Association between prenatal maternal anxiety and/or stress and offspring's cognitive functioning: A meta-analysis.

This meta-analysis examined the relationship between prenatal maternal stress and/or anxiety and the outcomes of children aged 3 months to 9 years. Of the 8754 studies published before June 2021 that were synthesized, 17 conducted in Western countries were included in the meta-analysis (Ntotal  = 23,307; Mmales 54%; Methnicity White 77%, Pacific 15%, African American/Black 10%, Middle Eastern 7%, Eastern 8%). Effect sizes ranged from -0.41 to 0.15. A weak negative association was found between prenatal stress and/or anxiety exposure and children's general intellectual development. Associations varied based on the type of exposure. Findings are limited to developed counties and cannot be generalized to low- and middle-income countries. Directions for maternal prenatal intervention and future studies are discussed.

Profiles of Functioning in 5.5-Year-Old Very Preterm Born Children in France: The EPIPAGE-2 Study.

OBJECTIVE: Very preterm born children are at risk for impairments in multiple neurodevelopmental domains, but outcomes vary between individuals. The present study aimed to distinguish subgroups with distinct profiles of functioning across motor, cognitive, behavioral, and psychosocial domains. These profiles were related to neonatal and social/environmental factors. METHOD: The sample included 1977 children born very preterm (<32 weeks' gestation) in 2011 from the French population-based EPIPAGE-2 cohort. Using latent profile analysis, subgroups of children were distinguished based on their functioning at 5.5 years. The relation between outcome profiles and neonatal and social/environmental factors was tested using multivariable multinomial logistic regression analysis. RESULTS: Four subgroups with distinct outcome profiles were distinguished: no deficit in any domain (45%); motor and cognitive deficits without behavioral/psychosocial deficits (31%); primarily behavioral and psychosocial deficits (16%); and deficits in multiple domains (8%). Male sex (odds ratio [OR] = 2.1-2.7), bronchopulmonary dysplasia (OR = 2.1-2.8), low parental education level (OR = 1.8-2.1), and parental non-European immigrant status (OR = 2.3-3.0) were independently associated with higher odds for all suboptimal outcome profiles compared to the favorable outcome profile. CONCLUSION: Among 5.5-year-old very preterm born children, subgroups can be distinguished with distinct outcome profiles that vary in severity, type, and combinations of deficits. This information is important for the development of interventions that are tailored to the needs of large subgroups of children across multiple domains of functioning. General neonatal and social/environmental factors may be useful for early identification of very preterm born children at risk for general rather than domain-specific impairments.

Voluntary and Involuntary Control of Attention in Adolescents Born Very Preterm: A Study of Eye Movements.

Very preterm birth is associated with attention deficits that interfere with academic performance. A better understanding of attention processes is necessary to support very preterm born children. This study examined voluntary and involuntary attentional control in very preterm born adolescents by measuring saccadic eye movements. Additionally, these control processes were related to symptoms of inattention, intelligence, and academic performance. Participants included 47 very preterm and 61 full-term born 13-years-old adolescents. Oculomotor control was assessed using the antisaccade and oculomotor capture paradigm. Very preterm born adolescents showed deficits in antisaccade but not in oculomotor capture performance, indicating impairments in voluntary but not involuntary attentional control. These impairments mediated the relation between very preterm birth and inattention, intelligence, and academic performance.

Neurocognitive processes underlying academic difficulties in very preterm born adolescents.

Very preterm birth is associated with academic difficulties, but the underlying neurocognitive mechanisms of these difficulties remain largely unclear. The present study aimed to assess the role of working memory (WM), attentional processes, and processing speed in academic difficulties of very preterm born adolescents at 13 years. Participants included 55 very preterm and 61 full-term adolescents. Academic performance, visuospatial WM, alerting, orienting, executive attention, sustained attention, and processing speed (simple and choice reaction time [RT]) were compared between groups. Mediation analyses with multiple, parallel mediators were performed to examine whether these functions mediate the relation between very preterm birth and academic performance. Very preterm born adolescents showed poorer reading comprehension, arithmetic, visuospatial WM, alerting, sustained attention, and choice RT than full-term controls. The relationship between very preterm birth and arithmetic was mediated by visuospatial WM, sustained attention, and choice RT. The relationship between very preterm birth and reading comprehension was mediated by visuospatial WM and choice RT. The findings indicate that very preterm birth affects arithmetic and reading comprehension through its negative effect on visuospatial WM, sustained attention, and processing speed. These neurocognitive processes may identify very preterm born children at risk for academic difficulties and could serve as targets for interventions.

Social Adjustment in Adolescents Born Very Preterm: Evidence for a Cognitive Basis of Social Problems.

OBJECTIVE: To increase the understanding of social adjustment and autism spectrum disorder symptoms in adolescents born very preterm by studying the role of emotion recognition and cognitive control processes in the relation between very preterm birth and social adjustment. STUDY DESIGN: A Dutch cohort of 61 very preterm and 61 full-term adolescents aged 13 years participated. Social adjustment was rated by parents, teachers, and adolescents and autism spectrum disorder symptoms by parents. Emotion recognition was assessed with a computerized task including pictures of child faces expressing anger, fear, sadness, and happiness with varying intensity. Cognitive control was assessed using a visuospatial span, antisaccade, and sustained attention to response task. Performance measures derived from these tasks served as indicators of a latent cognitive control construct, which was tested using confirmatory factor analysis. Mediation analyses were conducted with emotion recognition and cognitive control as mediators of the relation between very preterm birth and social problems. RESULTS: Very preterm adolescents showed more parent- and teacher-rated social problems and increased autism spectrum disorder symptomatology than controls. No difference in self-reported social problems was observed. Moreover, very preterm adolescents showed deficits in emotion recognition and cognitive control compared with full-term adolescents. The relation between very preterm birth and parent-rated social problems was significantly mediated by cognitive control but not by emotion recognition. Very preterm birth was associated with a 0.67-SD increase in parent-rated social problems through its negative effect on cognitive control. CONCLUSIONS: The present findings provide strong evidence for a central role of impaired cognitive control in the social problems of adolescents born very preterm.

EEG profiles and associated neurodevelopmental outcomes after very preterm birth.

OBJECTIVES: To assess brain oscillations in very preterm and full-term born adolescents and explore subgroups based on integrative patterns of brain oscillations with different frequencies. Additionally, subgroups were related to functional outcomes and very preterm birth. METHODS: A Dutch cohort of 53 very preterm and 61 full-term born adolescents aged 13 years participated. Resting-state electroencephalography was recorded. Absolute and relative delta, theta, alpha, and beta power were compared between groups. Latent class analysis (LCA) was used to identify subgroups with distinct activity patterns and to relate these patterns to intelligence, academic performance, motor skills, and very preterm birth. RESULTS: Very preterm adolescents exhibited decreased relative beta activity. LCA with four classes showed the best model fit. The class with the highest level of delta and lowest levels of theta, alpha, and beta power was associated with lowest intelligence, academic, and motor estimates. Very preterm born adolescents were more likely than controls to be members of this class. CONCLUSION: Very preterm born adolescents showed altered oscillatory activity, indicating long-lasting effects of very preterm birth on brain functioning. Distinct activity patterns were associated with both functional outcomes and very preterm birth. SIGNIFICANCE: Specific patterns of brain oscillations may serve as biomarkers for poor functional outcome after very preterm birth.

Implicit Learning Abilities in Adolescents Born Very Preterm.

Very preterm birth is associated with neurodevelopmental impairments and outcomes have not improved over the last decades. Insight in learning processes is important for the development of effective interventions. Implicit learning is of particular interest because of its independence from working memory processes that are affected by preterm birth. This study examined implicit learning abilities in 49 very preterm and 61 full-term 13-year-old adolescents. The degree of implicit learning was not different between groups. This indicates intact implicit learning abilities in adolescents born very preterm. Implicit learning strategies may be beneficial for skill learning in very preterm born children.

Academic trajectories of very preterm born children at school age.

OBJECTIVES: To characterise the developmental trajectories of arithmetic, reading comprehension and spelling abilities of very preterm and full-term born children during primary school. DESIGN: A longitudinal analysis of academic performance data of very preterm and full-term born children was performed. Academic performance was assessed in grade 1-6 of primary school using a pupil monitoring system, with 11 measurements of arithmetic and spelling performance and 7 measurements of reading comprehension. Data were analysed using mixed-effects models. PATIENTS: A Dutch cohort of 52 very preterm children born between 2001-2003 and 58 full-term controls participated. RESULTS: No group-by-time interactions were found for any of the academic domains, indicating no differences in progress between groups. Through the course of primary school, very preterm born children scored on average 0.53 SD lower on arithmetic (95% CI -0.71 to -0.35, p<0.001), 0.31 SD on reading comprehension (95% CI -0.48 to -0.14, p<0.001) and 0.21 SD on spelling (95% CI -0.37 to -0.05, p=0.01) compared with full-term peers. CONCLUSIONS: This is the first longitudinal study to show that the academic difficulties of very preterm born children persisted during primary school. Their progression was similar to full-term born peers, suggesting intact learning abilities. This provides opportunities for interventions to improve the academic outcomes of very preterm born children.

Executive Function Computerized Training in Very Preterm-Born Children: A Pilot Study.

OBJECTIVE: Attention problems are one of the most pronounced and documented consequences of very preterm birth (gestational age ≤32 weeks). However, up to now, there is no research published on suitable interventions at school age aimed to overcome these problems. Research in this population did show that executive functions (EFs) are strongly associated with inattention. BrainGame Brian is a newly developed computerized training, in which, in 25 training sessions, the core EFs, including working memory, impulse control, and cognitive flexibility, are trained. This pilot study aimed to examine the feasibility of studying BrainGame Brian in very preterm-born children with attention problems. DESIGN: Pilot feasibility intervention study with one baseline and one follow-up assessment. MATERIALS AND METHODS: Feasibility was measured by the participation rate, dropout rate, and user experiences with regard to effort, training characteristics, and recommendation to others. From a larger cohort study, 15 very preterm-born children at age 10 years with parent-reported attention problems on the Child Behavior Checklist/6-18 years were invited to participate in this pilot study. BrainGame Brian was performed for a period of 6 weeks. Training outcome measures included visual working memory, impulse control, cognitive flexibility, speed variability, and parent-rated attention, for which pre- and post-training differences were examined at the group level by the Wilcoxon signed-rank test as well as for each individual child separately by the reliable change index. RESULTS: Twelve of 15 children and their parents agreed to participate and 11 children successfully completed BrainGame Brian in the 6-week period. Parents were positive about training characteristics and lack of interference with schooling, but scored the effort as high. We found clinically significant changes in visual working memory and speed variability in post-training assessments. CONCLUSION: BrainGame Brian is a feasible intervention for very preterm-born children with attention problems.

Cognitive Outcomes of Children Born Extremely or Very Preterm Since the 1990s and Associated Risk Factors: A Meta-analysis and Meta-regression.

Importance: Despite apparent progress in perinatal care, children born extremely or very preterm (EP/VP) remain at high risk for cognitive deficits. Insight into factors contributing to cognitive outcome is key to improve outcomes after EP/VP birth. Objective: To examine the cognitive abilities of children of EP/VP birth (EP/VP children) and the role of perinatal and demographic risk factors. Data Sources: PubMed, Web of Science, and PsycINFO were searched without language restriction (last search March 2, 2017). Key search terms included preterm, low birth weight, and intelligence. Study Selection: Peer-reviewed studies reporting intelligence scores of EP/VP children (<32 weeks of gestation) and full-term controls at age 5 years or older, born in the antenatal corticosteroids and surfactant era, were included. A total of 268 studies met selection criteria, of which 71 covered unique cohorts. Data Extraction and Synthesis: MOOSE guidelines were followed. Data were independently extracted by 2 researchers. Standardized mean differences in intelligence per study were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using multivariate, random-effects meta-regression analysis. Main Outcomes and Measures: Primary outcome was intelligence. Covariates included gestational age, birth weight, birth year, age at assessment, sex, race/ethnicity, socioeconomic status, small for gestational age, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, sepsis, and postnatal corticosteroid use. Results: The 71 included studies comprised 7752 EP/VP children and 5155 controls. Median gestational age was 28.5 weeks (interquartile range [IQR], 2.4 weeks) and the mean age at assessment ranged from 5.0 to 20.1 years. The median proportion of males was 50.0% (IQR, 8.7%). Preterm children had a 0.86-SD lower IQ compared with controls (95% CI, -0.94 to -0.78, P < .001). Results were heterogeneous across studies (I2 = 74.13; P < .001). This heterogeneity could not be explained by birth year of the cohort. Multivariate meta-regression analysis with backward elimination revealed that BPD explained 65% of the variance in intelligence across studies, with each percent increase in BPD rate across studies associated with a 0.01-SD decrease in IQ (0.15 IQ points) (P < .001). Conclusions and Relevance: Extremely or very preterm children born in the antenatal corticosteroids and surfactant era show large deficits in intelligence. No improvement in cognitive outcome was observed between 1990 and 2008. These findings emphasize that improving outcomes after EP/VP birth remains a major challenge. Bronchopulmonary dysplasia was found to be a crucial factor for cognitive outcome. Lowering the high incidence of BPD may be key to improving long-term outcomes after EP/VP birth.

Academic performance of children born preterm: a meta-analysis and meta-regression.

BACKGROUND: Advances in neonatal healthcare have resulted in decreased mortality after preterm birth but have not led to parallel decreases in morbidity. Academic performance provides insight in the outcomes and specific difficulties and needs of preterm children. OBJECTIVE: To study academic performance in preterm children born in the antenatal steroids and surfactant era and possible moderating effects of perinatal and demographic factors. DESIGN: PubMed, Web of Science and PsycINFO were searched for peer-reviewed articles. Cohort studies with a full-term control group reporting standardised academic performance scores of preterm children (<37 weeks of gestation) at age 5 years or older and born in the antenatal steroids and surfactant era were included. Academic test scores and special educational needs of preterm and full-term children were analysed using random effects meta-analysis. Random effects meta-regressions were performed to explore the predictive role of perinatal and demographic factors for between-study variance in effect sizes. RESULTS: The 17 eligible studies included 2390 preterm children and 1549 controls. Preterm children scored 0.71 SD below full-term peers on arithmetic (p<0.001), 0.44 and 0.52 SD lower on reading and spelling (p<0.001) and were 2.85 times more likely to receive special educational assistance (95% CI 2.12 to 3.84, p<0.001). Bronchopulmonarydysplasia explained 44% of the variance in academic performance (p=0.006). CONCLUSION: Preterm children born in the antenatal steroids and surfactant era show considerable academic difficulties. Preterm children with bronchopulmonarydysplasia are at particular risk for poor academic outcome.

A randomised trial of enteral glutamine supplementation for very preterm children showed no beneficial or adverse long-term neurodevelopmental outcomes.

AIM: This study evaluated the long-term effects of enteral glutamine supplementation on neurodevelopmental outcomes of a Dutch cohort of very preterm children at 13 years of age. METHODS: The cohort was enrolled in a randomised placebo-controlled trial between 2001 and 2003 in which infants received glutamine- or alanine-supplemented enteral nutrition during the first month of life. Participants were invited for follow-up at a mean age of 13.30 years. Motor, neurocognitive, academic and behavioural outcomes were assessed in 61 children. RESULTS: No differences were found between the groups regarding motor, intellectual, academic and behavioural functioning. Forward span visuospatial working memory performance was better in the controls (crude/adjusted model: d = 0.67/0.64, p = 0.02/0.02), but no difference was found for backward span. After the data were adjusted for confounders, the groups differed regarding parent-rated attention (crude/adjusted model: d = 0.47/0.73, p = 0.07/0.003), but both groups scored within the normal range. CONCLUSION: This was the first study on the long-term effects of enteral glutamine supplementation on the neurodevelopmental outcomes of very preterm children. Our study provided no evidence that enteral glutamine supplementation had any beneficial or adverse effects on the children's motor, neurocognitive, academic and behavioural outcomes at 13 years of age.