Search

BACKGROUND: Few studies have tracked growth in children born extremely preterm (EP, <28 weeks' gestation) beyond late adolescence. The relationships between growth parameters (including weight and BMI) through childhood and adolescence with later cardiometabolic health, are unclear in those born EP. We aimed to (i) compare growth from 2 to 25 years between EP and controls; and in the EP group (ii) determine the associations of growth parameters with cardiometabolic health. METHODS: Prospective state-wide cohort of all EP livebirths in Victoria, Australia, in 1991-1992 and contemporaneous term-born controls. Z-scores for weight (z-weight), height (z-height) and BMI (z-BMI) at 2, 5, 8, 18 and 25 years, and cardiometabolic health at 25 years (body composition, glucose tolerance, lipid profiles, blood pressure, exercise capacity) were measured. Growth trajectories were compared between groups using mixed models. The relationships between z-BMI changes/year, and being overweight at different ages, with cardiometabolic health were explored using linear regression. FINDINGS: Z-weight and z-BMI were lower in EP than controls, but the gap decreased with age due to a more rapid rate of rise in z-weight and a decrease in z-height in the EP group compared with controls. Greater increases in z-BMI/year in the EP group were associated with poorer cardiometabolic health [coefficient (95% CI) per 0.1 z-BMI increase/year: visceral fat volume (cm3) 217.8 (160.9, 274.7), triglycerides (mmol/L) 0.45 (0.20, 0.71), systolic blood pressure (mmHg) 8.9 (5.8, 12.0), and exercise capacity (BEEP test maximum level -1.2 (-1.7, -0.7)), all p < 0.001]. The association between being overweight with poorer cardiometabolic health strengthened with age. INTERPRETATION: The catch-up in weight and BMI by young adulthood in survivors born EP may not be desirable as it is associated with poorer cardiometabolic health. The associations of being overweight from mid-childhood with poorer cardiometabolic hea

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if: (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), potential systemic side effects of corticosteroids, cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity). DISCUSSION: Combining budesonide with surfactant for intratracheal administration is a simple intervention that may r

AIM: Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long-term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. METHODS: Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016-2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. RESULTS: Seventy-six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92-3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) -1.3 (-2.7, 0.1) and motor composite score adjusted coefficient (95% CI) -1.3 (-2.8, 0.2). CONCLUSION: Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes.

There have been many studies demonstrating children born very preterm exhibit brain white matter microstructural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (<30 weeks' gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and increased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and con

BACKGROUND: This study examined differences in ADHD symptoms and diagnosis between preterm and term-born adults (≥18 years), and tested if ADHD is related to gestational age, birth weight, multiple births, or neonatal complications in preterm borns. METHODS: (1) A systematic review compared ADHD symptom self-reports and diagnosis between preterm and term-born adults published in PubMed, Web of Science, and PROQUEST until April 2021; (2) a one-stage Individual Participant Data(IPD) meta-analysis (n = 1385 preterm, n = 1633 term; born 1978-1995) examined differences in self-reported ADHD symptoms[age 18-36 years]; and (3) a population-based register-linkage study of all live births in Finland (01/01/1987-31/12/1998; n = 37538 preterm, n = 691,616 term) examined ADHD diagnosis risk in adulthood (≥18 years) until 31/12/2016. RESULTS: Systematic review results were conflicting. In the IPD meta-analysis, ADHD symptoms levels were similar across groups (mean z-score difference 0.00;95% confidence interval [95% CI] -0.07, 0.07). Whereas in the register-linkage study, adults born preterm had a higher relative risk (RR) for ADHD diagnosis compared to term controls (RR = 1.26, 95% CI 1.12, 1.41, p < 0.001). Among preterms, as gestation length (RR = 0.93, 95% CI 0.89, 0.97, p < 0.001) and SD birth weight z-score (RR = 0.88, 95% CI 0.80, 0.97, p < 0.001) increased, ADHD risk decreased. CONCLUSIONS: While preterm adults may not report higher levels of ADHD symptoms, their risk of ADHD diagnosis in adulthood is higher. IMPACT: Preterm-born adults do not self-report higher levels of ADHD symptoms, yet are more likely to receive an ADHD diagnosis in adulthood compared to term-borns. Previous evidence has consisted of limited sample sizes of adults and used different methods with inconsistent findings. This study assessed adult self-reported symptoms across 8 harmonized cohorts and contrasted the findings with diagnosed ADHD in a population-based register-linkage study. Preterm-born

BACKGROUND: Moderate-late preterm (MLP; 32 to <37 weeks' gestation) birth is associated with reduced expiratory airflow during child, adolescent and adult years. However, some studies have reported only minimal airflow limitation and hence it is unclear if clinical assessment in later life is warranted. Our aim was to compare maximal expiratory airflow in children and adults born MLP with term-born controls, and with expected norms. METHODS: We systematically reviewed studies reporting z-scores for spirometric indices (forced expired volume in 1 second [FEV1], forced vital capacity [FVC], FEV1/FVC ratio and forced expiratory flow at 25-75% of FVC [FEF25-75%]) from participants born MLP aged five years or older, with or without a term-born control group from 4 databases (MEDLINE, CINAHL, Embase, Emcare). Publications were searched for between the 22nd of September 2021 to the 29th of September 2021. A meta-analysis of eligible studies was conducted using a random effects model. The study protocol was published in PROSPERO (CRD #42021281518). FINDINGS: We screened 4970 articles and identified 18 relevant studies, 15 of which were eligible for meta-analysis (8 with term-born controls and 7 without). Compared with controls, MLP participants had lower z-scores (mean difference [95% confidence interval] I2) for FEV1: -0.22 [-0.35, -0.09] 49.3%, FVC: -0.23 [-0.4, -0.06] 71.8%, FEV1/FVC: -0.11 [-0.20 to -0.03] 9.3% and FEF25-75%: -0.27 [-0.41 to -0.12] 21.9%. Participants born MLP also had lower z-scores, on average, when compared with a z-score of 0 (mean [95% CI] I2) for FEV1: -0.26 [-0.40 to -0.11] 85.2%, FVC: -0.18 [-0.34 to -0.02] 88.3%, FEV1/FVC: -0.24 [-0.43 to -0.05] 90.5% and FEF25-75%: -0.33 [-0.54 to -0.20] 94.7%. INTERPRETATION: Those born MLP had worse expiratory airflows than those born at term, and compared with norms, although reductions were modest. Clinicians should be aware that children and adults born MLP may be at higher risk of obstructive lung diseas

OBJECTIVES: Children born very preterm (VP) are susceptible to a range of cognitive impairments, yet the effects of VP birth on long-term, episodic, and prospective memory remains unclear. This study examined episodic and prospective memory functioning in children born VP compared with their term-born counterparts at 13 years. METHOD: VP (n = 81: born <30 weeks' gestation) and term (n = 26) groups were aged between 12 and 14 years. Children completed: (i) standardized verbal and visuospatial episodic memory tests; and (ii) an experimental time- and event-based prospective memory test that included short-term (within assessment session) and long-term (up to 1-week post-session) tasks. Parents completed a questionnaire assessing memory functions in everyday life. RESULTS: The VP group performed worse on all measures of verbal and visuospatial episodic memory than the term group. While there were no group differences in event-based or long-term prospective memory, the VP group performed worse on time-based and short-term prospective memory tasks than term-born counterparts. Parents of children born VP reported more everyday memory difficulties than parents of children born at term, with parent-ratings indicating significantly elevated rates of everyday memory challenges in children born VP. CONCLUSIONS: Children born VP warrant long-term surveillance, as challenges associated with VP birth include memory difficulties at 13 years. This study highlights the need for greater research and clinical attention into childhood functional memory outcomes.

OBJECTIVE: To evaluate 13-year outcomes of a randomized controlled trial of preventive care (VIBeS Plus) for infants born very preterm and their parents and examine whether possible effects of intervention varied by family social risk. STUDY DESIGN: Families were randomized to an intervention arm (n = 61) or a standard care arm (n = 59). The intervention was delivered at home by psychologists and physiotherapists over the infants' first year, focusing on infant development and parental mental health. At 13 years corrected age, cognitive, motor, and behavioral outcomes, and parental mental health were assessed. Primary estimands were between-group mean differences, estimated using multiple imputed regression models. RESULTS: Follow-up included 81 surviving children (69%). There was little evidence of benefits of the intervention for IQ, attention, executive functioning, working memory, and academic skills regardless of level of social risk. Specifically, mean differences in adolescent cognitive outcomes ranged from -2.0 units (95% CI, -9.9 to 5.9) in favor of standard treatment to 5.1 units (95% CI, -2.3 to 12.5) favoring the intervention. A group-by-social risk interaction was observed only for adolescent motor outcomes, with mean differences favoring the intervention for those at higher social risk (balance, 4.9; 95% CI, 1.3-8.5; total motor, 3.2; 95% CI, 0.3-6.2), but not those at lower social risk (balance, -0.3; 95% CI, -2.4 to 1.9; total motor, 0.03; 95% CI, -1.9 to 2.0). Mean differences in adolescent behavior and parental mental health ranged from -6.6 (95% CI -13.8, 0.5) to -0.2 (95% CI, -1.9 to 1.4) and -1.8 (95% CI, -4.1 to 0.6) to -1.7 (95% CI, -4.3 to 1.0), respectively, indicating a pattern of fewer symptoms in the intervention group. CONCLUSIONS: Benefits of the intervention persisted for adolescent behavior, with better motor outcomes observed in those from socially disadvantaged families. Replication with larger samples, multiple informant reports, a

AIM: To determine the relationship between early motor repertoire and 2-year neurodevelopment in infants born extremely preterm (<28 weeks' gestation) or extremely-low-birthweight (ELBW) (<1000g). METHOD: This was a geographical prospective cohort of 139 infants born extremely preterm/ELBW (mean gestational age 26.7 weeks, standard deviation [SD] 2.0, 68/139 [49%] male), with parent-recorded videos suitable for scoring the General Movements Assessment (GMA). Motor repertoire was assessed using the Motor Optimality Score-Revised (MOS-R), with and without the fidgety movement subsection, and the GMA alone at 12 to 13+6 weeks corrected age and 14 to 15+6 weeks corrected age. At 2 years corrected age, impaired development was defined as Bayley Scales of Infant and Toddler Development, Third Edition motor and cognitive development scores 1SD or less relative to controls born at term; paediatricians diagnosed cerebral palsy (CP). RESULTS: Greater MOS-R scores at 14 to 15+6 weeks corrected age were associated with lower odds of CP (odds ratio [OR] per 1-point increase=0.83, 95% confidence interval [CI]=0.71-0.99), and motor (OR=0.93, 95% CI=0.87-0.99), or cognitive impairment (OR=0.94, 95% CI=0.88-0.99). Absent/abnormal GMA at 14 to 15+6 weeks was associated with CP and motor delay. There was little evidence that MOS-R scores at 12 to 13+6 weeks were associated with neurodevelopmental outcomes at 2 years. INTERPRETATION: Poorer MOS-R scores and absent/abnormal GMA, scored from parent-recorded videos at 14 to 15+6 weeks gestational age, are associated with CP and developmental impairment in 2-year-old infants born extremely preterm/ELBW.

BACKGROUND: The relationship between early postnatal brain development and neurobehaviour at term-equivalent age (TEA) remains uncertain. AIM: We aimed to explore relationships between early postnatal cranial ultrasonography (cUS) linear measures of brain size and brain growth with neurobehaviour at TEA in infants born <30 weeks' gestational age (GA). STUDY DESIGN: Prospective observational cohort study. SUBJECTS: 137 infants born <30 weeks' GA without major brain injury on neonatal cUS. OUTCOME MEASURES: Neurobehaviour at TEA assessed using the General Movements Assessment (GMA) and Hammersmith Neonatal Neurological Examination (HNNE). RESULTS: The GMA was administered in 115/137 (84%) infants; 80 (70%) presented with abnormal general movements (GMs) (79 poor repertoire, 1 cramped synchronised). The HNNE was assessed in 106/137 (77%) infants; 52 (49%) had a suboptimal total score. With respect to brain size, larger measures of the corpus callosum length (CCL) and right anterior horn width (AHW) at 1-month were related to lower risk of abnormal GMs, and larger measures of the biparietal diameter at 1-week and 2-months were related to lower risk of a suboptimal HNNE. As for brain growth, increases of the CCL and transcerebellar diameter between birth and 1-month, and left and right AHWs between 1- and 2-months, were related to lower risk of abnormal GMs. CONCLUSION: Early postnatal brain size and brain growth were related to neurobehaviour at TEA in infants born <30 weeks' GA. This study provides preliminary evidence for the prognostic utility of early postnatal cUS linear measures as potential markers of neurodevelopment in later childhood.

OBJECTIVE: The objective of this study was to determine whether school readiness differs between children born <30 weeks' gestation who are classified as at risk for developmental coordination disorder (DCD) and those who are not. METHODS: This study was a prospective cohort study of children born <30 weeks' gestation. Children were classified as at risk for DCD at a corrected age of 4 to 5 years if they scored <16th centile on the Movement Assessment Battery for Children-Second Edition (MABC-2), had a full scale IQ score of ≥80 on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV), and had no cerebral palsy. Children were assessed on 4 school readiness domains: (1) health/physical development [Physical Health domain of Pediatric Quality of Life Inventory (PedsQL), Pediatric Evaluation of Disability Inventory Computer Adaptive Test, and Little Developmental Coordination Disorder Questionnaire], (2) social-emotional development (Strengths and Difficulties Questionnaire and PedsQL psychosocial domains), (3) cognitive skills/general knowledge (WPPSI-IV), and (4) language skills (WPPSI-IV). RESULTS: Of 123 children assessed, 16 were ineligible (IQ < 80 or cerebral palsy: n = 15; incomplete MABC-2: n = 1); 28 of 107 (26%) eligible children were at risk for DCD. Children at risk for DCD had poorer performance on all school readiness domains, with group differences of more than 0.4 SD in health/physical development, social-emotional development, and language skills and up to 0.8 SD for cognitive skills/general knowledge compared with those not at risk of DCD. CONCLUSION: Being at risk for DCD in children born <30 weeks' gestation is associated with challenges in multiple school readiness domains, not only the health/physical domain.

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.

Objectives To compare the parenting environment and the relationships between parenting behaviors and concurrent child neurobehavioral outcomes at 2 years of corrected age between children born moderate-to-late preterm (MLP; 32-36 weeks of gestation) and at term (≥37 weeks of gestation). Study design Participants were 129 children born MLP and 110 children born at term and their mothers. Mothers’ parenting behaviors (sensitivity, structuring, nonintrusiveness, nonhostility) were assessed at 2 years of corrected age using the Emotional Availability Scales. Child cognitive and language development were assessed using the Bayley Scales of Infant and Toddler Development, and social–emotional competence using the Infant Toddler Social and Emotional Assessment. Results Mothers of children born MLP and at term displayed similar parenting behaviors overall, with slightly lower nonintrusiveness in mothers of children born MLP (adjusted mean difference −0.32 [–0.60, −0.04]; P = .03). In both groups of children, greater maternal sensitivity was associated with better cognitive development (P < .001 MLP; P = .02 term), increased maternal structuring was associated with better social–emotional competence (P = .02 MLP; P = .03 term), and higher maternal nonintrusiveness was associated with better cognitive, language, and social-emotional outcomes (all P < .04). Greater maternal sensitivity and structuring were associated with better language development in children born MLP but not in children born at term. Conclusions Parenting behaviors are important for neurobehavioral outcomes in children born MLP and at term. Language development may be more strongly influenced by select parenting behaviors in children born MLP compared with children born at term.

BACKGROUND: Children born very preterm (< 32 weeks' gestation) are at greater risk of motor impairment and executive/attentional dysfunctions than term-born children; however, little is known about how functional tasks, including walking, may be affected by very preterm birth. RESEARCH QUESTION: How does the gait pattern of preschool-age children born < 30 weeks compare with term-born controls under a variety of walking conditions? METHODS: In this prospective cohort study, children born < 30 weeks and at term were assessed at 4.5-5 years' corrected age, blinded to birth group. Four walking conditions were assessed using the GAITRite® system: preferred speed, cognitive dual-task, motor dual-task, and tandem walking. Gait variables analysed included speed, cadence, step length, step time, base of support (BOS), and single and double support time. Spatiotemporal variables were compared between groups using linear regression, adjusting for lower-limb length, corrected age at assessment, and number of trials. RESULTS: 224 children (112 < 30 weeks and 112 term-born) were assessed. Gait variables of children born < 30 weeks did not differ from their term-born peers when walking at their preferred speed, except for higher BOS variability (mean difference [MD] = 0.19 cm, 95% confidence interval [CI] 0.10, 0.27, p < 0.001). Under the motor dual-task condition, children born < 30 weeks walked faster (MD= 3.06 cm/s, 95% CI 0.14, 5.97, p = 0.040), with a longer step length (MD= 1.10 cm, 95%CI 0.19, 2.01, p = 0.018), and a wider BOS (MD= 0.37 cm, 95%CI 0.06, 0.67, p = 0.019). In cognitive dual-task and tandem conditions, children born < 30 weeks walked with a wider BOS compared with term-born peers (MD= 0.43 cm, 95%CI 0.05, 0.81, p = 0.028; and MD= 0.30 cm, 95%CI 0.09, 0.51, p = 0.005, respectively). SIGNIFICANCE: This research highlights the need to consider the walking performance of preschool-age children born < 30 weeks under challenging conditions, such as dual-task or tand

Very preterm (VP) birth is associated with an increased risk for later neurodevelopmental and behavioural challenges. Although the neurobiological underpinnings of such challenges continue to be explored, previous studies have reported brain volume and morphology alterations in children and adolescents born VP compared with full-term (FT)-born controls. How these alterations relate to the trajectory of brain maturation, with potential implications for later brain ageing, remains unclear. In this longitudinal study, we investigate the relationship between VP birth and brain development during childhood and adolescence. We construct a normative 'brain age' model to predict age over childhood and adolescence based on measures of brain cortical and subcortical volumes and cortical morphology from structural MRI of a dataset of typically developing children aged 3-21 years (n = 768). Using this model, we examined deviations from normative brain development in a separate dataset of children and adolescents born VP (<30 weeks' gestation) at two timepoints (ages 7 and 13 years) compared with FT-born controls (120 VP and 29 FT children at age 7 years; 140 VP and 47 FT children at age 13 years). Brain age delta (brain-predicted age minus chronological age) was, on average, higher in the VP group at both timepoints compared with controls, however this difference had a small to medium effect size and was not statistically significant. Variance in brain age delta was higher in the VP group compared with controls; this difference was significant at the 13-year timepoint. Within the VP group, there was little evidence of associations between brain age delta and perinatal risk factors or cognitive and motor outcomes. Under the brain age framework, our results may suggest that children and adolescents born VP have similar brain structural developmental trajectories to term-born peers between 7 and 13 years of age.

AIM: To investigate the strength of the independent associations of mathematics performance in children born very preterm (<32wks' gestation or <1500g birthweight) with attending postsecondary education and their current employment status in young adulthood. METHOD: We harmonized data from six very preterm birth cohorts from five different countries and carried out one-stage individual participant data meta-analyses (n=954, 52% female) using mixed effects logistic regression models. Mathematics scores at 8 to 11 years of age were z-standardized using contemporary cohort-specific controls. Outcomes included any postsecondary education, and employment/education status in young adulthood. All models were adjusted for year of birth, gestational age, sex, maternal education, and IQ in childhood. RESULTS: Higher mathematics performance in childhood was independently associated with having attended any postsecondary education (odds ratio [OR] per SD increase in mathematics z-score: 1.36 [95% confidence interval {CI}: 1.03, 1.79]) but not with current employment/education status (OR 1.14 per SD increase [95% CI: 0.87, 1.48]). INTERPRETATION: Among populations born very preterm, childhood mathematics performance is important for adult educational attainment, but not for employment status.

BACKGROUND AND OBJECTIVES: Children born very preterm (<32 weeks' gestation) have more neurodevelopmental problems compared with term-born peers. Aberrant fidgety movements (FMs) are associated with adverse motor outcomes in children born very preterm. However, associations of aberrant FMs combined with additional movements and postures to give a motor optimality score-revised (MOS-R) with school-aged cognitive and motor outcomes are unclear. Our aim with this study was to determine those associations. METHODS: Of 118 infants born <30 weeks' gestation recruited into a randomized controlled trial of early intervention, 97 had a general movements assessment at 3 months' corrected age and were eligible for this study. Early motor repertoire including FMs and MOS-R were scored from videos of infant's spontaneous movement at 3 months' corrected age. At 8 years' corrected age, cognitive and motor performances were evaluated. Associations of early FMs and MOS-R with outcomes at 8 years were determined using linear regression. RESULTS: Seventy-eight (80%) infants with early motor repertoire data had neurodevelopmental assessments at 8 years. A higher MOS-R, and favorable components of the individual subscales of the MOS-R, including the presence of normal FMs, were associated with better performance for general cognition, attention, working memory, executive function and motor function at 8 years; eg, presence of normal FMs was associated with a 21.6 points higher general conceptual ability score (95% confidence interval: 12.8-30.5; P < .001) compared with absent FMs. CONCLUSIONS: Favorable early motor repertoire of infants born <30 weeks is strongly associated with improved cognitive and motor performance at 8 years.

INTRODUCTION: Docosahexaenoic acid (DHA) is an omega-3 (n-3) fatty acid that accumulates into neural tissue during the last trimester of pregnancy, as the fetal brain is undergoing a growth spurt. Infants born <29 weeks' gestation are deprived the normal in utero supply of DHA during this period of rapid brain development. Insufficient dietary DHA postnatally may contribute to the cognitive impairments common among this population. This follow-up of the N-3 fatty acids for improvement in respiratory outcomes (N3RO) randomised controlled trial aims to determine if enteral DHA supplementation in infants born <29 weeks' gestation during the first months of life improves cognitive development at 5 years of age corrected for prematurity. METHODS AND ANALYSIS: N3RO was a randomised controlled trial of enteral DHA supplementation (60 mg/kg/day) or a control emulsion (without DHA) in 1273 infants born <29 weeks' gestation to determine the effect on bronchopulmonary dysplasia (BPD). We showed that DHA supplementation did not reduce the risk of BPD and may have increased the risk.In this follow-up at 5 years' corrected age, a predefined subset (n=655) of children from five Australian sites will be invited to attend a cognitive assessment with a psychologist. Children will be administered the Wechsler Preschool and Primary Scale of Intelligence (fourth edition) and a measure of inhibitory control (fruit stroop), while height, weight and head circumference will be measured.The primary outcome is full-scale IQ. To ensure 90% power, a minimum of 592 children are needed to detect a four-point difference in IQ between the groups.Research personnel and families remain blinded to group assignment. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/17/WCHN/187). Caregivers will give informed consent prior to taking part in this follow-up study. Findings of this study will be disseminated through peer

BACKGROUND: Magnesium sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal magnesium sulphate is used currently and its association with cerebral palsy in children born <28 weeks' gestation. MATERIALS AND METHODS: Participants comprised all survivors born <28 weeks' gestational age in the state of Victoria in 2016-17, and earlier, in 1991-92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016-17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016-17, the proportions of children exposed to antenatal magnesium sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to magnesium sulphate. RESULTS: Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016-17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25-0.94; P = 0.032). Data were available for 213/215 (99%) survivors born in 2016-17, of whom 147 (69%) received magnesium sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to magnesium sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08-0.96; P = 0.043). CONCLUSIONS: Antenatal magnesium sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors.

BACKGROUND: Management of livebirths at 22-24 weeks' gestation in high-income countries varies widely and has changed over time. AIMS: Our aim was to determine how rates of active management and infant survival of livebirths at 22-24 weeks varied with perinatal variables known at birth, and over time in Victoria, Australia. MATERIALS AND METHODS: We conducted a population-based cohort study of all 22-24 weeks' gestation live births, free of lethal congenital anomalies in 2009-2017. Rates of active management and survival to one year of age were reported. 'Active management' was defined as receiving resuscitation at birth or nursery admission for intensive care. RESULTS: Over the nine-year period, there were 796 eligible live births. Overall, 438 (55%) were actively managed: 5% at 22 weeks, 45% at 23 weeks and 90% at 24 weeks' gestation, but rates of active management did not vary substantially over time. Of livebirths actively managed, 263 (60%) survived to one year: 0% at 22 weeks, 50% at 23 weeks and 66% at 24 weeks. Apart from gestational age, being born in a tertiary perinatal centre and increased size at birth were associated with survival in those actively managed, but sex and plurality were not. Survival rates of actively managed infants rose over time (adjusted odds ratio 1.09 per year; 95% CI 1.01-1.18; P = 0.03). CONCLUSIONS: Although active management rates did not change substantially over time in Victoria, an overall increase in infant survival was observed. With increasing gestational age, rates of active management and infant survival rapidly rose.

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.

AIM: To assess the causal effect of being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g), compared with being born at term, on neurodevelopment and social-emotional development at 2 years' corrected age. METHODS: Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term-born controls. Children were assessed at 2 years' corrected age with the Bayley Scales of Infant and Toddler Development-3rd edition and the Infant-Toddler Social and Emotional Assessment. Delay was defined as <-1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. RESULTS: A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social-emotional competence (4.1 [1.6, 10.2]). CONCLUSION: Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social-emotional competence at 2 years' corrected age. Close developmental surveillance, including social-emotional development, is recommended.

Over the last decade, the use of proteomics in the setting of prematurity has increased and has enabled researchers to successfully identify biomarkers for an array of associated morbidities. The objective of this scoping review was to identify the existing literature, as well as any knowledge gaps related to proteomic biomarker discoveries in the setting of prematurity. A scoping review was conducted using PubMed, Embase and Medline databases following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The study selection process yielded a total of 700 records, of which 13 studies were included in this review. Most studies used a tandem Mass Spectrometry (MS/MS) proteomics approach to identify key biomarkers. The corresponding studies identified proteins associated with retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), late onset sepsis (LOS) and gestational age. This scoping review demonstrates the limited use of proteomics to identify biomarkers associated with severe complications of prematurity. Further research is warranted to identify biomarkers of other important morbidities associated with prematurity, such as intraventricular haemorrhage (IVH) and cerebral palsy, and to investigate the mechanisms associated with these outcomes.

BACKGROUND: Decision-making for infants born at 23-25 weeks involves counselling parents about survival and major disability risks. Accurate information is needed for parents to make informed decisions about their baby's care. AIMS: To determine if perinatal clinicians had accurate perceptions of outcomes of infants born at 23-25 weeks' gestation, and if accuracy had changed over a decade. MATERIALS AND METHODS: A web-based survey was sent to midwives, nurses, neonatologists, and obstetricians working in tertiary and non-tertiary hospitals, and the neonatal retrieval service in the state of Victoria in 2020. A similar survey had been completed in 2010. Clinicians' estimates of survival and major neurodevelopmental disability rates were compared with true rates for actively managed infants overall, and by infant birthplace and gestational age, and professional workplace and discipline. Accuracy of outcomes was compared between eras. RESULTS: Overall, 165 surveys were received. Participants underestimated survival (absolute mean difference [%] -14.4%; [95% confidence interval (CI) -16.6 to -12.3]; P < 0.001) and overestimated major disability (absolute mean difference 32.7%; [95% CI 29.7 to 35.8]; P < 0.001) rates overall, and at each week of gestation, and were worse for outborn compared with inborn infants. Perceptions of clinicians in tertiary centres were similar to those of non-tertiary clinicians. Nurses/midwives were more pessimistic, and paediatricians were more optimistic. Clinicians' perceptions of outcome were less accurate in 2020 than in 2010. CONCLUSIONS: Most perinatal clinicians underestimate survival and overestimate major disability of infants born at 23-25 weeks' gestation, which may translate into overly pessimistic counselling of parents.

INTRODUCTION: Children born moderate to late preterm (MLP, 32-36 weeks' gestation) account for approximately 85% of all preterm births globally. Compared with children born at term, children born MLP are at increased risk of poor neurodevelopmental outcomes. Despite making up the largest group of preterm children, developmental outcomes of children born MLP are less well studied than in other preterm groups. This study aimed to (1) compare neurodevelopmental, respiratory health and brain magnetic resonance imaging (MRI) outcomes between children born MLP and term at 9 years of age; (2) examine the differences in brain growth trajectory from infancy to 9 years between children born MLP and term; and in children born MLP; (3) examine the relationship between brain development and neurodevelopment at 9 years; and (4) identify risk factors for poorer outcomes at 9 years. METHODS AND ANALYSIS: The "LaPrem" (Late Preterm MRI Study) study is a longitudinal cohort study of children born MLP and term controls, born at the Royal Women's Hospital in Melbourne, Australia, between 2010 and 2013. Participants were recruited in the neonatal period and were previously followed up at 2 and 5 years. This 9-year school-age follow-up includes neuropsychology, motor and physical activities, and lung function assessments, as well as brain MRI. Outcomes at 9 years will be compared between birth groups using linear and logistic regressions. Trajectories of brain development will be compared between birth groups using mixed effects models. The relationships between MRI and neurodevelopmental outcomes, as well as other early predictors of poor 9-year outcomes, will be explored using linear and logistic regression. ETHICS AND DISSEMINATION: This study was approved by the human research ethics committee at the Royal Children's Hospital, Melbourne, Australia. Study outcomes will be disseminated through peer-reviewed publications, conference presentations and social media.

INTRODUCTION: During the last trimester of pregnancy, the fetal brain undergoes a rapid growth spurt and accumulates essential nutrients including docosahexaenoic acid (DHA). This takes place ex-utero for infants born <29 weeks' gestation, without the in-utero provisions of DHA. Infants born <29 weeks' are more likely to experience behavioural and emotional difficulties than their term-born counterparts. It has been hypothesised that supplementing preterm infants with dietary DHA may alleviate insufficiency and subsequently prevent or minimise behavioural problems. This protocol describes a follow-up of infants born <29 weeks gestation who were enrolled in a randomised controlled trial (RCT) of DHA supplementation. We aim to determine whether DHA supplementation improves the behaviour, and general health of these infants. METHODS AND ANALYSIS: Infants born <29 weeks' gestation were enrolled in a multicentre blinded RCT of enteral DHA supplementation. Infants were randomised to receive an enteral emulsion that provided 60 mg/kg/day of DHA or a control emulsion commenced within the first 3 days of enteral feeding, until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Families of surviving children (excluding those who withdrew from the study) from the Australian sites (up to 955) will be invited to complete a survey. The survey will include questions regarding child behavioural and emotional functioning, executive functioning, respiratory health and general health. We hypothesise that the DHA intervention will have a benefit on the primary outcome, parent-rated behaviour and emotional status as measured using the Total Difficulties score of the Strengths and Difficulties Questionnaire. Detecting a 2-point difference between groups (small effect size of 0.25 SD) with 90% power will require follow-up of 676 participants. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the st

Children born very preterm (VPT; <32 weeks' gestation) have alterations in brain white matter and poorer math ability than full-term (FT) peers. Diffusion-weighted magnetic resonance imaging studies suggest a link between white matter microstructure and math in VPT and FT children, although longitudinal studies using advanced modelling are lacking. In a prospective longitudinal cohort of VPT and FT children we used Fixel-Based Analysis to investigate associations between maturation of white matter fibre density (FD), fibre-bundle cross-section (FC), and combined fibre density and cross-section (FDC) and math computation ability at 7 (n = 136 VPT; n = 32 FT) and 13 (n = 130 VPT; n = 44 FT) years, as well as between change in white matter and math computation ability from 7 to 13 years (n = 103 VPT; n = 21 FT). In both VPT and FT children, higher FD, FC and FDC in visual, sensorimotor and cortico-thalamic/thalamo-cortical white matter tracts were associated with better math computation ability at 7 and 13 years. Longitudinally, accelerated maturation of the posterior body of the corpus callosum (FDC) was associated with greater math computation development. White matter-math associations were similar for VPT and FT children. In conclusion, white matter maturation is associated with math computation ability across late childhood, irrespective of birth group.

BACKGROUND: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants. METHODS: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight <1500 g and/or gestational age <32 weeks), 2) normal birth weight/term-born control group (birth weight >2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555). FINDINGS: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups. INTERPRETATION: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders

OBJECTIVE: To identify attention profiles at 7 and 13 years, and transitions in attention profiles over time in children born very preterm (VP; <30 weeks' gestation) and full term (FT), and examine predictors of attention profiles and transitions. METHODS: Participants were 167 VP and 60 FT children, evaluated on profiles across five attention domains (selective, shifting and divided attention, processing speed, and behavioral attention) at 7 and 13 years using latent profile analyses. Transitions in profiles were assessed with contingency tables. For VP children, biological and social risk factors were tested as predictors with a multinomial logistic regression. RESULTS: At 7 and 13 years, three distinct profiles of attentional functioning were identified. VP children were 2-3 times more likely to show poorer attention profiles compared with FT children. Transition patterns between 7 and 13 years were stable average, stable low, improving, and declining attention. VP children were two times less likely to have a stable average attention pattern and three times more likely to have stable low or improving attention patterns compared with FT children. Groups did not differ in declining attention patterns. For VP children, brain abnormalities on neonatal MRI and greater social risk at 7 years predicted stable low or changing attention patterns over time. CONCLUSIONS: VP children show greater variability in attention profiles and transition patterns than FT children, with almost half of the VP children showing adverse attention patterns over time. Early brain pathology and social environment are markers for attentional functioning.

In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital. The time babies and parents spend together in the early developmental period, during the hospitalisation and when the baby is discharged home, is crucial for optimal child development and bonding. Yet care givers who have a baby admitted to neonatal intensive or special care for extended periods are not currently entitled to any extra parental leave payments in Australia. We recommend the Australian Paid Parental Leave Act is changed to allow primary carers access to 1 week of extra parental leave pay for every week in hospital (for babies admitted to hospital for more than 2 weeks), up to a maximum of 14 weeks. For fathers and partners of these babies, we recommend an additional 2 weeks of extra Dad and Partner Pay. The net cost, taking into account likely productivity benefits, would be less than 1.5% of the current cost of the scheme and would improve health and socio-economic outcomes for the baby, family and society.

Abstract Objective Mothers of infants born very preterm (VPT) are at high risk of mental health difficulties. However, less is known about the course of fathers’ depressive and anxiety symptoms over time, and the implications this may have for early parenting behaviors. Methods In total, 100 fathers of 125 infants born VPT (<30 weeks’ gestation) completed questionnaires assessing depressive and anxiety symptoms shortly after their infant’s birth, and when their infant reached term-equivalent age, 3 months, 6 months, and 12 months’ corrected age. At 12 months’ corrected age, fathers’ parenting behaviors were assessed using the Emotional Availability Scales. Longitudinal latent class analysis was used to identify trajectories of fathers’ depressive and anxiety symptoms, and linear regression equations examined relationships between these trajectories and fathers’ parenting behaviors. Results For both depressive and anxiety symptoms, two distinct trajectories were identified. For depression, most fathers were assigned to the persistently low symptom trajectory (82%), while the remainder were assigned to the persistently high symptom trajectory (18%). For anxiety, 49% of fathers were assigned to the persistently low symptom trajectory, while 51% were assigned to the trajectory characterized by moderate symptoms over the first postnatal year. There were no significant differences in parenting behaviors between fathers assigned to the different depressive and anxiety symptom trajectories. Conclusions Fathers of infants born VPT are at risk of chronic depressive and anxiety symptoms over the first postnatal year, highlighting the need for screening and ongoing support.

BACKGROUND/OBJECTIVES: The Vulval disease Quality of Life Index (VQLI) is a new tool that assesses the burden of vulval disease on quality of life (QoL). Our objective was to assess the correlation between VQLI score and clinician-rated severity scores, overall patient itch/discomfort, disease duration, sexual activity, and age, in vulval lichen sclerosus (VLS) at a vulval disorders clinic. METHODS: A retrospective case note review, including consecutive women with VLS who attended the clinic between April and October 2018. Outcome measures include the VQLI score, clinician-rated severity score, and patient symptom score. RESULTS: A total of 109 women with VLS were included. On multivariable analysis, there was evidence of a positive relationship between VQLI scores and the total clinician-rated score (mean increase in VQLI score per unit increase in clinician score 1.34, 95% confidence interval [CI] 0.31, 2.38; P = 0.01); the relationship was stronger for the cutaneous component. There was little evidence for relationships of the VQLI with the patient's age, sexual activity or time since onset of symptoms. There was strong evidence for a positive relationship between VQLI score and overall itch/discomfort score (mean increase 2.38, 95% CI 1.88, 2.88; P < 0.001). New and follow-up data were obtained on sequential visits for 12 women, among whom the VQLI score dropped a mean -2.75 points between visits (95% CI -6.05, 0.55; P = 0.094). CONCLUSION: The clinician-rated severity correlates with the impact of VLS on QoL. The VQLI captures information included in a patient itch/discomfort score, which can be easily incorporated into routine assessment.

Serial regional brain growth from the newborn period to adolescence has not been described. Here, we measured regional brain growth in 216 very preterm (VP) and 45 full-term (FT) children. Brain MRI was performed at term-equivalent age, 7 and 13 years in 82 regions. Brain volumes increased between term-equivalent and 7 years, with faster growth in the FT than VP group. Perinatal brain abnormality was associated with less increase in brain volume between term-equivalent and 7 years in the VP group. Between 7 and 13 years, volumes were relatively stable, with some subcortical and cortical regions increasing while others reduced. Notably, VP infants continued to lag, with overall brain size generally less than that of FT peers at 13 years. Parieto-frontal growth, mainly between 7 and 13 years in FT children, was associated with higher intelligence at 13 years. This study improves understanding of typical and atypical regional brain growth.

BACKGROUND: Very preterm (VP) children are at risk of memory and emotional impairments; however, the neural correlates remain incompletely defined. This study investigated the effect of VP birth on white matter tracts traditionally related to episodic memory and emotion. METHODS: The cingulum, fornix, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation were reconstructed using tractography in 144 VP children and 33 full-term controls at age 7 years. RESULTS: Compared with controls, VP children had higher axial, radial, and mean diffusivities and neurite orientation dispersion, and lower volume and neurite density in the fornix, along with higher neurite orientation dispersion in the medial forebrain bundle. Support vector classification models based on tract measures significantly classified VP children and controls. Higher fractional anisotropy and lower diffusivities in the cingulum, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation were associated with better episodic memory, independent of key perinatal risk factors. Support vector regression models using tract measures did not predict episodic memory and emotional outcomes. CONCLUSIONS: Altered tract structure is related to adverse episodic memory outcomes in VP children, but further research is required to determine the ability of tract structure to predict outcomes of individual children. IMPACT: We studied white matter fibre tracts thought to be involved in episodic memory and emotion in VP and full-term children using diffusion magnetic resonance imaging and machine learning. VP children have altered fornix and medial forebrain bundle structure compared with full-term children. Altered tract structure can be detected using machine learning, which accurately classified VP and full-term children using tract data. Altered cingulum, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation structure was associated with poorer episodic memory

BACKGROUND: There is increasing evidence that parental determinants of offspring early life development begin well before pregnancy. OBJECTIVES: We established the Victorian Intergenerational Health Cohort Study (VIHCS) to examine the contributions of parental mental health, substance use, and socio-economic characteristics before pregnancy to child emotional, physical, social, and cognitive development. POPULATION: Men and women were recruited from the Victorian Adolescent Health Cohort (VAHCS), an existing cohort study beginning in 1992 that assessed a representative sample of 1943 secondary school students in Victoria, Australia, repeatedly from adolescence (wave 1, mean age 14 years) to adulthood (wave 10, mean age 35 years). METHODS: Victorian Adolescent Health Cohort participants with children born between 2006 and 2013 were recruited to VIHCS and invited to participate during trimester three, at 2 months postpartum, and 1 year postpartum. Parental mental health, substance use and socio-economic characteristics were assessed repeatedly throughout; infant characteristics were assessed postnatally and in infancy. Data will be supplemented by linkage to routine datasets. A further follow-up is underway as children reach 8 years of age. PRELIMINARY RESULTS: Of the 1307 infants born to VAHCS participants between 2006 and 2013, 1030 were recruited to VIHCS. At VIHCS study entry, 18% of recruited parents had preconception common mental disorder in adolescence and young adulthood, 18% smoked daily in adolescence and young adulthood, and 6% had not completed high school. Half of VIHCS infants were female (48%), 4% were from multiple births, and 7% were preterm (<37 weeks' gestation). CONCLUSIONS: Victorian Intergenerational Health Cohort Study is a prospective cohort of 1030 children with up to nine waves of preconception parental data and three waves of perinatal parental and infant data. These will allow examination of continuities of parental health and health risks

BACKGROUND: Preterm birth (PTB) and small for gestational age (SGA) are increasingly prevalent, with major consequences for health and development into later life. There is emerging evidence that some risk processes begin before pregnancy. We report on associations between maternal and paternal common mental disorders (CMD) before and during pregnancy and offspring PTB and SGA. METHODS: 398 women with 609 infants and 267 men with 421 infants were assessed repeatedly for CMD symptoms before pregnancy between age 14 and 29 and during pregnancy. Associations between preconception and antenatal CMD symptoms and offspring gestational age/PTB and size for gestational age/SGA were estimated using linear and Poisson regression. FINDINGS: In men, persistent preconception CMD across adolescence and young adulthood predicted offspring PTB after adjustment for ethnicity, education, BMI and adolescent substance use (adjusted RR 7·0, 95% CI 1·8,26·8), corresponding to a population attributable fraction of 31% of preterm births. In women, antenatal CMD symptoms predicted offspring PTB (adjusted RR 4·4, 95% CI 1·4,14·1). There was little evidence of associations with SGA. INTERPRETATION: This first report of an association between paternal preconception mental health and offspring gestational age, while requiring replication in larger samples, complements earlier work on stress in animals, and further strengthens the case for expanding preconception mental health care to both men and women. FUNDING: National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Australian Rotary Health, Colonial Foundation, Perpetual Trustees, Financial Markets Foundation for Children (Australia), Royal Children's Hospital Foundation, Murdoch Children's Research Institute, Australian Research Council.

Brain atlases providing standardised identification of neonatal brain regions are key in investigating neurological disorders of early childhood. Our previously developed Melbourne Children's Regional Infant Brain (M-CRIB) and M-CRIB 2.0 neonatal brain atlases provide standardised parcellation of 100 brain regions including cortical, subcortical, and cerebellar regions. The aim of this study was to extend M-CRIB atlas coverage to include 54 white matter (WM) regions. Participants were 10 healthy term-born neonates that were used to create the initial M-CRIB atlas. WM regions were manually segmented based on T2 images and co-registered diffusion tensor imaging-based, direction-encoded colour maps. Our labelled regions imitate the Johns Hopkins University neonatal atlas, with minor anatomical modifications. All segmentations were reviewed and approved by a paediatric radiologist and a neurosurgery research fellow for anatomical accuracy. The resulting neonatal WM atlas comprises 54 WM regions: 24 paired regions, and six unpaired regions comprising five corpus callosum subdivisions, and one pontine crossing tract. Detailed protocols for manual WM parcellations are provided, and the M-CRIB-WM atlas is presented together with the existing M-CRIB cortical, subcortical, and cerebellar parcellations in 10 individual neonatal MRI data sets. The novel M-CRIB-WM atlas, along with the M-CRIB cortical and subcortical atlases, provide neonatal whole brain MRI coverage in the first multi-subject manually parcellated neonatal atlas compatible with atlases commonly used at older time points. The M-CRIB-WM atlas is publicly available, providing a valuable tool that will help facilitate neuroimaging research into neonatal brain development in both healthy and diseased states.

Longitudinal studies measuring changes in cortical morphology over time are best facilitated by parcellation schemes compatible across all life stages. The Melbourne Children's Regional Infant Brain (M-CRIB) and M-CRIB 2.0 atlases provide voxel-based parcellations of the cerebral cortex compatible with the Desikan-Killiany (DK) and the Desikan-Killiany-Tourville (DKT) cortical labelling schemes. This study introduces surface-based versions of the M-CRIB and M-CRIB 2.0 atlases, termed M-CRIB-S(DK) and M-CRIB-S(DKT), with a pipeline for automated parcellation utilizing FreeSurfer and developing Human Connectome Project (dHCP) tools. Using T2-weighted magnetic resonance images of healthy neonates (n = 58), we created average spherical templates of cortical curvature and sulcal depth. Manually labelled regions in a subset (n = 10) were encoded into the spherical template space to construct M-CRIB-S(DK) and M-CRIB-S(DKT) atlases. Labelling accuracy was assessed using Dice overlap and boundary discrepancy measures with leave-one-out cross-validation. Cross-validated labelling accuracy was high for both atlases (average regional Dice = 0.79-0.83). Worst-case boundary discrepancy instances ranged from 9.96-10.22 mm, which appeared to be driven by variability in anatomy for some cases. The M-CRIB-S atlas data and automatic pipeline allow extraction of neonatal cortical surfaces labelled according to the DK or DKT parcellation schemes.

OBJECTIVES: It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN: Prospective longitudinal cohort study. SETTING: The State of Victoria, Australia. PARTICIPANTS: All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES: Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS: Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS: Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.

Aim To link data from a large maternal perinatal trial with the Australian Cerebral Palsy Register (ACPR) to identify children with cerebral palsy (CP). Method Deidentified data from the Australasian Collaborative Trial of Magnesium Sulphate (ACTOMgSO4) and the ACPR were linked. Children born from 1996 to 2000 at Australian hospitals who survived and had 2‐year paediatric assessments were included. Children identified with CP in: (1) both the ACTOMgSO4 (2y) and the ACPR (5y), (2) the ACTOMgSO4 only, and (3) the ACPR only were compared. Results We included 913 children (492 males, 421 females; mean gestational age at birth 27.8wks [standard deviation 2.1wks]; range 23.0–40.0wks). Eighty‐four children received a CP diagnosis: 35 by the ACTOMgSO4 and the ACPR, 29 by the ACTOMgSO4 only, and 20 by the ACPR only. The ACTOMgSO4 diagnosed 76.2% (95% confidence interval [CI] 65.9–84.1) and the ACPR identified 65.5% (95% CI 54.7–74.9). Children born in states/territories with long‐standing versus more recently established registers were more likely to be included on the ACPR (p<0.05). Interpretation Linking deidentified perinatal trial data with the ACPR was achieved. Limitations of both strategies for identifying children with CP in this era (late 1990s and early 2000s) probably explain many of the differences observed, and inform future linkage studies and evaluations of CP‐preventive interventions. What this paper adds Randomized trial data were linked with the Australian Cerebral Palsy Register. Trial (2y) and register (up to 5y) diagnoses of cerebral palsy (CP) differed. States with long‐standing registers were more likely to include children with CP.

BACKGROUND: Of all newborns, 1%-2% are born very preterm (VP; <32 weeks) or with very low birthweight (VLBW; ≤1500 g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow-up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; www.apic-preterm.org). Joint analyses require data harmonisation, highlighting the importance of consistent assessment methodologies. OBJECTIVE: To present an expert recommendation on Common Core Assessments to be used in follow-up assessments of adults born preterm. METHODS: Principles of Common Core Assessments were discussed at APIC meetings. Experts for each specific outcome domain wrote the first draft on assessments pertaining to that outcome. These drafts were combined and reviewed by all authors. Consensus was reached by discussion at APIC meetings. RESULTS: We present a recommendation by APIC experts on consistent measures to be used in adult follow-up assessments. CONCLUSIONS: The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing