Early life nutrition and the opportunity to influence long-term health: an Australasian perspective.

There are now significant data to support the hypothesis that early life nutrition in the fetus, infant and young child can have profound effects on long-term health. This review considers some of this evidence with specific reference to the current burden of disease in Australia and New Zealand. As the findings of further research become available, recommendations on optimizing early life nutrition should be formulated and made widely available as part of the preventative health policy agenda in both Australia and New Zealand.

Erwinia amylovora pyrC mutant causes fire blight despite pyrimidine auxotrophy.

Erwinia amylovora bacteria cause fire blight disease, which affects apple and pear production worldwide. The Erw. amylovora pyrC gene encodes a predicted dihydroorotase enzyme involved in pyrimidine biosynthesis. Here, we discovered that the Erw. amylovora pyrC244::Tn5 mutant was a uracil auxotroph. Unexpectedly, the Erw. amylovora pyrC244::Tn5 mutant grew as well as the wild-type in detached immature apple and pear fruits. Fire blight symptoms caused by the pyrC244::Tn5 mutant in immature apple and pear fruits were attenuated compared to those caused by the wild-type. The pyrC244::Tn5 mutant also caused severe fire blight symptoms in apple tree shoots. A plasmid-borne copy of the wild-type pyrC gene restored prototrophy and symptom induction in apple and pear fruit to the pyrC244::Tn5 mutant. These results suggest that Erw. amylovora can obtain sufficient pyrimidine from the host to support bacterial growth and fire blight disease development, although de novo pyrimidine synthesis by Erw. amylovora is required for full symptom development in fruits. Significance and impact of the study: This study provides information about the fire blight host-pathogen interaction. Although the Erwinia amylovora pyrC mutant was strictly auxotrophic for pyrimidine, it grew as well as the wild-type in immature pear and apple fruits and caused severe fire blight disease in apple trees. This suggests that Erw. amylovora can obtain sufficient pyrimidines from host tissue to support growth and fire blight disease development. This situation contrasts with findings in some human bacterial pathogens, which require de novo pyrimidine synthesis for growth in host blood, for example.

Prebiotics in infants for prevention of allergic disease and food hypersensitivity.

BACKGROUND: The composition of the intestinal microflora may be different in individuals with atopic eczema from those without this condition, and such differences may precede the development of eczema. Prebiotics are nondigestible food components that benefit the host by selectively stimulating the growth or activity of non-pathogenic bacteria in the colon. Prebiotics (commonly oligosaccharides) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens. OBJECTIVES: To determine the effect of prebiotics given to infants for the prevention of allergic disease or food hypersensitivity. SEARCH STRATEGY: This included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (1966 - February 2007), EMBASE, PREMEDLINE, abstracts of conference proceedings and citations of published articles, and expert informants. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared the use of a prebiotic to no prebiotic; or the use a specific prebiotic compared to a different prebiotic. DATA COLLECTION AND ANALYSIS: Assessment of trial quality, data extraction and synthesis of data were performed using standard methods of the Cochrane Neonatal Review Group. MAIN RESULTS: Seven studies were eligible for inclusion. Only two studies reported an allergic disease outcome for 432 infants. Study quality was reasonable, although Moro 2006 reported 20% post-randomisation losses. Moro 2006 enrolled hydrolysed formula fed infants at high risk of allergy and reported a significant reduction in eczema in infants up to six months of age (RR 0.42, 95% CI 0.21, 0.84). Ziegler 2007 enrolled formula fed infants who were not selected on the basis of risk for allergy and reported no significant difference in eczema up to four months of age (RR 1.62, 95% CI 0.62, 4.26). Meta-analysis of the two studies found no significant difference in eczema, but significant heterogeneity was detected. Differences were potentially attributable to differences in infant risk, prebiotic formulation or measurement of eczema. Analysis of five studies reporting measures of infant growth found no consistent adverse effects. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the role of prebiotic supplementation of infant formula for prevention of allergic disease and food hypersensitivity. One small trial of prebiotic oligosaccharides with excess losses reported a reduction in eczema in high risk formula fed infants. Further trials are needed to determine whether this finding persists over a longer period of time, applies to other manifestations of allergic disease, is associated with reductions in allergen sensitisation, and is reproducible.

Probiotics in infants for prevention of allergic disease and food hypersensitivity.

BACKGROUND: The composition of the intestinal microflora may be different in individuals with atopic eczema from those without this condition, and such differences may precede the development of eczema. Probiotics are live bacteria that colonize the gastrointestinal tract and provide a health benefit to the host. Probiotics added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens. OBJECTIVES: To determine the effect of probiotics given to infants for the prevention of allergic disease or food hypersensitivity. SEARCH STRATEGY: This included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (1966 - February 2007), EMBASE, PREMEDLINE, abstracts of conference proceedings and citations of published articles, and expert informants. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compare the use of a probiotic to no probiotic; or the use a specific probiotic compared to a different probiotic; or a probiotic with added prebiotic to control. DATA COLLECTION AND ANALYSIS: Assessment of trial quality, data extraction and synthesis of data were performed using standard methods of the Cochrane Neonatal Review Group. MAIN RESULTS: Twelve studies were eligible for inclusion. Allergic disease and / or food hypersensitivity outcomes were assessed by 6 studies enrolling 2080 infants, but outcomes for only 1549 infants were reported. Studies generally had adequate randomisation, allocation concealment and blinding of treatment. However, the findings of this review should be treated with caution due to excess losses in patient follow-up (17% to 61%). Meta-analysis of five studies reporting the outcomes of 1477 infants found a significant reduction in infant eczema (typical RR 0.82, 95% CI 0.70, 0.95). However, there was significant and substantial heterogeneity between studies. One study reported that the difference in eczema between groups persisted to 4 years age. When the analysis was restricted to studies reporting atopic eczema (confirmed by skin prick test or specific IgE), the findings were no longer significant (typical RR 0.80, 95% CI 0.62, 1.02). All studies reporting significant benefits used probiotic supplements containing L. rhamnosus and enrolled infants at high risk of allergy. No other benefits were reported for any other allergic disease or food hypersensitivity outcome. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the addition of probiotics to infant feeds for prevention of allergic disease or food hypersensitivity. Although there was a reduction in clinical eczema in infants, this effect was not consistent between studies and caution is advised in view of methodological concerns regarding included studies. Further studies are required to determine whether the findings are reproducible.

Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.

BACKGROUND: Allergies and food reactions are common and may be associated with foods including adapted cow's milk formula. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance. However, it is unclear whether hydrolysed formula can be advocated for prevention of allergy and food intolerance in infants without evidence of allergy or food intolerance. OBJECTIVES: To determine the effect of feeding hydrolysed formulas on allergy and food intolerance in infants and children compared to adapted cow's milk or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit, including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. The review was updated with searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966-March 2006), EMBASE (1980-March 2006) and CINAHL (1982-March 2006) and previous reviews including cross references. SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with >80% follow up of participants were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model. MAIN RESULTS: Two trials compared early, short term hydrolysed formula to human milk feeding. No significant difference in infant allergy or childhood cow's milk allergy (CMA) were reported. No eligible trial compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to cow's milk formula feeding. No significant benefits were reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00). Ten eligible studies compared prolonged feeding with hydrolysed formula versus cow's milk formula in high risk infants. Meta-analysis found a significant reduction in infant allergy (seven studies, 2514 infants; typical RR 0.79, 95% CI 0.66, 0.94), but not in the incidence of childhood allergy (two studies, 950 infants; typical RR 0.85, 95% CI 0.69, 1.05). There was no significant difference in infant eczema (eight studies, 2558 infants, typical RR 0.84, 95% CI 0.68, 1.04), childhood eczema incidence (two studies, 950 infants, typical RR 0.83, 95% CI 0.63, 1.10), childhood eczema prevalence (one study, 872 infants; RR 0.66, 95% CI 0.43, 1.02), or infant or childhood asthma, rhinitis and food allergy. One study reported a significant reduction in infants with CMA with confirmed atopy (RR 0.36, 95% CI 0.15, 0.89). Subgroup analysis of trials blinded to formula found no significant difference in infant allergy (four studies, 2156 infants; typical RR 0.87, 95% CI 0.69, 1.08) or childhood allergy incidence (one study, 872 infants; RR 0.91, 95% CI 0.73, 1.14). No eligible trial examined the effect of prolonged hydrolysed formula feeding on allergy beyond early childhood. There is evidence that preterm or low birthweight infants fed a hydrolysed preterm formula have significantly reduced weight gain, but not in other growth parameters (head circumference or length). Studies in term infants report no adverse effects on growth. Subgroup analysis of trials of partially hydrolysed versus cow's milk formula found a significant reduction in infant allergy (six studies, 1391 infants; typical RR 0.79, 95% CI 0.65, 0.97) but not childhood allergy, or infant or childhood asthma, eczema or rhinitis. Methodological concerns were the same as for the overall analysis. Analysis of trials of extensively hydrolysed formula versus cow's milk formula found no significant differences in allergy or food intolerance. Infants fed extensively hydrolysed formula compared with partially hydrolysed formula had a significant reduction in food allergy (two studies, 341 infants; typical RR 0.43, 95% CI 0.19, 0.99), but there was no significant difference in all allergy or any other specific allergy incidence. Comparing extensively hydrolysed casein containing formula with cow's milk formula, one study (431 infants) reported a significant reduction in childhood allergy incidence (RR 0.72, 95% CI 0.53, 0.97). Meta-analysis found a significant reduction in infant eczema (three studies, 1237 infants; typical RR 0.71, 95% CI 0.51, 0.97). One study reported a significant reduction in childhood eczema incidence (RR 0.66, 95% CI 0.44, 0.98) and prevalence (RR 0.50, 95% CI 0.27, 0.92). AUTHORS' CONCLUSIONS: There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy compared to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is limited evidence that prolonged feeding with a hydrolysed formula compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. In view of methodological concerns and inconsistency of findings, further large, well designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed.

Soy formula for prevention of allergy and food intolerance in infants.

BACKGROUND: Allergies and food reactions in infants and children are common and may be associated with a variety of foods including adapted cow's milk formula. Soy based formulas have been used to treat infants with allergy or food intolerance. However, it is unclear whether they can help prevent allergy and food intolerance in infants without clinical evidence of allergy or food intolerance. OBJECTIVES: To determine the effect of feeding adapted soy formula compared to human milk, cow's milk formula or a hydrolysed protein formula on preventing allergy or food intolerance in infants without clinical evidence of allergy or food intolerance. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. Updated searches were performed of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966-March 2006), EMBASE (1980-March 2006), CINAHL (1982-March 2006) and previous reviews including cross references. SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of an adapted soy formula to human milk, an adapted cow's milk or a hydrolysed protein formula for feeding infants without clinical allergy or food intolerance in the first six months of life. Only trials with > 80% follow up of participants and reported in group of assignment were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Where no heterogeneity of treatment effect was found, the fixed effect model was used for meta-analysis. Where significant or apparent heterogeneity was found, results were reported using the random effects model and potential causes of the heterogeneity were sought. MAIN RESULTS: Three eligible studies enrolling high risk infants with a history of allergy in a first degree relative were included. No eligible study enrolled infants fed human milk. No study examined the effect of early, short term soy formula feeding. All compared prolonged soy formula to cow's milk formula feeding. One study was of adequate methodology and without unbalanced allergy preventing co-interventions in treatment groups. One study with unclear allocation concealment and 19.5% losses reported a significant reduction in infant allergy, asthma and allergic rhinitis. However, no other study reported any significant benefits from the use of a soy formula. Meta-analysis found no significant difference in childhood allergy incidence (2 studies; typical RR 0.73, 95% CI 0.37, 1.44). No significant difference was reported in one study in infant asthma (RR 1.10, 95% CI 0.86, 1.40), infant eczema (RR 1.20, 95% CI 0.95, 1.52), childhood eczema prevalence (RR 1.10, 95% CI 0.73, 1.68), infant rhinitis (RR 0.94, 95% CI 0.76, 1.16) or childhood rhinitis prevalence (RR 1.20, 95% CI 0.73, 2.00). Meta-analysis found no significant difference in childhood asthma incidence (3 studies, 728 infants; typical RR 0.71, 95% CI 0.26, 1.92), childhood eczema incidence (2 studies, 283 infants; typical RR 1.57, 95% CI 0.90, 2.75) or childhood rhinitis incidence (2 studies, 283 infants; typical RR 0.69, 95% CI 0.06, 8.00). One study reported no significant difference in infant CMPI (RR 1.09, 95% CI 0.45, 2.62), infant CMA (RR 1.09, 95% CI 0.24, 4.86), childhood soy protein allergy incidence (RR 3.26, 95% CI 0.36, 29.17) and urticaria. No study compared soy formula to hydrolysed protein formula. AUTHORS' CONCLUSIONS: Feeding with a soy formula cannot be recommended for prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance. Further research may be warranted to determine the role of soy formulas for prevention of allergy or food intolerance in infants unable to be breast fed with a strong family history of allergy or cow's milk protein intolerance.

Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants.

BACKGROUND: Parenteral nutrition solutions, formula milks, and human breast milk contain insufficient iodine to meet recommended intakes for preterm infants. Iodine deficiency may exacerbate transient hypothyroxinaemia in preterm infants and this may be associated with adverse respiratory or neurological outcomes. OBJECTIVES: To assess the evidence from randomised controlled trials that dietary supplementation with iodine reduces mortality and morbidity in preterm infants. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2005), MEDLINE (1966 - November 2005), EMBASE (1980 - November 2005), CINAHL (1982 - November 2005), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared a policy of supplementing enteral or parenteral feeds with iodine (more than 30 micrograms per kilogram per day) versus placebo or no supplementation in preterm infants. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewers, and synthesis of data using relative risk, risk difference and weighted mean difference. The primary outcomes for this review were neonatal mortality, death before hospital discharge, and longer term neurodevelopmental outcomes including severe neurodevelopmental disability. MAIN RESULTS: We found only one randomised controlled trial (N = 121) that fulfilled the review eligibility criteria (Rogahn 2000). The participants were infants born before 33 weeks' gestation (but most were of birth weight greater than 1000 grams). The primary aim of this trial was to assess the effect of iodine supplementation on thyroid function. The investigators did not detect any statistically significant effects on the plasma levels of thyroxine (free and total), triiodothyronine, or thyrotrophin in preterm infants (measured up to 40 weeks' post-conceptional age). Only one infant died and the trial was therefore underpowered to detect an effect on mortality. The trial did not assess the effect of the intervention on neurodevelopmental morbidity. There was not a statistically significant difference in the incidence of chronic lung disease. AUTHORS' CONCLUSIONS: There are insufficient data at present to determine whether providing preterm infants with supplemental iodine (to match fetal accretion rates) prevents morbidity and mortality in preterm infants. Future randomised controlled trials of iodine supplementation should focus on extremely preterm and extremely low birth weight infants, the group at greatest risk of transient hypothyroxinaemia. These trials should aim to assess the effect of iodine supplementation on clinically important outcomes including respiratory morbidity and longer term neurodevelopment.

Soy formula for prevention of allergy and food intolerance in infants.

BACKGROUND: Allergies and food reactions in infants and children are common and may be associated with foods including adapted cow's milk formulas. Soy based formulas have been used to treat infants with allergy or food intolerance. However, it is unclear whether they can be advocated for the prevention of allergy and food intolerance in infants without clinical evidence of allergy or food intolerance. OBJECTIVES: In infants without clinical evidence of allergy or food intolerance, to determine whether feeding them an adapted soy formula compared to human milk, cow's milk formula or a hydrolysed protein formula prevents allergy or food intolerance. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used including searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2003), MEDLINE (1966 - January 2004), EMBASE (1980 - January 2004), CINAHL (1982 - December 2003) and previous reviews including cross references. SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of an adapted soy formula to human milk, an adapted cow's milk or a hydrolysed protein formula for infant feeding in the first 6 months. Only trials with > 80% follow up of participants and reported in group of assignment were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each reviewer. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model where no heterogeneity of treatment effect existed, and a random effects model when heterogeneity was found. MAIN RESULTS: Five eligible studies were found, all enrolling infants at high risk of allergy on the basis of a family history of allergy in a first degree relative. All studies compared use of a soy to a cow's milk formula. Two studies also included a group fed a formula containing hydrolysed protein. No eligible study enrolled infants fed human milk. No study examined the effect of early, short term soy formula feeding. Three studies were of good methodology and did not have unbalanced allergy-preventing co-interventions in the treatment groups. Comparing soy to cow's milk formula, one study with unclear allocation concealment and 19.5% losses to follow up reported a reduction in cumulative incidence of childhood allergy, asthma and allergic rhinitis. No other study reported a significant benefit for any allergy or food intolerance. Analysis found no significant difference in allergy cumulative incidence in infancy (one study: RR 1.02, 95% CI 0.69, 1.49) or childhood (3 studies: typical RR 0.73, 95% CI 0.37, 1.44) and no significant difference in cumulative incidence or period prevalence of any specific allergy or food intolerance in infancy or childhood. Analysis of studies comparing soy to a hydrolysed formula found a significant increase in infant (one study: RR 1.67, 95% CI 1.03, 2.69) and childhood allergy cumulative incidence (one study: RR 1.55, 95% CI 1.02, 2.35), infant eczema cumulative incidence (2 studies: typical RR 2.34, 95% CI 1.51, 3.62) and childhood food allergy period prevalence (one study: RR 1.81, 95% CI 1.09, 3.02). REVIEWERS' CONCLUSIONS: Feeding with a soy formula should not be recommended for the prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance.

Steroid therapy for meconium aspiration syndrome in newborn infants.

BACKGROUND: Meconium aspiration syndrome may cause severe respiratory distress in the newborn infant, with an associated high morbidity and mortality. A chemical pneumonitis is believed to occur secondary to bile, bile acids and pancreatic secretions contained in meconium. It has therefore been hypothesised that corticosteroids may be of benefit in the management of this condition through their anti-inflammatory properties. OBJECTIVES: The objective of this review was to determine whether steroid therapy for meconium aspiration syndrome decreases the morbidity and mortality associated with this condition without adverse effects. SEARCH STRATEGY: Searches were made of PREMEDLINE and MEDLINE from 1966 to April 2003, CINAHL back to 1982, Current Contents back to 1998, The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2003) and Oxford Database of Perinatal Trials. The search included cross-referencing of previous reviews, and a review of abstracts, conference and symposia proceedings published in Pediatric Research from 1993 to 2003. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials comparing steroid treatment to no steroid treatment for neonates with meconium aspiration syndrome were considered for this review. DATA COLLECTION AND ANALYSIS: The methodological quality of each trial was assessed independently by each author. Data were extracted, analysed and results reviewed independently by each author. Meta-analysis was performed with RevMan 4.2, using the fixed effects model. Mean difference (MD) and weighted mean differences (WMD) with 95% confidence intervals in brackets for continuous variables and Relative Risk (RR) with 95% confidence intervals for categorical data were reported. MAIN RESULTS: Three randomised controlled trials were identified. Two trials, by Wu 1999 (50 participants) and Yeh 1977 (35 participants), were included in the review. The trial by Davey 1995, as yet unpublished, was excluded from this review as insufficient information about methodology and results were available. On meta-analysis, there was no significant reduction in mortality [typical RR 0.95 (0.20, 4.58)]. A small but significant increase in duration of oxygen therapy was seen with the use of steroids [WMD 30.0 hours (8.4, 51.6)]. There was no significant difference in duration of hospital stay in the study by Wu 1999 [MD 0.00 days (-3.09, 3.09)]. Duration of mechanical ventilation was reported by Wu 1999 with no significant difference seen [MD -1.10 days (-2.79, 0.59)]. Incidence of air leak was reported by Yeh 1977 with no significant difference detected [RR 0.64 (0.18, 2.26)]. Long-term outcome was not reported in either of the two studies. REVIEWER'S CONCLUSIONS: At present, there is insufficient evidence to assess the effects of steroid therapy in the management of meconium aspiration syndrome. A further large randomised controlled trial assessing potential benefits and harm would be required to determine its role.

Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.

BACKGROUND: Allergies and food reactions are common and may be associated with foods including adapted cow's milk formulas. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance, and have been advocated for prevention of allergy and food intolerance in infants. OBJECTIVES: To determine whether use of hydrolysed formulas for infant feeding prevents allergy and food intolerance. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used including searches of the Cochrane Controlled Trials Register (2003, Issue 1), MEDLINE (1966 - January 2003), EMBASE (1980 - January 2003) and CINAHL (1982 - January 2003) and previous reviews including cross references. SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with >80% follow up of participants were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each reviewer. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model. MAIN RESULTS: Eighteen trials met criteria for inclusion. No eligible trials compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to human milk feeding and reported no significant difference in infant allergy or childhood cow's milk allergy (CMA). Two trials compared early, short term hydrolysed formula to cow's milk formula feeding with no significant benefits reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00).Seven studies compared prolonged feeding of hydrolysed formula to cow's milk formula without using co-interventions for allergy prevention. Meta-analysis of 4 studies (386 infants) found a significant reduction in allergy incidence in infancy (typical RR 0.63, 95% CI 0.47, 0.85; RD -0.15, 95% CI -0.25, -0.06). One study reported a significant reduction in allergy incidence in childhood (RR 0.54, 95% CI 0.36, 0.81). Significant reductions were found in asthma prevalence in childhood, eczema incidence in infancy and prevalence in childhood, food allergy prevalence in childhood, and CMA incidence in infancy. All studies enrolled infants at high risk of allergy. Only three trials comparing prolonged hydrolysed formula feeding to cow's milk formula feeding were considered of good methodology. Only one of these trials demonstrated a benefit into childhood (5 years of age). No eligible trials examined the effects of prolonged hydrolysed formula feeding on allergy beyond early childhood. Costs were not reported. Three trials compared prolonged feeding with an extensive to a partially hydrolysed formula and reported no significant difference in allergy incidence in infancy. REVIEWER'S CONCLUSIONS: There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy in preference to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is evidence that prolonged feeding with a hydrolysed compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. Further trials are required to determine if significant clinical benefits persist beyond 5 years of age and if there is any additional benefit from use of an extensive compared to a partially hydrolysed formula. Incremental costs of formula and the effect on compliance should be measured.

Developmental outcome of preterm infants after surfactant therapy: systematic review of randomized controlled trials.

OBJECTIVES: To review neuro-developmental outcome at 1 and 2 years of age following randomized controlled trials (RCT) of neonatal surfactant therapy. METHODS: A systematic review of the MEDLINE, Embase and Cochrane Controlled Trial Register databases, searching for RCT of surfactant replacement therapy with follow-up outcomes, was carried out. The main outcome measures were severe and mild disability at 1 and 2 years plus composite adverse outcome of death and/or severe disability. RESULTS: A meta-analysis using odds ratios was carried out on 13 RCT. There were a total of 2218 treated and 2090 control infants who underwent follow up at 1 year of age. There were 303 treated and 292 control infants with follow up at between 18 months and 2 years of age. Surfactant therapy was associated with a lower rate of mild disability at 1 year (OR 0.79; 95% CI 0.66-0.95). There was a reduction in the combined adverse outcome (death or severe disability rate) at 1 year (OR 0.8; 95% CI 0.72-0.89). Neither the 1 year nor the 2 year follow-up examination showed a statistical difference in the severe disability rate between the control and treated group. CONCLUSION: Surfactant therapy increases survival without an increase in subsequent morbidity at 1 and 2 years of age.

Umbilical cord blood lactate in normal infants: comparison between two methods of measurement.

OBJECTIVES: Firstly, to determine the accuracy of the Radiometer ABL 625 lactate electrode (Radiometer Medical Pty Ltd, Nunawading, Victoria, Australia) by comparing the lactate values obtained by this method to those obtained with the Hitachi 917 lactate analyser (Boehringer Mannheim Corporation, Charlottetown, Prince Edward Island, Canada). Secondly, to determine the effect of delay in measurement on blood lactate levels. METHODOLOGY: Umbilical venous (UCV) blood samples were obtained from healthy term infants delivered vaginally. Lactate levels were measured with the Radiometer ABL 625 lactate electrode in the Neonatal Intensive Care Unit, Westmead Hospital and with the Hitachi 917 lactate analyser in 49 paired samples. In addition 26 UCV blood samples were placed in ice slurry and a further 26 samples at room temperature and blood lactate was measured at 5-min intervals for 30 min to determine the change of lactate levels with time. RESULTS: The lactate levels obtained from the Radiometer ABL 625 lactate electrode were consistently lower than the levels obtained from the Hitachi 917 lactate analyser (mean difference - 0.24), but the correlation was high (r = 0.97). The blood lactate levels increased at the rate of 0.012 mmol/L per min if the blood was left at room temperature. The lactate levels remained stable for 20 min if the blood was placed in ice slurry. CONCLUSION: The Radiometer ABL 625 lactate electrode was easy to use and there was high correlation with the values obtained by the standard laboratory method. The blood specimen must be place in an ice slurry if a delay in analysis is anticipated.

Effect of method of defining the active patient population on measured immunization rates in predominantly Medicaid and non-Medicaid practices.

OBJECTIVE: To examine the effect of patient selection criteria on immunization practice assessment outcomes. METHODS: In 3 high- (50%-85%) and 7 low- (<25%) Medicaid pediatric practices in urban eastern Virginia, we assessed immunization rates of children 12 and 24 months old comparing the standard criteria (charts in the active files excluding those that documented the child moved or went elsewhere) with 3 alternative criteria for selecting active patients: 1) follow-up: the chart contained a complete immunization record or the patient was found to be active in the practice through follow-up contact by phone or mail; 2) seen in the past year: the chart indicated that the patient was seen in the practice in the past year; 3) consecutive: patients that were seen consecutively for any reason. RESULTS: Of the 1823 charts assessed in the high- and low-Medicaid practices, follow-up identified 61% and 83% as active patients; 78% and 95% were ever seen in the past year. At 24 months, mean practice immunization rates were lower for standard (70%) than all 3 alternative criteria (78%-86%). Immunization rate differences between standard and alternative criteria were greater in high- (17%-23%) than low-Medicaid practices (5%-13%). CONCLUSION: The standard for practice assessment should be based on a consistent definition of active patients as the immunization rate denominator.

Improving immunization rates in private pediatric practices through physician leadership.

OBJECTIVE: To determine whether a physician-led quality improvement initiative can improve immunization rates in participating private practices. DESIGN: Surveys of private pediatric practices at 6-month intervals over an 18-month period. SETTING: Ten private pediatric practices in Norfolk and Virginia Beach, Va. PATIENTS: Children aged 9 to 30 months attending the private practices. INTERVENTIONS: Practice immunization rates were assessed and presented to practices on 4 occasions at 6-month intervals. A physician leader convened an immunization task force meeting following the first 3 assessments to review practice guidelines, examine data, and discuss practice changes. MAIN OUTCOME MEASURES: Practice immunization rates for patients at age 24 months, with 3- and 12-month immunization rates as secondary outcomes. RESULTS: The mean practice immunization rate at age 24 months increased significantly (P<.05) from 50.9% at baseline to 69.7%. Rates also increased at age 3 months, from 75.5% to 88.9%, and at age 12 months, from 72.9% to 84.6%. The median age at administration of the fourth dose of diphtheria toxoid, tetanus toxoid, and pertussis vaccine decreased (P<.05) from 17.6 to 16.8 months. Physicians also reported making additional changes, including improved record keeping and screening for immunizations at every visit. CONCLUSION: A quality improvement initiative enabling physician leadership can improve preschool immunization practices and coverage levels in pediatric practices.

The purpose and functions of immunization information systems within health care organizations.

Abroad coalition of public and private health care organizations advocate the development of computerized immunization information systems as a key national strategy for achieving and sustaining high immunization coverage levels. However, widespread adoption requires greater awareness of the purpose, functions, and value of an immunization information system within health care organizations. We propose that the purpose of an immunization information system is to increase the efficiency and effectiveness of immunization-related practices and identify 9 potential functions that accomplish this purpose through improving patient care and practice management. When implementing an immunization information system within a practice setting, health care providers must consider technological and organizational issues. Health care providers should also look beyond their particular practice setting and establish public-private partnerships to create a system that links immunization data from all health care providers.

Current concepts in asthma management.

This short paper investigates the effects of prophylaxis on re-admission rates at the Royal Alexandra Hospital for Children, Camperdown, New South Wales.

In vitro evaluation of ocular irritants using corneal protein profiles.

This report represents the first application of tissue isoelectric focusing to establish reference human and rabbit corneal protein profiles and to study the corneal response to ocular irritants. The methods developed in this study provide a direct, semiquantitative comparison of tissue-irritant interactions without the potential limitations of standard homogenization and extraction procedures. The in vitro exposure of corneal sections to acetic acid (1 and 4%) and ammonium hydroxide (0.25 and 2%) solutions resulted in selective modifications of tissue protein profiles which were evaluated by scanning densitometry. Direct comparison of the rabbit and human corneal protein changes induced by in vitro irritant action revealed a similar acid/base effect on a common rabbit and human corneal protein band (pI 8.1).

The effect of gold foil electrode position on the electroretinogram in human subjects.

Photopic ERGs were recorded in two human subjects using gold foil electrodes mounted at various positions in the lower fornix. The peak to peak amplitude of the b-wave was reduced in both subjects when the centre of the electrode was placed beyond 15 mm from the medial side of the limbus. The implicit time of the a-wave and the b-wave was not dependent on electrode position. These results emphasize the importance of correct placement of gold foil electrodes.

Influence of acidity level in simulated rain on disease progress in four plant pathosystems.

Field investigations were performed in 1984-1985 on the effects of acidity level in simulated rain on disease dynamics in four pathosystems: alfalfa leaf spot (ALS), peanut leaf spot (PLS), potato late blight (PLB), and soybean brown spot (SBS). Studies were performed in an ambient rain exclusion apparatus with simulated rain acidity levels of pH 2.8, 3.6, 4.2, 4.8, or 5.6 and four plots per pH level. In 1984 for ALS and PLB, rain was simulated three times a week at 6-8 mm per event. For PLS and SBS in 1984 and for PLB, PLS, and SBS in 1985, rain was simulated twice a week at 13-16 mm per event with a 10 min pause halfway through each event. Disease was assessed three times a week. In 1984, no significant effect of acidity level in simulated rain on disease severity was detected in any pathosystem. Severity of PLB differed among treatments in 1985 with significant quadratic and cubic components for the dose-response relationship. PLS severity decreased with increasing level of acidity in simulated rain in 1985 and the dose-response relationship was linear. No differences in severity of ALS or SBS due to acidity of simulated rain were found. Thus, disease response to acidity of simulated rain is system dependent.