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.

DNA methylation and general psychopathology in childhood: an epigenome-wide meta-analysis from the PACE consortium.

The general psychopathology factor (GPF) has been proposed as a way to capture variance shared between psychiatric symptoms. Despite a growing body of evidence showing both genetic and environmental influences on GPF, the biological mechanisms underlying these influences remain unclear. In the current study, we conducted epigenome-wide meta-analyses to identify both probe- and region-level associations of DNA methylation (DNAm) with school-age general psychopathology in six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was examined both at birth (cord blood; prospective analysis) and during school-age (peripheral whole blood; cross-sectional analysis) in total samples of N = 2178 and N = 2190, respectively. At school-age, we identified one probe (cg11945228) located in the Bromodomain-containing protein 2 gene (BRD2) that negatively associated with GPF (p = 8.58 × 10-8). We also identified a significant differentially methylated region (DMR) at school-age (p = 1.63 × 10-8), implicating the SHC Adaptor Protein 4 (SHC4) gene and the EP300-interacting inhibitor of differentiation 1 (EID1) gene that have been previously implicated in multiple types of psychiatric disorders in adulthood, including obsessive compulsive disorder, schizophrenia, and major depressive disorder. In contrast, no prospective associations were identified with DNAm at birth. Taken together, results of this study revealed some evidence of an association between DNAm at school-age and GPF. Future research with larger samples is needed to further assess DNAm variation associated with GPF.

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.

Maternal social support during and after pregnancy and child cognitive ability: examining timing effects in two cohorts.

BACKGROUND: Maternal anxiety, depression, and stress during and after pregnancy are negatively associated with child cognitive development. However, the contribution of positive maternal experiences, such as social support, to child cognitive development has received less attention. Furthermore, how maternal experience of social support during specific developmental periods impacts child cognitive development is largely unknown. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 5784) and the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study (PREDO; n = 420), we investigated the associations between maternal perceived social support during and after pregnancy and child's general cognitive ability at 8 years of age, assessed with the Wechsler Intelligence Scale for Children (WISC). Bayesian relevant life course modeling was used to investigate timing effects of maternal social support on child cognitive ability. RESULTS: In both cohorts, higher maternal perceived social support during pregnancy was associated with higher performance on the WISC, independent of sociodemographic factors and concurrent maternal symptoms of depression and anxiety. In ALSPAC, pregnancy emerged as a sensitive period for the effects of perceived social support on child cognitive ability, with a stronger effect of social support during pregnancy than after pregnancy on child cognitive ability. CONCLUSIONS: Our findings, supported from two prospective longitudinal cohorts, suggest a distinct role of maternal perceived social support during pregnancy for cognitive development in children. Our study suggests that interventions aimed at increasing maternal social support during pregnancy may be an important strategy for promoting maternal and child well-being.

Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children.

Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4-12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7-65.6%, and hence the predictive significance of the model, and mediated 60.8-75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.

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.

Positive maternal mental health during pregnancy and mental and behavioral disorders in children: A prospective pregnancy cohort study.

BACKGROUND: The role of positive maternal mental health during pregnancy in child mental health remains largely unknown. We investigated whether positive maternal mental health during pregnancy is associated with lower hazards of mental and behavioral disorders in children and mitigates the adverse effects of negative maternal mental health. METHODS: Among 3,378 mother-child dyads of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study, mothers reported their positive mental health biweekly throughout pregnancy with the Positive and Negative Affect Schedule, the Spielberger State Anxiety Inventory Curiosity scale, and a visual analogue scale for social support, and negative mental health with the Center for Epidemiologic Studies Depression Scale. We extracted data on their mental and behavioral disorder diagnoses from a nationwide medical register. This register provided data on their children's mental and behavioral disorder diagnoses as well, from birth until 8.4-12.8 (Median = 10.2, Interquartile Range 9.7-10.8) years of age. RESULTS: A positive maternal mental health composite score during pregnancy was associated with a lower hazard of any mental and behavioral disorder among all children [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI) 0.71 - 0.87] and among children of mothers experiencing clinically relevant depressive symptoms during pregnancy [HR = 0.80, 95%CI 0.64 - 1.00] and/or mental and behavioral disorders before or during pregnancy [HR = 0.69, 95%CI 0.55-0.86]. These associations were independent of covariates. CONCLUSIONS: Children whose mothers had more positive mental health during pregnancy were less likely to develop mental and behavioral disorders. Protective effects were seen also among children of mothers facing mental health adversities before or during pregnancy.

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.

Positive maternal mental health during pregnancy and psychiatric problems in children from early childhood to late childhood.

Negative maternal mental health during pregnancy increases the risk of psychiatric problems in children, but research on the potential benefits of positive maternal mental health during pregnancy is scarce. We investigated associations between positive maternal mental health composite score, based on reports of maternal positive affect, curiosity, and social support during pregnancy, and children's psychiatric problems (Child Behavior Checklist) at ages 1.9-5.9 and 7.1-12.1 years among 2636 mother-child dyads of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study. For each standard deviation higher positive maternal mental health score during pregnancy, total psychiatric problems were 1.37 (95% confidence interval (CI) -1.79,-0.95) t-scores lower in early childhood and 1.75 (95% CI -2.24,-1.26) t-scores lower in late childhood. These associations were independent of covariates and of negative maternal mental health. Total psychiatric problems remained stably lower from early childhood to late childhood in children of mothers with higher positive mental health during pregnancy, whereas they increased in children of mothers with lower positive mental health. Positive maternal mental health in child's late childhood partially mediated the effects of positive maternal mental health during pregnancy on children's psychiatric problems. Supporting positive maternal mental health may benefit mothers and children.

Prenatal maternal and cord blood vitamin D concentrations and negative affectivity in infancy.

Higher maternal vitamin D concentration during pregnancy is associated with better child mental health. Negative affectivity, an early-emerging temperamental trait, indicates an increased risk of psychopathology. We investigated if maternal early/mid-pregnancy 25-hydroxyvitamin D (25(OH)D) and neonatal cord blood 25(OH)D concentrations are associated with Negative affectivity in infancy. We studied term-born infants from the vitamin D Intervention in Infants study (VIDI, n = 777, follow-up rate 80%, Finland), and the Generation R Study (n = 1505, follow-up rate 40%, Netherlands). We measured maternal serum 25(OH)D at 6-27 weeks (VIDI) or 18-25 weeks (Generation R) of pregnancy, and cord blood 25(OH)D at birth (both cohorts). Caregivers rated infant Negative affectivity at 11.7 months (VIDI) or 6.5 months (Generation R) using the Revised Infant Behavior Questionnaire. Using linear regression, we tested associations between 25(OH)D and Negative affectivity adjusted for infant age, sex, season of 25(OH)D measurement, maternal age, education, smoking, and body-mass-index. Per 10 nmol/l increase in maternal early/mid-pregnancy 25(OH)D, infant Negative affectivity decreased by 0.02 standard deviations (95% confidence interval [CI] - 0.06, - 0.004) in VIDI, and 0.03 standard deviations (95% CI - 0.03, - 0.01) in Generation R. Cord blood 25(OH)D was associated with Negative affectivity in Generation R (- 0.03, 95% CI - 0.05, - 0.01), but not VIDI (0.00, 95% CI - 0.02, 0.02). Lower maternal 25(OH)D concentrations were consistently associated with higher infant Negative affectivity, while associations between cord blood 25(OH)D concentrations and Negative affectivity were less clear. Maternal vitamin D status during early- and mid-pregnancy may be linked with early-emerging differences in offspring behavior.

Maternal exposure to childhood maltreatment and mental and behavioral disorders in children.

Exposure to maltreatment in childhood is associated with lifelong risk of mental and behavioral disorders. Whether the effects extend to the next generation remains unclear. We examined whether maternal exposure to childhood abuse and neglect in her own childhood were associated with mental and behavioral disorders and psychiatric symptoms in her children, and whether maternal lifetime mental and behavioral disorders or lower education level mediated or added to the effects. Mothers (n = 2252) of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction cohort study completed the Childhood Trauma Questionnaire and reported on their education and their 7.0-12.1-year-old children's psychiatric symptoms using the Strengths and Difficulties Questionnaire. We identified lifetime mental and behavioral disorder diagnoses for the mothers and diagnoses for their children from birth (2006-2010) until 8.4-12.8 years (12/31/2018) from Care Register for Health Care. We found that maternal exposure to childhood abuse, but not neglect, was associated with higher hazards of mental and behavioral disorders (hazard ratio 1.20, 95% confidence interval 1.06-1.37) in children. These associations were partially mediated by maternal mental and behavioral disorders and education (proportion of effect size mediated: 23.8% and 15.1%, respectively), which together with maternal exposure to childhood abuse added to the hazard of mental and behavioral disorders in children. Similar associations were found for maternal exposure to childhood abuse and neglect with psychiatric symptoms in children. To conclude, maternal exposure to childhood maltreatment is associated with mental and behavioral disorders and psychiatric symptoms in children. Our findings call for interventions to prevent intergenerational transmission.

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.

Reaction times, learning, and executive functioning in adults born preterm.

BACKGROUND: This study examines cognitive functioning in adults born across the range of prematurity with appropriate or small for gestational age (SGA) birth weight compared with full-term controls. METHODS: ESTER Preterm Birth Study participants without severe disabilities, comprising 133 early preterm (<34 weeks, 17% SGA), 241 late preterm (34 + 0-36 + 6 weeks, 13% SGA), and 348 full-term subjects, performed the Cogstate® test at a mean age of 23.3 (SD = 1.2) years. Subtests measured paired associate learning, psychomotor function, executive function, spatial memory efficiency, visual memory, attention, working memory, visual learning, and emotional cognition. Data were analyzed with linear regression, full models adjusted for prenatal and postnatal factors and socioeconomic position. RESULTS: Early preterm, late preterm, and full-term participants showed similar abilities in almost all subtests. Early preterm participants had 0.6 fewer moves/10 s (95% CI: -1.0; -0.2, full model) and late preterm and SGA participants had 1.3 fewer moves/10 s (95% CI: -2.1; -0.4) than full-term controls in the Groton Maze Learning Test, indicating weaker spatial memory efficiency. CONCLUSIONS: Adults born across the range of prematurity on average lack major defects in cognitive abilities. Cognitive problems may persist to adulthood only among those born the smallest: very preterm or preterm and SGA. IMPACT: Although preterm birth is a risk for the developing brain, adults born preterm as a group showed similar cognitive performance to their full-term peers. Children born preterm across gestational ages show defects in cognitive domains. With a supportive environment, many of them have the potential to catch up with those born at term. The unfavorable effect of late preterm birth on cognitive functions in childhood may not persist to adulthood; in this study, adults born late preterm showed similar cognitive functioning to adults born full-term. The deficits in cognitive function in adults born preterm detected by earlier studies mainly concern those born the smallest, i.e., very preterm or preterm and small for gestational age.

Maternal Hypertensive Pregnancy Disorders and Mental and Behavioral Disorders in the Offspring: a Review.

PURPOSE OF REVIEW: We review here recent original research and meta-analytic evidence on the associations of maternal hypertensive pregnancy disorders and mental and behavioral disorders in the offspring. RECENT FINDINGS: Seven meta-analyses and 11 of 16 original research studies published since 2015 showed significant associations between maternal hypertensive pregnancy disorders and offspring mental and behavioral disorders. Evidence was most consistent in meta-analyses and high-quality cohort studies. The associations, independent of familial confounding, were observed on different mental and behavioral disorders in childhood and schizophrenia in adulthood. Preterm birth and small-for-gestational age birth emerged as possible moderators and mediators of the associations. Cross-sectional and case-control studies yielded inconsistent findings, but had lower methodological quality. Accumulating evidence from methodologically sound studies shows that maternal hypertensive pregnancy disorders are associated with an increased risk of mental and behavioral disorders in the offspring in childhood. More studies on adult mental disorders are needed.

Common Core Assessments in follow-up studies of adults born preterm-Recommendation of the Adults Born Preterm International Collaboration.

BACKGROUND: Of all newborns, 1%-2% are born very preterm (VP; <32 weeks) or with very low birthweight (VLBW; ≤1500 g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow-up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; www.apic-preterm.org). Joint analyses require data harmonisation, highlighting the importance of consistent assessment methodologies. OBJECTIVE: To present an expert recommendation on Common Core Assessments to be used in follow-up assessments of adults born preterm. METHODS: Principles of Common Core Assessments were discussed at APIC meetings. Experts for each specific outcome domain wrote the first draft on assessments pertaining to that outcome. These drafts were combined and reviewed by all authors. Consensus was reached by discussion at APIC meetings. RESULTS: We present a recommendation by APIC experts on consistent measures to be used in adult follow-up assessments. CONCLUSIONS: The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing on current gaps in knowledge. It includes sections on study design, cardiometabolic and related biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction.

Maternal depression and inflammation during pregnancy.

BACKGROUND: Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions. METHODS: We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records. RESULTS: Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26-1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17-0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00-0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12-0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction). CONCLUSIONS: Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.

Associations of antenatal glucocorticoid exposure with mental health in children.

BACKGROUND: Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children. METHODS: We included 4708 women and their children, born 2006-2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child's birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age. RESULTS: Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76-4.32), 3.61 (2.19-5.95), 3.29 (1.86-5.82), and 6.04 (3.25-11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children. CONCLUSIONS: Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.

Predictors of early motor trajectories from birth to 5 years in neonatal at-risk and control children.

AIM: To describe motor development in preschool children, to identify perinatal, neonatal and social environmental risk factors of poor motor development, and to replicate results in a second cohort. METHODS: Two prospective samples in Germany (Bavarian Longitudinal Study, BLS) and Finland (Arvo Ylppö Longitudinal Study, AYLS) assessed 4741 and 1423 children from birth to 56 months, respectively. Motor functioning was evaluated at birth, and 5, 20 and 56 months. Perinatal, neonatal and social environmental information was collected at birth and 5 months. RESULTS: Two distinct motor trajectories were identified: low (BLS: n = 4486 (94.6%), AYLS: n = 1391 (97.8%)) and high (BLS: n = 255 (5.4%), AYLS: n = 32 (2.2%)) degree of motor difficulties. High degree of motor difficulties was predicted by neonatal complications, abnormal neonatal neurological status, duration of hospitalisation and poor parent-infant relationships. Although neonatal complications and poor parent-infant relationships did not significantly predict high degree of motor difficulties in the AYLS, the trends identified were similar to those obtained from the BLS. CONCLUSION: Early identification of children at-risk of motor difficulties across infancy and toddlerhood may help referring those children to interventions earlier. Modifiable risk factors, such as parent-infant relationships, may be addressed by intervention strategies to prevent children from developing motor difficulties.

ADHD symptoms are associated with decreased activity of fast sleep spindles and poorer procedural overnight learning during adolescence.

ADHD and its subclinical symptoms have been associated with both disturbed sleep and weakened overnight memory consolidation. As sleep spindle activity during NREM sleep plays a key role in both sleep maintenance and memory consolidation, we examined the association between subclinical ADHD symptoms and sleep spindle activity. Furthermore, we hypothesized that sleep spindle activity mediates the effect of ADHD symptoms on overnight learning outcome in a procedural memory task. We studied these questions in a community-based cohort of 170 adolescents (58% girls, mean age = 16.9, SD = 0.1 years), who filled in the Adult ADHD Self-Report Scale (ASRS-v1.1), and underwent an overnight sleep EEG coupled with a mirror tracing task before and after sleep. Elevated ADHD symptoms were associated with weaker fast sleep spindle activity, and poorer overnight learning in the procedural memory test. However, sleep spindles, contrary to the hypothesis, did not mediate the association between ADHD symptoms and overnight learning. Our results showed that a higher level of ADHD symptoms in adolescence is associated with similar alterations in sleep spindle activity as observed in many neuropsychiatric conditions and might contribute to altered synaptic connectivity and sleep fragmentation observed in ADHD.