Mangesh Deshmukh

Fish oil (SMOFlipid) and olive oil lipid (Clinoleic) in very preterm neonates

Objectives: Fat emulsions used in Australia for parenteral nutrition in preterm neonates have been based on either soybean oil or olive oil (OO). OO lipid Clinoleic has a high ratio of n-6 to n-3 fatty acids (9:1); this may not be ideal for long-chain polyunsaturated fatty acids supply. Newly available SMOFlipid has an appropriate ratio of n-6 to n-3 fatty acids (2.5:1). SMOFlipid also contains OO (25%), coconut oil (30%), and soybean oil (30%). The aims of the study were to evaluate the safety of the SMOFlipid and to test the hypothesis that SMOFlipid would lead to increased omega-3 long-chain polyunsaturated fatty acid levels and reduced oxidative stress as compared with Clinoleic in preterm neonates (<30 weeks). Methods: Preterm neonates (23–30 weeks) were randomised to receive Clinoleic or SMOFlipid emulsion for 7 days. Investigators and outcome assessors were masked to allocation. Plasma F2-isoprostanes (lipid peroxidation marker), red blood cell fatty acids, and vitamin E were measured before and after the study. Blood culture positive sepsis and growth were monitored for safety. Results: Thirty of 34 participants completed the study. Both emulsions were well tolerated without any adverse events. F2-isoprostane levels were reduced in the SMOFlipid group as compared with baseline. Eicosapentanoic acid and vitamin E levels were significantly increased in the SMOFlipid group. Oleic acid and linoleic acid levels were increased in both groups. No significant differences were noted in poststudy docosahexaenoic acid levels in both groups despite higher levels of docosahexaenoic acid in SMOFlipid. Conclusions: SMOFlipid was safe, well tolerated, and showed beneficial effect in terms of reduction of oxidative stress by reducing lipid peroxidation levels in high-risk preterm neonates.

Antenatal corticosteroids for neonates born before 25 Weeks—A systematic review and meta-analysis

Background Efficacy of antenatal corticosteroids before 25 weeks of gestation is unclear. Objective To assess and compare neonatal outcomes following ANC exposure at 22, 23 and 24 weeks of gestation by conducting systematic review and meta- analysis. Methods A systematic review of randomised controlled trials (RCT) and non-RCTs reporting on neonatal outcomes after exposure to ANC up to 246 weeks of gestation using the Cochrane systematic review methodology. Databases Pubmed, CINAHL, Embase, Cochrane Central library, and online abstracts of conference proceedings including the Pediatric Academic Society (PAS) were searched in Feb 2017. Primary outcome was in-hospital mortality defined as death before discharge during the first admission. Secondary outcomes included severe intraventricular hemorrhage (IVH> grade III and IV)/or periventricular leukomalacia (PVL), necrotising enterocolitis (NEC >stage II) and chronic lung disease (CLD). Meta-analysis was performed using a random-effects model. The level of evidence (LOE) was summarised using the GRADE guidelines. Main results There were no RCTs; 8 high quality non-RCTs were included in the review. Meta-analysis showed reduction in mortality [N = 10109; OR = 0.47(0.39–0.56), p<0.00001; LOE: Moderate] and severe IVH and PVL [N = 5084; OR = 0.71(0.61–0.82), p<0.00001; LOE: Low] after exposure to ANC in neonates born <25 weeks. There was no significant difference in CLD [N = 4649; OR = 1.19(0.85–1.65) p = 0.31; LOE: Low] and NEC [N = 5403; OR = 0.95 (0.76–1.19) p = 0.65; LOE: Low]. Mortality was comparable in neonates born at 22, 23 or 24 weeks. Conclusion Moderate to low quality evidence indicates that exposure to ANC is associated with reduction in mortality and IVH/or PVL in neonates born before 25 weeks.

Meconium Evacuation for Facilitating Feed Tolerance in Preterm Neonates: A Systematic Review and Meta-Analysis

Background: A delayed passage of meconium is considered as a risk factor for feed intolerance in preterm neonates. Objectives: The aim of this study was to review the effects of different therapeutic agents for meconium evacuation on feed tolerance in preterm neonates. Methods: A systematic review of randomised controlled trials (RCTs) of different therapeutic agents for meconium evacuation in preterm neonates (gestation <32 weeks and/or birth weight <1,500 g) using the Cochrane systematic review methodology was undertaken. Databases including Google Scholar were searched in January 2016. The primary outcome was the time to reach full feeds (TFF; ≥120 ml/kg feeds with stoppage of parenteral nutrition >24 h). Secondary outcomes included necrotising enterocolitis (NEC), weight at discharge and adverse effects. The results were summarised as per the GRADE guidelines. Results: Six RCTs (2 each of glycerine suppository and enema, 1 normal saline enema and 1 oral osmotic contrast agent; n = 442) with a low or unclear risk of bias were included. The pooled estimate (random effects model) showed no reduction in TFF [mean difference (MD) -0.03, 95% CI -2.47, 2.41, p = 0.98; level of evidence: low]. No differences in NEC [risk ratio (RR) 1.71, 95% CI 0.63, 4.65, p = 0.30; level of evidence: low] and weight at discharge (MD -0.08, 95% CI -0.30, 0.15, p = 0.50; level of evidence: low) were found. The trial assessing oral osmotic contrast agents reported a trend towards a higher incidence of NEC ≥ stage II. There were no other adverse effects. Conclusion: Limited low-quality evidence indicates that prophylactic glycerine suppository, small volume glycerine/normal saline enema or oral osmotic contrast agents to evacuate meconium did not reduce TFF in preterm neonates. Large, well-designed trials are essential to study this clinically significant issue.

Effect of gastric lavage on feeding in neonates born through meconium-stained liquor: a systematic review

Objective To evaluate the efficacy and safety of gastric lavage (GL) in neonates born through meconium-stained liquor (MSL). Design A systematic review of randomised controlled trials by searching databases MEDLINE (from 1966), EMBASE (from1980), CINAHL, Cochrane Central Register of Controlled Trials, Google Scholar and proceedings of Pediatric Academic Society meetings (2002–2014). Setting Delivery room/Neonatal ward. Patients Neonates with gestation >34 weeks and birth weight ≥1800 g born through MSL. Interventions Prophylactic GL versus no intervention before first feed. Main outcome measure Feeding intolerance, defined as inability to initiate/upgrade feeds due to problems such as retching, vomiting, regurgitation and gastric residuals. Results A total of six studies (GL: 918, no GL: 966) were included in the review. Meta-analysis using fixed-effects model showed decreased incidence of feed intolerance following GL ((81/918 (8.8%) vs 114/966 (11.8%); risk ratio (RR): 0.71 (95% CI 0.55 to 0.93)). However, the results were not significant when random-effects model was used (RR: 0.78 (95% CI 0.55 to 1.09)). No significant adverse effects of GL were reported. Conclusions Routine GL immediately after birth may improve feed tolerance in neonates born through MSL. However, the evidence is limited, with probable small-study bias and high risk of bias in a number of the included studies. Well-designed studies with adequate sample size are essential to confirm these findings.

Antenatal corticosteroids in impending preterm deliveries before 25 weeks’ gestation

Antenatal corticosteroid (ANC) use before 25 weeks’ gestation is controversial. Our previous systematic review (eight observational studies, n=10 109) showed that ANC exposure was associated with significantly reduced mortality and severe intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL) in neonates born <25 weeks. We update our review by adding data (n=3334) from a recent study. We used Cochrane methodology and summarised the results using GRADE (The Grading of Recommendations Assessment, Development and Evaluation) guidelines. Nine high-quality observational studies were included. Meta-analysis (random effects model) showed reduced mortality (n=13 443; OR=0.48 (95% CI 0.42 to 0.55) P<0.00001; level of evidence (LOE): moderate) and IVH or PVL (n=8418; OR=0.70 (95% CI 0.63 to 0.79), P<0.00001; LOE: moderate) in neonates born <25 weeks exposed to ANC. There was no difference in necrotising enterocolitis (NEC) ≥stage II (n=8737; OR=1.01 (95% CI 0.84 to 1.22), P=0.89; LOE: low); incidence of chronic lung disease (CLD) was higher (n=7983; OR=1.32 (95% CI 1.04 to 1.67), P=0.02; LOE: low) in ANC group. Composite outcomes of death/major morbidities (eg, severe IVH, NEC, CLD) were improved after ANC exposure.

Probiotics for the management of neonatal hyperbilirubinemia: a systematic review of randomized controlled trials

Abstract Background: Neonatal jaundice requiring phototherapy is associated with significant socioeconomic burden including hospital readmission, prolonged hospital stay, and separation of the baby from mother. Objectives: To assess the efficacy and safety of probiotics in reducing the need for phototherapy and its duration in neonatal hyperbilirubinemia. Methods: A systematic review of randomized controlled trials (RCTs) of probiotic supplementation for prevention or treatment of jaundice in neonates (any gestation or weight) using the Cochrane methodology. Primary outcome was the duration of phototherapy. Secondary outcomes included incidence of jaundice, total serum bilirubin (TSB) level at 24, 48, 72, 96 h, and day 7, duration of hospital stay, and adverse effects (e.g. probiotic sepsis). Results were summarized as per GRADE guidelines. Results: Nine RCTs (prophylactic: six trials, N = 1761; therapeutic: three trials, N = 279) with low to high risk of bias were included. Meta-analysis (random-effects model) showed probiotic supplementation reduced duration of phototherapy [N = 415, mean difference (MD): −11.80 (−17.47, −6.13); p < .0001; level of evidence (LOE): low]. TSB was significantly reduced at 96 h [MD: −1.74 (−2.92, −0.57); p = .004] and 7 d [MD: −1.71 (−2.25, −1.17); p < .00001; LOE: low] after probiotic treatment. Prophylactic probiotics did not reduce the incidence of jaundice significantly [N = 1582, relative risk (RR): 0.56 (0.25, 1.27); p = .16; LOE: low]. There were no probiotic-related adverse effects. Conclusion: Limited low-quality evidence indicates that probiotic supplementation may reduce the duration of phototherapy in neonates with jaundice. Routine use of probiotics to prevent or treat neonatal jaundice cannot be recommended. Large well-designed trials are essential to confirm these findings.

Strategies for managing transient tachypnoea of the newborn - a systematic review

Abstract Objective: To conduct a systematic review of strategies for the management of transient tachypnoea of the newborn (TTN). Methods: The Cochrane Collaboration and PRISMA guidelines were used for conducting and reporting this systematic review, respectively. The Cochrane Central Register of Controlled Trials, PubMed, CINAHL and EMBASE databases were searched in February 2016. Only randomised and quasi-randomised controlled trials (RCTs) assessing any intervention for the management of TTN in infants <7 days of age, born at 35 or more weeks with a clinical diagnosis of TTN were eligible for inclusion. Primary outcomes included the duration of respiratory support, oxygen support, tachypnoea and hospitalisation. Results: Nine RCTs with moderate risk of bias were included. The interventions assessed included furosemide (2 trials, n = 100), inhaled salbutamol (2 trials, n = 94), inhaled epinephrine (1 trial, n = 20), restrictive fluids (2 trials, n = 146) and non-invasive ventilation (2 trials, n = 80). Amongst all interventions, inhaled salbutamol significantly reduced the duration of hospitalisation (2 trials, n = 94) [mean difference (MD) - 1.63 days (95% CI −2.71 to −0.55); p = 0.003] and duration of oxygen requirement (1 trial, n = 37) [MD - 43.10 h (95% CI −81.82 to −4.38; p = 0.03] without adverse effects. Conclusion: Limited low-quality evidence exists on the effects of different management strategies for TTN. The safety and efficacy of inhaled salbutamol in the treatment of TTN can be assessed in a large RCT.

Wastage of standardised parenteral nutrition solution – a challenge for neonatal units

Abstract Background: Standardised parental nutrition (PN) has been used in many neonatal intensive care unit (NICU). Easy accessibility, better provision of nutrients, reduced prescription errors and cost savings are some of its benefits. Fixed large volume (e.g. 750–1000 mL) and short expiry limit (48 hrs) along with changing metabolic needs of neonates leads to significant wastage of PN solution. Objective: To evaluate wastage of PN solution in our 22-bedded NICU. Methods: The audit was conducted over 21-month period (July 2015–April 2017). Data on PN use (e.g. type, duration, infused volume, residual after use) was obtained from hospital records. The discarded volume of PN was estimated after subtracting the administered volume based on the rate of infusion from the total volume in the bag. Cumulative “discarded” volume as percentage of the total “supplied” volume was calculated. Results: A total of 305-PN bags (Standardised: Preterm: 222, Term: 83) were used. The estimated total used, discarded, and percentage discarded volumes for standard preterm and term PN were 78.1, 88 L, 53% and 33.5, 49.7 L, and 59.8%, respectively. Conclusions: There was more than 50% wastage of PN solution in our NICU. The estimated cost of this PN wastage was around 21,000 AUD over 21 months. Strategies such as minipack should be explored to prevent such losses.

Strategies for Medical Management of Pediatric Eosinophilic Esophagitis.

Objective: Eosinophilic esophagitis (EoE) is associated with significant morbidity in children. Strategies for optimizing its outcomes are hence essential. We aimed to review the strategies for medical management of EoE in children. Methods: We conducted a systematic review of randomized controlled trials (RCTs) of medical interventions in children with EoE, using the Cochrane methodology. Databases including PubMed, EMBASE, CINAHL, Cochrane Central Library, and Google scholar were searched up to March 2016. Primary outcomes included histological (peak eosinophil count) and symptomatic remission. Secondary outcomes were improvement in endoscopic and other histological parameters and adverse effects. Results: A total of 5 RCTs (N = 448) with low to unclear risk of bias were included. The interventions included topical oral steroids, swallowed enteral steroids and anti- interleukin (IL)5 agent. Pooling of data from all trials was not possible owing to significant heterogeneity in interventions. Meta-analysis of data (N = 141) from 3 RCTs (oral viscous budesonide: 2, fluticasone: 1) showed significant histological remission in the intervention versus control group participants (risk difference: 10.32 [95% confidence interval: 3.04, 35.03]; P = 0.0002), level of evidence—low. Compared with anti-IL5 agent, the trials assessing steroids reported high rates of clinical remission. Clinical remission did not correlate with histological improvement in any trial. Except for systemic corticosteroids, there were no significant adverse effects related to other interventions. Conclusions: Limited low-quality evidence exists on the effects of various interventions in children with EoE. The beneficial effects of swallowed steroid need to be confirmed in large well-designed RCTs.

103 A Randomised Trial Comparing Fish Oil (Smoflipid) vs. Olive Oil Lipid Emulsion (Clinoleic) in Preterm (< 30 Weeks) Neonates

Background Fat emulsions used in Australia for PN in preterm neonates have been based on either soybean oil (SO) or olive oil (OO). OO based lipid Clinoleic has high ratio of n-6 to n-3 fatty acids (9:1) this may not be ideal for LC-PUFA supply. Newly available SMOFlipid has appropriate ratio n-6 to n-3 fatty acids (2.5:1). SMOFlipid also contains OO (25%), coconut oil (30%) and SO (30%). Better lipid clearance, reducing the risk of liver toxicity, reduced oxidative stress, lower immune-activity and anti-inflammatory effects are other potential advantages of SMOFlipid. Method Preterm neonates (23–30 weeks) were randomised to receive Clinoleic or SMOFlipid emulsion for 7days using a standard protocol. Investigators and outcome assessors were masked to allocation. Plasma F2-Isoprostanes (lipid peroxidation marker), RBC fatty acids, vitamin-E were measured before and after the study. Blood culture positive sepsis and growth was monitored for safety. Results 30/34 participants (Clinoleic-15, SMOFlipid-15) completed the study. Both emulsions were well tolerated without any adverse events. F2-isoprostane levels were reduced in SMOFlipid group as compared to baseline. Eicosapentanoic acid (EPA) and vitamin-E levels were significantly increased in SMOFlipid group. Oleic and Linoleic acid levels were increased in both groups. No significant differences were noted in post study Docosahexaenoic acid (DHA) levels in both groups despite higher levels of DHA in SMOFlipid. Conclusions SMOFlipid was safe, well tolerated and also showed beneficial effect in terms of reduction of oxidative stress by reducing lipid peroxidation levels in high risk preterm neonates.