Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: a Nordic cohort study.

BACKGROUND AND AIMS: The SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. The aim was to evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds. METHODS: A multinational cohort study was conducted using nationwide register data in Denmark, Finland, Norway, and Sweden and comprising all 8.9 million individuals residing in each of the four countries. Participants were followed for an inpatient diagnosis of myocarditis. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis comparing vaccination schedules, with associated 95% confidence intervals (CIs). Country-specific results were combined in meta-analyses. RESULTS: A total of 8.9 million residents were followed for 12 271 861 person-years and 1533 cases of myocarditis were identified. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after the second dose [IRR 2.08 (95% CI 1.31-3.33) and 8.89 (2.26-35.03), respectively]. For females, the corresponding IRR was only estimable for BNT162b2, 3.99 (0.41-38.64). The corresponding absolute risks following the third dose of BNT162b2 and mRNA-1273 in males were 0.86 (95% CI 0.53-1.32) and 1.95 (0.53-4.99) myocarditis events within 28 days per 100 000 individuals vaccinated, respectively. In females, the corresponding absolute risks following the third dose of BNT162b2 were 0.15 (0.04-0.39) events per 100 000 individuals vaccinated. No deaths occurred within 30 days of vaccine-related cases. CONCLUSIONS: The results suggest that a booster dose is associated with increased myocarditis risk in adolescents and young adults. However, the absolute risk of myocarditis following booster vaccination is low.

Physical activity and cognitive function in adults born very preterm or with very low birth weight-an individual participant data meta-analysis.

OBJECTIVE: Individuals born very preterm (<32 weeks of gestation) or with very low birthweight (<1500g) have lower cognitive function compared with term-born peers. Furthermore, some studies suggest that they are less physically active as young adults than controls, but the relationship between physical activity and cognitive function remains unclear. We performed an individual participant data meta-analysis to examine whether being born preterm/with very low birth weight is associated with physical activity in adulthood and examined if cognitive function mediates this association. STUDY DESIGN: Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase. RESULTS: Five cohorts with 1644 participants aged 22-28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments. CONCLUSION: Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

Cardiometabolic health in adults born with very low birth weight-a sibling study.

BACKGROUND: Preterm survivors have increased risk for impaired cardiometabolic health. We assessed glucose regulation and cardiometabolic biomarkers in adult very low birth weight (VLBW, <1500 g) survivors, using siblings as controls. METHODS: VLBW-participants were matched with term-born, same-sex siblings. At mean age 29.2 years (SD 3.9), 74 VLBW-adults and 70 siblings underwent a 2-h 75 g oral glucose tolerance test and blood tests for assessment of cardiometabolic biomarkers. RESULTS: Of participants, 23 (31%) VLBW and 11 (16%) sibling-controls met World Health Organization criteria for impaired glucose regulation (OR adjusted for age and sex 2.5, 95% CI: 1.1 to 5.8). Adjusting for age and sex, VLBW-participants showed 9.2% higher 2-h glucose (95% CI: 0.4% to 18.8%) than their siblings. Also, fasting (13.4%, -0.3% to 29.0%) and 2-h free fatty acids (15.6%, -2.4% to 36.9%) were higher in VLBW-participants. These differences were statistically significant only after further adjusting for confounders. No statistically significant differences were found regarding other measured biomarkers, including insulin resistance, atherogenic lipid profiles or liver tests. CONCLUSIONS: VLBW-adults showed more impaired fatty acid metabolism and glucose regulation. Differences in cardiometabolic biomarkers were smaller than in previous non-sibling studies. This may partly be explained by shared familial, genetic, or environmental factors. IMPACT: At young adult age, odds for impaired glucose regulation were 3.4-fold in those born at very low birth weight, compared to same-sex term-born siblings. Taking into consideration possible unmeasured, shared familial confounders, we compared cardiometabolic markers in adults born preterm at very low birth weight with term-born siblings. Prematurity increased risk for impaired glucose regulation, unrelated to current participant characteristics, including body mass index. In contrast to previous studies, differences in insulin resistance were not apparent, suggesting that insulin resistance may partially be explained by factors shared between siblings. Also, common cardiometabolic biomarkers were similar within sibling pairs.

Mental health, pain and tiredness in adults born very preterm or with very low birthweight.

AIM: Adults born preterm have increased risk of mental health problems and other neurodevelopmental conditions. We aimed to investigate associations of mental health with pain and tiredness in adults born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) and at term, and whether these associations are influenced by physical activity. METHODS: As part of an EU Horizon 2020 project, individual participant data from six prospective cohort studies were harmonised for 617 VP/VLBW and 1122 term-born participants. Mental health was assessed by the Achenbach System of Empirically Based Assessment Adult Self-Report. Pain and tiredness were harmonised based on specific items from self-reported questionnaires. Associations between mental health and pain or tiredness were explored by linear regression. RESULTS: An increase in the mental health scales internalising, externalising and total problems was associated with increased pain and tiredness in the preterm and term group alike. Results were maintained when adjusting for physical activity. CONCLUSION: The findings indicate that associations between mental health, pain and tiredness in adults are independent of gestation or birthweight. Future research should explore other potential mechanisms that may underlie the increased risk of mental health problems in the preterm population.

Body composition in adults born preterm with very low birth weight.

BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age. IMPACT: In mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height. First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults. Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.

Clinical outcomes of myocarditis after SARS-CoV-2 mRNA vaccination in four Nordic countries: population based cohort study.

Objective: To investigate the clinical outcomes of myocarditis associated with mRNA vaccines against the SARS-CoV-2 virus compared with other types of myocarditis. Design: Population based cohort study. Setting: Nationwide register data from four Nordic countries (Denmark, Finland, Norway, and Sweden), from 1 January 2018 to the latest date of follow-up in 2022. Participants: The Nordic myocarditis cohort; 7292 individuals aged ≥12 years who had an incident diagnosis of myocarditis as a main or secondary diagnosis, in a population of 23 million individuals in Denmark, Finland, Norway, and Sweden. Main outcome measures: Heart failure, or death from any cause within 90 days of admission to hospital for new onset myocarditis, and hospital readmission within 90 days of discharge to hospital for new onset myocarditis. Clinical outcomes of myocarditis associated with SARS-CoV-2 mRNA vaccination, covid-19 disease, and conventional myocarditis were compared. Results: In 2018-22, 7292 patients were admitted to hospital with new onset myocarditis, with 530 (7.3%) categorised as having myocarditis associated with SARS-CoV-2 mRNA vaccination, 109 (1.5%) with myocarditis associated with covid-19 disease, and 6653 (91.2%) with conventional myocarditis. At the 90 day follow-up, 62, nine, and 988 patients had been readmitted to hospital in each group (vaccination, covid-19, and conventional myocarditis groups, respectively), corresponding to a relative risk of readmission of 0.79 (95% confidence interval 0.62 to 1.00) and 0.55 (0.30 to 1.04) for the vaccination type and covid-19 type myocarditis groups, respectively, compared with the conventional myocarditis group. At the 90 day follow-up, 27, 18, and 616 patients had a diagnosis of heart failure or died in the vaccination type, covid-19 type, and conventional myocarditis groups, respectively. The relative risk of heart failure within 90 days was 0.56 (95% confidence interval 0.37 to 0.85) and 1.48 (0.86 to 2.54) for myocarditis associated with vaccination and covid-19 disease, respectively, compared with conventional myocarditis; the relative risk of death was 0.48 (0.21 to 1.09) and 2.35 (1.06 to 5.19), respectively. Among patients aged 12-39 years with no predisposing comorbidities, the relative risk of heart failure or death was markedly higher for myocarditis associated with covid-19 disease than for myocarditis associated with vaccination (relative risk 5.78, 1.84 to 18.20). Conclusions: Compared with myocarditis associated with covid-19 disease and conventional myocarditis, myocarditis after vaccination with SARS-CoV-2 mRNA vaccines was associated with better clinical outcomes within 90 days of admission to hospital.

Incidence of sinus thrombosis with thrombocytopenia-A nation-wide register study.

Safe vaccination is essential for mitigation of the COVID-19 pandemic. Two adenoviral vector vaccines, ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson&Johnson/Janssen) have shown to be effective and they are distributed globally, but reports on serious cerebral venous sinus thrombosis (CVST) associated with thrombocytopenia, have emerged. Our objective was to evaluate the background incidence of CVST with thrombocytopenia and to compare it to incidences following COVID-19 vaccines. We conducted a register-based nation-wide cohort study in Finland, including all 5.5 million individuals alive in Finland, 1 Jan 2020. COVID-19 vaccinations registered in the National Vaccination Register served as the exposure. We detected CVST admissions or hospital visits recorded in the hospital discharge register from Jan 1, 2020 through April 2, 2021. We confirmed the diagnosis of CVST and thrombocytopenia (platelet count <150,000 per cubic millimeter) using radiology reports and laboratory data. By Poisson regression, we compared the baseline incidences to the risks within four weeks after COVID-19 vaccinations. Out of the 167 CVST episodes identified in the registers, 117 were confirmed as CVST, 18 of which coincided with thrombocytopenia (baseline incidence 0.18 per 28 days per million persons). We found 2 episodes of CVST with thrombocytopenia within 28 days of the first ChAdOx1 nCov-19 vaccination (among 200,397 vaccinated, aged 16 or above). No cases were found following the first mRNA vaccine dose among 782,604 vaccinated. The background incidence of CVST combined with thrombocytopenia was minuscule compared to the incidence during the weeks following the ChAdOx1 nCov-19 vaccination. Accurate estimation of the baseline incidence is essential in the critical appraisal of the benefit-risk of any vaccination program.

School grades and educational attainments of adolescents and young adults born preterm.

Attendance in special education (SE) is more common among individuals born preterm than among those born at term. Less is known about school grades of those born preterm in mainstream education (ME), and how these grades predict later educational attainment. This population-based register-linkage study assessed (1) attendance in SE, and then focused on those in ME by assessing (2) school grades at 16 year, (3) completed educational level at 25 year, and (4) school grades as predictors for completed education by gestational age (GA) with full-term birth (39-41 completed weeks) as reference. The sample comprised 223,744 individuals (10,521 preterm, 4.7%) born in Finland (1/1987-9/1990). Of the sample, 4.9% attended SE. Those born preterm had up to 5.5-fold rates for SE. In ME, those born extremely preterm (EPT) had marginally lower mathematics grades compared with full-term counterparts, whilst those born late preterm or early term had slightly higher grades. Those born EPT or very preterm had lower physical education grades in ME. However, the minor differences in school grades according to GA appear not to translate into educational differences in young adulthood. The associations between school grades at 16 year and completed education at 25 year did not vary by GA.

Sudden Hearing Loss Following Vaccination Against COVID-19.

Importance: Spontaneous adverse reaction reports of sudden hearing loss have been observed, and a population-based cohort study conducted in Israel showed an increase in the incidence of sudden sensorineural hearing loss (SSNHL) following vaccination with messenger RNA COVID-19 vaccine BNT162b2 (Pfizer-BioNTech). However, in this setting, the possibility of confounding remained. Objective: To assess a potential association between COVID-19 vaccinations and SSNHL. Design, Setting, and Participants: This register-based country-wide retrospective cohort study of 5.5 million Finnish residents was conducted from January 1, 2019, to April 20, 2022, and included all individuals who were identified from the population information system who were alive or born during the study period except individuals who had SSNHL during 2015 to 2018 according to specialized care derived diagnosis codes for SSNHL (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code H91.2) as a primary or secondary diagnosis. Exposures: The a priori primary risk period was 0 to 54 days following each COVID-19 vaccination. The risk periods for different vaccine doses did not overlap so that a later vaccine exposure ended the previous risk period. The secondary risk period was from 55 days following each COVID-19 vaccination until a subsequent COVID-19 vaccination. A secondary analysis included a risk time from 0 to 54 days following a positive polymerase chain reaction test result for SARS-CoV-2. Main Outcomes and Measures: The incidences of SSNHL following COVID-19 vaccination were compared with the incidences before the COVID-19 epidemic in Finland. The Poisson regression model included calendar time, age, sex, diabetes, cardiovascular disease, other chronic diseases, and the number of visits in primary health care. Results: For the 5.5 million Finnish residents included in the study, the comparison time comprised 6.5 million person-years, the primary risk time of 1.7 million person-years, and the secondary risk time of 2.1 million person-years. Before the COVID-19 epidemic in Finland, 18.7/100 000 people received a diagnosis of SSNHL annually. The study data suggested no increased risk for SSNHL following any COVID-19 vaccination. In particular, adjusted incidence rate ratios with 95% confidence intervals for the BNT162b2 vaccine's 3 doses were 0.8 (95% CI, 0.6-1.0), 0.9 (95% CI, 0.6-1.2), and 1.0 (95% CI, 0.7-1.4), respectively. There was no association between SARS-CoV-2 infection and an increased incidence of SSNHL. Conclusions and Relevance: The results of this cohort study show no evidence of an increased risk of SSNHL following COVID-19 vaccination. The study accounted for previous disease and other potential confounding factors. These results are based on diagnosis codes in specialized care but still need to be verified in settings that are capable of evaluating the degree of hearing loss.

ADHD symptoms and diagnosis in adult preterms: systematic review, IPD meta-analysis, and register-linkage study.

BACKGROUND: This study examined differences in ADHD symptoms and diagnosis between preterm and term-born adults (≥18 years), and tested if ADHD is related to gestational age, birth weight, multiple births, or neonatal complications in preterm borns. METHODS: (1) A systematic review compared ADHD symptom self-reports and diagnosis between preterm and term-born adults published in PubMed, Web of Science, and PROQUEST until April 2021; (2) a one-stage Individual Participant Data(IPD) meta-analysis (n = 1385 preterm, n = 1633 term; born 1978-1995) examined differences in self-reported ADHD symptoms[age 18-36 years]; and (3) a population-based register-linkage study of all live births in Finland (01/01/1987-31/12/1998; n = 37538 preterm, n = 691,616 term) examined ADHD diagnosis risk in adulthood (≥18 years) until 31/12/2016. RESULTS: Systematic review results were conflicting. In the IPD meta-analysis, ADHD symptoms levels were similar across groups (mean z-score difference 0.00;95% confidence interval [95% CI] -0.07, 0.07). Whereas in the register-linkage study, adults born preterm had a higher relative risk (RR) for ADHD diagnosis compared to term controls (RR = 1.26, 95% CI 1.12, 1.41, p < 0.001). Among preterms, as gestation length (RR = 0.93, 95% CI 0.89, 0.97, p < 0.001) and SD birth weight z-score (RR = 0.88, 95% CI 0.80, 0.97, p < 0.001) increased, ADHD risk decreased. CONCLUSIONS: While preterm adults may not report higher levels of ADHD symptoms, their risk of ADHD diagnosis in adulthood is higher. IMPACT: Preterm-born adults do not self-report higher levels of ADHD symptoms, yet are more likely to receive an ADHD diagnosis in adulthood compared to term-borns. Previous evidence has consisted of limited sample sizes of adults and used different methods with inconsistent findings. This study assessed adult self-reported symptoms across 8 harmonized cohorts and contrasted the findings with diagnosed ADHD in a population-based register-linkage study. Preterm-born adults may not self-report increased ADHD symptoms. However, they have a higher risk of ADHD diagnosis, warranting preventive strategies and interventions to reduce the presentation of more severe ADHD symptomatology in adulthood.

Risk-Taking Behavior of Adolescents and Young Adults Born Preterm.

OBJECTIVES: To study sexually transmitted Chlamydia trachomatis infections (STCTs), teenage pregnancies, and payment defaults in individuals born preterm as proxies for engaging in risk-taking behavior. STUDY DESIGN: Our population-based register-linkage study included all 191 705 children alive at 10 years (8492 preterm [4.4%]) born without malformations in Finland between January 1987 and September 1990 as each mother's first child within the cohort. They were followed until young adulthood. We used Cox regression to assess the hazards of STCTs, teenage pregnancies, payment defaults, criminal offending, and substance abuse by gestational age. Gestational age was considered both as a continuous and categorical (extremely, very, moderately, late preterm, early term, post term, and full term as reference) exposure. RESULTS: A linear dose-response relationship existed between gestational age and STCT and teenage pregnancy; adjusted hazard for STCT decreased by 1.6% (95% CI, 0.7%-2.6%), and for teenage pregnancy by 3.3% (95% CI, 1.9%-4.8%) per each week decrease in gestational age. Those born extremely preterm (23-27 completed weeks) had a 51% (95% CI, 31%-83%) lower risk for criminal offending than their full-term born counterparts, and those born very preterm (range, 28-31 weeks) had a 28% (95% CI, 7%-53%) higher hazard for payment defaults than those born at full term. Gestational age was not associated with substance abuse. CONCLUSIONS: The lower risk-taking that characterizes people born preterm seems to generalize to sexual and to some extent criminal behavior. Those born very preterm are, however, more likely to experience payment defaults.

Abdominal adipose tissue and liver fat imaging in very low birth weight adults born preterm: birth cohort with sibling-controls.

Preterm birth at very low birth weight (VLBW, < 1500 g) is associated with an accumulation of cardiovascular and metabolic risk factors from childhood at least to middle age. Small-scale studies suggest that this could partly be explained by increased visceral or ectopic fat. We performed magnetic resonance imaging on 78 adults born preterm at VLBW in Finland between 1978 and 1990 and 72 term same-sex siblings as controls, with a mean age of 29 years. We collected T1-weighted images from the abdomen, and magnetic resonance spectra from the liver, subcutaneous abdominal adipose tissue, and tibia. The adipose tissue volumes of VLBW adults did not differ from their term siblings when adjusting for age, sex, and maternal and perinatal factors. The mean differences were as follows: subcutaneous - 0.48% (95% CI - 14.8%, 16.3%), visceral 7.96% (95% CI - 10.4%, 30.1%), and total abdominal fat quantity 1.05% (95% CI - 13.7%, 18.4%). Hepatic triglyceride content was also similar. VLBW individuals displayed less unsaturation in subcutaneous adipose tissue (- 4.74%, 95% CI - 9.2%, - 0.1%) but not in tibial bone marrow (1.68%, 95% CI - 1.86%, 5.35%). VLBW adults displayed similar adipose tissue volumes and hepatic triglyceride content as their term siblings. Previously reported differences could thus partly be due to genetic or environmental characteristics shared between siblings. The VLBW group displayed less unsaturation in subcutaneous abdominal adipose tissue, suggesting differences in its metabolic activity and energy storage.

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents.

Importance: Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged. Objective: To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age. Design, Setting, and Participants: Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden. Exposures: The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2. Main Outcomes and Measures: Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals. Results: Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar. Conclusions and Relevance: Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.

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.

Brain Volumes and Abnormalities in Adults Born Preterm at Very Low Birth Weight.

OBJECTIVES: To assess radiographic brain abnormalities and investigate volumetric differences in adults born preterm at very low birth weight (<1500 g), using siblings as controls. STUDY DESIGN: We recruited 79 adult same-sex sibling pairs with one born preterm at very low birth weight and the sibling at term. We acquired 3-T brain magnetic resonance imaging from 78 preterm participants and 72 siblings. A neuroradiologist, masked to participants' prematurity status, reviewed the images for parenchymal and structural abnormalities, and FreeSurfer software 6.0 was used to conduct volumetric analyses. Data were analyzed by linear mixed models. RESULTS: We found more structural abnormalities in very low birth weight participants than in siblings (37% vs 13%). The most common finding was periventricular leukomalacia, present in 15% of very low birth weight participants and in 3% of siblings. The very low birth weight group had smaller absolute brain volumes (-0.4 SD) and, after adjusting for estimated intracranial volume, less gray matter (-0.2 SD), larger ventricles (1.5 SD), smaller thalami (-0.6 SD), caudate nuclei (-0.4 SD), right hippocampus (-0.4 SD), and left pallidum (-0.3 SD). We saw no volume differences in total white matter (-0.04 SD; 95% CI, -0.13 to 0.09). CONCLUSIONS: Preterm very low birth weight adults had a higher prevalence of brain abnormalities than their term-born siblings. They also had smaller absolute brain volumes, less gray but not white matter, and smaller volumes in several gray matter structures.

Preterm birth and subsequent timing of pubertal growth, menarche, and voice break.

BACKGROUND: We evaluated pubertal growth and pubertal timing of participants born preterm compared to those born at term. METHODS: In the ESTER Preterm Birth Study, we collected growth data and measured final height of men/women born very or moderately preterm (<34 gestational weeks, n = 52/55), late preterm (34-<37 weeks, 94/106), and term (≥37 weeks, 131/151), resulting in median 9 measurements at ≥6 years. Timing of menarche or voice break was self-reported. Peak height velocity (PHV, cm/year) and age at PHV (years) were compared with SuperImposition by Translation And Rotation (SITAR) model (sexes separately). RESULTS: Age at PHV (years) and PHV (cm/year) were similar in all gestational age groups. Compared to term controls, insignificant differences in age at PHV were 0.1 (95% CI: -0.2 to 0.4) years/0.2 (-0.1 to 0.4) for very or moderately/late preterm born men and -0.0 (-0.3 to 0.3)/-0.0 (-0.3 to 0.2) for women, respectively. Being born small for gestational age was not associated with pubertal growth. Age at menarche or voice break was similar in all the gestational age groups. CONCLUSIONS: Timing of pubertal growth and age at menarche or voice break were similar in participants born preterm and at term. IMPACT: Pubertal growth and pubertal timing were similar in preterm and term participants in a relatively large cohort with a wide range of gestational ages. Previous literature indicates that small for gestational age is a risk for early puberty in term born children. This was not shown in preterm children. While our study had limited power for children born very preterm, all children born preterm were not at increased risk for early puberty.

Preterm birth and the risk of chronic disease multimorbidity in adolescence and early adulthood: A population-based cohort study.

BACKGROUND: People who were born prematurely have high risks of many individual diseases and conditions in the early part of the life course. However, our knowledge of the burden of multiple diseases (multimorbidity) among prematurely born individuals is limited. We aimed to investigate the risk and patterns of chronic disease multimorbidity in adolescence and early adulthood among individuals born across the spectrum of gestational ages, comparing preterm and full-term born individuals. METHODS AND FINDINGS: We used individual-level data from linked nationwide registers to examine the associations of gestational age at birth with specialised healthcare records of ≥2 chronic diseases (multimorbidity) in adolescence (age 10-17 years) and early adulthood (age 18-30 years). Our study population comprised 951,116 individuals (50.2% females) born alive in Finland between 1st January 1987 and 31st December 2006, inclusive. All individuals were followed from age 10 years to the onset of multimorbidity, emigration, death, or 31 December 2016 (up to age 30 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for multimorbidity using flexible parametric survival models. During 6,417,903 person-years at risk (median follow-up: 7.9 years), 11,919 individuals (1.3%) had multimorbidity in adolescence (18.6 per 10,000 person-years). During 3,967,419 person-years at risk (median follow-up: 6.2 years), 15,664 individuals (1.7%) had multimorbidity in early adulthood (39.5 per 10,000 person-years). Adjusted HRs for adolescent multimorbidity, comparing preterm to full-term born individuals, were 1.29 (95% CI: 1.22 to 1.36) and 1.26 (95% CI: 1.18 to 1.35) in females and males, respectively. The associations of preterm birth with early adult multimorbidity were less marked, with the adjusted HRs indicating 1.18-fold risk in females (95% CI: 1.12 to 1.24) and 1.10-fold risk in males (95% CI: 1.04 to 1.17). We observed a consistent dose-response relationship between earlier gestational age at birth and increasing risks of both multimorbidity outcomes. Compared to full-term born males, those born at 37-38 weeks (early term) had a 1.06-fold risk of multimorbidity in adolescence (95% CI: 0.98 to 1.14) and this risk increased in a graded manner up to 6.85-fold (95% CI: 5.39 to 8.71) in those born at 23-27 weeks (extremely premature), independently of covariates. Among females, the same risks ranged from 1.16-fold (95% CI: 1.09 to 1.23) among those born at 37-38 weeks to 5.65-fold (95% CI: 4.45 to 7.18) among those born at 23-27 weeks. The corresponding risks of early adult multimorbidity were similar in direction but less marked in magnitude, with little difference in risks between males and females born at 36-37 weeks but up to 3-fold risks observed among those born at 23-27 weeks. CONCLUSIONS: Our findings indicate that an earlier gestational age at birth is associated with increased risks of chronic disease multimorbidity in the early part of the life course. There are currently no clinical guidelines for follow-up of prematurely born individuals beyond childhood, but these observations suggest that information on gestational age would be a useful characteristic to include in a medical history when assessing the risk of multiple chronic diseases in adolescent and young adult patients.

Optimism in adults born preterm: Systematic review and individual-participant-data meta-analysis.

AIM: Preterm birth(<37 gestational weeks) is associated with numerous adversities, however, data on positive developmental outcomes remain limited. We examined if preterm and term born(≥37 gestational weeks) adults differ in dispositional optimism/pessimism, a personality trait associated with health and wellbeing. We assessed if birth weight z-score, neurosensory impairments and parental education modified the outcome. METHODS: We systematically searched PubMed and Web of Science for cohort or case-control studies(born ≥ 1970) with data on gestational age and optimism/pessimism reported using the Life-Orientation-Test-Revised in adulthood(≥18 years). The three identified studies(Helsinki Study of Very Low Birth Weight Adults; Arvo Ylppö Longitudinal Study; Avon Longitudinal Study of Parents and Children) provided data for the two-step random-effects linear regression Individual-Participant-Data meta-analysis. RESULTS: Preterm and term borns did not differ on optimism(p = 0.76). Preterms scored higher on pessimism than term borns(Mean difference = 0.35, 95%Confidence Interval 0.36, 0.60, p = 0.007), although not after full adjustment. Preterm born participants, but not term born participants, with higher birth weight z-score, had higher optimism scores (0.30 raw score units per standard deviation increase, 95% CI 0.10, 0.49, p = 0.003); preterm vs term x birth weight z-score interaction p = 0.004). CONCLUSIONS: Preterm and term born adults display similar optimism. In preterms, higher birth weight may foster developmental trajectories promoting more optimistic life orientations.

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

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