Plasma ammonia concentrations in extremely low birthweight infants in the first week after birth: secondary analysis from the ProVIDe randomized clinical trial.

BACKGROUND: Little is known about normative ammonia concentrations in extremely low birthweight (ELBW) babies and whether these vary with birth characteristics. We aimed to determine ammonia concentrations in ELBW babies in the first week after birth and relationships with neonatal characteristics and protein intake. METHODS: Arterial blood samples for the measurement of plasma ammonia concentration were collected within 7 days of birth from ProVIDe trial participants in six New Zealand neonatal intensive care units. RESULTS: Three hundred and twenty-two babies were included. Median (range) gestational age was 25.7 (22.7-31.6) weeks. Median (interquartile range (IQR)) ammonia concentration was 102 (80-131) µg/dL. There were no statistically significant associations between ammonia concentrations and birthweight or sex. Ammonia concentrations were weakly correlated with mean total (Spearman's rs = 0.11, P = 0.047) and intravenous (rs = 0.13, P = 0.02) protein intake from birth, gestational age at birth (rs = -0.13, P = 0.02) and postnatal age (rs = -0.13, P = 0.02). CONCLUSIONS: Plasma ammonia concentrations in ELBW babies are similar to those of larger and more mature babies and only weakly correlated with protein intake. Currently, recommended thresholds for investigation of hyperammonaemia are appropriate for ELBW babies. Protein intake should not be limited by concerns about potential hyperammonaemia.

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.

Long-term nitrogen dioxide exposure assessment using back-extrapolation of satellite-based land-use regression models for Australia.

Assessing historical exposure to air pollution in epidemiological studies is often problematic because of limited spatial and temporal measurement coverage. Several methods for modelling historical exposures have been described, including land-use regression (LUR). Satellite-based LUR is a recent technique that seeks to improve predictive ability and spatial coverage of traditional LUR models by using satellite observations of pollutants as inputs to LUR. Few studies have explored its validity for assessing historical exposures, reflecting the absence of historical observations from popular satellite platforms like Aura (launched mid-2004). We investigated whether contemporary satellite-based LUR models for Australia, developed longitudinally for 2006-2011, could capture nitrogen dioxide (NO2) concentrations during 1990-2005 at 89 sites around the country. We assessed three methods to back-extrapolate year-2006 NO2 predictions: (1) 'do nothing' (i.e., use the year-2006 estimates directly, for prior years); (2) change the independent variable 'year' in our LUR models to match the years of interest (i.e., assume a linear trend prior to year-2006, following national average patterns in 2006-2011), and; (3) adjust year-2006 predictions using selected historical measurements. We evaluated prediction error and bias, and the correlation and absolute agreement of measurements and predictions using R2 and mean-square error R2 (MSE-R2), respectively. We found that changing the year variable led to best performance; predictions captured between 41% (1991; MSE-R2 = 31%) and 80% (2003; MSE-R2 = 78%) of spatial variability in NO2 in a given year, and 76% (MSE-R2 = 72%) averaged over 1990-2005. We conclude that simple methods for back-extrapolating prior to year-2006 yield valid historical NO2 estimates for Australia during 1990-2005. These results suggest that for the time scales considered here, satellite-based LUR has a potential role to play in long-term exposure assessment, even in the absence of historical predictor data.

Oxygen saturation and outcomes in preterm infants.

BACKGROUND: The clinically appropriate range for oxygen saturation in preterm infants is unknown. Previous studies have shown that infants had reduced rates of retinopathy of prematurity when lower targets of oxygen saturation were used. METHODS: In three international randomized, controlled trials, we evaluated the effects of targeting an oxygen saturation of 85 to 89%, as compared with a range of 91 to 95%, on disability-free survival at 2 years in infants born before 28 weeks' gestation. Halfway through the trials, the oximeter-calibration algorithm was revised. Recruitment was stopped early when an interim analysis showed an increased rate of death at 36 weeks in the group with a lower oxygen saturation. We analyzed pooled data from patients and now report hospital-discharge outcomes. RESULTS: A total of 2448 infants were recruited. Among the 1187 infants whose treatment used the revised oximeter-calibration algorithm, the rate of death was significantly higher in the lower-target group than in the higher-target group (23.1% vs. 15.9%; relative risk in the lower-target group, 1.45; 95% confidence interval [CI], 1.15 to 1.84; P=0.002). There was heterogeneity for mortality between the original algorithm and the revised algorithm (P=0.006) but not for other outcomes. In all 2448 infants, those in the lower-target group for oxygen saturation had a reduced rate of retinopathy of prematurity (10.6% vs. 13.5%; relative risk, 0.79; 95% CI, 0.63 to 1.00; P=0.045) and an increased rate of necrotizing enterocolitis (10.4% vs. 8.0%; relative risk, 1.31; 95% CI, 1.02 to 1.68; P=0.04). There were no significant between-group differences in rates of other outcomes or adverse events. CONCLUSIONS: Targeting an oxygen saturation below 90% with the use of current oximeters in extremely preterm infants was associated with an increased risk of death. (Funded by the Australian National Health and Medical Research Council and others; BOOST II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry numbers, ACTRN12605000055606 and ACTRN12605000253606.).

Independent Validation of National Satellite-Based Land-Use Regression Models for Nitrogen Dioxide Using Passive Samplers.

Including satellite observations of nitrogen dioxide (NO2) in land-use regression (LUR) models can improve their predictive ability, but requires rigorous evaluation. We used 123 passive NO2 samplers sited to capture within-city and near-road variability in two Australian cities (Sydney and Perth) to assess the validity of annual mean NO2 estimates from existing national satellite-based LUR models (developed with 68 regulatory monitors). The samplers spanned roadside, urban near traffic (≤100 m to a major road), and urban background (>100 m to a major road) locations. We evaluated model performance using R2 (predicted NO2 regressed on independent measurements of NO2), mean-square-error R2 (MSE-R2), RMSE, and bias. Our models captured up to 69% of spatial variability in NO2 at urban near-traffic and urban background locations, and up to 58% of variability at all validation sites, including roadside locations. The absolute agreement of measurements and predictions (measured by MSE-R2) was similar to their correlation (measured by R2). Few previous studies have performed independent evaluations of national satellite-based LUR models, and there is little information on the performance of models developed with a small number of NO2 monitors. We have demonstrated that such models are a valid approach for estimating NO2 exposures in Australian cities.

Randomized controlled trial of oxygen saturation targets in very preterm infants: two year outcomes.

OBJECTIVE: To assess whether an oxygen saturation (Spo2) target of 85%-89% compared with 91%-95% reduced the incidence of the composite outcome of death or major disability at 2 years of age in infants born at <28 weeks' gestation. STUDY DESIGN: A total 340 infants were randomized to a lower or higher target from <24 hours of age until 36 weeks' gestational age. Blinding was achieved by targeting a displayed Spo2 of 88%-92% using a saturation monitor offset by ±3% within the range 85%-95%. True saturations were displayed outside this range. Follow-up at 2 years' corrected age was by pediatric examination and formal neurodevelopmental assessment. Major disability was gross motor disability, cognitive or language delay, severe hearing loss, or blindness. RESULTS: The primary outcome was known for 335 infants with 33 using surrogate language information. Targeting a lower compared with a higher Spo2 target range had no significant effect on the rate of death or major disability at 2 years' corrected age (65/167 [38.9%] vs 76/168 [45.2%]; relative risk 1.15, 95% CI 0.90-1.47) or any secondary outcomes. Death occurred in 25 (14.7%) and 27 (15.9%) of those randomized to the lower and higher target, respectively, and blindness in 0% and 0.7%. CONCLUSIONS: Although there was no benefit or harm from targeting a lower compared with a higher saturation in this trial, further information will become available from the prospectively planned meta-analysis of this and 4 other trials comprising a total of nearly 5000 infants.

A national satellite-based land-use regression model for air pollution exposure assessment in Australia.

Land-use regression (LUR) is a technique that can improve the accuracy of air pollution exposure assessment in epidemiological studies. Most LUR models are developed for single cities, which places limitations on their applicability to other locations. We sought to develop a model to predict nitrogen dioxide (NO2) concentrations with national coverage of Australia by using satellite observations of tropospheric NO2 columns combined with other predictor variables. We used a generalised estimating equation (GEE) model to predict annual and monthly average ambient NO2 concentrations measured by a national monitoring network from 2006 through 2011. The best annual model explained 81% of spatial variation in NO2 (absolute RMS error=1.4 ppb), while the best monthly model explained 76% (absolute RMS error=1.9 ppb). We applied our models to predict NO2 concentrations at the ~350,000 census mesh blocks across the country (a mesh block is the smallest spatial unit in the Australian census). National population-weighted average concentrations ranged from 7.3 ppb (2006) to 6.3 ppb (2011). We found that a simple approach using tropospheric NO2 column data yielded models with slightly better predictive ability than those produced using a more involved approach that required simulation of surface-to-column ratios. The models were capable of capturing within-urban variability in NO2, and offer the ability to estimate ambient NO2 concentrations at monthly and annual time scales across Australia from 2006-2011. We are making our model predictions freely available for research.

The effects of routine administration of probiotics on the length of central venous line usage in extremely premature infants.

Rajput N, Filipovska J, Hewson M. The effects of routine administration of probiotics on the length of central venous line usage in extremely premature infants. Turk J Pediatr 2017; 59: 20-27. The objective of this study was to determine whether the routine use of probiotics was associated with earlier removal of peripherally inserted central catheter (PICC) lines in extremely premature infants born ≤28 weeks' gestation. This study was a retrospective, observational, cohort study in infants born ≤28 weeks gestation in the 2 years before [No Probiotic Group (NPG)] and after [Probiotic Group (PG)] the commencement of the routine use of probiotics (lnfloran®) in a large tertiary neonatal intensive care unit in the North Island of New Zealand. Age at the removal of PICC line in patients whose first PICC lines were inserted before day 14 and remained in-situ for at least 4 days was compared using Kaplan-Meir Survival Analysis on SPSS 22.0®. We studied PICC line infections as a secondary outcome measure. We compared 120 PICC lines in NPG and 130 PICC lines in PG. Mean age at removal was 25.9 [(95% Confidence Intervals (CI)=22.6 - 29.2)] days in NPG and 23.1 (95% CI=20.9 - 25.2) days in PG. The result was independent of birth weight, gender, type of PICC line and age at insertion but related significantly to gestation at birth (p < 0.001). There was no difference in the incidence or the microbiologic profile of PICC line infections between the study groups. PICC lines were removed 2.8 days earlier in infants receiving probiotics (p=0.070), which can have potential benefits with reduced infection and other risks due to earlier removal of PICC lines.

A randomised, controlled trial of heparin in total parenteral nutrition to prevent sepsis associated with neonatal long lines: the Heparin in Long Line Total Parenteral Nutrition (HILLTOP) trial.

BACKGROUND: Infections are common complications of neonatal long lines. Heparin has been shown to prolong the effective duration of neonatal long lines and to reduce the ability of bacteria to adhere to foreign surfaces, but the effect of heparin on rates of infection is uncertain. OBJECTIVE: The goal of this study was to evaluate the effect of heparin on the frequency of episodes of catheter-related sepsis (CRS) in infants receiving total parenteral nutrition (TPN) through a neonatal long line. DESIGN/METHODS: This randomised, controlled, double blind, single-centre clinical trial compared heparin at 0.5 IU/ml with no heparin in TPN infused through a neonatal long line, with episodes of CRS as the primary outcome. RESULTS: 210 infants were enrolled (TPN with heparin n=102, TPN without heparin n=108). There was a statistically significant reduction in all episodes of culture-positive CRS in those infants with heparin added to the TPN compared with those without heparin (p=0.04; RR 0.57, 95% CI 0.32 to 0.98; number needed to treat 9, 95% CI 4.6 to 212.4). CONCLUSIONS: The addition of heparin at 0.5 IU/ml to TPN infused through a neonatal long line reduces the incidence of culture-positive CRS.

Severe congenital Factor VII deficiency associated with the 13q deletion syndrome.

The first reported case of clinically significant congenital Factor VII deficiency in association with the 13q deletion syndrome is presented. It illustrates the importance of knowledge of the specific genes involved in gross deletion syndromes and adds to the current clinical experience of this rare disease.