Preschool Mathematics and Literacy Skills and Educational Attainment in Adolescents Born Preterm and Full Term.

OBJECTIVES: To test whether preschool academic skills were associated with educational attainment in adolescence and whether associations differed between individuals born preterm and at full term. STUDY DESIGN: This prospective cohort study comprised 6924 individuals, including n = 444 (6.4%) adolescents born preterm (<37 weeks of gestation) from the Avon Longitudinal Study of Parents and Children. Preschool academic (mathematics and literacy) skills were rated by teachers at 4-5 years. Educational attainment at 16 years was informed by attaining a General Certificate of Secondary Education (GCSE) in key subjects mathematics and English. Logistic regressions assessed the association between preterm birth, preschool mathematics, and GCSE Mathematics and between preterm birth, preschool literacy, and GCSE English. RESULTS: Similar numbers of adolescents born preterm and at term achieved a GCSE in mathematics and English (53.6 % vs 57.4% and 59.5% vs 63.9%, respectively; P values > .05). Higher preschool academic skill scores in mathematics were associated with greater odds of attaining GCSE Mathematics and preschool literacy skills were associated with GCSE English. Adolescents born preterm with higher preschool mathematics (OR: 1.51, CI: 1.14, 2.00) and literacy skills (OR: 1.57, CI: 1.10, 2.25) were more likely to attain GCSEs in the respective subject than their term-born counterparts with equal levels of preschool skills. CONCLUSIONS: Preschool academic skills in mathematics and literacy are associated with educational attainment of preterm and term-born individuals in adolescence. Children born prematurely may benefit more from preschool mathematics and literacy skills for academic and educational success into adolescence than term-born individuals.

The association between early regulatory problems and adult peer relationship quality is mediated by the brain's allostatic-interoceptive system.

BACKGROUND: Early regulatory problems (RPs), i.e., problems with crying, sleeping, and/or feeding during the first years, increase the risk for avoidant personality traits in adulthood, associated with social withdrawal and anxiety. Even more, RPs are linked with functional alterations in the adult default mode and salience networks, comprising the brain's allostatic-interoceptive system (AIS) and playing a role in social interactions. We investigated whether RPs assessed in infancy are associated with difficulties in adult peer relationships mediated by functional alterations of the AIS. METHODS: As part of a large case-controlled prospective study, 42 adults with previous RPs and 70 matched controls (mean age = 28.48, SD = 2.65, 51% male) underwent fMRI during rest. The analysis focused on the intrinsic functional connectivity (iFC) of key nodes of the AIS. Peer relationship quality was assessed via a semi-structured Life Course Interview and the YASR scale. In these same individuals, RPs were assessed at ages 5, 20 and 56 months. RESULTS: RPs in infancy were associated with lower-quality peer relationships and enhanced functional connectivity of the AIS nodes in adulthood, with a stronger effect for multiple and persistent RPs compared with transient-multiple or single-persistent RPs. Importantly, iFC changes of the dorsal mid insula, a primary interoceptive cortex with frontal and temporal regions, mediated the relationship between early RPs and adult peer relationship quality. CONCLUSIONS: Results indicate long-lasting social and neural changes associated with early RPs. Our findings further implicate the AIS in both interoceptive and social processes, while indicating the need for early screening of early RPs.

Recommendations for data collection in cohort studies of preterm born individuals - The RECAP Preterm Core Dataset.

BACKGROUND: Preterm birth (before 37 completed weeks of gestation) is associated with an increased risk of adverse health and developmental outcomes relative to birth at term. Existing guidelines for data collection in cohort studies of individuals born preterm are either limited in scope, have not been developed using formal consensus methodology, or did not involve a range of stakeholders in their development. Recommendations meeting these criteria would facilitate data pooling and harmonisation across studies. OBJECTIVES: To develop a Core Dataset for use in longitudinal cohort studies of individuals born preterm. METHODS: This work was carried out as part of the RECAP Preterm project. A systematic review of variables included in existing core outcome sets was combined with a scoping exercise conducted with experts on preterm birth. The results were used to generate a draft core dataset. A modified Delphi process was implemented using two stages with three rounds each. Three stakeholder groups participated: RECAP Preterm project partners; external experts in the field; people with lived experience of preterm birth. The Delphi used a 9-point Likert scale. Higher values indicated greater importance for inclusion. Participants also suggested additional variables they considered important for inclusion which were voted on in later rounds. RESULTS: An initial list of 140 data items was generated. Ninety-six participants across 22 countries participated in the Delphi, of which 29% were individuals with lived experience of preterm birth. Consensus was reached on 160 data items covering Antenatal and Birth Information, Neonatal Care, Mortality, Administrative Information, Organisational Level Information, Socio-economic and Demographic information, Physical Health, Education and Learning, Neurodevelopmental Outcomes, Social, Lifestyle and Leisure, Healthcare Utilisation and Quality of Life. CONCLUSIONS: This core dataset includes 160 data items covering antenatal care through outcomes in adulthood. Its use will guide data collection in new studies and facilitate pooling and harmonisation of existing data internationally.

Mental health, pain and tiredness in adults born very preterm or with very low birthweight.

AIM: Adults born preterm have increased risk of mental health problems and other neurodevelopmental conditions. We aimed to investigate associations of mental health with pain and tiredness in adults born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) and at term, and whether these associations are influenced by physical activity. METHODS: As part of an EU Horizon 2020 project, individual participant data from six prospective cohort studies were harmonised for 617 VP/VLBW and 1122 term-born participants. Mental health was assessed by the Achenbach System of Empirically Based Assessment Adult Self-Report. Pain and tiredness were harmonised based on specific items from self-reported questionnaires. Associations between mental health and pain or tiredness were explored by linear regression. RESULTS: An increase in the mental health scales internalising, externalising and total problems was associated with increased pain and tiredness in the preterm and term group alike. Results were maintained when adjusting for physical activity. CONCLUSION: The findings indicate that associations between mental health, pain and tiredness in adults are independent of gestation or birthweight. Future research should explore other potential mechanisms that may underlie the increased risk of mental health problems in the preterm population.

Participation in club sport in childhood is associated with mental health in preterm and term born adolescents.

Preterm born individuals have an increased risk for mental health problems. Participation in club sport is associated with better mental health but the causal direction is unclear. It is not known whether this association could also be found in preterm children. Data from term born (N = 10,368), late preterm (N = 630), and very to moderately preterm born (N = 243) children from the Millennium Cohort Study at the ages of 3, 5, 7, 11, and 14 years were used. Longitudinal associations between the parent-reported Strengths and Difficulties questionnaire (SDQ) and club sport participation (days per week) were analysed using multigroup structural equation modelling, adjusting for gender, maternal depression, parental education; motor problems and attrition were controlled for. Multi-group structural equation modelling showed that children with more peer relationship problems, emotional symptoms, conduct problems or hyperactivity-inattention were less likely to participate in club sport at subsequent assessment time points. More days with club sport participation was associated with lower levels of emotional symptoms and peer relationship problems but not conduct problems or hyperactivity-inattention at subsequent ages. Results were similar in all gestational age groups. Club sport participation predicts lower levels of peer relationship and emotional problems in subsequent waves while it is also predicted by lower levels of emotional problems, peer relationship problems, conduct problems and hyperactivity-inattention in preceding waves. Since no differences in the relationship between SDQ subscales and club sport participation were seen with regard to gestational age groups, club sport should be encouraged in all children.

Problems in peer relationships and low engagement in romantic relationships in preterm born adolescents: effects of maternal warmth in early childhood.

This study examined whether maternal warmth in early childhood moderates the association between preterm birth and problems in peer relationships and low engagement in romantic relationships in adolescence. We studied 9193 individuals from the Millennium Cohort Study in the United Kingdom, 99 (1.1%) of whom were born very preterm (VPT; < 32 weeks of gestation) and 629 (6.8%) moderate-to-late preterm (MLPT; 32-36 weeks gestation). Maternal warmth was reported by the mothers when their children were 3 years old. Peer relationship problems were reported by both the participants and their mothers at 14 and 17 years. Further, participants reported their engagement in romantic relationships at 14 and 17 years. All outcome variables were z-standardized, and the moderation effect was examined via hierarchical linear regressions. Compared to full-term birth, both MLPT and VPT birth were associated with lower engagement in romantic relationships at 17 years of age (b = .04, p = .02; b = .11, p = .02, respectively), and VPT birth was associated with increased peer relationship problems at 14 (b = .29, p = .01) and 17 years of age (b = .22, p = .046). Maternal warmth in early childhood was similarly associated with lower peer relationship problems in MLPT, VPT and full-term born adolescents. However, there was no influence of maternal warmth on engagement in romantic relationships at 17 years of age. There is no major modifying effect of maternal warmth in early childhood on the association between PT birth and peer relationship problems and low engagement in romantic relationships at 14 and 17 years of ages.

Sibling and peer bullying victimization in adolescence: Masculinity, femininity, and the moderating role of sex and popularity.

INTRODUCTION: We investigated whether gender-typed traits (masculinity and femininity) contemporaneously predicted self-reported peer victimization, peer-reported peer victimization, and sibling victimization. We also tested the moderating role of sex and popularity. METHODS: A sample of 2782 British pupils aged 11-16 from Central England, UK was screened for bullying involvement and popularity using self-report and peer nominations, and a subsample of 704 (52.7% girls) completed a measure of gender-typed traits (masculinity and femininity). RESULTS: Hierarchical multiple regression analyses revealed that low levels of masculine traits were associated with greater risk of self-reported peer victimization, there were no associations with peer-reported peer victimization, and low levels of feminine traits were associated with greater risk of self-reported sibling victimization. The effects were not moderated by sex, while popularity decreased the risk of self- and peer-reported peer victimization. CONCLUSIONS: Bullying prevention interventions could benefit from including the positive facets of feminine and masculine traits.

Indirect evidence for altered dopaminergic neurotransmission in very premature-born adults.

While animal models indicate altered brain dopaminergic neurotransmission after premature birth, corresponding evidence in humans is scarce due to missing molecular imaging studies. To overcome this limitation, we studied dopaminergic neurotransmission changes in human prematurity indirectly by evaluating the spatial co-localization of regional alterations in blood oxygenation fluctuations with the distribution of adult dopaminergic neurotransmission. The study cohort comprised 99 very premature-born (<32 weeks of gestation and/or birth weight below 1500 g) and 107 full-term born young adults, being assessed by resting-state functional MRI (rs-fMRI) and IQ testing. Normative molecular imaging dopamine neurotransmission maps were derived from independent healthy control groups. We computed the co-localization of local (rs-fMRI) activity alterations in premature-born adults with respect to term-born individuals to different measures of dopaminergic neurotransmission. We performed selectivity analyses regarding other neuromodulatory systems and MRI measures. In addition, we tested if the strength of the co-localization is related to perinatal measures and IQ. We found selectively altered co-localization of rs-fMRI activity in the premature-born cohort with dopamine-2/3-receptor availability in premature-born adults. Alterations were specific for the dopaminergic system but not for the used MRI measure. The strength of the co-localization was negatively correlated with IQ. In line with animal studies, our findings support the notion of altered dopaminergic neurotransmission in prematurity which is associated with cognitive performance.

Risk-Taking Behavior of Adolescents and Young Adults Born Preterm.

OBJECTIVES: To study sexually transmitted Chlamydia trachomatis infections (STCTs), teenage pregnancies, and payment defaults in individuals born preterm as proxies for engaging in risk-taking behavior. STUDY DESIGN: Our population-based register-linkage study included all 191 705 children alive at 10 years (8492 preterm [4.4%]) born without malformations in Finland between January 1987 and September 1990 as each mother's first child within the cohort. They were followed until young adulthood. We used Cox regression to assess the hazards of STCTs, teenage pregnancies, payment defaults, criminal offending, and substance abuse by gestational age. Gestational age was considered both as a continuous and categorical (extremely, very, moderately, late preterm, early term, post term, and full term as reference) exposure. RESULTS: A linear dose-response relationship existed between gestational age and STCT and teenage pregnancy; adjusted hazard for STCT decreased by 1.6% (95% CI, 0.7%-2.6%), and for teenage pregnancy by 3.3% (95% CI, 1.9%-4.8%) per each week decrease in gestational age. Those born extremely preterm (23-27 completed weeks) had a 51% (95% CI, 31%-83%) lower risk for criminal offending than their full-term born counterparts, and those born very preterm (range, 28-31 weeks) had a 28% (95% CI, 7%-53%) higher hazard for payment defaults than those born at full term. Gestational age was not associated with substance abuse. CONCLUSIONS: The lower risk-taking that characterizes people born preterm seems to generalize to sexual and to some extent criminal behavior. Those born very preterm are, however, more likely to experience payment defaults.

ADHD symptoms and diagnosis in adult preterms: systematic review, IPD meta-analysis, and register-linkage study.

BACKGROUND: This study examined differences in ADHD symptoms and diagnosis between preterm and term-born adults (≥18 years), and tested if ADHD is related to gestational age, birth weight, multiple births, or neonatal complications in preterm borns. METHODS: (1) A systematic review compared ADHD symptom self-reports and diagnosis between preterm and term-born adults published in PubMed, Web of Science, and PROQUEST until April 2021; (2) a one-stage Individual Participant Data(IPD) meta-analysis (n = 1385 preterm, n = 1633 term; born 1978-1995) examined differences in self-reported ADHD symptoms[age 18-36 years]; and (3) a population-based register-linkage study of all live births in Finland (01/01/1987-31/12/1998; n = 37538 preterm, n = 691,616 term) examined ADHD diagnosis risk in adulthood (≥18 years) until 31/12/2016. RESULTS: Systematic review results were conflicting. In the IPD meta-analysis, ADHD symptoms levels were similar across groups (mean z-score difference 0.00;95% confidence interval [95% CI] -0.07, 0.07). Whereas in the register-linkage study, adults born preterm had a higher relative risk (RR) for ADHD diagnosis compared to term controls (RR = 1.26, 95% CI 1.12, 1.41, p < 0.001). Among preterms, as gestation length (RR = 0.93, 95% CI 0.89, 0.97, p < 0.001) and SD birth weight z-score (RR = 0.88, 95% CI 0.80, 0.97, p < 0.001) increased, ADHD risk decreased. CONCLUSIONS: While preterm adults may not report higher levels of ADHD symptoms, their risk of ADHD diagnosis in adulthood is higher. IMPACT: Preterm-born adults do not self-report higher levels of ADHD symptoms, yet are more likely to receive an ADHD diagnosis in adulthood compared to term-borns. Previous evidence has consisted of limited sample sizes of adults and used different methods with inconsistent findings. This study assessed adult self-reported symptoms across 8 harmonized cohorts and contrasted the findings with diagnosed ADHD in a population-based register-linkage study. Preterm-born adults may not self-report increased ADHD symptoms. However, they have a higher risk of ADHD diagnosis, warranting preventive strategies and interventions to reduce the presentation of more severe ADHD symptomatology in adulthood.

The association of early regulatory problems with behavioral problems and cognitive functioning in adulthood: two cohorts in two countries.

BACKGROUND: Regulatory problems (RPs; excessive crying, sleeping, or feeding difficulties) that co-occur (i.e., multiple) or are persistent have been associated with cognitive and behavioral problems in childhood. However, it remains unknown if multiple or persistent RPs are associated with cognitive and behavioral problems in adulthood. METHODS: This large prospective longitudinal study (N = 759) was conducted in two cohorts in Germany (N = 342) and Finland (N = 417). RPs were assessed at 5, 20, and 56 months via the same standardized parental interviews and neurological examinations. In young adulthood, questionnaires were used to assess behavioral problems. Cognitive functioning was assessed with IQ tests. We examined the effects of multiple or persistent RPs on the outcomes via analysis of covariance tests and logistic regression controlled for the influence of cohort. RESULTS: Of 163 participants with RPs, 89 had multiple and 77 had persistent RPs. Adults who had early multiple or persistent RPs (N = 151) reported more internalizing (p = .001), externalizing (p = .020), and total behavioral problems (p = .001), and, specifically, more depressive (p = .012), somatic (p = .005), avoidant personality (p < .001), and antisocial personality problems (p = .006) than those who never had RPs (N = 596). Participants with multiple or persistent RPs were more likely to receive any ADHD diagnoses (p = .017), particularly of hyperactive/impulsive subtype (p = .032). In contrast, there were no associations between multiple or persistent RPs and IQ scores in young adulthood. CONCLUSIONS: The results indicate long-lasting associations between multiple or persistent RPs and behavioral problems. Thus, screening for early RPs could help to identify children who are at risk for later behavioral problems.

Comparative evaluation of the health utilities index mark 3 and the short form 6D: evidence from an individual participant data meta-analysis of very preterm and very low birthweight adults.

BACKGROUND: The most appropriate preference-based health-related quality of life (HRQoL) instruments for trials or research studies that ascertain the consequences of individuals born very preterm and/or low birthweight (VP/VLBW) are not known. Agreement between the HUI3 and SF-6D multi-attribute utility measures have not been previously investigated for VP/VLBW and normal birthweight or term-born controls. This study examined the agreement between the outputs of the HUI3 and SF-6D measures among adults born VP/VLBW and normal birthweight or term born controls. METHODS: We used two prospective cohorts of individuals born VP/VLBW and controls contributing to the 'Research on European Children and Adults Born Preterm' (RECAP) consortium which assessed HRQoL using two preference-based measures. The combined dataset of individual participant data (IPD) included 407 adult VP/VLBW survivors and 367 controls, ranging in age from 18 to 26 years. Bland-Altman plots, intra-class correlation coefficients, and generalized linear mixed models in a one-step approach were used to examine agreement between the measures. RESULTS: There was significant discordance between the HUI3 and SF-6D multi-attribute utility measures in the VP/VLBW sample, controls, and in the combined samples. Agreement between the HUI3 and SF-6D multi-attribute utility measures was weaker in controls compared with VP/VLBW individuals. CONCLUSIONS AND RELEVANCE: The HUI3 and SF-6D each provide unique information on different aspects of health status across the groups. The HUI3 better captures preterm-related changes to HRQoL in adulthood compared to SF-6D. Studies focused on measuring physical or cognitive aspects of health will likely benefit from using the HUI3 instead of the SF-6D, regardless of gestational age at birth and birthweight status.

Associations of crying, sleeping, and feeding problems in early childhood and perceived social support with emotional disorders in adulthood.

BACKGROUND: Multiple or persistent crying, sleeping, or feeding problems in early childhood (regulatory problems) are associated with increased internalizing symptoms in adulthood. Unknown is whether early regulatory problems are associated with emotional disorders in adulthood, and what psychosocial factors may provide protection. We tested whether early childhood multiple or persistent regulatory problems are associated with a higher risk of (a) any mood and anxiety disorder in adulthood; (b) perceiving no social support in adulthood; and (c) whether social support provides protection from mood and anxiety disorders among participants who had multiple/persistent regulatory problems and those who never had regulatory problems. METHODS: Data from two prospective longitudinal studies in Germany (n = 297) and Finland (n = 342) was included (N = 639). Regulatory problems were assessed at 5, 20, and 56 months with the same standardized parental interviews and neurological examinations. In adulthood (24-30 years), emotional disorders were assessed with diagnostic interviews and social support with questionnaires. RESULTS: Children with multiple/persistent regulatory problems (n = 132) had a higher risk of any mood disorder (odds ratio (OR) = 1.81 [95% confidence interval = 1.01-3.23]) and of not having any social support from peers and friends (OR = 1.67 [1.07-2.58]) in adulthood than children who never had regulatory problems. Social support from peers and friends provided protection from mood disorders, but only among adults who never had regulatory problems (OR = 4.03 [2.16-7.94]; p = .039 for regulatory problems x social support interaction). CONCLUSIONS: Children with multiple/persistent regulatory problems are at increased risk of mood disorders in young adulthood. Social support from peers and friends may, however, only provide protection from mood disorders in individuals who never had regulatory problems.

Parenting knowledge and parenting self-efficacy of mothers with borderline personality disorder and depression: "I know what to do but think I am not doing it".

Borderline personality disorder (BPD) is a complex mental health condition often associated with previous childhood adversity including maladaptive parenting. When becoming a parent themselves, mothers with BPD have difficulties with various parenting cognitions and practices, but unknown is whether they have appropriate knowledge of sensitive parenting. This study explored whether differences in parenting knowledge or self-efficacy are specific to BPD or also found in mothers with depression, and whether symptom severity or specific diagnosis better explain parenting perceptions. Mothers with BPD (n = 26), depression (n = 25) or HCs (n = 25) completed a Q-sort parenting knowledge task and a parenting self-efficacy questionnaire. Results showed mothers with BPD had the same knowledge of sensitive parenting behaviors as mothers with depression and healthy mothers. Self-reported parenting self-efficacy was lower in mothers with BPD and depression compared with healthy mothers, with symptom severity most strongly associated. A significant but low correlation was found between parenting self-efficacy and knowledge. Findings suggest that mothers with BPD and depression know what good parenting is but think they are not parenting well. Mental health difficulties are not associated with parenting knowledge, but symptom severity appears to be a common pathway to lower parenting self-efficacy. Future interventions should test whether reduction of symptom severity or positive parenting feedback could improve parenting self-efficacy.

Changes in neonatal morbidity, neonatal care practices, and length of hospital stay of surviving infants born very preterm in the Netherlands in the 1980s and in the 2000s: a comparison analysis with identical characteristics definitions.

BACKGROUND: This study evaluates changes in the neonatal morbidity, the neonatal care practices, and the length of hospital stay of surviving very preterm (VP) infants born in the Netherlands in the 1980s and in the 2000s; a period over which historical improvements were introduced into neonatal care. We, herein, also study whether these changes in neonatal morbidity, neonatal care practices and length of hospital stay are associated with sociodemographic, prenatal, and infant characteristics. METHODS: Two community-based cohorts from 1983 (POPS) and 2002-03 (LOLLIPOP) have provided the perinatal data for our study. The analysis enrolled 1,228 participants born VP (before the 32nd week of gestation) and surviving to 2 years of age without any severe congenital malformation. A rigorous harmonisation protocol ensured a precise comparison of the cohorts by using identical definitions of the perinatal characteristics. RESULTS: In 2003, mothers were older when giving birth, had higher multiple birth rates, and significantly more parents had received higher education. In 2003, less VP infants had severe intraventricular haemorrhage and sepsis and relatively more received continuous positive airway pressure, mechanical ventilation and caffeine therapy than in 1983. Antenatal corticosteroids and surfactant therapy were provided only in 2003. The length of the stay in the neonatal intensive care unit and in hospital had decreased in 2003 by 22 and 11 days, respectively. Differences persisted after adjustment for sociodemographic, prenatal, and infant characteristics. CONCLUSIONS: Neonatal morbidities of the surviving VP infants in this study have not increased, and exhibit improvements for various characteristics in two cohorts born 20 years apart with comparable gestational age and birth weight. Our data suggest that the improvements found are associated with more advanced therapeutic approaches and new national protocols in place, and less so with sociodemographic changes. This analysis provides a basis for further comparative analyses of the health and the development of VP children, particularly with regard to long-term outcomes.

Comparing behavioural outcomes in children born extremely preterm between 2006 and 1995: the EPICure studies.

BACKGROUND: Children born extremely preterm (EP) are at increased risk of neurocognitive and behavioural morbidity. Here, we investigate whether behavioural outcomes have changed over time concomitant with increasing survival following EP birth. METHODS: Comparison of outcomes at 11 years of age for two prospective national cohorts of children born EP in 1995 (EPICure) and 2006 (EPICure2), assessed alongside term-born children. Behavioural outcomes were assessed using the parent-completed Strengths and Difficulties Questionnaire (SDQ), DuPaul Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), and Social Communication Questionnaire (SCQ). RESULTS: In EPICure, 176 EP and 153 term-born children were assessed (mean age: 10.9 years); in EPICure2, 112 EP and 143 term-born children were assessed (mean age: 11.8 years). In both cohorts, EP children had higher mean scores and more clinically significant difficulties than term-born children on almost all measures. Comparing outcomes for EP children in the two cohorts, there were no significant differences in mean scores or in the proportion of children with clinically significant difficulties after adjustment for confounders. Using term-born children as reference, EP children in EPICure2 had significantly higher SDQ total difficulties and ADHD-RS hyperactivity impulsivity z-scores than EP children in EPICure. CONCLUSIONS: Behavioural outcomes have not improved for EP children born in 2006 compared with those born in 1995. Relative to term-born peers, EP children born in 2006 had worse outcomes than those born in 1995. There is an ongoing need for long-term clinical follow-up and psychological support for children born EP.

Economic costs and health utility values associated with extremely preterm birth: Evidence from the EPICure2 cohort study.

BACKGROUND: Preterm birth is associated with adverse health and developmental sequelae that impose a burden on finite resources and significant challenges for individuals, families and societies. OBJECTIVES: To estimate economic outcomes at age 11 associated with extremely preterm birth using evidence from a whole population study (EPICure2 study). METHODS: The study population comprised a sample of children born at ≤26 completed weeks of gestation during 2006 in England (n = 200) and a comparison group of classmates born at term (n = 143). Societal costs were estimated using parent and teacher reports of service utilisation, and valuations of work losses and additional care costs to families. Utility scores for the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) were generated using UK and Canadian value sets. Generalised linear regression was used to estimate the impact of extremely preterm birth on societal costs and utility scores. RESULTS: Unadjusted mean societal costs that excluded provision of special educational support in mainstream schools during the 11th year after birth were £6536 for the extremely preterm group and £3275 for their classmates, generating a difference of £3262 (95% confidence interval [CI] £1912, £5543). The mean adjusted cost difference was £2916 (95% CI £1609, £4224), including special educational needs provision in mainstream schools increased the adjusted cost difference to £4772 (95% CI £3166, £6378). Compared with birth at term, extremely preterm birth generated mean-adjusted utility decrements ranging from 0.13 (95% CI 0.09, 0.18) based on the UK HUI2 statistical inference tariff to 0.28 (95% CI 0.18, 0.37) based on the Canadian HUI3 tariff. CONCLUSIONS: The adverse economic impact of extremely preterm birth persists into late childhood. Further longitudinal studies conducted from multiple perspectives are needed to understand the magnitude, trajectory and underpinning mechanisms of economic outcomes following extremely preterm birth.

Mathematical performance in childhood and early adult outcomes after very preterm birth: an individual participant data meta-analysis.

AIM: To investigate the strength of the independent associations of mathematics performance in children born very preterm (<32wks' gestation or <1500g birthweight) with attending postsecondary education and their current employment status in young adulthood. METHOD: We harmonized data from six very preterm birth cohorts from five different countries and carried out one-stage individual participant data meta-analyses (n=954, 52% female) using mixed effects logistic regression models. Mathematics scores at 8 to 11 years of age were z-standardized using contemporary cohort-specific controls. Outcomes included any postsecondary education, and employment/education status in young adulthood. All models were adjusted for year of birth, gestational age, sex, maternal education, and IQ in childhood. RESULTS: Higher mathematics performance in childhood was independently associated with having attended any postsecondary education (odds ratio [OR] per SD increase in mathematics z-score: 1.36 [95% confidence interval {CI}: 1.03, 1.79]) but not with current employment/education status (OR 1.14 per SD increase [95% CI: 0.87, 1.48]). INTERPRETATION: Among populations born very preterm, childhood mathematics performance is important for adult educational attainment, but not for employment status.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Emotional problems and peer victimization in adolescents born very preterm and full-term: Role of self-control skills in childhood.

The aim of the current study was to examine whether self-control skills in childhood moderate the association between very preterm birth (<32 weeks of gestational age) and emotional problems and peer victimization in adolescence. We used data from four prospective cohort studies, which included 29,378 participants in total (N = 645 very preterm; N = 28,733 full-term). Self-control was mother-reported in childhood at 5-11 years whereas emotional problems and peer victimization were both self- and mother-reported at 12-17 years of age. Findings of individual participant data meta-analysis showed that self-control skills in childhood do not moderate the association between very preterm birth and adolescence emotional problems and peer victimization. It was shown that higher self-control skills in childhood predict lower emotional problems and peer victimization in adolescence similarly in very preterm and full-term borns.