Longitudinal Preterm Cerebellar Volume: Perinatal and Neurodevelopmental Outcome Associations.

Impaired cerebellar development is an important determinant of adverse motor and cognitive outcomes in very preterm (VPT) infants. However, longitudinal MRI studies investigating cerebellar maturation from birth through childhood and associated neurodevelopmental outcomes are lacking. We aimed to compare cerebellar volume and growth from term-equivalent age (TEA) to 7 years between VPT (< 30 weeks' gestation or < 1250 g) and full-term children; and to assess the association between these measures, perinatal factors, and 7-year outcomes in VPT children, and whether these relationships varied by sex. In a prospective cohort study of 224 VPT and 46 full-term infants, cerebellar volumes were measured on MRI at TEA and 7 years. Useable data at either time-point were collected for 207 VPT and 43 full-term children. Cerebellar growth from TEA to 7 years was compared between VPT and full-term children. Associations with perinatal factors and 7-year outcomes were investigated in VPT children. VPT children had smaller TEA and 7-year volumes and reduced growth. Perinatal factors were associated with smaller cerebellar volume and growth between TEA and 7 years, namely, postnatal corticosteroids for TEA volume, and female sex, earlier birth gestation, white and deep nuclear gray matter injury for 7-year volume and growth. Smaller TEA and 7-year volumes, and reduced growth were associated with poorer 7-year IQ, language, and motor function, with differential relationships observed for male and female children. Our findings indicate that cerebellar growth from TEA to 7 years is impaired in VPT children and relates to early perinatal factors and 7-year outcomes.

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age.

BACKGROUND AND PURPOSE: Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth. MATERIALS AND METHODS: Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7-27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression. RESULTS: A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter. CONCLUSIONS: Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development.

Prognostic neurodevelopmental testing of preterm infants: do we need to change the paradigm?

Longitudinal follow-up with assessment of developmental status at about 2 years of age is routine for high-risk newborns. The results of these assessments can be used for many purposes, including helping physicians, parents, and teachers plan educational or developmental interventions. These assessments also provide outcome measures for clinical research studies. Outcome results may also serve as a source of information for clinicians when counseling parents regarding provision of care for extreme preterm infants. Consideration should be given to use of different outcome metrics based on the purpose for testing. Categorization of composite cognitive, motor and neurosensory findings to define levels of impairment should be limited to research. Planning for individual interventions is better guided by descriptive findings. Current tools for assessing neurodevelopmental status at 2 years of age have important limitations. First, outcomes at early ages do not always predict function later in life. They are, at best, an estimate of longer-term outcomes, with important individual variation. For infants without severe neurologic injury, postnatal environmental factors play a predominant role in determining long-term cognitive and academic outcomes. Further investigations should assess quality of life and other considerations that are important for parents when making decisions about neonatal intensive care unit care for their infant.

The Baby Moves prospective cohort study protocol: using a smartphone application with the General Movements Assessment to predict neurodevelopmental outcomes at age 2†years for extremely preterm or extremely low birthweight infants.

INTRODUCTION: Infants born extremely preterm (EP; <28 weeks' gestation) and/or with extremely low birth weight (ELBW; <1000 g birth weight) are at increased risk for adverse neurodevelopmental outcomes. However, it is challenging to predict those EP/ELBW infants destined to have long-term neurodevelopmental impairments in order to target early intervention to those in most need. The General Movements Assessment (GMA) in early infancy has high predictive validity for neurodevelopmental outcomes in preterm infants. However, access to a GMA may be limited by geographical constraints and a lack of GMA-trained health professionals. Baby Moves is a smartphone application (app) developed for caregivers to video and upload their infant's general movements to be scored remotely by a certified GMA assessor. The aim of this study is to determine the predictive ability of using the GMA via the Baby Moves app for neurodevelopmental impairment in infants born EP/ELBW. METHODS AND ANALYSIS: This prospective cohort study will recruit infants born EP/ELBW across the state of Victoria, Australia in 2016 and 2017. A control group of normal birth weight (>2500 g birth weight), term-born (≥37 weeks' gestation) infants will also be recruited as a local reference group. Parents will video their infant's general movements at two time points between 3 and 4 months' corrected age using the Baby Moves app. Videos will be scored by certified GMA assessors and classified as normal or abnormal. Parental satisfaction using the Baby Moves app will be assessed via survey. Neurodevelopmental outcome at 2 years' corrected age includes developmental delay according to the Bayley Scales of Infant and Toddler Development-III and cerebral palsy diagnosis. ETHICS AND DISSEMINATION: This study was approved by the Human Research and Ethics Committees at the Royal Children's Hospital, The Royal Women's Hospital, Monash Health and Mercy Health in Melbourne, Australia. Study findings will be disseminated via peer-reviewed publications and conference presentations.

A high burden of late-onset sepsis among newborns admitted to the largest neonatal unit in central Vietnam.

OBJECTIVE: The objective of this study is to determine the prevalence, causes and outcome of sepsis in hospitalized neonates in the largest neonatal unit in central Vietnam. STUDY DESIGN: A 1-year prospective cohort study of newborns admitted to the neonatal unit in Da Nang. A sepsis work-up including blood culture was undertaken before commencing antibiotics for neonates with suspected sepsis. RESULT: Of 2555 neonatal admissions, 616 neonates had 729 episodes of suspected invasive sepsis. A pathogen was isolated from blood in 115 (16%) episodes in 106 neonates. The prevalence of early-onset sepsis (EOS) was 8 (95% confidence interval (CI): 4 to 11) per 1000 admissions, and of late-onset sepsis (LOS) was 34 (95% CI: 27 to 41) per 1000 admissions. Of 86 neonates with LOS, 69 (80%) also fulfilled the criteria for nosocomial sepsis. The commonest bacterial causes of EOS were coagulase-negative Staphylococcus (CoNS) and Staphylococcus aureus, and of LOS were Acinetobacter, CoNS and Klebsiella pneumoniae. Fungal sepsis occurred in 35 neonates of which most were nosocomial sepsis. In vitro resistance to multiple antibiotics was common among Gram-negative bacteria. Antibiotics were prescribed and given to 68% of all admissions, and 14% of all admissions received four or more different antibiotics. The case fatality rate for confirmed sepsis was 46%. CONCLUSION: Late-onset, nosocomial sepsis was common and associated with a high mortality in hospitalized newborns in the largest neonatal unit in central Vietnam. These findings highlighted the need for improved infection control measures and antibiotic stewardship, which have since been implemented.

Extremely preterm birth and adolescent mental health in a geographical cohort born in the 1990s.

BACKGROUND: Preterm birth confers risk for poor outcome, including mental health problems. Survival of extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g) infants increased in the 1990s but psychiatric outcomes in older adolescents born preterm since 1990 are not well documented. This study aimed to characterize mental health and personality traits in a prospective geographical cohort of adolescents born EP/ELBW in Victoria, Australia in 1991 and 1992. METHOD: At age 18 years, 215 EP/ELBW and 157 normal birthweight (>2499 g) control adolescents completed the Structured Clinical Interview for DSM-IV Disorders, Axis 1 Non-Patient version (SCID-I/NP), the Children's Interview for Psychiatric Syndromes (ChIPS) attention deficit hyperactivity disorder (ADHD) module, and questionnaires assessing recent depression and anxiety symptoms and personality traits. RESULTS: ADHD prevalence was significantly elevated in EP/ELBW adolescents compared with controls [15% v. 7%; odds ratio (OR) 2.67, 95% confidence interval (CI) 1.08-6.58]. Aside from ADHD, however, EP/ELBW and control adolescents reported very similar outcomes, with other lifetime diagnoses identified in 23% of EP/ELBW and 21% of controls. These were predominantly mood and anxiety disorders (21% EP/ELBW, 20% controls). The groups did not differ in recent depression or anxiety symptoms assessed using questionnaires, and personality traits were also similar. CONCLUSIONS: ADHD was more prevalent in EP/ELBW adolescents than controls, which is consistent with some, but not all, reports on preterm survivors born before the 1990s, and younger preterm children born in the 1990s. The high rates of anxiety and mood disorders were similar in both groups, and comparable with population-based estimates.

Longitudinal predictors of psychiatric disorders in very low birth weight adults.

The purpose of this study was to determine risk and protective factors for adult psychiatric disorders in very low birth weight (VLBW, birth weight <1,501 g) survivors. 79 of 154 (51%) VLBW subjects recruited at birth were assessed in early adulthood (24-27 years). Participants were screened for a psychiatric disorder; those elevated were invited to attend a structured clinical interview to determine a clinical diagnosis. Longitudinal variables measured from birth and at ages 2, 5, 14 and 18 years were included in analyses. Perinatal, developmental and social environmental risk factors failed to predict psychiatric disorder in adulthood in this cohort of VLBW survivors. Instead, low self-esteem at age 18 (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1, 1.11, p = 0.05) and the adult social environment (high rates of negative life event stress at the time of assessment: OR = 1.39, CI = 1.10, 1.76, p = 0.02), contributed significantly to adult psychiatric outcomes.

High signal intensity on T2-weighted MR imaging at term-equivalent age in preterm infants does not predict 2-year neurodevelopmental outcomes.

BACKGROUND AND PURPOSE: DEHSI on T2-weighted MR imaging in preterm infants at term-equivalent age has been regarded as an unfavorable marker for neurodevelopmental outcome. The aim of this study was to examine the relationship between the presence and extent of DEHSI and neurodevelopmental outcomes. MATERIALS AND METHODS: We evaluated the MR images of 160 preterm infants at term-equivalent age. The presence of DEHSI was evaluated in separate regions and classified into 5 grades based on the extent of DEHSI. We also examined within those infants with DEHSI, whether typical signal-intensity characteristics of the posterior periventricular crossroads region were visible. Finally, ADC and FA values within the white matter were analyzed. Neurodevelopmental outcomes were assessed at 2-year corrected age with a standardized neurologic examination and the BSID-II. RESULTS: The grade of DEHSI had significant linear trends with increasing ADC and a trend toward lower FA values. However, there was no relationship between the degree of DEHSI and 2-year neurodevelopmental outcomes. In contrast, 13 infants with DEHSI who did not have visible posterior crossroads had poorer neurodevelopmental outcomes compared with infants with visible posterior crossroads. CONCLUSIONS: Although DEHSI may represent disturbances in white matter structure, as illustrated by its relationship to altered ADC and FA values, there is no relationship to short-term neurodevelopment outcome unless there are invisible posterior crossroads, representing a severe form of global high T2 signal intensity.

Prevalence of psychiatric diagnoses in preterm and full-term children, adolescents and young adults: a meta-analysis.

BACKGROUND: Preterm (PT) birth and low birth weight (LBW) are high-prevalence events that are associated with adverse outcomes in the longer term, with vulnerability increasing as maturity at birth decreases. Psychiatric symptomatology appears heightened in PT/LBW survivors, though there are some discordant findings from studies using questionnaire measures, particularly with respect to anxiety and depressive symptoms. METHOD: This article synthesises findings from research using clinical psychiatric diagnostic criteria in PT/LBW individuals aged 10-25 years compared with term-born peers. Key outcomes of interest were the rates of individuals receiving any psychiatric diagnosis and the number of diagnoses of anxiety or depressive disorders. RESULTS: A literature search for studies reporting prevalence of 'any diagnosis' yielded five studies that met inclusion criteria, with a total of 565 PT/LBW and 533 control individuals. Also, five studies were found that reported rates of anxiety/depression (692 PT/LBW and 605 control individuals). The risk of these outcomes was increased for PT/LBW individuals compared with controls [any diagnosis: odds ratio (OR) 3.66, 95% confidence interval (CI) 2.57-5.21; anxiety or depressive disorder: OR 2.86, 95% CI 1.73-4.73]. CONCLUSIONS: The studies reviewed here indicate that, in addition to monitoring and management of medical and cognitive sequelae, the psychological well-being of PT/LBW individuals should be a key part of ongoing care.

Changing long-term outcomes for infants 500-999 g birth weight in Victoria, 1979-2005.

OBJECTIVE: To determine the survival and neurological outcome at 2 years of age of extremely low birthweight (ELBW, birth weight 500-999 g) infants born in the state of Victoria compared with term controls, and contrasted with ELBW cohorts from previous eras. DESIGN AND SETTING: A population-based cohort study of consecutive ELBW infants born during 2005 in the state of Victoria, and also in 1979-1980, 1985-1987, 1991-1992 and 1997. PARTICIPANTS: All 257 live births free of lethal malformations weighing 500-999 g in 2005, 220 randomly selected term, normal birthweight (birth weight >2499 g) controls, and equivalent cohorts born in earlier eras. MAIN OUTCOME MEASURES: Survival rates and quality-adjusted survival rates at 2 years of age, contrasted between cohorts. RESULTS: Of 257 ELBW live births in 2005, 66.9% survived to 2 years of age, significantly lower than the survival rate of 75.2% for 1997 (odds ratio (OR) 0.67, 95% CI 0.45 to 0.99, p=0.046), but not after adjustment for confounders of birth weight, gestational age and gender (adjusted OR 0.73, 95% CI 0.46 to 1.16, p=0.18). This was a reversal of the steady increase in survival rates up to 1997. Rates of blindness, severe developmental delay and severe disability were significantly lower in 2005 than in ELBW survivors from previous eras. Consequently the difference in the quality-adjusted survival rates between 2005 and 1997 was only -3.8% (95% CI -11.4% to 3.7%, p=0.32). CONCLUSIONS: Regional survival rates for ELBW infants have plateaued since the late 1990s, but the neurosensory outcome in survivors has improved in 2005.

Changes in neurodevelopmental outcome at age eight in geographic cohorts of children born at 22-27 weeks' gestational age during the 1990s.

BACKGROUND: The survival rate for children born with gestational ages 22-27 weeks is increasing, and this may be associated with higher rates of disability. The aims of this study were to determine the outcomes at age eight for a regional cohort of children born at 22-27 weeks during 1997, and to compare their rates of disability with a cohort of the same gestational age born in 1991-1992. METHODS: Consecutive children with gestational ages in the range 22-27 weeks born in the state of Victoria, Australia, in 1997 and matched term controls were assessed at 8 years. Outcomes included blindness, deafness, cerebral palsy (CP) and intellectual impairment and disabilities caused by these impairments. These outcomes were compared with a cohort of 22-27-week and term children born in 1991-1992 in the same region. RESULTS: Follow-up rates for the 1997 cohort at 8 years of age were 95% (144/151) for 22-27 weeks survivors and 89% (173/195) for controls. Rates of disability were substantially higher in the preterm cohort than the controls. The 1997 and 1991-1992 preterm cohorts had similar rates of moderate or severe disability (19%), however the rate of mild impairment was greater in 1997 (40% vs 24%). Rates of disability were almost identical in control groups. Intellectual impairment and CP were the major reasons for the higher rates of disability. CONCLUSIONS: The high prevalence of adverse neurodevelopmental outcome in children born at 22-27 weeks compared with term controls at school age persists, and may even be increasing over time.

The stability of the diagnosis of developmental disability between ages 2 and 8 in a geographic cohort of very preterm children born in 1997.

OBJECTIVE: Studies reporting the developmental outcomes for very preterm (VPT) children often focus on development at age 2 years. The aim of this study was to assess the stability of the rates of diagnosis of developmental disability from age 2 to 8 years in a regional cohort of VPT and extremely low-birth weight (ELBW) children and compare these with term controls. METHODS: VPT (22-27 completed weeks of gestation) and ELBW (birth weight 500-999 g) children and matched term controls born in Victoria, Australia, in 1997 were enrolled at birth in a regional prospective longitudinal study. Outcomes were assessed at ages 2 and 8 years. RESULTS: Of the 283 VPT/ELBW live births, 71% survived to age 8 years and 94% were assessed. Of the 199 controls, 100% survived to age 8 years and 86.9% were assessed. At age 2 years, the rates of nil, mild, moderate and severe disabilities in the VPT/ELBW children were respectively 51.9%, 20.9%, 13.4% and 13.9%; and at age 8 years, 43.9%, 36.9%, 10.7% and 8.6%. The Cohen κ statistic revealed poor agreement between disability status at ages 2 and 8 years for VPT/ELBW children (0.20, p<0.001) but a higher level of agreement (0.37, p<0.001) for the control children. This was primarily driven by differences in classification of cognitive disability between ages 2 and 8 years. CONCLUSIONS: Developmental outcomes at age 2 years are only a moderate predictor of long-term outcome and are not a reliable end point for follow-up studies of VPT and ELBW children.

Abnormal white matter signal on MR imaging is related to abnormal tissue microstructure.

BACKGROUND AND PURPOSE: White matter signal-intensity abnormalities (WMSA) on MR imaging are related to adverse neurodevelopmental outcome in extremely preterm infants. Diffusion tensor imaging (DTI) may detect alterations in cerebral white matter microstructure and thus may help confirm the pathologic basis of WMSA. This study aimed to relate regional DTI measures with severity of WMSA in very preterm infants. MATERIALS AND METHODS: One hundred eleven preterm infants (birth weight, <1250 g and/or gestational age, <30 weeks) were scanned at term-equivalent age (1.5T). WMSA were classified as normal, focal, or extensive. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial (lambda1), and radial ([lambda2 + lambda3]/2) diffusivity were calculated in 12 regions of interest placed in the bilateral posterior limbs of the internal capsule, frontal (superior and inferior), sensorimotor, and occipital (superior and inferior) white matter regions. Data were compared by using 1-way analysis of variance, with a Bonferroni correction for multiple comparisons. RESULTS: Thirty-nine infants had normal, 59 infants had focal, and 13 infants had extensive WMSA. Compared with infants with normal or focal WMSA, infants with extensive WMSA had significantly lower FA in the internal capsule (P < .001), right inferior frontal regions (P < .05), and right superior occipital regions (P = .01); and higher radial diffusivity in the right internal capsule (P = .005), bilateral sensorimotor (P < .05), and right superior occipital regions (P < .05). Compared with infants with normal WMSA, infants with extensive WMSA had significantly higher ADC in bilateral sensorimotor regions (P < .01) and right superior occipital regions (P = .01), and lower axial diffusivity in the bilateral sensorimotor regions (P < .05). CONCLUSIONS: There are significant region-specific changes in ADC, FA, radial diffusivity, and axial diffusivity in preterm infants with extensive WMSA. Altered radial diffusivity was most prominent. This implies that disrupted premyelinating oligodendroglia is the major correlate with extensive WMSA rather than axonal pathology.

A novel quantitative simple brain metric using MR imaging for preterm infants.

BACKGROUND AND PURPOSE: The application of volumetric techniques to preterm infants has revealed brain volume reductions. Such quantitative data are not available in routine neonatal radiologic care. The objective of this study was to develop simple brain metrics to compare brain size in preterm and term infants and to correlate these metrics with brain volumes from volumetric MR imaging techniques. MATERIALS AND METHODS: MR images from 189 preterm infants <30 weeks' gestational age or <1250 g birthweight scanned at term-equivalent age and 36 term infants were studied. Fifteen tissue and fluid measures were systematically evaluated on 4 selected sections. The results were correlated with total brain, gray matter, white matter, and CSF volumes. RESULTS: The mean bifrontal, biparietal, and transverse cerebellar diameters were reduced (-11.6%, 95% confidence interval [CI], -13.8% to -9.3%; -12%, 95% CI, -14% to -9.8%; and -8.7%, 95% CI, -10.5% to -7% respectively) and the mean left ventricle diameter was increased (+22.3%, 95% CI, 2.9%-41.6%) in preterm infants (P < .01). Strong correlations were found between the bifrontal and biparietal measures with total brain tissue volume, whereas the size of the ventricles and the interhemispheric measure correlated with CSF volume. Intraobserver reliability was high (intraclass correlation coefficients [ICC], >0.7), where interobserver agreement was acceptable for tissue measures (ICC, >0.6) but lower for fluid measures (ICC, <0.4). CONCLUSIONS: Simple brain metrics at term-equivalent age showed smaller brain diameters and increased ventricle size in preterm infants compared with full-term infants. These measures represent a reliable and easily applicable method to quantify brain growth and assess brain atrophy in this at-risk population.

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

BACKGROUND: Epidemiological and basic science evidence suggests that magnesium sulphate before birth may be neuroprotective for the fetus. OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate as a neuroprotective agent when given to women considered at risk of preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (October 2006), CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE (1966 to October 2006), EMBASE (1980 to October 2006), Current Contents (1992 to October 2006), references of retrieved articles, and abstracts submitted to the Society for Pediatric Research (1996 to 2006). SELECTION CRITERIA: Randomised controlled trials of antenatal magnesium sulphate therapy given to women threatening or likely to give birth at less than 37 weeks' gestational age. DATA COLLECTION AND ANALYSIS: We independently extracted data regarding clinical outcomes including paediatric mortality, neurologic outcome of survivors (including blindness, deafness, cerebral palsy and major neurosensory disability), and maternal complications and side-effects. At least two authors assessed trial eligibility and quality, and extracted data. MAIN RESULTS: Four trials (3701 babies) were eligible for this review. No statistically significant effect of antenatal magnesium sulphate therapy was detected on any major paediatric outcome, including mortality (e.g., paediatric mortality relative risk (RR) 0.97; 95% confidence interval (CI) 0.74 to 1.28; four trials; 3701 infants), and neurological outcomes in the first few years of life, including cerebral palsy (RR 0.77; 95% CI 0.56 to 1.06; four trials; 3701 infants), neurological impairments or disabilities. There were also no significant effects of antenatal magnesium therapy on combined rates of mortality with neurologic outcomes. There was a significant reduction in the rate of substantial gross motor dysfunction (RR 0.56; 95% CI 0.33 to 0.97; two trials; 2848 infants). There were higher rates of minor maternal side-effects in the magnesium groups, but no significant effects on major maternal complications. AUTHORS' CONCLUSIONS: The role for antenatal magnesium sulphate therapy as a neuroprotective agent for the preterm fetus is not yet established. Given the possible beneficial effects of magnesium sulphate on gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurologic effects, particularly on motor or cognitive function. Further information will be available from one of the studies where outcomes are being evaluated again at eight to nine years of age, and from another trial currently in progress.

Developmental coordination disorder at 8 years of age in a regional cohort of extremely-low-birthweight or very preterm infants.

The aims of this study were to determine the motor outcome of extremely-low-birthweight (ELBW; <1000g) or very preterm (<28wks) children compared with normal birthweight (NBW) children, to establish the perinatal associations of developmental coordination disorder (DCD) and its cognitive and behavioural consequences. Participants were consecutive surviving ELBW or very preterm children and randomly selected NBW(>2499g) children born in the state of Victoria, Australia, in 1991 or 1992. Main outcomes were: (1) results of the Movement Assessment Battery for Children (MABC) at 8 years of age; (2) cognitive function; (3) academic progress; and (4) behaviour. Of 298 consecutive ELBW/very preterm survivors, 255 (85.6%; 117 males, 138 females) had the MABC at a mean age of 8 years 8 months. More ELBW/very preterm children (9.5%) had DCD than the NBW group (2%, p=0.001). Only male sex increased the likelihood of DCD in ELBW/very preterm children (p=0.017). ELBW/very preterm children with DCD had worse cognitive function and academic test scores (up to 1SD below those without DCD); they also had more adaptive behaviour and externalizing problems, but not internalizing problems. DCD is more common in ELBW/very preterm children, has few perinatal correlates, and is associated with poor cognitive and academic performance as well as increased behaviour problems.

Early developmental intervention programs post hospital discharge to prevent motor and cognitive impairments in preterm infants.

BACKGROUND: Infants born preterm are at increased risk of developing cognitive and motor impairments compared with infants born at term. Early developmental interventions have been used in the clinical setting with the aim of improving the overall functional outcome for these infants. However, the benefit of these programs remains unclear. OBJECTIVES: To review the effectiveness of early developmental intervention post-discharge from hospital for preterm (< 37 weeks) infants on motor or cognitive development. SEARCH STRATEGY: The Cochrane Neonatal Review group search strategy was used to identify randomised and quasi-randomised controlled trials of early developmental interventions post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE Advanced, CINAHL, PsychINFO and EMBASE (1966 through February 2006). SELECTION CRITERIA: Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programs that commenced within the first 12 months of life for infants born at < 37 weeks with no major congenital abnormalities. Intervention could commence as an inpatient; however, a post discharge component was necessary to be included in this review. The outcome measures were not pre-specified other than that they had to assess cognitive and/or motor ability. The rates of intellectual impairment, cerebral palsy and development co-ordination disorder were also documented. DATA COLLECTION AND ANALYSIS: Data were extracted and entered by two independent review authors. Cognitive and motor outcomes were pooled in three age groups - infant (0 to 2 years), preschool (3 to < 5 years) or school age (5 to 17 years). Meta-analysis was carried out using RevMan 4.2 to determine the effects of early developmental intervention in the short (0 to 2 years), medium (3 to < 5 years) and long term (5 to 17 years). Subgroup analysis was carried out in relation to; gestational age, birthweight, brain injury, commencement of intervention, focus of intervention and study quality. MAIN RESULTS: Sixteen studies met the inclusion criteria (2379 randomised patients). Six of these studies were RCTs and had strong methodological quality. There was variability with regard to the focus and intensity of the intervention, and in length of follow-up. Meta-analysis concluded that intervention improved cognitive outcomes at infant age (developmental quotient [DQ]: standard mean difference [SMD] 0.46 SD; 95% CI 0.36 0.57; P < 0.0001), and at preschool age (intelligence quotient [IQ]; SMD 0.46 SD; 95%CI 0.33, 0.59; P < 0.0001). However, this effect was not sustained at school age (IQ; SMD 0.02 SD; 95% CI -0.10, 0.14; P = 0.71). There was significant heterogeneity between studies for cognitive outcomes at infant and school ages. There was little evidence of an effect of early intervention on motor outcomes in the short, medium or long-term, but there were only two studies reporting outcomes beyond 2 years. AUTHORS' CONCLUSIONS: Early intervention programs for preterm infants have a positive influence on cognitive outcomes in the short to medium term. However, there was significant heterogeneity between the interventions included in this review. Further research is needed to determine which early developmental interventions are the most effective at improving cognitive and motor outcomes, and on the longer-term effects of these programs. Cost-effectiveness and access to services should also be evaluated since they are important factors when considering implementation of an early developmental intervention program for a preterm infant.

Newer approaches to the diagnosis of early onset neonatal sepsis.

Accurate and timely diagnosis of early onset neonatal sepsis remains challenging to the clinician and the laboratory. A test with a rapid turnaround time with 100% sensitivity, rather than high specificity, which allows accurate diagnosis and appropriate antimicrobial treatment or which allows antibiotics to be safely withheld in non-infected infants, is desirable. Many potential markers (acute phase reactants, cell surface markers, cytokines) are not routinely available to the laboratory, and most likely combinations of markers will ensure greater diagnostic accuracy. In the future, molecular biology techniques offer the prospect of rapid identification of both pathogens and antimicrobial resistance markers.

Neurodevelopmental sequelae of intraventricular haemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants.

BACKGROUND: Major grades of intraventricular haemorrhage (IVH) are associated with adverse neurodevelopmental sequelae in early childhood but the extent of problems in specific cognitive areas, such as executive function, and the contribution of lesser grades of IVH to neurodevelopmental problems at school age are not well described. AIMS: To determine the neuromotor, cognitive and educational outcome of extremely low birthweight (ELBW, birthweight <1000 g) or very preterm (<28 weeks) infants at 8 years of age related to the severity of IVH diagnosed in the newborn period. DESIGN: Regional cohort study. PATIENTS: Consecutive surviving children of either birthweight <1000 g or gestational age <28 weeks born in the state of Victoria in 1991 or 1992. MAIN OUTCOME MEASURES: Neurological impairments and disabilities, cognitive function and academic progress. RESULTS: Of 298 consecutive ELBW/very preterm survivors 270 (90.6%) with cranial ultrasound data were assessed at 8 years of age. Cerebral palsy, poor motor performance and major neurosensory disability were more prevalent with increasing severity of IVH. Cognitive functioning across domains was worse with increasing severity of IVH. Most of the differences were attributable to the few (n=6) survivors who had grade 4 IVH; there were few substantial differences between survivors with lesser grades of IVH. CONCLUSIONS: Neurodevelopmental dysfunction at school age in ELBW/very preterm survivors varies little with increasing severity of IVH, with the exception of grade 4 IVH.

Neonatal resuscitation 3: manometer use in a model of face mask ventilation.

BACKGROUND: Adequate ventilation is the key to successful neonatal resuscitation. Positive pressure ventilation (PPV) is initiated with manual ventilation devices via face masks. These devices may be used with a manometer to measure airway pressures delivered. The expiratory tidal volume measured at the mask (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation. AIM: To assess the effect of viewing a manometer on the peak inspiratory pressures used, the volume delivered, and leakage from the face mask during PPV with two manual ventilation devices in a model of neonatal resuscitation. METHODS: Participants gave PPV to a modified resuscitation mannequin using a Laerdal infant resuscitator and a Neopuff infant resuscitator at specified pressures ensuring adequate chest wall excursion. Each participant gave PPV to the mannequin with each device twice, viewing the manometer on one occasion and unable to see the manometer on the other. Data from participants were averaged for each device used with the manometer and without the manometer separately. RESULTS: A total of 7767 inflations delivered by the 18 participants were recorded and analysed. Peak inspiratory pressures delivered were lower with the Laerdal device. There were no differences in leakage from the face mask or volumes delivered. Whether or not the manometer was visible made no difference to any measured variable. CONCLUSIONS: Viewing a manometer during PPV in this model of neonatal resuscitation does not affect the airway pressure or tidal volumes delivered or the degree of leakage from the face mask.