Importance Therapeutic hypothermia (TH) is the standard of care to improve outcomes following neonatal hypoxic-ischemic encephalopathy (HIE), but mortality and morbidity remain high, prompting research into treatment adjuncts. Objective To assess whether erythropoietin (EPO) plus TH improves outcomes in infants with moderate or severe HIE. Design, Setting, and Participants The PAEAN (Preventing Adverse Outcomes of Neonatal Hypoxic Ischaemic Encephalopathy with Erythropoietin) study was a phase 3, multicenter, double-blinded, placebo-controlled randomized clinical trial conducted in 24 neonatal intensive care units in Australia, New Zealand, and Singapore. Infants 35 weeks’ gestation or older, less than 23 hours old, with perinatal depression (umbilical cord arterial pH <7.0 or base excess ≥12 mmol/L or, at 10 minutes, Apgar score ≤5 or still receiving resuscitation), and moderate or severe HIE (modified Sarnat criteria) who had commenced TH within 6 hours of birth were eligible for inclusion. Study recruitment was conducted between May 2016 and March 2021, with data collection completed in September 2024. Data analysis was performed from September 2024 to October 2025. Intervention Intravenous EPO, 1000 IU/kg (5 doses over the first week), or placebo. Main Outcomes and Measures The primary outcome was a composite of death or moderate or severe motor or cognitive disability using standardized neurological and developmental assessments at 2 years. Moderate or severe disability comprised motor deficit (diagnosis of cerebral palsy with Gross Motor Function Classification Scale score ≥2) or moderate or severe cognitive deficit using Bayley Scales of Infant Development, Third Edition. Secondary outcomes included death, disabilities alone, and safety. Results From 2016 to 2021, 313 infants were randomized (EPO: n = 156; placebo: n = 157). Baseline characteristics (including mean [SD] gestational age at birth: 39.4 [1.7] weeks vs 39.3 [1.6] weeks and ratio of moderate:severe encephalopathy: 78%:22% vs 77%:23%) and loss to follow-up (10.2% overall) were similar across both groups. There were 67 (42.9%) and 59 (37.6%) female infants, respectively. There was no significant difference in the primary outcome (EPO: 47 of 138 [34.1%] vs placebo: 41 of 143 [28.7%]; relative risk, 1.19; 95% CI, 0.84-1.68; P = .33), in secondary outcomes (death: 22 of 146 [15.1%] vs 18 of 149 [12.1%]; P = .45; cerebral palsy: 22 of 120 [18.3%] vs 22 of 127 [17.3%]; motor deficit: 13 of 120 [10.8%] vs 15 of 127 [11.8%]; cognitive deficit: 20 of 113 [17.7%] vs 16 of 118 [13.6%]), or in any safety outcomes. Conclusions and Relevance Per the results of this multicenter randomized clinical trial, EPO did not demonstrate any adjunctive effect to hypothermia, but no safety concerns were evident. Trial Registration anzctr.org.au Identifier: ACTRN12614000669695
Brain Magnetic Resonance Imaging (MRI) of high-risk infants in the neonatal period (from 26 weeks postmenstrual age to Term Equivalent Age (TEA)) is increasingly being used for the detection of brain injuries, and the early prognostication of adverse outcomes such as Cerebral Palsy (CP). While most imaging is performed around TEA in clinical practice for infants born preterm (<37 weeks of gestation), this would often require families to return to hospital for imaging. In this work, we extract structural biomarkers from MRI acquired both before and at TEA in a cohort of very preterm infants from the PPREMO and PREBO studies (n = 100), to determine if either time-point, or both combined, are predictive of both Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) and the Neuro-sensory Motor Developmental Assessment (NSMDA) at 2 years. Using multivariable regression, moderately strong and statistically significant associations were found between brain structure on both early and TEA MRIs with 2-year outcomes (r = 0.39-0.55 for early MRI, r = 0.37-0.49 for Term MRI, r = 0.37-0.56 for early and TEA MRI combined). Importantly, brain biomarkers associated with early childhood outcomes from MRIs were identified, including white and grey matter volumes, deep grey matter and cerebellar volumes, and gyrification and surface area across the whole cortex. Early MRI showed the best prognostic accuracy along with combining timepoints, indicating the potential clinical benefit of Early MRI in predicting adverse outcomes.
OBJECTIVE:To determine the predictive accuracy of an early high risk of cerebral palsy (CP) classification for CP diagnosed by 2 years' corrected age within an implementation study of international clinical CP guidelines. DESIGN:Implementation cohort study. SETTING:Eleven Australian neonatal intensive care units. PATIENTS:453 infants born 2019-21 <28 weeks' gestation, or ≥28 weeks with other newborn-detectable risk factors for CP. INTERVENTIONS:Implementation included providing professional development for clinicians, technology (smartphone app) and health network peer support. Infants were classified as high risk of CP if they had abnormal findings on at least two of the following three assessments: neonatal neuroimaging, General Movements Assessment at 3-4 months or Hammersmith Infant Neurological Examination. MAIN OUTCOME MEASURES:Baseline perinatal data and 2-year outcome data were collected from medical record review. Any parent-report of CP at the 2-year interview was confirmed by medical records and/or a paediatrician's report. We calculated predictive values for high risk of CP classification for confirmed CP at 2 years. RESULTS:We obtained 2-year outcomes from 425 infants (95%). High risk of CP was classified in 105 (25%) of these infants at a mean age of 3.5 months (SD 2.5). This classification demonstrated 91% sensitivity (95% CI 82% to 96%), 90% specificity (95% CI 86% to 93%) and 90% accuracy (95% CI 87% to 93%) for predicting CP, with a mean age of diagnosis of 10.8 months (SD 6.3). CONCLUSION:Being classified as high risk of CP using a combination of neuroimaging, General Movements Assessment and/or Hammersmith Infant Neurological Examination can predict CP by 2 years of age with high accuracy.
Aims: This study aimed to (1) evaluate associations between Early and Term structural MRI (sMRI) brain abnormality scores and adverse motor outcomes at 6-years corrected age (CA), (2) determine their diagnostic accuracy in predicting adverse motor outcomes and cerebral palsy (CP) at 6-years CA. Methods: Infants born < 31-weeks gestational age (GA) returning for 6-year follow-up were included. Early and Term sMRI were scored using a validated method, deriving white matter, cortical grey matter, deep grey matter, cerebellar and global brain abnormality scores (GBAS). At 6-years CA, Movement Assessment Battery for Children-2nd Edition (MABC-2) was administered. Linear regression assessed associations between Early and Term GBAS/subscale scores and 6-year MABC-2 total score. For diagnostic accuracy, sMRI scores were categorised as none/mild vs moderate/severe, MABC-2 cut-off < 5th percentile, and CP as present/absent. Results: Infants had Early MRI (n = 123) at mean PMA 32.5-weeks (median GA 28.4-weeks; mean birthweight 1101 g) and n = 114 had Term MRI (Mean PMA 40.8-weeks). Nine had CP and n = 116 had MABC-2 scores. Early (B: -1.92; p <0.001) and Term (B: -1.67; p < 0.01) GBAS were negatively associated with MABC-2 scores. Both Early and Term GBAS had high specificity (Sp) and low sensitivity (Se) in predicting MABC-2 < 5th percentile (Early: Se 36 %, Sp 82 %; Term: Se 28 %, Sp 93 %) and predicted CP with high Se and Sp (Early: Se 78 %, Sp 78 %; Term: Se 75 %, Sp 89 %). Conclusion: High Sp of Early and Term MRI predicting an outcome on MABC-2 may help accurately identify infants unlikely to develop motor impairments at 6-years CA.
BACKGROUND:Infants born very preterm (VPT) are at increased risk of neurodevelopmental impairments. The Test of Infant Motor Performance (TIMP) is an assessment used to evaluate an infant's gross motor skills, however, understanding of its predictive accuracy in VPT infants is limited. AIMS:To determine the accuracy of the TIMP assessed at term equivalent age (TEA), and 3 months corrected age (CA), to identify motor or cognitive impairment at 12 months CA in VPT infants. METHOD:This prospective observational cohort study recruited 202 infants born at <31wks gestational age (GA). At TEA and 3 months CA the TIMP was performed. At 12 months CA the following neurodevelopmental assessments were conducted; Alberta Infant Motor Scale (AIMS), Neurological Sensory Motor Development Assessment (NSMDA) and Bayley Scale of Infant and Toddler Development 3rd edition (Bayley III). RESULTS:The TIMP had higher specificity than sensitivity across all four outcome measures. Using a cut off-of ≤ -0.5 at TEA, TIMP z-scores demonstrated low sensitivity and specificity for motor outcomes on the NSMDA (sensitivity 61 %, specificity 50 %), AIMS (sensitivity 59 %, specificity 50 %) and Bayley III (sensitivity 56 %, specificity 51 %). Area under the curve analyses showed that the TIMP assessed at 3 months had greater accuracy than at TEA in identifying neurodevelopmental impairments at 12 months CA. CONCLUSIONS:The TIMP assessed at TEA and 3 months CA correctly identified the majority of VPT infants without motor and cognitive impairments. However, it missed VPT infants who developed adverse neurodevelopmental outcomes by 12 months CA.
Objectives The Breathing for Life Trial (BLT) was a multicentre randomised controlled trial testing the hypothesis that a fractional exhaled nitric oxide-based intervention to guide asthma therapy in pregnancy improves perinatal outcomes. While BLT was negative based on selected outcomes, the conduct of the trial over 7 years showed potential for assessing the broader research impacts and returns on investment in BLT. The aim of this study was to retrospectively assess and report on the impact and value of BLT to show accountability for the research investment in what was deemed a ‘negative’ trial.Methods The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred method. FAIT combines three validated methods, including a modified Payback framework, an economic analysis of return on investment and a narrative account of the impact generated from the research. Data collection was done via document analysis of BLT administrative and research records and review of relevant websites/databases.Results BLT delivered a return on investment of $6.7 million in leveraged grants, fellowships and consultancies and conservatively returned $2.44 for every dollar invested. The research trained and upskilled 18 midwives and obstetricians in evidence-based asthma management in pregnancy and improved research capability of six PhD students. Specialised equipment purchased by BLT is now being repurposed to undertake other research in regional Australia, saving further research investment. Of the 1200 mothers who were part of BLT, 508 now have written asthma plans, 268 had a clinically significant improvement in their asthma control score and the proportion who improved their asthma plan knowledge increased by 58 percentage points from 12 to 70%.Conclusion This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report more broadly on the impact of and returns on research investment in a clinical trial.Trial registration number ACTRN12613000202763; Post results.
Fetal growth restriction (FGR) impacts 5%–10% of pregnancies and is associated with increased risk of mortality and morbidity. Although adverse neurodevelopmental outcomes are observed in up to 50% of FGR infants, a diagnosis of FGR does not indicate the level of risk for an individual infant and these infants are not routinely followed up to assess neurodevelopmental outcomes. Identifying FGR infants at increased risk of adverse neurodevelopmental outcomes would greatly assist in providing appropriate support and interventions earlier, resulting in improved outcomes. However, current methods to detect brain injury around the time of birth lack the sensitivity required to detect the more subtle alterations associated with FGR. Blood biomarkers have this potential. This systematic review assessed the current literature on blood biomarkers for identifying FGR infants at increased risk of adverse neurodevelopmental outcomes at >12 months after birth. Four databases were searched from inception to 22 February 2024. Articles were assessed for meeting the inclusion criteria by two reviewers. The quality of the included article was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. A summary of findings is presented as insufficient articles were identified for meta-analysis. Excluding duplicates, 1,368 records were screened with only 9 articles considered for full text review. Only one article met all the inclusion criteria. Quality assessment indicated low risk of bias. Both blood biomarkers investigated in this study, neuron specific enolase and S100B, demonstrated inverse relationships with neurodevelopmental assessments at 2 years. Four studies did not meet all the inclusion criteria yet identified promising findings for metabolites and cytokines which are discussed here. These findings support the need for further research and highlight the potential for blood biomarkers to predict adverse outcomes.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369242, Identifier CRD42022369242.
The neurovascular unit (NVU) within the brain is a multicellular unit that synergistically acts to maintain blood–brain barrier function and meet cerebral metabolic demand. Recent studies have indicated disruption to the NVU is associated with neuropathology in the perinatal brain. Infants with fetal growth restriction (FGR) are known to be at increased risk of neurodevelopmental conditions including motor, learning, and behavioural deficits. There are currently no neuroprotective treatments for these conditions. In this review, we analyse large animal studies examining the effects of FGR on the perinatal NVU. These studies show altered vascularity in the FGR brain as well as blood–brain barrier dysfunction due to underlying cellular changes, mediated by neuroinflammation. Neuroinflammation is a key mechanism associated with pathological effects in the FGR brain. Hence, targeting inflammation may be key to preserving the multicellular NVU and providing neuroprotection in FGR. A number of maternal and postnatal therapies with anti-inflammatory components have been investigated in FGR animal models examining targets for amelioration of NVU disruption. Each therapy showed promise by uniquely ameliorating the adverse effects of FGR on multiple aspects of the NVU. The successful implementation of a clinically viable neuroprotective treatment has the potential to improve outcomes for neonates affected by FGR. Impact Disruption to the neurovascular unit is associated with neuropathology in fetal growth restriction. Inflammation is a key mechanism associated with neurovascular unit disruption in the growth-restricted brain. Anti-inflammatory treatments ameliorate adverse effects on the neurovascular unit and may provide neuroprotection.
BACKGROUND:Very preterm infants are at increased risk of neurodevelopmental impairments. The Neonatal Visual Assessment (NVA) assesses visual function and outcomes and has been used to assess early neurodevelopmental outcomes. This study aimed to compare NVA results of very preterm and term-born infants and to calculate the sensitivity and specificity of the NVA at term equivalent age (TEA) and three months corrected age (CA) to predict motor and cognitive outcomes at 12 months CA in very preterm infants. METHODS:This prospective observational cohort study recruited infants born before 31 weeks gestation and a healthy term-born control group. The NVA was assessed at TEA and three months CA, and neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development, Third Edition; Neurosensory Motor Developmental Assessment; Alberta Infant Motor Scale) were performed at 12 months CA. The sensitivity and specificity of the NVA to predict outcomes were calculated based on a previously published optimality score. RESULTS:248 preterm (54 % male) and 46 term-born infants (48 % male) were analysed. The mean NVA scores of preterm and term-born infants were significantly different at TEA (preterm 3.1±2.1; term-born 1.2±1.7, p < 0.001). The NVA had moderate sensitivity (59-78 %) and low specificity (25-27 %) at TEA, and low sensitivity (21-28 %) and high specificity (86-87 %) at three months CA for the prediction of preterm infants' outcomes at 12 months CA. CONCLUSION:The NVA at TEA and three months CA was not a strong predictor of motor and cognitive impairments in this contemporary cohort of very preterm infants.
ObjectiveTo describe the implementation of the international guidelines for the early diagnosis of cerebral palsy (CP) and engagement in the screening process in an Australian cohort of infants with neonatal risk factors for CP.Study designProspective cohort study of infants with neonatal risk factors recruited at <6 months CA from 11 sites in the states of Victoria, New South Wales, and Queensland, Australia. First, we implemented a multi-modal knowledge translation strategy including barrier identification, technology integration and special interest groups. Screening was implemented as follows: infants with clinical indications for neuroimaging underwent magnetic resonance imaging and/or cranial ultrasound. The General Movements Assessment (GMA) was recorded clinically or using an app (Baby Moves). Infants with absent or abnormal fidgety movements on GMA videos were offered further assessment using the Hammersmith Infant Neurological Examination (HINE). Infants with atypical findings on 2/3 assessments met criteria for high risk of CP.ResultsOf the 597 infants (56% male) recruited, 95% (n=565) received neuroimaging, 90% (n=537) had scorable GMA videos (2% unscorable/8% no video), and 25% (n=149) HINE. Overall, 19% of the cohort (n=114/597) met criteria for high risk of CP, 57% (340/597) had at least two normal assessments (of neuroimaging, GMA or HINE), and 24% (n=143/597) had insufficient assessments.ConclusionsEarly CP screening was implemented across participating sites using a multi-modal knowledge translation strategy. Although the COVID-19 pandemic affected recruitment rates, there was high engagement in the screening process. Reasons for engagement in early screening from parents and clinicians warrant further contextualization and investigation.
Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA)-matched sibling cord blood cells. Twelve participants with cerebral palsy aged 2–12 years received cord blood cell infusions as part of a phase I trial of umbilical blood infusion for cerebral palsy. Digital droplet PCR analysis of DNA copy number variants specific to donor and recipient was used to assess donor DNA clearance at five timepoints post-infusion, a surrogate measure of cell clearance. Donor cells were cleared by 3 months post-infusion in 11/12 participants. When detected, donor DNA was at a fraction of 0.01–0.31% of total DNA with no signs of graft-versus-host disease in any participant. The donor DNA clearance times provided by this study have important implications for understanding the safety of allogeneic cord blood cell infusion for cerebral palsy and translational tissue engineering or regenerative medicine research in other disorders.
AIM:To evaluate the predictive validity of the Hammersmith Neonatal Neurological Examination (HNNE) performed early (at 32 weeks postmenstrual age) and at term-equivalent age (TEA) for 12-month motor outcomes in infants born very preterm.METHOD:This was a diagnostic study using data from a prospective birth cohort. A total of 104 infants born preterm at less than 31 weeks gestational age (males n = 61; mean = 28 weeks 1 day [SD 1 week 6 days], range 23 weeks 1 day-30 weeks 6 days) underwent HNNE early and at TEA, which were scored by comparison with term data. Motor outcomes at 12 months corrected age were determined using the Bayley Scales of Infant and Toddler Development, Third Edition (scores ≤85). Cut-off points were determined using receiver operating characteristic curves.RESULTS:Sixteen (15%) infants born preterm had motor impairment at 12 months corrected age. The HNNE total score cut-off points with the best combination of sensitivity and specificity at early and TEA assessments were 15.2 or lower (sensitivity 77%, 95% confidence interval [CI] = 46%-95%; specificity 74%, 95% CI = 63%-83%) and 23.5 or lower (sensitivity 67%, 95% CI = 38%-88%; specificity 66%, 95% CI = 54%-76%) respectively. The most predictive subscale at the early assessment was reflexes (sensitivity 86%, 95% CI = 57%-98%; specificity 62%, 95% CI = 51%-72%; cut-off point ≤3); at TEA, it was spontaneous movements (sensitivity 73%, 95% CI = 45%-92%; specificity 60%, 95% CI = 48%-70%; cut-off point ≤2).INTERPRETATION:The HNNE provides moderate predictive accuracy for motor outcome at 12 months corrected age in infants born very preterm. Although modest at both time points, early assessment had stronger predictive ability for motor outcomes than TEA when scored using term data, highlighting the value of performing the HNNE earlier in the neonatal period. Performing HNNE earlier may assist risk stratification when planning follow-up services.
Neuroinflammation is a hallmark of hypoxic-ischemic injury and can be characterized by the activation of glial cells and the expression of inflammatory cytokines and chemokines. Interleukin (IL)-1β and tumor necrosis factor (TNF)α are among the best-characterized early response cytokines and are often expressed concurrently. Several types of central nervous system cells secrete IL-1β and TNFα, including microglia, astrocytes, and neurons, and these cytokines convey potent pro-inflammatory actions. Chemokines also play a central role in neuroinflammation by controlling inflammatory cell trafficking. Our aim was to characterise the evolution of early neuroinflammation in the neonatal piglet model of hypoxic-ischemic encephalopathy (HIE). Piglets (< 24 h old) were exposed to HI insult, and recovered to 2, 4, 8, 12 or 24H post-insult. Brain tissue from the frontal cortex and basal ganglia was harvested for assessment of glial cell activation profiles and transcription levels of inflammatory markers in HI piglets with comparison to a control group of newborn piglets. Fluorescence microscopy was used to observe microglia, astrocytes, neurons, degenerating neurons and possibly apoptotic cells, and quantitative polymerase chain reaction was used to measure gene expression of several cytokines and chemokines. HI injury was associated with microglial activation and morphological changes to astrocytes at all time points examined. Gene expression analyses of inflammation-related markers revealed significantly higher expression of pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin 1 beta (IL-1β), chemokines cxc-chemokine motif ligand (CXCL)8 and CXCL10, and anti-inflammatory cytokine transforming growth factor (TGF)β in every HI group, with some region-specific differences noted. No significant difference was observed in the level of C-X-C chemokine receptor (CCR)5 over time. This high degree of neuroinflammation was associated with a reduction in the number of neurons in piglets at 12H and 24H in the frontal cortex, and the putamen at 12H. This reduction of neurons was not associated with increased numbers of degenerating neurons or potentially apoptotic cells. HI injury triggered a robust early neuroinflammatory response associated with a reduction in neurons in cortical and subcortical regions in our piglet model of HIE. This neuroinflammatory response may be targeted using novel therapeutics to reduce neuropathology in our piglet model of neonatal HIE.
Fetal growth restriction (FGR) and small for gestational age (SGA) infants have increased risk of mortality and morbidity. Although both FGR and SGA infants have low birthweights for gestational age, a diagnosis of FGR also requires assessments of umbilical artery Doppler, physiological determinants, neonatal features of malnutrition, and in utero growth retardation. Both FGR and SGA are associated with adverse neurodevelopmental outcomes ranging from learning and behavioral difficulties to cerebral palsy. Up to 50% of FGR, newborns are not diagnosed until around the time of birth, yet this diagnosis lacks further indication of the risk of brain injury or adverse neurodevelopmental outcomes. Blood biomarkers may be a promising tool. Defining blood biomarkers indicating an infant's risk of brain injury would provide the opportunity for early detection and therefore earlier support. The aim of this review was to summarize the current literature to assist in guiding the future direction for the early detection of adverse brain outcomes in FGR and SGA neonates. The studies investigated potential diagnostic blood biomarkers from cord and neonatal blood or serum from FGR and SGA human neonates. Results were often conflicting with heterogeneity common in the biomarkers examined, timepoints, gestational age, and definitions of FGR and SGA used. Due to these variations, it was difficult to draw strong conclusions from the results. The search for blood biomarkers of brain injury in FGR and SGA neonates should continue as early detection and intervention is critical to improve outcomes for these neonates.
Abstract IntroductionWe showed in a Phase 2 RCT that oral Sildenafil during term labour halves the need for operative birth for suspected fetal distress. To assess if Sildenafil reduces adverse perinatal outcomes, we describe a Phase 3 RCT (iSEARCH) and the rationale for an individual participant data prospective meta-analysis (IPD PMA) of RCTs in high-income countries and a mega-trial in low- and middle-income countries.Methods and analysisiSEARCH will enrol 3200 women in term labour, yielding >80% power to determine whether oral administration of up to three 50 mg doses of Sildenafil versus placebo reduces the relative risk of intrapartum hypoxia, determined as a primary composite endpoint of ten perinatal outcomes, by 35% (from 7% to 4.55%). We also outline the rationale for (i) an IPD PMA of RCTs in about 14,000 women in Australia and other countries with low perinatal mortality rates which would yield 90% power to test if oral Sildenafil achieves a more moderate and realistic reduction of 20% in the relative risk of this composite endpoint and (ii) a mega-trial in about 50,000 women in countries with moderate or high perinatal mortality rates to test if oral Sildenafil achieves a similarly moderate and realistic 20% reduction in the relative risk of a composite endpoint comprising intrapartum stillbirth or 7-day neonatal mortality. Secondary aims will be to evaluate the rate of operative birth for fetal distress, its cost-effectiveness, and developmental and educational outcomes.
Background and objectiveIn newborns, it is often difficult to accurately differentiate between seizure and non-seizure based solely on clinical manifestations. This highlights the importance of electroencephalogram (EEG) in the recognition and management of neonatal seizures. This paper proposes an effective algorithm for the detection of neonatal seizure using multichannel EEG.MethodsNeonatal EEG changes morphology as it alternates between seizure and non-seizure states. A new signal complexity measure based on matching pursuit (MP) decomposition is proposed and used to detect transitions between these two states. The new measure, referred to as weighted structural complexity (WSC), was used for the detection of seizures in 30 newborn EEG records. Multiple IIR filters and an MP-based filter were designed and used to remove artifacts from the EEG data. Geometrical correlation between the EEG data channels was applied to reduce the number of false detections caused by remnant artifacts. The seizure detector's performance was assessed using several epoch-based (e.g., accuracy) and event-based (GDR = good detection rate and FD/h = false detections per hour) metrics.ResultsCompared to the neurologist marking, the proposed detector was able to detect EEG seizures with 94% accuracy, 90.9% GDR, and 0.14 FD/h (95% CI: [0.06, 0.34]).ConclusionsThe high performance of the MP-based detector may have significant implications for the accurate diagnosis of neonatal seizures and the appropriate use of anticonvulsants and ongoing clinical assessment and care of the newborn.
Identify predictors of maternal bonding and responsiveness for mothers of very preterm infants (< 32 weeks gestational age) at 6 weeks and 12 months corrected-age (CA). Cross-sectional and longitudinal study containing 39 mothers of very preterm infants. At 6 weeks CA maternal self-efficacy made a significant unique contribution to the variance in self-reported maternal bonding and responsiveness (21% and 26%, respectively). At 12 months CA maternal trauma symptoms, depressive symptoms and self-efficacy made a significant unique contribution to the variance in bonding (14%, 9% and 9%, respectively). Maternal self-efficacy made a significant 31% unique contribution to the variance in responsiveness. The combined effects of maternal trauma symptoms, depressive symptoms and self-efficacy at 6 weeks CA predicted maternal responsiveness at 12 months CA (p = .042). Supporting maternal self-efficacy is key to facilitating bonding and responsiveness up to 12 months CA following a very preterm birth. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12612000194864.