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4B BAPM/NNS: Brain

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4.7 NEONATAL RESUSCITATION AND CHILDHOOD COGNITIVE OUTCOMES

D. E. Odd, A. Whitelaw, D. Gunnell, G. Lewis. University of Bristol, Bristol, UK

Background: Neonatal encephalopathy has been considered an essential marker for perinatal cerebral injury. However, milder insults may cause subtle defects in functioning. The evidence for the long-term impact of such milder insults is contentious. The aim is to determine whether infants receiving resuscitation after birth have reduced IQ scores in childhood.

Methods: The study is based on 11 513 term infants from the Avon Longitudinal Study of Parents and Children. Three groups were defined: infants who received resuscitation at birth but no further neonatal care (n  =  818); those receiving resuscitation who developed subsequent encephalopathy (n  =  63) and those not requiring resuscitation or further care (n  =  10 632). Cognition was assessed at 8 years with a low score defined as an IQ of <80. Results were adjusted for other covariates. Chained equations were used to impute missing values of covariates only.

Results: Resuscitated infants without encephalopathy had an increased risk of low global IQ (odds ratio (OR) 1.65 (1.13 to 2.41)) and some evidence for a low verbal IQ (OR 1.41 (0.89 to 2.22)). They had similar performance IQ to the reference group (OR 1.03 (0.75 to 1.42). Infants with encephalopathy had an increased risk of low global (OR 6.21 (1.59 to 24.33)) and performance (OR 4.60 (1.49 to 14.19)) IQ and weak evidence for an increased risk of a poor verbal IQ (OR 1.95 (0.23 to 16.36)).

Conclusions: Infants who received resuscitation had an increased risk of low IQ scores, even if they remained well in the neonatal period. These data are supportive of the “continuum of reproductive casualty” and support the association between mild fetal compromise and cognition.

4.8 EXTREMELY PRETERM CHILDREN AT 11 YEARS: HOW DO THEY FARE AT SCHOOL?

S. Johnson1, D. Wolke2, N. Marlow1. 1University of Nottingham, Nottingham, UK, 2University of Warwick, Warwick, UK

Academic attainment and special educational needs (SEN) were assessed in a whole population of children born <26 weeks in the United Kingdom and Ireland in 1995 (EPICure Study). 219 (71%) of 308 survivors were assessed with a comparison group of 153 classmates born at term (mean age 10 years 11 months). Standardised tests of reading and maths were administered and teachers completed questionnaires regarding academic attainment and SEN provision. Extremely preterm children had significantly lower reading (−18 points; −22 to −15) and maths (−27 points; −31 to −23) scores than classmates. 30% of extremely preterm children were classified with serious impairment (scores −2 SD) in reading and 45% with serious impairment in maths, compared with 1.3% of classmates. 29 (13%) extremely preterm children attended a special school. In mainstream schools, teachers rated 50% of extremely preterm children with performance below the class average in national curriculum subjects compared with 5% of classmates (odds ratio (OR) 18; 8 to 41). 55% of extremely preterm children had SEN compared with 11% of classmates (OR 10; 6 to 18) and 58% received additional educational resources compared with 13% of classmates (OR 10; 5 to 17). 24% of extremely preterm children in mainstream schools in England had a “Statement of SEN” documenting the child’s complex learning difficulties and resource needs, compared with 0.8% of classmates (OR 40; 5 to 300). Extremely preterm children are at risk for learning impairments and require a high degree of SEN resource provision at 11 years. Such provision may increase as extremely preterm children approach the transition to secondary education.

4.9 PATTERN AND TIMING OF BRAIN INJURY ON ADMISSION SCANS ASSESSED USING CRANIAL ULTRASOUND IN INFANTS WITH NEONATAL ENCEPHALOPATHY COMPARED WITH LOW-RISK INFANTS IN MULAGO UNIVERSITY HOSPITAL, KAMPALA, UGANDA

C. F. Hagmann1, N. J. Robertson1, M. Nakakeeto3, D. Acolet2, F. Cowan2. 1EGA UCL Institute for Women’s Health, University College London, London, UK, 2Department of Paediatrics, Hammersmith Hospital, Imperial College, London, UK, 3Neonatal Unit, Mulago University Hospital, Kampala, Uganda

Introduction: The incidence of term neonatal encephalopathy (NE) in low-resource settings is 8/1000 livebirths.1 A safety and feasibility study of hypothermia for NE was undertaken at Mulago Hospital.

Aims: To assess, using cranial ultrasound (cUS), the pattern and timing of brain injury on admission in infants with NE compared with controls.

Methods: Term infants with NE admitted to the special care baby unit were screened for eligibility and scanned after random assignment using the z.oneUltra cUS machine. Normal term infants were recruited from postnatal wards. cUS data were classified by consensus into one out of eight injury categories from the predominant pattern and severity of change.2 Abnormality equal to or greather than category 4 within 24 h of delivery suggested injury starting before birth; scans >24 h were not used for such comment.

Results: See table.

Conclusions: White matter (WM) plus basal ganglia (BG)/thalamic injury is the predominant pattern of abnormality; BG/thalamic or WM abnormality alone occurred less often. Such abnormality did not occur in controls. No established atrophy was seen but the data suggest that injury affecting BG/thalami plus WM may start before birth in 45% of infants with early scans.

4.10 PROTON MAGNETIC RESONANCE SPECTROSCOPY AND THE FETAL BRAIN IN NORMALLY GROWN AND GROWTH-RESTRICTED FETUSES

L. Story, M. Damodaram, M. Wylezinska-Arridge, S. Kumar, M. Rutherford. Imperial College, London, UK

Introduction: Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique for assessing the metabolism of human tissue. Brain proton MRS can predict prognosis after perinatal hypoxic ischaemia in neonates: decreased levels of N-acetyl aspartate (NAA), a neuronal marker and high lactate being associated with poor neurodevelopmental outcome.

This study uses advanced MRI techniques to investigate the effects of intrauterine growth restriction (IUGR) on fetal brain development and hypothesises that IUGR will be associated with lower NAA levels and increased lactate in the brain.

Methods: Women are scanned at 1.5 Tesla, following conventional imaging, spectra are acquired with a PRESS_SV sequence at three echo times of 270, 136 and 42 ms. Spectral analysis is performed using JMRUI software. Signals are summed, spectra phased and referenced to the water peak and peaks identified by their chemical shift.

Results: To date 13 fetuses have been scanned, four controls and nine with IUGR, one a recent intrauterine death. Median gestational age was 28 + 4 weeks (range 23–34). 13 acquisitions were analyzable, four normal fetuses, nine with IUGR. Demonstrable peaks included NAA, choline, creatine and Myo-inositol in all spectra. Lactate was identified in three fetuses: all severe IUGR including the recent intrauterine death.

Conclusions: MRS of the fetal brain is a challenging technique because of fetal motion but shows promise for studying the in-vivo metabolism of the fetal brain. The significance of lactate and its relationship to other parameters of fetal growth and development and placental function is being investigated.

4.11 TREATMENT WITH COOLING FOLLOWING PERINATAL ASPHYXIA: PRELIMINARY DATA FROM THE UK TOBY COOLING REGISTER

D. V. Azzopardi1, B. W. Strohm2, E. Juszczak2. 1Imperial College, London, UK, 2NPEU University of Oxford, Oxford, UK

The UK TOBY Cooling Register was established in December 2006, following completion of recruitment into the TOBY study. The TOBY study is a randomised trial of whole-body cooling to 33.5°C rectal for 72 h after perinatal asphyxia. 325 babies were recruited to the TOBY study over 4 years and the results of the study will be available after the 18-month follow-up assessment data have been analyzed, late in 2008.

Following completion of recruitment, many TOBY study investigators intended to offer cooling as a treatment for babies born with neonatal encephalopathy on the basis of existing evidence from published studies.1 The UK TOBY Cooling Register of treatment with moderate hypothermia was set up in order to collect data about all episodes of induced hypothermia for the treatment of neonatal encephalopathy in the United Kingdom.

The aims of the register are: to determine the likely demand in the United Kingdom for treatment of newborn infants with cooling; to identify adverse events associated with treatment with cooling; to ensure uniform clinical management to a high standard in a high-risk group of infants; to support further clinical trials of neuroprotection after asphyxia.

Since the inception of the register in December 2006, 132 infants have been notified (up to January 2008) from 28 centres. Cooling was initiated at x(y − z)2 h after birth, and was maintained within the target range of 33–34°C rectal x(y − z)%1 of cooling period.3 Details of patient characteristics, neurological state, complications and outcome at discharge from hospital will be discussed.

  • 74.3 (interquartile range 61.6–84.9)%.

  • 4 h 15 min (20 min–11:00 h).

  • Data analyzed on 107 patients so far.

4.12 A RANDOMISED PILOT FEASIBILITY STUDY OF THERAPEUTIC HYPOTHERMIA FOR NEONATAL ENCEPHALOPATHY IN A LOW-RESOURCE SETTING IN EQUATORIAL AFRICA

N. J. Robertson1, M. Nakakeeto2, C. F. Hagmann1, E. Allen3, F. M. Cowan4, D. Acolet4, D. Elbourne3, A. Costello5, I. Jacobs1. 1EGA UCL Institute for Women’ Health, University College London, London, UK, 2Neonatal Unit, Mulago Hospital, Kampala, Uganda, 3Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK, 4Department of Paediatrics and Imaging Sciences, Imperial College, London, UK, 5International Perinatal Care Unit, Institute of Child Health, London, UK

Background: Therapeutic hypothermia is a promising therapy for neonatal encephalopathy (NE) in the developed world;3 results cannot be directly transferred to low-resource settings.

Aims: To determine the feasibility of whole-body cooling to 33–34°C for 72 h using simple methods and the temperature profile over the first 80 h in term NE infants undergoing standard care in Mulago Hospital, Kampala, Uganda.

Methods: The local ethics committee approved the study. After informed consent, babies were randomly assigned to standard care plus cooling with “cool” water bottles or standard care.

Results: Between 27 July 2007 and 31 October 2007, 110 term infants with NE admitted to the neonatal unit were screened. 36 infants were eligible for inclusion (see table).

Conclusions: Initial rectal temperatures were similar in therapeutic hypothermia and standard care groups. Screening, randomisation and cooling to 33–34°C over 72 h with water bottles was feasible in this low-resource setting. Suggestions of adverse outcomes make rigorous randomised trials to determine safety and efficacy of therapeutic hypothermia in low-resource settings imperative.

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