Trends in survival, perinatal morbidities and two-year neurodevelopmental outcomes in extremely low-birthweight infants over four decades.

BACKGROUND: Although outcomes for infants born extremely low birthweight (ELBW; <1000 g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. OBJECTIVE: To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years' corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. METHODS: Analysis of data from discrete population-based prospective cohort studies of all live births free of lethal anomalies with birthweight 500-999 g in the state of Victoria, Australia, over 6 eras: 1979-80, 1985-87, 1991-92, 1997, 2005 and 2016-17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two-year neurodevelopmental outcomes. RESULTS: More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979-80, 70%; 2016-17, 84%), and more were offered active care (1979-80, 58%; 2016-17, 90%). Survival to 2 years rose substantially, from 25% in 1979-80 to 80% in 2016-17. In survivors, rates of any assisted ventilation rose from 75% in 1979-80 to 99% in 2016-17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two-year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979-80 to 30 in 2016-17, but annual numbers free of major disability increased much more, from 31 in 1979-80 to 147 in 2016-17. CONCLUSIONS: Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability.

Potential indirect impacts of the COVID-19 pandemic on children: a narrative review using a community child health lens.

▪In this narrative review, we summarise the vast and burgeoning research on the potential and established indirect impacts on children of the COVID-19 pandemic. We used a community child health lens to organise our findings and to consider how Australia might best respond to the needs of children (aged 0-12 years). ▪We synthesised the literature on previous pandemics, epidemics and natural disasters, and the current COVID-19 pandemic. We found clear evidence of adverse impacts of the COVID-19 pandemic on children that either repeated or extended the findings from previous pandemics. ▪We identified 11 impact areas, under three broad categories: child-level factors (poorer mental health, poorer child health and development, poorer academic achievement); family-level factors that affect children (poorer parent mental health, reduced family income and job losses, increased household stress, increased abuse and neglect, poorer maternal and newborn health); and service-level factors that affect children (school closures, reduced access to health care, increased use of technology for learning, connection and health care). ▪There is increasing global concern about the likely disproportionate impact of the current pandemic on children experiencing adversity, widening existing disparities in child health and developmental outcomes. ▪We suggest five potential strategy areas that could begin to address these inequities: addressing financial instability through parent financial supplements; expanding the role of schools to address learning gaps and wellbeing; rethinking health care delivery to address reduced access; focusing on prevention and early intervention for mental health; and using digital solutions to address inequitable service delivery.

Psychotropic medication prescribing trends in a developmental-behavioural clinic during the COVID-19 pandemic.

AIM: Psychotropic medication prescribing among children with developmental-behavioural and mental health problems appears to be rising globally. We aim to examine the effects of the COVID-19 pandemic and rapid introduction of telehealth consultations on the prescribing trends and medication change in a large paediatric public hospital developmental-behavioural outpatient service. METHODS: Data for developmental-behavioural outpatient encounters from 23 March 2019 to 22 March 2021 were extracted from the electronic medical record; representing the 12 months following the conversion to telehealth consultations during the onset of COVID-19 pandemic and the 12 months prior to this change. Excel and Statistical Package for the Social Sciences were used to calculate percentages and logistic regression to compare psychotropic prescribing trends during both periods. RESULTS: During the pandemic, there were a total of 3201 encounters (92.0% telehealth), compared with 2759 encounters (1.6% telehealth) during the previous year. Despite the higher number of encounters during the pandemic, the rates of encounters with psychotropic medication prescriptions reduced compared to the previous 12 months (19.8% vs. 29.3%). Prescriptions made during COVID-19 were more likely to be provided at review visits, patients ≥12 years and during consultant led encounters. The reduction in prescriptions involved both new and follow-up psychotropic medications. The majority of follow-up medication dosages were left unchanged. CONCLUSIONS: Psychotropic prescribing rates were lower during the COVID-19 pandemic. Fewer new medications were commenced and most medication dosages were unchanged.

Investigating the brain structural connectome following working memory training in children born extremely preterm or extremely low birth weight.

Children born extremely preterm (EP, <28 weeks' gestation) or extremely low birth weight (ELBW, <1,000 g) are a vulnerable population at high risk of working memory impairments. We aimed to examine changes in the brain structural connectivity networks thought to underlie working memory performance, after completion of a working memory training program (Cogmed) compared with a placebo program in EP/ELBW children. This was a double-blind, placebo-controlled randomized trial (the Improving Memory in a Preterm Randomised Intervention Trial). Children born EP/ELBW received either the Cogmed or placebo program at 7 years of age (n = 91). A subset of children had magnetic resonance imaging of the brain immediately pre- and 2 weeks post-training (Cogmed n = 28; placebo n = 27). T1 -weighted and diffusion-weighted images were used to perform graph theoretical analysis of structural connectivity networks. Changes from pre-training to post-training in structural connectivity metrics were generally similar between randomized groups. There was little evidence that changes in structural connectivity metrics were related to changes in working memory performance from pre- to post-training. Overall, our results provide little evidence that the Cogmed working memory training program has training-specific effects on structural connectivity networks in EP/ELBW children.

Audit of paediatrician recognition of children's vulnerability to harm at the Royal Children's Hospital, Melbourne.

AIM: Vulnerable children can be defined as those at risk of child abuse and neglect and long-term adverse health, neurodevelopmental and behavioural outcomes. This study examined whether a cohort of paediatricians and advanced trainees at the Royal Children's Hospital, Melbourne, recognised children's vulnerability. METHODS: We reviewed the clinical note in the electronic medical record (EMR) for 425 new patients presenting to five paediatric clinics between 1 July 2017 and 31 December 2017. We examined paediatrician documentation of adverse childhood experiences (ACE), risk and resilience factors, referrals for intervention to improve psychosocial well-being and the application of 'vulnerable child' alert flags in the EMR to indicate vulnerability to harm. Children were deemed vulnerable if the paediatrician explicitly stated it in the EMR, if the child had a 'vulnerable child' alert placed in their record or had an appropriate referral for management of neurodevelopmental trauma. RESULTS: Of the original cohort, 8% was documented as vulnerable, 21% had a referral for intervention and 2% had a 'vulnerable child' alert. Overall, paediatricians infrequently documented ACE, risk and protective factors. The odds of identifying vulnerability increased with each added risk factor recorded (odds ratio (OR) 2.6, P < 0.001, 95% confidence interval (1.9-3.5)), with an ACE score was >4 (OR 72, P < 0.001 (14.3-361)) and decreased with each added protective factor recorded (OR 0.6, P < 0.001 (0.5-0.8)). CONCLUSION: Paediatricians infrequently document ACE, risk and protective factors and rarely 'flag' children's vulnerability to harm. Identification of the vulnerable child is correlated with documentation of risk and resilience factors at the initial consultation.

Working memory training and brain structure and function in extremely preterm or extremely low birth weight children.

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety-one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45-min sessions, 5 days a week over 5-7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task-based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level-dependent (BOLD) signal during an n-back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n-back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group-by-time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training-induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831.

Who is prescribing psychotropic medications in a public developmental-behavioural clinical service and how often?

AIM: Psychotropic prescribing by paediatricians is increasingly common, and there is considerable variation in care provided. The aims of this study were to examine current rates of psychotropic prescribing in the developmental-behavioural outpatient clinics at the Royal Children's Hospital's Centre for Community Child Health, and to compare rates between paediatric consultants and advanced trainees. METHODS: Data were extracted for appointment encounters from electronic medical records across 12 months in 2017. Patient demographics, provider and medication order data were analysed using Excel and STATA to calculate logistic regression, standard deviation, percentages and means. RESULTS: From 5069 encounters, there were 847 (16.7%) that included psychotropic prescribing. Advanced trainees prescribed psychotropic medications in only 4.4% of their encounters compared with consultants who prescribed these medications in 23% of encounters (P < 0.001). Stimulants were the most commonly prescribed psychotropic medication (62%), either alone (86.3%) or in combination (13.7%). CONCLUSIONS: Psychotropic prescribing rates were lower than expected. Advanced trainees may need more experience in psychotropic prescribing.

Long-Term Academic Functioning Following Cogmed Working Memory Training for Children Born Extremely Preterm: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of Cogmed Working Memory Training compared with a placebo program in improving academic functioning 24 months post-training in extremely preterm/extremely low birth weight 7-year-olds. STUDY DESIGN: A multicenter double-blind, placebo-controlled randomized controlled trial was conducted across all tertiary neonatal hospitals in the state of Victoria, Australia. Participants were 91 extremely preterm/extremely low birth weight 7-year-old children born in Victoria in 2005. Children were randomly assigned to either the Cogmed or placebo arm and completed the Cogmed or placebo program (20-25 sessions of 35-40 minutes duration) at home over 5-7 weeks. Academic achievement (word reading, spelling, sentence comprehension, and mathematics) was assessed 24 months post-training, as well as at 2 weeks and 12 months post-training, via standardized testing inclusive of working memory, attention, and executive behavior assessments. Data were analyzed using an intention-to-treat approach with mixed-effects modeling. RESULTS: There was little evidence of any benefits of Cogmed on academic functioning 24 months post-training, as well as on working memory, attention, or executive behavior at any age up to 24 months post-training compared with the placebo program. CONCLUSIONS: We currently do not recommend administration of Cogmed for early school-aged children born extremely preterm/extremely low birth weight to improve academic functioning. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000124831.

Models of care in neurodevelopmental-behavioural paediatrics.

In Australia, children with developmental-behavioural presentations experience large variations in both access to specialist health care and in the care they receive from specialists. A recent survey of members of the Neurodevelopmental and Behavioural Paediatric Society of Australasia confirmed that this variation persists even among public services provided by paediatric doctors with a special interest in this field. In this article, we discuss the challenges of establishing a single model of developmental-behavioural paediatric care and set out principles of best practice in the field. An essential part of working towards excellence in care involves defining our outcomes, utilising standardised measures, collecting systematic data, working in partnership with families to address their concerns and goals, participating in reflective practice and demonstrating a willingness to change current practice based on the results.

Rates of early intervention services in children born extremely preterm/extremely low birthweight.

AIM: To determine the rates of early intervention (EI) service use in extremely preterm (EP, <28 weeks' gestation) or extremely low birthweight (ELBW, <1000 g) infants between 1991 and 2013, and identify biological or socio-economic factors associated with receiving EI. METHODS: Participants comprised consecutive EP or ELBW survivors born in 1991-1992, 1997 or 2005 in Victoria, Australia, and randomly selected, matched term-born controls. The main outcome measure was parent-reported EI participation up to 8 years of age. Neurodevelopmental outcomes and socio-economic risk factors were compared with EI participation to identify associations among the preterm groups. RESULTS: The rates of EI were higher in the preterm groups than the control groups overall (odds ratio 4.29, 95% confidence interval 3.28, 5.59, P < 0.001), and the rates of EI rose significantly over time - from 42% in the 1991-1992 preterm cohort to 64% in the 2005 preterm cohort. Among the preterm groups, post-natal corticosteroid therapy, cystic periventricular leukomalacia and surgery in the newborn period were all independently associated with increased odds of receiving EI. Increased severity of disability was associated with higher rates of EI. The majority (95%) of preterm children with a physical impairment received EI, compared with only 73% of children with a cognitive impairment alone. EI participation rates were independent of social risk. CONCLUSION: EI participation is high in the EP population, and rates of EI use have increased over time. Contrary to previous reports, social risk factors were not found to be associated with EI use.

Recognition of attachment difficulties and developmental trauma is the responsibility of all paediatricians.

This article provides an overview of attachment theory, developmental trauma and trauma-informed care for paediatricians. The impact of difficult or impoverished parent-child relationships on brain development and long-term health is now well known. Recent neuroscience research reveals the adverse neurological impacts of developmental trauma and supports the biological basis of attachment theory. There is also an increasing body of evidence that childhood adversity is common and impacts physical and mental health throughout the life-span. Comprehensive paediatric assessment should include an understanding of attachment difficulties and developmental trauma. Viewing children and their families through a 'trauma-informed lens' can provide critical insights into their clinical presentation and care needs. All paediatricians should be providing and practicing trauma-informed care.

Altered posterior cingulate brain metabolites and cognitive dysfunction in preterm adolescents.

BACKGROUND: Extremely preterm (EP, <28 wk gestation) individuals have increased the risk of cognitive deficits compared with controls. The posterior cingulate region has an important role in cognitive function, but how this is affected by preterm birth is unknown. We aimed to compare brain metabolite ratios of neurons and cell membranes between EP 18-y olds and controls, and explore the association between metabolite ratios and cognitive outcomes. METHOD: A regional cohort of 150 EP and 134 controls were recruited for the study. Cerebral metabolites were measured using proton magnetic resonance spectroscopy (MRS) obtained from a left posterior cingulate voxel. Total N-acetylaspartate (tNAA, neuronal marker)/total creatine (tCr), and total choline (tCho, cell membrane marker)/tCr ratios were compared between groups using linear regression. Metabolite ratios were correlated with tests of general intelligence (IQ), memory, and attention using linear or logistic regression. RESULTS: Compared with controls, EP had lower tNAA/tCr (mean difference (95% CI) of -2.27% (-4.09, -0.45)) and tCho/tCr (mean difference (95% CI) of -11.11% (-20.37, -1.85)), all P = 0.02. Higher tCho/tCr correlated with better IQ in the EP group only; whereas higher tNAA/tCr ratios correlated with better scores in working memory and attention in both groups. CONCLUSION: EP birth is associated with long-term brain metabolite ratio alterations. This may underlie poorer cognitive performance in EP survivors.

A simple screen performed at school entry can predict academic under-achievement at age seven in children born very preterm.

AIM: We aimed to compare the academic outcomes of a cohort of children born very preterm (VPT, <32 weeks of gestation) and children born at term at age 7 years and assess the ability of a pre-academic skill screen at age five to predict later academic impairment in children born VPT at age seven. METHODS: One hundred ninety-four children born VPT (born with either gestational age <30 weeks or birthweight <1250 g) and 70 controls born at term from a prospective birth cohort were compared on academic outcomes (Wide Range Achievement Test, WRAT4) at age seven using regression analyses. Receiver-operating characteristic curves were used to determine whether pre-academic skills (Kaufman Survey of Early Academic and Language Skills, K-SEALS) at age five predicted academic impairment at age seven in 174 of the VPT cohort. RESULTS: At the age of 7 years, children born VPT had lower mean word reading (-9.7, 95% CI: -14.7 to -4.6), spelling (-8.3, 95% CI: -13.3 to -3.3) and math computation (-10.9, 95% CI: -15.3 to -6.5) scores (all P-values ≤0.001) compared with controls born at term, even after adjusting for social risk and time since school commencement. In terms of pre-academic screening, the Numbers, Letters and Words subtest of the K-SEALS had adequate sensitivity and specificity (70-80%) for predicting children with academic impairment at age seven. CONCLUSIONS: Children born VPT underperformed in academic outcomes at age seven compared with controls born at term. A pre-academic screening tool used at school entry can predict children born VPT at risk of academic impairment at age seven who could benefit from targeted early intervention.

Abnormalities in orbitofrontal cortex gyrification and mental health outcomes in adolescents born extremely preterm and/or at an extremely low birth weight.

Extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) infants are at high risk of aberrant neurodevelopment. Sulcogyral folding patterns of the orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (> 2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent-reported metacognition scores overall (P = 0.008) and better self-reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects.

Masked hypertension in extremely preterm adolescents.

AIM: Extremely preterm (EPT, born <28 weeks gestation) or extremely low birthweight (ELBW, birthweight <1000 g) individuals are at increased risk of high blood pressure (BP) and cardiovascular disease. We compared office BP measurements with 24-h ambulatory BP measurement (ABP) in EPT/ELBW individuals at age 18 years and term controls, and determined the sensitivity and specificity of office BP in predicting masked hypertension (24-h ABP measurements > 130/80). METHODS: All EPT/ELBW individuals and matched term control adolescents born in Victoria, Australia, between 1991 and 1992 were recruited. A subset of this cohort was seen at 18 years, and researchers blinded to birth status measured office BP and ABP. We established the office BP thresholds that had the highest sensitivity and specificity in predicting masked hypertension. RESULTS: EPT/ELBW (N = 120) individuals had higher mean BP measurements at 18 years, compared with controls (N = 71). Although there were no significant differences in rates of high BP between groups, high proportions of both EPT/ELBW (43.3%) and term control (36.6%) participants met criteria for masked systolic hypertension. In EPT/ELBW individuals, office systolic BP measurement of ≥122.5 mmHg predicted masked systolic hypertension (sensitivity 79%, specificity 74%). Office diastolic BP measurement of ≥75.5 mmHg predicted masked diastolic hypertension (sensitivity 77%, specificity, 77%). CONCLUSIONS: At age 18 years, EPT/ELBW individuals have higher systolic and diastolic BP, compared with controls. Office BP may be an adequate screen for masked hypertension in EPT/ELBW survivors, but further research is needed to identify accurate ABP thresholds for masked hypertension for young Australians.

The cost of long-term follow-up of high-risk infants for research studies.

AIMS: Neonatal intensive care is expensive, and thus it is essential that its long-term outcomes are measured. The costs of follow-up studies for high-risk children who survive are unknown. This study aims to determine current costs for the assessment of health and development of children followed up in our research programme. METHODS: Costs were determined for children involved in the research follow-up programme at the Royal Women's Hospital, Melbourne, over the 6-month period between 1st January 2012 and 30th June 2012. The time required for health professionals involved in assessments in early and later childhood was estimated, and converted into dollar costs. Costs for equipment and data management were added. Estimated costs were compared with actual costs of running the research follow-up programme. RESULTS: A total of 134 children were assessed over the 6-month period. The estimated average cost per child assessed was $1184, much higher than was expected. The estimated cost to assess a toddler was $1149, whereas for an 11-year-old it was $1443, the difference attributable to the longer psychological and paediatric assessments. The actual average cost per child assessed was $1623. The shortfall of $439 between the actual and estimated average costs per child arose chiefly because of the need to pay staff even when participants were late or failed to attend. CONCLUSIONS: The average costs of assessing children at each age for research studies are much higher than expected. These data are useful for planning similar long-term follow-up assessments for high-risk children.

Association between postnatal dexamethasone for treatment of bronchopulmonary dysplasia and brain volumes at adolescence in infants born very preterm.

OBJECTIVES: To compare brain volumes in adolescents who were born extremely preterm (<28 weeks gestation) who had received postnatal dexamethasone, and to determine if there was a postnatal dexamethasone dose-response effect on brain volumes. STUDY DESIGN: Geographical cohort study of extremely preterm adolescents born in 1991-1992 in Victoria, Australia. T1-weighted magnetic resonance imaging was performed at 18 years of age. Segmented and parcellated brain volumes were calculated using an automated segmentation method (FreeSurfer) and compared between groups, with and without adjustment for potential confounders. The relationships between total postnatal dexamethasone dose and brain volumes were explored using linear regression. RESULTS: Of the 148 extremely preterm participants, 55 (37%) had received postnatal dexamethasone, with a cumulative mean dose of 7.7 mg/kg. Compared with participants who did not receive postnatal dexamethasone, those who did had smaller total brain tissue volumes (mean difference -3.6%, 95% CI [-7.0%, -0.3%], P value = .04) and smaller white matter, thalami, and basal ganglia volumes (all P < .05). There was a trend of smaller total brain and white matter volumes with increasing dose of postnatal dexamethasone (regression coefficient -7.7 [95% CI -16.2, 0.8] and -3.2 [-6.6, 0.2], respectively). CONCLUSIONS: Extremely preterm adolescents who received postnatal dexamethasone in the newborn period had smaller total brain tissue volumes than those who did not receive postnatal dexamethasone, particularly white matter, thalami, and basal ganglia. Vulnerability of brain tissues or structures associated with postnatal dexamethasone varies by structure and persists into adolescence.

Long term follow up of high risk children: who, why and how?

BACKGROUND: Most babies are born healthy and grow and develop normally through childhood. There are, however, clearly identifiable high-risk groups of survivors, such as those born preterm or with ill-health, who are destined to have higher than expected rates of health or developmental problems, and for whom more structured and specialised follow-up programs are warranted. DISCUSSION: This paper presents the results of a two-day workshop held in Melbourne, Australia, to discuss neonatal populations in need of more structured follow-up and why, in addition to how, such a follow-up programme might be structured. Issues discussed included the ages of follow-up, and the personnel and assessment tools that might be required. Challenges for translating results into both clinical practice and research were identified. Further issues covered included information sharing, best practice for families and research gaps. SUMMARY: A substantial minority of high-risk children has long-term medical, developmental and psychological adverse outcomes and will consume extensive health and education services as they grow older. Early intervention to prevent adverse outcomes and the effective integration of services once problems are identified may reduce the prevalence and severity of certain outcomes, and will contribute to an efficient and effective use of health resources. The shared long-term goal for families and professionals is to work toward ensuring that high risk children maximise their potential and become productive and valued members of society.