Children born very preterm (VPT) are known to be at high risk of under-achievement in mathematics. However the nature of these difficulties is poorly understood. In this study, a regionally representative cohort of 102 children born VPT and a comparison group of 108 children born full term (FT) during 1998-2000 were followed from birth to nine years. At age nine, children were tested using the Woodcock-Johnson III maths fluency subtest, and teacher reports of mathematical achievement and curriculum-based (numeracy project) achievement data were collected. The data was analysed using group comparisons and multiple regression. Parent and teacher ratings of executive function at age six were included as predictors. Findings indicated that children born VPT had elevated rates of mathematical difficulties across all measures including the standardised and curriculum-based measures, and teacher ratings. They also had higher rates of mathematical learning disability. With the exception of curriculum-based measures, these results remained significant even after controlling for socioeconomic status and severe neurodevelopmental impairment. Children born VPT showed particular difficulty using operational strategies, rather than with factual knowledge, and this effect was most marked for addition and multiplication. As well as difficulties in mathematics, children born VPT also showed more difficulty than children born FT in almost all areas of executive function. Difficulties with working memory at age six were significantly associated with poor performance in aspects of curriculum-based measures at age nine.

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Very preterm birth is an important developmental and public health concern, with clear evidence to suggest that very preterm children may be at long term risk of neurodevelopmental impairment and educational difficulties. Although a great deal is known about the neurodevelopmental outcomes associated with very preterm birth,comparatively little is known about the social competence of children born very preterm during the important early childhood period. Therefore, as part of a prospective, longitudinal study, this research examined the social competence of 105 children born very preterm (birth weight <1,500 g and/or gestational age ≤33 weeks) and 108 full term comparison children (gestational age 37-40 weeks) at age 4 years (corrected for extent of prematurity at birth). The aims of this study were 1) to examine the social competence of a regional cohort of children born very preterm and full term comparison children at age four years, 2) to identify infant clinical factors and socio-familial characteristics associated with poor social competence amongst children born very preterm, and 3) to examine the predictive validity of social competence problems amongst both very preterm and full term preschoolers in relation to school academic functioning and behavioural adjustment at age 6 years. At age 4, children were assessed using a range of parent and/or teacher completed questionnaires, spanning emotional regulation, behavioural adjustment and interpersonal social behaviour. Measures included the Emotion Regulation Checklist, the Infant-Toddler Symptoms Checklist, the Strengths and Difficulties Questionnaire, the Behaviour Rating Inventory of Executive Functioning “ Preschool version and the Penn Interactive Peer Play Scale. In addition, as part of a structured research assessment, children completed a battery of false belief tasks and a short form version of the Weschler Preschool and Primary Scales of Intelligence. Two years later at age 6, school teachers qualitatively rated children's behavioural adjustment and academic achievement in math, reading, spelling and language comprehension compared to their classroom peers. Results showed that relative to their full term peers, some children born very preterm tended to score less well across several areas of social competence. Specifically, parent report showed that children born very preterm were more likely to be characterised by higher levels of emotional dysregulation (p=.002) as well as a range of behavioural adjustment problems, spanning inhibitory control problems (p=.03), hyperactivity/inattention (p=.01), conduct problems (p=.01) and emotional symptoms (p=.008). While elevated rates of behavioural adjustment difficulties were also evident amongst very preterm children within the preschool environment, group differences were not statistically significant. However, a statistical trend towards elevated risk of inhibitory control problems amongst very preterm children in the preschool environment was noted (p=.09). Further, children born very preterm were at around a four-fold risk of emotional regulation difficulties of clinical significance,as well as being around 1.5 times more likely to exhibit clinically significant externalising and internalising behavioural difficulties and interpersonal social problems at age 4 years. In contrast, the interpersonal social behaviours and the extent of social cognitive understanding were largely similar across both groups. This pattern of findings remained largely unchanged following statistical control for the selection effects of family socio-economic status. Amongst children born very preterm, significant infant clinical and sociofamilial predictors of both emotional dysregulation and externalizing behaviour were male gender (p=.008/p=.006), neonatal indomethacin (p=.002/p=.005) and elevated maternal anxiety (p=.009/p=.002). Emotional dysregulation was also predicted by low socio-economic status (p=.002). In contrast, internalising behaviour was predicted only by low birth weight (p=.03). Finally, across both groups significant associations were found between overall social competence problems at age 4 years and later school adjustment with those very preterm and full term preschoolers characterised by poor social competence being at elevated risk of a range of behavioural adjustment difficulties and poor academic functioning in reading, spelling and math at age 6 years (corrected). Links between poor social competence and later behavioural adjustment remained across both groups following statistical control for child IQ, while associations with academic functioning were largely attenuated. By age 4 years a number of very preterm children are beginning to display elevated levels of emotional dysregulation, hyperactivity/inattention, conduct problems and emotional symptoms. Further, a substantial proportion of very preterm children may be at risk of developing clinically significant difficulties with these most pronounced in terms of emotional regulation abilities. Children's abilities to regulate their emotions and behaviour represent important building blocks for their later social and emotional functioning. Further, these abilities will likely influence the extent to which children are able to successfully transition to school. Therefore,alongside other important aspects of development, these findings highlight the importance of monitoring the social abilities of preschoolers who were born very preterm across a range of developmental domains and contexts. Preschoolers characterised by emotional, behavioural and/or interpersonal difficulties could then receive targeted intervention aimed at facilitating their social competence prior to school entry.

Very preterm birth is an important developmental and public health concern, with clear evidence to suggest that very preterm children may be at long term risk of neurodevelopmental impairment and educational difficulties. Although a great deal is known about the neurodevelopmental outcomes associated with very preterm birth,comparatively little is known about the social competence of children born very preterm during the important early childhood period. Therefore, as part of a prospective, longitudinal study, this research examined the social competence of 105 children born very preterm (birth weight <1,500 g and/or gestational age ≤33 weeks) and 108 full term comparison children (gestational age 37-40 weeks) at age 4 years (corrected for extent of prematurity at birth). The aims of this study were 1) to examine the social competence of a regional cohort of children born very preterm and full term comparison children at age four years, 2) to identify infant clinical factors and socio-familial characteristics associated with poor social competence amongst children born very preterm, and 3) to examine the predictive validity of social competence problems amongst both very preterm and full term preschoolers in relation to school academic functioning and behavioural adjustment at age 6 years. At age 4, children were assessed using a range of parent and/or teacher completed questionnaires, spanning emotional regulation, behavioural adjustment and interpersonal social behaviour. Measures included the Emotion Regulation Checklist, the Infant-Toddler Symptoms Checklist, the Strengths and Difficulties Questionnaire, the Behaviour Rating Inventory of Executive Functioning “ Preschool version and the Penn Interactive Peer Play Scale. In addition, as part of a structured research assessment, children completed a battery of false belief tasks and a short form version of the Weschler Preschool and Primary Scales of Intelligence. Two years later at age 6, school teachers qualitatively rated children's behavioural adjustment and academic achievement in math, reading, spelling and language comprehension compared to their classroom peers. Results showed that relative to their full term peers, some children born very preterm tended to score less well across several areas of social competence. Specifically, parent report showed that children born very preterm were more likely to be characterised by higher levels of emotional dysregulation (p=.002) as well as a range of behavioural adjustment problems, spanning inhibitory control problems (p=.03), hyperactivity/inattention (p=.01), conduct problems (p=.01) and emotional symptoms (p=.008). While elevated rates of behavioural adjustment difficulties were also evident amongst very preterm children within the preschool environment, group differences were not statistically significant. However, a statistical trend towards elevated risk of inhibitory control problems amongst very preterm children in the preschool environment was noted (p=.09). Further, children born very preterm were at around a four-fold risk of emotional regulation difficulties of clinical significance,as well as being around 1.5 times more likely to exhibit clinically significant externalising and internalising behavioural difficulties and interpersonal social problems at age 4 years. In contrast, the interpersonal social behaviours and the extent of social cognitive understanding were largely similar across both groups. This pattern of findings remained largely unchanged following statistical control for the selection effects of family socio-economic status. Amongst children born very preterm, significant infant clinical and sociofamilial predictors of both emotional dysregulation and externalizing behaviour were male gender (p=.008/p=.006), neonatal indomethacin (p=.002/p=.005) and elevated maternal anxiety (p=.009/p=.002). Emotional dysregulation was also predicted by low socio-economic status (p=.002). In contrast, internalising behaviour was predicted only by low birth weight (p=.03). Finally, across both groups significant associations were found between overall social competence problems at age 4 years and later school adjustment with those very preterm and full term preschoolers characterised by poor social competence being at elevated risk of a range of behavioural adjustment difficulties and poor academic functioning in reading, spelling and math at age 6 years (corrected). Links between poor social competence and later behavioural adjustment remained across both groups following statistical control for child IQ, while associations with academic functioning were largely attenuated. By age 4 years a number of very preterm children are beginning to display elevated levels of emotional dysregulation, hyperactivity/inattention, conduct problems and emotional symptoms. Further, a substantial proportion of very preterm children may be at risk of developing clinically significant difficulties with these most pronounced in terms of emotional regulation abilities. Children's abilities to regulate their emotions and behaviour represent important building blocks for their later social and emotional functioning. Further, these abilities will likely influence the extent to which children are able to successfully transition to school. Therefore,alongside other important aspects of development, these findings highlight the importance of monitoring the social abilities of preschoolers who were born very preterm across a range of developmental domains and contexts. Preschoolers characterised by emotional, behavioural and/or interpersonal difficulties could then receive targeted intervention aimed at facilitating their social competence prior to school entry.

Sammanfattning Mål: Tidigare studier visar att delar av den fysiska och psykiska tillväxten och utvecklingen hos för tidigt födda barn kan påverkas av den förkortade graviditetsperioden. De odontologiska aspekterna av prematuritet har ännu inte till fullo studerats. Syftet med denna studie är att undersöka om tandmognaden påverkas av för tidig födsel och om enskilda tänder i högre utsträckning är mer påverkade.Material och Metod: I studien deltog 116 barn: 36 extremt för tidigt födda barn (extremely preterm - EPT), 38 mycket för tidigt födda barn (very preterm – VPT) och 42 fullgångna kontroller (controls – C). Panoramaröntgenbilder analyserades av fem kalibrerade observatörer, enligt en metod som utvecklats av Demirjian och Goldstein. Röntgenbilderna avidentifierades och mognadsgraden av de 7 permanenta tänderna i underkäkens vänstra sida (tand 31-37) bedömdes enligt ett 8-stegs system. De 7 bedömningarna adderades sedan till en tandmognadspoäng (maturity score) som motsvarade barnets tandmognadsgrad. Detta möjliggjorde jämförelser på såväl gruppnivå som tandnivå. Observatörernas tillförlitlighet och metodens reproducerbarhet utvärderades genom att 27 slumpvis utvalda röntgenbilder bedömdes ytterligare en gång. Statistiska analyser utfördes av studiens resultat samt av reproducerbarheten.Resultat: Resultatet, med hänsyn till variationer i observatörernas bedömningar, visade att EPT-gruppen hade en genomsnittlig tandmognadspoäng mellan 81.9 och 86.7, VPT 85.2-89.1 och kontrollgruppen 88.1-91.0. Samtliga fem observatörer uppvisade statistiskt signifikanta skillnader mellan EPT-gruppen och kontrollgruppen (p≤0.006). På tandnivå uppvisade alla observatörer en signifikant fördröjning (p≤0.002) av tandmognaden för tand 37 när EPT-gruppen jämfördes mot kontrollgruppen. Signifikanta skillnader mellan ett flertal andra tänder erhölls men konsensus mellan observatörerna saknades. Överensstämmelsen inom varje enskild observatör (intra-observer agreement) beräknades med ett Kappa-test, där resultaten varierade mellan 0.16-1.00. Kappa-beräkningen av reproducerbarheten mellan samtliga observatörer (inter-observer agreement) varierade mellan 0.31-0.71.Slutsats: Resultaten i denna studie tyder på en allmän försening av tandmognaden vid 9 års ålder hos de extremt för tidigt födda barnen (EPT), jämfört med fullgångna barn (C). En förkortad gestationsperiod tycks indikera en fördröjning av tandmognaden jämfört med tandmognaden hos fullgångna barn.

Many parents experience high levels of stress after the birth of a premature infant admitted to a neonatal intensive care unit (NICU) given the often fragile status of their infant and the numerous medical interventions necessary to stabilize the infant. Previous research has found that parents of very preterm (VPT; <32 weeks‟ gestation) infants often experience high levels of stress, particularly in relation to feelings of having lost their parental role. Of particular concern are findings which suggest that such symptoms may last beyond the immediate hospitalization period to have an adverse effect on the parental ability to provide quality infant care-giving at home. However, little is known about the paternal NICU stress response, the role of stressors external to the NICU environment and the perceptions of NICU staff. Against this background, aims of this thesis were: 1) to describe and compare sources of NICU stress for mothers and fathers of VPT infants, 2) to identify key predictors of parental NICU stress, 3) to describe staff perceptions of parental NICU stress, and 4) to identify parental stressors external to the NICU. Two cohorts of parents of VPT infants were studied: 11 mothers and 10 fathers of VPT infants (<32 weeks' gestation) admitted to a level III NICU, Christchurch Women's Hospital; and 68 mothers and 68 fathers of VPT infants (<30 weeks' gestation) who participated in the Victorian Infant Brain Studies, admitted to the Royal Women‟s Hospital NICU, Melbourne. Twenty-three NICU nurses from Christchurch Women‟s Hospital, level III NICU were also interviewed. The Parental Stressors Scale: NICU (PSS: NICU) determined sources of stress among parents. NICU nurses completed an adapted version of the PSS: NICU that measured nursing staffs‟ perceptions of parental NICU stress. Parents also completed the Life Events Scale on upsetting life events from the previous 12 months. An external stressors scale which measured stress relating to finances, transport and childcare was developed and completed by parents and staff. Familial demographic and infant clinical information was collected from birth records and hospital databases. Results showed across both cohorts studied that mothers reported significantly higher levels of NICU stress than fathers on the “sights and sounds”, “infant appearance”, and “loss of parental role” subscales on the PSS: NICU (p < .05). The number of upsetting life events (B = .33, p = .01)) and paternal level of NICU stress predicted maternal NICU stress (B = .23, p = .03). Maternal NICU stress also predicted paternal NICU stress (B = .37, p = .01). Staff consistently overestimated parental stress levels (p < .05). The most stressful item on the external stressors scale reported by parents and staff was “fitting in everything else I have to do”. Findings emphasize the need for increased awareness of NICU-specific and NICU-external factors contributing to parental stress. Research into the extent to which staff perceptions of parent experiences may affect the quality of staff-parent relations in the NICU is also warranted. These findings contribute to our understanding of the parental experience of having a preterm infant in the NICU and implications for practice and future research are discussed.

Contexte: Le retard de croissance intra-utérin (RCIU) désigne l’incapacité du fœtus à atteindre son potentiel de croissance déterminé génétiquement en raison de diverses causes. Il est défini le plus souvent par un poids de naissance inférieur au 10ème percentile pour l’âge gestationnel sur les courbes néonatales. Ce travail de thèse a comme objectif de répondre aux questions non-résolues sur la définition et les conséquences du RCIU dans le contexte de la grande prématurité: (1) Quelle est la meilleure définition du RCIU à utiliser pour identifier les enfants à risque ? (2) Quels sont les risques de mortalité et de morbidités néonatales respiratoires et neurologiques associés au RCIU et existe-t-il des interactions avec les pathologies de la grossesse responsables de cette naissance très prématurée ? (3) Quel est l’impact du RCIU sur le devenir neuro-développemental à 2 ans, en particulier chez les enfants nés extrêmement prématurément ? Méthodes: Nous avons utilisé deux sources de données. L’étude MOSAIC (Models for OrganiSing Access to Intensive Care for Very Preterm Babies in Europe) est une étude européenne en population qui porte sur l’ensemble des naissances survenues entre 22 et 31 semaines d’aménorrhée en 2003 dans dix régions européennes. Les enfants ont été suivis jusqu’à la sortie d’hospitalisation (population d’étude : 4525 enfants). La deuxième source est une cohorte d’enfants nés avant 27SA qui ont été hospitalisés dans le service de réanimation néonatale à l'hôpital de Port-Royal de 1999 à 2008 et qui ont eu un examen pédiatrique et une évaluation selon l’échelle de Brunet-Lézine qui inclut quatre domaines du développement global de l’enfant : la motricité globale, la motricité fine, le langage et l’interaction sociale (445 enfants admis, 268 enfants suivis à 2 ans). Résultats: Dans les deux populations, les risques de décès et de dysplasie broncho-pulmonaire étaient plus élevés pour les enfants ayant un poids de naissance <10éme percentile des courbes néonatales, mais également pour des enfants avec un poids plus élevé (entre le 10éme et le 24éme percentile des courbes néonatales ou <10ème percentile des courbes fœtales). Par contre, il n’y avait pas de lien entre les complications neurologiques et le faible poids, ni d’interaction avec les pathologies de la grossesse. Le RCIU était associé à un risque élevé du retard neurocognitif à deux ans d’âge corrigé chez les extrêmes prématurés, surtout dans le domaine de la motricité fine et de l’interaction sociale mais pas dans le domaine du langage et de la motricité globale. Nous n’avons pas trouvé d’association entre le RCIU et le risque d’infirmité motrice cérébrale à deux ans d’âge corrigé. Conclusions: L’utilisation du 10ème percentile des courbes néonatales n’est pas adaptée pour identifier l’impact du RCIU chez les grands prématurés ; l’utilisation de multiples seuils ou de courbes de croissance fœtale est nécessaire. Le RCIU accroit les risques de mortalité et de dysplasie broncho-pulmonaire, mais n’est pas associé aux lésions cérébrales sévères ; ces associations sont observées dans différents contextes périnatals (pathologies vasculaires et infectieuses, et naissances à des âges gestationnels très précoces). Le RCIU représente un facteur pronostic défavorable pour le neuro-développement à moyen terme. Nos résultats soulèvent de nouvelles questions sur le suivi adapté pour les enfants ayant un RCIU après leur sortie de l’hôpital et aussi sur les éventuels mécanismes biologiques pouvant expliquer les liens entre le RCIU avec une morbidité respiratoire et certains domaines du développement neurocognitif à moyen terme. / Background: Intrauterine growth restriction (IUGR) refers to the inability of the fetus to achieve its genetically determined growth potential due to various causes. Most often, it is defined by a birth weight less than the 10th percentile for gestational age using neonatal growth curves. This thesis aims to answer unresolved questions about the definition and consequences of IUGR in the context of very preterm birth: (1) what is the best definition of IUGR for identifying children at risk? (2) What are the risks of mortality and neonatal respiratory and neurological morbidity associated with IUGR and are there interactions with the underlying pregnancy complications responsible for the very preterm birth? (3) What is the impact of IUGR on neurodevelopmental at 2 years, especially for children born extremely preterm ? Methods: We used two data sources. The MOSAIC study (Models for Organising Access to Intensive Care for Very Preterm Babies in Europe) is a European population-based study that included all births occurring between 22 and 31 weeks of gestation in 2003 in ten European regions. The children were followed until hospital discharge (study population = 4525 infants). The second source is a cohort of children born before 27 weeks of GA who were hospitalized in the neonatal intensive care unit at the Port Royal Hospital from 1999 to 2008 and had a pediatric examination and Brunet-Lézine (BL) neurodevelopmental assessment at 2 years of corrected age (445 children in the cohort, 268children followed at 2 years). The BL assessment includes four areas of child development: gross motor, fine motor, language and social interaction skills. Results: In both populations, the risk of death and bronchopulmonary dysplasia were higher for children with a birth weight <10th percentile of neonatal growth curves but also for children with a higher birth weight (between the 10th and the 24th percentile of neonatal growth curves or <10th percentile of fetal growth curves). In contrast, there was no link between neurological complications and low birth weight and no interactions with pregnancy complications. IUGR was associated with neurocognitive delay among extremely preterm children evaluated at two years of corrected age, especially for fine motor and social interaction skills, but not for language and gross motor skills. We did not find any association between IUGR and the risk of cerebral palsy at two years of corrected age. Conclusions: The use of the 10th percentile of neonatal growth curves is not suitable for identifying the impact of IUGR in very preterm infants; using higher thresholds or fetal growth curves is necessary. IUGR increased the risks of mortality and bronchopulmonary dysplasia, but was not associated with severe brain damage; these associations are observed in multiple clinical contexts (vascular and infectious pregnancy complications, and births at very early gestational ages). IUGR is a risk factor for poor medium-term neuro-development. Our results raise new questions about the appropriate surveillance for children with IUGR after discharge from the hospital and also about possible biological mechanisms that could explain the relationship between IUGR and respiratory morbidity and neurocognitive development.

Objectif : Le suivi néonatal introduit une classification des enfants selon leur niveau de handicap : aucun, léger-modéré ou sévère. Les critères de classification, déterminés par des médecins et chercheurs, ne tiennent pas compte des opinions parentales. Lors de ce projet de maîtrise, les perspectives parentales concernant leur enfant prématuré à 18 mois d’âge corrigé ont été explorées. Hypothèse : L’hypothèse formulée était que les perspectives parentales différeraient des normes établies par les professionnels de la santé. Méthode : 190 enfants prématurés <29 semaines ont eu une évaluation standardisée, permettant la classification selon leur niveau de handicap. Les parents ont répondu aux questions : « Quelles sont vos inquiétudes concernant votre enfant? » et « Nommez les meilleures choses à propos de votre enfant. » Leurs réponses ont été analysées en ayant recours à une méthodologie qualitative et corrélées au niveau de handicap présenté par leur enfant. Résultats : Dans cette cohorte, 49% des enfants n’avaient aucun problème de développement, 43% avaient une atteinte légère à modérée et 8% une atteinte sévère. Les principaux thèmes positifs invoqués par les parents incluaient la personnalité (61%), le bonheur (40%), le développement et les progrès (40%), ainsi que la santé physique (11%). Les inquiétudes parentales principales comprenaient le développement (56%) et la santé physique (24%). Il n’y avait pas d’association entre les thèmes positifs et le niveau de handicap. Les parents d’enfants ayant une atteinte légère-modérée étaient davantage inquiets du développement de leur enfant. Conclusion : Les perspectives parentales concernant leurs enfants prématurés sont balancées, et en majorité positives. L’inclusion des perspectives parentales dans la recherche concernant le devenir des enfants prématurés est importante. Ce projet a permis la création d’un questionnaire quantitatif présenté à un plus grand groupe de parents, subventionné par les IRSC. / Objective: Measuring outcomes of premature birth is essential for quality control, research, patient care and information. At 18 months corrected age, children are classified into categories of severe, mild-moderate or no neurodevelopmental impairment (NDI). Outcomes of interest have been chosen by physicians and researchers, never including parental perspectives. The aim of this thesis was to explore parental perspectives regarding their preterm child. Hypothesis: The hypothesis was that parents’ perspectives and concerns would differ from those assessed by professionals. Method: This survey included 190 infants born <29 weeks of gestational age in one tertiary university health center. Infants underwent detailed developmental assessment and were classified according to NDI. Parents were asked two open-ended questions: “What concerns you most about your child?” and “Please describe the best things about your child”. Open-ended questions were analyzed using qualitative methodology, then correlated with level of NDI. Results: In this cohort, 49%, 43% and 8% had no, mild to moderate, and severe NDI. The main positive themes invoked by parents included their child’s personality (61%), happiness (40%), developmental outcome/progress (40%) and physical health (11%). Main themes regarding parental concerns included: neurodevelopment (56%) and physical health (24%). There was no association between positive themes and categories of NDI, but parents of children with mild-moderate NDI reported more concerns about development. Conclusions: Parents of preterm infants have a balanced perspective of their children, mostly positive. Neonatal outcome research would benefit from incorporating parental perspectives regarding their child, balancing prognostic information about preterm birth. This thesis project has led to the creation of a qualitative questionnaire which is now deployed through a CIHR Child-Bright initiative considering parent-important outcomes.