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Preterm Birth and Childhood Psychiatric Disorders
Samantha Johnson1 and Neil Marlow2Received 11 November 2010; Accepted 14 December 2010
Top of pageAbstractEpidemiologic studies have, for many years, identified preterm birth as a significant risk factor for psychiatric disorders. There has been a recent resurgence of interest in neurobehavioral outcomes after preterm birth. In this article, we review clinical cohort studies of the prevalence, etiology, and risk factors for psychiatric sequelae in ex preterm children. Studies using diagnostic psychiatric evaluations are few in number but typically report a 3 to 4 fold increased risk for disorders in middle childhood. Our review of studies reveals a behavioral phenotype characterized by an increased risk for symptoms and disorders associated with inattention, anxiety, and social difficulties. The most contemporary studies have also reported a markedly increased prevalence of autism spectrum disorders (ASD) in preterm populations. Our examination of the correlates and comorbidities of psychiatric disorders is indicative of a different causative pathway that may be associated with altered brain development after preterm birth. For a long time, a range of biological insults, including preterm birth and LBW, were considered nonspecific triggers for later disorders (1). More recently, epidemiologic studies in the general population have identified significant inverse incremental associations with birthweight and/or GA at birth: the risk and prevalence of psychiatric morbidity increase as birthweight and GA decrease (2). Although these associations are not confined to those with very LBW (VLBW; birthweight g) or very preterm birth (VPT; wk gestation), the risk is greatest for these groups (2,3).
The casual pathway to these disorders must be interpreted in the context of the known neurologic sequelae of preterm birth, namely focal brain injury and altered brain development (11). These are manifest in the relationship between immaturity and CP (12) and low intelligent quotient (IQ) (13,14)/learning difficulties (15), respectively. The prevalence of impaired outcomes rises more steeply as GA falls below 32 wk and thus one might predict that psychiatric morbidity would be most prevalent in such populations. Where birthweight has been used to define populations, there may be differences in outcomes stemming from the excess of children born after fetal growth restriction, which have independent effects on psychiatric morbidity (16).
Several studies have now followed the progress of very immature cohorts born in the 1980s and 1990s through to adolescence and adult life, and have sought to define the full spectrum of impairment, including psychiatric disorders. We place emphasis on population based studies, particularly for cohorts born in the 1990s, because these reflect the Hermes birkin bags fake most contemporaneous outcomes relevant to current public health concerns. In this article, we review clinical studies of outcomes in middle childhood and beyond and present an overview of behavioral and psychiatric morbidity in relation to neurodevelopmental correlates and early predictors of disorders in preterm populations.
Top of pagePrevalence and Profile of Behavior ProblemsThe majority of studies investigating morbidity for preterm ( wk)/LBW ( g) cohorts have used behavioral screening questionnaires, such as the widely used Child Behavior Checklist (CBCL) (17). These provide cost and time efficient measures for large scale use. There is less consensus for children born moderate to late preterm (32 wk of gestation); some report an excess of behavior problems (31,32), whereas others report no significant difference from term peers (33). A GA related gradient in outcomes is supported by a number of studies in which the prevalence of behavior problems was greater in those born at lower gestations or with LBW (26,34).
Variable findings are reported regarding the risk for internalizing and externalizing problems. In a meta analysis of 16 case control studies of school aged VPT/VLBW children published in 1980 9 of 13 studies reported an increase in internalizing symptoms and 9 of 12 in externalizing symptoms (18). In a later meta analysis of nine case control studies of VPT (here defined as birth wk)/VLBW children published between 1998 and 2008, parents rated their children as having more internalizing problems but combined effect sizes for parent and teacher rated externalizing problems were nonsignificant (35). More recent studies continue to report conflicting results regarding the risk for internalizing (28,31,34) and externalizing problems (23). Given the inverse relationship with maturity, some of this difference may be due simply to heterogeneity in population definitions.
There is greater consensus at the narrowband level in terms of behavioral profiles identified. Hille et al. (36) report cross cultural outcomes in four population based ELBW cohorts born in 1977 and assessed using the CBCL. Externalizing scores were not elevated in any cohort and internalizing scores were increased only in one. In contrast, all four cohorts had significantly increased scores for social, thought, and attention scales (elevated by 0.5 SD relative to country specific controls) and there was a marked absence of aggressive/delinquent behavior. In one cohort, scores for somatic complaints and anxiety/depression were also elevated. Similarly, in a more contemporary population of Swedish EPT children born 1990 social, thought, and attention scales were 0.75 SD higher than controls (28). Studies using other popular screening tools, such as the Strengths and Difficulties Questionnaire (37), typically reveal a similar profile of increased risk for attention/hyperactivity, social, and emotional problems in preterm/LBW populations (19,24,29,38,39).
It is notable that the majority of studies report higher group mean scores on both broadband and narrowband scales, even where the proportion of children scoring in the abnormal range is not significantly increased. This implies that many children may have symptoms that fail to reach clinical significance. This is a consistent finding in studies using dimensional measures of symptomatology in VPT/VLBW populations, particularly for ADHD and ASD.
Although differences in screening tools, population definitions and age at assessment make direct comparisons of prevalence rates difficult, consistencies confirm a behavioral phenotype characterized by inattention/hyperactivity, social, and emotional difficulties and, in general, a greater risk for internalizing rather than externalizing problems, which are more frequent at lower GAs. In the next section, we provide evidence to show that these findings are mirrored in diagnostic studies of psychiatric morbidity in preterm populations, which are characterized by significantly increased rates of ADHD, ASD, and emotional disorders.
Top of pagePrevalence and Prediction of Psychiatric DisordersStudies using diagnostic evaluations are required to provide definitive evidence of an increased prevalence of disorders in preterm/LBW populations. There is a relative paucity of such studies as psychiatric evaluations are costly and difficult to implement in large scale investigations. Although the majority of those that exist have used questionnaires that yield symptom data corresponding with Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria (40), a small number have used more rigorous evaluations. Despite very different methodologies, these report similar prevalence estimates across a range of different populations (Table 1). (41,42) reported 24 to 27% prevalence of disorders in ELBW children. These rates were not significantly increased compared with controls, and in both studies, the risk of disorders was specific to ADHD. In the first study of psychopathology in ELBW children born in the 1990s, Hack et al. (43) reported a significant excess of psychiatric morbidity compared with controls with 32% prevalence of disorders in ELBW children. In all three studies, the prevalence of disorders in the control group (15 was higher than the 10% typically observed in the general population (44) and may thus reflect that the measures were essentially screening tools.
We are aware of only five diagnostic studies (Table 1), of which four have reported 22 to 27% prevalence of disorders in LBW/VLBW children born in the 1980s (16,19,45,46). In the UK EPICure Study, a national prospective cohort study of all births wk of gestation in the UK and replica hermes bag Ireland in 1995, we have reported that 23% met criteria for DSM IV TR (40) defined psychiatric disorders, rising to 25% after imputation to account for selective loss to follow up of more impaired survivors (Fig. 1) (47). Overall, these five studies have reported remarkably similar prevalence estimates and ORs indicating a 3 to 4 fold increased risk for psychiatric disorders in childhood. In VPT populations, males have typically been found to be at greater risk for neuro cognitive impairment compared with females and may therefore be at increased risk for psychiatric sequelae (48,49). However, results regarding gender differences for psychiatric disorders are more equivocal with some reporting a increased risk of disorders for ELBW boys (45) and not others (16,19,46,47). However, variation in the pattern of comorbidities is of greater theoretical significance and is described in the following sections.
Early identification of those at risk for psychiatric disorders would facilitate timely psychiatric referral and provision of support for children and their families. Studies attempting to identify early predictors of psychiatric disorders have produced inconsistent findings. Some report no associations with neonatal variables (19,46), whereas others have reported significant associations with LBW, decreasing GA and smaller head circumference (50). Among EPT children at 11 y of age, we observed no significant univariate associations with any neonatal variables although there was marginally greater risk for boys and vaginal breech deliveries and, in some analyses, neonatal necrotizing enterocolitis. In contrast, we found greater predictive accuracy using later neurodevelopmental measures; in particular, parent reported internalizing behavior problems at 2.5 y and conduct and attentional problems, and neurocognitive impairment at 6 y were associated with psychiatric disorders at 11 y (47). In all these studies, significant associations were found after adjustment for socioeconomic factors and thus highlight the overwhelming effect of perinatal risk (50). Thus, longitudinal neurodevelopmental assessments and behavioral screening may highlight those children who are at risk for later psychiatric morbidity, providing the opportunity for early diagnosis and intervention. Early predictors of specific psychiatric disorders are discussed in the following sections.
Top of pageAttention Deficit/Hyperactivity DisorderADHD is the most prevalent and frequently studied psychiatric disorder in preterm/LBW populations. All but one (51) of the earliest studies using DSM based questionnaires reported a significant excess of ADHD with prevalence rates ranging 16 to 19% and ORs of 2 to 3 in VLBW/ELBW children (41,42,52). More recent studies report prevalence estimates of 9 to 11% in VPT/VLBW (26,53) and 17 to 20% in EPT/ELBW children (26,27), indicating a GA related gradient (26). The pooled relative risk (RR) for ADHD in VPT/VLBW survivors in six studies was 2.64 (95% CI, 1.85 (18) and a recent epidemiological study has reported an RR of 2.7 (95% CI, 1.8 in children born wk (6).
Of the five diagnostic studies, four reported varying prevalence estimates ranging from 7 to 23% in LBW/VLBW children born in the 1980s (Table 2) (16,19,45,46). Increased risk has also been described in cohorts born in the 1990s: 11.5% prevalence in EPT children (Fig. 1) (47) and 17% in those with ELBW (43). Although these two studies used measures with different diagnostic accuracy, the ORs of 4.3 and 4.2, respectively, are remarkably similar. Thus, existing reports indicate a 2 to 3 fold increased risk for ADHD in VPT/VLBW children and a 4 fold increased risk in those born EPT/ELBW (Table 2). First, the male predominance in ADHD in the general population (44) is typically not observed in preterm cohorts (16,19,47).
Finally, VLBW/VPT birth appears to be associated with a greater risk for symptoms of inattention than hyperactivity/impulsivity. Using rating scales that differentiate these Hermes bag season with the main color coordination two dimensions, preterm children were found to have significantly higher mean scores than controls for inattention but not hyperactivity (16). In more recent studies of VPT, EPT, and ELBW children, there are markedly larger effect sizes for inattention compared with hyperactivity as rated by both parents and teachers (43,55). Parallel findings are reported in diagnostic studies using DSM IV based definitions (Table 2). In an early study, Botting et al. found higher rates of ADHD/inattentive (ADHD/I) compared with ADHD/hyperactive (ADHD/H) subtype disorders in VLBW children. In two more recent studies, the excess risk for ADHD in EPT/ELBW children was accounted for by a specific risk for ADHD/I and ADHD/H were not significantly increased in comparison with term children (43,47). We also observed that there was no significant increase in hyperkinetic disorders classified using International Classification of Diseases (ICD) 10 (56) criteria, in which features of hyperactivity are required for diagnosis (47). It thus seems preferable to use DSM IV TR (40) classifications in preterm children.
These converging strands of evidence are indicative of a different causative pathway for ADHD in preterm populations. VPT/VLBW birth is associated with cognitive impairment and impaired brain growth, evidenced by structural abnormalities on MRI (11,57,58). A number of studies have provided evidence indicative of a mediating role of neurodevelopmental factors in the relationship between preterm birth and ADHD, with significant group differences being accounted for by the high prevalence of cognitive impairment in EPT/ELBW children (41,42,47). Indredavik et al. (62) found that ADHD symptoms were associated with reduction in white matter volumes and thinning of the corpus callosum in VLBW adolescents after adjustment for sex and socioeconomic factors. The correlation between symptoms and white matter volume was due to a specific association with inattention scores. Skranes et al. (63) also found that inattention but not hyperactivity scores were associated with fractional anisotropy measurements of white matter in VLBW adolescents. They also found that ADHD was associated with lower fractional anisotropy values in six different anatomical areas and speculate that this may be indicative of disturbed white matter connectivity in extensive areas throughout the fake hermes leather handbags brain. In contrast to classical ADHD, children with ADHD/I can be considered as having a childhood onset dysexecutive syndrome that is characterized by social difficulties related to shyness and withdrawal, internalizing problems, an absence of aggression/delinquent behavior, academic difficulties, and primary deficits in working memory and processing speed (67). Hyperactivity in preterm survivors may be accounted for by poor general cognitive ability, but inattention may be a specific feature of development after preterm birth that is associated with specific executive deficits. This is supported by Nadeau et al. (71) who observed that general cognitive ability mediated the relationship between EPT birth and hyperactivity, whereas the relationship between EPT birth and inattention was mediated specifically by working memory.
Samantha Johnson1 and Neil Marlow2Received 11 November 2010; Accepted 14 December 2010
Top of pageAbstractEpidemiologic studies have, for many years, identified preterm birth as a significant risk factor for psychiatric disorders. There has been a recent resurgence of interest in neurobehavioral outcomes after preterm birth. In this article, we review clinical cohort studies of the prevalence, etiology, and risk factors for psychiatric sequelae in ex preterm children. Studies using diagnostic psychiatric evaluations are few in number but typically report a 3 to 4 fold increased risk for disorders in middle childhood. Our review of studies reveals a behavioral phenotype characterized by an increased risk for symptoms and disorders associated with inattention, anxiety, and social difficulties. The most contemporary studies have also reported a markedly increased prevalence of autism spectrum disorders (ASD) in preterm populations. Our examination of the correlates and comorbidities of psychiatric disorders is indicative of a different causative pathway that may be associated with altered brain development after preterm birth. For a long time, a range of biological insults, including preterm birth and LBW, were considered nonspecific triggers for later disorders (1). More recently, epidemiologic studies in the general population have identified significant inverse incremental associations with birthweight and/or GA at birth: the risk and prevalence of psychiatric morbidity increase as birthweight and GA decrease (2). Although these associations are not confined to those with very LBW (VLBW; birthweight g) or very preterm birth (VPT; wk gestation), the risk is greatest for these groups (2,3).
The casual pathway to these disorders must be interpreted in the context of the known neurologic sequelae of preterm birth, namely focal brain injury and altered brain development (11). These are manifest in the relationship between immaturity and CP (12) and low intelligent quotient (IQ) (13,14)/learning difficulties (15), respectively. The prevalence of impaired outcomes rises more steeply as GA falls below 32 wk and thus one might predict that psychiatric morbidity would be most prevalent in such populations. Where birthweight has been used to define populations, there may be differences in outcomes stemming from the excess of children born after fetal growth restriction, which have independent effects on psychiatric morbidity (16).
Several studies have now followed the progress of very immature cohorts born in the 1980s and 1990s through to adolescence and adult life, and have sought to define the full spectrum of impairment, including psychiatric disorders. We place emphasis on population based studies, particularly for cohorts born in the 1990s, because these reflect the Hermes birkin bags fake most contemporaneous outcomes relevant to current public health concerns. In this article, we review clinical studies of outcomes in middle childhood and beyond and present an overview of behavioral and psychiatric morbidity in relation to neurodevelopmental correlates and early predictors of disorders in preterm populations.
Top of pagePrevalence and Profile of Behavior ProblemsThe majority of studies investigating morbidity for preterm ( wk)/LBW ( g) cohorts have used behavioral screening questionnaires, such as the widely used Child Behavior Checklist (CBCL) (17). These provide cost and time efficient measures for large scale use. There is less consensus for children born moderate to late preterm (32 wk of gestation); some report an excess of behavior problems (31,32), whereas others report no significant difference from term peers (33). A GA related gradient in outcomes is supported by a number of studies in which the prevalence of behavior problems was greater in those born at lower gestations or with LBW (26,34).
Variable findings are reported regarding the risk for internalizing and externalizing problems. In a meta analysis of 16 case control studies of school aged VPT/VLBW children published in 1980 9 of 13 studies reported an increase in internalizing symptoms and 9 of 12 in externalizing symptoms (18). In a later meta analysis of nine case control studies of VPT (here defined as birth wk)/VLBW children published between 1998 and 2008, parents rated their children as having more internalizing problems but combined effect sizes for parent and teacher rated externalizing problems were nonsignificant (35). More recent studies continue to report conflicting results regarding the risk for internalizing (28,31,34) and externalizing problems (23). Given the inverse relationship with maturity, some of this difference may be due simply to heterogeneity in population definitions.
There is greater consensus at the narrowband level in terms of behavioral profiles identified. Hille et al. (36) report cross cultural outcomes in four population based ELBW cohorts born in 1977 and assessed using the CBCL. Externalizing scores were not elevated in any cohort and internalizing scores were increased only in one. In contrast, all four cohorts had significantly increased scores for social, thought, and attention scales (elevated by 0.5 SD relative to country specific controls) and there was a marked absence of aggressive/delinquent behavior. In one cohort, scores for somatic complaints and anxiety/depression were also elevated. Similarly, in a more contemporary population of Swedish EPT children born 1990 social, thought, and attention scales were 0.75 SD higher than controls (28). Studies using other popular screening tools, such as the Strengths and Difficulties Questionnaire (37), typically reveal a similar profile of increased risk for attention/hyperactivity, social, and emotional problems in preterm/LBW populations (19,24,29,38,39).
It is notable that the majority of studies report higher group mean scores on both broadband and narrowband scales, even where the proportion of children scoring in the abnormal range is not significantly increased. This implies that many children may have symptoms that fail to reach clinical significance. This is a consistent finding in studies using dimensional measures of symptomatology in VPT/VLBW populations, particularly for ADHD and ASD.
Although differences in screening tools, population definitions and age at assessment make direct comparisons of prevalence rates difficult, consistencies confirm a behavioral phenotype characterized by inattention/hyperactivity, social, and emotional difficulties and, in general, a greater risk for internalizing rather than externalizing problems, which are more frequent at lower GAs. In the next section, we provide evidence to show that these findings are mirrored in diagnostic studies of psychiatric morbidity in preterm populations, which are characterized by significantly increased rates of ADHD, ASD, and emotional disorders.
Top of pagePrevalence and Prediction of Psychiatric DisordersStudies using diagnostic evaluations are required to provide definitive evidence of an increased prevalence of disorders in preterm/LBW populations. There is a relative paucity of such studies as psychiatric evaluations are costly and difficult to implement in large scale investigations. Although the majority of those that exist have used questionnaires that yield symptom data corresponding with Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria (40), a small number have used more rigorous evaluations. Despite very different methodologies, these report similar prevalence estimates across a range of different populations (Table 1). (41,42) reported 24 to 27% prevalence of disorders in ELBW children. These rates were not significantly increased compared with controls, and in both studies, the risk of disorders was specific to ADHD. In the first study of psychopathology in ELBW children born in the 1990s, Hack et al. (43) reported a significant excess of psychiatric morbidity compared with controls with 32% prevalence of disorders in ELBW children. In all three studies, the prevalence of disorders in the control group (15 was higher than the 10% typically observed in the general population (44) and may thus reflect that the measures were essentially screening tools.
We are aware of only five diagnostic studies (Table 1), of which four have reported 22 to 27% prevalence of disorders in LBW/VLBW children born in the 1980s (16,19,45,46). In the UK EPICure Study, a national prospective cohort study of all births wk of gestation in the UK and replica hermes bag Ireland in 1995, we have reported that 23% met criteria for DSM IV TR (40) defined psychiatric disorders, rising to 25% after imputation to account for selective loss to follow up of more impaired survivors (Fig. 1) (47). Overall, these five studies have reported remarkably similar prevalence estimates and ORs indicating a 3 to 4 fold increased risk for psychiatric disorders in childhood. In VPT populations, males have typically been found to be at greater risk for neuro cognitive impairment compared with females and may therefore be at increased risk for psychiatric sequelae (48,49). However, results regarding gender differences for psychiatric disorders are more equivocal with some reporting a increased risk of disorders for ELBW boys (45) and not others (16,19,46,47). However, variation in the pattern of comorbidities is of greater theoretical significance and is described in the following sections.
Early identification of those at risk for psychiatric disorders would facilitate timely psychiatric referral and provision of support for children and their families. Studies attempting to identify early predictors of psychiatric disorders have produced inconsistent findings. Some report no associations with neonatal variables (19,46), whereas others have reported significant associations with LBW, decreasing GA and smaller head circumference (50). Among EPT children at 11 y of age, we observed no significant univariate associations with any neonatal variables although there was marginally greater risk for boys and vaginal breech deliveries and, in some analyses, neonatal necrotizing enterocolitis. In contrast, we found greater predictive accuracy using later neurodevelopmental measures; in particular, parent reported internalizing behavior problems at 2.5 y and conduct and attentional problems, and neurocognitive impairment at 6 y were associated with psychiatric disorders at 11 y (47). In all these studies, significant associations were found after adjustment for socioeconomic factors and thus highlight the overwhelming effect of perinatal risk (50). Thus, longitudinal neurodevelopmental assessments and behavioral screening may highlight those children who are at risk for later psychiatric morbidity, providing the opportunity for early diagnosis and intervention. Early predictors of specific psychiatric disorders are discussed in the following sections.
Top of pageAttention Deficit/Hyperactivity DisorderADHD is the most prevalent and frequently studied psychiatric disorder in preterm/LBW populations. All but one (51) of the earliest studies using DSM based questionnaires reported a significant excess of ADHD with prevalence rates ranging 16 to 19% and ORs of 2 to 3 in VLBW/ELBW children (41,42,52). More recent studies report prevalence estimates of 9 to 11% in VPT/VLBW (26,53) and 17 to 20% in EPT/ELBW children (26,27), indicating a GA related gradient (26). The pooled relative risk (RR) for ADHD in VPT/VLBW survivors in six studies was 2.64 (95% CI, 1.85 (18) and a recent epidemiological study has reported an RR of 2.7 (95% CI, 1.8 in children born wk (6).
Of the five diagnostic studies, four reported varying prevalence estimates ranging from 7 to 23% in LBW/VLBW children born in the 1980s (Table 2) (16,19,45,46). Increased risk has also been described in cohorts born in the 1990s: 11.5% prevalence in EPT children (Fig. 1) (47) and 17% in those with ELBW (43). Although these two studies used measures with different diagnostic accuracy, the ORs of 4.3 and 4.2, respectively, are remarkably similar. Thus, existing reports indicate a 2 to 3 fold increased risk for ADHD in VPT/VLBW children and a 4 fold increased risk in those born EPT/ELBW (Table 2). First, the male predominance in ADHD in the general population (44) is typically not observed in preterm cohorts (16,19,47).
Finally, VLBW/VPT birth appears to be associated with a greater risk for symptoms of inattention than hyperactivity/impulsivity. Using rating scales that differentiate these Hermes bag season with the main color coordination two dimensions, preterm children were found to have significantly higher mean scores than controls for inattention but not hyperactivity (16). In more recent studies of VPT, EPT, and ELBW children, there are markedly larger effect sizes for inattention compared with hyperactivity as rated by both parents and teachers (43,55). Parallel findings are reported in diagnostic studies using DSM IV based definitions (Table 2). In an early study, Botting et al. found higher rates of ADHD/inattentive (ADHD/I) compared with ADHD/hyperactive (ADHD/H) subtype disorders in VLBW children. In two more recent studies, the excess risk for ADHD in EPT/ELBW children was accounted for by a specific risk for ADHD/I and ADHD/H were not significantly increased in comparison with term children (43,47). We also observed that there was no significant increase in hyperkinetic disorders classified using International Classification of Diseases (ICD) 10 (56) criteria, in which features of hyperactivity are required for diagnosis (47). It thus seems preferable to use DSM IV TR (40) classifications in preterm children.
These converging strands of evidence are indicative of a different causative pathway for ADHD in preterm populations. VPT/VLBW birth is associated with cognitive impairment and impaired brain growth, evidenced by structural abnormalities on MRI (11,57,58). A number of studies have provided evidence indicative of a mediating role of neurodevelopmental factors in the relationship between preterm birth and ADHD, with significant group differences being accounted for by the high prevalence of cognitive impairment in EPT/ELBW children (41,42,47). Indredavik et al. (62) found that ADHD symptoms were associated with reduction in white matter volumes and thinning of the corpus callosum in VLBW adolescents after adjustment for sex and socioeconomic factors. The correlation between symptoms and white matter volume was due to a specific association with inattention scores. Skranes et al. (63) also found that inattention but not hyperactivity scores were associated with fractional anisotropy measurements of white matter in VLBW adolescents. They also found that ADHD was associated with lower fractional anisotropy values in six different anatomical areas and speculate that this may be indicative of disturbed white matter connectivity in extensive areas throughout the fake hermes leather handbags brain. In contrast to classical ADHD, children with ADHD/I can be considered as having a childhood onset dysexecutive syndrome that is characterized by social difficulties related to shyness and withdrawal, internalizing problems, an absence of aggression/delinquent behavior, academic difficulties, and primary deficits in working memory and processing speed (67). Hyperactivity in preterm survivors may be accounted for by poor general cognitive ability, but inattention may be a specific feature of development after preterm birth that is associated with specific executive deficits. This is supported by Nadeau et al. (71) who observed that general cognitive ability mediated the relationship between EPT birth and hyperactivity, whereas the relationship between EPT birth and inattention was mediated specifically by working memory.
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