Long-lasting effects of very preterm birth on brain structure in adulthood: A systematic review and meta-analysis.

Early life experiences, such as very preterm (VP) birth, can affect brain and cognitive development. Several prior studies investigated brain structure in adults born VP; synthesising these studies may help to provide a clearer understanding of long-term effects of VP birth on the brain. We systematically searched Medline and Embase for articles that investigated brain structure using MRI in adulthood in individuals born VP (<32 weeks' gestation) or with very low birth weight (VLBW; <1500 g), and controls born at term or with normal birth weight. In total, 77 studies met the review inclusion criteria, of which 28 studies were eligible for meta-analyses, including data from up to 797 VP/VLBW participants and 518 controls, aged 18-33 years. VP/VLBW adults exhibited volumetric, morphologic and microstructural alterations in subcortical and temporal cortical regions compared with controls, with pooled standardised mean differences up to - 1.0 (95% confidence interval: -1.2, -0.8). This study suggests there is a persisting neurological impact of VP birth, which may provide developmental neurobiological insights for adult cognition in high-risk populations.

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

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

Health-Related Quality-of-Life Outcomes of Very Preterm or Very Low Birth Weight Adults: Evidence From an Individual Participant Data Meta-Analysis.

BACKGROUND AND OBJECTIVE: Assessment of health-related quality of life for individuals born very preterm and/or low birthweight (VP/VLBW) offers valuable complementary information alongside biomedical assessments. However, the impact of VP/VLBW status on health-related quality of life in adulthood is inconclusive. The objective of this study was to examine associations between VP/VLBW status and preference-based health-related quality-of-life outcomes in early adulthood. METHODS: Individual participant data were obtained from five prospective cohorts of individuals born VP/VLBW and controls contributing to the 'Research on European Children and Adults Born Preterm' Consortium. The combined dataset included over 2100 adult VP/VLBW survivors with an age range of 18-29 years. The main exposure was defined as birth before 32 weeks' gestation (VP) and/or birth weight below 1500 g (VLBW). Outcome measures included multi-attribute utility scores generated by the Health Utilities Index Mark 3 and the Short Form 6D. Data were analysed using generalised linear mixed models in a one-step approach using fixed-effects and random-effects models. RESULTS: VP/VLBW status was associated with a significant difference in the Health Utilities Index Mark 3 multi-attribute utility score of - 0.06 (95% confidence interval - 0.08, - 0.04) in comparison to birth at term or at normal birthweight; this was not replicated for the Short Form 6D. Impacted functional domains included vision, ambulation, dexterity and cognition. VP/VLBW status was not associated with poorer emotional or social functioning, or increased pain. CONCLUSIONS: VP/VLBW status is associated with lower overall health-related quality of life in early adulthood, particularly in terms of physical and cognitive functioning. Further studies that estimate the effects of VP/VLBW status on health-related quality-of-life outcomes in mid and late adulthood are needed.

The Bayley Social-Emotional Scale and the Assessment of Preterm Infants: a systematic review / Escala Socioemocional Bayley e Avaliação de Bebês Prematuros: uma revisão sistemática / Escala Socioemocional de Bayley y Evaluación para Bebés Prematuros: una revisión sistemática

The Bayley scale is one of the most widely used instruments for assessing infant development. This article aimed to systematically review the contribution of the Bayley social-emotional scale in the assessment of social-emotional development in preterm infants. This systematic review followed PRISMA guidelines and was registered in PROSPERO. According to the inclusion criteria, 19 articles were selected from electronic databases. The results indicate reduced rates in evaluating the scale for children with lower gestational age, birth weight, and the association with environmental, biological, and hospital clinical factors. However, no analysis was found between the axes that guide the social-emotional development milestones present in the Bayley assessment and the developmental outcomes of preterm children. Bayley's social-emotional scale and other assessment methods can jointly compose a detailed and sensitive protocol for preterm infants regarding early childhood emotional health care. (AU)

A escala Bayley é um dos instrumentos mais utilizados para avaliação do desenvolvimento infantil. O objetivo deste artigo foi realizar uma revisão sistemática sobre a contribuição da escala socioemocional, pertencente à Bayley, na avaliação de crianças prematuras. A revisão seguiu as recomendações PRISMA e foi registrada no PROSPERO. Conforme critérios de inclusão, 19 artigos foram selecionados a partir de bancos de dados eletrônicos. Os resultados indicam índices reduzidos na avaliação da escala para crianças com menor idade gestacional, peso ao nascer e a associação com fatores ambientais, biológicos e clínicos hospitalares. No entanto, não foram encontradas análises entre os eixos que orientam os marcos de desenvolvimento socioemocional, presentes na avaliação Bayley e os resultados do desenvolvimento das crianças prematuras. A escala socioemocional da Bayley e outros métodos de avaliação podem conjuntamente compor um protocolo detalhado e sensível destinado ao cuidado da saúde emocional de crianças nascidas prematuras. (AU)

La escala Bayley es uno de los instrumentos más utilizados para la evaluación del desarrollo infantil. El propósito del artículo fue revisar sistemáticamente la contribución de la escala socioemocional de Bayley en la evaluación de bebés prematuros. La revisión siguió las recomendaciones PRISMA y fue registrada en PROSPERO. Según los criterios de inclusión, se seleccionaron 19 artículos de bases de datos electrónicas. Los resultados indican índices reducidos en la evaluación de la escala para niños con menor edad gestacional, peso al nacer asociaciados con factores ambientales, biológicos y clínicos hospitalarios. Sin embargo, no se encontraron análisis entre los ejes que orientan los hitos del desarrollo socioemocional, presentes en la evaluación Bayley, y los resultados del desarrollo de los niños prematuros. La Escala Socioemocional de Bayley y otros métodos de evaluación pueden formar en conjunto un protocolo detallado y sensible para el cuidado de la salud emocional de niños prematuros. (AU)

Health-related quality of life from 20 to 32 years of age in very low birth weight individuals: a longitudinal study.

BACKGROUND: Preterm birth with very low birth weight (VLBW, birth weight < 1500 g) is associated with health problems later in life. How VLBW individuals perceive their physical and mental health-related quality of life (HRQoL) is important to understand their putative burden of disease. Previous studies have shown mixed results, and longitudinal studies into adulthood have been requested. This study aimed to investigate differences in HRQoL between preterm VLBW and term born individuals at 32 years of age, and to study changes in HRQoL from 20 to 32 years. METHODS: In a geographically based longitudinal study, 45 VLBW and 68 term born control participants completed the Short Form 36 Health Survey (SF-36) at 32 years of age. Data from three previous timepoints was also available (20, 23 and 28 years of age). The SF-36 yields eight domain scores as well as a physical and a mental component summary. Between-group differences in these variables were investigated. We also performed subgroup analyses excluding individuals with disabilities, i.e., cerebral palsy and/or low estimated intelligence quotient. RESULTS: At 32 years of age, the physical component summary was 5.1 points lower (95% confidence interval (CI): 8.6 to 1.6), and the mental component summary 4.1 points lower (95% CI: 8.4 to - 0.3) in the VLBW group compared with the control group. For both physical and mental component summaries there was an overall decline in HRQoL from 20 to 32 years of age in the VLBW group. When we excluded individuals with disabilities (n = 10), group differences in domain scores at 32 years were reduced, but physical functioning, bodily pain, general health, and role-emotional scores remained lower in the VLBW subgroup without disabilities compared with the control group. CONCLUSION: We found that VLBW individuals reported lower HRQoL than term born controls at 32 years of age, and that HRQoL declined in the VLBW group from 20 to 32 years of age. This was in part, but not exclusively explained by VLBW individuals with disabilities.

Multidisciplinary and neuroimaging findings in preterm born very low birthweight individuals from birth to 28 years of age: A systematic review of a Norwegian prospective cohort study.

BACKGROUND: Children born preterm with very low birthweight (VLBW) face long-lasting neurodevelopmental challenges, where multidisciplinary assessments are warranted. The International Classification of Functioning, Disability and Health (ICF) provides a framework for understanding and conceptualising these outcomes. OBJECTIVES: We aimed to review clinical and neuroimaging findings from birth to adulthood in a Norwegian cohort of individuals born preterm with VLBW (gestational age <37 weeks, birthweight ≤1500 g) within the framework of ICF. DATA SOURCES: We searched PubMed and Embase for articles reporting results of the Norwegian University of Science and Technology (NTNU) Low Birth Weight in a Lifetime Perspective study. STUDY SELECTION AND DATA EXTRACTION: We included original articles reporting proportions of adverse outcomes, mean group differences, risk factors or associations between outcomes. Data were extracted according to ICF's two-level classification. Body functions and structures comprised outcomes of brain structures, cognition, mental health, vision, pain and physical health. Activities and participation comprised motor skills, general and social functioning, education, employment, and health-related quality of life. SYNTHESIS: We performed a qualitative synthesis of included articles. Where mean (SD) was reported, we calculated group differences in SD units. RESULTS: Fifty-eight publications were included. Within body functions and structures, increased prevalence of brain structure pathology, lower cognitive performance, mental health problems, visual and physical health impairments through childhood, adolescence and young adulthood were reported among preterm VLBW participants compared with controls. Within activities and participation, motor problems, lower general and social functioning, and lower academic attainment were found. Perinatal factors were associated with several outcomes, and longitudinal findings suggested persistent consequences of being born preterm with VLBW. CONCLUSIONS: Being born preterm with VLBW has long-term influences on body functions and structures, activities and participation. The ICF is appropriate for assessing general domains of functioning and guiding the management of individuals born preterm with VLBW.

Co-regulation and parenting stress over time in full-term, very low birthweight preterm, and psycho-socially at-risk infant-mother dyads: Implications for fostering the development of healthy relationships.

From birth, mothers and infants co-regulate their interactions that are shaped by their socio-emotional development, relationship history, current circumstances, and goals. However, few studies have longitudinally explored co-regulation in the context of medical and psycho-social risk. The present 4-wave longitudinal study sought to shed light on factors associated with co-regulation over time in infants from 6- to 48-months. The objectives were to 1) identify differences in co-regulation among low- and at-risk infant-mother dyads, 2) explore changes in co-regulation over time, and 3) explore the associations between infant-mother co-regulation and parenting stress in these low- and at-risk groups over time. Participants included three groups of infant-mother dyads (full-term [FT], n = 48; very low birthweight/preterm [VLBW/preterm] born 26-32 weeks, weighing 800-1500 g, n = 61; psycho-socially at-risk where parents had histories of socioeconomic disadvantage, n = 54) followed longitudinally at 6-, 12-, 18-, and 48-months of age. Dyads engaged in a free play in their homes that was coded for co-regulation using Fogel, de Koeyer, Secrist, Sipherd, Hafen, and Fricke's (2003) Revised Relational Coding System (RRCS), and mothers reported on their level of parenting stress. Results from MANOVAs at each time point indicated significant differences between the groups at 18-months, with psycho-socially at-risk dyads engaging in more one-sided interactions than FT and VLBW/preterm dyads, and more dysregulation and miscommunication than VLBW/preterm dyads. Multi-level models of co-regulation revealed that dyads became progressively less synchronous from 6- to 12-months, followed by greater synchrony and mutual reciprocity from 12-months onwards. Parenting stress was associated with less synchrony and less mutual reciprocity amongst the at-risk groups. Maternal education was associated with greater engagement and girls tended to engage in more synchronous interactions than boys. Our results underscore the value and implications of considering background risk and concurrent parent perceptions in the development and reciprocity of parent-infant co-regulation and their subsequent relationships from infancy onwards.

Relationship of withdrawn, anxious/depressed and attention problems to cognitive performance in preterm children at 18 months and 36 months of age.

OBJECTIVE: A positive significant association has been found between behavior problems and lower cognition in very low birthweight (VLBW) preterm children at school age, but there is relatively little information about whether such an association exists in toddlers and on the continuity of this association. The aim of this study was to assess if there is a relationship between behavior problems and cognitive performance in VLBW preterm children at 18 months post conception and 3 years old, independent of socioeconomic status and sex. METHOD: Parents of 124 preterm children completed a behavior rating questionnaire (Child Behavior Checklist 1.5-5) to measure behavior problems characteristic of preterm children (Withdrawn, Anxious/Depressed, and Attention Problems). Children completed the Cognitive Scale of the Bayley Scales of Infant Development-III at 18 months and the Wechsler Preschool and Primary Scale (III or IV) at 36 months old. Socioeconomic status (SES), sex, and diagnoses of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) at 3 years were recorded for each child. RESULTS: Withdrawn problems at 18 months were associated with lower cognitive scores at 18 months and both Withdrawn problems at 18 months and 36 months were associated with lower cognitive scores at 36 months. Increases in Attention Problems scores from 18 to 36 months were associated with decreases in cognitive scores over that period. Lower SES was associated with lower cognitive scores at 36 months and decreases in cognitive scores between 18 and 36 months. Sex was not related to behavior problems or cognition. Diagnoses of ASD and ADHD were significantly associated with increased Withdrawn behavior and Attention Problems, respectively. CONCLUSIONS: The early association of Withdrawn behaviors with less favorable cognitive performance at 18 months and 36 months and the relationship between increases in Attention Problems with decreases in cognitive scores between the toddler and preschool period indicate the need for early assessment of and intervention for behavior problems, as well as concurrent cognitive delays, in VLBW preterm children.

Development of a risk calculator to predict attention-deficit/hyperactivity disorder in very preterm/very low birth weight newborns.

BACKGROUND: Very preterm/very low birth weight (VP/VLBW) newborns can have lifelong morbidities, as attention-deficit/hyperactivity disorder (ADHD). Clinicians have no markers to discriminate which among those individuals will develop later ADHD, based only on the clinical presentation at birth. Our aim was to develop an individualized risk calculator for ADHD in VP/VLBW newborns. METHODS: This retrospective prognostic study included a consecutive sample of all VP/VLBW children (gestational age <32 weeks and/or birth weight <1.5 kg) born between 2010 and 2012 from a clinical cohort in a Brazilian tertiary care hospital. Children were clinically assessed at 6 years of age for ADHD using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The least absolute shrinkage and selection operator (LASSO) method was used for model-building. RESULTS: Ninety-six VP/VLBW children were assessed at 6 years of age (92% follow-up), of whom 32 (33%) were diagnosed with ADHD. The area under the ROC curve (AUC) for ADHD prediction based on seven parameters (late-onset sepsis confirmed by blood culture, necrotizing enterocolitis, neonatal seizures, periventricular leukomalacia, respiratory distress syndrome, length of hospital stay, and number of maternal ADHD symptoms) was .875 (CI, 0.800-0.942, p < .001; AUC corrected for optimism with bootstrapping: .806), a performance that is comparable to other medical risk calculators. Compared to approaches that would offer early intervention to all, or intervention to none, the risk calculator will be more useful in selecting VP/VLBW newborns, with statistically significant net benefits at cost:benefits of around 1:2 to around 10:6 (range of ADHD risk thresholds of 32%-62%, respectively). It also showed specificity for ADHD compared to other prevalent child psychopathologies. CONCLUSIONS: The risk calculator showed good performance for early identification of VP/VLBW newborns at high risk of future ADHD diagnosis. External validity in population-based samples is needed to extend clinical usefulness.

Social Functioning in Adults Born Very Preterm: Individual Participant Meta-analysis.

CONTEXT: There is a lack of research on individual perceptions of social experiences and social relationships among very preterm (VP) adults compared with term-born peers. OBJECTIVE: To investigate self-perceived social functioning in adults born VP (<32 weeks' gestation) and/or with very low birth weight (VLBW) (<1500g) compared with term-born adults (≥37 weeks' gestation) using an individual participant data (IPD) meta-analysis. DATA SOURCES: Two international consortia: Research on European Children and Adults born Preterm and Adults Born Preterm International Collaboration. STUDY SELECTION: Cohorts with outcomes assessed by using the Adult Self-Report Adaptive Functioning scales (friends, spouse/partner, family, job, and education) in both groups. DATA EXTRACTION: IPD from 5 eligible cohorts were collected. Raw-sum scores for each scale were standardized as z scores by using mean and SD of controls for each cohort. Pooled effect size was measured by difference (Δ) in means between groups. RESULTS: One-stage analyses (1285 participants) revealed significantly lower scores for relationships with friends in VP/VLBW adults compared with controls (Δ -0.37, 95% confidence interval [CI]: -0.61 to -0.13). Differences were similar after adjusting for sex, age, and socioeconomic status (Δ -0.39, 95% CI: -0.63 to -0.15) and after excluding participants with neurosensory impairment (Δ -0.34, 95% CI: -0.61 to -0.07). No significant differences were found in other domains. LIMITATIONS: Generalizability of research findings to VP survivors born in recent decades. CONCLUSIONS: VP/VLBW adults scored their relationship with friends lower but perceived their family and partner relationships, as well as work and educational experiences, as comparable to those of controls.

Emotion regulation from infancy to toddlerhood: Individual and group trajectories of full-term and very-low-birthweight preterm infants.

Adaptive emotion regulation begins with infants operating jointly with their parents to regulate their emotions, which fosters the development of independent regulation. Little is known about when or how this transition occurs, or the impact of factors such as parental availability or premature birth status. The current study examined the use of self-soothing, attentional distraction, and dyadic regulation in full-term and healthy very-low-birthweight (VLBW) preterm infant-mother dyads at 5 ½, 12, and 18 months of age. At 5 ½ months, dyads participated in the Still-Face procedure. At 12 and 18 months, dyads participated in two free-play interactions, a puzzle task, and an interference task. Emotion regulation behaviors were coded using two systematic, observational systems. Results indicated that infants used less self-soothing and attentional distraction and more dyadic regulation as they aged. Increased use of self-soothing at earlier ages predicted increased use of dyadic regulation at subsequent ages. Toddlers used more independent, attention-seeking, and escape behavior during periods of maternal unavailability. There were no significant differences between full-term and VLBW/preterm toddlers' emotion regulation behaviors. Results from the current study contribute to the understanding of normative development of emotion regulation and the risk associated with prematurity.

Chronic post-traumatic stress in mothers of very low birth weight preterm infants born before 32 weeks of gestation. / Estrés postraumático crónico en madres de prematuros de muy bajo peso nacidos antes de las 32 semanas de gestación.

Background: The birth of very low birth weight (VLBW) preterm infants causes stress in mothers, which may continue for over 6 months. This is called chronic post-traumatic stress disorder (CPTSD). Objective: To detect CPTSD frequency and symptoms among mothers of VLBW preterm infants born before 32 weeks of gestation. Methods: Cross-sectional cohort study in mothers using a survey based on the Davidson Trauma Scale. Results: A total of 172 surveys were administered but 146 were included; 82 (56 %) did not have stress symptoms, while 64 (44 %) had CPTSD. Mothers with CPTSD accounted for 46.8 % of preterm infants born at ≤ 28 weeks versus 31.7 % in those without CPTSD (p = 0.032). Preterm infants with a birth weight < 1000 g were significantly more frequent among mothers with CPTSD, 53 % versus 34 % among those without stress (p = 0.011). No differences were observed in neonatal morbidity (p = 0.072). Severe morbidity in preterm infants was significantly more common among those with CPTSD, 43.8 % versus 28 % (p ≤ 0.004).Mothers who had a lower education accounted significantly for more cases of CPTSD (p = 0.013). No significant differences were seen in maternal age (p = 0.313), children's age (p = 0.405), and length of stay (p = 0.316). Conclusion: Among the mothers of VLBW preterm infants, 44 % had CPTSD, and this was significantly more common among those who had preterm infants born at ≤28 weeks, a birth weight <1000 g, severe morbidity, and a lower level of education.

Antecedentes. Los prematuros de muy bajo peso al nacer suelen generar estrés en sus madres, que puede persistir más de seis meses luego del nacimiento. Este trastorno se denomina estrés postraumático crónico (EPTC). Objetivo. Detectar frecuencia y síntomas del EPTC en madres de prematuros de muy bajo peso al nacer menores de 32 semanas de gestación. Métodos. Estudio transversal, mediante una encuesta voluntaria autoadministrada a madres con embarazo único. Se empleó la Escala de trauma de Davidson. Resultados. Se realizaron 172 encuestas; se eliminaron 26 incompletas. De 146 madres incorporadas, 64 (el 44 %) presentaron estrés. Las madres con EPTC tuvieron un 46,8 % de prematuros nacidos < 28 semanas vs. un 31,7 % en madres sin EPTC (p: 0,032). Los prematuros con peso < 1000 g fueron más frecuentes en madres con EPTC, el 53 % vs. el 34 % en madres sin estrés (p: 0,011). No hubo diferencias entre grupos de madres en morbilidad neonatal (p: 0,072). La morbilidad grave fue más frecuente en madres con EPTC, el 44 %. vs. el 28 % (p: < 0,004). Las madres con menor escolaridad tuvieron EPTC significativamente mayor (p: 0,013). No hubo diferencias en la edad materna (p: 0,313), edad de los niños (p: 0,405) y días de hospitalización en la Unidad (p: 0,316). Conclusión. El 44 % de las madres de prematuros de muy bajo peso al nacer tuvieron EPTC, significativamente más frecuente en prematuros ≤ 28 semanas, con peso < 1000 g, morbilidad grave y menor escolaridad materna.

Psychiatric symptoms and risk factors in adults born preterm with very low birthweight or born small for gestational age at term.

BACKGROUND: We aimed to examine psychiatric symptoms in adults born preterm with very low birthweight or born at term small for gestational age compared with normal birthweight peers, and examine associations with perinatal factors and childhood motor and cognitive function. METHODS: In this longitudinal cohort study, one preterm born group with very low birthweight (VLBW: birthweight ≤1500 g), one term-born Small for Gestational Age (SGA: birthweight <10th percentile) group and one term-born non-SGA control group, were assessed at 26 years of age. Primary outcomes were scores on self-reported questionnaires: Achenbach System of Empirically Based Assessment - Adult Self-Report, The Autism-Spectrum Quotient and Peters et al. Delusions Inventory. Exposure variables were perinatal data, while childhood motor and cognitive function were examined as possible early markers. RESULTS: Both the preterm VLBW and the term SGA group reported higher levels of attention, internalizing and externalizing problems compared to the control group. In addition, the VLBW participants reported more critical items and a higher proportion had intermediate level autistic traits, while the SGA participants reported more intrusive behavior. Increasing length of respiratory support and hospital stay in the neonatal period, and motor problems in early adolescence, were associated with adult psychiatric symptoms in the VLBW group. CONCLUSIONS: Psychiatric symptoms were frequent in the preterm VLBW group and also in the term-born SGA group. Those who were sickest as babies were most at risk. Motor problems can possibly serve as an early marker of adult psychiatric symptoms in low birthweight individuals.

Reaching skills of infants born very preterm predict neurodevelopment at 2.5 years.

The purpose was to investigate associations between quality of reaching for moving objects at 8 months corrected age and neurodevelopment at 2.5 years in children born very preterm (gestational age (GA), 24-31 weeks). Thirtysix infants were assessed while reaching for moving objects. The movements were recorded by a 3D motion capture system. Reaching parameters included aiming, relative length of the reach, number of movement units, proportion of bimanual coupled reaches and number of hits. Neurodevelopment was assessed at 2.5 years by the Bayley Scales of Infant Development III. There were strong associations between infant reaching kinematics and neurodevelopment of cognition and language but the patterns differed: in children born extremely preterm (GA < 28 weeks), planning and control of reaching was strongly related to outcome, while in children born very preterm (GA 28-31 weeks) number of hits and bimanual strategies were of greater relevance. In conclusion, for extremely preterm infants, basic problems on how motion information is incorporated with action planning prevail, while in very preterm infants the coordination of bimanual reaches is more at the focus. We conclude that the results reflect GA related differences in neural vulnerability and that early motor coordination deficits have a cascading effect on neurodevelopment.

Associations of Hormonal Biomarkers With Mental Health and Healthy Behaviors Among Mothers of Very-Low-Birthweight Infants.

OBJECTIVES: To examine the concurrent use of self-report questionnaires and hormonal biomarkers, specifically levels of testosterone and cortisol, along with demographic variables and corrected age (CA) in the assessment of mental health and healthy behaviors among mothers of very-low-birthweight (VLBW, BW < 1,500 g) infants at five time points over 2 years post birth. METHOD: Data on 40 mothers from a neonatal intensive care unit of a tertiary medical center in the southeast United States were collected from the medical record, standard questionnaires for the mother (depressive symptoms, perceived stress, anxiety, mental health status, parenting stress, and healthy lifestyle behaviors), and biochemical measurement of maternal testosterone and cortisol using enzyme immunoassay at birth, 40 weeks' postmenstrual age, and 6, 12, and 24 months CA. RESULTS: Maternal self-report of mental health improved from birth to 6 or 12 months then worsened at 24 months. Mixed linear models showed that mothers with higher testosterone levels had more depressive symptoms and smoked more, whereas mothers with higher cortisol levels had healthier behaviors and exercised more. Testosterone levels were negatively correlated with cortisol levels. Marital status, education, and health insurance were the most predictive demographic variables for the levels of hormonal biomarkers, mental health, and healthy behaviors. CONCLUSIONS: The use of self-report and biochemical measurement was effective in assessing maternal mental health and healthy behaviors over 2 years post birth, when mothers of VLBW infants tend to experience more mental health problems and parenting difficulties than mothers of normal-BW full-term infants.

Internalizing symptoms in very low birth weight preschoolers: Symptom level and risk factors from four rating perspectives in a controlled multicenter study.

BACKGROUND: Preterm births rates of infants with very low birth weight (VLBW < 1500 g) are increasing. Prematurity poses several risks for emotional child development, e.g., internalizing symptoms. Our understanding of this condition in young children is limited, for at preschool age, symptoms have mostly been assessed from the mother's perspective only. METHODS: As part of the longitudinal HaFEn cohort-study in Hamburg, Germany, we measured the level of internalizing symptoms in VLBW and term preschoolers as well as predictors from four informants' perspectives: mother, father, teacher, and child. A multilevel model was constructed to examine predictors of internalizing symptoms. n = 104 VLBW and n = 79 term children were included. RESULTS: From both their parents' perspective, children with VLBW had a significantly higher level of internalizing symptoms. From the teacher's and child's own perspectives, there were no significant mean group differences. In the multilevel analyses, the results were different regarding the four perspectives. VLBW did not predict internalizing symptoms. From mother's perspective, her own postpartum psychological distress, and from father's perspective, his postpartum and current psychological distress predicted a higher level of internalizing symptoms in their offspring. From teacher's perspective, socio-economic status predicted internalizing symptoms. LIMITATIONS: The sample size was relatively small. Exclusion criteria and drop out of families could have created some selection bias. CONCLUSIONS: Our findings point to the importance of early identification of parental postpartum psychological distress given the potential for later internalizing symptoms in their children or the perception of their offspring as vulnerable and symptomatic, which may also impact the child's development.

Language in 2-year-old children born preterm and term: a cohort study.

PURPOSE: Language skills are critical. Children born very preterm are vulnerable to language problems, but further work is needed to determine characteristics and specific predictors of language problems in this population. We aimed to compare language outcomes between 2-year-old children born <30 weeks and their term-born peers; and to explore risk factors for language difficulties in this cohort. DESIGN: Language at 2 years was examined in 134 children born <30 weeks and 133 children born at term using the Bayley Scales of Infant and Toddler Development - 3rd Edition (Bayley-3) and the Communication and Symbolic Behaviour Scale: Developmental Profile (Infant Toddler Checklist) (CSBS:DP). Outcomes were compared between groups. Factors hypothesised to predict language outcome were examined in the preterm group: gestational age at birth, birth weight z-score, sex, hearing loss, multilingualism, maternal education, brain abnormality on MRI, medical risk and oromotor concerns at 12 months. RESULTS: Children born <30 weeks performed more poorly on the CSBS:DP (particularly the social and symbolic composites) and the language scale of the Bayley-3 at 2 years than term-born peers. Lower gestational age at birth, male sex, hearing loss and multilingualism predicted poorer language scores. CONCLUSIONS: Despite improvements in medical management, children born very preterm exhibit language delays at 2 years of age, with specific deficits in social communication and symbolic skills. Significant predictors of poorer language outcomes were similar to those in the general population (male sex, hearing loss, multilingualism), suggesting that further work is needed to establish which specific factors place preterm-born children at heightened risk.

The dual nature of hypothalamic-pituitary-adrenal axis regulation in dyads of very preterm infants and their mothers.

The co-regulation of the hypothalamic-pituitary-adrenal (HPA) axis in mother-infant dyads is thought to be key for infant and child development. Nonetheless, previous literature presents some inconsistencies that might at least partially be due to the presence of risk conditions and the use of different statistical approaches to measure HPA axis co-regulation. Very preterm (VPT) birth represents one of these risk conditions as the early foundation of mother-infant interaction is disrupted. Both VPT infants and their mothers present evidence of altered HPA axis regulation. Nonetheless, the comparison of mother-infant HPA axis co-regulation in VPT infants compared to full-term (FT) ones has not been previously investigated. In this study, 3-month-old (corrected age) VPT infants and FT counterparts with their mothers took part in a well-validated stress-inducing laboratory task (i.e., double Face-to-Face Still-Face, FFSF paradigm). Salivary cortisol samples were obtained before (Baseline) and after (Early reactivity, Late reactivity and Recovery) the FFSF procedure. Dyadic HPA axis co-regulation was assessed at each sample time-point (i.e., in-moment coupling) as well as across samples (i.e., in-time synchrony). Significant in-moment coupling emerged at Baseline, Late reactivity and Recovery for FT infants' dyads only. An overlying pattern of salivary cortisol trajectories emerged between mothers and infants in the VPT group, whereas a more complex pattern of reciprocal and complementary co-regulation was found for FT infants' dyads. Although both groups gave evidence of HPA axis co-regulation, dyads of VPT infants appear to be less able to adapt reciprocally and dynamically to stressful conditions. These findings suggest that multiple approaches to account for dyadic HPA axis co-regulation should be used in order to depict the complex pattern of biological rhythms coordination in mother-infant dyads.

Telomere length and salivary cortisol stress reactivity in very preterm infants.

During the Neonatal Intensive Care Unit (NICU) stay, very preterm (VPT) infants are exposed to life-saving yet pain-inducing skin-breaking procedures (i.e., NICU pain-related stress) which contribute to the programming of hypo-responsive HPA axis development during the first months of life. Unfortunately, to date the mechanisms linking NICU pain-related stress and altered HPA axis regulation are only limitedly known. Telomere length (TL) regulation is an epigenetic mechanism previously shown to be affected by early stress exposures and capable of associating with HPA axis reactivity in children. In VPT infants, NICU pain-related stress was found to associate with decreased TL from birth to discharge, but there is no evidence for the association between TL and HPA axis in these infants. In this study, we prospectively examined the relationship between NICU pain-related stress and HPA axis reactivity to an age-appropriate socio-emotional condition (i.e., the Still-Face Procedure, SFP) in healthy VPT infants at 3-month corrected age. NICU pain-related stress was computed as the ratio between the number of skin-breaking procedures and length of NICU stay. A differential score (i.e., ∆TL) was obtained subtracting TL at birth from TL at discharge. A normalized (log10) cortisol reactivity index (CRI) was obtained by averaging post-stress (20 min after SFP) salivary cortisol sample on baseline value. A regression model controlling for neonatal and socio-demographic confounders showed that ∆TL was the only significant predictor of CRI. Although preliminary, these findings contribute to our knowledge of the mechanisms linking early exposures to adversity and later in life regulation of the HPA axis in VPT infants.