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Background: Children born very preterm (VPT; <32 weeks) are at increased risk of executive functioning (EF) difficulties. But less is known about the nature and extent of these executive difficulties during late adolescence, particularly across multiple EF domains and in response to varying degrees of executive demand., Methods: Using data from a prospective longitudinal study, this paper describes the EF profiles of 92 VPT and 68 full-term (FT) adolescents at age 17 years. Relations between gestational age (GA) and later EF performance, in addition to neonatal predictors, were examined., Results: VPT-born adolescents performed less well than FT adolescents across the domains of working memory, planning, and cognitive flexibility, with the largest differences observed for those born <28 weeks GA (effect sizes -0.6 to -1.0 SD), and when task demands were high. The effects of GA on EF outcome were fully mediated by neonatal medical complexity ( b  = 0.169, t  = -1.73) and term equivalent white matter abnormalities ( b  = 0.107, t  = -3.33)., Conclusion: Findings support the need for long-term cognitive support for individuals born very preterm, particularly those exposed to high levels of medical and neurological risk, with these factors largely explaining associations between GA and EF outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Woodward, Moor and Austin.)

Objective: Low-income White and older adults of color face barriers to depression care. Our purpose is to describe the methods and challenges encountered during the implementation of a randomized controlled trial to test the effectiveness of a peer support depression care intervention for low-income White and older adults of color during the COVID-19 pandemic., Methods: Peer Enhanced Depression Care (Peers) is an 8-week community-based intervention that uses peer mentors who are trained and supervised to provide social support and self-care skills to depressed older adults. The effectiveness of the intervention in reducing depression will be evaluated by following a sample of older adults recruited in the community over a 12-month period. Target enrollment is 160 older adults. We hypothesize that participants randomized to the Peer Enhanced Depression Care intervention will experience greater decrease in depressive symptoms compared to participants randomized to the social interaction control. We provide lessons learned regarding the recruitment of BIPOC and White low-income older adults and peer mentors during the COVID-19 pandemic., Results: Recruitment challenges occurred in primary care clinics that were unable to accommodate recruitment efforts during the pandemic. This led to focused outreach to community-based organizations serving older adults. Challenges to participant recruitment have included barriers related to stigma, distrust, as well as unfamiliarity with research. Peer mentor recruitment was facilitated by existing government-supported resources., Conclusions: This study will provide knowledge regarding the effectiveness, mechanism, and processes of delivering an informal psychosocial intervention such as peer support to a vulnerable older adult population., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 μL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE)., Design: Multicentre, prospective, randomised controlled, non-inferiority clinical trial., Setting: Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021., Patients: Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE., Interventions: The intervention: microdrop (approximately 7 μL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered., Main Outcome Measures: The primary outcome measure was an ophthalmologist-determined successful ROPEE., Results: One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction -0.05 to 0.05) and for Māori (95% CI no continuity correction -0.02 to 0.19)., Conclusion: VLD microdrops enable safe and effective screening for ROPEE in both Māori and non-Māori preterm infants., Trial Registration Number: ACTRN12619000795190., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the epidemiology and population trends of early-onset sepsis in very preterm neonates admitted to neonatal intensive care units (NICU) in Australia and New Zealand., Design: Retrospective observational cohort study using a dual-nation registry database., Setting: 29 NICUs that have contributed to the Australian and New Zealand Neonatal Network., Participants: Neonates born at <32 weeks' gestation born between 2007 and 2018 and then admitted to a NICU., Main Outcome Measures: Microorganism profiles, incidence, mortality and morbidity., Results: Over the 12-year period, 614 early-onset sepsis cases from 43 178 very preterm admissions (14.2/1000 admissions) were identified. The trends of early-onset sepsis incidence remained stable, varying between 9.8 and 19.4/1000 admissions (linear trend, p=0.56). The leading causative organisms were Escherichia coli ( E. coli ) (33.7%) followed by group B Streptococcus ( GBS ) (16.1%). The incidence of E. coli increased between 2007 (3.2/1000 admissions) and 2018 (8.3/1000 admissions; p=0.02). Neonates with E. coli had higher odds of mortality compared with those with GBS (OR=2.8, 95% CI 1.2 to 6.1). Mortality due to GBS decreased over the same period (2007: 0.6/1000 admissions, 2018: 0.0/1000 admissions; p=0.01). Early-onset sepsis tripled the odds of mortality (OR=3.0, 95% CI 2.4 to 3.7) and halved the odds of survival without morbidity (OR=0.5, 95% CI 0.4 to 0.6)., Conclusion: Early-onset sepsis remains an important condition among very preterm populations. Furthermore, E. coli is a dominant microorganism of very preterm early-onset sepsis in Australia and New Zealand. Rates of E. coli have been increasing in recent years, while GBS -associated mortality has decreased., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Caring for a child born preterm places significant emotional and financial burdens on family relationships. This paper examines (a) the extent to which children born very and extremely preterm are more likely to experience parental change/caregiver instability than children born full term, (b) predictors of parental change/s for preterm infants, and (c) whether exposure to parental change/caregiver instability increases child neurodevelopmental risk. Data were collected as part of a prospective longitudinal study of 110 very preterm and 113 full-term born infants and their parents studied from birth to corrected age 12 years. At ages 2, 4, 6, 9 and 12 years, detailed information was collected about the frequency and nature of all parent/caregiver changes for 3-6 monthly intervals of each child's life. At age 12, all children completed a comprehensive neurodevelopmental evaluation of their emotional and behavioural adjustment, cognition, and educational achievement. Results showed that children born very preterm were at increased risk of experiencing parental/caregiver changes, with this risk being greatest for those born extremely preterm. Neonatal medical complexity, family socioeconomic disadvantage, maternal psychological wellbeing, and child neurodevelopmental impairment were associated with a higher risk of parental change. Preterm birth and exposure to parental change/instability contributed additively to poorer child outcomes. Findings support the need for family-focused neonatal and postnatal care strategies for high-risk infants, to support parents as well as their infants to optimize child health and developmental outcomes.

Aim: To compare the mental health and neurodevelopmental profiles of school-age children born very preterm, with and without an anxiety disorder, and to identify neonatal medical, psychosocial, and concurrent neurodevelopmental correlates., Method: A regional cohort of 102 (51 males, 51 females) children born very preterm (mean [SD] gestation at birth=28wks [2], range=23-31wks) was studied from birth to age 9 years alongside a comparison group of 109 (58 males, 51 females) children born at term (mean [SD] gestation at birth=40wks [1], range=38-41wks). At age 9 years, all children underwent a neurodevelopmental evaluation while parents were interviewed using the Development and Well-Being Assessment to diagnose a range of DSM-IV childhood psychiatric disorders. Detailed information was also available about the children's neonatal medical course and postnatal psychosocial environment, including maternal mental health and parenting., Results: At age 9 years, 21% (n=21) of very preterm and 13% (n=14) of term-born children met diagnostic criteria for an anxiety disorder. Clinically-anxious children born very preterm were characterized by higher rates of comorbid mental health (odds ratio [OR]=11.5, 95% confidence interval [CI]=3.8-34.7), social (OR=6.2, 95% CI=2.1-18.4), motor (OR=4.4, 95% CI=1.6-12.2), and cognitive (OR=2.6, 95% CI=1.0-7.0) problems than those without an anxiety disorder. Concurrent maternal mental health and child social difficulties were the strongest independent correlates of early-onset child anxiety disorders., Interpretation: Children born very preterm who developed an early-onset anxiety disorder were subject to high rates of comorbid problems. Findings highlight the importance of addressing both maternal and child mental health issues to optimize outcomes in this high-risk population. What this paper adds One out of five school-age children born very preterm are likely to meet DSM-IV diagnostic criteria for an anxiety disorder. Half of these children born very preterm with an early-onset anxiety disorder have comorbid attention-deficit/hyperactivity disorder. Other neurodevelopmental correlates of early-onset anxiety disorders include lower cognitive ability, motor problems, and peer social difficulties. Concurrent maternal mental health and child social adjustment problems were the strongest correlates of early-onset anxiety disorder risk among children born very preterm., (© 2021 Mac Keith Press.)

Background and Objectives: Children born very preterm (VPT) are at high risk of cognitive impairment that impacts their educational and social opportunities. This study examined the predictive accuracy of assessments at 2, 4, 6, and 9 years in identifying preterm children with cognitive impairment by 12 years., Methods: We prospectively studied a regional cohort of 103 children born VPT (≤32 weeks' gestation) and 109 children born term from birth to corrected age 12 years. Cognitive functioning was assessed by using age-appropriate, standardized measures: Bayley Scales of Infant Development, Second Edition (age 2); Wechsler Preschool and Primary Scale of Intelligence (ages 4 and 6); and Wechsler Intelligence Scale for Children, Fourth Edition (ages 9 and 12)., Results: By 12 years, children born VPT were more likely to have severe (odds ratio 3.9; 95% confidence interval 1.1-13.5) or any (odds ratio 3.2; 95% confidence interval 1.8-5.6) cognitive impairment compared with children born term. Adopting a severe cognitive impairment criterion at age 2 under-identified 44% of children born VPT with later severe impairment, whereas a more inclusive earlier criterion identified all severely affected children at 12 years. Prediction improved with age, with any delay at age 6 having the highest sensitivity (85%) and positive predictive value (66%) relative to earlier age assessments. Inclusion of family-social circumstances further improved diagnostic accuracy., Conclusions: Cognitive risk prediction improves with age, with assessments at 6 years offering optimal diagnostic accuracy. Intervention for children with early mild delay may be beneficial, especially for those raised in socially disadvantaged family contexts., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: Children born to opioid-dependent mothers are at risk of adverse neurodevelopment. The magnitude of this risk remains inconclusive., Objective: To conduct a meta-analysis of studies that assessed neurodevelopmental outcomes of children aged 0 to 12 years born to opioid-dependent mothers, compared with children born to nonopioid-dependent mothers, across general cognitive, language, motor, and social-emotional domains., Data Sources: PubMed, CINAHL, PsycINFO, and Google Scholar databases., Study Eligibility Criteria: English-language publications between January 1993 and November 2018, including prenatally opioid-exposed and nonopioid-exposed comparison children, reporting outcomes data on standardized assessments., Study Appraisal and Synthesis Methods: Two reviewers independently extracted data. Pooled standardized mean differences (SMDs) were analyzed using random effects models. Risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale., Results: Across 16 studies, individual domain outcomes data were examined for between 93 to 430 opioid-exposed and 75 to 505 nonopioid-exposed infants/children. Opioid-exposed infants and children performed more poorly than their nonopioid-exposed peers across all outcomes examined, demonstrated by lower infant cognitive (SMD = 0.77) and psychomotor scores (SMD = 0.52), lower general cognition/IQ (SMD = 0.76) and language scores (SMD = 0.65-0.74), and higher parent-rated internalizing (SMD = 0.42), externalizing (SMD = 0.66), and attention problems (SMD = 0.72)., Limitations: Most studies examined early neurodevelopment; only 3 reported school-age outcomes thereby limiting the ability to assess longer-term impacts of prenatal opioid exposures., Conclusions and Implications of Findings: Children born to opioid-dependent mothers are at modest- to high-risk of adverse neurodevelopment at least to middle childhood. Future studies should identify specific clinical and social factors underlying these challenges to improve outcomes., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the school readiness of a regional cohort of prenatally methadone-exposed children across 5 domains and to examine factors contributing to impairment risk., Methods: Data were drawn from a single-center, prospective longitudinal study. One hundred children born to women in methadone maintenance treatment and 110 randomly identified non-methadone-exposed children were studied from birth (2003-2008) to age 4.5 years. At 4.5 years, children underwent comprehensive assessment of their physical/motor development, social-emotional skills, approaches to learning, language development, and cognitive functioning. Predictors of children's overall school readiness were examined, including the extent of prenatal substance exposure (number and quantity of different substances), social risk, maternal mental health, infant clinical factors, and the quality of the home environment at age 18 months Home Observation for Measurement of the Environment (HOME) score., Results: Methadone-exposed children had higher rates of delay/impairment across all outcome domains (odds ratios 4.0-5.3), with 72% impaired in at least 1 domain. Multiple problems were also common, affecting 48% of methadone-exposed children compared with 15% of control children. The mean number of school readiness domains impaired increased, with increasing prenatal substance exposure (rate ratio [RR] = 1.05 [1.01-1.11]), higher social risk (RR = 1.35 [1.20-1.53]), male sex (RR = 1.69 [1.27-2.25]), and lower HOME scores indicating a poorer quality postnatal environment (RR = 0.96 [0.94-0.99])., Conclusion: Children born to opioid-dependent mothers are at high risk of impaired school readiness, with multiple domain problems being common. Impaired school readiness was associated with greater maternal prenatal substance use, higher social risk, male sex, and lower-quality caregiving environments.

Individuals born very preterm (<32 weeks gestation) are at increased risk for neuromotor impairments. The ability to characterize the structural and functional mechanisms underlying these impairments remains limited using existing neuroimaging techniques. Resting state-functional magnetic resonance imaging (rs-fMRI) holds promise for defining the functional network architecture of the developing brain in relation to typical and aberrant neurodevelopment. In 58 very preterm and 65 term-born children studied from birth to age 12 years, we examined relations between functional connectivity measures from low-motion rs-fMRI data and motor skills assessed using the Movement Assessment Battery for Children, 2nd edition. Across all subscales, motor performance was better in term than very preterm children. Examination of relations between functional connectivity and motor measures using enrichment analysis revealed between-group differences within cerebellar, frontoparietal, and default mode networks, and between basal ganglia-motor, thalamus-motor, basal ganglia-auditory, and dorsal attention-default mode networks. Specifically, very preterm children exhibited weaker associations between motor scores and thalamus-motor and basal ganglia-motor network connectivity. These findings highlight key functional brain systems underlying motor development. They also demonstrate persisting developmental effects of preterm birth on functional connectivity and motor performance in childhood, providing evidence for an alternative network architecture supporting motor function in preterm children., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: To describe the survival, in-hospital morbidity, brain metrics and two-year neurodevelopmental outcomes of two extremely preterm cohorts and discuss the contribution of changes in clinical practice to these outcomes., Methods: Retrospective comparative cohort study, of two cohorts of neonates born <28 weeks gestation: 47 infants born 1998-2000 and 39 infants 2006-2009., Results: Comparing historical to the contemporary cohort respectively, admission temperature (35.9 degrees C, 36.5) and CRIB (Clinical Risk Index in Babies) score (5.4, 3.1) improved. Inotrope support fell significantly (55.3%, 28.2%). High frequency ventilation days fell (8.0, 2.7). CPAP days increased significantly (32.2, 47.9). Chronic lung disease at 36 weeks corrected age fell significantly (61.7%, 38.5%). Red cell transfusions decreased in number (7.1, 4.8) and volume (96.2ml/kg, 70.4ml/kg). Retinopathy of prematurity (ROP) rates dropped significantly (66.0%, 28.2%). Survival was not significantly different. Nutritional improvements included shorter days to first enteral feed (3.4, 2.0), target protein (5.4, 4.3) and lipid levels (7.1, 4.1) with better breastfeeding rates at discharge (19.2%, 38.5%). By 36 weeks z scores for weight (-0.90, -0.39) were improved but not length (-1.94, -1.26) or head circumference (-0.72, -0.69). MRI brain metrics showed a significant improvement in bifrontal (59.2, 65.9), biparietal (73.7, 79.3) and transcerebellar diameter (50.6, 52.6) with improved neurodevelopmental outcome at two years., Conclusion: The contemporary cohort had better initial physiological stability, less chronic lung disease and retinopathy, improved body growth at 36 weeks and brain metrics at term equivalent. Improvement in neurodevelopment at two years has been seen and further analysis will be important to understand the impact of the changes in clinical care.

Objectives: To document associations between confirmed and suspected neonatal infection and motor, cognitive, educational, and mental health outcomes of very preterm (VPT)-born children at 9 years of age; to examine the potential intervening role of cerebral white matter abnormalities (WMAs) and structural development on term magnetic resonance imaging., Study Design: A regional cohort of 110 infants born VPT in Christchurch, New Zealand were studied from birth to age of 9 years. Confirmed infection was defined as positive blood, cerebrospinal fluid or urine culture, and/or necrotizing enterocolitis ≥ stage 2. Suspected infection was defined as ≥ 5 days of antibiotics with evidence of clinical correlates. At term gestational equivalence, infants underwent structural magnetic resonance imaging. At age 9 years, neuromotor function, IQ, educational achievement, and mental health were assessed., Results: During hospitalization, 25% of VPT infants had confirmed and 23% had suspected infection. Longer-term neurodevelopmental impairments were largely confined to infants with confirmed infection (relative risk 1.4-3.1, vs uninfected). After accounting for other neonatal factors, these infants were at increased risk of severe motor impairment (OR 3.3, 95% CI 1.3-8), attention deficit hyperactivity disorder (ADHD) (OR 3.6, 95% CI 1.6-8), and IQ delay (OR 2.0, 95% CI 1-3.9). Cerebral WMAs contributed to associations between confirmed infection and motor and IQ impairments but not to ADHD (P = .005)., Conclusions: Confirmed neonatal infection heightens VPT infants' risk for neurodevelopmental impairment. WMA appears to be an important intervening factor linking infection and severe motor and IQ impairments. Further analysis of the neurologic mechanism accounting for ADHD in infants with infection is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Children born very preterm (VPT) are at high risk of educational delay, yet few guidelines exist for the early identification of those at greatest risk. Using a school readiness framework, this study examined relations between preschool neurodevelopmental functioning and educational outcomes to age 9 years., Methods: The sample consisted of a regional cohort of 110 VPT (≤ 32 weeks' gestation) and 113 full-term children born during 1998-2000. At corrected age 4 years, children completed a multidisciplinary assessment of their health/motor development, socioemotional adjustment, core learning skills, language, and general cognition. At ages 6 and 9, children's literacy and numeracy skills were assessed using the Woodcock-Johnson III Tests of Achievement., Results: Across all readiness domains, VPT children were at high risk of delay/impairment (odds ratios 2.5-3.5). Multiple problems were also more common (47% vs 16%). At follow-up, almost two-thirds of VPT children were subject to significant educational delay in either literacy, numeracy or both compared with 29% to 31% of full-term children (odds ratios 3.4-4.4). The number of readiness domains affected at age 4 strongly predicted later educational risk, especially when multiple problems were present. Receiver operating characteristic analysis confirmed ≥ 2 readiness problems as the optimal threshold for identifying VPT children at educational risk., Conclusions: School readiness offers a promising framework for the early identification of VPT children at high educational risk. Findings support the utility of ≥ 2 affected readiness domains as an effective criterion for referral for educational surveillance and/or additional support during the transition to school., (Copyright © 2014 by the American Academy of Pediatrics.)

Objective: Examine sources, predictors and child outcomes associated with neonatal intensive care unit (NICU)-related stress for mothers of infants born very preterm (VPT)., Study Design: Participants were 133 mothers of VPT infants admitted to a regional level-III NICU. At term equivalent, mothers completed the Parental Stressor Scale: NICU and were interviewed about their psychological well-being and family circumstances. Infant clinical data were also collected. At corrected age 4 years, 49 children were assessed for cognition, language and socio-emotional development., Result: Mothers reported moderate to low stress, with parental role alteration considered most stressful and parent-staff communications least stressful. Predictors of overall stress included maternal educational underachievement, stressful life events, postnatal depression and infant unsettled-irregular behavior. NICU-related stress was associated with child anxiety and poorer language development., Conclusion: Parental well-being is an important focus of care in the neonatal setting. Strategies are needed to optimize early engagement and reduce stress levels to assist improved child outcomes.

Aims: This paper describes the emotional and behavioural adjustment of children born very preterm (VPT) at early school age. Of particular interest was the degree of agreement between parents and teachers, and the extent of situational (parent or teacher) and pervasive (parent and teacher reported) adjustment problems., Methods: A regionally representative cohort of 104 VPT (≤33 weeks gestation) and 108 full-term (FT) children born during 1998-2000 was studied prospectively to age six. At corrected age six, child emotional and behavioural adjustment was assessed using the parent and teacher rated strengths and difficulties questionnaires., Results: According to parents, 6-year-old VPT children had odds of emotional, inattention/hyperactivity and peer problems that were 2.7 to 3.8 times higher than their FT peers. Similar difficulties were identified by teachers, but odds were much lower and nonsignificant (1.1-1.8). Agreement between parents and teachers was lower in the VPT than the FT group (mean alternative chance-correlated coefficient , AC(1) = 0.63 vs. 0.80). Examination of the extent of pervasively identified adjustment problems showed that VPT children had higher rates of emotional (6% vs. 1%) and inattention/hyperactivity problems (12% vs. 6%) than FT children., Conclusions: Early school age, VPT children are at increased risk of pervasive emotional problems and inattention/hyperactivity, although these risks are relatively modest. The use of multiple informants to assess VPT children's well-being is important to minimise the effects of report source bias and the over-identification of adjustment problems in children born VPT., (© 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Objectives: Neurodevelopmental outcomes associated with preterm birth are of major health and educational concern. This study examined the neuromotor, cognitive, language and emotional/behavioural outcomes of a regional cohort of 4-year-old children born extremely preterm (EPT: 23-27 weeks' gestation), very preterm (VPT: 28-33 weeks) and full term (FT: 38-41 weeks). Of particular interest were children's risks of impairment across multiple neurodevelopmental domains., Methods: Data were gathered as part of a prospective longitudinal study of 105 very preterm (< or = 33 weeks gestation) and 107 FT children born during 1998-2000. At 4 years corrected age, children underwent a comprehensive multidisciplinary assessment that included a paediatric neurological examination, cognitive and language testing, and an assessment of child emotional and behavioural adjustment., Results: At age 4 years, compared to FT children, EPT and VPT children had increased risks of cerebral palsy (EPT 18%, VPT 15%, FT 1%), cognitive delay (EPT 33%, VPT 36%, FT 13%), language delay (EPT 29%, VPT 29%, FT 10%) and emotional/behavioural adjustment problems (EPT 37%, VPT 13%, FT 11%). EPT and VPT children were three times more likely to have multiple domain impairments than FT children (EPT 30%, VPT 29%, FT 10%)., Conclusions: A substantial proportion of preschool children born very preterm show clinically significant problems in at least one neurodevelopmental domain, with impairment in multiple domains being common. There is a need to monitor preschool development across a range of functional domains and to consider the likely cascading effects of multiple impairments on later development.

Aims: To assess neurodevelopmental outcome at 2 years for neonatal intensive care unit (NICU) admissions compared with controls, and to trial a parent-reporting scheme., Methods: All infants admitted to the NICU at Christchurch Women's Hospital over a 12-month period and whose parents were domiciled in a defined geographical region were eligible for study, together with every eighth term infant not admitted (to a total of 300). Parents completed a two-page questionnaire on their child's 2nd birthday. All infants <28 weeks gestation and a random 300 NICU admissions and 108 controls underwent a paediatric examination and Bayley II assessment at 2 years of age., Results: A total of 387 NICU infants (86% eligible) and 306 controls were enrolled. At 2 years of age, 276 NICU infants (89% survivors) and 94 controls (87%) had some follow up. For infants of <33 weeks, 33-36 weeks, > or =37 weeks gestation and controls, the percentage >1 SD below the mean on the Bayley Mental Development Index scales were 33.3, 36.5, 44.6 and 24.1, respectively (P= 0.03); on the Psychomotor Developmental Index scales were 30.0, 29.1, 41.1 and 19.5 (P= 0.02) and the percentage with any cerebral palsy were 11.1, 2.8, 5.2 and 1.2., Conclusions: At 2 years of age, NICU graduates have more developmental problems than controls across a range of measures. In many cases, term NICU graduates have the least favourable outcome. There was only moderate agreement between parents' reporting of moderate or severe developmental disability by means of a questionnaire, compared with professionals (kappa statistic 0.38), with parents tending to underestimate problems.

Aims: To describe the neonatal course and morbidity of all infants admitted to the regional neonatal intensive care unit (NICU) at Christchurch Women's Hospital (CWH) and to compare these with term control infants who were not admitted, in one calendar year. Infants in both NICU and control cohorts were enrolled in a 2-year follow-up study., Methods: All infants born over a 12-month period from February 2001 and admitted to the NICU, whose parents were domiciled in a defined geographical region, were eligible for study, together with every eighth healthy infant born at term and not admitted (to a total of 300). Comprehensive perinatal and neonatal data were collected for all enrolled infants., Results: A total of 387 NICU infants (86% eligible) were enrolled in the study together with 306 controls. Forty-one percent of NICU admissions were term and 40% were 33-36 weeks gestation. Term NICU infants were more likely to be born following induction of labour or by Caesarean section (34%, of which 50% were pre-labour) than control infants (18%, of which 32% were pre-labour). Infants of <28, 28-32, 33-36 and > or =37 weeks accounted for 74, 16, 7 and 3% of assisted ventilation days and 18, 31, 31 and 20% of total baby days, respectively., Conclusions: The need for assisted ventilation and length of NICU stay was inversely proportional to gestation. However, preterm infants of 28 weeks gestation and greater, as well as term infants, account for a high proportion of the NICU workload.

Purpose: Premature infants are at increased risk of impaired visual performance related to both cortical and subcortical pathways for oculomotor control. The hypothesis for the current study was that preterm infants with impaired saccades, smooth pursuit, and binocular eye alignment at age 2 years would have smaller occipital brain volumes at term equivalent, as measured by volumetric magnetic resonance (MR) techniques, than would preterm infants without such abnormalities., Methods: Study participants consisted of 68 infants from a representative regional cohort of 100 preterm infants born between 23 and 33 weeks' gestation. At term equivalent, all infants underwent MR imaging, and the images were coregistered, tissue segmented into five cerebral tissue subtypes, and further subdivided into eight regions for each hemisphere. At 2 years corrected, all infants completed a comprehensive orthoptic evaluation performed by a single examiner., Results: Twenty-four (35%) of the 68 infants had abnormal oculomotor control at 2 years, including abnormalities in saccadic movements (n = 7), smooth pursuit (n = 14), or strabismus (n = 9, four with esotropia and five with exotropia). When compared with preterm infants without visuomotor impairment, these infants had significantly smaller inferior occipital region brain tissue volumes bilaterally (n = 24 vs. n = 44; total tissue, mean +/- SD, left, 37.9 +/- 7.4 cm(3) vs. 43.7 +/- 7.4 cm(3); mean difference [95% CI] -5.7 [-9.4 to -2.0] cm(3), P = 0.003; right, 36.8 +/- 7.1 cm(3) vs. 41.4 +/- 6.2 cm(3), mean difference -4.6 [-7.9 to -1.3] cm(3), P = 0.007). This difference remained significant after adjusting for intracranial volume (ICV; left, mean difference -3.5 [-6.7 to -0.2] cm(3), P = 0.04; right, mean difference -2.4 [-5.2 to -0.4] cm(3), P = 0.09). Within this region, the cortical gray matter volume was the most significantly reduced (left, 20.4 +/- 6.2 cm(3) vs. 25.4 +/- 5.6 cm(3), mean difference -3.1 [-5.7 to -0.5] cm(3), P = 0.02; right 21.0 +/- 5.4 cm(3) vs. 24.9 +/- 5.0 cm(3), mean difference -2.2 [-4.4 to 0.0] cm(3), P = 0.05, ICV adjusted). Abnormalities in saccadic eye movements accounted for the largest effect on inferior occipital regional brain volumes (left side, P = 0.02)., Conclusions: Volumetric MR imaging techniques demonstrated an overall reduction in the inferior occipital regional brain volumes in preterm infants at term corrected who later exhibit impaired oculomotor function control. These findings assist in understanding the neuroanatomic correlates of later visual difficulties experienced by infants born prematurely.

Aim: Very preterm infants represent major consumers of health services following neonatal discharge. We examined the health service utilisation of a regional cohort of very preterm infants over the first 2 years of life, including the association with neurodevelopmental outcome., Methods: A regionally based 2-year cohort of 100 very preterm infants along with a comparison sample of 104 full term control infants matched for sex, time and place of birth were recruited. Perinatal and social background factors that predispose very preterm infants to increased risk of subsequent general practitioner (GP) and hospital service use were identified. At 2 years, all children underwent a neurodevelopmental assessment, Bayley Scales of Infant Development (BSID-II). Details of children's medical contacts obtained by parent interview were cross-checked against GP and hospital records/databases., Results: Very preterm infants had a similar number of GP visits to term infants but more outpatient hospital visits. Fifty-three (55%) very preterm infants were admitted to hospital on 131 occasions compared with 26 (26%) term infants on 37 occasions (p<0.001). The main reason for hospitalisation in the preterm cohort was respiratory disorder. The frequency of hospital admissions was significantly related to birthweight (P=0.01), gestational age (P<0.001) and the number of people living in the family household (P=0.02). No associations were found between hospital admission and neurodevelopment at 2 years., Conclusion: Very preterm infants had higher rates of hospital admissions and visits than term infants unrelated to neurodevelopmental outcome at 2 years of age. These findings highlight that very preterm birth is associated with ongoing health morbidity.

Background: In medication safety research studies medication related events are often classified by type, seriousness, and degree of preventability, but there is currently no universally reliable "gold standard" approach. The reliability (reproducibility) of this process is important as the targeting of prevention strategies is often based on specific categories of event. The aim of this study was to determine the reliability of reviewer judgements regarding classification of paediatric inpatient medication related events., Methods: Three health professionals independently reviewed suspected medication related events and classified them by type (adverse drug event (ADE), potential ADE, medication error, rule violation, or other event). ADEs and potential ADEs were then rated according to seriousness of patient injury using a seven point scale and preventability using a decision algorithm and a six point scale. Inter- and intra-rater reliabilities were calculated using the kappa (kappa) statistic., Results: Agreement between all three reviewers regarding event type ranged from "slight" for potential ADEs (kappa = 0.20, 95% CI 0.00 to 0.40) to "substantial" agreement for the presence of an ADE (kappa = 0.73, 95% CI 0.69 to 0.77). Agreement ranged from "slight" (kappa = 0.06, 95% CI 0.02 to 0.10) to "fair" (kappa = 0.34, 95% CI 0.30 to 0.38) for seriousness classifications but, by collapsing the seven categories into serious versus not serious, "moderate" agreement was found (kappa = 0.50, 95% CI 0.46 to 0.54). For preventability decision, overall agreement was "fair" (kappa = 0.37, 95% CI 0.33 to 0.41) but "moderate" for not preventable events (kappa = 0.47, 95% CI 0.43 to 0.51)., Conclusion: Trained reviewers can reliably assess paediatric inpatient medication related events for the presence of an ADE and for its seriousness. Assessments of preventability appeared to be a more difficult judgement in children and approaches that improve reliability would be useful.

Background: Systemic fungal infection has increased in prevalence in neonatal intensive care units (NICU) caring for very low birth weight infants. It is associated with a prolonged stay and an increase in morbidity and mortality. An assessment of the use of oral prophylactic antifungals to prevent systemic infection is needed., Objectives: To assess whether the prophylactic administration of oral antifungal agents to very preterm infants reduces the occurrence of systemic fungal infection., Search Strategy: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Searches were carried out up to July 2003 on the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, 2003), MEDLINE from 1966, EMBASE from 1980, CINAHL from 1992. Abstracts from SPR (1993 - 2003) and ESPR (1995 to 2002) were hand searched., Selection Criteria: Randomized and quasi randomized controlled trials in very low birth weight or very preterm infants in which an oral antifungal agent was compared with placebo or no treatment or another oral antifungal agent, Data Collection and Analysis: Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of the trial quality and data extraction undertaken by each author. Results were reported using relative risk (RR) and risk difference (RD) and weighted mean difference (WMD). 95% confidence intervals were reported., Main Results: We identified three eligible trials, one comparing nystatin with no treatment (67 infants), one comparing miconazole with placebo (600 infants), and one comparing nystatin with fluconazole (21 infants). As the two trials comparing nystatin or miconazole with placebo or no treatment were clinically quite different, meta-analysis was not performed. In the trial of nystatin versus no treatment, systemic fungal infection was significantly reduced [RR 0.19 (0.04,0.78)] in the group treated with nystatin. In the study comparing miconazole with placebo there was no significant effect on systemic fungal infection [RR 1.32 (0.46,3.75)]. Neither study found a significant effect on mortality, and there was no significant difference in the mean number of days infants received ventilation or stayed in the neonatal intensive care unit. In the small trial comparing oral fluconazole with nystatin, no significant difference in systemic fungal infection [RR 0.17 (0.01, 2.84)] or mortality [RR 0.17 (0.01, 2.84)] was reported. Adverse drug reactions were not reported in any study., Reviewer's Conclusions: There is insufficient evidence to support the use of prophylactic oral antifungal agents in very low birth weight infants in the neonatal intensive care unit. Randomised controlled trials in current neonatal practice settings are needed, comparing oral antifungal agents with placebo and with each other and including an assessment of side effects, in order to determine whether oral antifungal agents have a role in preventing systemic fungal infections in preterm infants.

Background: Selenium is an essential trace element and component of a number of selenoproteins including glutathione peroxidase, which has a role in protecting against oxidative damage. Selenium is also known to play a role in immunocompetence. Blood selenium concentrations in newborns are lower than those of their mothers and lower still in preterm infants. In experimental animals low selenium concentrations appear to increase susceptibility to oxidative lung disease. In very preterm infants low selenium concentrations have been associated with an increased risk of chronic neonatal lung disease and retinopathy of prematurity., Objectives: To assess the benefits and harms of selenium supplementation in preterm or very low birthweight infants., Search Strategy: Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), MEDLINE (1966-May 2003), and Embase (1980-May 2003). The reference lists of recent trials were also searched and abstracts from the Society for Pediatric Research from 1990 were hand-searched., Selection Criteria: Randomised controlled trials which compared selenium supplementation either parenterally or enterally with placebo or nothing from soon after birth in preterm or very low birthweight infants and which reported clinical outcomes were considered for the review., Data Collection and Analysis: Data on selenium supplementation dose, formulation and route of administration; mortality, oxygen requirement at 28 days and 36 weeks post-menstrual age, retinopathy of prematurity, and one or more episodes of sepsis; blood selenium and glutathione peroxidase concentrations at or close to 28 days, were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group., Main Results: Three eligible trials were identified. Two trials, including one trial with a much larger sample size than the others combined, were from geographical areas with low population selenium concentrations. Meta-analysis of the pooled data showed a significant reduction in the proportion of infants having one or more episodes of sepsis associated with selenium supplementation [summary RR 0.73 (0.57, 0.93); RD -0.10 (-0.17, -0.02); NNT 10 (5.9, 50)]. Supplementation with selenium was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity., Reviewer's Conclusions: Supplementing very preterm infants with selenium is associated with benefit in terms of a reduction in one or more episodes of sepsis. Supplementation was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. Supplemental doses of selenium for infants on parenteral nutrition higher than those currently recommended may be beneficial. The data are dominated by one large trial from a country with low selenium concentrations and may not be readily translated to other populations.

Background: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease., Methods: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency., Results: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity., Conclusions: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.

Objective: To examine the association between plasma vitamin A levels and outcome measures in very low birthweight (VLBW) infants, including meta-analysis of all observational studies., Design: A prospective observational longitudinal study of plasma vitamin A levels measured in the cord blood; maternal blood in the first 48 h after delivery; and the infants' blood at 48 h, 7 days and 28 days of age and correlated with antenatal and postnatal events. A meta-analysis of all published observational studies on the association of vitamin A with respiratory outcome in the VLBW infant was undertaken., Patients: Fifty-seven infants (88% of all eligible) VLBW infants (< 1500 g) admitted from January through October 1993 to one of two regional neonatal intensive care units in the South Island of New Zealand., Results: Exposure to antenatal steroids led to a significant increase in infant cord plasma vitamin A levels (P = 0.003), but no influence on infant plasma vitamin A levels at any other time. Exposure to postnatal steroids produced a significant rise in infant plasma vitamin A levels between 7 and 28 days (P = 0.008). After controlling for gestational age, antenatal and postnatal steroid exposure, low vitamin A levels at 48 h increased the risk of developing chronic lung disease (odds ratio for 50 microg/l decrease: 2.04, 95% CI 1.19-5.77) and bronchopulmonary dysplasia (odds ratio 1.96, 95% CI 1.14-6.87). On combining our results in meta-analysis with those of other published prospective observational studies, infants with chronic lung disease had lower plasma vitamin A levels at all times., Conclusions: Our results support an association between low plasma vitamin A levels and adverse outcome in the VLBW infant.

Objective: To explore the hypothesis that excessive iron loads may increase the formation of free radicals and the development of retinopathy of prematurity in preterm infants, we carried out a prospective observational study of the association between transfusion volume, iron status, and retinopathy.

Aims: A three dose oral regimen for vitamin K prophylaxis was introduced as an alternative to a single intramuscular injection in August 1992. An assessment of the acceptance of this regimen was needed to determine if the risk of developing haemorrhagic disease of the newborn had altered., Methods: A survey of compliance with the recommendations was made using a telephone questionnaire to 179 parents., Results: One hundred and fifty three breast fed infants received oral vitamin K. Repeated doses were given to 133 (97%) of 138 breast fed infants at 1 week and 115 (94%) of 122 breast fed infants at 6 weeks. Twenty three of the infants were given the third dose of vitamin K later than recommended., Conclusion: Although the majority of infants received all three recommended doses, a quarter of infants given oral prophylaxis are at an increased risk of haemorrhagic disease of the newborn in our sample population.

Plasma vitamin A and E levels were inadequate in very low birth weight infants receiving a continuous infusion of a parenteral multivitamin preparation, 1.5 ml/kg per day, in dextrose-amino acid solution. A new delivery system using 2 ml/kg per day, infused for 6 hours from the first day of life, avoided loss during infusion and significantly improved plasma vitamin A and E levels during the first 28 days of life in very low birth weight infants.

Cerebral blood flow velocity was assessed during infusion of indomethacin over 30 minutes. Eleven preterm infants with symptomatic patent ductus arteriosus were studied on 12 occasions. Indomethacin infusion was associated with a significant reduction in time averaged mean velocity (TAMV), peak systolic velocity (PSV), and end diastolic velocity in both the anterior cerebral artery and middle cerebral artery. The fall in the TAMV and PSV was gradual with maximal change 30-40 minutes after the start of the infusion. It was concluded that administration of indomethacin by slow infusion produces haemodynamic alterations to the cerebral circulation comparable in magnitude with changes described with bolus administration. Indomethacin remains a useful and effective treatment for patent ductus arteriosus in preterm infants, but should continue to be used with caution.

The turnover of the artificial surfactant Exosurf after its administration to infants with respiratory distress syndrome was studied. High performance liquid chromatography was used to compare the phosphatidylcholine (PC) composition of serial endotracheal tube secretions from three groups of infants. There were 22 infants who received two doses of Exosurf in 24 hours (group 1), 10 infants who received four doses in 36 hours (group 2), and 41 control infants who did not receive Exosurf. Two parameters were studied: (i) dipalmitoylphosphatidylcholine (DPPC), which is present in both Exosurf and endogenous surfactant, expressed as a percentage of total PC (% DPPC) and (ii) the ratio of DPPC to the entirely endogenous palmitoyloleoylphosphatidylcholine (DPPC:POPC ratio). The administration of Exosurf produced changes in endotracheal tube aspirate PC composition that were detectable for over one week. Four doses of Exosurf in 36 hours prolonged the persistence of these changes compared with two doses in 24 hours, but the numbers of infants were small, and should not be over-interpreted. We conclude that after giving two doses of Exosurf, further doses might best be delayed until after two days, and that further clinical evaluation of dosage regimens is required.