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Offspring Reports on Parental Place of Upbringing

Is It Valid?

Timm, Signe; Schlünssen, Vivi; Benediktsdottir, Bryndis; Bertelsen, Randi Jacobsen; Bråbäck, Lennart; Holm, Mathias; Jogi, Rain; Malinovschi, Andrei; Svanes, Cecilie; Frydenberg, Morten

doi: 10.1097/EDE.0000000000000988
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Department of Public Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark, signe.timm@ph.au.dk

Department of Public Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark, National Research Centre for Working Environment, Copenhagen, Denmark

Faculty of Medicine, University of Iceland, Reykjavík, Iceland, Primary Health Care Center, Gardabaer, Iceland

Institute of Clinical Science, University of Bergen, Bergen, Norway

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

Section of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

Department of Pulmonology (ARKS), University of Tartu, Tartu, Estonia

Clinical Physiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway

Department of Public Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark

The RHINE/RHINESSA study (Respiratory Health in Northern Europe/Respiratory Health in Northern Europe, Spain, and Australia) was supported by grants from the Faculty of Health, Aarhus University, Denmark (Project No. 240008); the Wood Dust Foundation (Project No. 444508795); the Danish Lung Association; the Swedish Heart and Lung Foundation; the Swedish Association Against Asthma and Allergy; the Swedish Association against Heart and Lung Disease; the Swedish Council for Working Life and Social Research; the Bror Hjerpstedt Foundation; the Vårdal Foundation for Health Care and Allergic Research; the Norwegian Research Council (Grant No. 214123, 230827/F20, 228174, and 135773/330); the Norwegian Asthma and Allergy Association, Helse Vest, Norway (Grant No. 911 631); the Icelandic Research Council; the University of Iceland Research Fund; the Icelandic GP’s Research Fund; the Estonian Science Foundation (Grant No. 4350); and the Estonian Research Council (Grant No. PUT562). For further information about funding sources, please consult www.rhinessa.net.

V.S. and C.S. are members of the COST BM1201 network. S.T. received a PhD scholarship from Aarhus University, Denmark. The other authors have no conflicts to report.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

Availability of data and material: The dataset is held and managed by the Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. Data cannot be made freely available as they are subject to secrecy in accordance with the Norwegian Public Access to Information and Secrecy Act, but can be made available to researchers on request (subject to a review of secrecy). Requests for data can be sent to the principal investigator of the Respiratory Health In Northern Europe, Switzerland, Spain, and Australia (RHINESSA): Cecilie Svanes, e-mail: cecilie.svanes@med.uib.no.

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To the Editor:

Exposure and disease across generations gain increasing interest, and information is often reported by family members, particularly offspring reporting about their parents. It is crucial to know the validity of secondhand information, but this is poorly investigated. A study on agreement in reported reproductive outcomes showed that husbands’ misclassification of their wives’ reproductive history was substantial and undermined the validity of the study.1 In contrast, two studies on maternal/paternal smoking concluded that offspring’s report of mother’s smoking prenatally and in childhood are good proxy measures for parent’s own report of smoking.2,3

Many studies have associated upbringing on a farm with a lower risk of subsequent asthma and hay fever, hypothesizing that the microbial richness on farms might play a key role.4–6 Farm living in early life seems to influence methylation of asthma-related genes, which suggests that the effect of farm upbringing might potentially be passed on to the next generation.7 However, it is not known if parental place of upbringing confers an effect on offspring’s asthma and hay fever via intergenerational or transgenerational pathways.

The present study includes questionnaire information on parental place of upbringing from two sources: the parents themselves and their offspring. We aimed to investigate the agreement between offspring’s and parent’s reporting of parental place of upbringing, which to our knowledge has not been investigated before.

We analyzed 4215 parent–offspring pairs. The parents were RHINE III participants (2010) born between 1945 and 1973 from Denmark, Norway, Sweden, Iceland, and Estonia, and their adult offspring (born between 1963 and 1998) who participated in the Respiratory Health In Northern Europe, Switzerland, Spain, and Australia (RHINESSA) study in 2012–2016. The cohorts are described in details elsewhere.8

Place of upbringing was based on the question “What term best describes the place you/your mother/your father lived most of the time before the age of 5 years?” with response categories: (1) farm with livestock, (2) farm without livestock, (3) village in a rural area, (4) small town, (5) suburb of city, and (6) inner city. We present to which degree the offspring misclassified their parent on whether or not the parent was brought up on a farm, by combining responses (1) and (2) into “farm,” and (3) to (6) into “not farm.” A parent was defined as misclassified if the offspring reported the opposite parental place of upbringing to the parent’s report. We have used the term “misclassification” although we are aware that it can be questioned whether parental own reports are correct.

Risk of misclassification is presented for all and stratified by parental-reported farm upbringing or not, and by offspring place of upbringing, sex, asthma, and hay fever (the two main outcomes of interest in the RHINESSA study).

Overall, 10% of offspring misclassified their parent’s place of upbringing (Figure). However, offspring misclassification was much higher regarding parents who reported being raised on farms (30%) than regarding parents not from farms (5%). Note that, if we were to consider parental farm upbringing as the target, this corresponds to a sensitivity of 70% and a specificity of 95%. In general, misclassification was not related to offspring asthma or hay fever status neither overall nor for subgroups (eFigure; http://links.lww.com/EDE/B467). However, misclassification was highly dependent on the combination of where a parent and an offspring were raised: the risk of misclassification among nonfarm-raised offspring with farm-raised parents was 33% compared with 8% among farm-raised offspring with farm-raised parents. Likewise, farm-raised offspring with nonfarm-raised parents misclassified 14% compared with 4% among nonfarm-raised offspring with nonfarm-raised parents. Results were similar across age groups, for males and females, and regarding mothers or fathers (data not shown).

FIGURE

FIGURE

Our main findings are that an apparently low rate of misclassification overall was masking patterns of higher misclassification within subgroups, and that offspring misclassification of parental place of upbringing was highly influenced by their own place of upbringing. One might speculate whether the understood definition of a “farm” might differ between generations. Another limitation of our study may be our inability to detect misclassification within the broad nonfarm category.

According to these results, secondhand information should be used with caution, as systematic misclassification may be encased and follow central characteristics of the responder or the concerned family member as seen in this case, where offspring tend to report the same for their parent as for themselves. If these patterns exist in other studies using secondhand information, this will in general challenge the validity of such data sources in epidemiologic research. In future studies, the data presented in this paper may facilitate quantitative bias analyses on comparable variables to look into the magnitude of bias from secondhand misclassification.

Signe Timm

Department of Public Health

Danish Ramazzini Centre

Aarhus University

Aarhus, Denmark

signe.timm@ph.au.dk

Vivi Schlünssen

Department of Public Health

Danish Ramazzini Centre

Aarhus University

Aarhus, Denmark

National Research Centre for Working Environment

Copenhagen, Denmark

Bryndis Benediktsdottir

Faculty of Medicine

University of Iceland

Reykjavík, Iceland

Primary Health Care Center

Gardabaer, Iceland

Randi Jacobsen Bertelsen

Institute of Clinical Science

University of Bergen

Bergen, Norway

Lennart Bråbäck

Department of Public Health and Clinical Medicine

Umeå University

Umeå, Sweden

Mathias Holm

Section of Occupational and Environmental Medicine

Sahlgrenska University Hospital

Gothenburg, Sweden

Rain Jogi

Department of Pulmonology (ARKS)

University of Tartu

Tartu, Estonia

Andrei Malinovschi

Clinical Physiology, Department of Medical Sciences

Uppsala University

Uppsala, Sweden

Cecilie Svanes

Centre for International Health

Department of Global Public Health and Primary Care

University of Bergen

Bergen, Norway

Department of Occupational Medicine

Haukeland University Hospital

Bergen, Norway

Morten Frydenberg

Department of Public Health

Danish Ramazzini Centre

Aarhus University

Aarhus, Denmark

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REFERENCES

1. Fikree FF, Gray RH, Shah F. Can men be trusted? A comparison of pregnancy histories reported by husbands and wives. Am J Epidemiol. 1993;138:237–242.
2. Pape K, Svanes C, Malinovschi A, et al. Agreement of offspring-reported parental smoking status: the RHINESSA generation study. BMC Public Health. 2019;19:94.
3. Simard JF, Rosner BA, Michels KB. Exposure to cigarette smoke in utero: comparison of reports from mother and daughter. Epidemiology. 2008;19:628–633.
4. Ege M, Mayer M. Exposure to environmental microorganisms and childhood asthma. N Engl J Med. 2011;364:701–709. Available at: http://www.nejm.org/doi/full/10.1056/nejmoa1007302. Accessed 8 December 2013.
5. Von Ehrenstein OS, Von Mutius E, Illi S, Baumann L, Böhm O, von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy. 2000;30:187–193.
6. Timm S, Frydenberg M, Janson C, et al. The urban-rural gradient in asthma: a population-based study in Northern Europe. Int J Environ Res Public Health. 2015;13:1–14.
7. Michel S, Busato F, Genuneit J, et al; PASTURE Study Group. Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy. Allergy. 2013;68:355–364.
8. Kuiper IN, Svanes C, Benediktsdottir B, et al. Agreement in reporting of asthma by parents or offspring - the RHINESSA generation study. BMC Pulm Med. 2018;18:122.

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