Common core assessments in follow-up studies of adults born preterm-Recommendation of the Adults Born Preterm International Collaboration

Of all newborns, 1%-2% are born very preterm (VP; <32 weeks) or with very low birthweight (VLBW; ≤1500 g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow-up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; www.apic-preterm.org). Joint analyses require data harmonisation, highlighting the importance of consistent assessment methodologies. To present an expert recommendation on Common Core Assessments to be used in follow-up assessments of adults born preterm. Principles of Common Core Assessments were discussed at APIC meetings. Experts for each specific outcome domain wrote the first draft on assessments pertaining to that outcome. These drafts were combined and reviewed by all authors. Consensus was reached by discussion at APIC meetings. We present a recommendation by APIC experts on consistent measures to be used in adult follow-up assessments. The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing on current gaps in knowledge. It includes sections on study design, cardiometabolic and related biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction. [Abstract copyright: © 2020 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.

Self-Reported Mental Health Problems Among Adults Born Preterm : A Meta-analysis

CONTEXT: Preterm birth increases the risk for mental disorders in adulthood, yet findings on abstract self-reported or subclinical mental health problems are mixed. OBJECTIVE: To study self-reported mental health problems among adults born preterm at very low birth weight (VLBW; DATA SOURCES: Adults Born Preterm International Collaboration. STUDY SELECTION: Studies that compared self-reported mental health problems using the Achenbach Young Adult Self Report or Adult Self Report between adults born preterm at VLBW (n = 747) and at term (n = 1512). DATA EXTRACTION: We obtained individual participant data from 6 study cohorts and compared preterm and control groups by mixed random coefficient linear and Tobit regression. RESULTS: Adults born preterm reported more internalizing (pooled beta =.06; 95% confidence interval.01 to.11) and avoidant personality problems (.11;.05 to.17), and less externalizing (-.10;-. 15 to-. 06), rule breaking (-.10;-. 15 to-. 05), intrusive behavior (-.14;-. 19 to-.09), and antisocial personality problems (-.09;-. 14 to-.04) than controls. Group differences did not systematically vary by sex, intrauterine growth pattern, neurosensory impairments, or study cohort. LIMITATIONS: Exclusively self-reported data are not confirmed by alternative data sources. CONCLUSIONS: Self-reports of adults born preterm at VLBW reveal a heightened risk for internalizing problems and socially avoidant personality traits together with a lowered risk for externalizing problem types. Our findings support the view that preterm birth constitutes an early vulnerability factor with long-term consequences on the individual into adulthood.Peer reviewe

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

Use of functional feeding strategies to protect Atlantic salmon from virally-induced inflammatory diseases- mechanistic insights revealed by transcriptomic analysis

Over the past few years one of the major concerns in the Atlantic salmon (Salmo salar) farming industry has been the increasing incidence and severity of inflammatory viral diseases. Heart and skeletal muscle inflammation (HSMI) and cardiomyopathy syndrome (CMS) are currently two of the most prevalent viral diseases in commercial Atlantic salmon farms in Norway. Mortality levels in both diseases are generally low but morbidity can be very high with the associated chronic inflammatory response lasting for several months. The consequent reduced growth performance is causing considerable financial impact as HSMI has become increasingly widespread in recent years. The impact of CMS is further exacerbated as it generally affects large fish close to harvest. HSMI lesions occur in the atrium and ventricle in the heart including inflammation and necrosis in epi- endo- and myocardium along with myositis of red skeletal muscle. CMS lesions are commonly observed in the spongy myocardium in the atrium and ventricle of the heart with severe mononuclear inflammation and necrosis. Furthermore, circulatory disturbances associated with reduced cardiac function cause multifocal liver steatosis and necrosis in both diseases. Currently there are no vaccines or any other effective treatments for these diseases and so alternative therapies that could potentially modulate the intensity of the inflammatory response could be crucial to improve the clinical manifestation of the diseases. Therefore, the overall aim of the present study was to evaluate the concept of “clinical nutrition” to improve the clinical symptoms of both viral diseases, HSMI and CMS, through the use of functional feeds formulated with reduced lipid content and increased proportions of anti-inflammatory fatty acids to moderate the apparently uncontrolled inflammatory response in the heart tissue associated with both diseases and also alleviate the secondary hepatic lesions. The experimental work consisted of three major dietary trials in Atlantic salmon in seawater. Two large trials investigated the effects of functional feeds in Atlantic salmon challenged with Atlantic salmon piscine reovirus (ASRV) and piscine myocarditis virus (PMCV), the causal agents of HSMI and CMS, respectively. In both trials, heart transcriptome, heart and liver histopathology and tissue lipid and fatty acid compositions and metabolism were determined post-infection in fish fed with the functional feeds in comparison with fish fed with a standard commercial feed formulation considered as a reference diet. All the functional feeds were formulated to have reduced digestible energy through lower dietary lipid and higher protein contents, and increased levels and proportions of anti-inflammatory long-chain polyunsaturated fatty acids (LC-PUFA), particularly eicosapentaenoic acid (EPA) compared with the reference diets. Histopathology, fatty acid composition and gene expression of heart were assessed over a long time-period of 16 weeks and 14 weeks post-challenge with ASRV and PMCV, respectively. Viral load in heart tissue, hepatic histopathology and fatty acid composition of liver and head kidney along with expression of the genes involved in the eicosanoid and LC-PUFA and eicosanoid biosynthesis pathways were also determined in the HSMI trial. The third trial was a nutritional trial evaluating the effects of dietary digestible energy content on lipid and fatty acid metabolism in salmon fed diets containing graded amounts of lipid. Fatty acid composition of liver and heart were assessed over 12 weeks, along with the hepatic expression of genes of lipid and fatty acid metabolism. The results of this research are presented in four chapters (Chapters 2-5) as four paper manuscripts. The manuscripts/Papers are either published (Chapter 2), in review (Chapter 3 and 4) or drafted for submission (Chapter 5) in appropriate peer-reviewed international journals. Chapter 2 and 3 correspond to the HSMI trial, Chapter 4 to the nutritional trial, and Chapter 5 to the CMS trial. Chapter 2 showed that viral load and histopathology scores were lower in fish fed the functional feeds, especially diet FF1, which displayed better performance. Diet strongly influenced the expression of genes related with the immune and inflammatory responses, with delayed expression in fish fed the functional feeds. Up-regulation of pro-inflammatory genes was correlated with the higher viral load observed at early-mid stages of the disease in fish fed the reference diet (ST). Expression of genes related with the immune response at 16-weeks post challenge reflected the differences in immunomodulation between the functional feeds, with fish fed diet FF1 showing lower expression. Therefore, severity of the heart lesions was correlated with the intensity of the immune response and could be associated with tissue anti-inflammatory LC-PUFA levels. Chapter 3 was focused on liver histopathology, fatty acid composition and LC-PUFA biosynthesis, along with phospholipid fatty acid composition and eicosanoid production in head kidney and heart tissue at early and late stages of ASRV infection. Liver was severely affected by the virus at the beginning of the infection in fish fed the reference ST diet, but the level of lesions were similar in all dietary groups at the end of the trial. Hepatic expression of fatty acyl desaturases was significantly depressed in fish fed the ST diet compare with fish fed the functional feeds despite the lower levels of dietary LC-PUFA in that feed. Thus endogenous production and bioavailability of anti-inflammatory LC-PUFA was potentially enhanced in fish fed the functional feeds. Changes in tissue lipid content, mobilization of fatty acids involved in inflammatory responses and changes in expression of transcription factors and genes involved in eicosanoid biosynthesis were more prominent in head kidney, confirming the important role of this organ in dietary immunomodulation after viral infection. To a lesser extent similar changes were observed in heart tissue, suggesting in situ production of eicosanoids could also be important. The unexpected effects of diet on expression of genes of LC-PUFA biosynthesis were specifically investigated in the trial described in Chapter 4. One aim of this study was to clarify whether dietary lipid content or viral infection was the cause of altered expression of desaturase genes between the different diets. Hepatic expression of other genes of lipid and fatty acid metabolism were also determined to evaluate metabolic changes associated with dietary lipid/energy level. In general, reduction of dietary energy and lipid contents while maintaining similar proportions of dietary fatty acids, led to a general up-regulation of genes involved in lipid biosynthetic pathways. Thus salmon fed lower energy diet showed increased liver expression of fatty acyl desaturases in comparison with fish fed higher energy levels. Heart transcriptomic data in Chapter 5 showed a similar delay in the inflammatory response in fish fed the functional feeds after PCMV infection as observed in the HSMI study. Modulation of inflammatory responses, similar to that previously described after ASRV infection, was also observed in fish fed the functional feeds. However, the differences in the expression of immune related genes and the level of heart lesions were not as prominent at mid-late stages of the disease as in fish fed FF1 in the HSMI trial. The present study demonstrated the beneficial effects of a clinical nutrition approach via functional feeds in two viral inflammatory diseases, HSMI and CMS, currently affecting farmed Atlantic salmon. Dietary immunomodulation increased the availability of anti-inflammatory LC-PUFA and significantly influenced the expression of the genes related with the immune/inflammatory response reducing the level and severity of cardiac and liver lesions and therefore improving the performance of fish suffering the diseases

Long-term motor outcomes of very preterm and/or very low birth weight individuals without cerebral palsy:a review of the current evidence

Abstract We reviewed literature on long-term motor outcomes of individuals aged five years or older born very preterm (VP: ≤32 weeks of gestation) or with very low birth weight (VLBW: ≤1500g), without cerebral palsy (CP). PubMed produced 2827 articles, whereof 38 were eligible. Assessed by standardised and norm-based motor tests, the Movement Assessment Battery for Children being the most widely used, VP/VLBW individuals showed poorer motor skills compared with term-born controls with differences of approximately 1 SD in magnitude. Some studies assessed subdomains and differences were present in fine motor/manual dexterity, ball skills and gross motor/balance. Prevalence of motor problems varied largely from 8–37% in studies with cut-off at the 5th percentile or −1.5 SD to 12–71% in studies with cut-off at the 15th percentile or −1 SD. This review shows that the degree of motor impairments continues to be substantial among VP/VLBW individuals who do not develop CP

Characteristics, course and outcome of patients receiving physiotherapy in primary health care in Norway: design of a longitudinal observational project

Background Physiotherapists (PTs) in primary health care manage patients with large variation in medical diagnosis, age, functional status, disability and prognosis. Lack of knowledge and systematically collected data from patients treated by PTs in primary health care has prompted this longitudinal observational physiotherapy project. This paper aims to describe a method for developing a database of patients managed by PTs in primary health care, with the main purpose to study patients’ characteristics, treatment courses and prognostic factors for favourable outcome. Methods This is a longitudinal observational project, following patients through their physiotherapy treatment periods in primary health care in Norway and until one year after inclusion. The project involves both private practitioners and municipally employed PTs working in primary health care in nine municipalities in Norway. The patients are recruited to three different cohorts depending on age and whether they are referred to a private practitioner or a municipally employed PT. All data are recorded electronically, transferred and stored securely. For all patients we have included extensive questionnaires to obtain information about demographics, disability and function, pain-related variables, psychosocial factors, treatments and evaluation of treatment as well as response to clinical tests. The PTs have access to use their own patients’ data. We have also prepared for linkage to national patient registers and data collected in population-based studies to be able to gather further important data. Discussion This project will have important implications for physiotherapy services in primary health care. The database contains more than 3000 patients, and data collection is ongoing. Data collected so far suggest that the patients included are representative of the larger population of patients treated by private practitioners or municipally employed PTs in Norway. This large scale prospective physiotherapy project will provide knowledge about the patient groups, applied treatments and short- and long-term outcome of the patients. Trial registration ClinicalTrials.gov Identifier: NCT03626389 . Registered on August 13th 2018 (retrospectively registered)

Body composition and physical fitness in adults born small for gestational age at term:a prospective cohort study

Abstract There is lack of research on body composition and physical fitness in individuals born small for gestational age (SGA) at term entering mid-adulthood. We aimed to investigate these outcomes in adults born SGA at term. This population-based cohort study included 46 adults born SGA with birth weight &lt; 10th percentile at term (gestational age ≥ 37 weeks) (22 women, 24 men) and 61 adults born at term with birth weight ≥ 10th percentile (35 women, 26 men) at 32 years. Body composition was examined anthropometrically and by 8-polar bioelectrical impedance analysis (Seca® mBCA 515). Fitness was measured by maximal isometric grip strength by a Jamar hand dynamometer, 40-s modified push-up test and 4-min submaximal step test. Participants born SGA were shorter than controls, but other anthropometric measures did not differ between the groups. Men born SGA had 4.8 kg lower grip strength in both dominant (95% CI 0.6 to 9.0) and non-dominant (95% CI 0.4 to 9.2) hand compared with controls. Grip strength differences were partly mediated by height. In conclusion, body composition and physical fitness were similar in adults born SGA and non-SGA at term. Our finding of reduced grip strength in men born SGA may warrant further investigation

Physical activity and associations with health-related quality of life in adults born small for gestational age at term:a prospective cohort study

Abstract Background: Adults born small for gestational age (SGA) have increased risk of adverse health outcomes. Physical activity (PA) is a key determinant of health and health-related quality of life (HRQoL). We aimed to investigate if being born SGA at term is associated with lower objectively measured and self-reported PA during adulthood. We also examined if objectively measured and self-reported PA were associated with HRQoL. Methods: As part of the 32-year follow-up in the NTNU Low Birth Weight in a Lifetime Perspective study, SGA and non-SGA control participants wore two tri-axial accelerometers for seven days (37 SGA, 43 control), and completed the International Physical Activity Questionnaire (IPAQ) (42 SGA, 49 control) and the Short Form 36 Health Survey (SF-36) (55 SGA, 67 control). Group differences in objectively measured daily metabolic equivalent of task (MET) minutes spent sedentary (lying, sitting), on feet (standing, walking, running, cycling), on the move (walking, running, cycling) and running/cycling, and group differences in self-reported daily MET minutes spent walking and in moderate and vigorous PA were examined using linear regression. Associations with SF-36 were explored in a general linear model. Results: Mean (SD) daily MET minutes on the move were 218 (127) in the SGA group and 227 (113) in the control group. There were no group differences in objectively measured and self-reported PA or associations with HRQoL. In the SGA group, one MET minute higher objectively measured time on the move was associated with 4.0 (95% CI: 0.6–6.5, p = 0.009) points higher SF-36 physical component summary. Conclusion: We found no differences in objectively measured and self-reported PA or associations with HRQoL between term-born SGA and non-SGA control participants in adulthood

Health-related quality of life in young adults born small for gestational age:a prospective cohort study

Abstract Background: Individuals born small for gestational age (SGA) have an increased risk of several adverse health outcomes, but their health-related quality of life (HRQoL) across young adulthood has yet to be studied. The main aim of this study was to investigate if being born SGA at term is associated with poor HRQoL at 32 years of age. A second aim was to explore longitudinal changes in HRQoL from age 20 to 32 years. Methods: In the prospective NTNU Low Birth Weight in a Lifetime Perspective study, 56 participants born SGA and 68 non-SGA control participants completed the Short Form 36 Health Survey (SF-36) at age 32 years to assess HRQoL. The SF-36 was also administrated at age 20 and 28 years. Longitudinal changes in the eight SF-36 domains and the two component summaries from 20 to 32 years were analyzed by linear mixed models. In total, 82 adults born SGA and 98 controls participated at least once and were included in the longitudinal analyses. Results: At age 32 years the participants born SGA scored 14.8 (95% CI 4.7 to 25.3) points lower in the SF-36 role-physical domain compared with the control group, i.e. more problems with work or other daily activities due to physical health problems. The longitudinal analyses showed significant group differences from 20 to 32 years in the role-emotional domain, and in the physical and mental component summaries. Among participants born SGA, the physical component summary decreased from age 20 to 28 years (-3.2, 95% CI -5.0 to -1.8), while the mental component summary (6.0, 95% CI 2.9 to 8.6) and role-emotional domain score (19.3, 95% CI 9.9 to 30.3) increased, but there were no further changes from 28 to 32 years. There were no longitudinal changes in the control group from 20 to 32 years. Conclusion: Overall, individuals born SGA at term reported similar HRQoL at age 32 years compared with non-SGA controls. Self-perceived mental health improved during young adulthood among individuals born SGA, while self-perceived physical health deteriorated. The latter findings warrant further investigation