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Purpose of ReviewCerebral palsy is the most common physical disability of childhood, but the rate is falling, and severity is lessening. We conducted a systematic overview of best available evidence (2012–2019), appraising evidence using GRADE and the Evidence Alert Traffic Light System and then aggregated the new findings with our previous 2013 findings. This article summarizes the best available evidence interventions for preventing and managing cerebral palsy in 2019.Recent FindingsEffective prevention strategies include antenatal corticosteroids, magnesium sulfate, caffeine, and neonatal hypothermia. Effective allied health interventions include acceptance and commitment therapy, action observations, bimanual training, casting, constraint-induced movement therapy, environmental enrichment, fitness training, goal-directed training, hippotherapy, home programs, literacy interventions, mobility training, oral sensorimotor, oral sensorimotor plus electrical stimulation, pressure care, stepping stones triple P, strength training, task-specific training, treadmill training, partial body weight support treadmill training, and weight-bearing. Effective medical and surgical interventions include anti-convulsants, bisphosphonates, botulinum toxin, botulinum toxin plus occupational therapy, botulinum toxin plus casting, diazepam, dentistry, hip surveillance, intrathecal baclofen, scoliosis correction, selective dorsal rhizotomy, and umbilical cord blood cell therapy.SummaryWe have provided guidance about what works and what does not to inform decision-making, and highlighted areas for more research.

Mesenchymal stromal cells (MSCs) have been under clinical investigation for the treatment of cerebral palsy (CP) for over a decade. However, the field has been limited by study heterogeneity and variable reports of efficacy. We conducted a scoping review of published and registered reports of MSC treatment for CP, with meta-analysis of Gross Motor Function Measure (GMFM) outcomes to summarize research and provide future recommendations. Thirty published reports and 10 registered trials were identified, including 1292 people with CP receiving MSCs. Most received ≥2 doses (72%) of umbilical cord tissue MSCs (75%), intrathecally (40%) or intravenously (38%), and 31% were treated via compassionate/Expanded access. MSC treatment was safe and meta-analyses demonstrated that MSCs conferred significant improvements in GMFM at 3 − (1.05 (0.19–1.92), p = 0.02), 6 − (0.97 (0.30–1.64), p = 0.005) and 12 months (0.99 (0.30–1.67), p = 0.005) post-treatment. Whilst MSCs are safe and improve GMFM outcomes in CP with large effect sizes, study and participant variability continues to confound data interpretation and limits subgroup analyses. With no published Phase 3 trials and high rates of compassionate access, the field would benefit from well-designed trials with unified outcomes. Additionally, data sharing to enable Individual Participant Data Meta-Analysis would support the determination of optimal source, route and dose to progress towards regulatory approval.

BackgroundThere has been little decline in neonatal mortality rates over recent decades, and this is now further challenged by the rising prevalence of antimicrobial resistance. In Australia, the incidence of neonatal sepsis is low on a global scale, yet there are increasingly frequent outbreaks of multidrug-resistant (MDR) infections in neonatal intensive care units, alongside rising rates of colonisation with MDR bacteria.MethodsWe analysed positive blood and cerebrospinal fluid cultures collected from infants (aged 0 to ≤180 days) across five clinical sites in Australia between 2010 and 2019, to determine evolving antimicrobial susceptibility profiles.ResultsAfter excluding presumed contaminants, we analysed 743 pathogenic bacterial isolates cultured from 624 neonates and infants with early-onset (≤72 hours), late-onset (>72 hours to ≤28 days) and very late-onset (>28 days to ≤180 days) infections. Escherichia coli (37%) and Streptococcus agalactiae (31%) were the primary pathogens responsible for early-onset bloodstream infections, while coagulase-negative staphylococci, E. coli and Staphylococcus aureus were responsible for most infections in older neonates and infants. Antimicrobial susceptibility to currently recommended empiric regimens remains high; however, gram-negative bacteria—including MDR bacteria—were responsible for an increasing proportion of very late-onset infections over the study period (22% in 2010–2014 vs 34% in 2015–2019; p=0.07).ConclusionsAlthough empiric antimicrobial regimens remain adequate for most pathogens causing infections in neonates and infants in Australia, there is an increasing burden of invasive infections caused by gram-negative bacteria. Ongoing surveillance is necessary to ensure empiric antimicrobial guidelines remain efficacious and appropriate.

Repetitive and prolonged experience of pain by infants in neonatal intensive care units (NICUs) may adversely affect growth and alter pain responses. The degree of infant prematurity and/or presence of neurological impairment (NI) may impact an infant's ability to behaviorally respond to pain. This study aimed to determine whether the scores on the mPAT, a widely used pain assessment tool, is impacted by postmenstrual age (PMA) at assessment, irrespective of neurological impairment. Data from medical records were collected on infants admitted to the NICU who underwent a pain assessment with the modified Pain Assessment Tool (mPAT) between March 2019 and September 2021. Total mPAT, behavioral, and physiological pain scores were independently analyzed using logistic regression to detect differences based on PMA categories (< 33 weeks, 33–36 weeks, ≥ 37 weeks) and presence of NI. Significant differences were indicated when p < 0.05. Of 204 infants sampled, 62% were male, and 71% were born at term‐age (i.e., ≥ 37 wks). Thirty‐six (18%) infants had a queried or confirmed NI and 28 (14%) infants were postsurgical. Logistic regression analysis showed that neither PMA nor presence of NI predicted pain for total mPAT scores (χ2 (3) = 3.9, p > 0.05) or physiological scores (χ2 (3) = 2.7, p > 0.05). Higher behavioral scores were 3.7 times (OR 0.27, 95% CI 0.10–0.77, p = 0.01) more likely in extremely‐to‐very preterm (< 33 weeks) infants when compared to term (≥ 37 weeks) infants. The mPAT may be suitable for clinicians to utilize when assessing infants in NICUs regardless of PMA or NI status. The higher behavioral responses in younger infants require further investigation in a future prospective study.

ObjectiveTo determine associations of low superior vena cava (SVC) flow (≤55 ml/kg/min) and low right ventricular output (RVO) (≤150 ml/kg/min) in preterm infants.Design/methodsAn observational study in infants <30 weeks gestation randomized to receive immediate (<10 s) or delayed cord clamping (DCC) (≥60 s).ResultsThe study enrolled 265 infants with a mean (SD) gestation 28 (2) weeks. Eighty-six (33%) infants had low SVC flow and 81 (31%) infants had low RVO. In multivariate analysis, low SVC flow was associated with gestation; low RVO was associated with DCC, gender and 5-minute Apgar; whereas mean RVO was negatively associated with both FiO2 and mean airway pressure (MAP) at 9 h and 24 h. Low SVC flow was associated with ductus arteriosus (DA) treatment. Infants with low RVO had higher mortality on univariate analysis, but this was not significant after adjusting for gestation.ConclusionsSVC flow was associated with gestation, whilst RVO was associated with placental transfusion, gender, condition at birth, and early respiratory adaptation. Compared to infants with normal values, more infants with low SVC flow were treated for DA, but infants with low RVO had no significant difference in mortality or morbidity.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

IntroductionDelayed cord clamping (DCC) is an evidence-based intervention that reduces mortality, anaemia and disability in infants born <37 weeks’ gestation who do not require immediate resuscitation. However, it is neither reliably recorded nor routinely implemented in Australia. The Wait a Minute or More (WAMM) study aims to reduce this gap between the evidence and practice by integrating timely sharing of cord clamping data with Evidence-based Practice for Improving Quality methods to increase the proportion of preterm infants receiving DCC for 60 s or longer (DCC60).MethodsThe WAMM study is a pragmatic stepped wedge cluster randomised trial (SW-CRT), informed by the Integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework. Up to 20 Australian maternity hospitals will participate in this pragmatic SW-CRT to evaluate if in (Population) infants <37 weeks’ gestation who do not need resuscitation, does (Intervention) the WAMM intervention (sharing of anonymised data on DCC60, together with a locally adapted quality improvement (QI) programme), compared with (Control) sharing of anonymised data on DCC60 alone, increase (primary Outcome) the proportion of infants receiving DCC60? At the end of 72 weeks, all sites will complete an 8-week period without the WAMM intervention to evaluate if implementation of DCC is sustained. Alongside the SW-CRT, an embedded process evaluation will assess the fidelity, acceptability, mechanisms of action and contextual barriers and enablers of the WAMM intervention.DiscussionUsing the stepped wedged design and guided by an explicit implementation framework (i-PARIHS), WAMM will provide information on the effectiveness and transferability of a locally adapted QI method to improve DCC60. If proven effective, ultimately scaling up the WAMM intervention globally will greatly improve childhood anaemia, death, disability and long-term costs.Trial registration numberACTRN12624000035527.

ObjectiveTo determine the effect of continuous wound infusion of local anaesthetic drug (bupivacaine) on total amount of systemic opioid use in the first 72 hours in newborn infants undergoing laparotomy.DesignA two-arm parallel, open-label randomised controlled trial.SettingA quaternary newborn intensive care unit.PatientsInfants>37 weeks of gestation undergoing laparotomy for congenital or acquired abdominal conditions.InterventionsContinuous wound infusion of local anaesthetic (bupivacaine) for the first 72 hours along with systemic opioid analgesia (catheter group) or only systemic opioid analgesia (opioid group).Main outcomeTotal amount of systemic opioid used within the first 72 hours post laparotomy.ResultsThe study was underpowered as only 30 of the expected sample size of 70 infants were enrolled. 16 were randomised to catheter group and 14 to opioid group. The two groups were similar at baseline. There was no significant difference between the groups for the primary outcome of median total systemic opioid use in the first 72 hours post laparotomy (catheter 431.5 µg/kg vs opioid 771 µg/kg, difference −339.5 µg/kg, 90% CIhigh 109, p value 0.28). There was no significant difference between the groups for any of the secondary outcomes including pain scores, duration of mechanical ventilation, time to reach full feeds and duration of hospital stay. There were no adverse events noted.ConclusionContinuous wound infusion of local anaesthetic along with systemic opioid analgesia is feasible. The lack of a difference in total systemic opioid use in the first 72 hours cannot be reliably interpreted as the study was underpowered.Trial registration numberACTRN12610000633088.

In this multicenter trial comparing immediate (≤10 seconds) with delayed (≥60 seconds) clamping of the umbilical cord after preterm birth, there was no significant difference between groups in the primary composite outcome of death or major morbidity by 36 weeks of postmenstrual age.

Background: The early neonatal circulatory transition usually occurs smoothly but occasionally it is incomplete or reverts to the fetal state of high pulmonary vascular resistance, resulting in significant neonatal morbidity. Objective: To define the normal values for echocardiographic parameters during the early transitional circulation in term infants. Methods: Two-dimensional, M-mode, pulsed and color flow Doppler echocardiography was used to assess healthy term infants in the first 4 h of life. Left and right ventricular outputs (LVO and RVO) and myocardial performance indices (MPI), left ventricular fractional shortening, end-systolic diameter and end-diastolic diameter, ductal size, shunt and peak velocities, tricuspid regurgitation and left pulmonary artery diastolic velocities were documented. Results: A total of 21 normal term infants were assessed with median gestation of 39 weeks, birth weight of 3,470 g and postnatal age of 3 h and 22 min. The median echocardiographic values were LVO 193 ml/kg/min, RVO 216 ml/kg/min, left MPI 0.41, right MPI 0.63, and fractional shortening 29%. The ductus was patent in all 21 infants with a median size of 2.3 mm; ductal flow was bidirectional in 86% with median peak left-to-right velocity of 1.07 m/s. The median left pulmonary artery diastolic velocity was 0.31 m/s and physiological tricuspid regurgitation was present in all infants. Conclusion: This study defines normal values for echocardiographic measurements in healthy term infants during the first 4 h after birth. These normative data may be useful in early identification of infants with abnormal circulatory transition, allowing more rapid determination of cardiovascular dysfunction.