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Seminars in Fetal & Neonatal Medicine 19 (2014) 97e104

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Seminars in Fetal & Neonatal Medicine


journal homepage: www.elsevier.com/locate/siny

Review

Growing up after extremely preterm birth: Lifespan mental health


outcomes
Samantha Johnson a, *, Neil Marlow b
a
b

Department of Health Sciences, University of Leicester, Leicester LE1 6TP, UK


Department of Academic Neonatology, Institute for Womens Health, University College London, London, UK

s u m m a r y
Keywords:
Attention decit hyperactivity disorder
Autism spectrum disorders
Comorbidity
Mental health
Outcomes
Preterm birth

There is growing interest in the long-term mental health sequelae of extremely preterm birth. In this paper we
review literature relating to mental health outcomes across the lifespan. Studies conducted in the preschool
years, school age and adolescence, and adulthood show continuity in outcomes and point to an increased risk
for inattention, socio-communicative problems and emotional difculties in individuals born extremely
preterm. Both behavioural and neuroimaging studies also provide evidence of a neurodevelopmental origin
for mental health disorders in this population. Here we summarise contemporary evidence and highlight key
methodological considerations for carrying out and interpreting studies in this eld.
2013 Elsevier Ltd. All rights reserved.

1. Introduction
Extremely preterm (EP) births, before 28 weeks of gestation,
continue to pose the greatest challenge for neonatal medicine.
Providing life-sustaining treatment, minimising environmental
stressors and supporting the family through a traumatic life event are
key challenges for neonatologists and other professionals involved in
perinatal care. For these babies and their families, however, the care
does not end there. The biological vulnerability conferred by EP birth,
which may be amplied through socio-economic disadvantage, can
have a profound impact on development with consequences that
extend across the lifespan. Although EP births comprise just 0.6% of all
births, morbidity is highest among these survivors [1,2]. Cognitive
impairments are the most frequent adverse outcomes [3,4], but there
is growing interest in the impact of preterm birth on mental health
and wellbeing. Here we review literature relating to mental health
outcomes following EP birth. Although we focus on reports from the
most contemporary cohorts, much may be gained through understanding outcomes for older cohorts now in adult life.

2. Studying mental health following extremely preterm birth


Mental health outcomes are generally evaluated as part of longitudinal studies which have, for the most part, sought to identify

* Corresponding author. Address: Department of Health Sciences, University of


Leicester, 22e28 Princess Road West, Leicester LE1 6TP, UK. Tel.: 44 (0) 116 252
5798; fax: 44 (0) 116 252 3272.
E-mail address: sjj19@le.ac.uk (S. Johnson).
1744-165X/$ e see front matter 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.siny.2013.11.004

the prevalence of disorders at various ages. Like all outcome


studies, these suffer the inherent problems of selective drop-out.
Some of the issues relating to the maintenance of cohorts have
recently been discussed [5]. Key aspects of cohort evaluations are:
 Having a clear denominator in order to evaluate how the ndings may be extrapolated to other studies and how representative they are of the population from which they are drawn.
 Evaluating the effect of drop-outs and, where necessary, supplementing the ndings with sensitivity analyses or imputation
techniques.
 Having due regard to these in drawing conclusions.
Single centre studies are more practical to manage, but groups
of babies born in individual hospitals may not be representative of
the wider population. Further challenges occur by the simple fact
that populations change over time, such that more contemporary
cohorts comprise a higher proportion of EP children making comparison with historical reports challenging. When studying outcomes it is important that there is a strong underlying hypothesis
and that pre-study power calculations using realistic estimates of
group differences are computed.
It is widely considered preferable to use diagnostic criteria for
studying mental health disorders and to facilitate comparison between studies, yet variation may still exist depending on the
measure used [6]. However, the often insurmountable economic
and practical challenges of implementing diagnostic interviews
mean that most studies have relied solely on behavioural questionnaires (see Johnson [7] and Arpi and Ferrari [8] for reviews).
These typically generate higher rates of individuals that score above

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the cut-off for clinically signicant problems than meet the criteria
for disorders. This is illustrated using data from the UK EPICure
Study (Fig. 1) [9]. As part of a follow-up at 11 years of age,
emotional, conduct, hyperactivity/inattention and peer relationship problems in a cohort of children born EP (<26 weeks) were
assessed using parent and teacher questionnaires; diagnoses of
corresponding disorders were obtained concurrently [10]. For all
domains, parents reported signicantly more problems than disorders and teachers reported more attention and peer problems
(Fig. 1). This begs the question of who is the most appropriate
respondent for assessing childhood psychopathology. It is welldocumented that parent and teacher reports are only modestly
correlated and that parents report higher rates of problems than
teachers or adolescents themselves, particularly for emotional
disorders [1117]. Obtaining multi-informant data is therefore
advocated for mental health assessment [18,19].
The use of dimensional measures is also advocated for studying
childhood psychopathology in order to quantify the degree to
which symptoms are manifest in individuals and populations [20e
23]. These considerations are particularly important for studying
mental health following EP birth in which there appears to be a
general population shift in psychopathology and a cluster of
symptoms that extends across diagnostic boundaries (see Section
4) [24e26]. As the expression of childhood psychopathology alters
with development, the nature, severity and frequency of behaviours that are considered typical at one age may be rated as pathological at another [20]. It is therefore important to use age- and
gender-specic norms and to obtain contemporaneous reference
data from term-born controls. Where possible, control groups
should be matched, or analyses adjusted, for confounding factors
such as age, sex and socio-economic status. There is controversy
over adjusting for IQ given statistical and theoretical limitations
[27,28] and the comorbidity of neurocognitive sequelae in EP
children (see Section 4.5). Parental mental health may also be a
confounder in light of the higher risk for psychopathology in the
offspring of those with disorders [29]. However, although parents
of preterm children are at risk for parenting stress and poor mental
health [30e32] medical, biological and neurodevelopmental variables are stronger predictors of childhood psychopathology in
preterm samples [33e36], and there is inconsistency in studies of

the relationship between parental mental health and preterm


childrens socio-emotional development [15,30,37,38]. These associations are likely to be bidirectional, potentially mediated by the
quality of parenteinfant interaction [30,39e41]. The importance of
parental mental health as a causal factor in EP childrens psychopathology requires elucidation in longitudinal studies. Parental
mental health is discussed further in this issue by Karli Treyvaud
(Chapter 10).
3. The preschool years
3.1. Behaviour and emotional problems in the preschool years
There is a surprising lack of research regarding behavioural
outcomes during the preschool years. Studies in infancy have
focused on the development of attachment relationships, temperament and parenteinfant interaction (see Korja et al. [42] and
Vanderbilt [43] for reviews). The assessment of early psychopathology becomes more rened from the age of 2e3 years when
well-standardised tools are available to identify clinically signicant difculties, such as the Child Behavior Checklist (CBCL) [44]
and the Strengths and Difculties Questionnaire (SDQ) [45].
Only a few recent studies have investigated outcomes in EP or
extremely low birthweight (ELBW) preschoolers (Table 1). In two
studies, children had more problems on all SDQ scales, suggesting a
generic risk for mental health problems following EP birth [46,47].
Interestingly, Elgen et al. [47] reported that 38% of EP children had
clinically signicant scores yet only 8% had been referred for psychiatric follow-up, highlighting the preponderance of subclinical
symptoms. In a longitudinal study, EP children had signicantly
poorer emotional and behavioural regulation than term-born
children at both 2 and 4 years of age (Table 1); moreover, they
showed less developmental gain than full-term and VP children,
which is suggestive of a specic vulnerability in the development of
early regulatory competence in EP children [48]. More recently,
Scott et al. [49] obtained multi-informant data on EP/ELBW children at 5 years of age. Using both a dimensional and diagnostic
approach, the authors reported greater specicity in outcomes
compared with earlier studies; only attention decit/hyperactivity
disorder (ADHD) symptoms were signicantly and consistently

Fig. 1. Prevalence of parent- and teacher-reported emotional, conduct, attention and peer problems and diagnoses of corresponding psychiatric disorders at 11 years of age among
219 children born extremely preterm (<26 weeks of gestation; EPICure Study) [10]. Asterisks denote signicant between-group differences between informant-rated Strengths and
Difculties Questionnaires and psychiatric diagnoses (P < 0.05). ADHD, attention decit hyperactivity disorder; ASD, autism spectrum disorders.

S. Johnson, N. Marlow / Seminars in Fetal & Neonatal Medicine 19 (2014) 97e104

99

Table 1
Prospective studies of behavioural and emotional problems and psychiatric disorders in extremely low birthweight (ELBW) or extremely preterm (EP) preschoolers born in the
1990s and beyonda.
Publication

Sample characteristics

Clark et al. [48]

Age (years)

Birth year

Preterm

Control

1998e2001
Single centre

N 39
<28 weeks

N 103

4
Woodward et al.[46]

1998e2000
Single centre

N 43
<28 weeks

N 107

Elgen et al. [47]

1999e2000
National

N 255
<28 weeks/<1000 g

N 1089

Scott et al. [49]

2001e2003
Single centre

N 148
<28 weeks/<1000 g

N 111

Domains with signicantly higher


mean scores in EP/ELBW children

Measure

Regulation

BRS

Regulation
Regulation
Emotional
Conduct
Hyperactivity/inattention
Peer relationship
Total difculties
Emotional
Conduct
Hyperactivity/inattention
Peer relationship
Total difculties
ADHD problems
ADHD problems
Affective problems
ADHD/inattentive
ODD

ERC
BRS
SDQ

SDQ

CBCL
TRF
P-ChIPS

BRS, Behaviour Rating Scale (abbreviated version) of the Bayley Scales of Infant Development, 2nd ed., rated by a researcher. ERC, Emotion Regulation Checklist (modied
version), rated by parents; SDQ, Strengths and Difculties Questionnaire; CBCL, Child Behavior Checklist; TRF, Teacher Report Form; P-ChIPS, Childrens Interview for Psychiatric Syndromes e Parent.
a
Studies are included where they report results for comparisons between EP/ELBW children and term-born controls.

this population [53]. Not only are screening tests associated with a
high rate of false positives, but the high prevalence of cognitive,
motor and sensory impairments in this population further confounds scores on these scales [50e52,54]. Importantly, these
studies have only used screening questionnaires and have not
implemented the M-CHAT follow-up interview to improve specicity. The predictive validity of positive screens and the true
prevalence of ASD in this population require investigation: studies
at school age may hold the answer (see Section 4).

increased, and there was a 2.5-fold increased risk for ADHD diagnoses (Table 1). Although parents and teachers rated higher
scores for affective and oppositional problems, respectively, no
other disorders were increased. These studies highlight an association between EP birth, regulatory problems and ADHD that is
already evident in the early years.
3.2. Early indicators of autism spectrum disorders (ASD)
An area gathering increasing interest is the risk for ASD in EP
infants (Table 2). In recent reports, 21e41% of EP [50,51] infants
screened positive for ASD at 18e24 months using the Modied
Checklist for Autism in Toddlers (M-CHAT) parent questionnaire. In
infants born at <27 weeks, 10e20% screened positive using a range
of ASD screening tools [52]. There is warranted concern that these
studies have substantially overestimated the true risk for ASD in

3.3. Predictive validity of early assessments


There is a paucity of longitudinal studies of behavioural outcomes in EP cohorts. Studies of VLBW children have indicated
moderate stability in problems over the preschool years [55,56] and
there is evidence that early screening is predictive of later mental

Table 2
Cohort studies that have investigated autism spectrum symptoms and disorders in extremely preterm and/or extremely low birthweight children.
Publication

Sample characteristics
Age (years)

The early years


Kuban et al. [50]

Moore et al. [51]

Stephens et al. [52]

School age and adolescence


Treyvaud et al. [60]
7
Hack et al. [24]

Johnson et al. [10]

11

Johnson et al. [25]

11

Prevalence of problems

Measure

M-CHAT

41%

M-CHAT

10%

PDD-2

P 0.08

DAWBA

0.6%
0
0
0
0
2.9%

ns
ns
P < 0.001
P 0.001 ns

CSI-4: autistic disorder


CSI-4: Asperger disorder
DAWBA: any ASD
DAWBA: autistic disorder
DAWBA: atypical autism
SCQ

Birth year

Preterm

Control

Preterm

Control

2002e2004
Regional
2006
National
2008e2009
Regional

N 988
<28 weeks
N 523
<26 weeks
N 554
<27 weeks

21%

e
e

2001e2003
Single centre
1992e1995
Single centre
1995
National

N 177
<30 weeks/<1250 g
N 219
<1000 g
N 219
<26 weeks

1995
National

N 219
<26 weeks

N 65
N 176
N 153

N 153

4.5%
2%
1%
8%
6.5%
1.5%
15.8%

P < 0.001

M-CHAT, Modied Checklist for Autism in Toddlers; PDD-2, Pervasive Developmental Disorders Screening Test, 2nd ed.; CSI-4, Child Symptom Inventory 4; DAWBA,
Development and Well Being Assessment; SCQ, Social Communication Questionnaire; ns, non-signicant.

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health [57]. In EP children, internalising behaviour problems at 2.5


years were a signicant predictor of disorders at 11 years of age,
whereas externalising difculties were not [10]. Scores on the CBCL
Withdrawn subscale have also been shown to be a signicant
predictor of later ASD symptoms [25], and scores on this and the
Emotionally Reactive subscale have also been associated with
positive M-CHAT screens [58]. Using a VP sample, Treyvaud et al.
[59] have also shown that internalising difculties, sociale
emotional competence and externalising problems at 2 years predicted emotional symptoms, peer problems and conduct problems
at 5 years, respectively. Socialeemotional problems at age 5 years
also predicted psychiatric disorders at age 7 years [60]. With such
specicity in prediction, it may be assumed that there is stability in
outcomes among EP children and that the early problems highlighted above will manifest in attention, emotional problems and
ASD later in childhood.
4. School age and adolescence
4.1. Dimensional studies
EP survivors are at high risk for clinically signicant problems
throughout middle childhood, with prevalence estimates of 18e
38% [24,26,61e63]. Studies have also shown that the mental health
problems of EP children have a greater impact on their daily living
than those of term-born controls [62,64]. Commensurate with the
temporal stability in neurodevelopmental outcomes [65], the rate
of mental health problems remains high despite advances in
neonatal care [61,64]. Whereas there is a greater risk for behaviour
problems in EP versus VP children [3,66], there is little evidence for
a gestation-related gradient within the EP group itself [62,64].
Compared with the preschool years, there is greater consistency
in ndings at school age. In three studies of six EP/ELBW cohorts,
the authors identied an excess of attention, social and thought or
emotional problems despite using different measures [61,64,67]. In
a study using multi-informant data to identify pervasive problems,
EP children had signicantly more problems on all scales but odds
ratios (ORs) were greatest for these three domains [62]. Conrad
et al. [14] also found that only depression/anxiety and hyperactivity/inattention were signicantly increased in ELBW children aged
7e16 years. These ndings thus point to a cluster of attention, social
and emotional problems in EP children [26].
4.2. Diagnostic studies
In a recent meta-analysis of ve studies [68], the authors reported a weighted OR of 3.66 for psychiatric disorders among

preterm children [68]. Three studies of EP/ELBW children report


consistently elevated risks for disorders with prevalence estimates
ranging 23e32% [10,24,60]. These also provide evidence for the
specic risk for attention and social problems in this population
(Table 3) [10,24]. In their VP cohort, Treyvaud et al. [60] did not
report a signicant increase in these disorders which the authors
acknowledge may be a result of low statistical power; however,
there was a trend for a higher rate of ADHD and anxiety disorders.
Thus there appears to be a pattern of elevated risk for symptoms
and disorders associated with ADHD, peer relationship problems
and emotional disorders, the cluster of which has been termed the
preterm behavioural phenotype [26].
The symptoms and correlates of ADHD and ASD in EP children
may indicate a different aetiology that is associated with aberrant
brain development. Indeed, Laucht et al. [29] have shown that
psychosocial and biological risk factors had independent effects on
behavioural outcomes; specically, psychosocial risk was more
strongly associated with externalising difculties whereas biological risk factors, such as preterm birth, were associated with isolated social and attention problems. Other studies have also noted
stronger associations of attention and peer problems with neurodevelopmental impairments [47]. Such studies provide increasing
support for an environmental, neurodevelopmental origin for
ADHD and ASD in EP children. Literature relating to ADHD and ASD
is summarised briey below.
4.3. Attention decit hyperactivity disorder
As noted earlier, Scott et al. [49] reported a 2.5-fold increased
risk for ADHD in EP children at 5 years of age; these ndings are
echoed later in childhood in which authors have reported ORs of
2.6e2.7 for ADHD in VP/VLBW children [69,70] and higher ORs of
4.2e4.3 for ADHD in those born EP/ELBW [10,24]. Dimensional
measures have indicated a generally increased liability to ADHD
symptoms in EP children and an excess of children with problems
who do not meet diagnostic criteria [66,71,72]. Increasing interest
has focused on the expression of ADHD symptoms in this population with a number of studies highlighting a higher risk for inattention relative to hyperactivity/impulsivity in terms of both
symptoms and disorders [10,34,38,73]. There is also a notable
absence of comorbid conduct disorders that are frequently
observed in general population samples (Table 3) [10,61,72]. It has
therefore been suggested that ADHD in preterm populations may
be better described as inattentive subtype disorders with a purer
neurodevelopmental origin [26,67,74]. The cognitive prole of EP
birth is characterised by core decits in working memory and
visuo-spatial skills which have been shown to mediate

Table 3
Mental health disorders in children born extremely preterm (EP) or with extremely low birthweight (ELBW) in the 1990s and beyond.
Publication

Sample characteristics
Age (years)

Scott et al. [49]

Treyvaud et al. [60]

Hack et al. [24]

Johnson et al. [10]

11

Prevalence of any disorder

Birth year

Preterm

Control

Index vs control

OR (95% CI)

2001e2003
Single centre
2001e2003
Single centre
1992e1995
Single centre

N 148
<28 weeks/<1000 g
N 177
<30 weeks/<1250 g
N 219
<1000 g

N 111

N 65

24% vs 9%

3.13 (1.27e7.71)

N 176

32% vs 15%

2.7 (1.6e4.5)

1995
National

N 219
<26 weeks

N 153

23% vs 9%

3.2 (1.7e6.2)

Disorders signicantly
increased in EP/ELBW
children

Measure

ADHD/combined
ADHD/hyperactive
None

P-ChIPS

ADHD (any)
ADHD/inattentive
ADHD/combined
Specic phobia
ADHD (any)
ADHD/inattentive
Emotional disorders
ASD

DAWBA
CSI-4

DAWBA

OR, odds ratio; CI, condence interval; P-ChIPS, Childrens Interview for Psychiatric Syndromes e Parent; CSI-4, Child Symptom Inventory 4; DAWBA, Development and WellBeing Assessment.

S. Johnson, N. Marlow / Seminars in Fetal & Neonatal Medicine 19 (2014) 97e104

101

performance on executive function and intelligence tests [75,76].


These core decits may also be implicated in the inattention difculties observed in EP children [73,77].
4.4. Autism spectrum disorders
Studies at school age have conrmed a signicantly increased
risk for ASD in EP children, and, as anticipated, the 4e8% prevalence
is markedly lower than the positive screen rate in infancy [24,25]. In
addition, almost twice as many children have clinically signicant
symptoms than have diagnoses [25]. As with ADHD, ASD may also
have a different origin in EP children that is again associated with
aberrant brain development [10,26,50]. ASD in EP children are
more closely associated with a smaller head circumference,
cognitive decits and neurological injuries than are ASD in the
general population [10,50,78,79]. Moreover, EP children have
greater symptoms on the dimensions of impaired social interaction
and communication than repetitive or stereotyped behaviour, the
latter of which is a core symptom domain in diagnostic classications [71,80]. As such, these symptoms may be better characterised
by a social communication disorder. Like ASD, these impairments
may be mediated by EP childrens cognitive decits that adversely
impact on their processing of social and emotional stimuli.
4.5. Comorbidity
The few studies addressing issues of comorbidity have reported
mixed results regarding the rate of comorbid mental health disorders in EP children compared with controls [10,24,49,60]. The most
consistent nding is the lack of comorbid ADHD and conduct disorders. What is perhaps a more pertinent question is to what extent
mental health disorders confer additional morbidity over other
neurodevelopmental sequelae. Numerous studies have shown that
mental health problems are associated with neurosensory, cognitive and motor impairments in this population and, in the majority
of cases, these do not account for the excess of mental health disorders [3,24,56,62]. In the EPICure Study, mental health disorders
conferred only a small degree of additional morbidity over neurodevelopmental disabilities in EP children (Fig. 2). However, it is
important to note that there is a substantial portion of children
whose parents and teachers report clinically signicant difculties
but who do not meet criteria for diagnoses (Fig. 1); thus the true
functional impact of mental health problems is likely to be far
greater than is suggested by the excess of psychiatric disorders
alone.
5. Mental health in adulthood
Emerging data from population registry linkage studies in
Scandinavia indicate a signicant increase in the risk of adult
mental health disorders with decreasing gestational age at birth.
Because of the relatively low population prevalence of these conditions, such large, and necessarily broad, studies are the only ones
to reliably report such ndings. Moster et al. [81] reported an
increased relative risk (RR) of ASD [9.5; 95% condence interval
(CI): 1.5, 36.2] and other disorders of psychological development,
behaviour and emotions (10.5; 5.6, 19.9) in Norwegian adults born
EP. Although the risk of schizophrenia was not signicantly
elevated, it is worth noting that the point prevalence was low even
though the population was censored at 36 years of age. In a further
study of treatment registration among adults in Norway, Halmoy
et al. [82] conrmed that EP survivors remain at increased risk for
ADHD in adulthood (adjusted RR: 5.0; 2.1, 11.8), and a Swedish
study of psychiatric hospitalisations to 23 years also reported
increased risk for non-affective psychosis, depressive disorder and

Fig. 2. Prevalence of moderate/severe neurodevelopmental disability and psychiatric


disorders in 219 11-year-old children born extremely preterm (<26 weeks of gestation)
and a comparison group of 153 classmates born at term (EPICure Study) [4,10].

bipolar affective disorder in adults born <32 weeks [83]. These


latter data conrm the earlier ndings of increased admissions for
psychiatric and addictive disorders [84]. Finally, a study by Crump
et al. [85] conrmed that young adults born EP were more
frequently prescribed psychotrophic medications, specically antipsychotics, antidepressants and hypnotics. As each of these
studies demonstrated a signicant dose effect of prematurity and
a gradation of increased risk with decreasing gestation, there is
apparent continuity of risk from the adolescent studies referred to
above.
Demonstrating this in smaller prospective cohort studies is
more difcult. Saigal et al. [86] reported greater internalised
behaviours in young adults, together with an increased rate of
prescriptions for antidepressants. Several studies of VLBW young
adults have demonstrated a signicant reduction in risk taking
behaviours and social interaction [72,87,88]. Most recently, Burnett et al. [89] have reported a sustained increase in the prevalence of ADHD in EP/ELBW adolescents at 18 years of age, but no
signicant excess of anxiety or mood disorders compared with
normal birth weight controls, using both diagnostic and
dimensional measures. This is somewhat unexpected given that
the majority of previous cohort and population registry linkage
studies have identied increased mood disorders in adolescence
and adulthood. This is therefore encouraging but it remains to be
seen whether such ndings are replicated in other post-1990
cohorts. Taken together, these studies show that although children remain at increased risk of psychiatric disorders in the long

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S. Johnson, N. Marlow / Seminars in Fetal & Neonatal Medicine 19 (2014) 97e104

term, the societal consequences of EP birth in young adulthood


appear to be somewhat less than anticipated, with better social
adaptation and quality of life than might once have been
predicted.
6. A biological basis for psychiatric morbidity
A biological basis for psychiatric disorders in EP survivors is
perhaps understandable after consideration of the effect of prematurity on brain development, which has been described as a
complex amalgam of destructive and developmental inuences
[90]. Studies using magnetic resonance imaging and computational
techniques have identied differences in the brains of EP children
and adults which may act as biomarkers for these evolving conditions [91]. These include not only ongoing adaptation to destructive
lesions, but more subtle differences in brain size/surface area [92]
and regional volumes such as the frontal and temporal cortex or
hippocampus [93], deep gray matter [94] and corpus callosum [95].
Reduced complexity of brain folding and abnormalities on functional activation imply altered developmental trajectories that
mirror impaired executive functions [96]. As discussed above, such
cognitive decits may underpin mental health symptoms and disorders in EP children [77,97].
Although ex-preterm brain structure and function in relation to
specic psychiatric disorders have not been investigated in large
populations of EP individuals, data from middle childhood suggests that structural alterations may be associated with behavioural ndings, for example with attention and internalising
behaviours (fractional anisotropy in a range of overlapping
areas),[98] socio-emotional development (hippocampal size) [99]
and wellbeing (cerebellar growth) [100]. As yet, such studies
have not been sufciently large or systematic to develop a picture
of the underlying neural basis for psychiatric disorders associated
with preterm birth, but the data suggest that there may be a
biological basis for the clinically observed excess of psychopathology in this population.
7. Conclusions
Studies of mental health outcomes following EP birth have
largely sought to document the prevalence of disorders in
middle childhood and adolescence, but reports of longer-term
outcomes are beginning to surface as contemporary cohorts
reach adulthood. Early attention and regulatory problems are
evident in the preschool years and, by childhood, the greater
specicity in outcomes points to a cluster of inattention, peer
relationship problems and emotional symptoms. Approximately
25% have psychiatric disorders but up to double those numbers
may have signicant difculties that impact on function. This
behavioural phenotype shows continuity into adult life with
increased risk for disorders, yet quality of life and social adaptation are better than may have once been anticipated. Mental
health symptoms appear to have a strong neurodevelopmental
origin which may be mediated by core cognitive decits associated with EP birth. Targeted screening for the cluster of mental
health problems associated with EP birth may be benecial for
detecting children with subclinical difculties, particularly during the preschool years when problems start to become evident.
Future studies are needed to identify resilience and risk factors
for mental health disorders and to further elucidate the role of
parental mental health in the evolution of psychopathology in
EP children. As more EP children continue to enter society, a
greater understanding of the aetiology and functional impact of
these disorders will aid in providing appropriate lifelong
support.

Practice points
 Children born extremely preterm may have attention,
emotional or peer relationship problems that do not meet
diagnostic criteria but which may impact on daily function, for which intervention may be beneficial.
 Screening for behaviour problems from 2 years of age
may aid in detecting children with early difficulties and
those at risk of later mental health disorders.
 Researchers and clinicians should consider including
mental health assessments as part of neurodevelopmental outcome evaluations.

Research directions
 Longitudinal studies are needed to investigate the evolution of mental health sequelae throughout the lifespan.
 The role of parental mental health in the development of
childhood psychopathology requires elucidation in this
population.
 More studies are required to understand the neurological
bases of mental health disorders in extremely preterm
children.

Funding sources
Neil Marlow receives a proportion of funding from the Department of Healths NIHR Biomedical Research Centres funding
scheme at UCLH/UCL.
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