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Shah P.,KEM Hospital for Women | Nathan E.,Women and Infants Research Foundation | Doherty D.,Women and Infants Research Foundation | Patole S.,KEM Hospital for Women | Patole S.,University of Western Australia
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2015

Background: Optimising enteral nutrition of extremely preterm neonates (EP: Gestation <28 weeks) with intrauterine growth restriction (IUGR) has always been difficult considering their higher risk of necrotising enterocolitis (NEC), and frequency of feed intolerance.Aim: To evaluate the nutritional outcomes in EP neonates with IUGR.Methods: Data on demographic characteristics, feeding details (e.g. type of milk, postnatal age at start), and outcomes to discharge or death were collected from the medical notes for all EP neonates, who survived first 72 h of life, between January 2009 and December 2010. A standardised feeding protocol was followed during the study period.Results: 38/220 (17.3%) EP neonates admitted during the study period had IUGR. The mean (IQR) age at start of minimal enteral nutrition [7 (5-10) versus 5 (4-8) days, p = 0.005), and nutritional (1 ml/2hourly) feeds [12 (8-15) versus 9 (7-13) days, p = 0.034] was significantly delayed in IUGR compared to non-IUGR neonates. IUGR neonates reached full enteral feeds (150 ml/kg/day) at a significantly late median (IQR) postnatal age [32 (21-40) versus 24 (17-31) days, p = 0.009), taking longer time to achieve this milestone [20 (15-34) versus 16 (12-4) days, p = 0.008). The incidence of postnatal growth restriction was significantly higher in IUGR versus non-IUGR (73% versus 45%, p = 0.003) neonates. The incidence of ≥ Stage II NEC was low [18/220 (8.1%)] to make valid statistical comparisons.Conclusion: Optimising enteral nutrition in growth restricted extremely preterm neonates is difficult using the current strategies for enteral nutrition. © 2014 Informa UK Ltd.

Shah P.,KEM Hospital for Women | Nathan E.,Women and Infants Research Foundation | Doherty D.,Women and Infants Research Foundation | Patole S.,KEM Hospital for Women | Patole S.,University of Western Australia
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2013

Background: Prolonged exposure to antibiotics (PEA) is associated with increased risk of necrotising enterocolitis (NEC), late onset sepsis (LOS) and death in preterm neonates. Aim: To evaluate PEA (≥4 d) for suspected (blood culture negative) sepsis and its association with NEC, LOS and death in extremely preterm (EP: Gestation <28 weeks) neonates. Methods: Data on demographic characteristics, antibiotic exposure for early onset sepsis (EOS) or LOS and outcomes to discharge/death were collected for 216 EP neonates admitted between 1/1/2009 and 31/12/2010. Results: All 216 neonates received antibiotics for suspected EOS; 120/216 (56%) had PEA. 137/216 who survived first 72 h of life, had suspected LOS [range 1-8 episodes], treated with antibiotics for median (IQR) duration of 8 (5-14) days. 89/216 had proven (blood culture positive) LOS [range 1-3 episodes], treated with antibiotics for median (IQR) duration of 10 (7-18) days. The incidence of and death due to ≥Stage II NEC was 17/216 (7.8%) and 5/17 (29.4%) respectively. PEA for suspected EOS was associated with proven LOS (OR: 2.1, 95% CI: 1.2-3.7, p = 0.013) after adjusting for gestation and IUGR, but not with NEC/death. Conclusion: PEA for ≥4 d for suspected EOS was associated with increased odds for proven LOS. © 2013 Informa UK Ltd.

Athalye-Jape G.,KEM Hospital for Women | More K.,KEM Hospital for Women | Patole S.,KEM Hospital for Women | Patole S.,University of Western Australia
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2013

Necrotising enterocolitis (NEC) continues to have significant mortality, and morbidity including neurodevelopmental impairment, especially in extreme preterm neonates needing surgery for the illness. The incidence of NEC has not changed significantly despite the advances in neonatal care. Preventing NEC thus remains a priority. Protecting the intestinal barrier function and controlling the excessive proinflammatory response by the preterm gut are perhaps the most important areas for research toward achieving this goal. Improved understanding of the role of innate immunity in the pathogenesis of the illness and progress in other areas means that novel strategies may become available for the prevention and treatment of NEC. Probiotics significantly reduce the risk of NEC. Evidence indicates that bovine lactoferrin could reduce both, sepsis and NEC. As new frontiers (e.g. oral erythropoietin, heparin binding epithelial growth factor, therapeutic hypothermia and stem cell therapy) are being explored, the benefits of antenatal glucocorticoids, breast milk and standardised feeding regimes must not be forgotten. Preventing sepsis and avoiding undue prolonged exposure to antibiotics and antacids will be equally important. Considering the multiple complex pathways involved in its pathogenesis, adopting a package of potentially better practices will be the most appropriate strategy for prevention and treatment of NEC. © 2013 Informa UK Ltd All rights reserved.

Ofek Shlomai N.,KEM Hospital for Women | Ofek Shlomai N.,Hebrew University of Jerusalem | Deshpande G.,Nepean Hospital Sydney | Deshpande G.,University of Sydney | And 4 more authors.
Neonatology | Year: 2013

Necrotizing enterocolitis (NEC) is a major cause of mortality (25%) and morbidity including recurrent sepsis, dependence on parenteral nutrition, need for surgery, and survival with short bowel syndrome in preterm very low birth weight infants. Mortality (45-100%) and morbidity including the risk of long-term neurodevelopmental impairment are higher in extremely preterm infants needing surgery for NEC. Systematic reviews of randomized controlled trials (RCT) indicate that probiotics significantly reduce the risk of NEC (RR 0.39; 95% CI 0.29-0.52; p < 0.00001) and all-cause mortality (RR 0.52; 95% CI 0.40-0.69; p < 0.00001) while facilitating enteral feeds in preterm infants. At present, data from 25 RCT (∼5,000 neonates) and reports on routine use (∼3,000 neonates) indicates that significant adverse effects of probiotics are rare. Despite the robust evidence, there is still reluctance in incorporating routine probiotic prophylaxis in clinical practice. If the goal is to have zero tolerance for NEC, then probiotic prophylaxis must be adopted as soon as possible. Current gaps in knowledge can be addressed by continued research while providing routine probiotic supplementation. We believe that the concept of evidence-based practice of medicine has been stretched too far in this case. Trial sequential analysis has already shown that the evidence for probiotic supplementation was conclusive after 10 trials. Results of the ongoing trials are unlikely to change the conclusions of the systematic reviews significantly. Currently we are at trial number 25; how many more trials do we need? What will it take to change clinical practice? © 2013 S. Karger AG, Basel.

Deshpande G.C.,Nepean Hospital Sydney | Deshpande G.C.,University of Sydney | Rao S.C.,KEM Hospital for Women | Rao S.C.,University of Western Australia | And 4 more authors.
BMC Medicine | Year: 2011

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. © 2011 Deshpande et al; licensee BioMed Central Ltd.

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