target for further research. Conclusion We hope that these evidence-based guidelines will help to optimise the use of probiotics in preterm neonates. Continued research is essential to provide answers to the current gaps in knowledge about probiotics.

Abstract Background The objective of this study was to systematically review randomized trials assessing therapeutic hypothermia as a treatment for term neonates with hypoxic ischemic encephalopathy. Methods The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL databases, reference lists of identified studies, and proceedings of the Pediatric Academic Societies were searched in July 2006. Randomized trials assessing the effect of therapeutic hypothermia by either selective head cooling or whole body cooling in term neonates were eligible for inclusion in the meta-analysis. The primary outcome was death or neurodevelopmental disability at ≥ 18 months. Results Five trials involving 552 neonates were included in the analysis. Cooling techniques and the definition and severity of neurodevelopmental disability differed between studies. Overall, there is evidence of a significant effect of therapeutic hypothermia on the primary composite outcome of death or disability (RR: 0.78, 95% CI: 0.66, 0.92, NNT: 8, 95% CI: 5, 20) as well as on the single outcomes of mortality (RR: 0.75, 95% CI: 0.59, 0.96) and neurodevelopmental disability at 18 to 22 months (RR: 0.72, 95% CI: 0.53, 0.98). Adverse effects include benign sinus bradycardia (RR: 7.42, 95% CI: 2.52, 21.87) and thrombocytopenia (RR: 1.47, 95% CI: 1.07, 2.03, NNH: 8) without deleterious consequences. Conclusion In general, therapeutic hypothermia seems to have a beneficial effect on the outcome of term neonates with moderate to severe hypoxic ischemic encephalopathy. Despite the methodological differences between trials, wide confidence intervals, and the lack of follow-up data beyond the second year of life, the consistency of the results is encouraging. Further research is necessary to minimize the uncertainty regarding efficacy and safety of any specific technique of cooling for any specific population.

Objective: To assess if high frequency jet ventilation (HFJV) is associated with reduced odds of death or discharge home on oxygen in preterm infants. Methods: A case control study (1 February 2010 - 1 June 2014) comparing the primary outcome as "death or discharge home on oxygen" in preterm infants who needed HFJV (Cases) versus those who did not (Controls). Controls were matched to cases (1:1) on gestation, birthweight, gender, place of birth, growth status, antenatal glucocorticoids, and dexamethasone as treatment for severe bronchopulmonary dysplasia (BPD). Logistic regression analysis was used to control for confounders. Results: Data on all preterm infants who needed HFJV (Cases: n = 50) and 50 controls during the study period were analysed. Primary outcome was more frequent in cases versus controls, but not significant after adjusting for mean airway pressure and adjuvant therapy (e.g. diuretics) [aOR: 1.46 (0.23-9.14), p = .687]. Death before discharge [odds ratios (OR): 6.00 (1.34-55.2), p = .013] was more frequent in cases; discharge on home oxygen [OR: 0.88 (0.27-2.76), p = 1.000] was comparable between groups. Duration of oxygen [adjusted hazard ratios (aHR): 1.23 (0.69-2.17), p = .475] and incidence of treatment warranting retinopathy of prematurity [aOR: 0.10 (0.01-1.96), p = .127] was not significant between cases versus controls. Conclusions: HFJV was not associated with reduced odds of death or discharge home on oxygen in preterm infants in our study. Adequately powered randomized trials are required to assess the efficacy and safety of HFJV in preterm infants. [ABSTRACT FROM AUTHOR]

Summary: Neonates with congenital gastrointestinal surgical conditions (CGISC) receive parenteral nutrition, get exposed to multiple courses of antibiotics, undergo invasive procedures, and are nursed in intensive care units. They do not receive early enteral feeding and have limited opportunities for skin to skin contact with their mothers. Many of these infants receive gastric acid suppression therapies. All these factors increase the risk of gut dysbiosis in these infants. Gut dysbiosis is known to be associated with increased risk of infections and other morbidities in ICU patients. Experimental studies have shown that probiotics inhibit gut colonization with pathogenic bacteria, enhance gut barrier function, facilitate colonization with healthy commensals, protect from enteropathogenic infection through production of acetate, reduce antimicrobial resistance, enhance innate immunity, and increase the maturation of the enteric nervous system and promote gut peristalsis. Through these mechanisms, probiotics have the potential to decrease the risk of sepsis and inflammation, improve feed tolerance and minimise cholestasis in neonates with CGISC. Among preterm non‐surgical infants, evidence from more than 35 RCTs and multiple observational studies have shown probiotics to be safe and beneficial. A RCT in neonates (N=24) with gastroschisis found that probiotic supplementation partially attenuated gut dysbiosis. Two ongoing RCTs (total N=168) in neonates with gastrointestinal surgical conditions are expected to provide feasibility data to enable the conduct of large RCTs. Rigorous quality assurance of the probiotic product, ongoing microbial surveillance and clinical vigilance are warranted while conducting such RCTs. [ABSTRACT FROM AUTHOR]

Background: The n-3 and n-6 fatty acids linolenic acid and linoleic acid are precursors of the n-3 and n-6 long chain fatty acids (LCPUFA). Infant formula has historically only contained the precursor fatty acids. Over the last few years, some manufacturers have added LCPUFA to formulae and marketed them as providing an advantage for the development of term infants., Objectives: To assess whether supplementation of formula with LCPUFA is safe and of benefit to term infants., Search Methods: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, April, 2011), MEDLINE (1966 to April 2011), EMBASE (1980 to April 2011), CINAHL (December 1982 to April 2011) and abstracts of the Society for Pediatric Research (1980 to 2010). No language restrictions were applied., Selection Criteria: Randomised and quasi randomised trials comparing LCPUFA supplemented vs. non-supplemented formula milk and with clinical endpoints were reviewed., Data Collection and Analysis: Methodological quality of studies was assessed using the guidelines of Cochrane neonatal review group. Data were sought regarding effects on visual acuity, neurodevelopmental outcomes and physical growth. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect., Main Results: Twenty-five randomised studies were identified; fifteen were included (n = 1889) and ten excluded.Visual acuity was assessed by nine studies. Visual evoked potential was used in six studies, two used Teller cards and one used both. Four studies reported beneficial effects while the remaining five did not.Neurodevelopmental outcome was measured by eleven studies. Bayley scales of infant development (BSID) was used in nine studies; only two showed beneficial effects. Meta-analysis did not show significant benefits of supplementation. One study followed the infants up to nine years of age and did not find benefit of supplementation. One study reported better novelty preference measured by Fagan Infant test at nine months. Another study reported better problem solving at 10 months. One study used Brunet and Lezine test to assess the developmental quotient and did not find beneficial effects.Physical growth was measured by thirteen studies; none found beneficial or harmful effects of supplementation. Meta-analysis found that supplemented group may have marginally lower weight at one year of age., Authors' Conclusions: Majority of the RCTS have not shown beneficial effects of LCPUFA supplementation on the neurodevelopmental outcomes of term infants. The beneficial effects on visual acuity have not been consistently demonstrated. Routine supplementation of term infant milk formula with LCPUFA can not be recommended.

Background: Controversy exists over whether longchain polyunsaturated fatty acids (LCPUFA) are essential nutrients for preterm infants, who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina., Objectives: The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to preterm infants., Search Strategy: Trials were identified by MEDLINE (1966 to December 2009), Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2009) and by checking reference lists of articles and conference proceedings., Selection Criteria: All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed., Data Collection and Analysis: All authors assessed eligibility and trial quality, two authors extracted data separately. Study authors were contacted for additional information., Main Results: Of the 17 trials included in the review, 13 were classified as of high quality. Visual acuity Visual acuity over the first year was measured by Teller or Lea acuity cards in eight studies, by VEP in six studies and by ERG in two studies. Most studies found no significant differences in visual assessment between supplemented and control infants.Development Three out of seven studies reported some benefit of LCPUFA on neurodevelopment in different populations at different postnatal ages. Meta-analysis of Bayley Scales of Infant Development of four studies at 12 months (N = 364) and three studies at 18 months (N = 494) post-term showed no significant effect of supplementation on neurodevelopment.Growth Four out of 15 studies reported benefits of LCPUFA on growth of supplemented infants at different postnatal ages. Two trials suggested that LCPUFA supplemented infants grow less well than controls. One trial reported mild reductions in length and weight z scores at 18 months. Meta-analysis of five studies showed increased weight and length at two months post-term in supplemented infants. Meta-analysis of four studies at 12 months (N = 271) and two studies at 18 months (N = 396) post-term showed no significant effect of supplementation on weight, length or head circumference., Authors' Conclusions: Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. On pooling of results, no clear long-term benefits or harms were demonstrated for preterm infants receiving LCPUFA-supplemented formula.