| 1. |
- Accordini, S., et al.
(författare)
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Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:4
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Tidskriftsartikel (refereegranskat)abstract
- Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited. We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18-47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers' smoking in pregnancy and fathers' smoking initiation in prepuberty as exposures; fathers' forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Delta) in expected z-scores related to fathers' and grandmothers' smoking history. Fathers' smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Delta z-score -0.36, 95% CI -0.63--0.10) and FVC (-0.50, 95% CI -0.80--0.20) compared with fathers' never smoking. Paternal grandmothers' smoking in pregnancy had a negative direct effect on fathers' FEV1/FVC -0.57, 95% CI -1.09--0.05) and a negative indirect effect on offspring's FEV1/FVC (-0.12, 95% CI -0.21--0.03) compared with grandmothers' not smoking before fathers' birth nor during fathers' childhood. Fathers' smoking in prepuberty and paternal grandmothers' smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.
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| 2. |
- Knudsen, G. T. M., et al.
(författare)
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Parents' smoking onset before conception as related to body mass index and fat mass in adult offspring: Findings from the RHINESSA generation study
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that parents' preconception exposures may influence offspring health. We aimed to investigate maternal and paternal smoking onset in specific time windows in relation to offspring body mass index (BMI) and fat mass index (FMI). We investigated fathers (n = 2111) and mothers (n = 2569) aged 39-65 years, of the population based RHINE and ECRHS studies, and their offspring aged 18-49 years (n = 6487, mean age 29.6 years) who participated in the RHINESSA study. BMI was calculated from self-reported height and weight, and FMI was estimated from bioelectrical impedance measures in a subsample. Associations with parental smoking were analysed with generalized linear regression adjusting for parental education and clustering by study centre and family. Interactions between offspring sex were analysed, as was mediation by parental pack years, parental BMI, offspring smoking and offspring birthweight. Fathers' smoking onset before conception of the offspring (onset >= 15 years) was associated with higher BMI in the offspring when adult (beta 0.551, 95%CI: 0.174-0.929, p = 0.004). Mothers' preconception and postnatal smoking onset was associated with higher offspring BMI (onset <15 years: beta 1.161, 95%CI 0.378-1.944; onset >= 15 years: beta 0.720, 95%CI 0.293-1.147; onset after offspring birth: beta 2.257, 95%CI 1.220-3.294). However, mediation analysis indicated that these effects were fully mediated by parents' postnatal pack years, and partially mediated by parents' BMI and offspring smoking. Regarding FMI, sons of smoking fathers also had higher fat mass (onset <15 years beta 1.604, 95%CI 0.269-2.939; onset >= 15 years beta 2.590, 95%CI 0.544-4.636; and onset after birth beta 2.736, 95%CI 0.621-4.851). There was no association between maternal smoking and offspring fat mass. We found that parents' smoking before conception was associated with higher BMI in offspring when they reached adulthood, but that these effects were mediated through parents' pack years, suggesting that cumulative smoking exposure during offspring's childhood may elicit long lasting effects on offspring BMI.
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| 3. |
- Lonnebotn, M., et al.
(författare)
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Parental Prepuberty Overweight and Offspring Lung Function
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- In a recent study we found that fathers' but not mothers' onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring's adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents' overweight on adult offspring's lung function within the paternal and maternal lines. We included 929 offspring (aged 18-54, 54% daughters) of 308 fathers and 388 mothers (aged 40-66). Counterfactual-based multi-group mediation analyses by offspring's sex (potential moderator) were used, with offspring's prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers' overweight before puberty had a negative indirect effect, mediated through sons' height, on sons' forced expiratory volume in one second (FEV1) (beta (95% CI): -144 (-272, -23) mL) and forced vital capacity (FVC) (beta (95% CI): -210 (-380, -34) mL), and a negative direct effect on sons' FVC (beta (95% CI): -262 (-501, -9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers' overweight before puberty had neither direct nor indirect effects on offspring's lung function. Fathers' overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons' adult height but not through sons' prepubertal overweight.
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| 4. |
- Sigurðardóttir, E. S., et al.
(författare)
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Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background The prevalence of obstructive sleep apnea is higher in women after menopause. This is suggested to be a result of an altered sex hormone balance but has so far not been confirmed in a population-based study. Objective To investigate whether serum concentration of estrogens and progesterone are associated with the prevalence of sleep apnea symptoms in middle-aged women of the general population. Methods We analyzed data from 774 women (40–67 years) from 15 study centers in seven countries participating in the second follow-up of the European Community Respiratory Health Survey (2010–2012). Multiple logistic regression models were fitted with self-reported symptoms of sleep apnea as outcomes and serum concentrations of various estrogens and progesterone as predictors. All analyses were adjusted for relevant covariates including age, BMI, education, study center, smoking habits, and reproductive age. Results Among all included women, a doubling of serum concentrations of estrone and progesterone was associated with 19% respectively 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of 17β-estradiol, estrone and estrone 3-sulfate was associated with 18%, 23% and 17% decreased odds of breathing irregularly, and a doubling of the progesterone concentration was further associated with 12% decreased odds of waking up suddenly with a chocking sensation. Other evaluated associations were not statistically significant. Conclusions Middle-aged women with low serum estrogen and progesterone levels are more likely to snore and report symptoms of obstructive sleep apnea.
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| 5. |
- Svanes, C., et al.
(författare)
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Cohort profile: the multigeneration Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort was established to (1) investigate how exposures before conception and in previous generations influence health and disease, particularly allergies and respiratory health, (2) identify susceptible time windows and (3) explore underlying mechanisms. The ultimate aim is to facilitate efficient intervention strategies targeting multiple generations. Participants RHINESSA includes study participants of multiple generations from ten study centres in Norway (1), Denmark (1), Sweden (3), Iceland (1), Estonia (1), Spain (2) and Australia (1). The RHINESSA core cohort, adult offspring generation 3 (G3), was first investigated in 2014-17 in a questionnaire study (N=8818, age 18-53 years) and a clinical study (subsample, n=1405). Their G2 parents participated in the population-based cohorts, European Community Respiratory Heath Survey and Respiratory Health In Northern Europe, followed since the early 1990s when they were 20-44 years old, at 8-10 years intervals. Study protocols are harmonised across generations. Findings to date Collected data include spirometry, skin prick tests, exhaled nitric oxide, anthropometrics, bioimpedance, blood pressure; questionnaire/interview data on respiratory/general/reproductive health, indoor/outdoor environment, smoking, occupation, general characteristics and lifestyle; biobanked blood, urine, gingival fluid, skin swabs; measured specific and total IgE, DNA methylation, sex hormones and oral microbiome. Research results suggest that parental environment years before conception, in particular, father's exposures such as smoking and overweight, may be of key importance for asthma and lung function, and that there is an important susceptibility window in male prepuberty. Statistical analyses developed to approach causal inference suggest that these associations may be causal. DNA methylation studies suggest a mechanism for transfer of father's exposures to offspring health and disease through impact on offspring DNA methylation. Future plans Follow-up is planned at 5-8 years intervals, first in 2021-2023. Linkage with health registries contributes to follow-up of the cohort.
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| 6. |
- Tjalvin, G., et al.
(författare)
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Maternal preconception occupational exposure to cleaning products and disinfectants and offspring asthma
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 149:1, s. 422-431
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging research suggests health effects in offspring after parental chemical exposures before conception. Many future mothers are exposed to potent chemicals at work, but potential offspring health effects are hardly investigated. Objective: We sought to investigate childhood asthma in relation to mother's occupational exposure to cleaning products and disinfectants before conception. Methods: The multicenter Respiratory Health In Northern Europe/Respiratory Health In Northern Europe, Spain and Australia generation study investigated asthma and wheeze starting at age less than 10 years in 3318 mother-offspring pairs. From an asthma-specific Job-Exposure Matrix and mothers' occupational history, we defined maternal occupational exposure to indoor cleaning agents (cleaning products/detergents and disinfectants) starting before conception, in the 2-year period around conception and pregnancy, or after birth. Never-employed mothers were excluded. Exposed groups include cleaners, health care workers, cooks, and so forth. Associations were analyzed using mixed-effects logistic regression and ordinary logistic regression with clustered robust SEs and adjustment for maternal education. Results: Maternal occupational exposure to indoor cleaning starting preconception and continuing (n = 610) was associated with offspring's childhood asthma: odds ratio 1.56 (95% CI, 1.05-2.31), childhood asthma with nasal allergies: 1.77 (1.13-2.77), and childhood wheeze and/or asthma: 1.71 (95% CI, 1.19-2.44). Exposure starting around conception and pregnancy (n = 77) was associated with increased childhood wheeze and/or asthma: 2.25 (95% CI, 1.03-4.91). Exposure starting after birth was not associated with asthma outcomes (1.13 [95% CI, 0.71-1.80], 1.15 [95% CI, 0.67-1.97], 1.08 [95% CI, 0.69-1.67]). Conclusions: Mother's occupational exposure to indoor cleaning agents starting before conception, or around conception and pregnancy, was associated with more childhood asthma and wheeze in offspring. Considering potential implications for vast numbers of women in childbearing age using cleaning agents, and their children, further research is imperative.
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| 7. |
- Triebner, K., et al.
(författare)
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Describing the status of reproductive ageing simply and precisely: A reproductive ageing score based on three questions and validated with hormone levels
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Equation 6. Quadratic logistic function approximating the function mu(B)(with age in years). Equation 1. Proportion of women who have regular menstruation for each number of reported menstruations in the last year(with period = number of periods per year, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months" and z = number of women answering "No, my periods have stopped", e.g. x(11) = number of women reporting regular menstruation among those who report 11 menstruations in the last 12 months). Equation 5. Biquadratic exponential function mu(A)depending of the number of periods. Equation 3. Age modification by smoking and oophorectomy. Equation 2. Proportion of women whose menstruations have already stopped, for each reported year of age(with age = age in years, x = number of women answering "Yes" to the question: "Do you have regular periods?", y = number of women answering "No, they have been irregular for a few months", z = number of women answering "No, my periods have stopped", e.g. x(40) = number of women reporting regular menstruations among those who are 40 years old). Equation 7. Final formula to calculate the reproductive ageing score (RAS)(with period being the number of periods per year and age as the age in years, modified according to smoking status and oophorectomy). Objective Most women live to experience menopause and will spend 4-8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause; categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers. Methods Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17 beta-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC). Results The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90-0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83-0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women. Conclusions The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials. Equation 4. The reproductive ageing score as an aggregation function of mu(A)and mu(B).
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| 8. |
- Vogt, E. C., et al.
(författare)
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Premature menopause and autoimmune primary ovarian insufficiency in two international multi-center cohorts
- 2022
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate markers of premature menopause (<40 years) and specifically the prevalence of autoimmune primary ovarian insufficiency (POI) in European women. Design: Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6870 women. Methods: Variables associated with the timing of menopause and hormone measurements of 17 beta-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis. Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI. Results: Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause >= 40 years. Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63-3.42). Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin. Conclusion: Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause. Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.
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