Search

Objectives Very preterm infants are at risk of cognitive impairment, but current capacity to predict at-risk infants is sub-optimal. Electroencephalography (EEG) has been used to assess brain function in development. This review investigates the relationship between EEG and cognitive outcomes in very preterm infants. Methods Two reviewers independently conducted a literature search in April 2018 using PubMed, CINAHL, PsycINFO, Cochrane Library, Embase and Web of Science. Studies included very preterm infants (born ≤34 weeks gestational age, GA) who were assessed with EEG at ≤43 weeks postmenstrual age (PMA) and had cognitive outcomes assessed ≥3 months of age. Data on the subjects, EEG, cognitive assessment, and main findings were extracted. Meta-analysis was undertaken to calculate pooled sensitivity and specificity. Results 31 studies (n = 4712 very preterm infants) met the inclusion criteria. The age of EEG, length of EEG recording, EEG features analysed, age at follow-up, and follow-up assessments were diverse. The included studies were then divided into categories based on their analysed EEG feature(s) for meta-analysis. Only one category had an adequate number of studies for meta-analysis: four papers (n = 255 very preterm infants) reporting dysmature/disorganised EEG patterns were meta-analysed and the pooled sensitivity and specificity for predicting cognitive outcomes were 0.63 (95% CI: 0.53–0.72) and 0.83 (95% CI: 0.74–0.89) respectively. Conclusions There is preliminary evidence that background EEG features can predict cognitive outcomes in very preterm infants. Reported findings were however too heterogeneous to determine which EEG features are best at predicting cognitive outcome.

Preterm infants often have poor cardiovascular function that is associated with adverse neurodevelopmental outcomes. Preterm infants may be vulnerable to hypovolaemia due to excessive vasodilatation and leaky capillaries. Following reduction in blood volume, cardiac output and mean arterial pressure were reduced to the same extent in term and preterm piglets. Cerebral blood flow was maintained following blood volume reduction in term but not in preterm piglets. Effective detection and treatment of functional hypovolaemia may reduce the risk of brain injury in preterm infants.Preterm infants often have impaired cardiovascular function that may contribute to poor neurodevelopmental outcomes. The study aimed to determine the effects of reduced blood volume on cardiovascular function, including cerebral blood flow, in preterm and term piglets. In preterm (97/115 days) and term piglets, up to 10% of the estimated blood volume was removed. Removal of blood was stopped if MAP dropped below 20 mmHg. Heart rate, cardiac contractility and relaxation, cardiac output, mean arterial pressure (MAP), and cerebral blood flow were measured at baseline and again after blood volume reduction. The volume of blood removed was less in preterm piglets than in term piglets (5.1 ± 1.8 vs. 7.7 ± 0.9 mL kg

Objectives Hypoxic ischaemic encephalopathy is a significant cause of mortality and morbidity in the term infant. Electroencephalography (EEG) is a useful tool in the assessment of newborns with HIE. This systematic review of published literature identifies those background features of EEG in term neonates with HIE that best predict neurodevelopmental outcome. Methods A literature search was conducted using the PubMed, EMBASE and CINAHL databases from January 1960 to April 2014. Studies included in the review described recorded EEG background features, neurodevelopmental outcomes at a minimum age of 12months and were published in English. Pooled sensitivities and specificities of EEG background features were calculated and meta-analyses were performed for each background feature. Results Of the 860 articles generated by the initial search strategy, 52 studies were identified as potentially relevant. Twenty-one studies were excluded as they did not distinguish between different abnormal background features, leaving 31 studies from which data were extracted for the meta-analysis. The most promising neonatal EEG features are: burst suppression (sensitivity 0.87 [95% CI (0.78–0.92)]; specificity 0.82 [95% CI (0.72–0.88)]), low voltage (sensitivity 0.92 [95% CI (0.72–0.97)]; specificity 0.99 [95% CI (0.88–1.0)]), and flat trace (sensitivity 0.78 [95% CI (0.58–0.91)]; specificity 0.99 [95% CI (0.88–1.0)]). Conclusion Burst suppression, low voltage and flat trace in the EEG of term neonates with HIE most accurately predict long term neurodevelopmental outcome. Significance This structured review and meta-analysis provides quality evidence of the background EEG features that best predict neurodevelopmental outcome. Lars Eriksson and Nicola Foxlee, librarians at The University of Queensland Health Science Library provided assistance in defining the search strategy. Dr. Robert Ware, senior biostatistical consultant, School of Population Health, The University of Queensland provided statistical assistance. This work was supported in part by a Grant from the Qatar National Research Fund under its National Priorities Research Program award number NPRP 6-885-2-364 . Scopus

To determine the prevalence, associated factors, and relationships between symptoms of depression, symptoms of posttraumatic stress (PTS), and relationship distress in mothers and fathers of very preterm (VPT) infants (

It is well documented that the American maternal mortality ratio has increased during the years 2000-2015. The Australian maternal mortality ratio, in contrast, has decreased during the same time period, a trend common among most Western countries.This study was a retrospective cohort study of cases of in-hospital maternal deaths in the Ochsner Health System (Louisiana, United States) and the Queensland Health System (Australia) from 1995 to 2013. The aim was to determine if American and Australian women have a similar rate of preventable maternal death and if the deaths were attributable to the same factors. A multidisciplinary team assessed medical records to determine preventability.Sixteen eligible medical records were identified in the Ochsner Health System and 15 in the Queensland Health System. In the American cohort, deaths in the private insurance group (n=5) were least likely to be preventable (Women from Louisiana, United States and Queensland, Australia have similar rates of preventable maternal death. No statistically significant factors explained trends in Australian maternal death; American maternal mortality was significantly associated with point of entry into prenatal care, likely influenced by insurance status. Furthermore, the majority of deaths in this group were complicated by hospital systems-based factors.

Aims To determine whether antenatal magnesium sulfate (MgSO 4 ) administration correlates with circulating sulfate level in very/extremely preterm infants, and specifically whether non-exposed infants become sulphate deficient. Methods Ion chromatography was used to measure plasma sulfate levels in preterm infants ( 4 . Results Within 24 hours after birth, supra-physiological plasma sulfate levels were measured in infants whose mothers received MgSO 4 (mean±SD mmol/L 774±397, n=26), whereas sulfate levels in the group without MgSO 4 (257±162, n=10) were similar to that found in term cord blood. At 3 days and at 1 and 4 weeks of age, babies without antenatal MgSO 4 had reduced plasma sulfate level (3d: 190±96, n=49; 1 wk 118±61, n=67; 4 wk 125±79, n=6) whereas the group with antenatal MgSO 4 therapy maintained normal levels (3d: 287±160, n=68; 1 wk 250±125, n=119; 4 wk 228±89, n=56). Conclusions These data positively correlate antenatal MgSO 4 administration with neonatal plasma sulfate levels, and suggest that unexposed preterm infants (who lack the capacity to generate sulphate) rapidly become sulphate depleted. Animal models and human studies demonstrate that sulphate is important for modulating brain development. It may be, therefore, that the neuroprotective benefit of antenatal MgSO 4 for preterm infants is attributable to the sulphate rather than the magnesium content. If sulfate neuroprotection is proven, then neonatal sulfate supplementation (in place of antenatal MgSO 4 ) may prove a simple and effective, low-cost, low-risk intervention universally available to all preterm infants to improve their chances of a normal neurodevelopmental outcome.

Spatio-temporal atlas is a useful tool in imaging studies of neurodevelopment, which characterizes the growth of brain, and allows the monitoring of its development. The imaging of preterm and term born infants provides opportunities to develop a series of spatio-temporal atlases that track the changes during the particular period of neurodevelopment between. The aim of this paper is to develop a spatio-temporal atlas of diffusion MRI for neonatal brains between 32 to 42 weeks postmenstrual age (PMA). We subdivided the cohort consisting of preterm- and term-born infants according to their PMA at the MRI scan based on a kernel ridge regression, and generated the atlases based on Fibre Orientation Distribution (FOD) reconstruction of the diffusion data.

Skin offers easy access, convenience and non-invasiveness for drug delivery and diagnosis. In principle, these advantages of skin appear to be attractive for critically ill patients given potential difficulties that may be associated with oral and parenteral access in these patients. However, the profound changes in skin physiology that can be seen in these patients provide a challenge to reliably deliver drugs or provide diagnostic information. Drug delivery through skin may be used to manage burn injury, wounds, infection, trauma and the multisystem complications that rise from these conditions. Local anaesthetics and analgesics can be delivered through skin and may have wide application in critically ill patients. To ensure accurate information, diagnostic tools require validation in the critically ill patient population as information from other patient populations may not be applicable. Refereed/Peer-reviewed

The aim of this systematic review was to determine the efficacy of parenting interventions for parents of preterm infants to improve child behavior. Randomized controlled trials (RCTs) of parenting interventions for parents of preterm infants were included. Searchers were conducted of PubMed from 1951 to April 2013, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1982 to April 2013, Scopus from 1966 to April 2013, PsycINFO from 1840 to April 2013, the Web of Science, and the Cochrane Library. Twelve RCTs were identified that assessed child behavior. Of these studies, only data from three were able to be pooled for meta-analysis: the Infant Health and Development Program (IHDP) at 3 years, the Mother-Infant Transaction Program (modified; MITP-M) at 5 years, and the Victorian Infant Brain Studies (VIBeS Plus) at 4 years. Outcome from this analysis revealed a small, but significant, effect on child behavior favoring the intervention (95% CI: 0.08-0.32; p = .001). There is evidence that preterm parenting interventions can improve child behavior. Streamlined interventions such as MITP-M and VIBeS Plus that have a strong focus on the mother-infant relationship may have greatest potential.

Subgaleal haemorrhage (SGH) is an important cause of preventable morbidity and mortality in the neonate. Its increased prevalence in recent years has coincided with the rise in the number of births assisted by vacuum extraction. Three deaths in Australia within the last 7 years have been the subject of two coronial inquests. Subsequent coronial reports have highlighted that neonatal death from SGH can be prevented if appropriate attention is paid to identification of risk factors, early diagnosis, close observation and aggressive treatment. To prevent unnecessary deaths, all involved in the care of the baby after birth need to be aware of the importance of prompt diagnosis, monitoring and early treatment of SGH.

Aim To systematically review the efficacy of parenting interventions in improving the quality of the relationship between mothers and preterm infants. Method Randomized or quasi-randomized controlled trials (RCT) of parenting interventions for mothers of preterm infants where mother–infant relationship quality outcomes were reported. Databases searched: The Cochrane Library, PubMed, CINAHL, PsycINFO and Web of Science. Results Seventeen studies met the inclusion criteria, 14 with strong methodological quality. Eight parenting interventions were found to improve the quality of the mother–preterm infant relationship. Conclusions Heterogeneity of the interventions calls for an integrated new parenting program focusing on cue-based, responsive care from the mother to her preterm infant to improve the quality of the relationship for these mother–preterm infant dyads.

Treatment of renal ischemia-reperfusion (IR) injury with recombinant human erythropoietin (rhEPO) reduces acute kidney injury and improves function. We aimed to investigate whether progression to chronic kidney disease associated with acute injury was also reduced by rhEPO treatment, using in vivo and in vitro models. Rats were subjected to bilateral 40-min renal ischemia, and kidneys were studied at 4, 7, and 28 days postreperfusion for renal function, tubular injury and repair, inflammation, and fibrosis. Acute injury was modulated using rhEPO (1,000 or 5,000 IU/kg, intraperitoneally) at the time of reperfusion. Renal tubular epithelial cells or fibroblasts in culture were subjected to hypoxia or oxidative stress, with or without rhEPO (200 IU/ml), and fibrogenesis was studied. The results of the in vivo model confirmed functional and structural improvement with rhEPO at 4 days post-IR ( P < 0.05). At 7 days post-IR, fibrosis and myofibroblast stimulation were increased with IR with and without rhEPO ( P < 0.01). However, at 28 days post-IR, renal fibrosis and myofibroblast numbers were significantly greater with IR plus rhEPO ( P < 0.01) compared with IR only. Mechanistically, rhEPO stimulated profibrotic transforming growth factor-β, oxidative stress (marker 8-hydroxy-deoxyguanosine), and phosphorylation of the signal transduction protein extracellular signal-regulated kinase. In vitro, rhEPO protected tubular epithelium from apoptosis but stimulated epithelial-to-mesenchymal transition and also protected and activated fibroblasts, particularly with oxidative stress. In summary, although rhEPO was protective of renal function and structure in acute kidney injury, the supraphysiological dose needed for renoprotection contributed to fibrogenesis and stimulated chronic kidney disease in the long term.

This study aimed to develop a time-frequency method for measuring directional interactions over time and frequency from scalp-recorded electroencephalographic (EEG) signals in a way that is less affected by volume conduction and amplitude scaling. We modified the time-varying generalized partial directed coherence (tv-gPDC) method, by orthogonalization of the strictly causal multivariate autoregressive model coefficients, to minimize the effect of mutual sources. The novel measure, generalized orthogonalized PDC (gOPDC), was tested first using two simulated models with feature dimensions relevant to EEG activities. We then used the method for assessing event-related directional information flow from flash-evoked responses in neonatal EEG. For testing statistical significance of the findings, we followed a thresholding procedure driven by baseline periods in the same EEG activity. The results suggest that the gOPDC method 1) is able to remove common components akin to volume conduction effect in the scalp EEG, 2) handles the potential challenge with different amplitude scaling within multichannel signals, and 3) can detect directed information flow within a subsecond time scale in nonstationary multichannel EEG datasets. This method holds promise for estimating directed interactions between scalp EEG channels that are commonly affected by the confounding impact of mutual cortical sources. Qatar National Research Fund under its National Priorities Research Program award number NPRP 09-465-2-174. European Community's Seventh Framework Program European Community FP7-PEOPLE-2009-IOF under Grant 254235. Scopus

Systemic reviews have shown that delaying the time of umbilical cord clamping can improve outcomes of preterm newborns. One such study found enhanced placental transfusion through delayed cord clamping, cord-palpation, or a combination of the 2 practices caused a lower infection and mortality rate when compared with immediate clamping. Despite this recent body of evidence, concerns exist about harm from delayed resuscitation and hyperbilirubinemia causing current professional guidelines to vary significantly.

Objective To determine the efficacy of a hospital-based intervention that transitions into existing community support, in enhancing developmental outcomes at 2 years of corrected age in infants born at less than 32 weeks. Study design In total, 323 families of 384 infants born

We propose and compare two multi-channel fusion schemes to utilize the information extracted from simultaneously recorded multiple newborn electroencephalogram (EEG) channels for seizure detection. The first approach is known as the multi-channel feature fusion. It involves concatenating EEG feature vectors independently obtained from the different EEG channels to form a single feature vector. The second approach, called the multi-channel decision/classifier fusion, is achieved by combining the independent decisions of the different EEG channels to form an overall decision as to the existence of a newborn EEG seizure. The first approach suffers from the large dimensionality problem. In order to overcome this problem, three different dimensionality reduction techniques based on the sum, Fisher’s linear discriminant and symmetrical uncertainty (SU) were considered. It was found that feature fusion based on SU technique outperformed the other two techniques. It was also shown that feature fusion, which was developed on the basis that there was inter-dependence between recorded EEG channels, was superior to the independent decision fusion.

AimsPerfluorocarbon administration increases cerebral blood flow. This can be mitigated by preventing a rise in carbon dioxide by adjusting pressure-controlled ventilation. Volume-controlled ventilation should prevent increases in arterial carbon dioxide and cerebral blood flow. This study aims to determine if cerebral blood flow is increased during administration of 10mL/kg of perfluorocarbon while using volume-controlled ventilation.

Infants born very preterm are at risk of developmental and behavioural problems and their parents are at risk of psychological distress and compromised parenting. This study has two key aims: (1) to identify, from the parents' own perspective, the unique aspects of parenting an infant born very preterm and (2) to assess parent preferences for support including opinions of a new, tailored parenting intervention, Prem Baby Positive Parenting Program (Triple P). A qualitative approach was taken with focus groups of 18 parents of infants born preterm and a thematic analysis conducted. Parents identified several unique aspects of parenting an infant born preterm including: difficulty coping with the stress of hospitalisation; institutionalisation to the hospital environment; a lack of preparation for the transition to parenthood; grief; isolation; getting into "bad parenting habits" of overnurturance and a lack of certainty about developmental expectations. Parents preferred parenting support that is tailored to parents of infants born preterm, has flexible delivery, enhances coping skills and the spousal relationship and is sensitive to the emotional context of parenting an infant born preterm. Understanding the experiences and the preferences of parents of infants born preterm is an important step in tailoring parenting interventions to fit their needs.

BACKGROUND AND PURPOSE: The diagnostic and prognostic potential of brain MR imaging before term-equivalent age is limited until valid MR imaging scoring systems are available. This study aimed to validate an MR imaging scoring system of brain injury and impaired growth for use at 29 to 35 weeks postmenstrual age in infants born at MATERIALS AND METHODS: Eighty-three infants in a prospective cohort study underwent early 3T MR imaging between 29 and 35 weeks9 postmenstrual age (mean, 32+2 ± 1+3 weeks; 49 males, born at median gestation of 28+4 weeks; range, 23+6–30+6 weeks; mean birthweight, 1068 ± 312 g). Seventy-seven infants had a second MR scan at term-equivalent age (mean, 40+6 ± 1+3 weeks). Structural images were scored using a modified scoring system which generated WM, cortical gray matter, deep gray matter, cerebellar, and global scores. Outcome at 12-months corrected age (mean, 12 months 4 days ± 1+2 weeks) consisted of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley III), and the Neuro-Sensory Motor Developmental Assessment. RESULTS: Early MR imaging global, WM, and deep gray matter scores were negatively associated with Bayley III motor (regression coefficient for global score β = −1.31; 95% CI, −2.39 to −0.23; P = .02), cognitive (β = −1.52; 95% CI, −2.39 to −0.65; P CONCLUSIONS: This clinically accessible MR imaging scoring system is valid for use at 29 to 35 weeks postmenstrual age in infants born very preterm. It enables identification of infants at risk of adverse outcomes before the current standard of term-equivalent age.

Intrauterine growth restriction (IUGR) is one of the most common causes of perinatal mortality and morbidity. White matter and neuronal injury are major pathophysiological features of the IUGR neonatal brain. GABA

GABA is a major neurotransmitter in the mammalian brain. In the mature brain GABA exerts inhibitory actions via the GABAA receptor (GABAAR); however, in the immature brain GABA provides much of the excitatory drive. We examined the expression of 3 predominant GABAA α-subunit proteins in the pig brain at various pre- and postnatal ages. Brain tissue was collected from piglets born via caesarean section at preterm ages 91, 97, 100, and 104 days' gestational age (GA), at term equivalent (114 days' GA, caesarean section) and at term, postnatal day 0 (P0) (spontaneous delivery, term = 115 days). Tissue was obtained from piglets at P4 and P7. Adult tissue from sows was collected postmortem after caesarean section. In all cortical regions and basal ganglia (1) α3 exhibited a significant increase in protein expression at 100 days' GA, (2) α3 expression decreased with age after 100 days' GA, (3) α1 increased with age, with peak expression at P7 in cortices, hippocampus, and thalamus, and (4) α2 protein expression remained relatively constant across the ages examined. The subunit expression of α3 was most abundant at preterm ages, with α1 the predominant subunit expressed postnatally. Immunofluorescent labelling revealed α1 expression on the somatic membranes of pyramidal cells in the cortex and hippocampus, and in the cerebellar Purkinje cells. Positive α3 labelling was apparent on interneurones in the cortex and hippocampus. The switch between dominant α-subunits may coincide with the functional change in GABAergic neurotransmission from excitation to inhibition. Brain growth in the pig closely reflects that in the term human, making the pig a valuable non-primate model for studying development and the effects of insults on the perinatal brain.

The GABA

Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety. The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants. Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels. Effects on maternal mood, anxiety and mother-infant attachment will also be measured. A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32 weeks and 6 days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12 months and 24 months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massage on neurodevelopment. An early intervention such as massage that is relatively easy to administer and could alter the trajectory of preterm infant brain development, holds potential to improve neurodevelopmental outcomes in this vulnerable population. Australian New Zealand Clinical Trials Registry: ACTRN12612000335897 . Date registered: 22/3/2012.

Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes. BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician-diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12–22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3–6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO

Seizures are a common manifestation of hypoxic-ischaemic brain injury in the neonate. In status epilepticus models alterations to GABA

There is a lack of research investigating parental self-efficacy in parents of infants born preterm as well as a paucity of parental self-efficacy measures that are domain-specific and theoretically grounded. This study aimed to compare parental self-efficacy in parents of infants born term, preterm and very preterm as well as to test whether parental self-efficacy mediates the relationship between psychological symptoms and parental competence. In order to achieve this, a new measure of parental self-efficacy and parental competence relevant for the preterm population and consistent with [Bandura, 1977], [Bandura, 1986] and [Bandura, 1989] conceptualisation of self-efficacy was developed. Participants included 155 parents, 83 of whom were parents of very preterm (GA < 32 weeks), 40 parents of preterm (GA < 37 weeks) and 32 parents of term born infants. Parents completed the Preterm Parenting & Self-Efficacy Checklist (the new measure), Family Demographic Questionnaire, Depression Anxiety Stress Scale and Self-Efficacy Questionnaire. This initial study indicates that the Preterm Parenting & Self-Efficacy Checklist has adequate content validity, construct validity, internal consistency and split half reliability. Contrary to expectations, parents of very preterm infants did not report significantly lower overall levels of parental self-efficacy or significantly higher levels of psychological symptoms compared to parents of preterm and term infants. Parental self-efficacy about parenting tasks mediated the relationship between psychological symptoms and self perceived parental competence as predicted. Clinical implications of the results and suggestions for future research are discussed.

Objective: This study examined the relationship between maternal postnatal depression (PND) at 6 weeks and first-year parenting stress for mothers of very preterm (gestation < 32 weeks) singleton children. Background: PND is reported as a strong predictor of parenting stress, but few studies examine the effectiveness of parenting interventions according to PND status. In the preterm population, the differential benefit mothers with PND experience from parenting interventions is also unclear. Methods: Validated questionnaires were used to collect information on both PND at 6 weeks and first-year parenting stress from 123 mothers of very preterm singleton children. Results: After adjusting for baseline birth and social risks, mothers who had PND at 6 weeks were more likely to experience parenting stress (OR 3.6, 95%CI 1.2, 12, p = 0.03) and have higher parental distress (OR 5.5, 95%CI 1.6, 18.0, p < 0.01) during the first postpartum year. Conclusion: When assessing the benefits of parenting interventions in reducing parenting stress, the effects of early PND in mothers of preterm infants should not be underestimated.

Introduction: Partial liquid ventilation may benefit the lung disease in preterm neonates but intratracheal instillation of perfluorocarbon increases cerebral blood flow and may cause brain injury. We aimed to determine if the effects of perfluorocarbon administration on cerebral blood flow vary by dose-volume, rate of administration, endotracheal tube portal of entry, or closely targeting PaCO2. Methods: Forty-two dosing events (in eleven rabbits) were randomised to different dosing strategies, including a sham (i.e., placebo/control) dose of air over 20 min, 20 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon slowly over 20 min, 10 mL/kg of perfluorocarbon moderately fast over 10 min, 10 mL/kg of perfluorocarbon rapidly over 5 min, 10 mL/kg of perfluorocarbon slowly over 20 min via the endotracheal tube tip lumen (as opposed to the proximal end of the tube used in all other groups), or 10 mL/kg of perfluorocarbon slowly over 20 min whilst targeting a PaCO2 of 45 - 50 mmHg. Blood gases, haemodynamics, cortical cerebral blood flow and carotid flow were recorded continuously for 30 minutes from the start of each dose. Results: Carotid flow increased with 20 mL/kg perfluorocarbon and cortical cerebral blood flow was significantly more variable. Carotid and cortical cerebral blood flow increased using 10 mL/kg or 20 mL/kg with no difference between the two dose-volumes. There was no difference in cerebral blood flow by rate of administration, but carotid blood flow was more variable during slow administration. There were no differences in the increase in cerebral blood flow by portal of entry. If PaCO2 was maintained between 45 - 50 mmHg there was no increase in cerebral blood flow and there was less variable carotid flow. Conclusions: Cerebral blood flow increases with perfluorocarbon dosing. This occurs regardless of the dose-volume of perfluorocarbon. These effects were mitigated by closely targeting PaCO2.

Over 10% of preterm infants develop major disabilities, 50% develop behavioural problems and 40% need special education (Huddy et al., 2001; Webster, 2003). Prem Baby Triple P is a new variant of the Positive Parenting Program (Triple P) adapted specifically for parents of very preterm infants. The aim of this study is to assess the acceptability of Prem Baby Triple P to parents of infants born preterm and to test whether parental attributions and parental perception of infant health/developmental status are barriers to intervention acceptability. One hundred and twenty-three parents of preterm infants participated, 83 parents of very preterm infants and 40 parents of preterm infants. In addition, 32 parents of term infants participated as a comparison group. The acceptability of Prem Baby Triple P was moderately high and did not differ significantly across the three groups. Parental attributions were not found to be barriers to intervention acceptability and parental perceptions that their infant is less healthy/developmentally delayed facilitated Prem Baby Triple P acceptance in parents of infants born very preterm. This suggests that the planned Prem Baby Triple P content is acceptable to parents of infants born very preterm and sensitised to medical and developmental issues. These findings, as social validation data, will contribute towards the further development of Prem Baby Triple P and a future randomised controlled trial.

Accurate assessment of neonatal body composition is essential to studies investigating neonatal nutrition or developmental origins of obesity. Bioelectrical impedance analysis or bioimpedance analysis is inexpensive, non-invasive and portable, and is widely used in adults for the assessment of body composition. There are currently no prediction algorithms using bioimpedance analysis in neonates that have been directly validated against measurements of fat-free mass (FFM). The aim of the study was to evaluate the use of bioimpedance analysis for the estimation of FFM and percentage of body fat over the first 4 months of life in healthy infants born at term, and to compare these with estimations based on anthropometric measurements (weight and length) and with skinfolds. The present study was an observational study in seventy-seven infants. Body fat content of infants was assessed at birth, 6 weeks, 3 and 4·5 months of age by air displacement plethysmography, using the PEA POD body composition system. Bioimpedance analysis was performed at the same time and the data were used to develop and test prediction equations for FFM. The combination of weight+sex+length predicted FFM, with a bias of

The effect of the dietary n-3 long-chain PUFA, DHA (22 : 6n-3), on the growth of pre-term infants is controversial. We tested the effect of higher-dose DHA (approximately 1 % dietary fatty acids) on the growth of pre-term infants to 18 months corrected age compared with standard feeding practice (0·2–0·3 % DHA) in a randomised controlled trial. Infants born n 657) were randomly allocated to receive breast milk and/or formula with higher DHA or standard DHA according to a concealed schedule stratified for sex and birth-weight ( P = 0·02) longer at 18 months corrected age. There was an interaction effect between treatment and birth weight strata for weight (P = 0·01) and length (P = 0·04). Higher DHA resulted in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age. Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth.

Erythropoietin (EPO) is a cytokine hormone with cytoprotective effects in many tissues including the brain. Although the benefits of administration of recombinant human EPO (rhEPO) for neonatal hypoxic brain injury have been demonstrated in neuronal tissue, the effect on non-neuronal cell populations is unclear. We tested the hypothesis that rhEPO would not only protect neuronal cells but also glial cells at a stage of brain development where their maturation was particularly sensitive, and also protect the vasculature. This was evaluated in a rat model of hypoxic injury. 1000 IU/kg rhEPO was delivered intraperitoneally at the start of 4 h hypoxia or normoxia. Treatment groups of neonatal rats (day of birth, at least N = 10 per group) were as follows: normoxia; normoxia plus rhEPO; hypoxia (8% FiO(2) delivered in temperature-controlled chambers); and hypoxia plus rhEPO. Day of birth in rats is equivalent to human gestation of 28-32 weeks. The effects of rhEPO administration, especially to non-neuronal cell populations, and the associated molecular pathways, were investigated. Apoptosis was increased with hypoxia and this was significantly reduced with rhEPO (p < 0.05). The neuronal marker, microtubule-associated protein-2, increased in expression (p < 0.05) when apoptosis was significantly reduced by rhEPO. In addition, compared with hypoxia alone, rhEPO-treated hypoxia had the following significant protein expression increases (p < 0.05): the intermediate filament structural protein nestin; myelin basic protein (oligodendrocytes); and glial fibrillary acidic protein (astrocytes). In conclusion, rhEPO protects the developing brain via anti-apoptotic mechanisms and promotes the health of non-neuronal as well as neuronal cell populations at a time when loss of these cells would have long-lasting effects on brain function.

The principal function of the γ-aminobutyric acid (GABA) system in the adult brain is inhibition; however, in the neonatal brain, GABA provides much of the excitatory drive. As the brain develops, transmembrane chloride gradients change and the inhibitory role of GABA is initiated and continues throughout juvenile and adult life. Previous studies have shown that GABAA receptor subunit expression is developmentally regulated, and it is thought that the change in GABA function from excitation to inhibition corresponds to the changeover in expression of ‘immature’ to ‘mature’ subunit isoforms. We examined the protein expression pattern and distribution of GABA type A (GABAA) receptor α1-, α3- and β2-subunits in the parietal cortex and hippocampus of the developing piglet brain. Four perinatal ages were studied; 14 days preterm (P–14), 10 days preterm (P–10), day of birth (P0) and at postnatal day 7 (P7). Animals were obtained by either caesarean section or spontaneous birth. Protein expression levels and subunit localization were analysed by Western blotting and immunohistochemistry, respectively. In the cortex and hippocampus, GABAA receptor α1-subunit showed greatest expression at P7 when compared to all other age groups (p < 0.05). In contrast, α3 expression in the cortex was elevated in preterm brain, peaking at P0, followed by a significant reduction by P7 (p < 0.05); a similar trend was observed in the hippocampus. GABAA receptor β2-subunit protein expression appeared relatively constant across all time points studied in both the cortex and hippocampus. Immunolabelling of the α1-, α3- and β2-subunits was observed throughout all cortical layers at every age. GABAA receptor α3-subunit appeared to show specific localization to layers V and VI whilst labelling for the β2-subunit was observed in layer IV. In the hippocampus of all animals, the α1- and β2-subunits were shown to immunolabel various cells and processes in the dentate gyrus (DG), CA1 and CA3; the α3-subunit was barely observed except at the stratum moleculare of the DG. We report for the first time the ontogenesis of GABAA receptor subunits α1, α3 and β2 in the perinatal pig brain.

Background: Infants born very preterm experience poor postnatal growth relative to intrauterine growth, but at term equivalent age, they have increased percentage body fat compared with infants born at term. Objectives: The aim of this study was to assess body composition in very preterm infants born before 32 weeks postmenstrual age and to compare this with infants born at 32–36 weeks of gestation. Methods: Percentage fat, fat mass and fat-free mass were measured in 87 very preterm infants born

Objective: Very preterm neonates are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit any lung disease but giving 30 mL/kg of perfluorocarbon when starting PLV increases cortical cerebral blood flow velocity. We aimed to determine if varying the initial dose of perfluorocarbon alters the effect on cerebral blood flow velocity when starting PLV. Methods: In this randomised, controlled trial with historical comparison 24 preterm lambs received one of three loading doses of intratracheal perfluorocarbon liquid over 20 min when starting PLV: 20, 30 or 40 mL/kg. Data on respiratory mechanics, haemodynamics and cerebral blood flow velocity, measured with laser Doppler, were collected continuously for 30 min from the start of dosing. Results: Cortical cerebral blood flow velocity increased over time in all three groups (two-way ANOVA, P= 0.007). There was no difference between groups (two-way ANOVA, P= 0.26). There was no difference between groups in cortical cerebral blood flow velocity variability (P= 0.68), blood pressure (P= 0.96) or heart rate (P= 0.46). The was no statistically significant difference in PaCO2 between groups measured at baseline and at 30 min after starting PLV (P= 0.51). Conclusions: Cortical cerebral blood flow velocity and its variability are not affected by varying doses of tracheal perfluorocarbon (20, 30 or 40 mL/kg) at the start of PLV in preterm lambs.

Infant body composition is affected by maternal obesity, which results in increased % body fat in the infant. With the rapidly increasing incidence of obesity, it is important that normative data are available for infant body composition that is not affected by this trend in maternal obesity. This study assessed body composition in infants born at term to women with a BMI between 18.5 and 25. Infant % body fat, fat mass (FM), and fat free mass (FFM) were assessed at birth, 6 wk, 3 mo, and 4.5 mo of age by air displacement plethysmography, using the PEA POD body composition system. The effects of age, gender, GA, and feeding mode on these parameters were assessed. The % body fat doubled between birth and 6 wk of age and then increased at a slower rate. FFM was higher in male infants at all ages, whereas % body fat was higher in female infants at 4.5 mo. There was a trend to increased % fat and decreased FFM in breastfed (BF) infants. The study provides unique data regarding changes in infant body composition and growth in infants born to women in the healthy weight range.

Neuronal losses are observed in the brain after neonatal hypoxia-ischemia (HI) however few studies have examined the effects of HI on specific neuronal phenotypes and their possible contribution to behavioural outcomes. In the present study we examined whether postnatal day 3 (P3) HI alters numbers of corticotropin-releasing factor (CRF) and neuropeptide-Y (NPY) neurons in the paraventricular nucleus of the hypothalamus (PVN), the bed nucleus of the stria terminalis (BNST) and the amygdala, 1 (P10) and 6 (P45) weeks after P3 HI. A significant reduction in the number of CRF-positive neurons in the PVN, central nucleus of the amygdala (CeA) and BNST ipsilateral to the carotid ligation 1 and 6 weeks after P3 HI was observed. There was also a significant reduction in the number of NPY-positive neurons in the PVN, amygdala and BNST ipsilateral to the carotid ligation 1 week after P3 HI. However after 6 weeks, only the number of PVN NPY-positive neurons decreased significantly. At 6 weeks post-insult, the number of CeA CRF-positive neurons was inversely associated with locomotor activity and exploratory behaviour in an open field. In contrast, no significant correlations between neuronal counts and early neurodevelopment tests performed on P10 were observed. Thus after P3 HI persistent losses of CRF- and NPY-positive neurons occur and the loss of CeA CRF neurons may provide a central anatomical mechanism underlying neurobehavioural deficits observed 6 weeks after P3 HI. © 2010 Elsevier B.V. All rights reserved.

Hypoxia-ischemia is a significant cause of brain damage in the human newborn and can result in long-term neurodevelopmental disability. The loss of oxygen and glucose supply to the developing brain leads to excitotoxic neuronal cell damage and death; such over-excitation of nerve cells can also manifest as seizures. The newborn brain is highly susceptible to seizures although it is unclear what role they have in hypoxic-ischemic (H/I) injury. The aim of this study was to determine an association between seizures and severity of brain injury in a piglet model of perinatal H/I and, whether injury severity was related to type of seizure, i.e. sub-clinical (electrographic seizures only) or clinical (electrographic seizures+physical signs). Hypoxia (4% O(2)) was induced in anaesthetised newborn piglets for 30 min with a final 10 min period of hypotension; animals were recovered and survived to 72 h. Animals were monitored daily for seizures both visually and with electroencephalogram (EEG) recordings. Brain injury was assessed with magnetic resonance imaging (MRI), (1)H-MR spectroscopy ((1)H-MRS), EEG and by histology (haematoxylin and eosin). EEG seizures were observed in 75% of all H/I animals, 46% displayed clinical seizures and 29% sub-clinical seizures. Seizure animals showed significantly lower background amplitude EEG across all post-insult days. Presence of seizures was associated with lower cortical apparent diffusion coefficient (ADC) scores and changes in (1)H-MRS metabolite ratios at both 24 and 72 h post-insult. On post-mortem examination animals with seizures showed the greatest degree of neuropathological injury compared to animals without seizures. Furthermore, clinical seizure animals had significantly greater histological injury compared with sub-clinical seizure animals; this difference was not apparent on MRI or (1)H-MRS measures. In conclusion we report that both sub-clinical and clinical seizures are associated with increased severity of H/I injury in a term model of neonatal H/I.

White matter damage is a significant problem in the human pre-term baby. Damage to white matter is usually associated with injury or insults to babies born prematurely, typically before 32 weeks' gestation, however there is increasing evidence of both grey and white matter damage occurring after 32 weeks' gestation. Astrocytes play a vital role in white matter, regulating molecules such as glutamate in the extracellular space and preventing excitotoxic damage to neighbouring oligodendrocytes and axons. We have previously described dramatic changes in grey matter astrocytes in response to a hypoxic/ischemic (H/I) insult around the time of birth. In this study, we have used GFAP immunohistochemistry and Golgi-Kopsch staining to examine the morphology of white matter astrocytes in control neonatal pig brains, and in the brains of animals exposed to the same (perinatal) H/I insult. We demonstrate that the areal percentage of the section occupied by GFAP-immunoreactive processes and cell bodies is significantly decreased (by 46%, P < 0.0001) in subcortical white matter from H/I brains. This loss of GFAP was accompanied by alterations in astrocyte morphology and an overall decrease in the size (field of section occupied by an individual astrocyte) of white matter astrocytes from 649 mu m(2) to 426 mu m(2), as revealed by Golgi-Kopsch staining and image analysis. These data suggest that astrocytes may contribute to the pathology of white matter damage following an H/I insult around the time of birth, and suggest that astrocytes may offer a novel target for therapies to improve outcomes after H/I. (C) 2010 Elsevier B.V. All rights reserved.

Background: Very preterm neonates can have severe lung disease and are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit the lung disease, but it is unknown whether the administration of intratracheal perfluorocarbon when starting PLV affects haemodynamics or cerebral blood flow. Objectives: To determine if haemodynamics or cerebral blood flow are affected in preterm lambs receiving a dose of perfluorocarbon when starting PLV. Methods: Sixteen preterm lambs were randomised to either PLV or conventional mechanical ventilation. An intratracheal loading dose of 30 ml/kg of perfluorocarbon liquid (PLV group) or air (sham group) was instilled over 20 min. Data were collected continuously for 30 min from the start of dosing. Results: Cortical cerebral blood flow velocity, measured continuously with laser Doppler, was increased in the PLV group during the administration of perfluorocarbon and immediately thereafter (p = 0.0026); the highest mean increase in the PLV group was 27%. There was no difference in cortical cerebral blood flow variability (p = 0.96). There was a slightly lower mean arterial blood pressure in the PLV group; the heart rate did not differ between groups. The PaCO2 was higher in the PLV group at 30 min – the difference between groups was not statistically significant (difference between means = 5.5 mm Hg, 95% confidence interval –2.7 to 13.7). Conclusions: Preterm lambs receiving a dose of tracheal perfluorocarbon at the start of PLV have an increased cortical cerebral blood flow velocity, but no change in cortical cerebral blood flow variability.

Astrocytes play a vital role in the brain; their structural integrity and sustained function are essential for neuronal viability, especially after injury or insult. In this study, we have examined the response of astrocytes to hypoxia/ischemia (H/I), employing multiple methods (immunohistochemistry, iontophoretic cell injection, Golgi-Kopsch staining, and D-aspartate uptake) in a neonatal pig model of H/I. We have identified morphological changes in cortical gray matter astrocytes in response to H/I. Initial astrocytic changes were evident as early as 8 h Post-insult, before histological evidence for neuronal damage. By 72 h post-insult, astrocytes exhibited significantly fewer processes that were shorter, thicker, and had abnormal terminal swellings, compared with astrocytes from control brains that exhibited a complex structure with multiple fine branching processes. Quantification and image analysis of astrocytes at 72 h post-insult revealed significant decreases in the average astrocyte size, from 686 lm2 in controls to 401 lm2 in H/I brains. Sholl analysis revealed a significant decrease (>60%) in the complexity of astrocyte branching between 5 and 20 lm from the cell body. D-Aspartate uptake studies revealed that the H/I insult resulted in impaired astrocyte function, with significantly reduced clearance of the glutamate analog, D-aspartate. These results suggest that astrocytes may be involved in the pathophysiological events of H/I brain damage at a far earlier time point than first thought. Developing therapies that prevent or reverse these astrocytic changes may potentially improve neuronal survival and thus might be a useful strategy to minimize brain damage after an H/I insult.

Objective: Changes in cerebral impedance in the newborn piglet are able to discriminate, within 1-2 h of acute hypoxia, between animals which will have a good neurological outcome, and those who have suffered more severe hypoxia resulting in poor outcome. The aim of this study was to determine if cerebral impedance could be used to identify those human infants with an encephalopathy following acute hypoxia who subsequently have a poor neurological outcome. It is these infants who may benefit most from neural rescue treatment. Methods: Twenty-four newborn term infants with evidence of severe acute intrapartum hypoxia and encephalopathy were studied. Bioimpedance spectroscopy was commenced as soon as possible after birth and repeated every 30 min until the infant was 12 h old. Neurodevelopmental outcome was assessed at 12 months of age. Results: Although cerebral impedance was different to control values, there was no significant difference in cerebral impedance between hypoxic babies with normal and those with abnormal development. Conclusion: Cerebral impedance was increased in hypoxic babies, as predicted from animal data, but the method was not suitable for discrimination of outcome. Significance: Cerebral impedance is not useful for early identification of infants who subsequently have a poor outcome after acute intrapartum hypoxia and who may benefit from neural rescue treatment.

Perinatal asphyxia is a significant contributor to neonatal brain injury. However, there is significant variability in neurological outcome in neonates after global hypoxia-ischemia. The aims of this study were to identify which physiological response/s during global hypoxia-ischemia influence the severity of brain injury and to assess their relative importance. Hypoxia/hypercapnia was induced in 20 anaesthetized piglets by reducing the inspired oxygen fraction to 10% and the ventilation rate from 30 to 10 breaths per minute for 45 min. Neurological outcome was assessed using functional markers including cerebral function amplitude (via electroencephalography) and cerebral impedance, and the structural marker microtubule associated protein-2 by immunohistochemistry at 6 h post hypoxia. Significant variability in neurological outcome was observed following the constant hypoxia/hypercapnia insult. There was a high degree of variability in cardiovascular function (mean arterial blood pressure and heart rate) and serum cortisol concentrations in response to hypoxia. More effective maintenance of cardiovascular function and higher serum cortisol concentrations were associated with a better outcome. These two variables were strongly associated with neurological outcome, and together explained 68% of the variation in the severity of neurological outcome. The variability in the cardiovascular and cortisol responses to hypoxia may be a more important determinant of neurological outcome then previously recognized.

Infants who suffer hypoxic-ischaemic encephalopathy (HIE) at birth are at increased risk of developmental disability. In this at-risk population, reliable, inexpensive and early identification of those children who are likely to require formal developmental assessment and intervention is needed.To evaluate the ability of the Ages and Stages Questionnaire (ASQ) to detect developmentally delayed children in an Australian population of infants who suffered HIE at birth.Fifty-five children who survived HIE were followed until 12-14 months of age. Test characteristics were calculated to examine the ability of the ASQ to appropriately identify developmentally delayed infants against this study's 'gold standard': the Bayley Scales of Infant Development II.Comparing the ASQ with the Bayley Scales of Infant Development II, the questionnaire had the following test characteristics: sensitivity 92%, specificity 95%, positive predictive value 92%, negative predictive value 95% when used to detect severe developmental delay; and sensitivity 67%, specificity 93%, positive predictive value 92%, negative predictive value 68% when used to detect both severe and mild developmental delay. However, the ASQ used at standard cut-offs failed to detect any of the children with mild delay.The ASQ is extremely effective for the detection of severe developmental delay in children who have suffered HIE at birth. Its capacity to identify those with milder delay is limited. The ability of the test to detect only those with severe developmental delay means that the ASQ is of little value as a screening tool in this population.