Parent screening questionnaires to detect cognitive and language delay at 2 years in high-risk infants: an analysis from the Victorian Infant Collaborative Study 2016-2017 cohort.

OBJECTIVE: To determine the accuracy of two developmental screening questionnaires to detect cognitive or language delay, defined using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), in children born extremely preterm (EP: <28 weeks' gestation) or extremely low birth weight (ELBW: <1000 g). DESIGN: Prospective cohort study. SETTING: State of Victoria, Australia. PATIENTS: 211 infants born EP/ELBW assessed at 2 years' corrected age (mean 2.2, SD 0.2). MAIN OUTCOME MEASURES: Cognitive and language delay (<-1 SD) on the Bayley-III. The screening questionnaires were the Parent Report of Children's Abilities-Revised (PARCA-R) and the Ages & Stages Questionnaires Third Edition (ASQ-3). RESULTS: The PARCA-R performed better than the ASQ-3, but neither questionnaire had substantial agreement with the Bayley-III to detect cognitive delay; kappa (95% CI): PARCA-R 0.43 (0.23, 0.63); ASQ-3 0.15 (-0.05, 0.35); sensitivity (95% CI): PARCA-R 70% (53%, 84%) ASQ-3 62% (47%, 76%); specificity (95% CI): PARCA-R 73% (60%, 84%) ASQ-3 53% (38%, 68%). When both tools were used in combination (below cut-off on at least one assessment), sensitivity increased to 78% (60%, 91%) but specificity fell to 45% (29%, 62%). Similar trends were noted for language delay on the Bayley-III, although kappa values were better than for cognitive delay. CONCLUSIONS: Neither screening questionnaire identified cognitive delay well, but both were better at identifying language delay. The PARCA-R detects delay on the Bayley-III more accurately than the ASQ-3. Sensitivity for detecting delay is greatest when the PARCA-R and ASQ-3 were used in combination, but resulted in lower specificity.

Relationships of Severity of Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes and Poor Respiratory Function at 7-8 Years of Age.

OBJECTIVE: To clarify the relationships of 3 definitions of severity of bronchopulmonary dysplasia (BPD) with adverse neurodevelopmental and respiratory outcomes at early school-age. STUDY DESIGN: Participants comprised 218 consecutive survivors to 7-8 years of age born either <28 weeks' gestation or weighing <1000 g in Victoria, Australia, in 2005. BPD was classified as none, grade 1 (mild), grade 2 (moderate), or grade 3 (severe), using 2 commonly accepted definitions: 1) Jobe2001, and 2) Higgins2018, and our own 3) Victorian Infant Collaborative Study (VICS) 2005, adapted from Jensen2019. Outcomes included major neurodevelopmental disability, low IQ and academic achievement, poor motor function, and poor respiratory function as assessed by spirometry. Outcomes for children with each grade of BPD were compared with children with no BPD. RESULTS: Of the 218 survivors, 132 (61%) had BPD on Jobe2001 criteria, and 113 (52%) had BPD on both Higgins2018 and VICS2005 criteria. Grade 1 on any criteria was not associated with any adverse neurodevelopmental outcomes. Grade 1 on both Higgins2018 and VICS2005 was associated with reduced spirometry, grade 2 on both Higgins2018 and VICS2005, and grade 3 on all criteria were associated with increased risk for both adverse neurodevelopmental and respiratory outcomes. CONCLUSIONS: Compared with no BPD, receiving additional oxygen up to 29% but no positive pressure support at 36 weeks' postmenstrual age increased the risk of abnormal respiratory function but not adverse neurodevelopment. Receiving ≥30% oxygen or any positive pressure support at 36 weeks increased the risk of both adverse outcomes.

Neurosensory, cognitive and academic outcomes at 8 years in children born 22-23 weeks' gestation compared with more mature births.

Despite providing intensive care to more infants born <24 weeks' gestation, data on school-age outcomes, critical for counselling and decision-making, are sparse. OBJECTIVE: To compare major neurosensory, cognitive and academic impairment among school-aged children born extremely preterm at 22-23 weeks' gestation (EP22-23) with those born 24-25 weeks (EP24-25), 26-27 weeks (EP26-27) and term (≥37 weeks). DESIGN: Three prospective longitudinal cohorts. SETTING: Victoria, Australia. PARTICIPANTS: All EP live births (22-27 weeks) and term-born controls born in 1991-1992, 1997 and 2005. MAIN OUTCOME MEASURES: At 8 years, major neurosensory disability (any of moderate/severe cerebral palsy, IQ <-2 SD relative to controls, blindness or deafness), motor, cognitive and academic impairment, executive dysfunction and poor health utility. Risk ratios (RRs) and risk differences between EP22-23 (reference) and other gestational age groups were estimated using generalised linear models, adjusted for era of birth, social risk and multiple birth. RESULTS: The risk of major neurosensory disability was higher for EP22-23 (n=21) than more mature groups (168 EP24-25; 312 EP26-27; 576 term), with increasing magnitude of difference as the gestation increased (adjusted RR (95% CI) compared with EP24-25: 1.39 (0.70 to 2.76), p=0.35; EP26-27: 1.85 (0.95 to 3.61), p=0.07; term: 13.9 (5.75 to 33.7), p<0.001). Similar trends were seen with other outcomes. Two-thirds of EP22-23 survivors were free of major neurosensory disability. CONCLUSIONS: Although children born EP22-23 experienced higher rates of disability and impairment at 8 years than children born more maturely, many were free of major neurosensory disability. These data support providing active care to infants born EP22-23.

Associations between physical activity and development in preschool-aged children born <30 weeks' gestation: a cohort study.

OBJECTIVE: To investigate the effect of physical activity (PA) on development (motor, cognitive, social-emotional) in children 4-5 years old born <30 weeks' gestation, and to describe subgroups of children at risk of low PA in this cohort. DESIGN: Longitudinal cohort study. PATIENTS: 123 children born <30 weeks were recruited at birth and assessed between 4 and 5 years' corrected age. MAIN OUTCOME MEASURES: Development was assessed using the Movement Assessment Battery for Children, Second Edition (MABC-2), Little Developmental Coordination Disorder Questionnaire (L-DCDQ), Wechsler Preschool and Primary Scale of Intelligence (Fourth Edition; WPPSI-IV), and Strengths and Difficulties Questionnaire (SDQ). To measure PA, children wore an accelerometer and parents completed a diary for 7 days. Effects of PA on developmental outcomes, and associations between perinatal risk factors and PA, were estimated using linear regression. RESULTS: More accelerometer-measured PA was associated with better MABC-2 aiming and catching scores (average standard score increase per hour increase in PA: 0.54, 95% CI 0.11, 0.96; p=0.013), and lower WPPSI-IV processing speed index scores (average composite score decrease per hour increase in PA: -2.36, 95% CI -4.19 to -0.53; p=0.012). Higher accelerometer-measured PA was associated with better SDQ prosocial scores. Major brain injury in the neonatal period was associated with less moderate-vigorous and less unstructured PA at 4-5 years. CONCLUSIONS: Higher levels of PA are associated with aspects of motor, cognitive and social-emotional skill development in children 4-5 years old born <30 weeks. Those with major brain injury in the neonatal period may be more vulnerable to low PA at preschool age.

A comparison of strategies for selecting auxiliary variables for multiple imputation.

Multiple imputation (MI) is a popular method for handling missing data. Auxiliary variables can be added to the imputation model(s) to improve MI estimates. However, the choice of which auxiliary variables to include is not always straightforward. Several data-driven auxiliary variable selection strategies have been proposed, but there has been limited evaluation of their performance. Using a simulation study we evaluated the performance of eight auxiliary variable selection strategies: (1, 2) two versions of selection based on correlations in the observed data; (3) selection using hypothesis tests of the "missing completely at random" assumption; (4) replacing auxiliary variables with their principal components; (5, 6) forward and forward stepwise selection; (7) forward selection based on the estimated fraction of missing information; and (8) selection via the least absolute shrinkage and selection operator (LASSO). A complete case analysis and an MI analysis using all auxiliary variables (the "full model") were included for comparison. We also applied all strategies to a motivating case study. The full model outperformed all auxiliary variable selection strategies in the simulation study, with the LASSO strategy the best performing auxiliary variable selection strategy overall. All MI analysis strategies that we were able to apply to the case study led to similar estimates, although computational time was substantially reduced when variable selection was employed. This study provides further support for adopting an inclusive auxiliary variable strategy where possible. Auxiliary variable selection using the LASSO may be a promising alternative when the full model fails or is too burdensome.

Transition to Adulthood for Extremely Preterm Survivors.

OBJECTIVE: To compare transition into adulthood of survivors born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g) in the postsurfactant era with term-born controls. METHODS: Prospective longitudinal cohort study of all EP/ELBW survivors born in the State of Victoria, Australia between January 1, 1991 and December 31, 1992 and matched term-born controls. Outcomes include educational attainment, employment, financial status, romantic partnering, living arrangements, parenthood, physical health and mental health, risk-taking behaviors, life satisfaction, and interpersonal relationships at 25 years. RESULTS: Data were available from 165 EP/ELBW and 127 control participants. Overall, there was little evidence for differences between the EP/ELBW and control groups on most comparisons after adjustment for social risk and multiple births. However, compared with controls, the EP/ELBW group was more likely to have their main source of income from government (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.21-5.13; P = .01) and to have never moved out of the parental home (aOR 2.13, 95% CI 1.27-3.58; P = .01), and fewer had ever engaged in smoking (aOR 0.52, 95% CI 0.28-0.98; P = .04), binge drinking (aOR 0.41, 95% CI 0.18-0.93; P = .03), or street drugs (aOR 0.56, 95% CI 0.32-0.98; P = .04). CONCLUSIONS: Aside from clinically important differences in main income source, leaving the parental home, and reduced risk-taking behavior, survivors born EP/ELBW in the era since surfactant was introduced are transitioning into adulthood similarly to term-born controls in some areas assessed but not all.

Growth from infancy to adulthood and associations with cardiometabolic health in individuals born extremely preterm.

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 health may provide a window for intervention. Funding: National Health and Medical Research Council of Australia.

Diagnostic accuracy of small-for-gestational-age status for infant mortality and school-age outcomes of live births <28 weeks' gestation: a cohort study.

OBJECTIVES: To determine the diagnostic accuracy of small-for-gestational-age (SGA; <10th centile) status for infant mortality and adverse school-age outcomes in infants born extremely preterm (EP; <28 weeks' gestation). DESIGN: Geographical cohort studies. SETTING: The state of Victoria, Australia. PATIENTS: For mortality, live births 22-27 weeks' gestation from 2009 to 2017 offered active care after birth. For school-age outcomes, survivors to 8 years' corrected age born in 1991-1992, 1997 or 2005. EXPOSURES: SGA <10th centile on four commonly used growth references: three derived from neonatal data (Fenton, UK-WHO and Intergrowth Newborn Size) and one from fetal data (Intergrowth Estimated Fetal Weight). MAIN OUTCOME MEASURES: (a) Infant mortality; (b) major neurodevelopmental disability, and poor performance on tests of IQ, academic achievement, motor function, and executive function. RESULTS: Infant mortality data were available for 2040 infants, and neurodevelopmental data for 499 children. Diagnostic accuracy of SGA status was low overall and varied with the growth reference. Positive predictive values for infant mortality ranged from 18% to 21%, only marginally higher than its 18% prevalence. Compared with a prevalence of 17%, positive predictive values for major neurodevelopmental disability ranged from 30% to 38% for the neonatal growth references but was only 20% for Intergrowth Estimated Fetal Weight. SGA status was also associated with lower IQ, poor academic achievement and poor motor performance. CONCLUSIONS: Among infants born EP, the diagnostic accuracy of SGA status was low for both infant mortality and adverse neurodevelopmental outcomes at school age, but importantly varied with the growth reference used to identify SGA status.

Health-related quality of life in adults born extremely preterm or with extremely low birth weight in the postsurfactant era: a longitudinal cohort study.

OBJECTIVES: To compare health-related quality of life (HRQoL) at 25 and 18 years in individuals born extremely preterm (EP, <28 weeks' gestation) or with extremely low birth weight (ELBW, birth weight <1000 g) with term-born (≥37 weeks) controls. Within the EP/ELBW cohort, to determine whether HRQoL differed between those with lower and higher IQs. METHODS: HRQoL was self-reported using the Health Utilities Index Mark 3 (HUI3) at 18 and 25 years by 297 EP/ELBW and 251 controls born in 1991-1992 in Victoria, Australia. Median differences (MDs) between groups were estimated using multiple imputation to handle missing data. RESULTS: Adults born EP/ELBW had lower HRQoL (median utility 0.89) at 25 years than controls (median utility 0.93, MD -0.040), but with substantial uncertainty in the estimate (95% CI -0.088 to 0.008) and a smaller reduction at 18 years (MD -0.016, 95% CI -0.061 to 0.029). On individual HUI3 items, there was suboptimal performance on speech (OR 9.28, 95% CI 3.09 to 27.93) and dexterity (OR 5.44, 95% CI 1.04 to 28.45) in the EP/ELBW cohort. Within the EP/ELBW cohort, individuals with lower IQ had lower HRQoL compared with those with higher IQ at 25 (MD -0.031, 95% CI -0.126 to 0.064) and 18 years (MD -0.034, 95% CI -0.107 to 0.040), but again with substantial uncertainty in the estimates. CONCLUSIONS: Compared with term-born controls, young adults born EP/ELBW reported poorer HRQoL, as did those with lower IQ compared with those with higher IQ in the EP/ELBW cohort. Given the uncertainties, our findings need corroboration.

Handling of missing data with multiple imputation in observational studies that address causal questions: protocol for a scoping review.

INTRODUCTION: Observational studies in health-related research often aim to answer causal questions. Missing data are common in these studies and often occur in multiple variables, such as the exposure, outcome and/or variables used to control for confounding. The standard classification of missing data as missing completely at random, missing at random (MAR) or missing not at random does not allow for a clear assessment of missingness assumptions when missingness arises in more than one variable. This presents challenges for selecting an analytic approach and determining when a sensitivity analysis under plausible alternative missing data assumptions is required. This is particularly pertinent with multiple imputation (MI), which is often justified by assuming data are MAR. The objective of this scoping review is to examine the use of MI in observational studies that address causal questions, with a focus on if and how (a) missingness assumptions are expressed and assessed, (b) missingness assumptions are used to justify the choice of a complete case analysis and/or MI for handling missing data and (c) sensitivity analyses under alternative plausible assumptions about the missingness mechanism are conducted. METHODS AND ANALYSIS: We will review observational studies that aim to answer causal questions and use MI, published between January 2019 and December 2021 in five top general epidemiology journals. Studies will be identified using a full text search for the term 'multiple imputation' and then assessed for eligibility. Information extracted will include details about the study characteristics, missing data, missingness assumptions and MI implementation. Data will be summarised using descriptive statistics. ETHICS AND DISSEMINATION: Ethics approval is not required for this review because data will be collected only from published studies. The results will be disseminated through a peer reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: This protocol is registered on figshare (https://doi.org/10.6084/m9.figshare.20010497.v1).

Long-lasting effects of very preterm birth on brain structure in adulthood: A systematic review and meta-analysis.

Early life experiences, such as very preterm (VP) birth, can affect brain and cognitive development. Several prior studies investigated brain structure in adults born VP; synthesising these studies may help to provide a clearer understanding of long-term effects of VP birth on the brain. We systematically searched Medline and Embase for articles that investigated brain structure using MRI in adulthood in individuals born VP (<32 weeks' gestation) or with very low birth weight (VLBW; <1500 g), and controls born at term or with normal birth weight. In total, 77 studies met the review inclusion criteria, of which 28 studies were eligible for meta-analyses, including data from up to 797 VP/VLBW participants and 518 controls, aged 18-33 years. VP/VLBW adults exhibited volumetric, morphologic and microstructural alterations in subcortical and temporal cortical regions compared with controls, with pooled standardised mean differences up to - 1.0 (95% confidence interval: -1.2, -0.8). This study suggests there is a persisting neurological impact of VP birth, which may provide developmental neurobiological insights for adult cognition in high-risk populations.

Mental health in young adults born extremely preterm or extremely low birthweight with contemporary neonatal intensive care.

BACKGROUND: For infants born in the contemporary era of neonatal care, little is known about adult mental health outcomes of extremely preterm birth (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g). This study aimed to compare attention deficit hyperactivity disorder (ADHD), anxiety, mood, and substance use disorder prevalence in young adults born EP/ELBW and normal birthweight (NBW; >2499 g) controls, and to compare change in prevalence of mental health symptoms and disorders from 18 to 25 years. METHODS: Participants were a prospective geographical cohort of 297 consecutive survivors born EP/ELBW during 1991-1992 and 260 NBW controls. At age 25 years, 174 EP/ELBW and 139 NBW participants completed the Adult ADHD Rating Scale, Structured Clinical Interview for DSM-IV Disorders, Beck Anxiety Inventory, and Center for Epidemiologic Studies Depression Scale-Revised. Data from follow-up at 18 years were also utilized. Multiple imputation was used to account for attrition. RESULTS: Mental health outcomes at 25 years were similar between groups: prevalence rates were ADHD 7% v. 5%; anxiety 32% v. 27%; mood 38% v. 35%; substance use 12% v. 14% in the EP/ELBW and NBW groups, respectively. In both groups, ADHD declined between 18 and 25 years [odds ratio (OR) per year = 0.87, 95% confidence interval (CI) 0.79-0.95], and generalized anxiety disorder and major depressive episode became more common (OR 1.22, 95% CI 1.10-1.35 per year; OR 1.20, 95% CI 1.10-1.30 respectively). CONCLUSIONS: This contemporary EP/ELBW cohort has comparable young adult mental health outcomes to controls, and similar patterns of change in mental health from late adolescence.

Long-term expiratory airflow of infants born moderate-late preterm: A systematic review and meta-analysis.

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 disease compared with term-born peers. Funding: This work is supported by grants from the National Health and Medical Research Council (Centre of Research Excellence #1153176, Project grant #1161304); Medical Research Future Fund (Career Development Fellowship to J.L.Y Cheong #1141354) and from the Victorian Government's Operational Infrastructure Support Programme. C. Du Berry's PhD candidature is supported by the Melbourne Research Scholarship and the Centre of Research Excellence in Newborn Medicine.

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.

Thirteen-Year Outcomes of a Randomized Clinical Trial of Early Preventive Care for Very Preterm Infants and Their Parents.

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, and assessment of quality of life-related outcomes is warranted. TRIAL REGISTRATION: http://www.anzctr.org.au/: ACTRN12605000492651.

Parent-recorded videos of infant spontaneous movement: Comparisons at 3-4 months and relationships with 2-year developmental outcomes in extremely preterm, extremely low birthweight and term-born infants.

BACKGROUND: Infants born extremely preterm (EP, <28-week gestational age) or extremely low birthweight (ELBW, <1000 g) are at risk of developmental delay and cerebral palsy (CP). The General Movements Assessment (GMA) and its extension, the Motor Optimality Score, revised (MOS-R) (assesses movement patterns and posture), may help to identify early delays. OBJECTIVES: To compare differences in the MOS-R scored from parent-recorded videos between infants born EP/ELBW and term-born infants, to determine relationships between the MOS-R and 2-year cognitive, language and motor outcomes and if any relationships differ between birth groups and the association of the GMA (fidgety) with CP. METHODS: A geographical cohort (EP/ELBW and term-control infants) was assessed using the MOS-R inclusive of the GMA at 3- to 4-month corrected age (CA), and the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at 2-year CA. Differences in mean total MOS-R between groups, relationships between MOS-R and 2-year outcomes and relationships between GMA (fidgety) and CP in infants born EP/ELBW were estimated using linear/logistic regression. RESULTS: Three hundred and twelve infants (147 EP/ELBW; 165 term) had complete MOS-R and Bayley-III assessments. Mean MOS-R was lower in infants born EP/ELBW than controls (mean difference -3.2, 95% confidence interval [CI] -4.2, -2.3). MOS-R was positively related to cognitive (ß [regression coefficient] = 0.71, 95% CI 0.27, 1.15), language (ß = 0.96, 95% CI 0.38, 1.54) and motor outcomes (ß = .89, 95% CI 0.45, 1.34). There was little evidence for interaction effects between birth groups for any outcome. Absent/abnormal fidgety movements were related to CP in children born EP/ELBW (risk ratio 5.91, 95% CI 1.48, 23.7). CONCLUSIONS: Infants born EP/ELBW have lower MOS-R than infants born at term. A higher MOS-R is related to better outcomes for 2-year development, with similar relationships in both birth groups. Absent/abnormal fidgety movements are related to CP in EP/ELBW survivors.

A comparison of multiple imputation strategies for handling missing data in multi-item scales: Guidance for longitudinal studies.

Medical research often involves using multi-item scales to assess individual characteristics, disease severity, and other health-related outcomes. It is common to observe missing data in the scale scores, due to missing data in one or more items that make up that score. Multiple imputation (MI) is a popular method for handling missing data. However, it is not clear how best to use MI in the context of scale scores, particularly when they are assessed at multiple waves of data collection resulting in large numbers of items. The aim of this article is to provide practical advice on how to impute missing values in a repeatedly measured multi-item scale using MI when inference on the scale score is of interest. We evaluated the performance of five MI strategies for imputing missing data at either the item or scale level using simulated data and a case study based on four waves of the Longitudinal Study of Australian Children (LSAC). MI was implemented using both multivariate normal imputation and fully conditional specification, with two rules for calculating the scale score. A complete case analysis was also performed for comparison. Based on our results, we caution against the use of a MI strategy that does not include the scale score in the imputation model(s) when the scale score is required for analysis.