Low dose or very low dose phenylephrine and cyclopentolate microdrops for retinopathy of prematurity eye examinations (The Little Eye Drop Study): a randomised controlled non-inferiority trial.

OBJECTIVE: To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 µL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE). DESIGN: Multicentre, prospective, randomised controlled, non-inferiority clinical trial. SETTING: Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021. PATIENTS: Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE. INTERVENTIONS: The intervention: microdrop (approximately 7 µL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered. MAIN OUTCOME MEASURES: The primary outcome measure was an ophthalmologist-determined successful ROPEE. RESULTS: One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction -0.05 to 0.05) and for Maori (95% CI no continuity correction -0.02 to 0.19). CONCLUSION: VLD microdrops enable safe and effective screening for ROPEE in both Maori and non-Maori preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12619000795190.

A Survey of Neonatal Nurses on Mydriatic Regimens Used in Neonatal Retinopathy of Prematurity Eye Examinations.

OBJECTIVE: This study was aimed to determine mydriatic regimen(s) used in neonatal units in Aotearoa, New Zealand (NZ), and Australia and to estimate the frequency of adverse drug events following mydriatic administration in preterm neonates. STUDY DESIGN: A cross-sectional survey was sent to neonatal nursing staff listed in the Australian and New Zealand Neonatal Network contact list. Participants were asked to state what mydriatic regimen they use, and to estimate the frequency of adverse drug events when eye drops were administered for retinopathy of prematurity eye examinations (ROPEE). RESULTS: Thirteen different mydriatic regimens were identified; phenylephrine 2.5% and cyclopentolate 0.5% (1 standard drop of each) was the most commonly used regimen. Two of the regimens exceeded adult doses and five regimens included a mydriatic that is equivalent to an adult dose. Following mydriatic instillation, the three most common adverse effects were apnea, tachycardia, and periorbital pallor. CONCLUSION: Low-concentration single-microdrop regimens are currently in use and resulting in successful ROPEE, yet doses exceeding adult doses are in use throughout Aotearoa, NZ, and Australian units. We know from this dataset that neonates are experiencing unwanted and potentially preventable, adverse effects associated with mydriatics, and every effort should be made to minimize this risk. KEY POINTS: · Thirteen different regimens are in use in Aotearoa, NZ, and Australia.. · Three regimens use doses in excess of adult doses.. · Phenylephrine 2.5% and cyclopentolate 0.5% (one standard drop of each) is the most common regimen.

Randomised controlled pilot trial comparing low dose and very low- dose microdrop administration of phenylephrine and cyclopentolate for retinopathy of prematurity eye examinations in neonates.

AIMS: To determine ifVery low dose mydriatic eye microdrop regimen sufficiently dilates the pupil (above 4.1 mm) compared with the currently used low dose mydriatic eye microdrop regimen.Cardiovascular, gastrointestinal and respiratory adverse effects occur following eye drop instillation. METHODS: Seventeen premature infants were recruited into this prospective, randomised controlled pilot trial in January 2017 to November 2018. Data were collected from the single-centre Neonatal Intensive Care Unit, Dunedin Hospital, New Zealand. The inclusion criteria were birth weight less than 1500 g or gestational age less than 31 weeks, or any premature infant requiring red reflex testing. Infants were randomised to receive either phenylephrine 1% or 0.5% and cyclopentolate 0.2% or 0.1%, 1 microdrop in both eyes. Efficacy outcome measures were pupil size at retinopathy of prematurity eye examination (ROPEE) and ophthalmologist rating of ease of screen. RESULTS: All participants had sufficient pupillary dilation for a successful ROPEE. Ophthalmologists rated the ROPEE as easy for 90% of all examinations. Pupil dilation measurements at the time of examination, mean±SD, 4.8±0.2 (95% CI 4.5 to 5.2) mm for treatment A and 5±0.2 (95%CI 4.6 to 5.4) mm for treatment B (p=0.61). There were no statistically significant differences between the groups for safety data. CONCLUSIONS: Very low dose microdrop administration of phenylephrine and cyclopentolate appears to be effective at sufficiently dilating the neonatal pupil for ROPEEs. Low dose and very low dose microdrop mydriatic regimens may also reduce the risk of unwanted adverse effects associated with these medicines. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (reference ACTRN12616001266459p).

Probiotics for Prevention of Severe Necrotizing Enterocolitis: Experience of New Zealand Neonatal Intensive Care Units.

Introduction: Necrotizing enterocolitis (NEC) affects mainly preterm infants, has a multifactorial etiology and is associated with intestinal dysbiosis and disordered immunity. Use of probiotics for prophylaxis is beneficial with studies indicating reduction in NEC ≥ stage 2, late onset sepsis (LOS) and mortality. However, not all studies have shown a reduction, there are questions regarding which probiotic to use, whether infants <1,000 g benefit and the risk of probiotic sepsis. All neonatal intensive care units in New Zealand (NZ) use probiotics and contribute to an international database (Australian and New Zealand Neonatal Network or ANZNN). Objective: To use ANZNN data to investigate the experience of NZ neonatal units with probiotics for NEC prevention in a setting where the baseline incidence of severe NEC was low, to compare results of 2 commonly used probiotic regimes and report on the extremely low birth weight subgroup. Method: Outcomes before (Pre group 2007-2010) and after (Probiotic group 2013-2015) starting routine probiotics for preterm infants <1,500 g or <32 weeks were compared. Clinicians reviewed cases to ensure they met database criteria. Five units used Infloran (Bifidobacterium bifidum and Lactobacillus acidophilus) and 1 unit used Lactobacillus GG (LGG) and bovine lactoferrin (bLF). Results: Four thousand five hundred and twenty nine infants were included and Pre and Probiotic groups were well-balanced with regard to gestation, birth weight and gender. The incidence of NEC in the Probiotic group was 1.6 and 2.7% in the pre group (corrected OR 0.62 CI 0.41-0.94). There was one case of probiotic sepsis. There was no significant difference between the Infloran and LGG/bLF combinations in regard to observed NEC rates. Late onset sepsis rates were significantly lower in the Probiotic group (p < 0.01). Conclusions: Introduction of probiotics for preterm infants in NZ has been associated with significant reductions in NEC and late onset sepsis.

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.

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.

Risk factors for Staphylococcus capitis pulsotype NRCS-A colonisation among premature neonates in the neonatal intensive care unit of a tertiary-care hospital: a retrospective case-control study.

BACKGROUND: A S. capitis strain called NRCS-A (S. capitis NRCS-A) has emerged as a cause of bloodstream infections and sepsis in neonatal intensive care units (NICUs) worldwide. AIM: To identify risk factors for S. capitis NRCS-A colonisation among neonates, Dunedin Hospital NICU, Dunedin, New Zealand, from September 2013 through March 2015. METHODS: Weekly axillary swabs categorised eligible neonates as a case or a control. A case was defined as a week ending with a neonate's first positive swab for S. capitis NRCS-A and a control as a week in which a neonate remained negative. Weekly exposures were abstracted from hospital medical records. Analyses were performed using conditional logistic regression. FINDINGS: The median (range) gestational age at birth of participants was 32.7 (23.1-41.3) weeks. Participants contributed 26 weeks of case data and 177 weeks of control data. On adjusted analysis compared with matched controls, cases had higher odds of requiring invasive mechanical ventilation (OR 3.6, 95% CI: 1.1-11.6, p=0.035) and of a patent ductus arteriosus (PDA) (OR 3.0, 95% CI: 1.0-9.0, p=0.044). Cases had lower odds of being part of a multiple birth (OR 0.24, 95% CI 0.08-0.73, p=0.001), having an area of inflamed skin (OR 0.31, 95% CI: 0.13-0.75, p=0.009), and specifically an area of inflamed axillary skin (OR 0.08, 95% CI: 0.01-0.50, p=0.006). CONCLUSIONS: We found that premature neonates with invasive mechanical ventilation and PDA had greater odds for S. capitis NRCS-A colonisation. Transmission may be mediated by increased staff contact, but prospective research is needed to confirm this.

In vitro validation of a method for neonatal urine collection and analysis.

OBJECTIVE: Urine collection and analysis is important for diagnosis, monitoring of clinical progress, and research in neonates. This study aims to validate a novel methodology for neonatal urine collection, which combines the convenience of cotton ball collection with accurate timing via a urine continence monitor. DESIGN: Laboratory model using a combined cotton ball and urinary incontinence monitor method with and without the presence of an impermeable membrane to prevent desiccation. MAIN OUTCOME MEASURES: Accuracy, bias and precision in measurement of urine volume, electrolytes (sodium, potassium, chloride), creatinine and gentamicin. Changes in analyte concentration over time, and evaporative loss of water, were tested using analysis of variance. The effects of time, temperature and humidity were explored using multivariate analysis of variance. RESULTS: With the use of an impermeable membrane, sodium concentration increased from a mean (SD) of 3.57% (0.68) at 1 min to 5.03% (0.74) at 120 min. There was no significant change in potassium, chloride or creatinine concentrations. Gentamicin concentration decreased by a mean (SD) of 9.05% (1.37) by 30 min. Multivariate analysis found that absolute change in weight, sodium and chloride were only dependent on duration. Gentamicin concentration was affected by duration, humidity and temperature. Relative evaporative loss was minimal at -0.58% (0.31), and the urinary continence monitor was 100% successful at detecting urination for all time points. CONCLUSIONS: This novel methodology provides a standardisable and practical method to collect small volumes of neonatal urine for accurate measurement of both urine output and analyte concentrations.

Systematic review of mydriatics used for screening of retinopathy in premature infants.

INTRODUCTION: Routine retinopathy of prematurity eye examinations are an important part of neonatal care, and mydriatic medicines are essential in dilating the pupil for the eye examination. There are concerns about the level of evidence for efficacy and safety of these mydriatic medicines. OBJECTIVE: This review evaluates both efficacy and safety evidence of mydriatics used during the retinopathy of prematurity eye examination. METHOD: Systematic literature review. RESULTS: There is limited evidence guiding clinical practice for safety and efficacy of mydriatics. The majority of publications are underpowered and with an unclear to high level of bias. There are a wide variety of mydriatic regimens evaluated for efficacy and safety, and multiple regimens are associated with case reports. CONCLUSIONS: Current international guideline seems unnecessarily high, especially when the reviewed literature suggest that lower doses are effective, albiet from underpowered studies. The lowest effective combination regimen appears to be phenylephrine 1% and cyclopentolate 0.2% (1 drop). Microdrop administration of this regimen would further increase the safety profile, however, efficacy needs to be assessed.

Newborn Vitamin K Prophylaxis: A Historical Perspective to Understand Modern Barriers to Uptake.

Since its initial discovery almost a century ago, vitamin K has been labeled as both lifesaving and malignancy causing. This has led to debate of not only its use in general but also regarding its appropriate dose and route. In this article, we review through a historical lens the past 90 years of newborn vitamin K from its discovery through to its modern use of preventing vitamin K deficiency bleeding (VKDB). Although researchers in surveillance studies have shown considerable reductions in VKDB following intramuscular vitamin K prophylaxis, ongoing barriers to the universal uptake of vitamin K prophylaxis remain. Reviewing the history of newborn vitamin K provides an opportunity for a greater understanding of the current barriers to uptake that we face. Although at times difficult, improving this understanding may allow us to address contentious issues related to parental and health professional beliefs and values as well as improve overall communication. The ultimate goal is to improve and maintain the uptake of vitamin K to prevent VKDB in newborns.

Genomic Analysis of Multiresistant Staphylococcus capitis Associated with Neonatal Sepsis.

Coagulase-negative staphylococci (CoNS), such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole-genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation, and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug resistant. Although similar to globally circulating NICU-associated S. capitis strains at a core-genome level, NZ NICU S. capitis isolates carried a novel stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable from environmental S. capitis isolates found on fomites, such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.

Multi-Locus Next-Generation Sequence Typing of DNA Extracted From Pooled Colonies Detects Multiple Unrelated Candida albicans Strains in a Significant Proportion of Patient Samples.

The yeast Candida albicans is an important opportunistic human pathogen. For C. albicans strain typing or drug susceptibility testing, a single colony recovered from a patient sample is normally used. This is insufficient when multiple strains are present at the site sampled. How often this is the case is unclear. Previous studies, confined to oral, vaginal and vulvar samples, have yielded conflicting results and have assessed too small a number of colonies per sample to reliably detect the presence of multiple strains. We developed a next-generation sequencing (NGS) modification of the highly discriminatory C. albicans MLST (multilocus sequence typing) method, 100+1 NGS-MLST, for detection and typing of multiple strains in clinical samples. In 100+1 NGS-MLST, DNA is extracted from a pool of colonies from a patient sample and also from one of the colonies. MLST amplicons from both DNA preparations are analyzed by high-throughput sequencing. Using base call frequencies, our bespoke DALMATIONS software determines the MLST type of the single colony. If base call frequency differences between pool and single colony indicate the presence of an additional strain, the differences are used to computationally infer the second MLST type without the need for MLST of additional individual colonies. In mixes of previously typed pairs of strains, 100+1 NGS-MLST reliably detected a second strain. Inferred MLST types of second strains were always more similar to their real MLST types than to those of any of 59 other isolates (22 of 31 inferred types were identical to the real type). Using 100+1 NGS-MLST we found that 7/60 human samples, including three superficial candidiasis samples, contained two unrelated strains. In addition, at least one sample contained two highly similar variants of the same strain. The probability of samples containing unrelated strains appears to differ considerably between body sites. Our findings indicate the need for wider surveys to determine if, for some types of samples, routine testing for the presence of multiple strains is warranted. 100+1 NGS-MLST is effective for this purpose.

tuf Gene Sequence Variation in Bifidobacterium longum subsp. infantis Detected in the Fecal Microbiota of Chinese Infants.

Members of the bacterial genus Bifidobacterium generally dominate the fecal microbiota of infants. The species Bifidobacterium longum is prevalent, but the B. longum subsp. longum and B. longum subsp. infantis strains that are known to colonize the infant bowel are not usually differentiated in microbiota investigations. These subspecies differ in their capacities to metabolize human milk oligosaccharides (HMO) and may have different ecological and symbiotic roles in humans. Quantitative PCR provides a quick analytical method by which to accurately ascertain the abundances of target species in microbiotas and microcosms. However, amplification targets in DNA extracted from samples need to be dependably differential. We evaluated the tuf gene sequence as a molecular target for quantitative PCR measurements of the abundances of B. longum subsp. infantis and B. longum subsp. longum in fecal microbiotas. This approach resulted in the detection of a tuf gene variant (operational taxonomic unit 49 [OTU49]) in Chinese infants that has sequence similarities to both B. longum subsp. infantis and B. longum subsp. longum We compared the genome sequence and growth and transcriptional characteristics of an OTU49 isolate cultured in HMO medium to those of other B. longum subsp. infantis cultures. We concluded from these studies that OTU49 belongs to B. longum subsp. infantis, that dependable quantitative PCR (qPCR) differentiation between the B. longum subspecies cannot be achieved by targeting tuf gene sequences, and that functional genes involved in carbohydrate metabolism might be better targets because they delineate ecological functions.IMPORTANCE High-throughput DNA sequencing methods and advanced bioinformatics analysis have revealed the composition and biochemical capacities of microbial communities (microbiota and microbiome), including those that inhabit the gut of human infants. However, the microbiology and function of natural ecosystems have received little attention in recent decades, so an appreciation of the dynamics of gut microbiota interactions is lacking. With respect to infants, rapid methodologies, such as quantitative PCR, are needed to determine the prevalences and proportions of different bifidobacterial species in observational and microcosm studies in order to obtain a better understanding of the dynamics of bifidobacterial nutrition and syntrophy, knowledge that might be used to manipulate the microbiota and perhaps ensure the better health of infants.

A minitablet formulation made from electrospun nanofibers.

The purpose of this study was to evaluate electrospun drug loaded nanofibers as a new matrix for minitablets. Prednisone, a poorly water-soluble drug, was loaded into povidone (polyvinylpyrrolidone, PVP) nanofibers using the process of electrospinning. The drug-loaded nanofiber mat was compressed into minitablets with a 2mm diameter and a height of 2.63±0.04mm. SEM analysis of the minitablet identified a nano-web structure with a nanofiber diameter in the range of 400-500nm. The minitablets met the requirements of the US Pharmacopeia with respect to content uniformity and friability. DSC and XRPD analysis of the minitablet indicated that the drug-polymer mixture was a one-phase amorphous system. XRPD analysis of the drug loaded nanofiber mat after 10-months of storage at ambient temperature showed no evidence of recrystallization of the drug. Solubility and dissolution properties of the drug formulated into a nanofiber mat and minitablet were evaluated. These results show that electrospun nanofibers may provide a useful matrix for the further development of minitablets.

Insulin resistance, glucagon-like peptide-1 and factors influencing glucose homeostasis in neonates.

OBJECTIVES: To explore the relationships between postmenstrual age (PMA), insulin, C-peptide, glucagon and blood glucose concentrations (BGCs) in preterm and term neonates. To compare glucagon-like peptide-1 (GLP-1) concentrations in fed versus never-fed neonates. DESIGN: Observational. SETTING: Dunedin Hospital Neonatal Intensive Care Unit, New Zealand. PATIENTS: Term or preterm euglycaemic neonates (102) receiving routine blood tests (343 samples). INTERVENTIONS: None: plasma was obtained from surplus samples from routine clinical care. MAIN OUTCOME MEASURES: Insulin, C-peptide, GLP-1 and glucagon concentrations were measured in temporal association with BGC. RESULTS: Insulin and C-peptide concentrations were elevated in very preterm infants (PMA≤32 weeks) and decreased to term; this relationship persisted when BGCs were accounted for. Generalised linear mixed models showed that insulin:C-peptide ratio and insulin:BGC ratio decreased significantly with increasing PMA (p<0.001). GLP-1 increased following initial oral feeds regardless of PMA (p<0.001). CONCLUSION: Preterm neonates exhibit insulin resistance in the absence of hyperglycaemia. Enteral feeds result in an increase in GLP-1. These factors are likely to contribute to the increased risk of hyperglycaemia in premature neonates (PMA<32 weeks).

Hyperglycaemic preterm neonates exhibit insulin resistance and low insulin production.

OBJECTIVES: To explore and compare the relationships between postmenstrual age (PMA), insulin, C-peptide and blood glucose concentrations (BGC) in hyperglycaemic and euglycaemic preterm neonates (PMA <30 weeks). DESIGN: Observational. SETTING: Dunedin Hospital Neonatal Intensive Care Unit, New Zealand. PATIENTS: Preterm neonates were recruited and included nine insulin-treated hyperglycaemic and 20 euglycaemic neonates. Samples for euglycaemic neonates were obtained from leftover blood, and for insulin-treated neonates, additional blood was collected at the same time as the patients' routine 4 hourly blood glucose test over a 24-hour period (six samples). MAIN OUTCOME MEASURES: Blood samples were collected, plasma was analysed for insulin and C-peptide and was measured in temporal association with BGC. RESULTS: The euglycaemic neonates had a mean PMA (SD) of 28 (1.4) weeks and the insulin-treated neonates had 25.5 (1.8) weeks. C-peptide plasma concentrations were significantly lower (p<0.01) in the insulin-treated hyperglycaemic neonates (51.7 (100) pmol/L; 200(208) pmol/L) indicating lower insulin production. Insulin plasma concentrations (r=-0.38), BGC (r=-0.38), C-peptide plasma concentrations (r=0.36) and insulin/C-peptide ratios (r=-0.49) were all significantly affected by PMA (p<0.01). As expected, insulin plasma concentrations were higher in the insulin-treated hyperglycaemic neonates (156 (161) pmol/L; 93.2 (63.1) pmol/L, p<0.01) confirming that intravenous exogenous insulin reached these neonates. CONCLUSIONS: This study demonstrates that preterm neonates exhibit insulin resistance, hyperglycaemic neonates have lower insulin production than euglycaemic neonates and treatment with exogenous insulin did not appear to suppress insulin production in these neonates.

Why do parents decline newborn intramuscular vitamin K prophylaxis?

OBJECTIVE: To explore the influencing factors and reasoning of parents who opt out of intramuscular vitamin K prophylaxis for their newborn. DESIGN: We conducted a qualitative study with 15 families from the Otago/Southland region of New Zealand. Semistructured interviews explored their choice to opt out of intramuscular vitamin K prophylaxis and thematic analysis was used to elucidate themes that captured important aspects of this parental decision-making process. RESULTS: Parents opt out of intramuscular vitamin K for a variety of reasons. These were clustered into three main themes: parents' beliefs and values (philosophy and spirituality), concerns about their child's welfare (pain and potential side effects) and external influencing factors (family, friends, media and health professionals). As part of a wider family hesitancy towards medical intervention, the majority of parents also raised concerns regarding other perinatal or childhood interventions. CONCLUSION: Many factors influence parental decision making and lead to a decision to opt out of newborn intramuscular vitamin K prophylaxis. Due to strong parallels with other common childhood interventions, these findings have relevance for vitamin K prophylaxis and for other healthcare interventions in childhood.

In-hospital morbidity and brain metrics of preterm neonates born 1998-2009.

AIMS: To describe the survival, in-hospital morbidity, brain metrics and two-year neurodevelopmental outcomes of two extremely preterm cohorts and discuss the contribution of changes in clinical practice to these outcomes. METHODS: Retrospective comparative cohort study, of two cohorts of neonates born <28 weeks gestation: 47 infants born 1998-2000 and 39 infants 2006-2009. RESULTS: Comparing historical to the contemporary cohort respectively, admission temperature (35.9 degrees C, 36.5) and CRIB (Clinical Risk Index in Babies) score (5.4, 3.1) improved. Inotrope support fell significantly (55.3%, 28.2%). High frequency ventilation days fell (8.0, 2.7). CPAP days increased significantly (32.2, 47.9). Chronic lung disease at 36 weeks corrected age fell significantly (61.7%, 38.5%). Red cell transfusions decreased in number (7.1, 4.8) and volume (96.2ml/kg, 70.4ml/kg). Retinopathy of prematurity (ROP) rates dropped significantly (66.0%, 28.2%). Survival was not significantly different. Nutritional improvements included shorter days to first enteral feed (3.4, 2.0), target protein (5.4, 4.3) and lipid levels (7.1, 4.1) with better breastfeeding rates at discharge (19.2%, 38.5%). By 36 weeks z scores for weight (-0.90, -0.39) were improved but not length (-1.94, -1.26) or head circumference (-0.72, -0.69). MRI brain metrics showed a significant improvement in bifrontal (59.2, 65.9), biparietal (73.7, 79.3) and transcerebellar diameter (50.6, 52.6) with improved neurodevelopmental outcome at two years. CONCLUSION: The contemporary cohort had better initial physiological stability, less chronic lung disease and retinopathy, improved body growth at 36 weeks and brain metrics at term equivalent. Improvement in neurodevelopment at two years has been seen and further analysis will be important to understand the impact of the changes in clinical care.

Haematocrit influences insulin concentration measurements in dried blood spots.

INTRODUCTION: A major barrier to conducting pharmacokinetic studies in neonates is the relatively large blood volume required by most assays. The use of dried blood spots (DBS) has potential to enable the use of smaller volumes and simplify sample processing and handling. AIM: The aim of this study is to determine the effect of haematocrit on insulin concentrations from DBS. METHODS: DBS of varying haematocrit (0.25-0.65) were prepared at three insulin plasma concentrations (10, 25, and 50 mU/L). DBS were analysed for insulin using the method developed by Butter et al. (2001). DBS and paired plasma samples were obtained from neonates at Dunedin Hospital NICU. RESULTS: Insulin chemiluminescence responses were significantly lower at higher haematocrit values (p < 0.05). All results showed high variability (CV% = 9-61%). Calculated whole blood concentrations were plotted against chemiluminescence and an exponential function [Formula: see text] fitted. Plasma insulin concentrations from neonatal DBS were typically higher than paired plasma samples. CONCLUSIONS: Haematocrit has a significant effect on insulin measurement by chemiluminescence when using DBS. Plasma insulin concentration could be determined when haematocrit was known. DBS insulin concentrations higher than plasma indicate that insulin may be present in red blood cells. However, measuring plasma insulin concentrations with DBS in neonates is not ideal due to high variability.