Life course data on obesity may enrich the quality of epidemiologic studies analysing health consequences of obesity. However, achieving such data may require substantial resources. We investigated the use of body silhouettes in adults as a tool to reflect obesity in the past. We used large population-based samples to analyse to what extent self-reported body silhouettes correlated with the previously measured (9–23 years) body mass index (BMI) from both measured (European Community Respiratory Health Survey, N = 3 041) and self-reported (Respiratory Health In Northern Europe study, N = 3 410) height and weight. We calculated Spearman correlation between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI ≥30) at ages 30 and 45 years. Spearman correlations between measured BMI age 30 (±2y) or 45 (±2y) and body silhouettes in women and men were between 0.62–0.66 and correlations for self-reported BMI were between 0.58–0.70. The area under the curve for identification of obesity at age 30 using body silhouettes vs previously measured BMI at age 30 (±2y) was 0.92 (95% CI 0.87, 0.97) and 0.85 (95% CI 0.75, 0.95) in women and men, respectively; for previously self-reported BMI, 0.92 (95% CI 0.88, 0.95) and 0.90 (95% CI 0.85, 0.96). Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men.
Intrauterine and early life has been accepted as important susceptibility windows for environmental exposure and disease later in life. Emerging evidence suggests that exposure before conception may also influence health in future generations. There has been little research on human data to support this until now. This review gives evidence from epigenetic as well as immunologic research, and from animal as well as human models, supporting the hypothesis that there may be important susceptibility windows before conception in relation to exposure such as obesity, diet, smoking and infections. It is likely that we can identify vulnerability windows in men and women in which interventions may have an impact on several generations in addition to individual health. Establishing vulnerability windows affecting health over future generations, and not only in the now or the near future of the individual, may provide tremendous opportunities for health policy and practice.
Background: We found that a father's overweight in puberty was associated with non-allergic asthma in his future offspring. Aim: We explored the associations of both fathers and their offsprings own weight gain throughout the lifespan with offspring non-allergic asthma. Methods: We analysed questionnaire data from 3018 adult offspring (age 18-50) and their 2153 fathers (age 39-66) participating in the RHINESSA/RHINE generation study in 10 ECRHS centres in North Europe, Spain and Australia. The associations of fathers9 and their offsprings weight gain was assessed by 9 body silhouettes (from lean to fat) self-reported for childhood, puberty and adult ages with non-allergic asthma in the offspring. It was analysed using a logistic regression model adjusted for parents and offspring variables, and cluster by family. Results: Non-allergic asthma was related to a weight gain of ≥2 body silhouettes from 8 years to puberty, both for fathers' weight gain (OR 1.69; 95% CI 1.05-2.72; adjusted for fathers asthma, offspring body mass index, smoking and education) and for their offspring weight gain (1.77 [1.12-2.79], adjusted for parents´ education, smoking and asthma, and fathers´ weight gain from age 8 to puberty). If the father was overweight at puberty, in addition to having gained weight, non-allergic asthma in the offspring was more than tripled (3.53[1.80-6.94]; weight gain and adjustment as given above). No effect of weight gain from puberty or within adulthood in fathers' or their offspring was observed. Conclusion: Non-allergic asthma was associated with weight gain from childhood to puberty. This was found both for personal weight gain and for having a father who gained weight.
BackgroundOverweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation.ObjectiveWe aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring.MethodsWe included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status.ResultsWe found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found.ConclusionOur findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health. Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health.
Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept.
Background: Our previous study suggests fathers’ but not mothers’ onset of overweight in prepuberty increased adult asthma in future offspring (Johannessen A, JACI 2020). Potential impact on offspring’s adult lung function, and mediation through offspring overweight or height, are not known. Objective: We studied two-generation causal associations to estimate the causal effects of parents’ overweight in specific time windows on offspring’s adult lung function. Methods: We included 929 adult offspring (age, 18-54 years, 54% daughters) of 308 fathers and 388 mothers (age, 40-66 years). Counterfactual-based mediation models with offspring’s sex as a potential moderator were used to assess the direct and indirect (mediated through offspring’s overweight and/or adult height) effects of parents’ overweight on offspring’s lung function (pre-bronchodilator FEV1, FVC and FEV1/FVC) in adulthood, within the paternal and maternal lines. Results: Fathers’ overweight before puberty had a negative direct effect on sons’ FVC [beta(95%CI): -251 (-478, -19) mL], and a negative indirect effect, mediated through sons’ height, on sons’ FEV1 [beta (95%CI): -148 (-281, -54) mL] and FVC [-213 (-384, -79) mL]. The effects were not mediated through offspring’s own overweight. No direct and indirect effects were found on FEV1 or FVC in daughters or within the maternal line. Conclusion: Fathers’ overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons, partly due to reduced adult height in the sons. The effects were not mediated through sons’ overweight. This was only found in the male line, from father to son.
Background While current height and weight is reported with high accuracy and can be measured with high precision, past height and weight is difficult to recall and retrieve. Body silhouettes at various ages through the life span have been used for this purpose, while to our knowledge the validity of past body silhouettes has not been validated. Aim of study To validate the use of body silhouettes for assessing retrospectively BMI at age 30 and 45 years, with height and weight reported 12 years prior to body silhouettes. Methods Respiratory Health In Northern Europe study (RHINE) is a population based cohort with random population samples of men and women, established in 1992 and followed up in 2000 and 2012. The study population comprised 3430 participants (1826 men and 1604 women) who reported body silhouettes in 2012 and height and weight in 2000. Of these 829 men and 1153 women where 30±2 years old and 997 men and 451 women were 45±2 years old, in 2000. Obesity was defined according to WHO criteria as BMI >30 kg/m2. We calculated Spearman correlation between BMI and body silhouettes and ROC Analyses for identifying obesity. Results Spearman correlation between BMI at age 30 and body silhouettes at age 30 was 0.69 and 0.57 for women and men, respectively, while the corresponding correlations for age 45 were 0.68 and 0.60, respectively. The area under the curve (AUC) for identification of obese women at age 30 was 0.92, while the corresponding AUC for men was 0.90. The optimal cut point for identification of obesity was body silhouette ≥5 for both men and women. Conclusions Reported past body silhouettes at ages 30 and 45 is a valid epidemiological tool to assess BMI retrospectively.
Background: Endometriosis, dysmenorrhea, and respiratory symptoms affect large numbers of women. A possible association between asthma and endometriosis has been suggested; however, this relationship is unclear. Dysmenorrhea is very common, and potential associations with asthma symptoms are not known. Aim: To study asthma symptoms associated with endometriosis and dysmenorrhea in women. Methods: We used data from the main and women's questionnaires of the Respiratory Health in Northern Europe study, which included data from women (aged 39-65 years) from Aarhus, Gothenburg, Umeå, Uppsala, Reykjavik, Tartu, and Bergen. Current asthma status was defined by asthma medication usage or asthma attacks in the past 12 months. Asthma symptoms were defined as having ≥3 asthma symptoms in the last 12 months. The data were analyzed using logistic regressions adjusted for age, body mass index, and smoking status. Results: Among 4778 study participants, 201 had endometriosis, and 2154 had dysmenorrhea. Current asthma and asthma symptoms were reported by 14.9% and 12.9%, respectively, of women with endometriosis compared with 9.1% and 9.2%, respectively, of women without endometriosis. The associations of current asthma and asthma symptoms with endometriosis were statistically significant (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.25-2.81; and OR: 1.56, 95% CI: 1.01-2.39, respectively). Similar associations were found for dysmenorrhea (current asthma: OR: 1.48, 95% CI: 1.21-1.81; ≥3 asthma symptoms: OR: 1.61, 95% CI: 1.31-1.97). Conclusion: Our study revealed that asthma symptoms were associated with both endometriosis and dysmenorrhea. The associations with dysmenorrhea, which affects a large proportion of women, were almost as strong as the associations with diagnosed endometriosis.
Background: Women with polycystic ovary syndrome (PCOS) have increased risk of pregnancy complications. Two previous randomized controlled trials (RCT) showed tendency to lower incidence of late miscarriages and preterm births among women with PCOS who received metformin during pregnancy compared to placebo. We aimed to explore whether metformin prevents late miscarriage and preterm birth in a third large RCT.
Methods: Randomized, double-blinded, multicenter study (14 centers in Norway, Sweden and Iceland) from 2012-2017. Women with PCOS, with a singleton pregnancy signed up for the study in first trimester of pregnancy. They received study-information at the booking visit or on the internet. In all 487 women were found eligible. Study-participants were randomized to metformin (2000mg/day) or placebo from 1st trimester to delivery. Primary endpoint was the composite incidence of late miscarriage and preterm birth. Secondary endpoints were gestational diabetes (GDM), preeclampsia and pregnancy-induced hypertension. We also present pooled data from all three RCTs.
Findings: In all 487 women were randomly assigned to metformin (n=244) or placebo (n=243), all included in the intention-to-treat (ITT) analysis. The composite incidence of late miscarriage and preterm birth was 12 in the metformin group, and 23 in the placebo-group (p=0·08 OR 0·50 (0·22- 1·08)). No difference in the incidence of GDM, preeclampsia or pregnancy induced hypertension was observed. Pooled ITT analyses on 800 women randomized to metformin (n=397) or placebo (n=403), showed 18 vs. 40 late miscarriages and preterm births (p= 0·004 OR 0·43 (0·24- 0·77)). No difference in the incidence of GDM, preeclampsia or pregnancy induced hypertension.
Interpretation: Metformin from 1st trimester to delivery reduces the risk of late miscarriage and preterm birth in women with PCOS. Metformin neither prevents, nor modifies the clinical course of GDM.
Clinical Trial Number: ClinicalTrials.gov number, NCT01587378, EudraCT number, 2011-002203-15.
Funding Statement: The Research Council of Norway, Novo Nordisk Foundation, St. Olavs University Hospital and the Norwegian University of Science and Technology.
Declaration of Interests: No authors report anything to declare.
Ethics Approval Statement: All participants signed an informed consent before inclusion. Ethical approvals were obtained from the Regional Committee for Health Research Ethics of Central Norway (REC number 2011/1434), the Regional Ethical Review Board in Stockholm (Dnmb: 2012/1200-31/2), and the National Bioethics Committee of Iceland (VSNb2012100011/03.10).
Background: Overweight is a known risk factor for personal asthma, but it is not known whether overweight may also increase asthma risk in the next generation. Aim: To examine if fathers' overweight in childhood, adolescence or adulthood is associated with offspring asthma. Methods: We included adult offspring (n=2818, mean age range 18-50 yrs) from the RHINESSA generation study including centres in Norway, Denmark, Iceland, Sweden, Estonia, Spain and Australia with fathers (n=2041, age range 37-66 yrs) studied in ECRHS/RHINE. Associations between allergic/non-allergic asthma in offspring and overweight assessed through self-reported body size in childhood (age 8), adolescence (voice break) and adulthood (age 30) was analysed using cluster-robust 2-level 2→2→1 mediation models. We adjusted for overweight, asthma, smoking and education in grandparents and mothers; age, asthma, smoking and education in fathers; and overweight, sex and age in offspring. Results: A total of 8.5% and 7.9% of offspring reported allergic and non-allergic asthma, respectively. Fathers reported overweight with a prevalence of 9.8% at age 8, 2.3% at voice break and 6.4% at age 30 (pre-conception). In the mediation analysis, fathers' overweight at voice break (but not in childhood or adulthood) was associated with offspring non-allergic asthma irrespective of offspring gender (relative risk ratio RRR = 2.29; 95%CI: 1.19, 4.41). No effect on offspring allergic asthma was found. Conclusion: Fathers' overweight in adolescence is associated with and increased risk of offspring non-allergic asthma, suggesting that factors long before conception may affect asthma in future generations.
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