Parental body size and offspring lung health: preparing for parenthood already in childhood?

Background: In parallel with the increase in asthma and allergies there has been a dramatic increase in overweight and obesity during the last decades. Being overweight or obese is a known risk factor for asthma, and overweight and obesity are believed to be detrimental to lung function across age groups regardless of asthma status. However, potential health effects of overweight/obesity for future offspring are not well investigated. While it has been known for quite some time that a mother’s health and behaviour shortly before and during pregnancy may affect her children’s health, emerging evidence suggests that also parents’ health and behaviours before conception – including fathers as well as mothers- could be of importance for the future health of the child. Potential effects of parental overweight for respiratory health in future offspring is not well studied and would require life course data on parental overweight/obesity. Such data are rarely available, and the use of figural body silhouettes from various ages might provide a possibility for retrospectively assessing body size at several time points in the past. Objectives: (I) Investigate the use of body silhouettes in adults as a tool to reflect past overweight/obesity, validated against previously measured or self-reported height and weight in the European Community Respiratory Health Survey (ECRHS) and the Respiratory Health In Northern Europe (RHINE) study, respectively. (II) Examine whether mothers’ and fathers’ overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. (III) Investigate whether a parent’s overweight in childhood, adolescence, or adulthood could be a cause of altered lung function in adult offspring. Material and methods: (I) Data from women and men participating in the second follow up of ECRHS (N= 3041) was used to validate the selected body silhouettes against previously measured height and weight in ECRHS (recall 9-23 years). Data from women and men participating in the first follow up of RHINE (N=3410) was used to validate the selected body silhouettes against previously self-reported height and weight in the initial RHINE study (9-13 years recall). We calculated Spearman correlations between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI ≥30). (II) 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 investigated in ECRHS. Associations of parental overweight status at age 8 years, puberty and age 30 years with offspring’s childhood overweight status and offspring’s asthma with or without nasal allergies were analysed using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analyses was performed to establish whether observed associations reflected direct or indirect effects mediated through offspring’s own overweight status. (III) We included 929 adult offspring (18-54 years, 54% daughters) investigated in the RHINESSA study, of 308 fathers and 388 mothers investigated in the ECRHS or RHINE follow-up studies (2011-2014). Counterfactual-based multi-group mediation analyses by offspring’s sex were used to assess whether the effects of parents’ overweight before puberty on adult offspring’s FEV1, FVC and FEV1/FVC were mediated through offspring’s pre-pubertal overweight and/or adult height, separately within each of the paternal and maternal lines. Results: (I) Spearman correlations between measured BMI age 30(±2y) and body silhouettes in women and men were between 0.62 and 0.66, and correlations for self-reported BMI ranged from 0.58 to 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). (II) We found a statistically significant effect of fathers’ onset of overweight in puberty for 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 of mother’s overweight was associated with offspring’s asthma. (III) Fathers’ overweight before puberty had a negative indirect effect, mediated through sons’ height, on sons’ FEV1[beta (95% CI): -144 (-272, -23) mL] and FVC [beta (95% CI): -210 (-380, -34) mL], and a negative direct effect on sons’ FVC [-262 (-501, -9) mL]. Statistically significant effects on FEV1/FVC were not observed. In the maternal line, mothers’ overweight before puberty had neither direct nor indirect effects on offspring’s lung function. Conclusions: Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men. Further, our work suggests 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. Finally, we found that fathers’ overweight starting before puberty appear to cause considerably lower FEV1 and FVC in their future sons. These effects could be partly mediated through sons’ adult height, but not through his pre-pubertal overweight. Implications: We have shown that the metabolic environment in male prepuberty might influence the health of the next generation. Closer scientific attention to male puberty in relation to future generations health may have profound implications and open new opportunities for targeted public health strategies. We speculate that while intervening in the prepuberty age window in one generation we might improve the health of two generations.Doktorgradsavhandlin

Polycystisk ovariesyndrom: svangerskapsomsorg og tidlig livsstilssamtale

Master i SykepleievitenskapSYKD395MAMD-SY

Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study

Background: Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life. Material and methods: This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics. Results: There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44–0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population. Conclusion: Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.publishedVersio

Body silhouettes as a tool to reflect obesity in the past

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

The Exposome Approach in Allergies and Lung Diseases: Is It Time to Define a Preconception Exposome?

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

Body silhouettes as a tool to reflect obesity in the past

<div><p>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.</p><p>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 <i>vs</i> 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.</p></div

Parental body size and offspring lung health: preparing for parenthood already in childhood?

Background: In parallel with the increase in asthma and allergies there has been a dramatic increase in overweight and obesity during the last decades. Being overweight or obese is a known risk factor for asthma, and overweight and obesity are believed to be detrimental to lung function across age groups regardless of asthma status. However, potential health effects of overweight/obesity for future offspring are not well investigated. While it has been known for quite some time that a mother’s health and behaviour shortly before and during pregnancy may affect her children’s health, emerging evidence suggests that also parents’ health and behaviours before conception – including fathers as well as mothers- could be of importance for the future health of the child. Potential effects of parental overweight for respiratory health in future offspring is not well studied and would require life course data on parental overweight/obesity. Such data are rarely available, and the use of figural body silhouettes from various ages might provide a possibility for retrospectively assessing body size at several time points in the past. Objectives: (I) Investigate the use of body silhouettes in adults as a tool to reflect past overweight/obesity, validated against previously measured or self-reported height and weight in the European Community Respiratory Health Survey (ECRHS) and the Respiratory Health In Northern Europe (RHINE) study, respectively. (II) Examine whether mothers’ and fathers’ overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. (III) Investigate whether a parent’s overweight in childhood, adolescence, or adulthood could be a cause of altered lung function in adult offspring. Material and methods: (I) Data from women and men participating in the second follow up of ECRHS (N= 3041) was used to validate the selected body silhouettes against previously measured height and weight in ECRHS (recall 9-23 years). Data from women and men participating in the first follow up of RHINE (N=3410) was used to validate the selected body silhouettes against previously self-reported height and weight in the initial RHINE study (9-13 years recall). We calculated Spearman correlations between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI ≥30). (II) 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 investigated in ECRHS. Associations of parental overweight status at age 8 years, puberty and age 30 years with offspring’s childhood overweight status and offspring’s asthma with or without nasal allergies were analysed using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analyses was performed to establish whether observed associations reflected direct or indirect effects mediated through offspring’s own overweight status. (III) We included 929 adult offspring (18-54 years, 54% daughters) investigated in the RHINESSA study, of 308 fathers and 388 mothers investigated in the ECRHS or RHINE follow-up studies (2011-2014). Counterfactual-based multi-group mediation analyses by offspring’s sex were used to assess whether the effects of parents’ overweight before puberty on adult offspring’s FEV1, FVC and FEV1/FVC were mediated through offspring’s pre-pubertal overweight and/or adult height, separately within each of the paternal and maternal lines. Results: (I) Spearman correlations between measured BMI age 30(±2y) and body silhouettes in women and men were between 0.62 and 0.66, and correlations for self-reported BMI ranged from 0.58 to 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). (II) We found a statistically significant effect of fathers’ onset of overweight in puberty for 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 of mother’s overweight was associated with offspring’s asthma. (III) Fathers’ overweight before puberty had a negative indirect effect, mediated through sons’ height, on sons’ FEV1[beta (95% CI): -144 (-272, -23) mL] and FVC [beta (95% CI): -210 (-380, -34) mL], and a negative direct effect on sons’ FVC [-262 (-501, -9) mL]. Statistically significant effects on FEV1/FVC were not observed. In the maternal line, mothers’ overweight before puberty had neither direct nor indirect effects on offspring’s lung function. Conclusions: Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men. Further, our work suggests 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. Finally, we found that fathers’ overweight starting before puberty appear to cause considerably lower FEV1 and FVC in their future sons. These effects could be partly mediated through sons’ adult height, but not through his pre-pubertal overweight. Implications: We have shown that the metabolic environment in male prepuberty might influence the health of the next generation. Closer scientific attention to male puberty in relation to future generations health may have profound implications and open new opportunities for targeted public health strategies. We speculate that while intervening in the prepuberty age window in one generation we might improve the health of two generations

Environmental impact on health across generations: policy meets biology. A review of animal and human models

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

MultiPaths Revisited - A novel approach using OpenFlow-enabled devices

This thesis presents novel approaches enhancing the performance of computer networks using multipaths. Our enhancements take the form of congestion-aware routing protocols. We present three protocols called MultiRoute, Step-Route, and finally PathRoute. Each of these protocols leverage both local and remote congestion statistics and build different representations (or views) of the network congestion by using an innovative representation of congestion for router-router links. These congestion statistics are then distributed via an aggregation protocol to other routers in the network. For many years, multipath routing protocols have only been used in simple situations, such as Link Aggregation and/or networks where paths of equal cost (and therefore equal delay) exist. But, paths of unequal costs are often discarded to the benefit of shortest path only routing because it is known that paths of unequal length present different delays and therefore cause out of order packets which cause catastrophic network performances. Further, multipaths become highly beneficial when alternative paths are selected based on the network congestion. But, no realistic solution has been proposed for congestion-aware multipath networks. We present in this thesis a method which selects alternative paths based on network congestion and completely avoids the issue of out of order packets by grouping packets into flows and binding them to a single path for a limited duration. The implementation of these protocols relies heavily on OpenFlow and NOX. OpenFlow enables network researchers to control the behavior of their network equipment by specifying rules in the routers flow table. NOX provides a simple Application Programming Interface (API) to program a routers flow table. Therefore by using OpenFlow and NOX, we are able to define new routing protocols like the ones which we will present in this thesis. We show in this thesis that grouping packets together, while not optimal, still provides a significant increase in network performance. More precisely we show that our protocols can, in some cases, achieve up to N times the throughput of Shortest Path (SP), where N is the number of distinct paths of identical throughput from source to destination. We also show that our protocols provide more predictable throughput than simple hash-based routing algorithms. %extend this with steproute and pathroute results. Todays networks provide more and more connections between any source-destination pair. Most of these connections remain idle until some failure occurs. Using the protocols proposed in this thesis, networks could leverage the added bandwidth provided by these currently idle connections. Therefore, we could increase the overall performance of current networks without replacing the existing hardware