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Background: In Germany, more than 40% of infants are born to immigrant parents. Increased survival rates of very preterm (below 32 weeks gestation at birth; VP) infants have not resulted in equally improved life chances and quality of life. More information on perinatal variations in outcomes according to social inequalities, migration background, and language barriers is needed. We tested whether mothers' immigrant status and language barriers are associated with perinatal health and short-term neonatal outcomes., Methods: The data are from the national multi-centre German Neonatal Network (GNN) cohort, including VP births from 2009 onwards. In total, 3606 ( n = 1738 female) children were assessed, and 919 ( n = 449 female) of these children had immigrant backgrounds. Immigrant status was operationalised as a binary variable based on the children's mothers' countries of birth (born in Germany vs. foreign-born). Self-reported home language (L1) was used to calculate the average linguistic distance to German as one continuous variable., Results: Mixed-effects models showed that two out of fourteen effects of interest survived the adjustment for known confounders and accounting for the nestedness of data within birth hospitals. Linguistic distance from mothers' L1s to German was independently associated with diagnoses of preeclampsia (OR = 1.01, 95% CI = [1.00, 1.01]). Infants of foreign-born mothers had higher odds for amniotic infection syndrome (AIS; OR = 1.45 [1.13, 1.86]) than infants of German mothers., Conclusions: Our findings from this large multi-centre longitudinal cohort of VP-born children indicate that maternal immigrant status and language barriers have limited impact on perinatal health and severe neonatal outcomes. This suggests that, regardless of background or language skills, there may be few inequalities in the perinatal health of pregnant women and their newborn preterm infants.

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., (© 2023. The Author(s).)

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., (© 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Background: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants., Methods: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight <1500 g and/or gestational age <32 weeks), 2) normal birth weight/term-born control group (birth weight >2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555)., Findings: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups., Interpretation: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders in individuals born VP/VLBW., Funding: Australia's National Health & Medical Research Council; CAPES (Coordenação de Aperfeiçoamento de Pessoal deNível Superior) - International Cooperation General Program; Canadian Institutes of Health Research Team Grant; National Council for Scientific and Technological Development (CNPq); Academy of Finland; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; European Union's Horizon 2020 research and innovation programme: Project RECAP-Preterm; European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL); Neurologic Foundation of New Zealand; MRC programme grant; Health Research Council of New Zealand; National Institutes of Health, USA; The Research Council of Norway; Joint Research Committee between St. Olavs Hospital and Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU); Liaison Committee between Central Norway Regional Health Authority and NTNU., Competing Interests: No declaration of interests., (© 2021 The Author(s).)

The normative transition to formal schooling confronts children with social challenges but also opportunities. Longitudinal research on how school entry impacts children's family and friend-ship relationships is scarce. This study investigated social relationship qualities with parents, siblings, and friends among 1110 children (49.9% female) from the prospective, population-based Bavarian Longitudinal Study at 6 years (before school entry) and 8 years using a forced-choice card-sorting task. Multivariate analyses of variance revealed significant effects of age (i.e., school entry) on social relationship qualities with mothers (Pillai's Trace (PT) = 0.28, F (9, 1101) = 47.73, p < 0.001), fathers (PT = 0.14, F (9, 1101) = 19.47, p < 0.001), siblings (PT = 0.27, F (9, 1101) = 46.14, p < 0.001), and friends (PT = 0.21, F (9, 1101) = 32.57, p < 0.001). On average, children reported higher levels of parental comfort after school entry. Companionable qualities increased in relationships with friends, whereas sibling relationships became more conflictual from preschool to early school age. Findings provide unique insights into how social relationships develop from preschool to early school age, supporting evidence of the growing importance of friends. Conflict was predominant and increasing in sibling relationships and should be considered more in future research.

Background: Adaptive computerized interventions may help improve preterm children's academic success, but randomized trials are rare. We tested whether a math training (XtraMath®) versus an active control condition (Cogmed®; working memory) improved school performance. Training feasibility was also evaluated., Methods: Preterm born first graders, N = 65 (28-35 + 6 weeks gestation) were recruited into a prospective randomized controlled multicenter trial and received one of two computerized trainings at home for 5 weeks. Teachers rated academic performance in math, reading/writing, and attention compared to classmates before (baseline), directly after (post), and 12 months after the intervention (follow-up). Total academic performance growth was calculated as change from baseline (hierarchically ordered-post test first, follow-up second)., Results: Bootstrapped linear regressions showed that academic growth to post test was significantly higher in the math intervention group (B = 0.25 [95% confidence interval: 0.04-0.50], p = 0.039), but this difference was not sustained at the 12-month follow-up (B = 0.00 [-0.31 to 0.34], p = 0.996). Parents in the XtraMath group reported higher acceptance compared with the Cogmed group (mean difference: -0.49, [-0.90 to -0.08], p = 0.037)., Conclusions: Our findings do not show a sustained difference in efficacy between both trainings. Studies of math intervention effectiveness for preterm school-aged children are warranted., Impact: Adaptive computerized math training may help improve preterm children's short-term school performance. Computerized math training provides a novel avenue towards intervention after preterm birth. Well-powered randomized controlled studies of math intervention effectiveness for preterm school-aged children are warranted.

Introduction: There is an increase in cases of mothers using opioids during pregnancy in the United States but research investigating mothers' psychosocial environments along with individual variability among this high-risk group of women is scarce., Methods: This mixed-methods study aims to examine the complex interplay of contextual risks and experiences of opioid-using mothers. A sample of 50 opioid-using biological mothers of infants diagnosed with neonatal opioid withdrawal syndrome (NOWS) were studied using a set of standardized and open-ended questions, along with medical records extraction., Results: A high-risk subgroup of 36 mothers was identified using cluster analysis, characterized by a distinct profile of psychosocial risk. Thematic content analysis revealed four themes: (1) barriers to communication and mistrust of health professionals, (2) limitations of access to health care and the amplification of disadvantages related to COVID-19, (3) lifelong consequences of adverse childhood experiences (ACEs), and (4) intimate partner violence and its influence on drug use., Conclusion: Our findings highlight important information toward health services provision for opioid-using women of childbearing age. Efforts to reduce opioid usage in mothers need to consider psychosocial and contextual risks.

Very preterm children (<32 weeks gestation at birth; VP) are at risk of developmental difficulties. Specific functional difficulties and delays in visual perception, fine motor, and visual-motor skills have received little research attention, although they are critical for daily life and school readiness. Our aim was to assess these skills in a contemporary cohort of 60 VP and 60 matched term-born children before school entry. We administered the Movement Assessment Battery for Children (M-ABC-2) and the Developmental Test of Visual Perception (DTVP-2). Linear and logistic regressions were run to test group differences in performance and rates of developmental delay in visual perception, fine motor, and visual-motor skills. Very preterm children had lower scores than term-born children in visual perception ( β = -0.25; p = 0.006), fine motor ( β = -0.44; p < 0.001), and visual-motor tasks ( β = -0.46; p < 0.001). The rate of developmental delay (<-1 SD) was higher among VP in visual perception (odds ratio (OR) = 3.4; 95% confidence interval (CI 1.1-10.6)), fine motor (OR = 6.2 (2.4-16.0)), and visual-motor skills (OR = 13.4 (4.1-43.9)) than in term-born controls. VP children are at increased risk for clinically relevant developmental delays in visual perception, fine motor, and visual-motor skills. Following up VP children until preschool age may facilitate early identification and timely intervention.

Refugees often parent under extreme circumstances. Parenting practices have implications for child outcomes, and parenting in the context of refugee resettlement is likely to be dynamic as parents negotiate a new culture. This study examined African origin mothers' infant care values and practices related to feeding, carrying, and daily activities following resettlement in the Southeastern region of the U.S. Ten African origin mothers were asked about their infant care practices through semi-structured interviews. Results indicated that mothers valued breastfeeding but often chose to use formula as a supplement or instead of breastfeeding. In addition, participants valued carrying their infants close to the body but used equipment such as strollers. Mothers expressed that perceptions of American culture and rules, social support, interactions with community agencies, and the need to engage in formal employment were factors that influenced their infant care practices.

Preterm birth (<37 weeks' gestation) has been associated with problems in social functioning. Whether social inhibition is specifically related to preterm birth and whether early parenting may protect against social inhibition difficulties is unknown. To explore effects of gestational age and early parent-infant relationships on social inhibition, 1314 children born at 26-41 weeks gestational age were studied as part of the prospective Bavarian Longitudinal Study. Early parent-infant relationship quality was assessed postnatally with the parent-infant relationship index. Social inhibition was assessed at age 6 years using an experimental procedure, in which nonverbal and verbal responses were coded into social inhibition categories (disinhibited, normally responsive, inhibited). Multinomial logistic regressions indicated that children with lower gestational age showed more socially disinhibited (nonverbal: OR = 1.27 [95% CI = 1.17-1.40], verbal: OR = 1.23 [95% CI 1.13-1.35]) and inhibited (nonverbal: OR = 1.21 [95% CI = 1.11-1.32], verbal: OR = 1.11 [95% CI = 1.01-1.21]) responses. Good early parent-infant relationships were associated with less verbal disinhibition (OR = 0.70 [95% CI = 0.52-0.93]). Findings suggest that children with lower gestational age are at greater risk to be both socially inhibited and disinhibited. Early parenting affected risk of abnormal social responses. Supporting early parent-infant relationships may reduce preterm children's risk for social difficulties.

Objective: Very preterm (<32 weeks gestation; VP) and/or very low birth weight (<1500g; VLBW) children often have cognitive and mathematic difficulties. It is unknown whether VP/VLBW children's frequent mathematic problems significantly add to the burden of negative life-course consequences over and above effects of more general cognitive deficits. Our aim was to determine whether negative consequences of VP/VLBW versus healthy term birth on adult wealth are mediated by mathematic abilities in childhood, or rather explained by more general cognitive abilities., Methods: 193 VP/VLBW and 217 healthy term comparison participants were studied prospectively from birth to adulthood as part of a geographically defined study in Bavaria (South Germany). Mathematic and general cognitive abilities were assessed at 8 years with standardized tests; wealth information was assessed at 26 years with a structured interview and summarized into a comprehensive index score. All scores were z-standardized., Results: At 8 years, VP/VLBW (n = 193, 52.3% male) had lower mathematic and general cognitive abilities than healthy term comparison children (n = 217, 47.0% male). At 26 years, VP/VLBW had accumulated significantly lower overall wealth than term born comparison adults (-0.57 (1.08) versus -0.01 (1.00), mean difference 0.56 [0.36-0.77], p < .001). Structural equation modeling confirmed that VP/VLBW birth (β = -.13, p = .022) and childhood IQ (β = .24, p < .001) both directly predicted adult wealth, but math did not (β = .05, p = .413). Analyses were controlled for small-for-gestational-age (SGA) birth, child sex, and family socioeconomic status., Conclusion: This longitudinal study from birth to adulthood shows that VP/VLBW survivors' general cognitive rather than specific mathematic problems explain their diminished life-course success. These findings are important in order to design effective interventions at school age that reduce the burden of prematurity for those individuals who were born at highest neonatal risk., Competing Interests: The authors have declared that no competing interests exist.

Recent research has increasingly questioned the bilingual advantage for executive functions (EF). We used structural equation modeling in a large sample of Turkish immigrant and German monolingual children (N = 337; aged 5-15 years) to test associations between bilingualism and EF. Our data showed no significant group differences between Turkish immigrant and German children's EF skills while taking into account maternal education, child gender, age, and working memory (i.e., digit span backwards). Moreover, neither Turkish immigrant children's proficiency in either language nor their home language environment predicted EF. Our findings offer important new evidence in light of the ongoing debate about the existence of a bilingual advantage for EF., Competing Interests: The authors have declared that no competing interests exist.

Aim: To identify neonatal predictors to allow a developmental prognosis of the cognitive abilities of survivors born very preterm/very low birthweight (VLBW) into adult life., Method: The Bavarian Longitudinal Study is a prospective whole-population study that followed 260 infants born very preterm/VLBW from birth to adulthood. Regression analyses examined which neonatal factors predicted adult IQ., Results: Neonatal morbidity, neonatal treatment, and early social environment of infants born very preterm/VLBW explained 37.6% of the variance in adult IQ. Seven unique early-life predictors of lower adulthood IQ were found: respiratory distress syndrome, intraventricular haemorrhage, problems with mobility, mechanical ventilation, less parenteral nutrition, low/middle socioeconomic status, and poor early parent-infant relationships. Specifically, modifiable factors such as mechanical ventilation predicted a drop of 0.43 IQ points for each day of treatment, adjusted for initial respiratory problems. Good early parent-infant relationships predicted an approximately 5-point increase in adult IQ, adjusted for other significant predictors such as socioeconomic status., Interpretation: Mechanical ventilation, parenteral feeding, and early parenting were identified as significant modifiable factors that were strongly related to adult IQ. Mechanical ventilation policies have changed but there is scope for early interventions that focus on positive parenting, which may reduce the adverse effects of very preterm/VLBW birth on cognitive abilities., (© 2017 Mac Keith Press.)

Allergy to the short ragweed (Ambrosia artemisiifolia) pollen is a major health problem. The ragweed allergen repertoire has been recently expanded with the identification of Amb a 11, a new major allergen belonging to the cysteine protease family. To better characterize Amb a 11, a recombinant proform of the molecule with a preserved active site was produced in Escherichia coli, refolded, and processed in vitro into a mature enzyme. The enzymatic activity is revealed by maturation following an autocatalytic processing resulting in the cleavage of both N- and C-terminal propeptides. The 2.05-Å resolution crystal structure of pro-Amb a 11 shows an overall typical C1A cysteine protease fold with a network of molecular interactions between the N-terminal propeptide and the catalytic triad of the enzyme. The allergenicity of Amb a 11 was confirmed in a murine sensitization model, resulting in airway inflammation, production of serum IgEs, and induction of Th2 immune responses. Of note, inflammatory responses were higher with the mature form, demonstrating that the cysteine protease activity critically contributes to the allergenicity of the molecule. Collectively, our results clearly demonstrate that Amb a 11 is a bona fide cysteine protease exhibiting a strong allergenicity. As such, it should be considered as an important molecule for diagnosis and immunotherapy of ragweed pollen allergy., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing.

Aim: Recent reports suggest that delayed school entry (DSE) may be beneficial for children with developmental delays. However, studies of the effects of DSE are inconclusive. This study investigated the effects of DSE versus age-appropriate school entry (ASE) on children's academic achievement and attention in middle childhood., Method: In total, 999 children (492 females, 507 males; 472 born preterm) were studied as part of a prospective population-based longitudinal study in Germany. Using a natural experimental design, propensity score matching was applied to create two matched groups who differed only in terms of DSE versus ASE. Teacher ratings of achievement in mathematics, reading, writing, and attention were obtained in Year 1, and standardized tests were administered at 8 years of age., Results: There was no evidence of a difference in the odds of DSE versus ASE children being rated as above average by teachers in Year 1. In contrast, the standardized mean test scores for DSE children were lower than ASE children's mean scores in all domains (mathematics: B=-0.28 [-0.51 to -0.06)], reading: B=-0.39 [-0.65 to -0.14], writing: B=-0.90 [-1.07 to -0.74], and attention: B=-0.58 [-0.79 to -0.36])., Interpretation: DSE did not affect teacher-rated academic performance. However, missing 1 year of learning opportunities was associated with poorer average performance in standardized tests at 8 years of age. Future research is needed to determine the long-term effect of DSE on academic achievement., (© 2015 Mac Keith Press.)

Aim: The knowledge and information needs of education professionals were assessed to determine how prepared they feel to support the growing number of preterm children entering schools today., Method: In a national survey, 585 teachers and 212 educational psychologists completed the Preterm Birth-Knowledge Scale (PB-KS) to assess knowledge of outcomes following preterm birth. Total scores (range 0-33) were compared between groups and the impact of demographic characteristics on knowledge was analysed. Training and information needs were also assessed., Results: Teaching staff (mean 14.7, SD 5.5) had significantly lower knowledge scores than educational psychologists (mean 17.1, SD 5.0; p<0.001); both had significantly lower scores than neonatal clinicians surveyed previously (mean 26.0, SD 3.6; p<0.001). Education professionals' poorest areas of knowledge related to the most frequent adverse outcomes following preterm birth. Only 16% of teaching staff had received training about preterm birth and more than 90% requested more information. Having a special educational needs role and being employed at least 16 years were associated with higher knowledge scores., Interpretation: Education professionals have poor knowledge of the needs of children born preterm and most feel ill-equipped to support them in school. As teachers have primary responsibility for providing long-term support for children born preterm, this is of significant public health and educational concern., (© 2015 Mac Keith Press.)

Objective: Cognitive deficits have been inconsistently described for late or moderately preterm children but are consistently found in very preterm children. This study investigates the association between cognitive workload demands of tasks and cognitive performance in relation to gestational age at birth., Methods: Data were collected as part of a prospective geographically defined whole-population study of neonatal at-risk children in Southern Bavaria. At 8;5 years, n = 1326 children (gestation range: 23-41 weeks) were assessed with the K-ABC and a Mathematics Test., Results: Cognitive scores of preterm children decreased as cognitive workload demands of tasks increased. The relationship between gestation and task workload was curvilinear and more pronounced the higher the cognitive workload: GA² (quadratic term) on low cognitive workload: R²  = .02, p<0.001; moderate cognitive workload: R²  = .09, p<0.001; and high cognitive workload tasks: R²  = .14, p<0.001. Specifically, disproportionally lower scores were found for very (<32 weeks gestation) and moderately (32-33 weeks gestation) preterm children the higher the cognitive workload of the tasks. Early biological factors such as gestation and neonatal complications explained more of the variance in high (12.5%) compared with moderate (8.1%) and low cognitive workload tasks (1.7%)., Conclusions: The cognitive workload model may help to explain variations of findings on the relationship of gestational age with cognitive performance in the literature. The findings have implications for routine cognitive follow-up, educational intervention, and basic research into neuro-plasticity and brain reorganization after preterm birth.

Aim: Mothers of very preterm children have been reported to behave less sensitively and to be more controlling. It is unknown whether this is the result of maternal factors or due to maternal adaptation to children's cognitive problems., Method: We investigated a geographically defined prospective whole-population sample of very low birthweight (<1500 g) or very preterm (<32 wks' gestation; VLBW/VP) children (n = 267, 124 females, 143 males) and a comparison group born at term (n = 298, 146 females, 152 males) in Germany. Mother-child interactions were videotaped during a play situation and analysed with a standardized coding system at children's mean ages of 6 years 3 months and 8 years 5 months., Results: At both 6 years 3 months and 8 years 5 months, VLBW/VP children were less task persistent and socially active (p<0.001) whereas their mothers behaved less sensitively and were more controlling than term mother-child dyads (p<0.001). Cross-sectional group differences in maternal behaviour remained when scores where adjusted for social factors but disappeared once adjusted for child IQ. High maternal sensitivity predicted higher task persistence (p<0.001), in particular in those children with cognitive problems., Interpretation: Mothers of VLBW/VP children adapt their behaviour to their children's level of cognitive functioning. High maternal sensitivity is particularly beneficial for task persistence in children with cognitive deficits., (© The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.)

Pressure overload (PO) first causes cardiac hypertrophy and then heart failure (HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction (TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology (GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes (alpha-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function (PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males (collagen 3, matrix metalloproteinase 2, TIMP2, and TGFbeta2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF.

The reallocation of metabolic resources is important for survival during periods of limited nutrient intake. This has an influence on diverse physiological processes, including reproduction, repair, and aging. One important aspect of resource allocation is the difference between males and females in response to nutrient stress. We identified several groups of genes that are regulated in a sex-biased manner under complete or protein starvation. These range from expected differences in genes involved in reproductive physiology to those involved in amino acid utilization, sensory perception, immune response, and growth control. A striking difference was observed in purine and the tightly interconnected folate metabolism upon protein starvation. From these results, we conclude that the purine and folate metabolic pathway is a major point of transcriptional regulation during resource allocation and may have relevance for understanding the physiological basis for the observed tradeoff between reproduction and longevity.

We have monitored global changes in gene expression in mouse liver in response to fasting and sugar-fed conditions using high-density microarrays. From approximately 20,000 different genes, the significantly regulated ones were grouped into specific signaling and metabolic pathways. Striking changes in lipid signaling cascade, insulin and dehydroepiandrosterone (DHEA) hormonal pathways, urea cycle and S-adenosylmethionine-based methyl transfer systems, and cell apoptosis regulators were observed. Since these pathways have been implicated to play a role in the aging process, and since we observe significant overlap of genes regulated upon starvation with those regulated upon caloric restriction, our analysis suggests that starvation may elicit a stress response that is also elicited during caloric restriction. Therefore, many of the signaling and metabolic components regulated during fasting may be the same as those which mediate caloric restriction-dependent life-span extension.