Preterm birth and behaviour problems in infants and preschoolage children: a review of the recent literature

Transcription

1 DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY REVIEW Preterm birth and behaviour in infants and preschoolage children: a review of the recent literature ELENA ARPI 1 FABRIZIO FERRARI 2 1 Occupational Medicine Services, Padua University Hospital, Padua; 2 Department of Neonatal Medicine University of Modena and Reggio Emilia, Modena, Italy. Correspondence to Fabrizio Ferrari, Department of Neonatal Medicine, University Hospital of Modena, Via Del Pozzo 71, Modena, Italy. fabrizio.ferrari@unimore.it PUBLICATION DATA Accepted for publication 24th January Published online 21st March ABBREVIATIONS BRS Behaviour Rating Scale BSID-II Bayley Scales of Infant Development, second edition CBCL Child Behavior Checklist SDQ Strength and Difficulties Questionnaire VLBW Very low birthweight The behaviour of children born preterm at school age are well known, but there have been few studies on the behaviour of preterm-born infants during infancy and at preschool age. Fourteen cohort studies published in PubMed and PsycINFO between 2000 and 2012 were reviewed with a focus on the type, occurrence, comorbidity, stability, prediction, perinatal, social, and relational risk factors for behaviour of preterm-born children in infancy (0 2y) and at preschool age (3 5y). The relational risk factor was considered in an additional four papers. Very-preterm, very-low-birthweight, and moderately-preterm children, in both age groups, show more behaviour than term-born comparison children even after perinatal and social risk factors and cognitive performance have been controlled for. Poor social/interactive skills, poor behavioural and emotional self-regulation, emotional difficulties, and reduced attention are the most common behaviour. Behaviour in infancy are predictive of later behaviour and they should be included in follow-up programmes. The survival of preterm infants has steadily increased over the last few decades thanks to continued progress in perinatal care. It was previously feared that this higher rate of survival among the preterm population came at the expense of an increase in severe impairments, but rates of cerebral palsy and sensory deficiencies have, in fact, decreased. 1 Conversely, the rates of subnormal cognitive function in infancy have remained unchanged during the last decades 2 and preterm infants remain at higher risk of later developmental abnormalities in childhood. 3 In particular, high-prevalence and low-severity disabilities such as learning disorders and behaviour are still common conditions in preterm-born children at school age. 3 5 The term behaviour is currently used for a wide spectrum of difficulties in behavioural self-regulation, including hyperactive/aggressive behaviour; interactive, attention, sleep, eating, and sensory sensitivity ; as well as anxiety, depression, and somatic symptoms. At school age, studies performed with screening questionnaires provide evidence of behaviour characterized by inattention/hyperactivity and social and emotional difficulties. 3,5 These findings are confirmed by studies based on psychiatric evaluations that yield diagnoses of psychiatric disorders. The most prevalent disorder is the inattentive subtype of attention-deficit hyperactivity disorder, with an estimated prevalence of 7 to 23%, followed by emotional disorders such as anxiety (9%), and autism spectrum disorders (3.6 8%). 4,5 As far as infancy is concerned, the behaviour of preterm infants were first mentioned in 1939, long before the intensive care era, when Shirley, 6 described a behavioural syndrome that was primarily characterized by motor and speech difficulties, hyperactivity, irascibility, susceptibility to distraction, shyness, and overdependence on the mother. Three decades later, in 1972, Drillien 7 described a picture of transient dystonia, typical of preterm infants, and reported a parental perception of behaviour such as irritability, constant crying and feeding difficulties, jitteriness, and hyper-reaction to noise, change of posture, cleaning, and bathing. The behaviour reported during the first year of life disappeared in the second. Since then, reports on the early behaviour of infants born preterm have been scant. To date, only a few inconclusive studies have investigated these during infancy and the preschool years. This paper looks at the type and occurrence of behaviour in preterm-born children in infancy and at preschool age, and in term-born comparison children or normative reference groups. As the aim of this review was to focus on the clinical relevance of behaviour, additional features such as comorbidity, stability, prediction (predictive value), and perinatal, social, and relational risk factors tied to behaviour were investigated. We reviewed the literature of the last 12 years to examine the behavioural outcome of children born preterm during a period with the most advanced neonatal intensive care. The review is limited to these 12 years to allow an 788 DOI: /dmcn The Authors. Developmental Medicine & Child Neurology 2013 Mac Keith Press

2 easier comparison across studies as new behavioural outcome measures considered in this article were introduced only in the last two decades. METHOD Two comprehensive searches for studies published in PubMed and PsycINFO from January 2000 to January 2012 were conducted. The key search terms used in single and/or combined form were behavioural/social-emotional/psychiatric, outcomes//disorder, preterm birth/preterm children/preterm infants, and preschool age/infancy. The search was limited to English-language articles and to children born preterm. Studies relating to infancy (0 2y) were distinguished from those relating to preschool age (3 5y). Studies not containing a detailed description of behavioural outcome or which were conducted with non-standardized assessment tools were excluded. The age at follow-up was considered to be the corrected age. A total of 14 cohort studies were included and, within each, the type, occurrence, comorbidity, stability, prediction, and risk factors were the subjects searched for. None of the 14 studies included mother infant interaction; therefore, this item was sought in an additional four papers that were not considered in the first search. The strategy of this second search was the same as for the 14 studies, but the key search terms were mother infant interactions, maternal anxiety/stress, and prematurity/preterm birth. Across the 14 studies, behavioural assessment was usually conducted by adopting screening questionnaires. Many of these questionnaires define behaviour according to the dimensional classification system that distinguishes externalizing behaviour usually including aggressive/hyperactive behaviour and sometimes attention (e.g. the Child Behavior Checklist for ages [CBCL/1.5 5]) from internalizing behaviour, including anxious/ depressed symptoms, somatic complaints, and withdrawal. The screening tools used in the 14 studies are described in Table I. TYPE AND OCCURRENCE OF BEHAVIOUR PROBLEMS AT AGE 0 TO 2 YEARS Only 5 out of the 14 studies addressed behaviour in infancy. Some features of these five studies, such as the size of the cohorts, the age of the infants at the time of assessment, the tests used, the exclusion criteria, and the type and occurrence of behaviour in the index and comparison groups, are reported in Table II. It can be seen that three studies were conducted on infants born in the 1990s 16,19,20 and two 17,18 on infants born in the 2000s. Only one study 16 was performed on infants younger than 1year,asecond 17 on infants aged 1, and the other three on children aged 2 years. The main findings of these five studies are reported here. Wolf et al. 16 found that VLBW children scored lower on motor quality, emotional regulation, and orientation/ engagement, i.e. the three dimensions of the Behavioural What this paper adds Multiple behaviour are common in preterm-born children in infancy and at preschool age. Rating Scale (BRS) of the second edition of the Bayley Scales of Infant Development (BSID-II), at 6 months of age. At age 1 year preterm-born infants, 17 assessed on the basis of a psychiatric evaluation with behavioural outcome classified according to the Diagnostic Classification Zero to Three, 21 displayed more psychiatric disorders than their term-born peers: 13% of preterm infants (vs 0%) fulfilled the criteria for multisystem developmental disorder, 4% (vs 0%) for regulatory disorders, and 24.6% (vs 6.7%) for disorders of emotional functioning. Spittle et al., 18 using the parent questionnaire Infant Toddler Socio-Emotional Assessment, found that, at the age of 2 years, children who were born very preterm were rated by their parents as having more internalizing and dysregulation, with lower scores in the competence domain. The dysregulation were apparent in eating difficulties and sensory hypersensitivity, and negative emotionality and low competence manifested in the form of reduced attention, imitation/pretend play, empathy, and mastery motivation. Group mean scores were within the reference range but continued to be higher once adjusted for social risk. In a study using the CBCL/ 2 3 in children aged 2 years who were born very preterm, Stoelhorst et al. 19 found that mean scores were higher than those expected in the general population only on the somatic scale. Another study 20 assessing very preterm-born children at the age of 2 to 3 years (mean age 29mo), using the BRS (BSID-II), partially confirmed the findings of the study by Wolf et al., 16 which was also performed using the BRS: very preterm children scored lower on orientation/engagement and motor quality, with no difference in emotional regulation. The results of the studies performed using the BRS of the BSID-II must be interpreted with caution considering that, as pointed out by Johnson and Marlow, 22 the psychometric proprieties of the BRS are weaker and have less value as a quantifiable outcome measure. Although the criteria to classify and assess psychopathology in infancy are not fully defined yet, 23 it is remarkable that all five studies considered agree that more behaviour are observed in preterm-born infants than in their term-born peers. The reliability of psychiatric diagnosis in infancy is still a matter of debate: infancy is the time when behaviour are difficult to recognize because of the multiple heterogeneous symptoms that may change in type and intensity, and even disappear from month to month. The integration of various information sources including questionnaires, validated interviews, and observational procedures of infant caregiver relationships, leading to a more integrated view of the infant and his or her family, would be particularly useful at this age. Some parent/caregiver questionnaires and observational coding Review 789

3 Table I: Screening tools used to assess childrens behaviour in the 14 studies: tool, author, age range, scales of investigated behavioural domains, and subdomains Assessment and author Age Scales CBCL/4 18 ASEBA questionnaire, Achenbach y Total problem Social Thought Attention Delinquent behaviour Sex CBCL/2 3 ASEBA 2 3y Total problem questionnaire, Achenbach 9 Sleep Somatic Destructive behaviour CBCL/1.5 5 ASEBA 1.5 2y Total problem questionnaire, Emotionally reactive Achenbach and Rescorla 10 Attention Sleep SDQ, Goodmann y Total difficulties Emotional symptoms (anxiety/depression symptoms) Conduct Hyperactivity/inattention Peer Emotionally reactive Prosocial behaviour (actions that benefit other people and children) FTF, Korkman et al y Social skills Emotional/behavioural Obsessive compulsive BRS of BSID-II, Bayley mo Emotional regulation Task persistence, attention Adaption to change Frustration tolerance ITSEA, Briggs- Gowan and Carter mo Activity/impulsivity Aggression/defiance Peer aggression BASC-2, Reynolds 2 21y and Kamphaus 15 Hyperactivity Aggression Motor quality Overall quality of muscle tone Fine/gross motor movements Depression/withdrawal General anxiety Separation distress Inhibition to novelty Anxiety Depression Somatization Delinquent behaviour Destructive behaviour Attention Orientation engagement Child s initiative, interaction with examiner Exploration/enthusiasm towards test materials Levels of positive affect and energy Dysregulation Sleep Negative emotionality Eating Sensory sensitivity Behavioural symptoms Atypicality Attention Competence Compliance Attention Imitation play Mastery motivation Empathy Prosocial peer relations Adaptive skills Adaptability Social skills Activities of daily living Functional communication CBCL, Child Behavior Checklist; ASEBA, Achenbach System of Empirically Based Assessment; SDQ, Strength and Difficulties Questionnaire; FTF, Five to Fifteen Questionnaire; BRS, Behaviour Rating Scale; BSID-II, Bayley Scales of Infant Development, second edition; IT- SEA, Infant Toddler Socio-Emotional Assessment; BASC-2, Behaviour Assessment System for Children, second edition. procedures with satisfactory psychometric properties for screening and/or close evaluations in infancy are already available and could achieve a more reliable psychiatric diagnosis in infancy. 24 TYPE AND OCCURRENCE OF BEHAVIOUR PROBLEMS AT AGE 3 TO 5 YEARS Nine of the 14 studies considered behaviour at preschool age. The size of the cohorts, the age at the time 790 Developmental Medicine & Child Neurology 2013, 55:

4 Table II: Features of the five studies that addressed behaviour in infancy (at age 0 2y), showing the reference, the number of infants in the two cohorts, the year of birth, corrected age at time of assessment, assessment tool used, exclusion criteria adopted, and the type and occurrence of behaviour in the index versus the comparison group Reference Index Control Age Test used Exclusion criteria Type and occurrence of behaviour 0 2y Index Comparison group Wolf VLBW et al. 16 (n=20) 1999 Janssens wks et al. 17 GA and/ or VLBW (n=69) Spittle et al. 18 VP b (n=188) Stoelhorst VP et al. 19 Janssen VP et al. 20 (n=158) (n=437) (n=10) (n=30) (n=70) Normative reference group Normative reference group 6mo BRS of BSID-II Congenital malformation, IVH grade III or IV, mother s drug use 1y DC: 0 3 Severe physical disabilities 2y ITSEA Major and lethal congenital abnormalities 2y CBCL/ y BRS of BSID-II Orientation/ engagement Emotional regulation Median 25th centile 75th centile Orientation/ engagement Emotional regulation Median 25th centile 75th centile < Motor quality Motor quality <0.001 n (%) a Axis I: primary diagnosis n (%) a Axis I: primary diagnosis No diagnosis 56 (81.2) No diagnosis 27 (90) < (0) Regulatory disorders 3 (4.4) Regulatory disorders MSDD 9 (13) MSDD 0 (0) 0 (0) Eating disorders Axis V: emotional functioning 1 (1.4) Eating disorders n (%) Axis V: emotional functioning No disorder 52 (75.4) No disorder 28 (93.3) <0.005 Yes disorder 17 (24.6) Yes disorder 2 (6.7) Mean SD Mean SD n (%) NS Dysregulation Dysregulation Competence Competence NA Mean SD Mean SD <0.05 Chromosomal neuromuscular disease, CP, mother s drug use, unable to undergo testing Anxious/ depressed Anxious/ depressed NS Sleep Sleep NS Somatic Somatic <0.05 Aggressive Aggressive <0.05 Destructive Destructive NS Total Total <0.05 Non-optimal range Orientation/ engagement Emotional regulation % Non-optimal range 18.1 Orientation/ engagement 13.3 Emotional regulation % 10 <0.01 p 10 NS Motor quality 16.5 Motor quality 10 <0.01 c a Prevalence was calculated retrospectively from data provided in the study. b <30wks gestation or <1250g. c p-value adjusted for social risk. VLBW, very low birthweight (<1500g); BRS, Behaviour Rating Scale; BSID-II, Bayley Scales of Infant Development, second edition; IVH, intraventricular haemorrhage; GA, gestational age; DC, diagnostic classification; MSDD, multisystem developmental disorder; ITSEA, Infant Toddler Socio-Emotional Assessment; NS, not significant; VP, very preterm ( 32wks gestation); CP, cerebral palsy. Review 791

5 of assessment, the tests used, the exclusion criteria, and the type and occurrence of behaviour in the index and comparison groups are reported in Table III. Five studies were performed on children born in the 2000s, three on children born in the 1990s, 25,26,32 and one on children born in the 1980s. 33 The comparison between these studies is made easier by the fact that the same tools were used in each, and most cohorts were of an adequately large size. Delobel Ayoub et al. 25 (EPIPAGE study) evaluated more than 1000 very preterm-born children at the age of 3 years and again at the age of 5 years 26 using the parent Strength and Difficulties Questionnaire (SDQ) form. At the age of 3 years, children showed more difficulties on every behavioural scale: hyperactivity, conduct, emotional symptoms, peer, and prosocial behaviour. The prevalence of total behaviour difficulties, obtained by summing the score of the four-symptom scales (hyperactivity/conduct/emotional/peer ), was 20% in very preterm-born children versus 9% in comparison children. 25 At the age of 5 years, children born very preterm still had more total behaviour difficulties, hyperactivity, emotional symptoms, and peer, with a prevalence double that of the comparison children. 26 These findings have been recently confirmed by two studies, 27,28 similarly performed with the SDQ, on children born in the 2000s. At the age of 5 years, 39% of children born very preterm were reported to have total behaviour difficulties on the parent (or teacher or both) SDQ form, compared with 8% in the comparison peer group. 27 In another sample of very preterm-born children aged 5 years, a higher mean total difficulties score was reported on the parent SDQ form. 28 Two further studies conducted with the CBCL/ and CBCL/ showed that the prevalence of total behaviour within the clinical range with the range indicating symptoms of psychopathology was higher in low-birthweight children (20% vs 10%) and children who were born very preterm/vlbw (13% vs 8.7%) than in the general population. A higher prevalence of clinical CBCL/1.5 5 scores in total (7.9% vs 4.9%), in externalizing and internalizing and in somatic complaints, was also found in children at the age of 4 years who were born moderately preterm. 31 Another study 29 also found more internalizing, externalizing, and obsessive compulsive and poorer social skills in children aged 5 who were born with a VLBW. Only one out of the 14 studies 30 did not find more behaviour in extremely low-birthweight children. In contrast to the findings of the other studies, children born with an extremely low birthweight at the age of 3 years scored lower than their term-born peers on adaptive social skills, but the difference is not significant if the corrected age is considered. In summary, the prevalence of one or more types of behaviour problem was higher in children who were born very preterm, VLBW, or also moderately preterm than in comparison children in both age groups (0 2y, 3 5y) and in all but one study. The various types of behaviour problem were heterogeneous in nature at both ages, but particularly in infancy, when poor interactive competencies, poor motor quality, reduced attention, reduced exploration of the environment, somatic symptoms, and poor capacity to regulate emotions and behavioural states were predominant. From age 3 to 5 years, hyperactivity and inattentive behaviour, anxiety/depression, and somatic symptoms and relational difficulties were prevalent. DEVELOPMENT OF BEHAVIOUR PROBLEMS Comorbidity Two studies 19,20 found that behaviour assessed at age 2 years tend to co-occur with delayed motor performance and neurological abnormalities. The Motor Scale and all three BRS scores of the BSID-II were correlated: motor performance was better when orientation/engagement, emotional regulation, and motor quality showed scores within the normal limit. 20 Within another cohort, 19 neurological abnormalities such as asymmetry, general hyper-/hypotonia, and hyper-/hypokinesia were associated with withdrawn behaviour detected by the CBCL/2 3. At preschool age, various studies confirm that both motor and cognitive impairments are associated with behaviour, and in the cognitive, motor, neurological, language, and behaviour domains co occur in 30 to 50% of very preterm-born children at age 5 years. 27,28 Two studies, 25,26 which investigated whether behaviour account for psychomotor and cognitive delay reported that the excess risk decreased slightly after adjustment for cognitive and motor impairments, but remained significant overall and for most separate types of. Stability Stability addresses the question Do behaviour remain stable over time?. No data on the stability of behaviour in infancy are available. Two longitudinal studies found that at preschool age the stability of behaviour in preterm children was approximately 50%. 26,33 In particular, the EPIPAGE study 26 found that 41% of very pretermborn children with a high total difficulties score at 5 years already had a high total difficulties score at 3 years, whereas 46% of those with a high score at age 3 years still had a high score at age 5 years. There was a tendency for children with cerebral lesions on neonatal ultrasound and behaviour at 3 years to continue to experience these at age 5 years. Prediction Prediction tries to answer the question Do behaviour in infancy and at preschool age predict at a later age?. No study included in our review explored the issue of prediction. However, one study, 34 not included in our review, is based on the same cohort of children investigated by two of the studies reviewed here. 18,28 It showed that social emotional difficulties in 792 Developmental Medicine & Child Neurology 2013, 55:

6 Table III: Features of the nine studies that addressed behaviour at preschool age (3 5y) showing the reference, the number of infants in the two cohorts, the year of birth, corrected age at time of assessment, assessment tool, exclusion criteria adopted, and the type and occurrence of behaviour in the index versus the comparison group Reference Index Control Age (y) Test used Exclusion criteria Type and occurrence of behaviour at 3 5y Index, % Comparison group, % p Delobel- Ayoub et al. 25 Delobel- Ayoub et al. 26 VP (n=1228), 1997 VP (n=1102), 1997 Potharst VP a (n=104), et al Roberts VP b (n=195), et al Rautava VP or VLBW et al. 29 (n=588), Baron ELBW (n=60), et al Potijk MP (n=916), et al (n=447) (n=375) (n=95) (n=70) (n=176) (n=90) (n=543) 3 SDQ Blindness, deafness, severe CP, multiple births 5 SDQ Blindness, deafness, severe CP, multiple births 5 SDQ Genetic syndrome, inappropriate IQ for age 5 SDQ Deafness, blindness, severe CP 5 FTF Major disparity between GA/ BW, lethal congenital malformation Total difficulties: 20 Total difficulties: 9 <0.01 <0.01 Hyperactivity/ inattention: 20 Hyperactivity/ inattention: 11 Conduct problem: 16 Conduct problem: 10 <0.01 Emotional symptoms: 15 Emotional symptoms: 10 <0.01 Peer : 14 Peer : 7 <0.01 Prosocial behaviour: 15 Prosocial behaviour: 11 <0.05 Total difficulties: 22 Total difficulties: Hyperactivity/ inattention: 18 Hyperactivity/ inattention: 9 Conduct problem: 11 Conduct problem: 10 NS Emotional symptoms: 21 Emotional symptoms: Peer : 20 Peer : Prosocial behaviour: 15 Prosocial behaviour: 12 NS Total difficulties: 38.5 Total difficulties: Mean SD Mean SD Total difficulties Total difficulties Social skills Behavioural Mean Mean RR d c,e 0.21 Social skills 0.16 Behavioural <0.05 c 1.49 < < <0.05 Obsessive compulsive 0.1 Obsessive compulsive 3 BASC-2 None Mean SD Mean SD 4 CBCL/1.5 5 Congenital malformation or syndrome 1.79 < NS NS Behavioural symptoms Behavioural symptoms NS Adaptive skills Adaptive skills NS Clinical range % Clinical range % c,f Total 7.9 Total 4.6 < < <0.05 Somatic complaints 5.9 Somatic complaints e 3.3 <0.05 Review 793

7 Table III: Continued Type and occurrence of behaviour at 3 5y Index, % Comparison group, % p Exclusion criteria Reference Index Control Age (y) Test used 5 CBCL/4 18 NA Clinical range % Clinical range % Normative reference group f Total 13.2 Total 8.7 < NS < <0.05 Social 2.5 Social 1.0 <0.05 Thought 3.2 Thought 1.2 <0.05 Attention 4.2 Attention 1.3 <0.05 Delinquent behaviour 2.7 Delinquent behaviour 1.0 <0.05 Reijneveld et al. 32 VP or VLBW (n=402), CBCL/2 3 NA Clinical range % Clinical range % NA 3y total y total 10 5y total y total 10 3 and 5 Normative reference group Grey et al. 33 LBW (n=804), 1985 a <30wks gestation or <1000g. b <30wks gestation or <1250g. c p-value adjusted for social risk. d RR, rate ratios refer to the comparison between the index and comparison group. e p-value calculated retrospectively from data provided in the study. For specific syndrome-scale only, significant differences are reported. VP, very preterm ( 32wks gestation); SDQ, Strength and Difficulties Questionnaire; CP, cerebral palsy; NS, not significant; VLBW, very low birthweight (<1500g); GA, gestational age; BW, birthweight; ELBW, extremely low birthweight; BASC-2, Behaviour Assessment System for Children, second edition; MP, moderately preterm (32 35wks gestation); CBCL, Child Behavior Checklist; LBW, low birthweight (<2500g). very preterm-born children aged 2 years specifically predict behaviour at age 5 years, even after accounting for cognitive development and social risk. difficulties at age 2 years predict emotional symptoms at age 5 years, whereas externalizing difficulties at age 2 years predict hyperactivity/inattention at age 5 years. Socio-emotional at age 2 years predict peer relationship at age 5 years. Consistent with these findings, Johnson et al. 4 found that parents report internalizing at age 2 years 6 months as the only independent variable associated with a psychiatric diagnosis in extremely preterm-born children at 11 years. THE RISK FACTORS FOR BEHAVIOUR PROBLEMS Perinatal, social, and relational factors may influence the occurrence of behaviour. Perinatal risk factors As far as the correlation between behaviour and gestational age is concerned, the results of the studies are inconsistent and the degree of preterm birth does not seem to be overtly associated with the occurrence of behaviour. Two studies 19,29 found increasing behaviour with decreasing gestational age, while others failed to find any significant relationship. 26,30,33 The EPI- PAGE study, which evaluated very preterm-born children at the age of 3 years, 25 reported a statistically non-significant trend towards more behaviour at the lowest gestational age. Some medical factors, such as the length of stay in a neonatal intensive care unit 25 and a prolonged need for artificial ventilation, 25,32 negatively affect behavioural outcome. Postnatal corticosteroid exposure is another risk factor that has been associated with a higher occurrence of attention, social, and total behaviour at age 5 years 32 and with lower behavioural competence at age 2 years. 18 Few studies have investigated patterns of cerebral abnormalities affecting behaviour. Ultrasound scan studies report inconsistent findings. 25,26,32 Reijeneveld et al. 32 found that very preterm-born children with grade 3 or 4 intraventricular haemorrhage had higher somatic complaint scores. In contrast, the EPIPAGE study did not find any correlation between intraventricular haemorrhage and behaviour in very preterm-born children at the age of 5 years; 26 however, in the same cohort intraventricular haemorrhage grade 4 was associated with an increase in total behaviour at 3 years, irrespective of neurodevelopmental delay. 25 In one study 18 in which magnetic resonance imaging (MRI) was performed at term-equivalent age, it was confirmed that moderate severe white matter abnormalities on MRI are associated with poorer attention and more peer relationship in children aged 2 who were born very preterm. The excess risk decreased after children with the above-mentioned medical factors were excluded, but remained significant for overall behaviour and for some specific behaviour types. 18,25,26, Developmental Medicine & Child Neurology 2013, 55:

8 Social risk factors In the studies examined, the term social risk factors refers primarily to parental educational level, maternal age at the time of birth, family structure, and socio-economic status. A higher social risk is strongly associated with increased behaviour. 18,19,25 27,31,32 However, the same papers stress that preterm-born children are at increased risk for various types of behaviour compared with term-born comparison children, even after controlling for social risks. 18,19,25 27,31,32 Relational risk factor Maternal mental well-being has been shown to relate to a child s behavioural outcome. 26,33 Recent studies 35,36 have identified a specific interactive pattern, with lower maternal sensitivity, higher maternal control, and unresponsiveness, that plays a precipitating role in the development of children born preterm. During infancy this dysfunctional interactive pattern correlates with a higher prevalence of eating, lower personal, social, and/or hearing speech abilities, 35 or a lower cognitive level, as well as lower social emotional competence and more internalizing. 36 Other studies have found this dysfunctional pattern to be related to maternal anxiety in neonatal intensive care units 37 or perinatal post-traumatic stress in mothers, 38 independently of social and perinatal factors. The implication is that clinical depression in mothers, as well as a more widespread conditions such as maternal anxiety, have a negative influence on mother infant interaction; this in turn affects both the behavioural and cognitive outcomes of the children. DISCUSSION Four main findings emerge from this review. First, starting from infancy and preschool age, the prevalence of one or more types of behaviour is higher in children born preterm than in term-born children, without any overt relationship with lower gestational age. Weaker behavioural domains are multiple and heterogeneous but remain fairly consistent at both ages: poor social/interactive skills, poor behavioural and emotional self-regulation, emotional difficulties, and reduced attention define the profile of behaviour found in the studies reviewed. Second, behaviour tend to co-occur with disabilities in the cognitive, motor, neurological, and language domains. Third, the length of hospitalization in neonatal intensive care units, a prolonged need for artificial ventilation, postnatal corticosteroids, ultrasound imaging and MRI abnormalities, disadvantaged social conditions, and some mother infant patterns of interaction are further risk factors for the development of behaviour. Fourth, behaviour in infancy predict later behaviour in childhood. Behaviour in this population should not be underestimated for a number of reasons. Behaviour difficulties in infancy predict later behaviour in childhood. If this finding is confirmed, infants at risk for later psychiatric disorders could be identified as early as infancy and preschool age. Moreover, the period of 0 to 5 years is crucial as this is when most of the neuropsychological, socio-emotional, and behavioural competences of the child develop, influencing one another and reaching a high level of integration. Social emotional and behaviour are potentially modifiable and the period of 0 to 5 years offers a unique opportunity for intervention, as the child s personality is not yet fully structured and the possibilities of achieving a change are greater than will be the case later on. Recent randomized controlled trials have demonstrated that the behavioural and social skills of children born preterm can be improved through specific intervention programmes. 18,39 Therefore the follow-up team needs to have multidisciplinary competences; outpatient checks on preterm-born children must cover various aspects of development. Specific attention must be focused on behavioural outcome, and screening questionnaires should be accompanied by direct observation of mother infant interaction. During infancy, the parents attitude to their child is crucial: the development of self-regulation and behavioural and social capacities occurs within the context of mother infant father interaction. The evaluation of risk factors, as demonstrated by some of the studies reviewed, confirms the need to observe the quality of interaction. The risk factors associated with behaviour in fact include perinatal/social factors and dysfunctional mother infant patterns of interaction, both of which have been shown to have an impact on the development of behaviour. The findings confirm the multifactorial origin of behaviour, which result from the interaction of perinatal, neurological, and environmental factors. Limitations This review encountered several limitations. The number and characteristics of the children, the tools adopted, and the methods of statistical analysis differed from one study to another, so comparing the findings was difficult. Moreover, most of the studies evaluated behaviour from the parents perspective only, but parents may overor underestimate the behaviour of their child. Therefore, the results of those studies should be interpreted with caution. It is nevertheless striking that similar results were reached despite the different tools and methodologies adopted. In this respect, the weakness of the review actually turned out to be its strength. Conclusion Behaviour in preterm-born children are common in infancy and persist during preschool and school years. They coexist with other developmental impairments and are potential markers of later behaviour and psychiatric disorders; therefore, they should not be allowed to go unrecognized. Behavioural assessment should be included as a crucial part of follow-up programmes starting from early infancy. Review 795

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