You are here

Article Text

Article menu

Download PDFPDF

Research paper
Cognitive maturation in preterm and term born adolescents
  1. M Allin1,
  2. M Walshe1,
  3. A Fern1,
  4. C Nosarti1,
  5. M Cuddy1,
  6. L Rifkin1,
  7. R Murray1,
  8. T Rushe2,
  9. J Wyatt3
  1. 1
    Institute of Psychiatry, King’s College, London, UK
  2. 2
    Department of Psychology, University of Manchester, Manchester, UK
  3. 3
    Department of Neonatal Paediatrics, Royal Free & University College Medical School, London, UK
  1. Dr Matthew Allin, Division of Psychological Medicine, Box 063, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK; matthew.allin{at}iop.kcl.ac.uk

Abstract

Background: Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm.

Methods: We carried out longitudinal neuropsychological testing in 94 very preterm individuals (VPT; before 33 weeks’ gestation) and 44 term born individuals at mean ages of 15.3 years (adolescence) and 19.5 years (young adulthood).

Results: Full scale, verbal and performance IQ and phonological verbal fluency were significantly lower in the VPT group than the term group at both ages. Repeated measures ANOVA showed only one group by time point interaction for semantic verbal fluency (F = 10.25; df = 107; p = 0.002). Paired-sample t tests showed that semantic verbal fluency increased significantly in the term group over adolescence (t = −5.10; df = 42; p<0.001), but did not increase in the VPT group (t = 0.141; df = 69; p = 0.889). For verbal IQ, there was a significant interaction between time point and sex (F = 4.48; df = 1; p = 0.036) with paired-sample t tests showing that verbal IQ decreased in males between adolescence and adulthood (t = 3.35; df = 71; p = 0.001), but did not change significantly in females (t = 0.20; df = 52; p = 0.845).

Conclusion: Decrements of intellectual functioning in VPT individuals persist into adulthood. Additionally, there is a deficit in the adolescent maturation of semantic verbal fluency in individuals born VPT.

https://doi.org/10.1136/jnnp.2006.110858

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Adolescence is a time of complex changes in behaviour, cognition, social interaction and brain structure. Neuropsychological abilities such as verbal fluency mature during this period,1 associated with a refining and restricting of fMRI activation patterns in the frontal lobe.2 Executive functions are generally refined with age, with “mature” levels of performance being attained in adolescence and young adulthood.3–5 Longitudinal imaging studies6–10 show that white matter generally increases through adolescence, most likely the result of ongoing myelination, whereas grey matter is generally decreasing, probably a consequence of synaptic pruning or of increased myelination in its underlying white matter.11 Maturation of specific areas of temporo-parietal white matter revealed by diffusion tensor imaging (DTI) may underlie the maturation of reading ability.12

    Less is known about how adolescent maturation is altered in individuals who have recovered from early neurodevelopmental insults—such as those born very preterm (VPT; before 33 weeks’ gestation) or of very low birth weight (VLBW; less than 1500 g). These individuals are at increased risk of perinatal brain damage and subsequent developmental delay, but little is known about their adolescent development. Neuropsychological deficits in these groups certainly persist into the teenage years—for example, Rushe et al13 found impairments of cognitive flexibility and phonological verbal fluency in a group of VPT 15-year-olds. There are also some reports that neuropsychological function may deteriorate with maturation. Botting et al. (1998)14 found a decline in cognitive measures between 6 and 12 years in a cohort of VLBW children. Saigal et al15 found a decline in mathematical ability between 8 years and early teens in extremely low birth weight (ELBW) individuals, although global cognitive function (measured by IQ) remained stable over this time. A recent study by O’Brien et al16 reported that IQ declines significantly between 8 and 14 years in VPT individuals. There is evidence that VLBW males are more susceptible than females to adverse developmental sequelae,17 but little is known about sex differences in cognitive maturation in VPT adolescents.

    In spite of such reports, few studies have yet followed up preterm individuals through adolescence and into adulthood. In this study we carried out neuropsychological evaluations in two groups of individuals: one VPT and the other term born, in adolescence and then again in young adulthood. We hypothesised that preterm individuals would show a decline in intellectual performance or a failure to make age-appropriate gains in performance, over this interval. We further hypothesised that this would be more evident in VPT males than females.

    METHODS

    Study participants

    Very preterm group

    A total of 406 infants born before 33 weeks’ gestation between 1982 and 1984 were admitted to the neonatal unit of University College Hospital (UCH) London within five days of birth and later discharged (VPT group). From this population, 302 survived and were recruited as part of a long-term follow-up study. The cohort was assessed at 1, 4, 8 and 15 years old using a battery of neuropsychological tests. These results have been extensively published.18 19 At 15 years, 111 of these individuals were assessed (the adolescent assessment). For the young adult assessment, these individuals were re-contacted. Ninety-four (85%) agreed to participate in further assessment. Preterm individuals who were not assessed did not differ significantly from those who were assessed in their gestational age (t = 1.55, df = 469, p = 0.12), Apgar scores at 1 minute (t = 0.84, df = 145, p = 0.40) and 5 minutes (t = 0.31, df = 145, p = 0.76), sex (χ2 = 0.82, df = 1, p = 0.37) or social class (χ2 = 1.3, df = 4, p = 0.87).

    Term group

    A group of 71 individuals born between 38 and 42 weeks’ gestation was recruited by advertisement in the local (South London) press for the adolescent assessments to act as controls. These same individuals were invited for the young adult assessments. Forty-four individuals (62%) were assessed at both time points.

    Neuropsychological testing

    General intellectual functioning

    An IQ measure was performed at both adolescent and young adult assessments. In adolescence the age-appropriate 8-item Wechsler Intelligence Scale for Children – Revised (WISC-R)20 was used. In young adulthood, the Wechsler Abbreviated Scale of Intelligence (WASI),21 a 4-subtest measure, was used. At each age, measures of verbal, performance and full-scale IQ were available.

    Verbal fluency

    Two domains of verbal fluency were assessed:

    1. phonological or letter fluency, using the Controlled Oral Word Association Test (COWAT),22 where participants are requested to produce words beginning with a given letter (in this case “F”, “A” and “S”) in 60 seconds.

    2. semantic (category) fluency, using the Animal Naming test, in which participants are required to produce as many names of animals as they can, in a trial lasting 60 seconds.23

    Verbal fluency assesses the executive system that enables initiation of response, mental flexibility and also the ability to use strategies such as clustering, where words are produced in subcategories, either phonological or semantic.24 In addition to executive functions, components of verbal fluency production include short-term memory of phonological information and simple word retrieval processes. In the analyses the following scores were used: (1) phonological verbal fluency (COWAT score calculated as the total number of words produced during the “F”, “A” and “S” trials); (2) category fluency (score calculated as the total number of words produced during the Animal Naming test). The COWAT and Animal Naming tests were administered at both adolescent and young adult assessments. Harrison et al25 reported test-retest reliability of 0.82 for phonological (FAS) and 0.68 semantic components of the COWAT.

    Neonatal cerebral ultrasound classification

    Ultrasound ratings were performed in the perinatal period using a linear ultrasound array. VPT subjects were divided into three groups on the basis of these ratings (0 =  normal; 1 =  uncomplicated periventricular haemorrhage; 2 =  periventricular haemorrhage and ventricular dilatation)26 (see table 1). Ultrasound ratings were available for the VPT group only.

    View this table:
    Table 1 Demographic characteristics of term and very preterm (VPT) groups

    Statistical analysis

    Data were analysed using Statistical Package for the Social Sciences (SPSS) v 12.0.1. Demographic data were analysed using independent-sample t tests or χ2 tests for categorical data. Longitudinal data were analysed using repeated-measures ANOVA, with time point (adolescent and young adult) (twofold) as within-subject independent variable, and sex and group as between-subject factors, covarying for subjects’ ages at both time points and for their socioeconomic status. Main effects were tested using models that did not include the interactions. Partial eta squared is reported as a measure of effect size. This measure provides an estimate of the proportion of the total variance accounted for by the factor under consideration. For example, a partial eta squared of 0.1 would indicate that the factor accounts for 10% of the overall variance. Longitudinal neuropsychological changes within groups were explored further using paired sample t tests. For some analyses, a measure of change in neuropsychological function was calculated using the formula: [adult score] – [adolescent score]. Relationships with perinatal variables were sought using Spearman correlations. To assess the effects of neonatal brain injury on adolescent cognitive maturation, a separate repeated measures ANOVA was performed using neonatal ultrasound severity as between-subjects factor, and time point as within-subject independent variable in the VPT group only. Statistical assumptions were checked and the data were screened for outlying values.

    RESULTS

    Demographic characteristics of the study groups

    Ninety-four VPT individuals (41 female; 53 male) and 44 term individuals (18 female; 26 male) were assessed at two time points: in adolescence (at a mean age of 15.3 years (SD 0.70; range 14–17) and in young adulthood (at a mean age of 19.5 years (SD 1.08; range 18–25)). Sex distribution did not differ between the groups (χ2 = 0.09; df = 1; p = 0.854). The groups were significantly different in social class distribution (Registrar General’s classification) (χ2 = 11.44; df = 4; p = 0.022). VPT individuals were slightly, but significantly, older than term individuals at both adolescent (t = −3.77; df = 135; p<0.001) and adult assessments (t = −3.62; df = 132; p<0.001) (see table 1). The neonatal characteristics of the VPT group have been published elsewhere.18 19 The results presented below include all patients on whom an assessment at both ages was available. Denominators may vary between different tests.

    Neuropsychological testing

    Results of IQ and verbal fluency tests in adolescence and adulthood in VPT and term groups are shown in table 2. For the following repeated-measures ANOVAs, the assumption that covariance matrices were equal across groups was tested using Box’s M test. This was significant only for verbal IQ (M = 19.34; F = 2.07; p = 0.028). The repeated measures ANOVA for vIQ was therefore adjusted using the Greenhouse-Geisser correction.

    View this table:
    Table 2 IQ and verbal fluency (VF) measures at adolescent and young adult assessments in the term and very preterm (VPT) groups (mean (SD))

    Full scale IQ

    Repeated measures ANOVA for full scale IQ (at two time points, covarying for social class and age at assessments) revealed a significant main effect of group (F = 10.89; df = 108; p = 0.001; partial eta squared = 0.092), but no significant main effect of sex or time point. There was a significant interaction between time point and sex (F = 5.52; df = 108; p = 0.021; partial eta squared = 0.049), but no significant interaction between time point and group, or between group and sex. There was no significant three-way interaction between time point, group and sex (see table 3).

    View this table:
    Table 3 Results of repeated-measures ANOVAs, with time point (adolescent and young adult) (twofold) as within-subject independent variable, and sex and group as between-subject factors, covarying for subjects’ ages at both time points and for their socioeconomic status (significant main effects and interactions are highlighted in bold type)

    In adolescence, full scale IQ was 11.1 points lower in the VPT group (t = 3.25; df = 124; p = 0.001). In adulthood, full-scale IQ was 8.9 points lower in the VPT group (t = 4.25; df = 138; p = 0.001) (see table 2). Among males, full-scale IQ decreased by 5.0 points between adolescence and adulthood (t = −3.75; df = 70; p<0.001). There was no significant change in full-scale IQ over this time in the females.

    Verbal IQ

    Repeated measures ANOVA for verbal IQ revealed a main effect of group (F = 9.66; df = 115; p = 0.002; partial eta squared = 0.077), but no significant main effect of sex or time point. There was a significant interaction between time point and sex (F = 4.48; df = 1; p = 0.036; partial eta squared = 0.038), but no significant interactions between time point and group or group and sex, and no significant three-way interaction between time point, group and sex (see table 3).

    Verbal IQ was significantly lower in the VPT group in adolescence (t = 3.63; df = 124; p<0.001) and adulthood (t = 3.44; df = 137; p = 0.002). Paired sample t tests showed that verbal IQ decreased in males between adolescence and adulthood (t = 3.35; df = 71; p = 0.001), but did not change significantly in females (t = 0.20; df = 52; p = 0.845).

    Performance IQ

    Repeated measures ANOVA for performance IQ revealed a main effect of group (F = 5.58; df = 112; p = 0.020; partial eta squared = 0.047), but no significant main effects of time point of sex. There were no significant interactions between time point and group; time point and sex; group and sex; or time point, group and sex (table 3).

    Performance IQ was lower in the VPT group in both adolescence (t = 2.52; df = 122; p = 0.013) and adulthood (t = 3.44; df = 138; p = 0.001).

    Phonological verbal fluency

    Repeated measures ANOVA for phonological verbal fluency revealed a significant main effect of group (F = 6.91; df = 116; p = 0.010; partial eta squared = 0.056) but no main effect of sex or time point. There were no significant interactions between time point and group; or between time point and sex; or between group and sex; or between time point, group and sex (see table 3).

    Phonological verbal fluency was significantly lower in the VPT group than the term group at both adolescent (t = 2.60; df = 133; p = 0.010) and adult (t = 2.73; df = 131; p = 0.007) assessments (see table 2).

    Semantic verbal fluency

    Repeated measures ANOVA for semantic verbal fluency revealed no significant main effect of group, sex or time point. There was a significant interaction between time point and group (F = 10.25; df = 107; p = 0.002; partial eta squared = 0.077) (see fig 1), but no significant interactions between time point and sex; or group and sex; or time point, group and sex (see table 3). Paired-sample t tests showed that semantic verbal fluency increased significantly in term group over adolescence (mean difference = −2.86; 95% confidence intervals (CI) −3.99, −1.73; t = −5.10; df = 42; p<0.001), but did not increase in the VPT group (mean difference = 0.086; 95% CI −1.13, 1.30; t = 0.141; df = 69; p = 0.889).

    Figure 1
    Figure 1 Estimated marginal means for the interaction between time point and group for semantic verbal fluency. VPT, very preterm.

    Associations between perinatal variables and cognitive maturation in the VPT group

    A measure of change in neuropsychological function over time was derived by subtracting the adolescent test results from the adult test results. Relationships between change scores and perinatal variables were sought using Spearman’s correlations as the change scores did not all follow a normal distribution. There were no significant correlations between neuropsychological change and birth weight and gestational age. To assess relationships between neonatal brain injury and neuropsychological maturation, we performed repeated measures ANOVA in VPT individuals with time point as within-subject independent variable and neonatal ultrasound classification as between-subject factor. There were no significant main effects of ultrasound severity, and no significant interactions between ultrasound classification and time point for any of the neuropsychological tests.

    DISCUSSION

    We have shown that decrements in neuropsychological performance are still present as VPT individuals enter early adulthood, with VPT individuals having lower verbal, performance and full-scale IQ, and phonological verbal fluency scores, at both adolescent and adult assessments. This indicates that neuropsychological deficits in VPT individuals persist into adulthood rather than being attenuated by maturation. There is little published evidence that is directly comparable to this study, and other longitudinal studies on this group have generally included participants at younger ages. For example, O’Brien et al16 followed up VPT individuals at 8 years and 15 years and found that the mean full-scale IQ (measured by the WISC-R) fell from 104 to 95 in a VPT group between 8 and 15 years. Similarly, Botting et al14 found a decline in cognitive performance between 6 and 12 years. Our results would indicate that further decline does not occur between 15 and 19 years. Methodological considerations compel us to treat these results with some caution. Comparison of neuropsychological testing at different ages, as reported here, is often complicated by the use of different assessment instruments at different ages. This is partly due to, and is further confounded by, the fact that the range of neuropsychological tests that can be performed increases greatly with age and maturation of the central nervous system. For example, an age-appropriate assessment for an 8 year old may differ markedly from an age-appropriate test for an 18 year old.

    Additionally, we have demonstrated an altered pattern of maturation of semantic verbal fluency in VPT individuals who did not make the same age-related gains that were seen in the term group. Little is known about normal adolescent cognitive maturation and the maturation of verbal fluency. Cohen et al27 reported that verbal fluency increases in children between 6 and 12 years. Tombaugh et al28 in a cross-sectional study, found that semantic fluency was more affected by the age of the subject than phonological fluency, whereas Matute et al1 also found age-related increases in both phonological and semantic verbal fluency. Here we provide evidence of maturation of both phonological and semantic verbal fluency, with performance on these tasks increasing between 15 and 19 years in normal adolescents. A similar pattern of maturation was found in the VPT group for phonological fluency, but VPT individuals did not show the age-related increases in semantic fluency that we found in the term group.

    Fu et al29 in an fMRI study found that phonological verbal fluency activates a network comprising the anterior cingulate, left inferior frontal, middle frontal and parietal cortex and the right cerebellum. This would suggest that the classical neuropsychological explanation of verbal fluency as a property of the dominant frontal lobe may be an over-simplification. Given the widespread reorganisation of brain structure and function in VPT and VLBW individuals, it is reasonable to suggest that tasks requiring the recruitment and coordination of several neural “modules” may be performed less well by these individuals. Previous work in a similar cohort of VPT individuals has shown a relationship between volume decrement of the cerebellum and intellectual functioning.30

    An explanation for the dissociation between semantic and phonological fluency maturation in the VPT group could be that semantic tasks require recruitment of more neural resources than letter fluency. Both tasks require activation of a phonological system, but the semantic task requires the additional activation of a “meaning” pathway.31 Converging evidence from structural26 32 and functional33 imaging in VPT and VLBW adolescents and adults suggests that such individuals have undergone considerable plastic reorganisation of the brain. This neural plasticity is beneficial in that it protects against gross functional disturbance, but it may give rise to a brain that has difficulty coping with increasing task demands.34

    Adolescent maturation of cognitive function may be related to the dynamic changes in brain structure that have been demonstrated over adolescence and early adulthood. Longitudinal imaging studies such as that of Sowell et al8 have demonstrated changes in Broca’s and Wernicke’s areas, which may underlie the rapidly changing cognitive and linguistic abilities. Early brain lesions acquired by VPT and VLBW individuals have been shown to cause focal and distributed abnormalities of structure.32 How this interacts with normal processes of brain maturation is currently not determined, but it may be that early lesions impede these relatively late neurodevelopmental changes such that the brain is unable to maintain a normal developmental trajectory, and neurodevelopment lags behind increasing cognitive demands. An alternative possibility is that the altered maturation of verbal fluency that we report is related to reduced speed of neural processing. Rose et al35 reported slower processing of information about faces in preterm infants up to 1 year when compared to term infants. It has even been suggested that processing speed reduction may account for as much as 60% of the IQ differences between VPT and term 11 year olds.36 Further follow up would be necessary to distinguish these two potential aetiologies.

    LIMITATIONS

    We should acknowledge several potential limitations of this study. Chief among these is the problem of comparing neuropsychological measures taken at different ages, using different versions of the Wechsler intelligence scales (the WISC-R in adolescence and the WASI in adulthood). To some extent this is an unavoidable consequence of longitudinal studies—the appropriate test may be different at different stages of cognitive maturation. We have used well-standardised measures to mitigate this. Additionally, there is a well-known tendency for IQ scores to increase over time37 38 and we used the WISC-R towards the end of its life (when it may have been overestimating IQ). Conversely, the WASI was relatively newly introduced and may have underestimated IQ in early adulthood. However, we would expect that such effects on IQ measurement would apply equally to males and females, whereas we have demonstrated differential effects. The identical test of verbal fluency was administered at both ages, and differences in the maturation of this cognitive domain are therefore less likely to be an artefact of testing. A further limitation is the slight (but statistically significant) difference in ages between the groups, with the VPT group being slightly older at both testing phases. However, this should have allowed the VPT group more “maturation time”, which would tend to attenuate rather than exaggerate our findings, and additionally we controlled for the effects of age in the statistical analyses.

    CONCLUSIONS

    VPT birth is associated with a decrement in general intellectual ability, which we have shown to persist into adulthood. Further, we have shown that normal maturational trajectory of semantic verbal fluency is not followed in VPT individuals. The course of maturation of other cognitive abilities that we did not test remains unclear. It is also not yet clear whether VPT individuals’ verbal fluency development lags behind that of their peers, and may therefore be able to “catch up”, or whether it represents an enduring deficit. Further follow up of VPT individuals into adulthood will be necessary to answer this question.

    Acknowledgments

    We thank the preterm and term born individuals who took part in this study.

    REFERENCES

    1. ↵
      1. Matute E,
      2. Rosselli M,
      3. Ardila A,
      4. et al
      . Verbal and nonverbal fluency in Spanish-speaking children. Developmental Neuropsychology 2004;26:647–60.
      OpenUrlCrossRefPubMedWeb of Science
    2. ↵
      1. Gaillard WD,
      2. Sachs BC,
      3. Witnah JR,
      4. et al
      . Developmental aspects of language processing: fMRI of verbal fluency in children and adults. Hum Brain Mapp 2003;18:176–85.
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      1. Luna B,
      2. Sweeney JA
      . The emergence of collaborative brain function: fMRI studies of the development of response inhibition. Ann N Y Acad Sci 2004;1021:296–309.
      OpenUrlCrossRefPubMedWeb of Science
      1. Zelazo PD
      . , Craik, FIM, Booth L. Executive function across the life span. Acta Psychologica 2004;115:167–83.
      OpenUrlCrossRefPubMed
    5. ↵
      1. Huizinga M,
      2. Dolan CV,
      3. van der Molen M
      . Age-related change in executive function: Developmental trends and a latent variable analysis. Neuropsychologia 2006;44:2017–36.
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      1. Sowell ER,
      2. Thompson PM,
      3. Holmes CJ,
      4. et al
      . In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience 1999;2:859–61.
      OpenUrlCrossRefPubMedWeb of Science
      1. Sowell ER,
      2. Thompson PM,
      3. Tessner KD,
      4. et al
      . Mapping continued brain growth and gray matter density reduction in dorsal frontal cortex: inverse relationships during postadolescent brain maturation. J Neurosci 2001;21:8819–29.
      OpenUrlAbstract/FREE Full Text
    8. ↵
      1. Sowell ER,
      2. Peterson BS,
      3. Thompson PM,
      4. et al
      . Mapping cortical change across the human life span. Nature Neurosci 2003;6:309–15.
      OpenUrlCrossRefPubMedWeb of Science
      1. Giedd JN,
      2. Blumenthal J,
      3. Jeffries NO,
      4. et al
      . Brain development during childhood and adolescence: a longitudinal MRI study. Nature Neuroscience 1999;2:861–3.
      OpenUrlCrossRefPubMedWeb of Science
    10. ↵
      1. Gogtay N,
      2. Giedd JN,
      3. Lusk L,
      4. et al
      . Dynamic mapping of human cortical development during childhood through early adulthood. PNAS 2004;101:8174–9.
      OpenUrlAbstract/FREE Full Text
    11. ↵
      1. Paus T
      . Mapping brain maturation and cognitive development during adolescence. Trends Cogn Sci 2005;9:60–8.
      OpenUrlCrossRefPubMedWeb of Science
    12. ↵
      1. Klingberg T,
      2. Hedehus M,
      3. Temple E,
      4. et al
      . Microstructure of temporo-parietal white matter as a basis for reading ability: Evidence from diffusion tensor magnetic resonance imaging. Neuron 2000;25:493–500.
      OpenUrlCrossRefPubMedWeb of Science
    13. ↵
      1. Rushe TM,
      2. Rifkin L,
      3. Stewart AL,
      4. et al
      . Neuropsychological outcome at adolescence of very preterm birth and its relation to brain structure. Dev Med Child Neurol 2001;43:226–33.
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      1. Botting N,
      2. Powls A,
      3. Cooke RWI,
      4. et al
      . Cognitive and educational outcome of very-low-birthweight children in early adolescence. Dev Med Child Neurol 1998;40:652–660.
      OpenUrlPubMedWeb of Science
    15. ↵
      1. Saigal S,
      2. Hoult LA,
      3. Streiner DL,
      4. et al
      . School difficulties at adolescence in a regional cohort of children who were extremely low birth weight. Pediatrics 2000;105:325–31.
      OpenUrlAbstract/FREE Full Text
    16. ↵
      1. O’Brien F,
      2. Roth S,
      3. Rifkin L,
      4. et al
      . The neurodevelopmental progress of infants less than 33 weeks into adolescence. Arch Dis Child 2004;89:207–11.
      OpenUrlAbstract/FREE Full Text
    17. ↵
      1. Stevenson DK,
      2. Verer J,
      3. Fanaroff AA,
      4. et al
      . Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage. Arch Dis Child Fetal Neonatal Ed 2000;83:F182–5.
      OpenUrlAbstract/FREE Full Text
    18. ↵
      1. Stewart AL,
      2. Rifkin L,
      3. Amess PN,
      4. et al
      . Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm. Lancet 1999;353:1653–7.
      OpenUrlCrossRefPubMedWeb of Science
    19. ↵
      1. Stewart AL,
      2. Costello AM deL,
      3. Hamilton PA,
      4. et al
      . Relationship between neurodevelopmental status of very preterm infants at one and four years. Dev Med Child Neurol 1989;31:756–65.
      OpenUrlPubMedWeb of Science
    20. ↵
      1. Wechsler D
      . The Wechsler Intelligence Scale for Children – revised. New York: The Psychological Corporation, 1974.
    21. ↵
      1. Wechsler D
      . Wechsler Abbreviated Scale of Intelligence. New York: The Psychological Corporation, 1999.
    22. ↵
      1. Benton AL,
      2. Hamsher KD
      . Multilingual Aphasia Examination. Iowa City: University of Iowa, 1976.
    23. ↵
      1. Goodglass H,
      2. Kaplan E
      . The Assessment of Aphasia and Related Disorders. 2nd Ed. Philadelphia: Lea & Febiger, 1983.
    24. ↵
      1. Spreen O,
      2. Strauss E
      . A compendium of neuropsychological tests. New York: Oxford University Press, 1991.
    25. ↵
      1. Harrison JE,
      2. Buxton P,
      3. Husain M,
      4. et al
      . Short test of semantic and phonological verbal fluency: Normal performance, validity and test-retest reliability. Br J Clinical Psychology 2000;39:181–91.
      OpenUrlCrossRef
    26. ↵
      1. Nosarti C,
      2. Al-Asady MHS,
      3. Frangou S,
      4. et al
      . Adolescents who were born very preterm have decreased brain volumes. Brain 2002;125:1616–23.
      OpenUrlAbstract/FREE Full Text
    27. ↵
      1. Cohen MJ,
      2. Morgan AM,
      3. Vaughn M,
      4. et al
      . Verbal fluency in children: Developmental issues and differential validity in distinguishing children with attention-deficit hyperactivity disorder and two subtypes of dyslexia. Arch Clin Neuropsychology 1999;1:433–43.
      OpenUrl
    28. ↵
      1. Tombaugh TN,
      2. Kozak J,
      3. Rees L
      . Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Arch Clinical Neuropsychology 1999;14:167–77.
      OpenUrlCrossRef
    29. ↵
      1. Fu CHY,
      2. Morgan K,
      3. Suckling J,
      4. et al
      . A functional magnetic resonance imaging study of overt letter verbal fluency using a clustered acquisition sequence: Greater anterior cingulate activation with increased task demand. NeuroImage 2002;17:871–9.
      OpenUrlCrossRefPubMedWeb of Science
    30. ↵
      1. Allin M,
      2. Matsumoto H,
      3. Santhouse AM,
      4. et al
      . Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term. Brain 2001;124:60–6.
      OpenUrlAbstract/FREE Full Text
    31. ↵
      1. Poldrack RA,
      2. Wagner AD,
      3. Prull MW,
      4. et al
      . Functional specialization for sematic and phonological processing in the left inferior prefrontal cortex. NeuroImage 1999;10:15–35.
      OpenUrlCrossRefPubMedWeb of Science
    32. ↵
      1. Allin M,
      2. Henderson M,
      3. Suckling J,
      4. et al
      . The effects of very low birth weight on brain structure in adulthood. Dev Med Child Neurol 2004;46:46–53.
      OpenUrlCrossRefPubMedWeb of Science
    33. ↵
      1. Santhouse AM,
      2. ffytche DH,
      3. Howard RJ,
      4. et al
      . The functional significance of perinatal corpus callosum damage: an fMRI study in young adults. Brain 2002;125:1782–92.
      OpenUrlAbstract/FREE Full Text
    34. ↵
      1. Keshavan M,
      2. Kennedy J,
      3. Murray RM
      1. Allin M,
      2. Nosarti C,
      3. Rifkin L,
      4. et al
      . Brain plasticity and long term function after early cerebral insult: the example of very preterm birth. In: Keshavan M, Kennedy J, Murray RM, eds. Neurodevelopment and Schizophrenia Cambridge University Press, 2005:89–107.
    35. ↵
      1. Rose SA,
      2. Feldman JF,
      3. Jankowski JJ
      . Processing speed in the 1st year of life: A longitudinal study of preterm and full-term infants. Developmental Psychology 2002;38:895–902.
      OpenUrlCrossRefPubMed
    36. ↵
      1. Rose SA,
      2. Feldman JF
      . Memory and processing speed in preterm children at eleven years: A comparison with full-terms. Child Development 1996;67:2005–21.
      OpenUrlCrossRefPubMedWeb of Science
    37. ↵
      1. Flynn JR
      . The mean IQ of Americans: massive gains 1932 to 1978. Psychol Bull 1984;95:29–51.
      OpenUrlCrossRefWeb of Science
    38. ↵
      1. Flynn JR
      . Massive IQ gains in 14 nations: what IQ tests really measure. Psychol Bull 1987;101:192–212.
      OpenUrlCrossRefWeb of Science

    Footnotes

    • Funding: The study was funded by the Wellcome Trust. Dr Allin is supported by the Peggy Pollak Fellowship in Developmental Psychiatry, Psychiatry Research Trust.

    • Competing interests: None.

    • Ethics approval: This study was approved at both adolescent and adult phases by the Medical Ethical Committee of the Institute of Psychiatry, King’s College London.

    • Patient consent: At adolescence, written informed consent was obtained from a parent or guardian. All participants provided further written informed consent in adulthood.