Early versus late administration of amino acids in preterm infants receiving parenteral nutrition.

BACKGROUND: Observational studies in preterm newborns suggest that delay in administering amino acids (AA) could result in a protein catabolic state and impact on growth and development. OBJECTIVES: The objective of this review was to compare the efficacy and safety of early versus late administration of intravenous AA in neonates born at < 37 weeks of gestation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries in March 2023. We checked the reference lists of included studies and studies/systematic reviews where subject matter related to the intervention or population examined in this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing early administration of AA with late administration in premature newborn infants. We defined early administration of AA solution as the administration of AA in isolation or with total parenteral nutrition within the first 24 hours of birth, and late administration as the administration of AA in isolation or with total parenteral nutrition after the first 24 hours of birth. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: Nine studies (383 participants) were eligible for inclusion in the review. All study participants were born at < 37 weeks of gestation and were inpatients in neonatal intensive care units. No studies reported growth during the first months of life as assessed by difference in weight. Early administration of AA may have little or no effect on growth in the first month of life as measured by length (mean difference (MD) 0.00, 95% confidence interval (CI) -0.41 to 0.41; 1 study; 21 participants; low-certainty evidence) and head circumference (MD 0.05, 95% CI -0.03 to 0.14; 2 studies; 87 participants; low-certainty evidence). No studies reported the discharge weight outcome. Early administration of AA may result in little to no difference in neurodevelopmental outcome assessed by Mental Developmental Index (MDI) of < 70 at two years of age (odds ratio 0.83, 95% CI 0.21 to 3.28; 1 study; 111 participants; low-certainty evidence). No studies reported all-cause mortality at 28 days and before discharge. Early administration of AA may result in a large increase in positive nitrogen balance in the first three days of life (MD 250.42, 95% CI 224.91 to 275.93; 4 studies; 93 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that there may be little to no difference between early and late administration of AA in growth (measured by length and head circumference during the first month after birth) and neurodevelopmental outcome (assessed by MDI of < 70). No RCTs reported on weight in the first month of life, mortality (all-cause mortality at 28 days and before discharge), or discharge weight. Low-certainty evidence suggests a large increase in positive nitrogen balance in preterm infants who received AA within 24 hours of birth. The clinical relevance of this observation is unknown. The number of infants in the RCTs included in the review was small, and there was clinical heterogeneity amongst trials. Adequately powered trials in infants < 37 weeks' gestation are required to determine optimal timing of initiation of AA. We identified two ongoing studies. Both studies will be recruiting infants ≥ 34 weeks of gestation and may or may not add to the outcome data for this review.

Standardised neonatal parenteral nutrition formulations - Australasian neonatal parenteral nutrition consensus update 2017.

BACKGROUND: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines. METHODS: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed. RESULTS: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed. CONCLUSIONS: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.

Infant formulas containing hydrolysed protein for prevention of allergic disease.

BACKGROUND: Infant formulas containing hydrolysed proteins have been widely advocated for preventing allergic disease in infants, in place of standard cow's milk formula (CMF). However, it is unclear whether the clinical trial evidence supports this. OBJECTIVES: To compare effects on allergic disease when infants are fed a hydrolysed formula versus CMF or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective, including extensively or partially hydrolysed formula (EHF/PHF). To determine whether infants at low or high risk of allergic disease, and whether infants receiving early short-term (first few days after birth) or prolonged formula feeding benefit from hydrolysed formulas. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 11), MEDLINE (1948 to 3 November 2017), and Embase (1974 to 3 November 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles and previous reviews for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We searched for randomised and quasi-randomised trials that compared use of a hydrolysed formula versus human milk or CMF. Outcomes with ≥ 80% follow-up of participants from eligible trials were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data from the included studies. Fixed-effect analyses were performed. The treatment effects were expressed as risk ratio (RR) and risk difference (RD) with 95% confidence intervals and quality of evidence using the GRADE quality of evidence approach. The primary outcome was all allergic disease (including asthma, atopic dermatitis, allergic rhinitis and food allergy). MAIN RESULTS: A total of 16 studies were included.Two studies assessed the effect of three to four days infant supplementation with an EHF while in hospital after birth versus pasteurised human milk feed. A single study enrolling 90 infants reported no difference in all allergic disease (RR 1.43, 95% CI 0.38 to 5.37) or any specific allergic disease up to childhood including cow's milk allergy (CMA) (RR 7.11, 95% CI 0.35 to 143.84). A single study reported no difference in infant CMA (RR 0.87, 95% CI 0.52 to 1.46; participants = 3559). Quality of evidence was assessed as very low for all outcomes.No eligible trials compared prolonged hydrolysed formula versus human milk feeding.Two studies assessed the effect of three to four days infant supplementation with an EHF versus a CMF. A single study enrolling 90 infants reported no difference in all allergic disease (RR 1.37, 95% CI 0.33 to 5.71; participants = 77) or any specific allergic disease including CMA up to childhood. A single study reported a reduction in infant CMA of borderline significance (RR 0.62, 95% CI 0.38 to 1.00; participants = 3473). Quality of evidence was assessed as very low for all outcomes.Twelve studies assessed the effect of prolonged infant feeding with a hydrolysed formula compared with a CMF. The data showed no difference in all allergic disease in infants (typical RR 0.88, 95% CI 0.76 to 1.01; participants = 2852; studies = 8) and children (typical RR 0.85, 95% CI 0.69 to 1.05; participants = 950; studies = 2), and no difference in any specific allergic disease including infant asthma (typical RR 0.57, 95% CI 0.31 to 1.04; participants = 318; studies = 4), eczema (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 2896; studies = 9), rhinitis (typical RR 0.52, 95% CI 0.14 to 1.85; participants = 256; studies = 3), food allergy (typical RR 1.42, 95% CI 0.87 to 2.33; participants = 479; studies = 2), and CMA (RR 2.31, 95% CI 0.24 to 21.97; participants = 338; studies = 1). Quality of evidence was assessed as very low for all outcomes. AUTHORS' CONCLUSIONS: We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergic disease. Very low-quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA. Further trials are recommended before implementation of this practice.We found no evidence to support prolonged feeding with a hydrolysed formula compared with a CMF for prevention of allergic disease in infants unable to be exclusively breast fed.

Higher versus lower amino acid intake in parenteral nutrition for newborn infants.

BACKGROUND: Sick newborn and preterm infants frequently are not able to be fed enterally, necessitating parenteral fluid and nutrition. Potential benefits of higher parenteral amino acid (AA) intake for improved nitrogen balance, growth, and infant health may be outweighed by the infant's ability to utilise high intake of parenteral AA, especially in the days after birth. OBJECTIVES: The primary objective is to determine whether higher versus lower intake of parenteral AA is associated with improved growth and disability-free survival in newborn infants receiving parenteral nutrition.Secondary objectives include determining whether:• higher versus lower starting or initial intake of amino acids is associated with improved growth and disability-free survival without side effects;• higher versus lower intake of amino acids at maximal intake is associated with improved growth and disability-free survival without side effects; and• increased amino acid intake should replace non-protein energy intake (glucose and lipid), should be added to non-protein energy intake, or should be provided simultaneously with non-protein energy intake.We conducted subgroup analyses to look for any differences in the effects of higher versus lower intake of amino acids according to gestational age, birth weight, age at commencement, and condition of the infant, or concomitant increases in fluid intake. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (2 June 2017), MEDLINE (1966 to 2 June 2017), Embase (1980 to 2 June 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 2 June 2017). We also searched clinical trials databases, conference proceedings, and citations of articles. SELECTION CRITERIA: Randomised controlled trials of higher versus lower intake of AAs as parenteral nutrition in newborn infants. Comparisons of higher intake at commencement, at maximal intake, and at both commencement and maximal intake were performed. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality, and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs) and assessed the quality of evidence using the GRADE approach. MAIN RESULTS: Thirty-two studies were eligible for inclusion. Six were short-term biochemical tolerance studies, one was in infants at > 35 weeks' gestation, one in term surgical newborns, and three yielding no usable data. The 21 remaining studies reported clinical outcomes in very preterm or low birth weight infants for inclusion in meta-analysis for this review.Higher AA intake had no effect on mortality before hospital discharge (typical RR 0.90, 95% CI 0.69 to 1.17; participants = 1407; studies = 14; I2 = 0%; quality of evidence: low). Evidence was insufficient to show an effect on neurodevelopment and suggest no reported benefit (quality of evidence: very low). Higher AA intake was associated with a reduction in postnatal growth failure (< 10th centile) at discharge (typical RR 0.74, 95% CI 0.56 to 0.97; participants = 203; studies = 3; I2 = 22%; typical RD -0.15, 95% CI -0.27 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 4 to 50; quality of evidence: very low). Subgroup analyses found reduced postnatal growth failure in infants that commenced on high amino acid intake (> 2 to ≤ 3 g/kg/day); that occurred with increased amino acid and non-protein caloric intake; that commenced on intake at < 24 hours' age; and that occurred with early lipid infusion.Higher AA intake was associated with a reduction in days needed to regain birth weight (MD -1.14, 95% CI -1.73 to -0.56; participants = 950; studies = 13; I2 = 77%). Data show varying effects on growth parameters and no consistent effects on anthropometric z-scores at any time point, as well as increased growth in head circumference at discharge (MD 0.09 cm/week, 95% CI 0.06 to 0.13; participants = 315; studies = 4; I2 = 90%; quality of evidence: very low).Higher AA intake was not associated with effects on days to full enteral feeds, late-onset sepsis, necrotising enterocolitis, chronic lung disease, any or severe intraventricular haemorrhage, or periventricular leukomalacia. Data show a reduction in retinopathy of prematurity (typical RR 0.44, 95% CI 0.21 to 0.93; participants = 269; studies = 4; I2 = 31%; quality of evidence: very low) but no difference in severe retinopathy of prematurity.Higher AA intake was associated with an increase in positive protein balance and nitrogen balance. Potential biochemical intolerances were reported, including risk of abnormal blood urea nitrogen (typical RR 2.77, 95% CI 2.13 to 3.61; participants = 688; studies = 7; I2 = 6%; typical RD 0.26, 95% CI 0.20 to 0.32; number needed to treat for an additional harmful outcome (NNTH) 4; 95% CI 3 to 5; quality of evidence: high). Higher amino acid intake in parenteral nutrition was associated with a reduction in hyperglycaemia (> 8.3 mmol/L) (typical RR 0.69, 95% CI 0.49 to 0.96; participants = 505; studies = 5; I2 = 68%), although the incidence of hyperglycaemia treated with insulin was not different. AUTHORS' CONCLUSIONS: Low-quality evidence suggests that higher AA intake in parenteral nutrition does not affect mortality. Very low-quality evidence suggests that higher AA intake reduces the incidence of postnatal growth failure. Evidence was insufficient to show an effect on neurodevelopment. Very low-quality evidence suggests that higher AA intake reduces retinopathy of prematurity but not severe retinopathy of prematurity. Higher AA intake was associated with potentially adverse biochemical effects resulting from excess amino acid load, including azotaemia. Adequately powered trials in very preterm infants are required to determine the optimal intake of AA and effects of caloric balance in parenteral nutrition on the brain and on neurodevelopment.

Trial of Music, Sucrose, and Combination Therapy for Pain Relief during Heel Prick Procedures in Neonates.

OBJECTIVE: To compare the effectiveness of music, oral sucrose, and combination therapy for pain relief in neonates undergoing a heel prick procedure. STUDY DESIGN: This randomized, controlled, blinded crossover clinical trial included stable neonates >32 weeks of postmenstrual age. Each neonate crossed over to all 3 interventions in random order during consecutive heel pricks. A video camera on mute mode recorded facial expressions, starting 2 minutes before until 7 minutes after the heel prick. The videos were later analyzed using the Premature Infant Pain Profile-Revised (PIPP-R) scale once per minute by 2 independent assessors, blinded to the intervention. The PIPP-R scores were compared between treatment groups using Friedman test. RESULTS: For the 35 participants, the postmenstrual age was 35 weeks (SD, 2.3) with an average weight of 2210 g (SD, 710). The overall median PIPP-R scores following heel prick over 6 minutes were 4 (IQR 0-6), 3 (IQR 0-6), and 1 (IQR 0-3) for the music, sucrose, and combination therapy interventions, respectively. The PIPP-R scores were significantly lower at all time points after combination therapy compared with the groups given music or sucrose alone. There was no difference in PIPP-R scores between the music and sucrose groups. CONCLUSIONS: In relatively stable and mature neonates, the combination of music therapy with sucrose provided better pain relief during heel prick than when sucrose or music was used alone. Recorded music in isolation had a similar effect to the current gold standard of oral sucrose. TRIAL REGISTRATION: www.anzctr.org.au ACTRN12615000271505.

WITHDRAWN: Infant formulas containing hydrolysed protein for prevention of allergic disease and food allergy.

BACKGROUND: Allergy is common and may be associated with foods, including cow's milk formula (CMF). Formulas containing hydrolysed proteins have been used to treat infants with allergy. However, it is unclear whether hydrolysed formulas can be advocated for prevention of allergy in infants. OBJECTIVES: To compare effects on allergy and food allergy when infants are fed a hydrolysed formula versus CMF or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective, including extensively or partially hydrolysed formula (EHF/PHF). To determine which infants at low or high risk of allergy and which infants receiving early, short-term or prolonged formula feeding may benefit from hydrolysed formulas. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group supplemented by cross referencing of previous reviews and publications (updated August 2016). SELECTION CRITERIA: We searched for randomised and quasi-randomised trials that compared use of a hydrolysed formula versus human milk or CMF. Trials with ≥ 80% follow-up of participants were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We independently assessed eligibility of studies for inclusion, methodological quality and data extraction. Primary outcomes included clinical allergy, specific allergy and food allergy. We conducted meta-analysis using a fixed-effect (FE) model. MAIN RESULTS: Two studies assessed the effect of three to four days' infant supplementation with an EHF whilst in hospital after birth versus pasteurised human milk feed. Results showed no difference in infant allergy or childhood cow's milk allergy (CMA). No eligible trials compared prolonged hydrolysed formula versus human milk feeding.Two studies assessed the effect of three to four days infant supplementation with an EHF versus a CMF. One large quasi-random study reported a reduction in infant CMA of borderline significance among low-risk infants (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.38 to 1.00).Prolonged infant feeding with a hydrolysed formula compared with a CMF was associated with a reduction in infant allergy (eight studies, 2852 infants; FE RR 0.82, 95% CI 0.72 to 0.95; risk difference (RD) -0.04, 95% CI -0.08 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 25, 95% CI 12.5 to 100) and infant CMA (two studies, 405 infants; FE RR 0.38, 95% CI 0.16 to 0.86). We had substantial methodological concerns regarding studies and concerns regarding publication bias, as substantial numbers of studies including those in high-risk infants have not comprehensively reported allergy outcomes (GRADE quality of evidence 'very low').Prolonged infant feeding with a hydrolysed formula compared with a CMF was not associated with a difference in childhood allergy and led to no differences in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy. Many of the analyses assessing specific allergy are underpowered.Subroup analyses showed that infant allergy was reduced in studies that enrolled infants at high risk of allergy who used a hydrolysed formula compared with a CMF; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF. Studies that enrolled infants at high risk of allergy; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF found a reduction in infant CMA. AUTHORS' CONCLUSIONS: We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergy. Very low-quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA.In infants at high risk of allergy not exclusively breast fed, very low-quality evidence suggests that prolonged hydrolysed formula feeding compared with CMF feeding reduces infant allergy and infant CMA. Studies have found no difference in childhood allergy and no difference in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy.Very low-quality evidence shows that prolonged use of a partially hydrolysed formula compared with a CMF for partial or exclusive feeding was associated with a reduction in infant allergy incidence and CMA incidence, and that prolonged use of an EHF versus a PHF reduces infant food allergy.

Infant formulas containing hydrolysed protein for prevention of allergic disease and food allergy.

BACKGROUND: Allergy is common and may be associated with foods, including cow's milk formula (CMF). Formulas containing hydrolysed proteins have been used to treat infants with allergy. However, it is unclear whether hydrolysed formulas can be advocated for prevention of allergy in infants. OBJECTIVES: To compare effects on allergy and food allergy when infants are fed a hydrolysed formula versus CMF or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective, including extensively or partially hydrolysed formula (EHF/PHF). To determine which infants at low or high risk of allergy and which infants receiving early, short-term or prolonged formula feeding may benefit from hydrolysed formulas. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group supplemented by cross referencing of previous reviews and publications (updated August 2016). SELECTION CRITERIA: We searched for randomised and quasi-randomised trials that compared use of a hydrolysed formula versus human milk or CMF. Trials with ≥ 80% follow-up of participants were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We independently assessed eligibility of studies for inclusion, methodological quality and data extraction. Primary outcomes included clinical allergy, specific allergy and food allergy. We conducted meta-analysis using a fixed-effect (FE) model. MAIN RESULTS: Two studies assessed the effect of three to four days' infant supplementation with an EHF whilst in hospital after birth versus pasteurised human milk feed. Results showed no difference in infant allergy or childhood cow's milk allergy (CMA). No eligible trials compared prolonged hydrolysed formula versus human milk feeding.Two studies assessed the effect of three to four days' infant supplementation with an EHF versus a CMF. One large quasi-random study reported a reduction in infant CMA of borderline significance among low-risk infants (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.38 to 1.00).Prolonged infant feeding with a hydrolysed formula compared with a CMF was associated with a reduction in infant allergy (eight studies, 2852 infants; FE RR 0.82, 95% CI 0.72 to 0.95; risk difference (RD) -0.04, 95% CI -0.08 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 25, 95% CI 12.5 to 100) and infant CMA (two studies, 405 infants; FE RR 0.38, 95% CI 0.16 to 0.86). We had substantial methodological concerns regarding studies and concerns regarding publication bias, as substantial numbers of studies including those in high-risk infants have not comprehensively reported allergy outcomes (GRADE quality of evidence 'very low').Prolonged infant feeding with a hydrolysed formula compared with a CMF was not associated with a difference in childhood allergy and led to no differences in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy. Many of the analyses assessing specific allergy are underpowered.Subroup analyses showed that infant allergy was reduced in studies that enrolled infants at high risk of allergy who used a hydrolysed formula compared with a CMF; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF. Studies that enrolled infants at high risk of allergy; used a PHF compared with a CMF; used prolonged and exclusive feeding of a hydrolysed formula compared with a CMF; and used a partially hydrolysed whey formula compared with a CMF found a reduction in infant CMA. AUTHORS' CONCLUSIONS: We found no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breast feeding for prevention of allergy. Very low-quality evidence indicates that short-term use of an EHF compared with a CMF may prevent infant CMA.In infants at high risk of allergy not exclusively breast fed, very low-quality evidence suggests that prolonged hydrolysed formula feeding compared with CMF feeding reduces infant allergy and infant CMA. Studies have found no difference in childhood allergy and no difference in specific allergy, including infant and childhood asthma, eczema and rhinitis and infant food allergy.Very low-quality evidence shows that prolonged use of a partially hydrolysed formula compared with a CMF for partial or exclusive feeding was associated with a reduction in infant allergy incidence and CMA incidence, and that prolonged use of an EHF versus a PHF reduces infant food allergy.

Quality of harness fit for normal and low birthweight infants observed among newborns in infant car seats.

INTRODUCTION: Child restraint fit is important for crash protection. For newborns, standards universally require a rear-facing restraint and some upper limit on size, but historically there has been no specification of a lower design limit and there is concern over whether low birthweight infants (LBW) are adequately restrained. The aim of this study was to determine the quality of harness fit for newborns of low and normal weight in a range of modern child restraints. METHODS: A convenience sample of infants (1.657-4.455 kg) were recruited from the postnatal ward and special care nursery <1 week from discharge. Infants (n=84) were assessed for harness fit in rear-facing-only restraints, convertible rear/forward restraints and a subset were assessed in a restraint specifically designed to accommodate LBW infants. Measures of harness fit were based on shoulder strap, crotch strap and buckle positioning. RESULTS: Less than 20% of infants achieved good harness fit, regardless of whether they were categorised as low (<2.5 kg) or normal weight. Rear-facing-only restraints were less likely to provide good fit than convertible restraints, in all measures of fit other than shoulder strap width. The proportions of infants achieving good fit were greater in the restraint designed for LBW infants than other restraint types. CONCLUSION: Poor accommodation continues to be a problem for LBW infants but is rectified in specifically designed restraints. Better specification of harness configuration for all rearward-facing restraints may be required to ensure adequate accommodation of normal birthweight infants.

Polyunsaturated fatty acid supplementation in infancy for the prevention of allergy.

BACKGROUND: Early dietary intakes may influence the development of allergic disease. It is important to determine if dietary polyunsaturated fatty acids (PUFAs) given as supplements or added to infant formula prevent the development of allergy. OBJECTIVES: To determine the effect of higher PUFA intake during infancy to prevent allergic disease. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE (1966 to 14 September 2015), EMBASE (1980 to 14 September 2015) and CINAHL (1982 to 14 September 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared the use of a PUFA with no PUFA in infants for the prevention of allergy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data from the included studies. We used fixed-effect analyses. The treatment effects were expressed as risk ratio (RR) with 95% confidence intervals (CI). We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: The search found 17 studies that assessed the effect of higher versus lower intake of PUFAs on allergic outcomes in infants. Only nine studies enrolling 2704 infants reported allergy outcomes that could be used in meta-analyses. Of these, there were methodological concerns for eight.In infants up to two years of age, meta-analyses found no difference in incidence of all allergy (1 study, 323 infants; RR 0.96, 95% CI 0.73 to 1.26; risk difference (RD) -0.02, 95% CI -0.12 to 0.09; heterogeneity not applicable), asthma (3 studies, 1162 infants; RR 1.04, 95% CI 0.80 to 1.35, I2 = 0%; RD 0.01, 95% CI -0.04 to 0.05, I2 = 0%), dermatitis/eczema (7 studies, 1906 infants; RR 0.93, 95% CI 0.82 to 1.06, I2 = 0%; RD -0.02, 95% CI -0.06 to 0.02, I2 = 0%) or food allergy (3 studies, 915 infants; RR 0.81, 95% CI 0.56 to 1.19, I2 = 63%; RD -0.02, 95% CI -0.06 to 0.02, I2 = 74%). There was a reduction in allergic rhinitis (2 studies, 594 infants; RR 0.47, 95% CI 0.23 to 0.96, I2 = 6%; RD -0.04, 95% CI -0.08 to -0.00, I2 = 54%; number needed to treat for an additional beneficial outcome (NNTB) 25, 95% CI 13 to ∞).In children aged two to five years, meta-analysis found no difference in incidence of all allergic disease (2 studies, 154 infants; RR 0.69, 95% CI 0.47 to 1.02, I2 = 43%; RD -0.16, 95% CI -0.31 to -0.00, I2 = 63%; NNTB 6, 95% CI 3 to ∞), asthma (1 study, 89 infants; RR 0.45, 95% CI 0.20 to 1.02; RD -0.20, 95% CI -0.37 to -0.02; heterogeneity not applicable; NNTB 5, 95% CI 3 to 50), dermatitis/eczema (2 studies, 154 infants; RR 0.65, 95% CI 0.34 to 1.24, I2 = 0%; RD -0.09 95% CI -0.22 to 0.04, I2 = 24%) or food allergy (1 study, 65 infants; RR 2.27, 95% CI 0.25 to 20.68; RD 0.05, 95% CI -0.07 to 0.16; heterogeneity not applicable).In children aged two to five years, meta-analysis found no difference in prevalence of all allergic disease (2 studies, 633 infants; RR 0.98, 95% CI 0.81 to 1.19, I2 = 36%; RD -0.01, 95% CI -0.08 to 0.07, I2 = 0%), asthma (2 studies, 635 infants; RR 1.12, 95% CI 0.82 to 1.53, I2 = 0%; RD 0.02, 95% CI -0.04 to 0.09, I2 = 0%), dermatitis/eczema (2 studies, 635 infants; RR 0.81, 95% CI 0.59 to 1.09, I2 = 0%; RD -0.04 95% CI -0.11 to 0.02, I2 = 0%), allergic rhinitis (2 studies, 635 infants; RR 1.02, 95% CI 0.83 to 1.25, I2 = 0%; RD 0.01, 95% CI -0.06 to 0.08, I2 = 0%) or food allergy (1 study, 119 infants; RR 0.27, 95% CI 0.06 to 1.19; RD -0.10, 95% CI -0.20 to -0.00; heterogeneity not applicable; NNTB 10, 95% CI 5 to ∞). AUTHORS' CONCLUSIONS: There is no evidence that PUFA supplementation in infancy has an effect on infant or childhood allergy, asthma, dermatitis/eczema or food allergy. However, the quality of evidence was very low. There was insufficient evidence to determine an effect on allergic rhinitis.

Pertussis vaccination coverage among Australian women prior to childbirth in the cocooning era: a two-hospital, cross-sectional survey, 2010 to 2013.

BACKGROUND: Recent pertussis epidemics have triggered implementation of cocooning, involving caregiver vaccination to indirectly protecting susceptible infants. AIM: To determine patient, provider and setting factors associated with maternal pertussis booster vaccination (dTpa) within 5-10 years before childbirth. MATERIALS AND METHODS: Cross-sectional survey using Health Belief Model constructs among postpartum women in a tertiary referral centre and a private hospital in Sydney, Australia. RESULTS: Pertussis vaccination was current among 33.7% of the 2483 new mothers (0.5% vaccinated during pregnancy). Women were more likely to be vaccinated if they had heard of 'whooping cough' from a health professional (OR: 2.59, P < 0.001, 95% CI: 1.70-3.95), were recommended the vaccine (OR: 2.48, P < 0.00, 95% CI: 1.55-4.00), perceived pertussis as 'severe' for adults (OR: 1.21, p0.009, 95% CI: 1.05-1.39) and 'common' within their community (OR: 1.38, P < 0.001, 95% CI: 1.18-1.61). They more often agreed that it was their parental responsibility to be vaccinated (OR: 1.61, P = 0.002, 95% CI: 1.19-2.18), and this would help prevent their baby from contracting pertussis (OR: 1.22, P = 0.046, 95% CI: 1.00-1.47). Vaccinated women were less likely to report vaccination barriers: time constraints (OR: 0.75, P < 0.001, 95% CI: 0.66-0.85) and having safety concerns (OR: 0.80, P < 0.001, 95% CI: 0.69-0.92). Additionally, their partners reported three times higher uptake (76% vs 49%; P < 0.001; 95% CI: 2.66-3.85). CONCLUSIONS: Current pertussis vaccination in only one in every three postpartum participants may indicate insufficient coverage to protect newborns. Practitioners are instrumental in raising awareness and addressing vaccine concerns. Integrating vaccination into routine obstetric care, whether antenatally or postnatally, may minimise barriers.

Standardised neonatal parenteral nutrition formulations - an Australasian group consensus 2012.

Standardised parenteral nutrition formulations are routinely used in the neonatal intensive care units in Australia and New Zealand. In 2010, a multidisciplinary group was formed to achieve a consensus on the formulations acceptable to majority of the neonatal intensive care units. Literature review was undertaken for each nutrient and recommendations were developed in a series of meetings held between November 2010 and April 2011. Three standard and 2 optional amino acid/dextrose formulations and one lipid emulsion were agreed by majority participants in the consensus. This has a potential to standardise neonatal parenteral nutrition guidelines, reduce costs and prescription errors.

Improved nutrient intake following implementation of the consensus standardised parenteral nutrition formulations in preterm neonates--a before-after intervention study.

BACKGROUND: New standardised parenteral nutrition (SPN) formulations were implemented in July 2011 in many neonatal intensive care units in New South Wales following consensus group recommendations. The aim was to evaluate the efficacy and safety profile of new consensus formulations in preterm infants born less than 32 weeks. METHODS: A before-after intervention study conducted at a tertiary neonatal intensive care unit. Data from the post-consensus cohort (2011 to 2012) were prospectively collected and compared retrospectively with a pre-consensus cohort of neonates (2010). RESULTS: Post-consensus group commenced parenteral nutrition (PN) significantly earlier (6 v 11 hours of age, p 0.005). In comparison to the pre-consensus cohort, there was a higher protein intake from day 1 (1.34 v 0.49 g/kg, p 0.000) to day 7 (3.55 v 2.35 g/kg, p 0.000), higher caloric intake from day 1 (30 v 26 kcal/kg, p 0.004) to day 3 (64 v 62 kcal/kg, p 0.026), and less daily fluid intake from day 3 (105.8 v 113.8 mL/kg, p 0.011) to day 7 (148.8 v 156.2 mL/kg, p 0.025), and reduced duration of lipid therapy (253 v 475 hr, p 0.011). This group also had a significantly greater weight gain in the first 4 weeks (285 v 220 g, p 0.003). CONCLUSIONS: New consensus SPN solutions provided better protein intake in the first 7 days and were associated with greater weight gain in the first 4 weeks. However, protein intake on day 1 was below the consensus goal of 2 g/kg/day.

Early versus late administration of amino acids in preterm infants receiving parenteral nutrition.

BACKGROUND: Observational studies in preterm newborns suggest that delay in administering amino acids could result in a protein catabolic state and could impact on growth and development. OBJECTIVES: To determine the effect of early administration of amino acids in premature newborns on growth, neurodevelopmental outcome, mortality and clinically important side effects. SEARCH METHODS: The standard search strategy of the Neonatal Review Group as outlined in The Cochrane Library was used. Relevant randomised controlled trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012 I ssue 9 ), MEDLINE, EMBASE and CINAHL from their earliest dates to September 2012. The trial registry portal of the World Health Organization's International Cilinical Trial Registry Platform and ClinicalTrials.gov (US National Institute of Health) was searched to identify ongoing and completed but unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing early administration of amino acids with late administration in premature newborn infants were included. Early administration of amino acid solution was defined as the administration of amino acids in isolation or with total parenteral nutrition within the first 24 hours of birth; late initiation was defined as the administration of amino acids in isolation or with total parenteral nutrition after the first 24 hours of birth. The primary outcome measures were growth, neurodevelopmental outcome and mortality at 28 days. The secondary outcomes were biochemical abnormalities, sepsis and mortality. DATA COLLECTION AND ANALYSIS: Both review authors independently selected trials, assessed trial quality and extracted data from the included studies. We contacted authors for further information. Fixed-effect analyses were performed. The treatment effect was expressed as mean difference for continuous variables and as risk difference and risk ratio for dichotomous variables. All results included 95% confidence intervals (CIs). MAIN RESULTS: Seven randomised controlled trials were included in this review. One randomised controlled trial reported no difference in crown-heel length and occipitofrontal head circumference by day 10. Four trials that enrolled 93 premature infants showed positive nitrogen balance (The mean difference with 95% CI was 250.42 (224.91 to 275.93 P value < 0.00001). Four trials showed a significant difference in the level of blood urea nitrogen (BUN) in the first 48 hours (P value < 0.00001). Early administration of amino acids did not result in metabolic acidosis in the first 24 hours. AUTHORS' CONCLUSIONS: There is no available evidence of the benefits of early administration of amino acids on mortality, early and late growth and neurodevelopment. There is evidence from four randomised controlled trials included in this review that early administration of amino acids is associated with a positive nitrogen balance. The clinical relevance of this finding is not known. Acid-base status and ammonia levels were normal in the infants who received amino acids early. Given the small number of infants in the randomised controlled trials included in this review, the clinical heterogeneity among them, and the lack of data on important clinical outcomes, there is insufficient evidence to guide practice regarding the early versus late administration of amino acids to infants less than 37 weeks gestation.

Prebiotics in infants for prevention of allergy.

BACKGROUND: Prebiotics (commonly oligosaccharides) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens. OBJECTIVES: To determine the effect of prebiotic given to infants for the prevention of allergy. SEARCH METHODS: We performed an updated search in August 2012 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8), MEDLINE, EMBASE, conference proceedings, citations, expert informants and clinical trials registries. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared the use of a prebiotic to no prebiotic, or a specific prebiotic compared to a different prebiotic in infants for prevention of allergy. DATA COLLECTION AND ANALYSIS: Assessment of trial quality, data extraction and synthesis of data were performed using the standard methods of The Cochrane Collaboration. MAIN RESULTS: The 2012 update identified 13 studies classified as ongoing or awaiting classification (yet to report allergy outcomes). Forty-three studies were excluded, primarily as no allergy data were reported, although none of these enrolled infants were at high risk of allergy. Four studies enrolling 1428 infants were eligible for inclusion. All studies were at high risk of attrition bias. Allergy outcomes were reported from four months to two years of age.Meta-analysis of two studies (226 infants) found no significant difference in infant asthma although significant heterogeneity was found between studies. Meta-analysis of four studies found a significant reduction in eczema (1218 infants, typical risk ratio 0.68, 95% CI 0.48 to 0.97; typical risk difference -0.04, 95% CI -0.07 to -0.00; number needed to treat to benefit (NNTB) 25, 95% CI 14 to > 100; P = 0.03). No statistically significant heterogeneity was found between studies. One study reported no significant difference in urticaria.No statistically significant subgroup differences were found according to infant risk of allergy or type of infant feed. However, individual studies reported a significant reduction in asthma and eczema from supplementation with a mixture of galacto- and fructo-oligosaccharide (GOS/FOS 9:1 ratio) (8 g/L) in infants at high risk of allergy; and in eczema from supplementation with GOS/FOS (9:1) (6.8 g/L) and acidic oligosacccharide (1.2 g/L) in infants not selected for allergy risk. AUTHORS' CONCLUSIONS: Further research is needed before routine use of prebiotics can be recommended for prevention of allergy in formula fed infants. There is some evidence that a prebiotic supplement added to infant feeds may prevent eczema. It is unclear whether the use of prebiotic should be restricted to infants at high risk of allergy or may have an effect in low risk populations; or whether it may have an effect on other allergic diseases including asthma.

Australasian neonatal intensive care enteral nutrition survey: implications for practice.

AIM: This survey investigated standardised feeding guidelines and nutrition policy in Australasian neonatal intensive care units and compared these with previously published surveys and international consensus nutrition recommendations. METHODS: An electronic survey on enteral nutrition comprising a wide range of questions about clinical practice was e-mailed to all 25 Australasian neonatal intensive care unit directors of tertiary perinatal centres. RESULTS: Twenty-five surveys were distributed; 24 (96%) were completed. All respondents preferred breast milk as the first feed. For infants <1000 g, 58% started feeds at 1 mL every 4 hours and 83% started enteral feeds on day 0-2 in the absence of contraindications. The identification of bile-stained gastric aspirates significant enough to withhold feeds varied. Multicomponent breast milk fortifiers were added by 58% when enteral feeds reached 150 mL/kg day, while 21% added these earlier at 120 mL/kg day or less. Iron supplementation was started at 4 weeks by 63% and at 6 weeks by 27%. Only 42% of units had a neonatal dietitian. Of the 24 units who responded, 58% had no written enteral feeding guidelines. CONCLUSION: Enteral nutrition was initiated earlier than in the past. Great variation remains in clinical practices. Nutritional implications are discussed. Standardisation of feeding guidelines and enteral nutrition policy based on current evidence and international consensus nutrition recommendations may be beneficial and should be encouraged.

Antibiotic regimens for the empirical treatment of newborn infants with necrotising enterocolitis.

BACKGROUND: Although the exact aetiology of necrotising enterocolitis (NEC) remains unknown, research suggests that it is multifactorial; suspected pathophysiological mechanisms include immaturity, intestinal ischaemia, disruption of intestinal mucosal integrity, formula feeding, hyperosmolar load to the intestine, infection and bacterial translocation. Various antibiotic regimens have been widely used in the treatment of NEC. OBJECTIVES: To compare the efficacy of different antibiotic regimens on mortality and the need for surgery in neonates with NEC. SEARCH METHODS: Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2012), Oxford Database of Perinatal Trials, MEDLINE (1966 to February 2012), EMBASE (1980 to February 2012) and CINAHL (1982 to February 2012). SELECTION CRITERIA: All randomised and quasi-randomised controlled trials where antibiotic regimens were used for treatment of NEC. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion was assessed independently by each review author. The criteria and standard methods of the Cochrane Neonatal Review Group were used to assess the methodological quality of the included trials. MAIN RESULTS: Two trials met the inclusion criteria. Faix 1988 randomised 42 premature infants with radiological diagnosis of NEC. Infants were randomised to receive either intravenous ampicillin and gentamicin or ampicillin, gentamicin and clindamycin. Hansen 1980 randomised 20 infants with NEC to receive intravenous ampicillin and gentamicin with or without enteral gentamicin.In the study by Faix 1988, there were no statistical differences in mortality (RR 1.10; 95% CI 0.32 to 3.83) or bowel perforation (RR 2.20; 95% CI 0.45 to 10.74) between the two groups although there was a trend towards higher rate of strictures in the group that received clindamycin (RR 7.20; 95% CI 0.97 to 53.36).The Hansen 1980 study showed no statistically significant difference in death, bowel perforation or development of strictures. AUTHORS' CONCLUSIONS: There was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC. There were concerns about adverse effects following the usage of clindamycin, related to the development of strictures. To address this issue a large randomised controlled trial needs to be performed.

Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity and impulsivity, and is associated with long-term social, academic and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Children and adolescents with ADHD have been shown to have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. OBJECTIVES: To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents. SEARCH METHODS: We searched the following databases in August 2011: CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE (1948 to July Week 3, 2011), EMBASE (1980 to 2011 Week 29), PsycINFO (1806 to current), CINAHL (1937 to current), BIOSIS (1969 to 30 July 2011), Science Citation Index (1970 to 30 July 2011), Social Science Citation Index (1970 to 30 July 2011), Conference Proceedings Citation Index - Science (1990 to 30 July 2011), Conference Proceedings Citation Index - Social Science and Humanities (1990 to 30 July 2011), Cochrane Database of Systematic Reviews (2011, Issue 7), DARE (2011 Issue 2), Dissertation Abstracts (via Dissertation Express) and the metaRegister of Controlled Trials (mRCT). In addition, we searched the following repositories for theses on 2 August 2011: DART, NTLTD and TROVE. We also checked reference lists of relevant studies and reviews for additional references. SELECTION CRITERIA: Two review authors independently assessed the results of the database searches. We resolved any disagreements regarding the selection of studies through consensus or, if necessary, by consultation with a third member of the review team. DATA COLLECTION AND ANALYSIS: Two members of the review team independently extracted details of participants and setting, interventions, methodology and outcome data. If differences were identified, we resolved them by consensus or referral to a third member of the team. We made all reasonable attempts to contact the authors where further clarification or missing data were needed. MAIN RESULTS: We included 13 trials with 1011 participants in the review. After screening 366 references, we considered 23 relevant and obtained the full text for consideration. We excluded five papers and included 18 papers describing the 13 trials. Eight of the included trials had a parallel design: five compared an omega-3 PUFA supplement to placebo; two compared a combined omega-3 and omega-6 supplement to placebo, and one compared an omega-3 PUFA to a dietary supplement. Five of the included trials had a cross-over design: two compared combined omega-3/6 PUFA to placebo; two compared omega-6 PUFA with placebo; one compared omega-3 to omega-6 PUFA, and one compared omega-6 PUFA to dexamphetamine. Supplements were given for a period of between four and 16 weeks.There was a significantly higher likelihood of improvement in the group receiving omega-3/6 PUFA compared to placebo (two trials, 97 participants; risk ratio (RR) 2.19, 95% confidence interval (CI) 1.04 to 4.62). However, there were no statistically significant differences in parent-rated ADHD symptoms (five trials, 413 participants; standardised mean difference (SMD) -0.17, 95% CI -0.38 to 0.03); inattention (six trials, 469 participants; SMD -0.04, 95% CI -0.29 to 0.21) or hyperactivity/impulsivity (five trials, 416 participants; SMD -0.04, 95% CI -0.25 to 0.16) when all participants receiving PUFA supplements were compared to those receiving placebo.There were no statistically significant differences in teacher ratings of overall ADHD symptoms (four trials, 324 participants; SMD 0.05, 95% CI -0.18 to 0.27); inattention (three trials, 260 participants; SMD 0.26, 95% CI -0.22 to 0.74) or hyperactivity/impulsivity (three trials, 259 participants; SMD 0.10, 95% CI -0.16 to 0.35).There were also no differences between groups in behaviour, side effects or loss to follow-up.Overall, there were no other differences between groups for any other comparison. AUTHORS' CONCLUSIONS: Overall, there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents. The majority of data showed no benefit of PUFA supplementation, although there were some limited data that did show an improvement with combined omega-3 and omega-6 supplementation.It is important that future research addresses current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, short follow-up times and other methodological weaknesses.

Octreotide as therapeutic option for congenital idiopathic chylothorax: a case series.

BACKGROUND: Octreotide, a somatostatin analogue, is used for the management of patients with refractory chylothorax although its safety and efficacy in neonates have not been evaluated in controlled clinical trials. We present one of the largest case series about the use of octreotide in congenital idiopathic chylothorax. METHODS: Six cases of congenital chylothorax (CC) were prospectively collected, who were managed with same unit protocol for octreotide. Mean (SD) gestation was 34.5 (±2.2) weeks, and birthweight was 3410 (±840.4) g. All infants required chest drains from day 1 of life, and the mean (SD) duration of insertion was 36.1 (±8.5) days. Octreotide was commenced at a median age of 13.5 days (range 8-22), given for a median duration of 20 days (range 12-27). The starting dose was 0.5-1 µg/kg/h with an increment of 1-2 µg/kg/day to a maximum of 10 µg/kg/day. Resolution of chylothorax was achieved in five patients, being resistant to treatment in the sixth patient. None had adverse effects from octreotide. Full enteral feeds were reached at a mean age of 44 days. CONCLUSION: Early commencement of octreotide is recommended although further reports to evaluate the safety and efficacy would add to the profile of this medication in the treatment of CC.