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.

Secular trends in frailty among community-dwelling 75-95-year-old cohorts over three decades in Helsinki, Finland.

BACKGROUND: Frailty Index (FI) reflects health, functioning and well-being of older people. It is valuable to compare how frailty has changed over time in ageing cohorts. This study aims to examine trends in frailty among 75-95-year-old men and women over three decades. METHODS: The Helsinki Ageing Study started in 1989 and includes repeated cross-sectional postal surveys every 10 years examining community-dwelling cohorts of older people (75, 80, 85, 90 and 95 years). FI comprises the same 36 items in each cohort. RESULTS: The mean FI was 0.22 (SD 0.12), 0.25 (SD 0.15), 0.26 (SD 0.15) and 0.23 (SD 0.15) in 1989, 1999, 2009 and 2019, respectively (P for linearity for crude values .11). Adjusted for age and sex, the four cohorts differed in their frailty the 2019 cohort having the lowest FI. This sex-adjusted difference was seen among 75-, 80-, 85- and 90-year-olds but not among 95-year-olds. FI decreased more among men than women (P for cohort <.001, P for sex <.01, P for interaction = .19). CONCLUSIONS: The prevalence of frailty among community-dwelling individuals aged 75, 80, 85 and 90 years-but not among those aged 95 years-has significantly decreased over the last decades. This positive trend may have important implications for health policies in societies with increasing longevity.

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.

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.

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.

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.

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.

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.

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.

Prevalence and persistence of Chlamydia trachomatis-specific antibodies after occasional and recurrent infections.

OBJECTIVES: Population-based Chlamydia trachomatis seroepidemiological studies help to identify trends in chlamydia infection. However, an improved understanding of the antibody response to infection is required when using serology to estimate cumulative incidence. Thus, the objectives of this longitudinal, retrospective, biobank-based study were to assess the appearance and persistence of C. trachomatis major outer membrane protein (MOMP)-specific serum IgG antibodies after infection and to evaluate the role of antibodies in providing protective immunity against recurrent infection. METHODS: Data of notified C. trachomatis infections in Finland were obtained from the National Infectious Diseases Register. Serum samples were acquired from the Finnish Maternity Cohort. 411 women with single chlamydia infection and 62 women with recurrent infections, and for whom suitable paired serum samples were available, were included in the study. Antibody appearance, persistence after infection and the impact of recurrent infections were evaluated. IgG antibodies specific for MOMP were measured from serum using an ELISA method. RESULTS: Anti-C. trachomatis MOMP-specific IgG antibodies were detected in 65.5% (269/411) of women within 3 months of notification of infection. In the absence of recurrent infection, seroprevalence declined to 34.5% (142/411) 3-10 years after the initial infection. The serum antibody levels at baseline correlated positively with seroprevalence at follow-up. Reinfection boosted the humoral immune response by increasing seroprevalence and the serum antibody levels. Seroprevalence within 3 months after first notification of infection was 65.5% (19/29) in women who were later diagnosed with recurrent infection, comparable with women with single notification of infection (65.5%, 269/411). CONCLUSIONS: Approximately one-third of women with single notification of chlamydia infection remain seropositive 3-10 years after the initial infection. The concentration of antibodies remained stable during the follow-up. Recurrent infection boosted the humoral immune response, but reinfection occurred despite the presence of pre-existing antibodies.

Smoking during pregnancy reduces vitamin D levels in a Finnish birth register cohort.

OBJECTIVE: Maternal vitamin D level in pregnancy may have implications for both the mother and fetus. Deficiency of vitamin D has been linked to several pregnancy complications and fetal skeletal health. Smoking has been associated with reduced serum level of the vitamin D metabolite, 25-hydroxyvitamin D (25(OH)D). DESIGN: A nested case-control study within the Finnish Maternity Cohort, a population-based cohort which includes first-trimester sera from 98 % of pregnancies in Finland since 1987. The selection consisted of women with uncomplicated pregnancies. We studied serum concentration of 25(OH)D in 313 non-smoking and forty-six self-reported smoking pregnant women. SETTING: We hypothesize that pregnant smokers may have an increased risk of low 25(OH)D levels especially during winter months. PARTICIPANTS: A control group from an unpublished pregnancy complication study consisting of 359 uncomplicated pregnancies. Individuals who reported that they do not smoke were considered 'non-smokers' (n 313) and those who reported continued smoking after the first trimester of pregnancy were considered 'smokers' (n 46). RESULTS: Smokers had significantly lower levels of 25(OH)D irrespective of sampling time (P<0·0001). Furthermore, during the low sun-exposure season, only 14 % of smokers met the guideline level of 40 nmol/l for serum 25(OH)D in comparison with 31 % of non-smokers. CONCLUSIONS: Expectant mothers who smoke have an increased risk of vitamin D deficiency during low sun-exposure months in northern regions. Further studies are needed to assess the associated risks for maternal and fetal health as well as possible long-term implications for the infant.

Population-Based Study of Prediagnostic Antibodies to Chlamydia trachomatis in Relation to Adverse Pregnancy Outcome.

BACKGROUND: Chlamydia trachomatis infection is one of the most common sexually transmitted reported bacterial infections worldwide. The well-known sequelae of chlamydial infection include pelvic inflammatory disease and tubal factor infertility, but the evidence linking C. trachomatis infection and adverse pregnancy outcome is inconsistent and has been largely based on case-control studies with limited study populations. We evaluated this link in a population-based longitudinal biobank health registry setting. METHODS: The association between C. trachomatis major outer membrane protein (MOMP) peptide-specific IgG antibodies and ectopic pregnancy, miscarriage, and preterm delivery was examined in a prospective case-control study nested in the Finnish Maternity Cohort. Ectopic pregnancy and miscarriage cases were identified through the Hospital Discharge Register 1998-2005; cases with preterm deliveries were identified through the Finnish Medical Birth register 1988-2005. Control samples were retrieved from the Finnish Maternity Cohort serum bank. A total of 800 cases of ectopic pregnancy, 800 cases of miscarriage, and 1350 cases of preterm birth were included. Equal number of pregnant women without the outcome diagnosis served as controls. The cases and controls were matched by sampling time, at the serum sampling and postal code district. RESULTS: Antichlamydial IgG antibodies were associated with ectopic pregnancy. Positive antibody levels were found in 21.0% of cases and 14.6% of controls (P = 0.001; odds ratio, 1.56; 95% confidence interval, 1.20-2.03). Previous exposure to C. trachomatis, as indicated by serum antibodies, doubled the risk of ectopic pregnancy within age and was highest among women 35 years or older. Antichlamydial IgG antibody rates between the cases with miscarriage (16.3% in cases vs. 16.8% in controls) or preterm delivery (18.1% vs. 18.1%) and controls did not differ. CONCLUSIONS: Our findings confirm the association between previous exposure to C. trachomatis and ectopic pregnancy. We found no association between C. trachomatis seropositivity and miscarriage or preterm birth.

Effect of physical exercise on cognitive performance in older adults with mild cognitive impairment or dementia: a systematic review.

Numerous studies have shown that physical exercise has positive effects on cognition in healthy adults. Less is known about the effectiveness of exercise interventions in older individuals already suffering from mild cognitive impairment (MCI) or dementia. The aim of this study was to systematically review the evidence from randomized controlled trials (RCTs) of the effects of physical exercise on cognition in older subjects with MCI or dementia. PubMed, Cochrane and DARE databases were systematically searched for RCTs using terms related to cognition and physical exercise. Altogether, 22 trials were found. The studies on older subjects with MCI reported some positive effects of physical exercise on cognition, mainly on global cognition, executive function, attention and delayed recall. However, most studies performed on older subjects with dementia showed no effect of exercise on cognition. The studies had methodological problems in defining dementia/MCI diagnosis, blinding, inadequate sample sizes and not reporting dropouts, compliance or complications. More studies of good quality on older adults with dementia are needed.

Changes over time in the Chlamydia trachomatis serotype distribution in Finnish women.

The distribution of Chlamydia trachomatis serotypes in the sexually active population may change over time. Serum from C. trachomatis seropositive women representing the 1980s, 1990s, and 2000s were available from a stratified random sample (11,067) of the Finnish Maternity Cohort for microimmunofluorescence-based classification. The C. trachomatis serotype distributions in the 1980s and 2000s were comparable, with serotypes G, E, and J being the most prevalent. In the 1990s the numbers of women seropositive for ≥ 2 serotypes peaked, and serotypes G/J were replaced by serotypes E/D. The temporary C. trachomatis serotype replacement parallels changes in the sexually active population in the 1990s in Finland.

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.

Infertility following trisomic pregnancies: A nationwide cohort study.

OBJECTIVE: To study whether gynecologic or reproductive disorders show association with trisomic conceptions. METHODS: This nationwide cohort study utilized the Registry of Congenital Malformations to identify women who had a trisomic pregnancy (n = 5784), either with trisomy 13 (T13; n = 351), trisomy 18 (T18; n = 1065) or trisomy 21 (T21; n = 4369) from 1987 to 2018. We used the Finnish Maternity cohort to match the cases to population controls (n = 34 422) on the age, residence, and timing of pregnancy. These data were cross-linked to the ICD-10 diagnoses of the national Care Registry for Health Care data on specialized health care in Finland during 1996 to 2019. Both inflammatory (ICD-10 diagnoses: N70-N77) and noninflammatory disorders of the genital tract (N80-N98) were studied. Crude odds ratios (ORs) with 95% CIs were calculated for associations between diagnoses and trisomic conceptions. RESULTS: The diagnosis of female infertility (N97) at any time was associated with trisomic conceptions (OR: 1.19, 95% CI: 1.08-1.32). In the subgroup analysis, this association was found for T18 (OR: 1.29, 95% CI: 1.03-1.61) and T21 (OR: 1.17, 95% CI: 1.04-1.32), but not for T13 (OR: 1.15, 95% CI: 0.75-1.72). When restricting the timing of the diagnosis of female infertility, an elevated OR was found only after the index pregnancy (OR: 1.81, 95% CI: 1.56-2.09). These increased odds for infertility after trisomic conceptions were observed both in women <35 years (T18 OR: 1.91, 95% CI: 1.21-3.00; T21 OR: 1.68, 95% CI: 1.31-2.14) and in women ≥35 years (T18 OR: 2.17, 95% CI: 1.40-3.33; T21 OR: 1.87; 95% CI: 1.47-2.39), but not after T13 conceptions. CONCLUSION: Our observational data suggest a link between trisomic conceptions and subsequent diagnoses of infertility but do not demonstrate causality. These data implicate that partially similar mechanisms might predispose to trisomy and infertility, regardless of maternal age.

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.

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.