Obstetrics and Gynaecology - Research Publications

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    Morbidity and mortality in hospitalised neonates in central Vietnam
    Tran, HT ; Doyle, LW ; Lee, KJ ; Dang, NM ; Graham, SM (WILEY, 2015-05)
    AIM: This study explored neonatal morbidity and mortality in hospitalised patients in central Vietnam and risk factors associated with mortality. METHODS: We conducted a prospective cohort study of all newborn infants (<28 days) hospitalised in a neonatal unit over a 1-year period and followed until discharge. The main outcome measures were case fatality rate and the rate of different clinical diagnoses. RESULTS: There were 2555 admissions during the study period. The leading primary causes of admissions were infections (41%), haematological problems such as jaundice (23%) and prematurity and its complications (18%). The overall case fatality rate was 8.6%, and it was 59% among very low-birthweight (<1500 g) neonates. Mortality was inversely associated with birthweight and gestational age. Of the 220 deaths, 57% occurred within the first 7 days of life. Although the causes of death were often multifactorial, the leading primary causes were infections (32%), prematurity and its complications (25%), birth defects (24%) and birth asphyxia (6%). Risk factors associated with death were being outborn, early gestational age, small for gestational age, confirmed sepsis and birth defects. CONCLUSION: Mortality rates were high among hospitalised neonates in central Vietnam, and this paper suggests interventions that might improve outcomes.
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    A high burden of late-onset sepsis among newborns admitted to the largest neonatal unit in central Vietnam
    Tran, HT ; Doyle, LW ; Lee, KJ ; Dang, NM ; Graham, SM (NATURE PUBLISHING GROUP, 2015-10)
    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.
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    The role of social risk in an early preventative care programme for infants born very preterm: a randomized controlled trial
    Spittle, AJ ; Treyvaud, K ; Lee, KJ ; Anderson, PJ ; Doyle, LW (WILEY, 2018-01)
    AIM: To examine the differential effects of an early intervention programme for infants born preterm on neurodevelopment and parental mental health according to family social risk. METHOD: One hundred and twenty infants born earlier than 30 weeks' gestation were randomized to early intervention (n=61) or control groups (n=59). Cognitive, language, and motor outcomes were assessed by blinded assessors at 2 years, 4 years, and 8 years, and primary caregivers completed questionnaires on their anxiety and depression. Outcomes at each time point were compared between groups using linear regression with an interaction term for social risk (higher/lower). RESULTS: There was evidence of interactions between intervention group and social risk for cognition at 2 years and 4 years, motor function at 4 years, and language at 8 years, with a greater intervention effect in children from higher social risk environments. In contrast, the impact of early intervention on parental depressive symptoms was greater for parents of lower social risk than for those of higher social risk. INTERPRETATION: Effects of early intervention on outcomes for children born preterm and their caregivers varied according to family social risk. Family social risk should be considered when implementing early intervention programmes for children born preterm and their families. WHAT THIS PAPER ADDS: Intervention is associated with better early cognitive functioning for children in higher social risk families. Positive effects of intervention for the high risk group were not sustained at school-age. Intervention has a greater effect on primary caregiver mental health in the lower social risk group compared with higher social risk.
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    Preterm and term-equivalent age general movements and 1-year neurodevelopmental outcomes for infants born before 30weeks' gestation
    Olsen, JE ; Allinson, LG ; Doyle, LW ; Brown, NC ; Lee, KJ ; Eeles, AL ; Cheong, JLY ; Spittle, AJ (WILEY, 2018-01)
    AIM: To examine the associations between Prechtl's General Movements Assessment (GMA), conducted from birth to term-equivalent age, and neurodevelopmental outcomes at 12 months corrected age, in infants born very preterm. METHOD: One hundred and thirty-seven infants born before 30 weeks' gestation had serial GMA (categorized as 'normal' or 'abnormal') before term and at term-equivalent age. At 12 months corrected age, neurodevelopment was assessed using the Alberta Infant Motor Scale (AIMS); Neurological, Sensory, Motor, Developmental Assessment (NSMDA); and Touwen Infant Neurological Examination (TINE). The relationships between GMA at four time points and 12-month neurodevelopmental assessments were examined using regression models. RESULTS: Abnormal GMA at all time points were associated with worse continuous scores on the AIMS, NSMDA, and TINE (p<0.05). Abnormal GMA before term and at term-equivalent age were associated with increased odds of mild-severe dysfunction on the NSMDA (odds ratio [OR] 4.26, 95% confidence interval [CI] 1.55-11.71, p<0.01; and OR 4.16, 95% CI 1.55-11.17, p<0.01 respectively) and abnormal GMA before term with increased odds of suboptimal-abnormal motor function on the TINE (OR 2.75, 95% CI 1.10-6.85, p=0.03). INTERPRETATION: Abnormal GMA before term and at term-equivalent age were associated with worse neurodevelopment at 12 months corrected age in children born very preterm. WHAT THIS PAPER ADDS: Abnormal general movements before term predict developmental deficits at 1 year in infants born very preterm. General Movements Assessment before term identifies at-risk infants born very preterm.
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    Predictive value of the Movement Assessment Battery for Children - Second Edition at 4years, for motor impairment at 8years in children born preterm
    Griffiths, A ; Morgan, P ; Anderson, PJ ; Doyle, LW ; Lee, KJ ; Spittle, AJ (WILEY, 2017-05)
    AIM: To assess the predictive validity at 4 years of the Movement Assessment Battery for Children - Second Edition (MABC-2) for motor impairment at 8 years in children born preterm. We also aimed to determine if sex, cognition, medical, or social risks were associated with motor impairment at 8 years or with a change in MABC-2 score between 4 years and 8 years. METHOD: Ninety-six children born at less than 30 weeks' gestation were assessed with the MABC-2 at 4 years and 8 years of age. Motor impairment was defined as less than or equal to the 5th centile. The Differential Ability Scales - Second Edition (DAS-II) was used to measure General Conceptual Ability (GCA) at 4 years, with a score <90 defined as 'below average'. RESULTS: There was a strong association between the MABC-2 total standard scores at 4 years and 8 years (59% variance explained, regression coefficient=0.80, 95% confidence interval [CI] 0.69-0.91, p<0.001). The MABC-2 at 4 years had high sensitivity (79%) and specificity (93%) for predicting motor impairment at 8 years. Below average cognition and higher medical risk were associated with increased odds of motor impairment at 8 years (odds ratio [OR]=15.3, 95% CI 4.19-55.8, p<0.001, and OR=3.77, 95% CI 1.28-11.1, p=0.016 respectively). Sex and social risk did not appear to be associated with motor impairment at 8 years. There was little evidence that any variables were related to change in MABC-2 score between 4 years and 8 years. INTERPRETATION: The MABC-2 at 4 years is predictive of motor functioning in middle childhood. Below average cognition and higher medical risk may be predictors of motor impairment.
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    Neurobehaviour at term-equivalent age and neurodevelopmental outcomes at 2 years in infants born moderate-to-late preterm
    Spittle, AJ ; Walsh, JM ; Potter, C ; Mcinnes, E ; Olsen, JE ; Lee, KJ ; Anderson, PJ ; Doyle, LW ; Cheong, JLY (WILEY, 2017-02)
    AIM: To examine the association between newborn neurobehavioural assessments and neurodevelopmental outcomes at 2 years in infants born moderate-to-late preterm (MLPT). METHOD: Two-hundred and one infants born MLPT (born 32-36+6 wks' gestation) were assessed with the Hammersmith Neonatal Neurological Examination (HNNE) and NICU Network Neurobehavioral Scale (NNNS), with suboptimal performance defined as scores lower than the 10th centile. Development was assessed at 2 years corrected age with the Bayley Scales of Infant and Toddler Development 3rd Edition, with delay defined as scores less than 1 standard deviation (SD) below the mean. The relationships between neurobehaviour at term and Bayley-III cognitive, language, and motor scales at 2 years were examined using linear regression. RESULTS: Increased odds for cognitive delay were associated with suboptimal HNNE total scores (odds ratio [OR] 2.66; 95% confidence interval [CI] 1.14-6.23, p=0.020) and suboptimal NNNS excitability (OR 3.01; 95% CI 1.33-6.82, p=0.008) and lethargy (OR 4.05; 95% CI 1.75-9.31, p=0.001) scores. Suboptimal lethargy scores on the NNNS were associated with increased odds of language (OR 5.64; 95% CI 1.33-23.85, p=0.019) and motor delay (OR: 6.86; 95% CI 1.64-28.71, p=0.08). INTERPRETATION: Suboptimal performance on specific aspects of newborn neurobehavioural assessments is associated with neurodevelopmental delay at 2 years in children born MLPT.
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    White matter microstructure is associated with language in children born very preterm
    Murner-Lavanchy, IM ; Kelly, CE ; Reidy, N ; Doyle, LW ; Lee, KJ ; Inder, T ; Thompson, DK ; Morgan, AT ; Anderson, PJ (ELSEVIER SCI LTD, 2018)
    Very preterm birth is associated with altered white matter microstructure and language difficulties, which may compromise communication, social function and academic achievement, but the relationship between these two factors is unclear. The aim of this study was to explore associations between white matter microstructure and language domains of semantics, grammar and phonological awareness at 7-years of age on a whole-brain level and within the arcuate fasciculus, an important language pathway, in very preterm and term-born children. Language was assessed in 145 very preterm-born (<30 weeks' gestation and/or <1250 g birth weight) and 33 term-born children aged 7 years. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), axon orientation dispersion and axon density were estimated from diffusion magnetic resonance images also obtained at 7 years. The correlation between diffusion values and language was assessed using Tract-Based Spatial Statistics (TBSS). The arcuate fasciculus was delineated using constrained spherical deconvolution tractography and diffusion parameters from this tract were related to language measures using linear regression. While there was evidence for widespread associations between white matter microstructure and language, there was little evidence of differences in these associations between very preterm and term-born groups. TBSS analyses revealed that higher FA and lower AD, RD, and MD in major fibre tracts, including those subserving language, were associated with better semantic, grammar and phonological awareness performance. Higher axon density in widespread fibre tracts was also associated with better semantic performance. The tractography analyses of the arcuate fasciculus showed some evidence for associations between white matter microstructure and language outcomes. White matter microstructural organisation in widespread fibre tracts, including language-relevant pathways, was associated with language performance in whole-brain and tract-based analyses. The associations were similar for very preterm and term-born groups, despite very preterm children performing more poorly across language domains.
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    Neonatal basal ganglia and thalamic volumes: very preterm birth and 7-year neurodevelopmental outcomes
    Loh, WY ; Anderson, PJ ; Cheong, JLY ; Spittle, AJ ; Chen, J ; Lee, KJ ; Molesworth, C ; Inder, TE ; Connelly, A ; Doyle, LW ; Thompson, DK (NATURE PUBLISHING GROUP, 2017-12)
    BackgroundThis study aims to (i) compare volumes of individual basal ganglia nuclei (caudate nucleus, pallidum, and putamen) and the thalamus between very preterm (VP) and term-born infants at term-equivalent age; (ii) explore neonatal basal ganglia and thalamic volume relationships with 7-year neurodevelopmental outcomes, and whether these relationships differed between VP and term-born children.Methods210 VP (<30 weeks' gestational age) and 39 term-born (≥37 weeks' gestational age) infants underwent brain magnetic resonance imaging at term-equivalent age, and deep gray matter volumes of interest were automatically generated. 186 VP and 37 term-born children were assessed for a range of neurodevelopmental measures at age 7 years.ResultsAll deep gray matter structures examined were smaller in VP infants compared with controls at term-equivalent age; ranging from (percentage mean difference (95% confidence intervals) -6.2% (-10.2%, -2.2%) for the putamen, to -9.5% (-13.9%, -5.1%) for the caudate nucleus. Neonatal basal ganglia and thalamic volumes were positively related to motor, intelligence quotient, and academic outcomes at age 7 years, with mostly similar relationships in the VP and control groups.ConclusionVP birth results in smaller basal ganglia and thalamic volumes at term-equivalent age, and these smaller volumes are related to a range of 7-year neurodevelopmental deficits in VP children.
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    Contribution of Brain Size to IQ and Educational Underperformance in Extremely Preterm Adolescents
    Cheong, JLY ; Anderson, PJ ; Roberts, G ; Burnett, AC ; Lee, KJ ; Thompson, DK ; Molloy, C ; Wilson-Ching, M ; Connelly, A ; Seal, ML ; Wood, SJ ; Doyle, LW ; Lidzba, K (PUBLIC LIBRARY SCIENCE, 2013-10-09)
    OBJECTIVES: Extremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (< 28 weeks) and term-born (≥ 37 weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls. METHODS: Longitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively. RESULTS: Brain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls. CONCLUSIONS: EP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP.
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    Preventing academic difficulties in preterm children: a randomised controlled trial of an adaptive working memory training intervention - IMPRINT study
    Pascoe, L ; Roberts, G ; Doyle, LW ; Lee, KJ ; Thompson, DK ; Seal, ML ; Josev, EK ; Nosarti, C ; Gathercole, S ; Anderson, PJ (BMC, 2013-09-16)
    BACKGROUND: Very preterm children exhibit difficulties in working memory, a key cognitive ability vital to learning information and the development of academic skills. Previous research suggests that an adaptive working memory training intervention (Cogmed) may improve working memory and other cognitive and behavioural domains, although further randomised controlled trials employing long-term outcomes are needed, and with populations at risk for working memory deficits, such as children born preterm.In a cohort of extremely preterm (<28 weeks' gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess the effectiveness of Cogmed in improving academic functioning 2 years' post-intervention. Secondary objectives are to assess the effectiveness of Cogmed in improving working memory and attention 2 weeks', 12 months' and 24 months' post-intervention, and to investigate training related neuroplasticity in working memory neural networks 2 weeks' post-intervention. METHODS/DESIGN: This double-blind, placebo-controlled, randomised controlled trial aims to recruit 126 extremely preterm/extremely low birthweight 7-year-old children. Children attending mainstream school without major intellectual, sensory or physical impairments will be eligible. Participating children will undergo an extensive baseline cognitive assessment before being randomised to either an adaptive or placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory training program consisting of 25 sessions completed over a 5 to 7 week period. Each training session takes approximately 35 minutes and will be completed in the child's home. Structural, diffusion and functional Magnetic Resonance Imaging, which is optional for participants, will be completed prior to and 2 weeks following the training period. Follow-up assessments focusing on academic skills (primary outcome), working memory and attention (secondary outcomes) will be conducted at 2 weeks', 12 months' and 24 months' post-intervention. DISCUSSION: To our knowledge, this study will be the first randomised controlled trial to (a) assess the effectiveness of Cogmed in school-aged extremely preterm/extremely low birthweight children, while incorporating advanced imaging techniques to investigate neural changes associated with adaptive working memory training, and (b) employ long-term follow-up to assess the potential benefit of improved working memory on academic functioning. If effective, Cogmed would serve as a valuable, available intervention for improving developmental outcomes for this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000124831.