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Perinatal with allergy, immunity, and infection

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G80 HUMAN MILK AND INFECTION IN PRETERM INFANTS: A SYSTEMATIC REVIEW

P. A. de Silva1, S. A. Spencer2, P. W. Jones3. 1Department of Physiology, Faculty of Medicine, Colombo, Sri Lanka; 2Neonatal Unit, Women and Children’s Division, University Hospital of North Staffordshire, Stoke-on-Trent; 3Department of Mathematics, Keele University, UK

Introduction: Among the many reasons used to advocate human milk feeding in preterm, low birthweight (LBW) infants is the surmise that human milk (HM) protects against infections. Clinical trials reporting an association between HM feeding and infection are few and the quality of existing research raises issues concerning interpretation of data from these trials.

Objective: To evaluate the available evidence on feeding HM v preterm formula on infection rates in preterm LBW infants.

Data Sources: Medline, Embase, Cinahl, Cochrane databases, previous reviews including cross references.

Selection Criteria: Any trials that investigated infection as an outcome of feeding HM v preterm formula in preterm infants <1500 g.

Results: Nine trials fulfilled the inclusion criteria. A total of 1136 infants (randomised controlled trials (RCT) n = 362, cohort studies n = 774) were studied. The number of exclusively HM fed infants were n = 113 (31.2 %) and n = 86 (11.1 %) in the RCTs and cohort studies, respectively. All nine trials reported significant reductions in infection rates in the HM groups compared with preterm formula. Methodological flaws relating to study design, sample size, varying definitions of HM feeding, and inadequate adjustment of covariates were present in all studies.

Conclusions: Despite the available data it is not possible to conclude that feeding HM protects preterm infants from infections. This review focuses on issues that affect the scientific validity and generalisability of the existing studies and the design of future studies that would circumvent the flaws found in current trials.

G81 PROPHYLACTIC INTRAVENOUS ANTIFUNGAL THERAPY FOR VLBW INFANTS: SYSTEMATIC REVIEW AND META-ANALYSIS

L. Clerihew1, N. Austin2, W. McGuire1. 1Tayside Institute of Child Health, Ninewells Hospital & Medical School, Dundee, UK; 2Neonatal Unit, Christchurch Women’s Hospital, Christchurch, New Zealand

Background: Invasive fungal infection is an increasingly common cause of mortality and morbidity in very low birth weight (VLBW) infants. As the diagnosis is often difficult, and treatment is often delayed, there is a need to assess whether antifungal prophylaxis is beneficial.

Aims: To assess the available evidence that prophylactic intravenous antifungal therapy prevents invasive fungal infection and reduces mortality and adverse neurodevelopmental outcomes in VLBW infants.

Methods: Cochrane systematic review and meta-analysis. We used the standard methods of the Cochrane Neonatal Review Group to identify and appraise randomised controlled trials that compared the effect of prophylactic intravenous antifungal therapy v placebo, or no drug, in VLBW infants. The primary outcomes were invasive fungal infection, death prior to hospital discharge, and longer term neurodevelopment.

Findings: We identified three trials enrolling a total of 214 infants.1,3 All compared the effect of prophylactic intravenous fluconazole v placebo. In meta-analyses, fluconazole prophylaxis was associated with a significantly reduced risk of invasive fungal infection (RR 0.20 (95% CI 0.07 to 0.64); NNT 8 (5 to 20)) and death (RR 0.44 (0.21 to 0.91); NNT 9 (5 to 50)). None of the trials reported longer term neurodevelopmental outcomes.

Conclusions: This systematic review suggests that there will be one fewer death in every nine infants treated with prophylactic fluconazole, but the 95% CI around this estimate of effect is wide. Further large randomised controlled trials are needed to give a more precise estimate of effect, and to assess the long term neurodevelopmental consequences of this intervention. There is also a need for further data on the effect on the emergence of antifungal resistance.

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G82 HEPATITIS B ANTENATAL SCREENING AND INFANT IMMUNISATION PROGRAMME—A REVIEW OF THE CURRENT PROBLEMS FACED

M. Nolan, D. Keady, P. Taylor, H. Mistry, M. Kyi, M. Atkins. Department of Diagnostic Virology, St Mary’s Hospital, Praed Street, London W2 1NY, UK

Background: Babies born to chronic hepatitis B carriers have a 25% risk of perinatal infection. Of those infants infected at birth, 90% will become chronic carriers, compared with 5–10% of individuals infected as adults. Universal antenatal screening for hepatitis B with subsequent neonatal hepatitis B virus (HBV) vaccination of at risk infants reduces the risk of chronic carriage by up to 90%, thus rendering this measure highly effective. In July 1998 the Department of Health (DoH) recommended that all pregnant women be offered antenatal screening for hepatitis B and that all health authorities make arrangements for such a screening programme and for appropriate immunisation and follow up of babies born to infected mothers.

Objectives: The correlation of HBV viral load and hepatitis B serological status was analysed on antenatal sera samples, to determine the reliability of serological status in assessing infectivity. In addition, characterisation of adherence with the 1998 DoH recommendations for hepatitis B antenatal screening and infant immunisation was viewed in an area of west London. Any existing problems with this programme were identified and missed opportunities for prevention of HBV perinatal infection reviewed.

Methods: All HBsAg positive antenatal women were included over a 2 year period. Demographic and HBV vaccination information was abstracted from antenatal, labour, and neonatal notes. Information on HBV vaccine course completion in the community was obtained. Any racial disparity in vaccine uptake was viewed. Serum quantification of hepatitis B viral DNA was performed on HBV infected antenatal patients. The viral loads obtained were matched with patient serological status, allowing review of serological status as a marker for infectivity in the antenatal setting.

Results: In our antenatal cohort the serological absence of HBeAg did not exclude viral replication. Of our samples, 31% of HBeAg negative samples had detectable HBV DNA, and 24% had HBV DNA of >104 copies/ml. For HBV vaccination, the numbers with no vaccine record rose steeply over the scheduled course and only 6% were known to have received the fourth dose of vaccine. Problems were assessed.

Conclusion: Serological absence of maternal HBeAg does exclude viral replication. Adherence to DoH recommendations for HBV perinatal disease prevention could be improved, reducing chronic hepatitis B carriage in newborns. Follow up serology could not be found on the majority of babies. Thus, the long term morbidity and economic burden secondary to missed opportunities for hepatitis B prevention is difficult to fully assess.

G83 IMPACT OF A MULTIFACTORIAL PREVENTION STRATEGY ON NOSOCOMIAL INFECTION IN A TERTIARY NEWBORN NEONATAL NURSERY

Aims: To reduce the rate and impact of nosocomial infection.

Methods: Infants requiring an intravascular device between Feb 02 and Feb 03 were included. The first 6 month interval (control) included surveillance of current practice. Staff participated in an education and hand washing session. The intervention began in the 7th month and included (a) changes to hand washing solutions, (b) standardisation of device insertion with specialised packs, (c) changes to skin antiseptic solutions (2% aqueous chlorhexidine and/or 1% chlorhexidine in ethanol), and (d) mandatory removal/replacement of all intravascular devices after 48 h with removal of all devices once enteral feeds were >120 mls/kg/day.

Measurements: Demographic data and details of all intravascular devices were collected. Blood stream infections were recorded. The rate of device related infection was calculated. Length of stay (LOS) and death were recorded.

Results: 676 newborns required 2719 devices. There was a significant reduction in device related infection (3.4 v 1.2 per 10000 device hours, p 0.006). There was weak evidence of reductions in median LOS (10 to 8 days, p 0.02) and mortality (7% to 5%, p 0.14). Four infants had complications from 2% aqueous chlorhexidine.

Conclusion: Implementation of a prevention strategy resulted in a reduction in device related infections. Modification of antiseptic solutions is needed to reduce complications from 2% aqueous chlorhexidine.

Abstract G83

G84 ASSOCIATION BETWEEN CYTOKINES AND HAEMODYNAMICS IN LOW BIRTHWEIGHT INFANTS

S. Victor, E. Gaillard, A. E. Harling, A. M. Weindling. Neonatal Intensive Care Unit, Liverpool Women’s Hospital and Department of Child Health, University of Liverpool

Introduction: Chorioamnionitis has been associated with white matter brain injury. The exact mechanism has not been clearly determined. Furthermore, the watershed distribution of white matter injury suggests that ischaemia may play a role. We hypothesised that elevated cytokine levels associated with chorioamnionitis may have an effect on the smooth muscle of the heart and vasculature. This study aimed to determine if elevated levels of cytokines were associated with decreased cardiac output and low blood pressure.

Methods: 21 infants with median gestational age of 27 weeks (range 23–30) and median birthweight of 935 g (470–1522) were studied during the first day after birth. Interleukin 10 (IL 10), IL 6, IL 1β, and Tumour Necrosis Factor α (TNF α) were measured in bronchoalveolar lavage samples using two techniques (bead array technology and standard ELISA). Left and right ventricular cardiac outputs were measured using echocardiography. Mean blood pressure was recorded using arterial catheters. Cerebral fractional oxygen extraction was measured in eight infants. Mann-Whitney tests were used to analyse differences.

Results: All data are given as (median, range). Nine infants with left ventricular output less than 150 ml/kg/min had significantly higher levels of IL 10 (209 pg/ml, 0–1113) than 13 infants with left ventricular output higher than 150 ml/kg/min (60 pg/ml, 0–629) (p 0.015). Five infants with right ventricular output less than 150 mls/kg/min had significantly higher levels of IL 10 (552 pg/ml, 110–1113) than 16 infants with right ventricular output higher than 150 ml/kg/min (44 pg/ml, 0–254) (p 0.004). Five infants with mean blood pressure less than 30 mm Hg had higher levels of IL 1β (p 0.008), TNF α (p 0.036), and IL 10 (p 0.055) than 16 infants with mean blood pressure more than 30 mm Hg. Cubic regression showed that cerebral fractional oxygen extraction increased at higher levels of IL 10 (Rsq 0.86; p 0.008).

Conclusion: High levels of cytokines are associated with low cardiac output and hypotension. Cytokines may have a depressant effect on cardiac function and vascular tone, which may decrease cerebral perfusion.

G85 THE ROLE OF HYPOXIA AND ENDOTOXIN IN A PIGLET MODEL OF ADVANCED NECROTISING ENTEROCOLITIS (NEC)

A. S. Dhillon1,2, W. Al-Salti3, J. M. Marshall1, A. D. Lander4, I. W. Booth4, A. K. Ewer2,4. 1University of Birmingham; 2Birmingham Women’s Hospital; 3Birmingham Children’s Hospital; 4Institute of Child Health, Birmingham, UK

Background: Hypoxia and bacterial colonisation are major risk factors for NEC.

Aim: To investigate the role of hypoxia and endotoxin (lipopolysaccharide, LPS), both singly and in combination, on the degree of intestinal damage in a neonatal piglet model of NEC.

Methods: 29 anaesthetised piglets, median age 2 days and weight 1861 g, were studied. Animals formed five groups: controls (n = 9); hypoxia (H) (n = 5); high dose LPS group (n = 5); H+low dose LPS (n = 5); and H+high dose LPS (n = 5). Heart rate, mean arterial blood pressure (MBP), and arterial acid base status were recorded. After 6 h the internal organs were removed for examination.

Results: All physiological parameters were stable in controls. In the H, LPS, and H+low LPS groups the pH remained stable throughout. However, the H+high LPS group became significantly more acidaemic (mean pH fell from 7.43 to 7.10; p<0.001). In the H group MBP remained stable throughout. However, in the three groups receiving LPS there was a fall in MBP. Degree of fall was significantly greater in the H+high LPS group (95 to 48 mm Hg, p 0.009). Pathological examination of the intestines from all controls was normal. In the H group and LPS group all intestines showed congestion and patchy mild neutrophil infiltration only. In one animal in the H group there was a small petechial mucosal haemorrhage in the caecum. Pathological examination of the H+low LPS group showed patchy intraluminal and mucosal intestinal haemorrhage in 2/5 and mucosal ulceration in 3/5. In the H+high LPS group there was epithelial apoptosis with inflammation in 1/5; villous irregularity and mucosal haemorrhage in 1/5, and mucosal ulceration and transmural haemorrhagic necrosis of the ileum and caecum in 3/5. Pneumatosis intestinalis was present in 4/10 of the combined insult groups. In all these cases the histological features were indistinguishable from those of human NEC.

Conclusion: These results indicate that hypoxia and endotoxin act synergistically to produce the intestinal lesions in our model for NEC. This may have important implications for the development of NEC in human infants.

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