Prediction of neurosensory disability in very low birth weight preterm infants. Structural and functional brain imaging and hearing screening at term age and follow-up of infants to a corrected age of 18 months

Marita Valkama

Department of Paediatrics, Department of Diagnostic Radiology and Department of Clinical Neurophysiology, University of Oulu, P.O.Box 5000, FIN-90014, University of Oulu, Finland

Abstract

The objectives were to study ultrasound (US), magnetic resonance imaging (MRI), single photon emission tomography (SPET) and brainstem auditory evoked potentials (BAEP) as structural and functional imaging methods for the prediction of later neuromotor outcome and to assess the reliability of auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free-field auditory behavioural responses (FF) for the prediction of permanent hearing loss.

The series comprised 51 surviving very low birth weight preterm infants born at <34 gestational weeks with a birth weight <1500 grams, taking 52 full-term infants as controls with respect to hearing screening and 21 with respect to brainstem function. The imaging examinations and hearing screening were performed at term age and follow-up continued to a corrected age of 18 months for the evaluation of neurodevelopment and hearing. MRI images were analysed with regard to the degree of myelination, parenchymal lesions, ventricular-brain ratios and widths of the extracerebral spaces, and the predictive value of the findings for later neuromotor development was assessed by comparison with US. In the SPET examinations (on 34 infants) relative regional perfusion levels and hemispheric asymmetries were evaluated in slices. The predictive value of perfusion defects in SPET was similarly assessed relative to US abnormalities. Brainstem size was measured by MRI, and brainstem function evaluated by BAEP, and results being used to predict neurosensory disability. Hearing was screened by means of ABR, TEOAE and FF, and the results used to predict permanent hearing loss.

Parenchymal lesions in MRI predicted cerebral palsy (CP) with a sensitivity of 82% and a specificity of 97%, the corresponding figures for US being 58% and 100%. Delayed myelination, ventricular-brain ratios and widths of the extracerebral spaces failed to predict CP. The sensitivity of perfusion defects in SPET for predicting CP was 82% and the specificity 70%, and correspondingly US attained a sensitivity of 73% and a specificity of 83%. The best brainstem dimensions for predicting neurosensory disability reached at sensitivity of 23–31% and a specificity of 97–100%. The best predictors in BAEP gave the sensitivity of 93% with a specificity of 57–59%. Bilateral failure in TEOAE predicted hearing loss with a sensitivity of 50% and with a specificity of 84%, and that in ABR with a sensitivity of 100% and a specificity of 98%. The FF examination showed a sensitivity of 50% and a specificity of 98%.

In conclusion, out of the brain imaging methods used here MRI was the best for predicting abnormal neuromotor outcome. Brainstem dimensions in MRI appear to predict neurosensory disability poorly, however, whereas BAEP shows a better prediction value, but is limited by a low specificity. ABR seems to be the best hearing screening method because it includes retrocochlear involvements in preterm infants.

Dedication

To my family

Table of Contents
Acknowledgements
Abbreviations
List of original papers
1. Introduction
2. Review of the literature
2.1. Definitions
2.2. Prevalence of neurosensory disability in preterm infants
2.3. Pathophysiology of brain damage in preterm infants
2.3.1. Maturational aspects
2.3.2. Haemorrhages and periventricular haemorrhagic infarction
2.3.3. Periventricular leukomalacia
2.4. Prediction of the outcome for preterm infants by neonatal brain imaging methods
2.4.1. Ultrasound
2.4.2. Magnetic resonance imaging
2.4.3. Single photon emission tomography
2.5. Neonatal brainstem auditory evoked potentials in preterm infants
2.6. Neonatal screening of hearing in preterm infants
2.6.1. Auditory brainstem responses
2.6.2. Transient evoked otoacoustic emissions
2.6.3. Free-field auditory examination
2.7. Neonatal neurological assessment and follow-up of preterm infants
3. Aims of the research
4. Subjects and methods
4.1. Subjects
4.2. Methods
4.2.1. Neonatal brain imaging
4.2.2. Brainstem auditory evoked potentials (III, IV)
4.2.3. Neonatal screening of hearing (IV)
4.2.4. Developmental follow-up and neurosensory outcome
4.2.5. Statistical methods
5. Results
5.1. Neurodevelopmental outcome
5.1.1. Cerebral palsy
5.1.2. Developmental outcome
5.2. Abnormalities in imaging examinations at term age and later neuromotor outcome
5.2.1. Ultrasound
5.2.2. Magnetic resonance imaging
5.2.3. Single photon emission tomography
5.3. Brainstem auditory evoked potentials
5.4. Screening of hearing at term age and permanent hearing loss
5.4.1. Screening of hearing
5.4.2. Hearing loss
5.5. Prediction of neurosensory outcome
6. Discussion
6.1. Subjects
6.2. Methods
6.2.1. Neurodevelopmental follow-up and outcome
6.3. Abnormalities in imaging examinations at term age and later neuromotor outcome
6.3.1. Ultrasound
6.3.2. Magnetic resonance imaging
6.3.3. Single photon emission tomography
6.4. Brainstem auditory evoked potentials
6.5. Screening of hearing and permanent hearing loss
6.6. Clinical implications
7. Conclusions
References
List of Tables
1. Definitions for a preterm infant and the first weight of the newborn after birth according to the International Classification of Diseases (31, 32).
2. A timetable of normal progress of myelination in MRI (76, 78).
3. Classification of haemorrhages in VLBW infants, according to Papile et al. (79).
4. Grading of the severity of germinal matrix-intraventricular haemorrhages from US scan, adapted from Volpe (27).
5. Classification of periventricular leukomalacia, according to de Vries (29).
6. Maturational patterns of cerebral blood flow according to brain single photon emission tomography (68, 96).
7. Clinical characteristics and neonatal morbidity of infants in series I-IV.
8. Summary of the main methods used in the term age examinations and the main outcome measures employed at a corrected age of 18 months in series I-IV.
9. The mean (SD) dimensions of the brainstem on T1-weighted brain magnetic resonance imaging (MRI) scan at term age in appropriate for gestational age (AGA) and small for gestational age (SGA) preterm infants (independent samples t test).
10. The mean (SD) dimensions of the brainstem on T1-weighted brain magnetic resonance imaging (MRI) scan at term age in preterm infants according to the neurosensory outcome (independent samples t test).
11. Numbers (n) of preterm infants with normal and abnormal findings in brain magnetic resonance imaging (MRI) and single photon emission tomography (SPET) examinations at term age in relation to findings in ultrasound (US) examinations in preterm infants with and without cerebral palsy (CP and non-CP) as an outcome at a corrected age of 18 months.
12. Performance of brain magnetic resonance imaging (MRI) and brain perfusion single photon emission tomography (SPET) at term age for the prediction of cerebral palsy as an outcome at a corrected age of 18 months in very low birth weight preterm infants with reference values for ultrasounds (US).
13. Brainstem dimensions in magnetic resonance imaging (MRI) and absence or abnormal peak and inter-peak latencies and the amplitude ratio V/I in brainstem auditory evoked potentials (BAEPs) at term age for the prediction of neurosensory disability in very low birth weight preterm infants at a corrected age of 18 months.
14. Auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAEs), and free-field auditory examination (FF) at term age for the prediction of permanent hearing loss in very low birth weight preterm infants at a corrected age of 18 months.
List of Figures
1. Failure results for the preterm and full-term infants in ABR, TEOAE and FF examinations at term post-conceptional age.
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