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Background Strategies to improve outcomes for Australian First Nations mothers and babies are urgently needed. Caseload midwifery, where women have midwife-led continuity throughout pregnancy, labour, birth and the early postnatal period, is associated with substantially better perinatal health outcomes, but few First Nations women receive it. We assessed the capacity of four maternity services in Victoria, Australia, to implement, embed, and sustain a culturally responsive caseload midwifery service. Methods A prospective, non-randomised research translational study design was used. Site specific culturally responsive caseload models were developed by site working groups in partnership with their First Nations health units and the Victorian Aboriginal Community Controlled Health Organisation. The primary outcome was to increase the proportion of women having a First Nations baby proactively offered and receiving caseload midwifery as measured before and after programme implementation. The study was conducted in Melbourne, Australia. Data collection commenced at the Royal Women's Hospital on 06/03/2017, Joan Kirner Women's and Children's Hospital 01/10/2017 and Mercy Hospital for Women 16/04/2018, with data collection completed at all sites on 31/12/2020. Findings The model was successfully implemented in three major metropolitan maternity services between 2017 and 2020. Prior to this, over a similar timeframe, only 5.8% of First Nations women (n = 34) had ever received caseload midwifery at the three sites combined. Of 844 women offered the model, 90% (n = 758) accepted it, of whom 89% (n = 663) received it. Another 40 women received standard caseload. Factors including ongoing staffing crises, prevented the fourth site, in regional Victoria, implementing the model. Interpretation Key enablers included co-design of the study and programme implementation with First Nations people, staff cultural competency training, identification of First Nations women (and babies)

Objective: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. Method(s): A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. Result(s): Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. Significance: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, i

Aim: This study aimed to determine the feasibility and parental acceptability of screening for congenital cytomegalovirus (cCMV) through saliva polymerase chain reaction in infants who did not pass their newborn hearing screening. Additionally, the utility (i.e. time to diagnosis and treatment) of this enhanced clinical pathway was evaluated. Method(s): The study was conducted through the Victorian Infant Hearing Screening Programme (VIHSP) across four maternity hospitals in Melbourne, Australia, during June 2019-March 2020. Parents were approached by VIHSP staff about obtaining a test for cytomegalovirus (CMV) at the time of their baby's second positive ('refer') result on the VIHSP screen. Participating parents collected a saliva swab for CMV polymerase chain reaction from their infants. Feasibility was determined by the proportion of 'referred' infants whose parents completed the salivary CMV screening test <=21 days of life. Acceptability was measured through parent survey. Result(s): Of 126 eligible families, 96 (76.0%) had salivary screening swabs taken <=21 days of life. Most families (>92.0%) indicated that screening was acceptable, straightforward and thought testing their baby for cCMV was a good idea. One infant screened positive on day 30, was diagnosed with cCMV via confirmatory testing by day 31 and commenced valganciclovir on day 32. Conclusion(s): Obtaining a saliva sample to screen for cCMV in infants who do not pass their newborn hearing screen is feasible and appears acceptable to parents. This targeted cCMV screening method could be an option where mothers are rapidly discharged from hospital, especially in the context of the COVID-19 pandemic.Copyright © 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Background: Regenerative cell therapies for various neonatal morbidities are increasingly entering early phase clinical trials. However, infusion protocols for delivering cells have been largely adopted from adult protocols and have not been evaluated in infants. We aimed to explore the effects of the different cell infusion parameters on cell delivery to define the optimum protocol for the administration of a leading cell therapy, human amnion epithelial cells (HAECS), to extremely preterm infants. Method(s): Standard cell infusion protocols were modelled, varying the infusion parameters including: albumin concentration (2% vs. 4%), syringe orientation (horizontal vs. vertical), IVline volume (0.2-2.2 ml), and flow rate (3-15 ml/HR). Result(s): The standard (previously published) cell infusion protocol delivered a mean (SD) of 20(9)% of intended HAEC dose. Increasing albumin concentration to 4%, positioning the syringe vertically, and decreasing IV-line volume to 0.6 ml increased cell delivery to a mean (SD) of 98(6)% of intended cell dose. Flow rate had little effect on dose delivery when other conditions were optimised. Conclusion(s): It is essential that cell infusion protocols are optimised for small volume delivery in preterm infants. We describe the refinement and validation of a cell infusion protocol that offers reliable delivery of intended cell doses, suitable for extremely preterm neonates. Previously published work should be viewed with caution given the possibility that only a fraction of intended cell dose was actually delivered.

INTRODUCTION: Bronchopulmonary dysplasia (BPD), an important sequela of preterm birth, is associated with long-term abnormalities of lung function and adverse neurodevelopmental outcomes. Inflammation, inhibition of secondary septation and vascular maldevelopment play key roles in the pathogenesis of BPD. Human amnion epithelial cells (hAECs), stem-like cells, derived from placental tissues are able to modulate the inflammatory milieu and, in preclinical studies of BPD-like injury, restore lung architecture and function. Allogeneic hAECs may present a new preventative and reparative therapy for BPD. METHODS AND ANALYSIS: In this two centre, phase Icell dose escalation study we will evaluate the safety of intravenous hAEC infusions in preterm infants at high risk of severe BPD. Twenty-four infants born at less than 29 weeks' gestation will each receive intravenous hAECs beginning day 14 of life. We will escalate the dose of cells contained in a single intravenous hAEC infusion in increments from 2million cells/kg to 10million cells/kg. Further dose escalation will be achieved with repeat infusions given at 5day intervals to a maximum total dose of 30million cells/kg (three infusions). Safety is the primary outcome. Infants will be followed-up until 2 years corrected age. Additional outcome measures include a description of infants' cytokine profile following hAEC infusion, respiratory outcomes including BPD and pulmonary hypertension and other neonatal morbidities including neurodevelopmental assessment at 2 years. ETHICS AND DISSEMINATION: This study was approved on the June12th, 2018 by the Human Research Ethics Committee of Monash Health and Monash University. Recruitment commenced in August 2018 and is expected to take 18 months. Accordingly, follow-up will be completed mid-2022. The findings of this study will be disseminated via peer-reviewed journals and at conferences. PROTOCOL VERSION: 5, 21 May 2018. TRIAL REGISTRATION NUMBER: ACTRN12618000920291; Pre-resul

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. Method(s): A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed. Result(s): 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. Conclusion(s): 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.Copyright © 2020 The Author(s).

Background & Aim: Background: Advances in neonatal intensive care have been associated with improved survival of preterm infants. But along with survival, the morbidity bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is also increasing. BPD is associated with adverse respiratory outcomes into adulthood and greater risk of adverse neurodevelopment. Infants born <= 28 weeks' gestation, during the canalicular phase of lung development prior to alveolar and distal capillary development, are at greatest risk of BPD. Disruption of lung maturation by the pro-inflammatory environment created by lifesaving neonatal intensive care interventions results in the BPD we see today - a disease characterised by arrested development with simplified alveoli and abnormal angiogenesis. As the role of inflammation in BPD comes into focus, cell therapy presents a promising intervention for its prevention. Human amnion epithelial cells (hAECs), stem-like cells derived from placental tissues, have multi-lineage potential, are immune privileged and, in small animal models are non-teratogenic. Preclinical work demonstrates the cells capacity to modulate the inflammatory environment to both prevent injury and aid repair of established injury in diverse models of lung disease. A first-in-human study recently demonstrated the safety of low dose hAECs in preterm infants with established BPD. However, hAECs are likely to have greater therapeutic potential when used to prevent lung injury thus, the next step in translation is to evaluate the safety of hAECs in less mature infants at high risk of developing BPD. Aim(s): To evaluate the safety of escalating doses of intravenous hAECs in infants born <= 28 weeks' gestation at high risk of BPD. Methods, Results & Conclusion Method: In this phase 1 study, 24 infants born at <=28 weeks' gestation at high risk of BPD will each receive intravenous hAECs from Day 14 of life. The infusion dose will escalate from 2 million cells/kg

Objective To determine the impact of one probiotics combination on the neurodevelopment of very preterm children at 2-5 years corrected gestational age (CA). Design Follow-up study of survivors of a double-blinded, placebo-controlled, randomised trial of probiotic effects on late-onset sepsis in very preterm infants that found reduced necrotising enterocolitis. setting 10 tertiary perinatal centres in Australia and New Zealand. Patients 1099 very preterm infants born <32 weeks' gestation and weighing <1500 g. Intervention Probiotics (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis) or placebo administered from birth until discharge home or term CA, whichever came sooner. Main outcome measures Major neurodevelopmental impairment comprised any of moderate/severe cerebral palsy (Gross Motor Function Classification System score 2-5), motor impairment (Bayley-III Motor Composite Scale <-2SD or Movement Assessment Battery for Children <15th centile if >>42 months' CA), cognitive impairment (Bayley-III Composite Cognitive or Language Scales <-2SD or Wechsler Preschool and Primary Scale of Intelligence Full Scale Intelligence Quotient <-2SD if >>42 months' CA), blindness or deafness. results Outcome data were available for 735 (67%) participants, with 71 deaths and 664/1028 survivors assessed at a mean age of 30 months. Survival free of major neurodevelopmental impairment was comparable between groups (probiotics 281 (75.3%) vs placebo 271 (74.9%); relative risk 1.01 (95% CI 0.93 to 1.09)). Rates of deafness were lower in probiotic-treated children (0.6% vs 3.4%). Conclusion Administration of the probiotics combination Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis to very preterm babies from soon after birth until discharge home or term CA did not adversely affect neurodevelopment or behaviour in early childhood.Copyright © Article author(s) (or their employer(s) unless otherwise stated in the text of the art

Background Infants of women with diabetes in pregnancy are at increased risk of hypoglycaemia, admission to a neonatal intensive care unit (NICU), and not being exclusively breastfed. Many clinicians encourage women with diabetes in pregnancy to express and store breastmilk in late pregnancy, yet no evidence exists for this practice. We aimed to determine the safety and efficacy of antenatal expressing in women with diabetes in pregnancy. Methods We did a multicentre, two-group, unblinded, randomised controlled trial in six hospitals in Victoria, Australia. We recruited women with pre-existing or gestational diabetes in a singleton pregnancy from 34 to 37 weeks' gestation and randomly assigned them (1:1) to either expressing breastmilk twice per day from 36 weeks' gestation (antenatal expressing) or standard care (usual midwifery and obstetric care, supplemented by support from a diabetes educator). Randomisation was done with a computerised random number generator in blocks of size two and four, and was stratified by site, parity, and diabetes type. Investigators were masked to block size but masking of caregivers was not possible. The primary outcome was the proportion of infants admitted to the NICU. We did the analyses by intention to treat; the data were obtained and analysed masked to group allocation. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000217909. Findings Between June 6, 2011, and Oct 29, 2015, we recruited and randomly assigned 635 women: 319 to antenatal expressing and 316 to standard care. Three were not included in the primary analysis (one withdrawal from the standard care group, and one post-randomisation exclusion and one withdrawal from the antenatal expressing group). The proportion of infants admitted to the NICU did not differ between groups (46 [15%] of 317 assigned to antenatal expressing vs 44 [14%] of 315 assigned to standard care; adjusted relative risk 1.06, 95% CI 0.66 to 1.46)