Maternal serum alpha-1 antitrypsin levels in spontaneous preterm and term pregnancies.

Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB.

Long-term results of the tuberous breast: What to expect after the primary correction process?

BACKGROUND AND AIMS: Tuberous breast is a rare anomaly affecting the development of mainly the female breast. It presents with varying degrees of hypoplasia in the breast base and skin. In some cases, herniation and widening of the areola is observed. The condition constitutes a great challenge for the reconstructive surgeon. In this study, the surgical cascades of implant and lipofilling corrections were compared with a focus on the need for re-interventions. METHODS: In total, 129 patients whose treatment regimen started between January 2010 and October 2020 were included in this study. Patients were categorized into two groups based on the volume correction method used (lipofilling versus implant). RESULTS: In 35 (27%) patients (41 breasts), breast volume increasement was executed with an implant, while 94 (73%) patients (169 breasts) underwent volume increasement with lipofilling. The mean number of operations during the primary correction process was 1.2 (range 1-5) for the implant group and 2.4 (range 1-5) for the lipofilling group. When assessing the need for re-operations within 5 years after completing the primary correction, 46% of patients in the implant group needed further surgeries, while the corresponding proportion for the lipofilling group was 21% (p = 0.04). There were six major complications, all of them in the implant group. CONCLUSION: Implant-based reconstruction is associated with more revision surgeries and major complications compared to autologous lipofilling corrections. Lipofilling offers a more durable result with less re-operations over time despite initial sequential primary surgeries.

Connecting cohorts of Finnish biobanks creates a research resource for the study of healthy ageing.

AIMS: Connecting cohorts with biobanks is a Finnish biobank collaboration, creating an infrastructure for the study of healthy ageing. We aimed to develop a model for data integration and harmonisation between different biobanks with procedures for joint access. METHODS: The heart of the collaboration is the integrated datasets formed by using data from three biobanks: (a) Arctic Biobank, hosting regional birth cohorts and cohorts of elderly; (b) hospital-affiliated Borealis Biobank of Northern Finland; and (c) THL Biobank, hosting population-based cohorts. The datasets were created by developing a data dictionary, harmonising cohort data and with a joint pseudonymisation process. RESULTS: The connecting cohorts with biobanks resource at its widest consists altogether of almost 1.4 million individuals from collaborating biobanks. Utilising data from 107,000 cohort participants, we created harmonised datasets that contain attributes describing metabolic risk and frailty for studies of healthy ageing. These data can be complemented with medical data available from Biobank Borealis and with samples taken at hospital settings for approximately 38,000 cohort participants. In addition, the harmonised connecting cohorts with biobanks datasets can be expanded with supplementary data and samples from the collaborating biobanks. CONCLUSIONS: The connecting cohorts with biobanks datasets provide a unique resource for research on ageing-related personalised healthcare and for real-world evidence studies. Following the FAIR principles on findability, accessibility, interoperability, and reusability, the reused and harmonised datasets are findable and made accessible for researchers. The same approach can be further utilised to develop additional datasets for other research topics.

Prediagnostic serum concentrations of per- and polyfluoroalkyl substances and risk of papillary thyroid cancer in the Finnish Maternity Cohort.

Human exposure to per- and polyfluoroalkyl substances (PFAS) occurs globally through contaminated food, dust, and drinking water. Studies of PFAS and thyroid cancer have been limited. We conducted a nested case-control study of prediagnostic serum levels of 19 PFAS and papillary thyroid cancer (400 cases, 400 controls) in the Finnish Maternity Cohort (pregnancies 1986-2010; follow-up through 2016), individually matched on sample year and age. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for log2 transformed and categorical exposures, overall and stratified by calendar period, birth cohort, and median age at diagnosis. We adjusted for other PFAS with Spearman correlation rho = 0.3-0.6. Seven PFAS, including perfluoroctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), N-ethyl-perfluorooctane sulfonamidoacetic acid (EtFOSAA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorohexane sulfonic acid (PFHxS) were detected in >50% of women. These PFAS were not associated with risk of thyroid cancer, except for PFHxS, which was inversely associated (OR log2 = 0.82, 95% CI: 0.70-0.97). We observed suggestive but imprecise increased risks associated with PFOA, PFOS, and EtFOSAA for those diagnosed at ages <40 years, whereas associations were null or inverse among those diagnosed at 40+ years (P-interaction: .02, .08, .13, respectively). There was little evidence of other interactions. These results show no clear association between PFAS and papillary thyroid cancer risk. Future work would benefit from evaluation of these relationships among those with higher exposure levels and during periods of early development when the thyroid gland may be more susceptible to environmental harms.

Maternal serum concentrations of per- and polyfluoroalkyl substances and childhood acute lymphoblastic leukemia.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia. METHODS: We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia (ALL) in full-term offspring (<15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (OR) and 95% confidence intervals (CI) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex. RESULTS: N­methyl­perfluorooctane sulfonamidoacetic acid (MeFOSAA) was associated with ALL in continuous models (per each doubling in levels: ORperlog2=1.22, CI = 1.07-1.39), with a positive exposure-response across categories (OR>90th percentile=2.52, CI = 1.33-4.78; p-trend = 0.01). While we found no relationship with perfluorooctane sulfonic acid (PFOS) overall, an association was observed in samples collected 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2=4.01, CI = 1.62-9.93). A positive association with perfluorononanoic acid was suggested among first births (p-interaction = 0.06). The MeFOSAA association was mainly limited to children diagnosed before age 5 (p-interaction = 0.02). We found no consistent patterns of association with other PFAS, nor differences by sex. CONCLUSIONS: These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of PFOS and with a precursor, MeFOSAA.

Serum ceramides in early pregnancy as predictors of gestational diabetes.

Ceramides contribute to the development of type 2 diabetes but it is uncertain whether they predict gestational diabetes (GDM). In this multicentre case-control study including 1040 women with GDM and 958 non-diabetic controls, early pregnancy (mean 10.7 gestational weeks) concentrations of four ceramides-Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)-were determined by a validated mass-spectrometric method from biobanked serum samples. Traditional lipids including total cholesterol, LDL, HDL and triglycerides were measured. Logistic and linear regression and the LASSO logistic regression were used to analyse lipids and clinical risk factors in the prediction of GDM. The concentrations of four targeted ceramides and total cholesterol, LDL and triglycerides were higher and HDL was lower among women with subsequent GDM than among controls. After adjustments, Cer(d18:1/24:0), triglycerides and LDL were independent predictors of GDM, women in their highest quartile had 1.44-fold (95% CI 1.07-1.95), 2.17-fold (95% CI 1.57-3.00) and 1.63-fold (95% CI 1.19-2.24) odds for GDM when compared to their lowest quartiles, respectively. In the LASSO regression modelling ceramides did not appear to markedly improve the predictive performance for GDM alongside with clinical risk factors and triglycerides. However, their adverse alterations highlight the extent of metabolic disturbances involved in GDM.

Association of medication use with falls and mortality among long-term care residents: a longitudinal cohort study.

BACKGROUND: Falls in long-term care are common. The aim of our study was to explore how medication use is associated with incidence of falls, related consequences, and all-cause mortality among long-term care residents. METHODS: Five hundred thirty two long-term care residents aged 65 years or older participated in this longitudinal cohort study in 2018-2021. Data on medication use were retrieved from medical records. Polypharmacy was defined as use of 5-10 medications and excessive polypharmacy as use of > 10 medications. The numbers of falls, injuries, fractures, and hospitalizations were collected from medical records over 12 months following baseline assessment. Participants were followed for three years for mortality. All analysis were adjusted for age, sex, Charlson Comorbidity Index, Clinical dementia rating, and mobility. RESULTS: A total of 606 falls occurred during the follow-up. Falls increased significantly with the number of medications used. Fall rate was 0.84/person-years (pyrs) (95% CI 0.56 to 1.13) for the non-polypharmacy group, 1.13/pyrs (95% CI 1.01 to 1.26) for the polypharmacy group, and 1.84/pyrs (95% CI 1.60 to 2.09) for the excessive polypharmacy group. Incidence rate ratio for falls was 1.73 (95% CI 1.44 to 2.10) for opioids, 1.48 (95% CI 1.23 to 1.78) for anticholinergic medication, 0.93 (95% CI 0.70 to 1.25) for psychotropics, and 0.91 (95% CI 0.77 to 1.08) for Alzheimer medication. The three-year follow-up showed significant differences in mortality between the groups, the lowest survival rate (25%) being in the excessive polypharmacy group. CONCLUSION: Polypharmacy, opioid and anticholinergic medication use predicted incidence of falls in long-term care. The use of more than 10 medications predicted all-cause mortality. Special attention should be paid to both number and type of medications when prescribing in long-term care.

The feasibility of a 6-month dietary intervention aiming to increase protein intake among community-dwelling older adults with low habitual protein intake: A secondary analysis of the PROMISS randomised controlled trial.

BACKGROUND: The PROMISS randomised controlled trial showed that personalised dietary advice increased protein intake and improved 400-m walk time and leg strength among community-dwelling older adults with a low habitual protein intake. This secondary analysis describes and further evaluates the methods and feasibility of the model used to carry out dietary intervention in the PROMISS randomised controlled trial. METHODS: In total, 185 participants (≥65 years, 54% women) with a habitual low protein intake (<1.0 g/kg adjusted body weight/day) in Finland and the Netherlands received personalised dietary advice and complimentary protein-enriched food products for 6 months with two main objectives: (1) to increase protein intake to ≥1.2 g/kg adjusted body weight/day (energy-neutral) and (2) to include each day a 'high-protein meal' containing ≥ 30-35 g of protein. The feasibility of the model was evaluated by the adoption of the advice, feedback from the participants, and practical experiences by the nutritionists. RESULTS: In all, 174 participants (93.5%) completed the intervention. At the 6-month follow-up, 41.8% reached both main objectives of the advice. The participants' general rating for the dietary advice was 8.6 (SD 1.0) (on a scale of 1-10; 10 indicating very good). Sticking to the advice was (very) easy for 79.2% of the participants. The nutritionists perceived the model feasible for the participants except for those with low food intake. CONCLUSIONS: The methods used in this model are mainly feasible, well-received and effective in increasing protein intake among community-dwelling older adults with low habitual protein intake.

Being actively engaged in life in old age: determinants, temporal trends, and prognostic value.

PURPOSE: Recently, the concept of successful ageing has shifted from healthy ageing to active ageing, the latter emphasising even more the subjective perspective. Active agency is a marker for better functioning. However, the concept of active ageing lacks a clear definition so far. The specific aims of the study were to identify the determinants of being actively engaged in life (BAEL), to explore the changes in BAEL over 3 decades, and to explore the prognostic value of BAEL. METHODS: This is a repeated cross-sectional cohort study of older (≥ 75 years) community-dwelling people in Helsinki in 1989 (N = 552), 1999 (N = 2396), 2009 (N = 1492), and 2019 (N = 1614). The data were gathered by a postal questionnaire at each time point. Being actively engaged in life was defined by two questions "Do you feel needed?" and "Do you have plans for the future?", which was further converted into BAEL score. RESULTS: An increasing temporal trend in BAEL score was observed through the study years. Male sex, good physical functioning and subjective health, and meaningful social contacts were determinants for higher BAEL score. Active agency measured by BAEL score predicted lower 15-year mortality. CONCLUSIONS: Older home-dwelling, urban Finnish people have become more actively engaged in recent years. The underlying causes are diverse but improved socioeconomic status observed over the study years was one of them. Social contacts and not feeling lonely were found to be determinants for being actively engaged. Two simple questions describing active engagement in life may help to predict mortality among older people.

Changes in symptom burden from 2019 to 2021 amongst community-dwelling older adults in Finland.

BACKGROUND: Symptom burden causes suffering amongst older adults and is associated with healthcare visits and prognosis. AIMS: We evaluated the prevalence of 10 symptoms and changes in symptom burden amongst home-dwelling older adults in 2019 and 2021 using Finnish cohort data. We analysed factors associated with symptom burden increase during follow-up. METHODS: Altogether 1,637 people aged 75+ participated in the Helsinki Ageing Study postal survey in 2019, where they reported the presence of 10 common symptoms over the past 2 weeks. Of them, 785 participated in a follow-up in 2021, where the same symptoms were queried. We compared the prevalence of various symptoms and symptom burden scores in the 2-year interval and evaluated factors associated with increased symptom burden during this time. RESULTS: Of participants, 33% reported at least one daily symptom in 2019 versus 44% in 2021. Symptom burden increased by a mean ratio of 1.29 between 2019 and 2021. The most common symptoms were joint pain, back pain, urinary incontinence and fatigue. The prevalence of four symptoms increased between 2019 and 2021: joint pain, urinary incontinence, dizziness and shortness of breath. Higher age, reduced functional capacity and comorbidities were associated with higher odds of symptom burden increase during follow-up. Psychological well-being (PWB) was strongly associated with lower odds of symptom burden increase in the logistic regression model. CONCLUSIONS: Symptom burden increased in our cohort aged 75+ between 2019 and 2021 before and during the COVID-19 pandemic. PWB was associated with lower odds of acquiring additional symptoms over time.

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.

Temporal Trends Over Two Decades in the Use of Anticholinergic Drugs Among Older Community-Dwelling People in Helsinki, Finland.

BACKGROUND: Knowledge of the adverse effects of drugs with anticholinergic properties (DAPs) has increased in recent decades. However, research on the temporal trends of the clinical use of DAPs is still sparse. OBJECTIVES: The aim of this study was to investigate the temporal trends of DAP use over two decades in the older community-dwelling population and to explore the medication classes contributing to the use of DAPs. METHODS: The study involved random samples of ≥ 75-year-old community-dwelling Helsinki citizens in 1999, 2009, and 2019 from the Helsinki Ageing Study. A postal questionnaire inquired about their health, functioning, and medications. The medications were categorized as DAPs according to Duran's list. In addition, we grouped DAPs into various medication groups. RESULTS: The prevalence and burden of DAPs on Duran's list showed a decreasing trend over the years. In 1999 the prevalence was 20% and the burden 0.35, in 2009 they were 22% and 0.35, respectively, and in 2019 they were 16% and 0.23, respectively. There were no differences in how the 75- and 80-year-olds used DAPs compared with those aged 85 years and older. The proportion of typical antipsychotics, benzodiazepines, hypnotics, urinary antispasmodics, and asthma/chronic obstructive pulmonary disease medications decreased, whereas the proportion of atypical antipsychotics, antidepressants, strong opioids, and antihistamines increased. In particular the use of mirtazapine increased-to 3.9% in 2019. In 2019 the three most prevalent groups of DAPs were antidepressants (7.4%), opioids (2.7%), and antihistamines (2.4%). CONCLUSIONS: The decrease in the use of DAPs on Duran's list is a welcome change. Although the use of old, strong DAPs has decreased, new DAPs have simultaneously emerged. Physicians need continuous education in prescribing DAPs and more recent information on the use and effects of DAPs is needed in order to decrease their exposure among the rapidly growing older population.

Secular trends in functional abilities, health and psychological well-being among community-dwelling 75- to 95-year-old cohorts over three decades in Helsinki, Finland.

Background: Life expectancy has increased markedly in the past decades. Thus, it is of great importance to understand how people are ageing and if the trajectories of health and disability are changing over time. This study aimed to examine trends in functional abilities and health in independent cohorts of people aged 75-95 over three decades. Methods: This Helsinki Ageing Study consists of repeated cross-sectional postal surveys examining independent cohorts of old people (75, 80, 85 and 90+ years old). This study combined data from four waves (1989, 1999, 2009 and 2019). Results: In the most recent wave, there was an increase in the portion of participants who were able to walk outdoors easily (75-year-olds p=0.03, 80-year-olds p=0.002, 85-year-olds p<0.001; p for linearity for the study year effect, all adjusted for sex). Fewer people in the youngest age group (75-year-olds) needed daily help from another person in 2019 compared to the earlier waves (p=0.02 for linearity for the study year). Over the past three decades, the proportions of self-reported good mobility have risen 8.7% (95% confidence interval (CI) 2.3-15.1) in 75-year-olds, 11.7% (95% CI 3.9-19.6) in 80-year-olds and 20.1% (95% CI 10.7-29.4) in 85-year-olds, after adjusting for sex. Furthermore, in 2019, more people rated their health as good and scored better in psychological well-being than in the previous waves among 75-, 80- and 85-year-olds. However, no improvements were found among 90+-year-olds in any of these variables. Conclusions: People between 75 and 85 years old are presently feeling and functioning better than their predecessors. This may be an important objective for both economics and health policy.

Human exposome assessment platform.

The Human Exposome Assessment Platform (HEAP) is a research resource for the integrated and efficient management and analysis of human exposome data. The project will provide the complete workflow for obtaining exposome actionable knowledge from population-based cohorts. HEAP is a state-of-the-science service composed of computational resources from partner institutions, accessed through a software framework that provides the world's fastest Hadoop platform for data warehousing and applied artificial intelligence (AI). The software, will provide a decision support system for researchers and policymakers. All the data managed and processed by HEAP, together with the analysis pipelines, will be available for future research. In addition, the platform enables adding new data and analysis pipelines. HEAP's final product can be deployed in multiple instances to create a network of shareable and reusable knowledge on the impact of exposures on public health.

Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders.

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case-control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82-1.18, p = 0.84) or as a categorical variable (25(OH)D < 30 nmol/L: adjusted OR 1.03, 95% CI 0.83-1.28, p = 0.77 compared to levels of >50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78-1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders.

Preserving Mobility in Older Adults with Physical Frailty and Sarcopenia: Opportunities, Challenges, and Recommendations for Physical Activity Interventions.

One of the most widely conserved hallmarks of aging is a decline in functional capabilities. Mobility loss is particularly burdensome due to its association with negative health outcomes, loss of independence and disability, and the heavy impact on quality of life. Recently, a new condition, physical frailty and sarcopenia, has been proposed to define a critical stage in the disabling cascade. Physical frailty and sarcopenia are characterized by weakness, slowness, and reduced muscle mass, yet with preserved ability to move independently. One of the strategies that have shown some benefits in combatting mobility loss and its consequences for older adults is physical activity. Here, we describe the opportunities and challenges for the development of physical activity interventions in people with physical frailty and sarcopenia. The aim of this article is to review age-related physio(patho)logical changes that impact mobility in old age and to provide recommendations and procedures in accordance with the available literature.