Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study.

BACKGROUND: Risk factors for cerebrovascular disease in adulthood are well known. However, research on individuals' risk factors throughout their life span has been limited. This prospective cohort study aims to determine the effect of body mass index (BMI) and its changes in adolescence and young adulthood on early onset cerebrovascular disease. METHODS: This study includes 10 491 people (5185 women) from the Northern Finland Birth Cohort 1966. Height, weight, and BMI were measured at ages 14 and 31 years. Sex- and age-specific BMI ranges were used to define overweight and obesity. Data on ischemic and hemorrhagic cerebrovascular diseases between ages 14 and 54 years were extracted from national hospital and death registers. Cox proportion hazard models (95% CI) were used to estimate associations between BMI or its changes and cerebrovascular disease, while adjusting for sex, smoking, educational level, BMI at the other time point, and age at menarche for women. Additionally, sex-BMI interactions were calculated. RESULTS: A total of 452 individuals (4.7%) experienced cerebrovascular disease during the follow-up. The risk of ischemic cerebrovascular disease was increased for overweight women at ages 14 years (hazard ratio [HR], 2.49 [95% CI, 1.44-4.31]) and 31 years (HR, 2.13 [95% CI, 1.14-3.97]), as well as for obese women at ages 14 years (HR, 1.87 [95% CI, 0.76-4.58) and 31 years (HR, 2.67 [95% CI, 1.26-5.65]), with normal weight as the reference. These results were independent of earlier or later BMI. Similar associations were not found among men. The risk of hemorrhagic cerebrovascular disease was increased at age 31 years both among obese women (HR, 3.49 [95% CI, 1.13-10.7) and obese men (HR, 5.75 [95% CI, 1.43-23.1). The risk of any cerebrovascular disease related to overweight at age 14 years was 2.09× higher among girls than boys (95% CI, 1.06-4.15). The risk of ischemic cerebrovascular disease related to obesity at age 31 years was 6.96× higher among women than men (95% CI, 1.36-35.7). CONCLUSIONS: Among women, being overweight in adolescence or young adulthood increases the risk of cerebrovascular disease, especially ischemic, independent of their earlier or later BMI.

Accelerometer-Measured Physical Activity, Fitness and Indicators of Cardiometabolic Risk among Rural Adolescents: A Cross-Sectional Study at 15-Year Follow-up of the MINIMat Cohort.

BACKGROUND: Little is known about the relationship of physical activity (PA) and fitness with cardiometabolic risk among rural adolescents in low- and middle-income countries. Thus, we examined the associations of PA and fitness with selected cardiometabolic indicators along with potential gender-based differences in a birth cohort of rural adolescents from southeast Bangladesh. METHODS: We utilized data from the 15-year follow-up of Maternal and Infant Nutrition Interventions in Matlab (MINIMat) cohort (n = 2253). Wrist-worn ActiGraph wGT3x-BT accelerometers were used to estimate sedentary time (ST) and PA. Fitness was assessed using: handgrip strength, standing long jump, and Chester Step Test. Anthropometric parameters, systolic blood pressure (SBP), and fasting lipid, insulin and glucose levels were measured. We calculated insulin resistance using the Homeostasis Model Assessment equation (HOMA-IR). Linear regression and isotemporal substitution models were fitted. RESULTS: The adolescents spent 64 min/day (inter-quartile range: 50-81) in moderate-to-vigorous physical activity (MVPA). A 10-minute-per-day higher vigorous PA (VPA) was associated with: 4.9% (95% confidence interval (CI): 2.9-6.8%) lower waist circumference (WC), 3.2 mmHg (95% CI: 1.5-4.8) lower SBP, 10.4% (95% CI: 2.9-17.3%) lower TG, and 24.4% (95% CI: 11.3-34.9%) lower HOMA-IR. MVPA showed similar associations of notably smaller magnitude. Except for WC, the associations were more pronounced among the boys. Substituting ST with VPA of equal duration was associated with lower WC, SBP, triglyceride and HOMA-IR. Grip strength was favorably associated with all indicators, displaying considerably large effect sizes. CONCLUSION: Our findings indicated beneficial roles of PA- particularly VPA- and muscular fitness in shaping cardiometabolic profile in mid-adolescence. VPA and grip strength may represent potential targets for preventive strategies tailored to adolescents in resource-limited settings.

Lifestyle-related factors in late midlife as predictors of frailty from late midlife into old age: a longitudinal birth cohort study.

BACKGROUND: Few studies have examined longitudinal changes in lifestyle-related factors and frailty. METHODS: We examined the association between individual lifestyle factors (exercise, diet, sleep, alcohol, smoking and body composition), their sum at baseline, their change over the 17-year follow-up and the rate of change in frailty index values using linear mixed models in a cohort of 2,000 participants aged 57-69 years at baseline. RESULTS: A higher number of healthy lifestyle-related factors at baseline was associated with lower levels of frailty but not with its rate of change from late midlife into old age. Participants who stopped exercising regularly (adjusted ß × Time = 0.19, 95%CI = 0.10, 0.27) and who began experiencing sleeping difficulties (adjusted ß × Time = 0.20, 95%CI = 0.10, 0.31) experienced more rapid increases in frailty from late midlife into old age. Conversely, those whose sleep improved (adjusted ß × Time = -0.10, 95%CI = -0.23, -0.01) showed a slower increase in frailty from late midlife onwards. Participants letting go of lifestyle-related factors (decline by 3+ factors vs. no change) became more frail faster from late midlife into old age (adjusted ß × Time = 0.16, 95% CI = 0.01, 0.30). CONCLUSIONS: Lifestyle-related differences in frailty were already evident in late midlife and persisted into old age. Adopting one new healthy lifestyle-related factor had a small impact on a slightly less steeply increasing level of frailty. Maintaining regular exercise and sleeping habits may help prevent more rapid increases in frailty.

Gestational diabetes is associated with the risk of offspring's congenital anomalies: a register-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder and a well-known risk factor for adverse pregnancy outcomes. There are conflicting findings on the association of GDM with the risk of congenital anomalies (CAs) in offspring. In this study, we aimed to determine study whether maternal GDM is associated with an increased risk of major CAs in offspring. METHODS: This Finnish Gestational Diabetes (FinnGeDi) register-based study included 6,597 women with singleton pregnancies and a diagnosis of GDM and 51,981 singleton controls with no diabetes identified from the Finnish Medical Birth Register (MBR) in 2009. Data from MBR were combined in this study with the Register of Congenital Malformations, which includes the data of CAs. We used logistic regression to calculate odds ratios (OR) for CAs, together with their 95% confidence intervals (CIs), adjusting for maternal age, parity, pre-pregnancy body mass index (BMI), and maternal smoking status. RESULTS: The risk of major CAs was higher in the GDM-exposed (n = 336, 5.09%) than in the non-exposed group (n = 2,255, 4.33%) (OR: 1.18, 95% CI: 1.05-1.33, p = 0.005). The adjusted OR (aOR) was 1.14 (95% CI: 1.00-1.30, p = 0.047). There was a higher overall prevalence of CAs, particularly chromosomal abnormalities (0.52% vs. 0.21%), in the GDM-exposed group (OR: 2.49, 95% Cl: 1.69-3.66, p < 0.001). The aOR was 1.93 (95% Cl: 1.25-2.99, p = 0.003). CONCLUSIONS: Offspring exposed to GDM have a higher prevalence of major CAs. Of note, risk factors other than GDM, such as older maternal age and a higher pre-pregnancy BMI, diminished the between group differences in the prevalence of major CAs. Nevertheless, our findings suggest that offspring exposed to maternal GDM are more likely to be diagnosed with a chromosomal abnormality, independent of maternal age, parity, pre-pregnancy BMI, and smoking.

Maternal Smoking During Pregnancy and Offspring's Risk for Bone Fracture in Childhood and Adolescence.

Conditions during gestation, such as maternal smoking, may affect offspring's bone structure. This could increase the offspring's risk of bone fractures during childhood. In this study, we aimed to assess the association between prenatal exposure to maternal smoking and childhood bone fracture risk. We used a register-based birth cohort that included all children born in Finland between January 1987 and September 1990. After exclusions, the final study population consisted of 220,699 persons. Using a unique national identification number, we linked the cohort data to the fracture diagnosis in specialty care and covariate data using the Medical Birth Register (MBR), Statistics Finland and Care Register for Health Care (CRHC). The fractures were analyzed in three groups: all fractures, non-high-energy fractures, and high-energy fractures. The analyses were adjusted for sex, parity, child's year of birth, mother's age at childbirth, mother's and father's educational level, and mother's fracture status. We tested the association in three age groups: <1 year, 1-<5 years, and 5-<15 years using Cox and (recurrent fractures) Poisson regression. A total of 18,857 (8.5%) persons had at least one bone fracture diagnosis before the age of 15 years. In the age group 5-<15 years, maternal smoking during pregnancy was associated with higher fracture risk in all of the studied fracture groups: hazard ratio (HR) = 1.12 (95% confidence interval [CI] 1.06-1.17) in all fractures, 1.13 (95% CI 1.07-1.19) in non-high-energy, and 1.15 (95% CI 1.00-1.32) in high-energy fractures. There were no significant associations in other age groups in any of the fracture groups. No statistically significant association between maternal smoking during pregnancy and offspring's risk of recurrent fractures was found. In conclusion, 5- to 15-year-olds whose mothers have smoked during pregnancy have an increased risk of bone fractures treated in specialty care. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study.

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.

Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries.

BACKGROUND: Preterm birth affects lungs in several ways but few studies have follow-up until adulthood. We investigated the association of the entire spectrum of gestational ages with specialist care episodes for obstructive airway disease (asthma and chronic obstructive pulmonary disease (COPD)) at age 18-50 years. METHODS: We used nationwide registry data on 706 717 people born 1987-1998 in Finland (4.8% preterm) and 1 669 528 born 1967-1999 in Norway (5.0% preterm). Care episodes of asthma and COPD were obtained from specialised healthcare registers, available in Finland for 2005-2016 and in Norway for 2008-2017. We used logistic regression to estimate odds ratios (ORs) for having a care episode with either disease outcome. RESULTS: Odds of any obstructive airway disease in adulthood for those born at <28 or 28-31 completed weeks were 2-3-fold of those born full term (39-41 completed weeks), persisting after adjustments. For individuals born at 32-33, 34-36 or 37-38 weeks, the odds were 1.1- to 1.5-fold. Associations were similar in the Finnish and the Norwegian data and among people aged 18-29 and 30-50 years. For COPD at age 30-50 years, the OR was 7.44 (95% CI 3.49-15.85) for those born at <28 weeks, 3.18 (95% CI 2.23-4.54) for those born at 28-31 weeks and 2.32 (95% CI 1.72-3.12) for those born at 32-33 weeks. Bronchopulmonary dysplasia in infancy increased the odds further for those born at <28 and 28-31 weeks. CONCLUSION: Preterm birth is a risk factor for asthma and COPD in adulthood. The high odds of COPD call for diagnostic vigilance when adults born very preterm present with respiratory symptoms.

Associations of low sex hormone-binding globulin and androgen excess in early pregnancy with fasting and post-prandial hyperglycaemia, gestational diabetes, and its severity.

AIMS: We studied whether androgen excess and low sex hormone-binding globulin (SHBG) measured in early pregnancy are independently associated with fasting and post-prandial hyperglycaemia, gestational diabetes (GDM), and its severity. MATERIALS AND METHODS: This nationwide case-control study included 1045 women with GDM and 963 non-diabetic pregnant controls. We measured testosterone (T) and SHBG from biobanked serum samples (mean 10.7 gestational weeks) and calculated the free androgen index (FAI). We first studied their associations with GDM and secondly with the type of hyperglycaemia (fasting, 1 and 2 h glucose concentrations during the oral glucose tolerance test), early-onset GDM (<20 gestational weeks) and the need for anti-diabetic medication. RESULTS: After adjustments for gestational weeks at sampling, pre-pregnancy BMI, and age, women with GDM had 3.7% (95% CI 0.1%-7.3%) lower SHBG levels, 3.1% (95% CI 0.1%-6.2%) higher T levels, and 4.6% (95% CI 1.9%-7.3%) higher FAI levels than controls. SHBG was inversely associated with fasting glucose, whereas higher FAI and T were associated with higher post-prandial glucose concentrations. Women with early-onset GDM had 6.7% (95% CI 0.7%-12.7%) lower SHBG levels and women who needed insulin for fasting hyperglycaemia 8.7% (95% CI 1.8%-14.8%) lower SHBG levels than other women with GDM. CONCLUSIONS: Lower SHBG levels were associated especially with early-onset GDM, higher fasting glucose and insulin treatment, whereas androgen excess was associated with higher post-prandial glucose values. Thus, a low SHBG level may reflect the degree of existing insulin resistance, while androgen excess might impair post-prandial insulin secretion.

Increased Oral Care Needs and Third Molar Symptoms in Women with Gestational Diabetes Mellitus: A Finnish Gestational Diabetes Case-Control Study.

(1) Hyperglycemia and oral pathology accelerate each other in diabetes. We evaluated whether gestational diabetes mellitus (GDM) is associated with self-reported increased oral health care needs and oral symptoms, including third molar symptoms, during pregnancy. (2) Pregnant women with (n = 1030) and without GDM (n = 935) were recruited in this multicenter Finnish Gestational Diabetes study in 2009-2012. Of the women with GDM, 196 (19.0%) receiving pharmacological treatment, 797 (77.0%) receiving diet treatment and 233 (23.0%) with recurrent GDM were analyzed separately. Oral health was assessed using structured questionnaires and analyzed by multivariable logistic regression adjusted for background risk factors. (3) Women with GDM were more likely to report a higher need for oral care than controls (31.1% vs. 24.5%; odds ratio (OR) 1.39; 95% confidence interval (CI) 1.14-1.69), particularly women with recurrent GDM (38.1% vs. 24.5%; OR 1.90; 95% CI 1.40-2.58). Women with pharmacologically treated GDM (46.9%) more often had third molar symptoms than controls (36.1%; OR 1.57; 95% CI 1.15-2.15) than women with diet-treated GDM (38.0%; OR 1.47; 95% CI 1.07-2.02). (4) GDM is associated with perceived oral care needs. Third molar symptoms were associated with pharmacologically treated GDM.

Bone mineral density in very low birthweight adults-A sibling study.

BACKGROUND: Children and adults born very low birthweight (VLBW, <1500 g) at preterm gestations have lower bone mineral density (BMD) and/or bone mineral content (BMC) than those born at term, but causality remains unknown. OBJECTIVES: Our aim was to assess BMD and BMC in adults born at VLBW in a sibling comparison setting to account for shared genetic and environmental confounders. METHODS: We conducted a cohort study of 77 adults born VLBW and 70 same-sex term-born siblings at mean age of 29 years. The primary outcome variables were BMD Z-scores, and BMC, of the femoral neck, lumbar spine, and whole body, measured using dual-energy X-ray absorptiometry. We analysed data by linear mixed models. RESULTS: The VLBW adults had a 0.25 (95% CI 0.02, 0.47) Z-score unit lower femoral neck BMD, and 0.35 (95% CI 0.16, 0.54) grams lower femoral neck BMC than their term-born siblings, after adjustment for sex, age, and maternal smoking. Additional adjustment for adult body size attenuated the results. Lumbar spine, and whole body BMC were also lower in the VLBW group. CONCLUSIONS: Individuals born at VLBW had lower BMC values at all three measurement sites, as well as lower femoral neck BMD Z-scores, compared to term-born siblings, partly explained by their smaller adult body size, but the differences were smaller than those reported previously with unrelated controls. This suggests that genetic or environmental confounders explain partly, but not exclusively, the association between preterm VLBW birth and adult bone mineralisation.

Clinical and biochemical signs of polycystic ovary syndrome in young women born preterm.

OBJECTIVE: It has been suggested that adverse early life exposures increase the risk of developing polycystic ovary syndrome (PCOS) in later life. We hypothesized that women born preterm would have more biochemical and clinical signs of PCOS than women born at term. DESIGN: The ESTER Preterm Birth Study participants were born in Northern Finland and identified from the Northern Finland Birth Cohort and the Finnish Medical Birth Register. Altogether, 74 women born very or moderately preterm (<34 gestational weeks, VMPT), 127 born late preterm (at 34-36 weeks, LPT), and 184 born full term (≥37 weeks, controls) were included in the analysis (mean age: 23.2 years). METHODS: We measured serum total testosterone and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI). PCOS according to the clinical and biochemical signs was defined either as hirsutism and oligoamenorrhea (via questionnaire) or as oligoamenorrhea and elevated testosterone levels (>2.4 nmol/L). RESULTS: Women born VMPT/LPT exhibited 33.0% (8.7, 62.8)/16.4% (-2.0, 38.1) higher testosterone, 28.5% (5.3, 45.9)/24.1% (5.6, 38.9) lower SHBG levels, and 64.6% (19.4, 127.1)/42.5% (11.1, 82.9) higher FAI than controls after adjusting for age and recruitment cohort, maternal BMI, smoking, and pregnancy disorders, parental education, history of hypertension, diabetes, myocardial infarction or stroke, and subject's birth weight s.d. Odds ratios for having PCOS were 1.67 (0.44, 6.23)/3.11 (1.26, 7.70). CONCLUSIONS: Women born preterm have a more hyperandrogenic hormonal profile, and those born LPT are approximately three times more likely at risk to have PCOS compared to women born at term.

Association of Very Preterm Birth or Very Low Birth Weight With Intelligence in Adulthood: An Individual Participant Data Meta-analysis.

Importance: Birth before 32 weeks' gestation (very preterm [VPT]) and birth weight below 1500 g (very low birth weight [VLBW]) have been associated with lower cognitive performance in childhood. However, there are few investigations of the association of neonatal morbidities and maternal educational levels with the adult cognitive performance of individuals born VPT or VLBW (VPT/VLBW). Objective: To assess differences in adult IQ between VPT/VLBW and term-born individuals and to examine the association of adult IQ with cohort factors, neonatal morbidities, and maternal educational level among VPT/VLBW participants. Data Sources: Systematic review of published data from PubMed and meta-analysis of individual participant data (IPD) of cohorts from 2 consortia (Research on European Children and Adults Born Preterm [RECAP] and Adults Born Preterm International Collaboration [APIC]). Study Selection: The meta-analysis included prospective longitudinal cohort studies that assessed the full-scale IQ of adults born VPT or VLBW and respective control groups comprising term-born adults. Data Extraction and Synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for analyses of individual participant data and identified 8 studies that provided data from 2135 adults (1068 VPT/VLBW and 1067 term-born participants) born between 1978 and 1995. Meta-analyses of IPD were performed using a 1-stage approach, treating VPT birth or VLBW and cohort as random effects. Main Outcomes and Measures: Full-scale IQ scores were converted to z scores within each cohort using the combined SD of VPT/VLBW participants and a control group of term-born participants, with scores centered on the mean of the control group. Results: A total of 426 records were identified and screened. After exclusions, 13 studies were included in the aggregate meta-analysis. The IPD meta-analysis included 8 of the 9 RECAP and APIC cohorts with adult IQ data. The mean (SD) age among the 8 IPD cohorts was 24.6 (4.3) years, and 1163 participants (54.5%) were women. In unadjusted analyses, VPT/VLBW participants had mean adult IQ scores that were 0.78 SD (95% CI, -0.90 to -0.66 SD) lower than term-born participants, equivalent to a difference of 12 IQ points. Among VPT/VLBW participants, lower gestational age (score difference per week of gestation, 0.11; 95% CI, 0.07-0.14), lower birth weight z scores (score difference per 1.0 SD, 0.21; 95% CI, 0.14-0.28), the presence of neonatal bronchopulmonary dysplasia (score difference, -0.16; 95% CI, -0.30 to -0.02) or any grade of intraventricular hemorrhage (score difference, -0.19; 95% CI, -0.33 to -0.05), and lower maternal educational level (score difference, 0.26; 95% CI, 0.17-0.35) were all significantly associated with lower IQ scores in adulthood. Conclusions and Relevance: In this IPD meta-analysis, lower gestational age, lower weight for gestational age, neonatal morbidities, and lower maternal educational levels were all important risk factors associated with lower IQ among young adults born VPT or VLBW.

Characteristics of epigenetic aging across gestational and perinatal tissues.

BACKGROUND: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns-especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues. RESULTS: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues. CONCLUSION: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.

Mortality Among Young Adults Born Preterm and Early Term in 4 Nordic Nations.

Importance: Adverse long-term outcomes in individuals born before full gestation are not confined to individuals born at extreme gestational ages. Little is known regarding mortality patterns among individuals born in the weeks close to ideal gestation, and the exact causes are not well understood; both of these are crucial for public health, with the potential for modification of risk. Objective: To examine the risk of all-cause and noncommunicable diseases (NCD) deaths among young adults born preterm and early term. Design, Setting, and Participants: This multinational population-based cohort study used nationwide birth cohorts from Norway, Sweden, Denmark, and Finland for individuals born between 1967 and 2002. Individuals identified at birth who had not died or emigrated were followed up for mortality from age 15 years to 2017. Analyses were performed from June 2019 to May 2020. Exposures: Categories of gestational age (ie, moderate preterm birth and earlier [23-33 weeks], late preterm [34-36 weeks], early term [37-38 weeks], full term [39-41 weeks] and post term [42-44 weeks]). Main Outcomes and Measures: All-cause mortality and cause-specific mortality from NCD, defined as cancer, diabetes, chronic lung disease, and cardiovascular disease (CVD). Results: A total of 6 263 286 individuals were followed up for mortality from age 15 years. Overall, 339 403 (5.4%) were born preterm, and 3 049 100 (48.7%) were women. Compared with full-term birth, the adjusted hazard ratios (aHRs) for all-cause mortality were 1.44 (95% CI, 1.34-1.55) for moderate preterm birth and earlier; 1.23 (95% CI, 1.18-1.29) for late preterm birth; and 1.12 (95% CI, 1.09-1.15) for early-term birth. The association between gestational age and all-cause mortality were stronger in women than in men (P for interaction = .03). Preterm birth was associated with 2-fold increased risks of death from CVD (aHR, 1.89; 95% CI, 1.45-2.47), diabetes (aHR, 1.98; 95% CI, 1.44-2.73), and chronic lung disease (aHR, 2.28; 95% CI, 1.36-3.82). The main associations were replicated across countries and could not be explained by familial or individual confounding factors. Conclusions and Relevance: The findings of this study strengthen the evidence of increased risk of death from NCDs in young adults born preterm. Importantly, the increased death risk was found across gestational ages up to the ideal term date and includes the much larger group with early-term birth. Excess mortality associated with shorter gestational age was most pronounced for CVDs, chronic lung disease, and diabetes.

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Glucose regulation and grip strength in adults: Findings from the Helsinki Birth Cohort Study.

AIM: This study aimed to assess the association between grip strength and glucose regulation in a cross-sectional setting. METHODS: Using data from the Helsinki Birth Cohort Study, 924 men and 953 women were studied at a mean age of 61.6 years. Grip strength was assessed in the dominant hand using a Newtest Grip Force dynamometer. A standard 2-h 75 g oral glucose tolerance test (OGTT) was used to define glucose regulation. The participants were classified into four groups: normoglycaemia, prediabetes (impaired fasting glucose or impaired glucose tolerance), newly diagnosed diabetes and previously known diabetes. The association between grip strength and glucose regulation was assessed using multiple linear regression models. RESULTS: Prediabetes was diagnosed in 32.2% and diabetes in 8.4% using the OGTT. A total of 7.8% of the individuals had previously known diabetes. Compared to individuals with normoglycaemia, grip strength was lower for those with newly diagnosed diabetes (-1.8 kg, 95% CI -3.2 to -0.5) as well as those with previously known diabetes (-1.8 kg, 95% CI -3.2 to -0.4) after adjusting for covariates (age, sex, body mass index, physical activity, education and smoking). No difference in grip strength was found when comparing those with prediabetes and normoglycaemia. CONCLUSION: In adults, grip strength was lower among those with known and newly diagnosed diabetes compared to those with normoglycaemia. Together with previous findings on associations between grip strength and chronic diseases, these results support the use of grip strength as an overall health marker in adults.

Migraine in children and adults born preterm: A nationwide register linkage study.

OBJECTIVE: Being born preterm is related to adverse health effects later in life. We studied whether preterm birth predicts the risk of migraine. METHODS: In this nationwide register study, we linked data from six administrative registers for all 235,624 children live-born in Finland (January 1987 to September 1990) and recorded in the Finnish Medical Birth Register. n = 228,610 (97.0%) had adequate data and were included. Migraine served as primary outcome variable and was stringently defined as a diagnosis from specialised health care and/or ≥2 reimbursed purchases of triptans. We applied sex- and birth year-stratified Cox proportional hazard regression models to compute hazard ratios and confidence intervals (95% confidence intervals) for the association between preterm categories and migraine. The cohort was followed up until an average age of 25.1 years (range: 23.3-27.0). RESULTS: Among individuals born extremely preterm (23-27 completed weeks of gestation), the adjusted hazard ratios for migraine was 0.55 (0.25-1.24) when compared with the full-term reference group (39-41 weeks). The corresponding adjusted hazard ratios and 95% confidence intervals for the other preterm categories were: Very preterm (28-31 weeks); 0.95 (0.68-1.31), moderately preterm (32-33 weeks); 0.96 (0.73-1.27), late preterm (34-36 weeks); 1.01 (0.91-1.11), early term (37-38 weeks); 0.98 (0.93-1.03), and post term (42 weeks); 0.98 (0.89-1.08). Migraine was predicted by parental migraine, lower socioeconomic position, maternal hypertensive disorder and maternal smoking during pregnancy. CONCLUSION: We found no evidence for a higher risk of migraine among individuals born preterm.

Predisposition to superimposed preeclampsia in women with chronic hypertension: endothelial, renal, cardiac, and placental factors in a prospective longitudinal cohort.

OBJECTIVE: To assess the contribution of maternal and placental factors to the development of superimposed preeclampsia in women with chronic hypertension. METHODS: Endothelial and renal function markers were serially assessed in 90 pregnant women with chronic hypertension and controls. RESULTS: Syndecan-1 concentrations were lower at 26-27+6 weeks in women with chronic hypertension who subsequently developed superimposed preeclampsia compared with those who did not. Decreased PlGF and raised urine albumin:creatinine ratio were also associated with development of superimposed preeclampsia. CONCLUSION: Decreased syndecan-1 and PlGF concentrations implicate endothelial glycocalyx disturbance and reduced placental angiogenic capacity, respectively, in the pathophysiology of superimposed preeclampsia.

Pregnancy outcomes according to the definition of gestational diabetes.

OBJECTIVE: To assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM. DESIGN: A retrospective cohort study. SETTING: Six secondary and tertiary delivery hospitals in Finland in 2009. POPULATION: Pregnant women (N = 4,033) and their offspring. METHODS: We used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs. MAIN OUTCOME MEASURES: GDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates. RESULTS: Among the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring's BWSDS and CS rate were higher than in controls. CONCLUSIONS: GDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia.

Physical Activity and Telomeres in Old Age: A Longitudinal 10-Year Follow-Up Study.

BACKGROUND: Telomeres are crucial parts of chromosomes that protect the genome. They shorten every time the cell replicates, and shorter telomeres have been associated with increasing age and with many health behaviours. There is inconclusive evidence on the association between physical activity (PA) and telomere length. OBJECTIVES: To examine how leisure-time PA (LTPA) is associated with telomere length and telomere attrition during 10 years of follow-up in elderly people. DESIGN: This study is a 10-year prospective follow-up study. METHOD: For this prospective study, we examined 1,014 subjects (mean age at baseline 60.8 years) from the Helsinki Birth Cohort Study (HBCS). Relative leukocyte telomere length (LTL) was measured with a quantitative real-time PCR and LTPA with a validated questionnaire. Multiple linear regression analyses were used to assess the association between sex-specific LTPA quartiles and LTL at baseline and change in LTL over 10 years. The analyses were adjusted for age, educational attainment, smoking, body fat percentage, oestrogen exposure in women and for follow-up time when applicable. RESULTS: At baseline, volume of LTPA was not associated with LTL in men (p = 0.66) or in women (p = 0.33). Among women, however, higher volume of LTPA at baseline was associated with greater shortening of LTL (p for linearity 0.040) during the 10-year follow-up. No association was found among men (p for linearity 0.75). CONCLUSIONS: Our findings suggest that PA has a sex-specific role in regulation of telomere length in the aging process as in our study a high volume of LTPA in elderly women, but not in men, was associated with more rapid telomere attrition.