Objective. To determine the frequency, nature, and severity of executive dysfunction (EDF) at 8 years of age in extremely low birth weight (ELBW)/very preterm infants who were born in the 1990s, compared with normal birth weight (NBW) control subjects.
Methods. A geographically determined cohort study was conducted in Victoria, Australia. The ELBW/very preterm cohort comprised 298 consecutive survivors at 2 years of age who had gestational ages <28 completed weeks or birth weights <1000 g and were born during 1991-1992. The NBW cohort comprised 262 randomly selected children of birth weight >2499 g matched on date of birth, gender, ethnicity, and health insurance status. The participation rate was 92% (275 of 298) for the ELBW/very preterm cohort and 85% (223 of 262) for the NBW cohort. Cognitive and behavioral measures of executive functioning were administered.
Results. The ELBW/very preterm cohort exhibited significant EDF compared with their NBW peers in all areas assessed. The cognitive assessment revealed global impairment rather than deficits in specific executive domains. The ELBW/very preterm children also displayed more behavioral problems indicative of EDF than the NBW children. Severe impairments were exhibited in only a small minority of ELBW/very preterm children. No statistical conclusions were altered after adjustment for sociodemographic variables or when children with substantial neurosensory impairment were excluded.
Conclusions. School-aged children who were born in the 1990s and were very preterm or had ELBW are at greater risk for developing EDF and require ongoing neuropsychological review throughout middle childhood.
Infants who are born prematurely are at increased risk for cognitive and educational impairments, with group means falling approximately one half to two thirds of an SD below normal birth weight (NBW) peers.1–4 Developmental delay is not the sole explanation for the neurodevelopmental deficits exhibited by preterm children, as learning problems persist throughout childhood and adolescence.2,5–10 For devising more effective intervention programs for preterm children, a greater understanding of their cognitive deficits is required. Identifying the nature of cognitive deficits associated with prematurity will also provide some indication of the neural systems compromised, which may in turn lead to medical interventions to enhance recovery from brain injury and early brain development.
Neuropsychological studies have reported impairments across a wide range of cognitive skills in preterm children,11–17 including executive function.18,19 Executive function (EF) refers to a collection of interrelated processes that are responsible for purposeful, goal-directed behavior and is important in a child’s cognitive functioning, behavior, emotional control, and social interaction.20 Cognitive processes associated with EF are numerous, but the principal elements include anticipation, goal selection, planning and organization, initiation of activity, self-regulation, mental flexibility, deployment of attention, working memory, and utilization of feedback.21 Executive dysfunction (EDF) is not a unitary disorder20 but represents a range of impairment profiles.
Although some evidence is available indicating increased risk of EDF in preterm children, research examining this association is limited. Deficits in planning ability, inhibition, and motor sequencing have been reported in a small sample of children (n = 30) of extremely low birth weight (ELBW),18 whereas spatial working memory impairments have been found in children who were born prematurely.19 Also, problems with spatial organization and mental flexibility have been reported to escalate as birth weight decreases.16,22 As survival rates of very preterm (<28 weeks) and ELBW (birth weight <1000 g) children have increased in the 1990s with improvements in perinatal care, the number of such children with EDF is likely to be greater. To the best of our knowledge, no published studies have assessed EF comprehensively in a large regional cohort of preterm children who were born in the 1990s. This study aimed to examine the frequency, nature, and severity of EDF in a large geographically defined cohort of school-aged children who were born at <28 weeks or with ELBW.
Of 568 consecutive live births with birth weights <1000 g or with gestational ages <28 completed weeks in Victoria, Australia, between January 1991 and December 1992, 298 (52.5%) survived to 2 years of age; these survivors composed the ELBW/very preterm cohort. The participation rate was 92.3% (275 of 298), and of the 23 children who were not assessed, 8 were lost, 11 refused, and 4 were inaccessible, usually living in another country. The mean gestational age at birth for the ELBW/very preterm participants was 26.7 weeks (SD: 1.9), with 73 (27%) children born earlier than 26 weeks and 138 (50%) born at 26 or 27 weeks. Their mean birth weight was 884 g (SD: 162), with 54 (20%) weighing <750 g and 172 (63%) weighing 750 to 999 g. Thirty-eight (14%) were small for gestational age as defined by birth weight >2 SD below that expected for gestational age and gender. Of the ELBW/very preterm participants, 253 (92%) children were born in level III perinatal centers, 202 (73%) received antenatal steroids, 91 (33%) were administered postnatal steroids, and 108 (39%) had surfactant therapy. Bronchopulmonary dysplasia was diagnosed for 163 (59%) infants, and 71 (26%) required surgery in the newborn period. On the basis of neonatal cranial ultrasound, 16 (6%) ELBW/very preterm infants had periventricular leukomalacia (PVL), while 18 (7%) had grade III/IV intraventricular hemorrhage (IVH). Significant neurosensory impairments were identified in 34 (12%) children; 3 were blind, 4 required hearing aids, and 29 had cerebral palsy (2 of whom were also blind).
The NBW cohort, also enrolled at birth, comprised 262 survivors from 265 randomly selected children who had birth weight >2499 g and were born in 1 of the 3 level III perinatal centers in Victoria. Each control was born on the expected date of birth for each child of birth weight <1000 g and was matched for gender, the mother’s country of birth (English speaking or not), and health insurance status (private health insurance or not). The participation rate was 85.1% (223 of 262), and of the 39 children who were not assessed, 22 were lost, 13 refused, and 4 were inaccessible. The mean gestational age at birth for the NBW participants was 39.3 weeks (SD: 1.4), and the mean birth weight was 3407 g (SD: 443). All children in the NBW group were born in level III perinatal centers, and 3 (1%) received antenatal steroids. Only 1 child in the NBW cohort received a diagnosis of a significant neurosensory impairment, which was cerebral palsy.
Participants were assessed when aged between 8 and 9 years, although 4 children were assessed just before their 8th birthday and another 4 children were assessed a few months after their 10th birthday. Age was corrected according to the child’s expected birth date as we have previously described a small but important reduction in IQ even at 8 to 9 years of age.23
Of the children who were not assessed at 8 years of age, 48% (30 of 63) were of low social class, but this was not significantly different from the rate of 46% of low social class in those who were assessed at 8. Nonparticipants tended to have lower psychometric test scores at 2 and 5 years of age than participants at the 8-year follow-up (age 2: Mental Developmental Index on the Bayley Scales of Infant Development, mean difference, −4.4, 95% confidence interval [CI], −11.7 to 3.3, P = .27; age 5: full-scale IQ on Wechsler Preschool and Primary Scale of Intelligence-Revised, mean difference, −6.8, 95% CI, −13.6 to −0.1, P = .046).
All children were enrolled in the newborn period in a prospective longitudinal study of growth and development throughout childhood. Written informed consent was obtained from parents of NBW children, but follow-up was considered routine clinical care for the ELBW/very preterm children. The study was approved by the Research and Ethics Committees of the Royal Women’s Hospital, Melbourne. Neuropsychological assessments were conducted by experienced psychologists who were unaware of children’s perinatal details. In addition to measures of EF, the Wechsler Intelligence Scale for Children-Third Edition24 was administered to have an estimate of general intellectual ability. With the exception of a supplementary subtest (Mazes), the entire Wechsler Intelligence Scale for Children-Third Edition battery was administered. Social class was determined by the occupation of the main income earner in the family; low social class identified families in which the main income earner was unskilled or unemployed. Twelve children in the ELBW/very preterm cohort were not assessed because of significant neurosensory impairment. Of the remaining children, some had incomplete data sets because of assessment difficulties or lack of parental compliance. Children were assessed for this component of the study between January 2000 and April 2002.
EF is a multidimensional construct that incorporates both cognitive and behavioral elements. The neuropsychological assessment included a battery of tests sensitive to specific executive processes. In addition, the parents of participants completed a questionnaire regarding behaviors associated with EDF.
Similarities24 assesses verbal conceptual reasoning, which refers to the ability to identify the concept/s linking words or themes. In Similarities, participants are presented with a series of word pairs (eg, wheel/ball, telephone/radio, ice/steam) for which they must identify and explain the common concept that the word pairs represent. Each response is scored (0, 1, or 2 points) according to the degree of abstraction. There are 19 word pairs, but the test is discontinued after 4 consecutive failures. Overall performance is judged according to age standardized scores that have a mean of 10 (SD: 3).
Digit Span24 assesses verbal working memory, which refers to the capacity to store temporarily and manipulate verbal information. Digit Span has 2 parts. First, participants are presented with a series of number sequences that the participant is required to repeat verbatim. The number sequence increases from 2 digits to 9 digits, with 2 trials for each sequence length. The task is discontinued when participants fail both trials of a sequence length. The second part of Digit Span is similar, although participants must now repeat the sequences in the reverse order. Overall performance is judged according to age-standardized scores that have a mean of 10 (SD: 3).
Block Design24 assesses spatial conceptualization, which refers to the ability to devise spatial patterns from multiple component parts. In Block Design, participants are required to create specific 2-dimensional geometric designs using 2-colored cubes (blocks). The number of cubes increases as the geometric designs become more difficult. Block Design consists of 12 designs, but the test is discontinued after 2 consecutive failures. Each design has a time limit, and depending on the completion time, the child can earn bonus points. Overall performance is judged according to age-standardized scores that have a mean of 10 (SD: 3).
Picture Arrangement24 assesses visual reasoning, which refers to the capacity to make logical inferences on the basis of visual stimuli/information. Picture Arrangement comprises 14 items in which the participant is presented with a set of colorful pictures in a mixed-up order that requires rearrangement into a logical story sequence. Overall performance is judged according to age-standardized scores that have a mean of 10 (SD: 3).
Tower of London25
The Tower of London assesses planning ability, which refers to the capacity to identify a sequence of steps or actions necessary to attain a specific goal. In the Tower of London, participants are instructed to rearrange a set of 3 colored balls on 3 posts of different height, in a nominated number of moves, so that it matches a specified configuration. The Tower of London comprises 12 items of increasing difficulty with the number of moves allowed to solve the problem varying from 2 to 5 depending on the difficulty of the item. As problems on the Tower of London become more difficult, performance is associated with the ability to plan ahead and select the appropriate sequence of moves. Performance of participants was determined by the number of items solved correctly (maximum score of 12).
Rey Complex Figure
The Rey Complex Figure26,27 assesses spatial organization and strategic decision making. Spatial organization refers to the ability to perceive and interpret complex spatial stimuli/information; strategic decision making refers to the capacity to plan ahead and devise efficient and effective strategies to attain a specific goal. In the Rey Complex Figure, participants are required to copy, as accurately as possible, a complex geometric figure consisting of a large rectangle, vertical and horizontal centerlines, 2 diagonals, and external attachments and internal sections of the large rectangle. The accuracy scoring procedure developed by Osterrieth28,29 was used to assess spatial organization (score range: 0-36), whereas the Rey Complex Figure-Organizational Strategy Score30 was used to measure strategic decision making (1 = poor; 2 = fragmented; 3 = part-configural; 4 = conceptual).
Behavior Rating Inventory of Executive Function
The Behavior Rating Inventory of Executive Function31 is a questionnaire that assesses behavioral manifestations of EF. In this study, the Parent version was administered. The BRIEF consists of 86 items, which provide 8 theoretically and empirically derived clinical scales (Inhibit, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Organization of Materials, and Monitor), 2 indices (Metacognitive and Behavioral Regulation), and 1 composite score (Global Executive Composite). Table 1 provides a description of the BRIEF parameters. BRIEF scores are age-gender standardized with a mean of 50 (SD: 10), with higher scores reflecting greater EDF. Scores ≥65 (ie, ≥1.5 SD above the normative mean) are considered to be abnormally elevated and representing clinically significant behavior problems. Internal consistency for the parent form of the BRIEF has been found to be high, ranging from 0.80 to 0.98.31 Clinical validity has been supported with a variety of diagnostic groups.31
Between-group differences (ELBW/very preterm vs NBW) for dichotomous outcome data were analyzed by χ2 analysis and for continuous data by t test as data were normally distributed. For the behavioral parameters with clinical cutoff scores, relative risks were calculated. For adjusting for potential confounding variables, data were also analyzed by multiple linear regression, when appropriate. Sociodemographic factors such as gender, ethnicity, language spoken at home, family structure, mother’s marital status, social class, and mother’s and father’s education were used as covariates in the multivariate analyzes. Furthermore, comparisons were repeated excluding children with significant neurosensory impairment (eg, cerebral palsy, blindness, deafness).
Within the ELBW/very preterm cohort, there was also interest in the contrast between the smallest (birth weight 500-749 g) and most immature (23-25 weeks’ gestation) survivors and their slightly heavier (birth weight 750-999 g) or more mature (26-27 weeks’ gestation) counterparts. These between-group comparisons were analyzed by t test and multiple linear regression when controlling for sociodemographic variables. The bivariate relationship between birth weight/gestational age and EF parameters were analyzed by Pearson correlation coefficient.
With the exception of children with missing data, the analyses included all children. With the numbers in each cohort assessed, we had 80% power of detecting differences in means between groups as small as 0.27 SD. P < .05 was considered statistically significant. As this study was primarily hypothesis generating rather than hypothesis proving and as each of the domains assessed was of individual interest, we did not reduce P values for multiple tests.
The sociodemographic characteristics and gender distribution of the ELBW/very preterm and NBW cohorts were similar (see Table 2). The mean ages of the ELBW/very preterm and NBW cohorts at the time of the assessment were 8.7 years and 8.9 years, respectively. English was the only language spoken at home for the majority of families in both the ELBW/very preterm and NBW cohorts, and ethnicity, based on mother’s race, was comparable. Significantly fewer mothers in the ELBW/very preterm cohort were married in comparison with mothers in the NBW cohort (χ2 = 6.7, P < .01), although the proportion of intact families was similar. Social class of the 2 cohorts did not differ; however, the proportions with at least 12 years of formal education were significantly greater in mothers (χ2 = 8.0, P < .01) and fathers (χ2 = 18.2, P < .001) in the NBW cohort. The cohorts differed significantly in terms of full-scale IQ (mean difference: −9.4; 95% CI: −12.1 to −6.7), with the ELBW/very preterm cohort within the average range (90-109) but nearly two thirds SD below their NBW peers.
Cognitive Assessment of EF
The ELBW/very preterm cohort scored significantly lower than their NBW peers on all cognitive parameters of EF, including verbal conceptual reasoning (Similarities: t476 = −4.2, P < .001), verbal working memory (Digit Span: t473 = −3.7, P < .001), spatial conceptualization (Block Design: t474 = −7.1, P < .001), visual reasoning (Picture Arrangement: t474 = −5.7, P < .001), planning ability (Tower of London: t464 = −2.6, P < .01), and spatial organization (Rey Complex Figure accuracy: t464 = −6.7, P < .001; Table 3). The strategic decision making (Rey Complex Figure strategy) of the ELBW/very preterm cohort was also poorer (χ2 = 11.2, P < .05), with 57% using poor strategies in comparison with 42% of the NBW children. Although the ELBW/very preterm cohort performed well below the NBW cohort across all cognitive parameters, the group means were generally within the average range. Small reductions in mean differences were found when analyses were repeated adjusting for sociodemographic variables, but no statistical conclusions were affected (see Table 3). Excluding children with significant neurosensory impairment also failed to alter the statistical conclusions.
Within the ELBW/very preterm cohort, children with birth weights 500 to 749 g scored lower on all cognitive parameters of EF than those with birth weights 750 to 999 g, and mean differences reached significance for spatial conceptualization (Block Design: mean difference: −1.6; 95% CI: −2.8 to −0.4), visual reasoning (Picture Arrangement: mean difference: −1.4; 95% CI: −2.6 to −0.2), and spatial organization (Rey Complex Figure accuracy: mean difference: −3.4; 95% CI: −5.9 to −0.9). Similarly, children with gestational ages 23 to 25 weeks scored lower on most cognitive parameters than those of gestational ages 26 to 27 weeks; however, the only mean difference to reach significance was spatial organization (Rey Complex Figure accuracy; mean difference: −3.0; 95% CI: −5.3 to −0.6). Controlling for sociodemographic variables did not alter the above findings. Within the ELBW/very preterm group, gestational age and birth weight correlated weakly with the cognitive parameters of EF (correlation coefficient range: 0.001-0.187).
Behavioral Assessment of EF
In comparison with the NBW cohort, the ELBW/very preterm cohort scored higher across all behavioral parameters of EF, including the Global Executive Composite (t448 = 3.3, P = .001), indicating an increased risk for EDF (Table 3). The ELBW/very preterm cohort did not differ significantly in terms of Behavioral Regulation, and of the clinical scales associated with this index score, only Shift was significantly elevated in the ELBW/very preterm cohort (t448 = 2.0, P = .048). The ELBW/very preterm cohort was significantly elevated on the Metacognition index score (t448 = 3.9, P < .001), as a result of higher scores on most of the associated clinical scales including Initiate (t448 = 3.1, P = .002), Working Memory (t448 = 5.1, P < .001), Planning/Organization (t448 = 3.4, P = .001), and Monitoring (t448 = 2.8, P = .006). As shown in Table 4, children in the ELBW/very preterm cohort were at increased risk for exhibiting clinically significant behavioral problems in the Shift (P = .016), Emotional Control (P = .028), Initiate (P = .012), Working Memory (P = .001), and Monitoring (P = .008) domains. Small reductions in mean differences again were observed when analyses were adjusted for sociodemographic variables (Table 3) or when analyses were repeated excluding children with significant neurosensory impairment. Statistical conclusions were largely unaffected by these additional analyses; however, the mean difference for Shift failed to reach significance when adjusting for differences in sociodemographic variables (mean difference: 1.6; 95% CI: −0.4 to 3.5) and when children with neurosensory impairment were excluded (mean difference: 1.7; 95% CI: −0.3 to 3.6).
Within the ELBW/very preterm cohort, children with birth weights 500 to 749 g did not differ on any of the behavioral parameters when compared with children with birth weights 750 to 999 g. Similarly, those with gestational ages 23 to 25 weeks were not elevated on any of the behavioral parameters when compared with those with gestational ages 26 to 27 weeks; however, this latter subgroup was slightly elevated on Emotional Control (mean difference: 4.0; 95% CI: 0.6-7.3). When adjusting for sociodemographic variables, the older gestational group was also found to be scoring higher on the Behavioral Regulation Index (mean difference: 3.5; 95% CI: 0.1-6.9), but no other statistical conclusions were altered. Gestational age and birth weight correlated weakly with the behavioral parameters of EF (range: 0.006-0.181).
Executive skills are important for cognitive and adaptive functioning; however, the analysis of executive processes in preterm children has been largely neglected. Furthermore, the few studies that have examined EDF in preterm samples have tended to use small samples, selective samples, or inadequate outcome measures. Thus, our understanding of the frequency, nature, and severity of EDF in this population is limited. In this study, we assessed both cognitive and behavioral elements of EF in a large regional cohort of school-aged children who were born very preterm (<28 weeks) or with ELBW. We found that the ELBW/very preterm cohort exhibited significant deficits across all cognitive parameters assessed, whereas their behavioral impairments were restricted mainly to the Metacognition domain.
Different patterns of deficits may represent EDF, and understanding the nature of the impairment in children who are born very preterm or with ELBW is crucial for remediation purposes. In our study, the cognitive assessment focused on reasoning ability, working memory, planning and organizational ability, and strategic decision making. The ELBW/very preterm cohort exhibited impairments in all of these areas when compared with NBW peers. The behavioral assessment supported these findings, with parental responses indicating that children in the ELBW/very preterm cohort have more trouble starting activities, generating new ideas and strategies, holding information in mind, planning a sequence of actions in advance, and organizing information and thoughts than children in the NBW cohort. Our cognitive assessment did not include tasks that assess impulse control, self-regulation, and mental flexibility; however, the behavioral assessment found that the ELBW/very preterm cohort experienced greater difficulties monitoring actions and shifting attention than NBW children. Children in the ELBW/very preterm cohort were no more impulsive than their NBW peers, despite previous studies reporting higher rates of attentional problems and attention-deficit/hyperactivity disorder.32–34 In summary, our ELBW/very preterm cohort born in the 1990s exhibited a global deficit in EF rather than a specific pattern of executive deficits. This is consistent with previous studies with preterm children who were born before the 1990s, which report impairments across a range of executive processes including planning ability, impulse control, motor sequencing, spatial working memory, spatial organization, and mental flexibility.16,18,19,22
The magnitude of the mean difference between the ELBW/very preterm and NBW cohorts averaged 0.5 SD for cognitive parameters (range: 0.25-0.8) and 0.25 SD for behavioral parameters (range: 0.1-0.5), but the means for the ELBW/very preterm cohort were generally within the average range. On the basis of the behavioral assessment, significantly more children in the ELBW/very preterm cohort were exhibiting clinically significant impairments than children in the NBW cohort. For example, children in the ELBW/very preterm cohort were 2 to 3 times more likely to be displaying significant problems in monitoring performance, holding information in mind, initiating activities and ideas, and shifting attention. The proportion of ELBW/very preterm children who exhibited clinically relevant problems was relatively small. For instance, the highest rate of clinical problems was identified in the Working Memory domain, with 20% scoring in the clinical range, and only 13% of the ELBW/very preterm cohort were in the clinical range on the Global Executive Composite. However, it is reasonable to assume that this ELBW/very preterm cohort was also at greater risk for “subtle” deficits, which also affect educational progress and adaptive functioning. Children who exhibit mild problems are less likely to arouse parental or teacher concerns, be referred for neuropsychological assessment, and receive specialist assistance.
Our overall findings were robust and were not affected when adjusting for important sociodemographic factors such as gender, ethnicity, mother’s marital status, family structure, language spoken at home, social class, and parental education. Similarly, statistical conclusions were largely unaffected when children with significant neurosensory impairment were excluded from the analyses. Children who were born with birth weights of 500 to 749 g performed more poorly on cognitive parameters than the heavier survivors (750-999 g), but no differences were observed on the behavioral parameters. Children who were born before 26 weeks of gestation tended to perform slightly poorer than their more mature (26-27 weeks) counterparts on cognitive parameters, but, counterintuitive, the more mature subgroup exhibited poorer behavioral regulation, especially in emotional control. Our correlational analyses revealed that birth weight and gestational age correlated weakly with EF parameters (cognitive and behavioral), indicating that other factors must also mediate outcome in this cognitive domain. Unfortunately, the numbers of children in this cohort with grade III/IV IVH (n = 18) and PVL (n = 16) were inadequate to examine the effects of these factors on outcome.
It is important to note that the cognitive deficits exhibited by this ELBW/very preterm cohort were not specific to EF. When compared with the NBW cohort, we found that the ELBW/very preterm cohort also had deficits in nonexecutive skills such as general knowledge (Information subtest24: mean difference: −1.4; 95% CI: −1.9 to −0.8), vocabulary (Vocabulary subtest24: mean difference: −0.9; 95% CI: −1.4 to −0.3), and visual analysis (Picture Completion24: mean difference: −1.3; 95% CI: −1.8 to −0.8). Thus, consistent with previous neuropsychological studies,11–17 children in the ELBW/very preterm cohort were at risk for impairment across a range of cognitive domains. Whether EDF in this population is a primary deficit or secondary to impairments in other domains is yet to be established and will be resolved only with neuroimaging studies. We do not have neuroimaging data at school age in this cohort.
The cognitive and educational problems associated with prematurity are thought to be related to brain anomalies. Periventricular white matter injury, or PVL, is the most common form of brain injury in preterm infants.35 Although the pathogenesis is not entirely clear, PVL is thought to be related to ischemia and can result in focal or diffused lesions.36 A recent report demonstrated that preterm infants with PVL had significantly less cerebral cortical gray matter and brain myelin at term than preterm infants without PVL or term control subjects,35 indicating that early brain insults involving the white matter are likely to impair later myelination and development of gray matter structures. Gray matter and white matter volumes increase dramatically during the third trimester, making brain development of preterm infants vulnerable even if acute brain insults such as PVL and IVH are not present. For example Hüppi et al37 found that between 29 and 41 weeks’ postconceptional age, total brain volumes increased 2.7-fold, cortical gray matter increased 4-fold, and myelinated white matter increased 5-fold (mostly after 36 weeks). Abnormalities of nutrition and metabolic functioning as well as environmental stresses may disrupt this period of rapid brain development, especially in infants with PVL.37 Neuroimaging studies of preterm children in middle childhood38 and adolescence39 support the view that prematurity affects brain development, resulting in long-term structural abnormalities. Such studies have reported disproportionately smaller volumes of the cortex, basal ganglia, amygdala, hippocampus, and corpus callosum as well as an increase in the size of the lateral ventricles in comparison with term control subjects.38,39
For EF, the prefrontal cortex is considered important. The neural systems underpinning EF are numerous, complex, and interrelated, involving prefrontal connections with virtually all other brain regions including the brainstem; occipital, temporal, and parietal lobes; and limbic and subcortical regions.21,40 EDF is not always associated with prefrontal pathology directly but may be related to network disconnections such as white matter damage or impairment to subcortical or posterior brain regions.41,42 Prefrontal neural networks are thought to be responsible for specific functions,41 and as such, the nature of impairment may assist to identify which networks are compromised. Children who are born very preterm or with ELBW seem to exhibit a general cognitive impairment including EDF, which is consistent with neuroimaging studies that report impaired myelination and reduced volumes for many subcortical and posterior structures.35,38
In summary, our study found that school-aged children who were born in the 1990s with ELBW or very preterm are at increased risk for developing EDF compared with their NBW peers. On the basis of our behavioral data, clinically significant difficulties were exhibited in a minority of ELBW/very preterm children; however, even “subtle” deficits may adversely affect academic achievement. As more of these children are now reaching school age, with survival rates in geographic cohorts 3 times higher in the 1990s compared with the 1970s, it is important that the nature of their cognitive deficits be understood by parents, teachers, and health professionals. We propose that preterm children require ongoing neuropsychological review throughout middle childhood so that impairments, such as EDF, can be identified early and intervention strategies can be implemented to reduce the long-term impact of their deficits. Also, additional research is needed to determine the specific brain abnormalities underlying the executive deficits so that preventive strategies, especially in the perinatal period, can be developed and introduced into clinical practice.
This study was supported in part by a grant from Health and Community Services, Victoria, and the National Health and Medical Research Council, Australia.
Participants: Convenor, Lex W. Doyle, MD, FRACP (Royal Women’s Hospital and University of Melbourne). Collaborators (in alphabetical order): Peter J. Anderson, PhD (Royal Women’s Hospital and Murdoch Childrens Research Institute); Catherine Callanan, RN (Royal Women’s Hospital); Elizabeth Carse, FRACP (Monash Medical Centre); Dan Casalaz, FRACP (the Mercy Hospital for Women); Margaret P. Charlton, MEdPsych (Monash Medical Centre); Noni Davis, FRACP (Royal Women’s Hospital); Julianne Duff, FRACP (Royal Women’s Hospital and the Mercy Hospital for Women); Geoffrey Ford, FRACP (Royal Women’s Hospital); Simon Fraser, FRACP (the Mercy Hospital for Women); Marie Hayes, RN (Monash Medical Centre) Mary Kaimakamis, BSc (Royal Women’s Hospital); Elaine Kelly, MA (Royal Women’s Hospital and the Mercy Hospital for Women); Gillian Opie, FRACP (the Mercy Hospital for Women); Andrew Watkins, FRACP (the Mercy Hospital for Women); Heather Woods, RN (the Mercy Hospital for Women); and Victor Yu, MD, FRACP (Monash Medical Centre).
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