Finnish Institute for Health and Welfare

Background Cardiovascular diseases (CVDs) are prevalent in older people, but few studies focus on developmental patterns in CVD medication directly after transition to statutory retirement. We thus aimed to identify trajectories of CVD medication after retirement, and their sociodemographic, work and health-related determinants. Methods We used complete register data of former employees of the City of Helsinki, Finland. All who reached their statutory retirement in 2000–2013, with five-year follow-up data (n = 6,505, 73% women), were included. Trajectories of CVD medication were identified with group-based trajectory modelling using data from Finnish Social Insurance Institution’s reimbursement register. Sociodemographic, work and health-related determinants of trajectory group membership were analysed using multinomial logistic regression. Results Six trajectories of CVD medication were distinguished: "constant low" (35%), “late increase” (6%), “early increase” (5%), "constant high" (39%), "high and decreasing " (8%), and "low and decreasing” (7%). The majority (74%) of the retirees fell into the "constant low" and "constant high" categories. Lower occupational class and increased pre-retirement sickness absence were associated with the "constant high" trajectory. Further, those with lower educational attainment were more prone to be in the “early increase” trajectory. Conclusions Individuals in lower socioeconomic positions or with a higher number of pre-retirement sickness absence may be considered at higher risk and might benefit from early interventions, e.g. lifestyle interventions and interventions targeting working conditions, or more frequent monitoring.

Purpose Our aim was to develop a nationwide, computer-based, Spine Register (FinSpine) for monitoring surgical activity, quality of surgery, long-term outcomes, and effectiveness of treatment. In this paper, we describe our experiences in the development and implementation of the register. Methods The register was developed by a steering group, consisting of orthopedic surgeons and neurosurgeons from the whole country. We strived to develop a register which would be in active use by spine surgeons and enable collection of Patient Reported Outcome and Experience Measures (PROMs and PREMs) automatically and prospectively. We are actively promoting the use of the register in order to gain a nationwide coverage and achieve high response-rates from both surgeons and patients. Results The use of FinSpine started in 2016 and it has been granted continuous funding from the Finnish Institute for Health and Welfare from the 1st of January 2023 onwards. Currently the register is used by 19/23 (83%) public hospitals and the use is expanding to private hospitals as well. The response-rate of surgeons is currently 80%. The response-rate of patients is on average 56% but reaches up to 90% in hospitals using register-coordinators. Conclusion The use of FinSpine is increasing. By gaining a larger coverage and completeness, the data can be used for research purposes which we believe will influence decision making and ultimately improve the outcomes and quality of life of the patients. Comparison with other national spine registers is possible, since FinSpine includes similar baseline characteristics and outcome measures (e.g., ODI, EQ-5D, VAS).

Despite the acceleration in the use of digital health technologies across different aspects of the healthcare system, the full potential of real-world data (RWD) and real-world evidence (RWE) arising from the technologies is not being utilised in decision-making. We examine current national efforts and future opportunities to systematically use RWD and RWE in decision-making in five countries (Estonia, Finland, Germany, Italy and the United Kingdom), and then develop a framework for promotion of the systematic use of RWD and RWE. A review assesses current national efforts, complemented with a three-round consensus building exercise among an international group of experts (n1 = 44, n2 = 24, n3 = 24) to derive key principles. We find that Estonia and Finland have invested and developed digital health-related policies for several years; Germany and Italy are the more recent arrivals, while the United Kingdom falls somewhere in the middle. Opportunities to promote the systematic use of RWD and RWE were identified for each country. Eight building blocks principles were agreed through consensus, relating to policy scope, institutional role and data collection. Promoting post-market surveillance and digital health technology vigilance ought to rely on clarity in scope and data collection with consensus reached on eight principles to leverage RWD and RWE.

Aim The aim of this study was to explore the relationship between sensory impairment and home care client's received care time. Design A cross‐sectional multi‐source study. Methods Data from a self‐reported staff survey on care time allocation were merged with registry data from the Resident Assessment Instrument registry (n = 1477). The data were collected during 1 week from 17 home care units in Finland in October 2021. The relationship between sensory impairment and clients received care time was examined using linear regression analyses. Results The linear regression analyses showed that having vision impairment alone increased care time, while dual sensory impairment resulted in decreased received care time. Hearing impairment alone was not statistically significantly associated with care time. Conclusion The holistic care need of home care clients with dual sensory impairment may not be adequate. To ensure equality and the individually tailored care of clients, further attention must be paid to clients with sensory impairments, especially those with dual sensory impairment. Furthermore, the competence of home care workers to encounter and communicate with clients with sensory impairment must be developed to support the holistic care. Implications for the patient care The sensory impairments of home care clients must be identified in time and considered in care planning and encountering clients. Impact As there is a risk that clients with dual sensory impairment are not able to fully express themselves, it is imperative that further attention is paid to clients with sensory impairments, to better understand and support this vulnerable group. Increased awareness and continuous education are needed to better identify and support home care clients with sensory impairment. Reporting Method The study adheres to the STROBE reporting guidelines. Patient or public contribution No patient or public contribution.

Type 1 diabetes (T1D) is characterized by the progressive destruction of pancreatic β-cells, leading to insulin deficiency and lifelong dependency on exogenous insulin. Higher estimates of heritability rates in monozygotic twins, followed by dizygotic twins and sib-pairs, indicate the role of genetics in the pathogenesis of T1D. The incidence and prevalence of T1D are alarmingly high in Kuwait. Consanguineous marriages account for 50–70% of all marriages in Kuwait, leading to an excessive burden of recessive allele enrichment and clustering of familial disorders. Thus, genetic studies from this Arab region are expected to lead to the identification of novel gene loci for T1D. In this study, we performed linkage analyses to identify the recurrent genetic variants segregating in high-risk Kuwaiti families with T1D. We studied 18 unrelated Kuwaiti native T1D families using whole exome sequencing data from 86 individuals, of whom 37 were diagnosed with T1D. The study identified three potential loci with a LOD score of ≥ 3, spanning across four candidate genes, namely SLC17A1 (rs1165196:pT269I), SLC17A3 (rs942379: p.S370S), TATDN2 (rs394558:p.V256I), and TMEM131L (rs6848033:p.R190R). Upon examination of missense variants from these genes in the familial T1D dataset, we observed a significantly increased enrichment of the genotype homozygous for the minor allele at SLC17A3 rs56027330_p.G279R accounting for 16.2% in affected children from 6 unrelated Kuwaiti T1D families compared to 1000 genomes Phase 3 data (0.9%). Data from the NephQTL database revealed that the rs1165196, rs942379, rs394558, and rs56027330 SNPs exhibited genotype-based differential expression in either glomerular or tubular tissues. Data from the GTEx database revealed rs942379 and rs394558 as QTL variants altering the expression of TRIM38 and IRAK2 respectively. Global genome-wide association studies indicated that SLC17A1 rs1165196 and other variants from SLC17A3 are associated with uric acid concentrations and gout. Further evidence from the T1D Knowledge portal supported the role of shortlisted variants in T1D pathogenesis and urate metabolism. Our study suggests the involvement of SLC17A1, SLC17A3, TATDN2, and TMEM131L genes in familial T1D in Kuwait. An enrichment selection of genotype homozygous for the minor allele is observed at SLC17A3 rs56027330_p.G279R variant in affected members of Kuwaiti T1D families. Future studies may focus on replicating the findings in a larger T1D cohort and delineate the mechanistic details of the impact of these novel candidate genes on the pathophysiology of T1D.

This article presents the results of a systematic literature review of research articles ( N = 72) to study the governance logic of integrated activation policies and the problems relating to reintegrating welfare benefits with services. The inductive study of the problems indicated in the literature demonstrates both the vertical and horizontal aspects of the governance of integrated activation at the street level: challenges are tied to the top‐down activation policy; requirements and strategies of delivering benefits and services; collaboration and coordination in delivery chains; and risks and inequality that streel‐level bureaucrats are trying to deal with in their work. The results point primarily to flaws in the vertical governance of activation, such as frontline work problems and collaborative practices between different actors and agencies. Moreover, some problems relating to collaboration and coordination, pointed towards the challenges in horizontal governance of activation. The article, however, demonstrates how the governance of integrated activation requires a coupling of these different streams of governance and understanding governance as a complex network of interdependencies and causal connections between institutions, organisations, and co‐production with end users.

Importance Cardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population. Objective To evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population. Design, Setting, and Participants This prospective nested case–control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023. Exposures A total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography–triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included. Main Outcomes and Measures Incident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register ( International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD. Results Of 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and β-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes. Conclusions and Relevance In this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.

Background Ageing of the population increases the prevalence and coexistence of many chronic diseases; a condition called multimorbidity. In Finland, information on the significance of multimorbidity and its relation to the sustainability of healthcare is scarce. Aim To assess the prevalence of multimorbidity, the transitions between patient groups with and without multiple diseases and the associated healthcare cost in Finland in 2017–2019. Methods A register-based cohort study covering all adults ( n = 3,326,467) who used Finnish primary or specialised healthcare services in 2017. At baseline, patients were classified as ‘non-multimorbid’, ‘multimorbid’ or ‘multimorbid at risk’ based on the recordings of a diagnosis of interest. The costs were calculated using the care-related patient grouping and national standard rates. Transition plots were drawn to observe the transition of patients and costs between groups during the two-year follow-up. Results At baseline, 62% of patients were non-multimorbid, 23% multimorbid and 15% multimorbid at risk. In two years, the proportion of multimorbid patients increased, especially those at risk. Within the multimorbid at-risk group, total healthcare costs were greatest (€5,027 million), accounting for 62% of the total healthcare cost of the overall patient cohort in 2019. Musculoskeletal diseases, cardiometabolic diseases and tumours were the most common and expensive chronic diseases contributing to the onset of multimorbidity. Conclusion Multimorbidity is causing a heavy burden on Finnish healthcare. The estimates of its effect on healthcare usage and costs should be used to guide healthcare planning.

Objective To assess whether electronic health record (EHR) data text mining can be used to improve register-based heart failure (HF) subtyping. EHR data of 43,405 individuals from two Finnish hospital biobanks were mined for unstructured text mentions of ejection fraction (EF) and validated against clinical assessment in two sets of 100 randomly selected individuals. Structured laboratory data was then incorporated for a categorization by HF subtype (HF with mildly reduced EF, HFmrEF; HF with preserved EF, HFpEF; HF with reduced EF, HFrEF; and no HF). Results In 86% of the cases, the algorithm-identified EF belonged to the correct HF subtype range. Sensitivity, specificity, PPV and NPV of the algorithm were 94–100% for HFrEF, 85–100% for HFmrEF, and 96%, 67%, 53% and 98% for HFpEF. Survival analyses using the traditional diagnosis of HF were in concordance with the algorithm-based ones. Compared to healthy individuals, mortality increased from HFmrEF (hazard ratio [HR], 1.91; 95% confidence interval [CI], 1.24–2.95) to HFpEF (2.28; 1.80–2.88) to HFrEF group (2.63; 1.97–3.50) over a follow-up of 1.5 years. We conclude that quantitative EF data can be efficiently extracted from EHRs and used with laboratory data to subtype HF with reasonable accuracy, especially for HFrEF.

Purpose Physically active pupils may be better and more resilient learners. However, it is unknown whether active school transport (walking or cycling to school) could affect educational and school-related mental health outcomes. We examined the associations of active school transport and leisure-time moderate-to-vigorous physical activity with perceived academic performance, self-reported competency in academic skills (concentration in classroom, writing, reading, and calculation), school burnout, and school enjoyment among Finnish adolescents. Methods We included 34103 eighth and ninth graders (mean age 15.4 years; 53% girls) from the nationwide School Health Promotion study cohort of 2015. We used logistic regression, adjusting for major sociodemographic, lifestyle, and physical activity covariates, to estimate the associations. Results We observed small but positive associations between active school transport and educational outcomes. For example, compared with non-active transport, 10-30 minutes of active school transport a day was associated with 30% higher odds of high perceived academic performance (OR 1.30, 95% CI 1.21-1.40) and 16% higher odds of high competency in reading (OR 1.16, 95% CI 1.07-1.26). Any dose of active school transport was also associated with higher school enjoyment, but no relationship with school burnout was observed. Compared with inactivity, higher doses of leisure-time physical activity were robustly associated with better educational outcomes. For example, the most physically active adolescents had 85% higher odds of high perceived academic performance (OR 1.85, 95% CI 1.65-2.08). Regarding competency in academic skills, the strongest association was observed for calculation (OR 1.57, 95% CI 1.39-1.77). Engaging in leisure-time physical activity, at any dose, was also associated with lower odds of school burnout, and higher odds of school enjoyment. Conclusions Compared with active school transport, engaging in leisure-time moderate-to-vigorous physical activity seems to be more strongly associated with high perceived academic performance, high competency in academic skills, and less school burnout among youth. Despite this, walking and cycling to school might lead to minor improvements in classroom performance and school enjoyment. Funding Source Juuso J. Jussila was supported by the Academy of Finland, Strategic Research Council (#336003).

Purpose Cognitive and physical functions are key factors for safe walking. As these functions deteriorate with age walking may be compromised among older adults. However, cognitive and physical decline may be attenuated with cognitive and physical training. This study investigated the associations between cognitive, especially executive, and physical functions and sex differences in these associations in physically inactive older adults. Additionally, the role of participant characteristics in cognitive and physical training-induced change in executive functions was investigated Methods 314 older adults aged 70-85 were recruited and randomized to PTCT (N = 155) or PT (N = 159). PT included two supervised training sessions a week and home exercises. PTCT included PT and cognitive training. Measurements were organized at baseline, 6 and 12 months. Physical functions were assessed with 10-meter maximal walking speed, 6-minutes walking distance, dual-task cost in walking speed, habitual walking speed and Short Physical Performance Battery (SPPB). Core skills of executive functions were assessed with Stroop (inhibition), Trail Making Test B (set shifting) and Letter Verbal Fluency (updating). Training compliance was based on participation in supervised training sessions. The data was analyzed with multiple linear regression analyses and longitudinal two-group linear path models. Results Mean age of the participants was 74.5. Results showed that Verbal Fluency test was positively associated with faster maximal and habitual walking speed (β = 0.272, p<0.001, β = 0.184, p = 0.009 respectively), longer 6-min walking distance (β = 0.242, p<0.001) and higher scores in SPPB (β = 0.234, p<0.001), additionally, TMT B-A was positively associated with higher scores in SPPB (β=-0.236, p<0.001). No significant sex-differences were found. Additionally, Stroop improved significantly more in women and participants in the low compliance subgroup who received PTCT compared to participant receiving PT (difference -8.758, p = 0.001 and difference in -8.405, p = 0.010 respectively) No other significant associations were observed. Conclusion Executive and physical functions are positively associated in older adults. The association depends on the physical task and the executive subdomain. Physical and cognitive training improves older adults’ executive functions. Women and participants who only occasionally engaged in training may gain additional benefits for inhibition from physical and cognitive training compared to physical training. Funding Academy of Finland (Grant no. 296843).

Objective To assess whether or to what extent maternal obesity during early pregnancy could increase the risk of offspring lower respiratory infections (LRI). Study design This population-based cohort included 688,457 live singleton births born in Denmark between 2004 and 2016. The exposure was maternal body mass index (BMI) during early pregnancy, and the outcome was LRI in offspring. Cox regression models were used to estimate hazard ratios with their 95% confidence intervals (CI) for the association. We also performed subanalysis stratified by the LRI onset age, number of infection episodes before the age of 3, infection pathogens, infection sites, duration of hospital stay due to LRI and allergic constitution of children. Results A total of 64,725 LRIs in offspring were identified during follow-up. Maternal overweight (BMI 25.0–29.9 kg/m ² ), moderate or severe obesity (BMI 30.0–39.9 kg/m ² ) and very severe obesity (BMI ≥40 kg/m ² ) were associated with a 7% (95% CI: 5%–9%), 16% (95% CI: 14%–19%) and 21% (95% CI: 13%–28%) increased risk of LRI in offspring, respectively. Higher maternal BMI was positively associated with earlier onset age, more episodes before the age of 3, and longer hospital stay of LRI in offspring. In addition, allergic constitution of offspring significantly enhanced the effect of maternal BMI on offspring LRI (44% increased risk, 95% CI: 5%–97% for very severe obesity). Conclusions Maternal BMI during early pregnancy might be a risk factor for offspring LRI, especially in children with allergic constitution.

Objectives To compare mortality and causes of death in scoliotic children with Cerebral palsy (CP) with and without scoliosis surgery. Methods National population-based registries were searched for children with CP and scoliosis with and without surgery for scoliosis and were analyzed for comorbidities, mortality, and causes of death. Results Two hundred and thirty-six had not been operated and 238 had been operated for scoliosis during the median follow-up of 17.8 (IQR 11.7-25.7) and 23.0 (IQR 18.4-28.2) years, respectively. Both groups had similar comorbidities. During the follow-up mortality was higher in the non-surgically treated group than in the surgically treated group (n=38/236, 16% and 8.7 per 1000 follow-up years vs. n=29/238, 12% and 5.3 per 1000 follow-up years, p=0.047). In patients with non-surgical treatment cause of death was respiratory in 76.3% (29/38) and 37.9% (11/29) in patients with surgical treatment of scoliosis (6.6 and 2.0 per 1000 follow-up years, p=0.002). Neurological causes of death were more common in surgically treated patients than in non-surgically treated patients, 44.8% (13/29) and 15.8% (6/38), respectively (3.0 and 1.1 per 1000 follow-up years, p=0.009). Discussion Surgical treatment of scoliosis associates to reduced mortality due to respiratory causes in children with cerebral palsy and scoliosis. Classification of Evidence This study provides Class IV evidence of the effects of spinal fusion on mortality of children with severe scoliosis due to CP.

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on ‘around the clock’ glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.

Background Obesity is associated with liver disease, but the best obesity-related predictor remains undefined. Controversy exists regarding possible synergism between obesity and alcohol use for liver-related outcomes (LRO). We assessed the predictive performance for LROs, and synergism with alcohol use, of abdominal obesity (waist-hip ratio, WHR), and compared it to overall obesity (body mass index, BMI). Methods Forty-thousand nine-hundred twenty-two adults attending the Finnish health-examination surveys, FINRISK 1992–2012 and Health 2000 studies, were followed through linkage with electronic healthcare registries for LROs (hospitalizations, cancers, and deaths). Predictive performance of obesity measures (WHR, waist circumference [WC], and BMI) were assessed by Fine-Gray models and time-dependent area-under-the-curve (AUC). Results There are 355 LROs during a median follow-up of 12.9 years (509047.8 person-years). WHR and WC emerge as more powerful predictors of LROs than BMI. WHR shows significantly better 10-year AUC values for LROs (0.714, 95% CI 0.685–0.743) than WC (0.648, 95% CI 0.617–0.679) or BMI (0.550, 95% CI 0.514–0.585) both overall and separately among men and women. WHR is predictive also in BMI strata. Absolute 10-year risks of LROs are more dependent on WHR than BMI. Moreover, WHR shows a significant supra-additive interaction effect with harmful alcohol use for liver-related outcomes (excess 10-year cumulative incidence of 2.8% from the interaction), which is not seen between BMI and harmful alcohol use. Conclusions WHR is a better predictor than BMI or WC for LROs, and WHR better reflects the synergism with harmful alcohol use. WHR should be included in clinical assessment when evaluating obesity-related risks for liver outcomes.

Background: The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring. Methods: Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015-19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios. Results: An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015-19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01-25.65] to 278.82 [278.20-279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85-45.84] to 93.77 [95% CI 93.46-94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45-1.76) to 7.76 (95% CI 7.46-8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015-19. Conclusion: Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

Background: Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10-18 years). Methods: We used population-wide data from Finland (1 187 610 adolescents born 1987-2006) and Norway (555 431 adolescents born 1998-2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23-27 weeks (extremely preterm), 28-31 weeks (very preterm), 32-33 weeks (moderately preterm), 34-36 weeks (late preterm), 37-38 weeks (early term), 39-41 weeks (term, reference category) and 42-44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10-18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence. Findings: Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19-2·39) for two health outcomes (PAF 9·0%; 8·3-9·6), and 4·22 (3·66-4·87) for four health outcomes (PAF 22·7%; 19·4-25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose-response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets. Interpretation: Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10-18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care. Funding: European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.

Aims: To investigate the associations between passive tobacco smoke exposure and daily smoking with a comprehensive metabolic profile, measured repeatedly from childhood to adulthood. Methods: Study cohort was derived from the Special Turku Coronary Risk Factor Intervention Project(STRIP). Smoking status was obtained by questionnaire, while serum cotinine concentrations were measured using gas chromatography. Metabolic measures were quantified by nuclear magnetic resonance metabolomics at 9(n = 539), 11(n = 536), 13(n = 525), 15(n = 488), 17(n = 455), and 19(n = 409) years. Association of passive tobacco smoke exposure with metabolic profile compared participants who reported less-than-weekly smoking and had serum cotinine concentration <1 ng/mL(no exposure) to those whose cotinine concentration was ≥10 ng/mL(passive tobacco smoke exposure). Associations of daily smoking with metabolic profile in adolescence were analysed by comparing participants reporting daily smoking to those reporting no tobacco use and having serum cotinine concentrations <1 ng/mL. Results: Passive tobacco smoke exposure was directly associated with the serum ratio of monounsaturated fatty acids to total fatty acids (β=0.34SD, [0.17-0.51], p < 0.0001) and inversely associated with the serum ratios of polyunsaturated fatty acids. Exposure to passive tobacco smoke was directly associated with VLDL particle size (β=0.28SD, [0.12-0.45], p = 0.001), and inversely associated with HDL particle size (β=-0.21SD, [-0.34-(-0.07)], p = 0.003). Daily smokers exhibited a similar metabolic profile to those exposed to passive tobacco smoke. These results persisted after adjusting for body mass index, STRIP study group allocation, dietary target score, pubertal status, and parental socio-economic status. Conclusions: Both passive and active tobacco smoke exposure during childhood and adolescence are detrimentally associated with circulating metabolic measures indicative of increased cardiometabolic risk.