Table 6.

Overview of key publications from RHINESSA/RHINE/ECRHS on preconception exposures as related to offspring respiratory outcomes, phenotypes across generations and validation studies relevant for multigeneration research

Exposure	Outcome	Exposure window	Main findings	Study cohorts	Reference
Smoking
Smoking	Non-allergic early onset asthma	Paternal prepuberty: paternal grandmother’s pregnancy	Fathers smoking in prepuberty associated with asthma in his offspring, in absence of grandmothers smoking during the father’s pregnancy.	RHINE	Svanes et al 21
Smoking	Allergic and non-allergic asthma	Paternal prepuberty; pregnancy	Fathers smoking in prepuberty associated with non-allergic asthma in his offspring; grandmothers smoking during mother’s fetal period associated with allergic asthma in her grandchild.	ECRHS	Accordini et al 22
Smoking	Lung function	Paternal prepuberty; grand-maternal pregnancy	Fathers smoking in prepuberty reduced offspring’s FEV1 and FVC; the grandmothers smoking during the father’s fetal period reduced the grandchild’s FEV1/FVC.	Parents: ECRHS Offspring: RHINESSA	Accordini et al 26
Occupational exposures
Welding	Non-allergic asthma	Paternal adolescence	Fathers’ preconception welding was associated with non-allergic asthma in offspring.	RHINE	Svanes et al 21
Allergens, reactive chemicals, micro-organisms and pesticides	Asthma	Before conception of child; preconception and postconception combined	Preconception maternal and paternal exposure to occupational agents not associated with asthma in offspring, expect higher early-onset asthma with mother exposure to allergens and/or reactive chemicals before and after conception	Parents: ECRHS Offspring: RHINESSA	Pape et al 36
Cleaning products and disinfectants	Asthma and/or wheeze	Before conception of child; around conception and pregnancy	Mother’s exposure to indoor cleaning starting before conception was associated with offspring’s childhood allergic and non-allergic asthma.	Parents: RHINE Offspring: RHINESSA	Tjalvin et al 37
Environmental exposures
Air pollution	Asthma and allergies	Parental childhood	Parental exposure to air pollution during childhood increased the risk of asthma and allergies in offspring.	RHINESSA	Kuiper et al 38
Farm exposure	Asthma	Parental childhood	Farm upbringing in previous generations was not associated with offspring asthma—either for parental or grandparental upbringing.	Parents: ECRHS/RHINE Offspring: RHINESSA	Timm et al 34
Metabolic and hormonal exposures
Overweight and weight gain	Non-allergic asthma	Paternal puberty	Paternal overweight and weight gain before puberty associated with offspring non-allergic asthma.	Parents: ECRHS/RHINE Offspring: RHINESSA	Johannessen et al 29
Overweight	Lung function	Paternal childhood/puberty	Paternal overweight during childhood and/or puberty may cause lower lung function in offspring.	Parents: ECRHS Offspring: RHINESSA	Lønnebotn et al 30
Infections and disease processes
Helminth infection	Allergies	Not known	Toxocara spp seropositivity in parents was associated with allergic outcomes in their offspring.	Parents: ECRHS Offspring: RHINESSA	Jogi et al 33
Bronchial hyper-responsiveness and level of specific IgEs	Asthma and allergies	Before conception of child	Parental asthmatic and allergic disease activity measured before conception was associated to offspring asthma and hay fever.	ECRHS	Bertelsen et al 32
Phenotype across generations
Sleep characteristics		Sleep-related symptoms and sleep duration more common in offspring with same outcome in parents, after adjusting for lifestyle factors, education and parity in both generations		Parents: ECRHS/RHINE Offspring: RHINESSA	Lindberg et al 39
Breathlessness		Breathlessness nearly doubled in offspring of parents with breathlessness, after adjusting for obesity, smoking, depression, asthma, lower lung function and female sex in both generations		Parents: ECRHS/RHINE Offspring: RHINESSA	Ekstrøm et al 40
Validation studies
Asthma reported by family members		Moderate to good agreement between self-reported asthma and asthma reported by family members, for offspring asthma reported by parents and vice versa, better fr childhood than adult onset asthma.		Parents: ECRHS/RHINE Offspring: RHINESSA	Kuiper et al 41
Parental smoking reported by offspring		Adults reported well their parents’ smoking during their childhood and their mother’ smoking when pregnant with them, when compared with the parents’ own report.		Parents: ECRHS/RHINE Offspring: RHINESSA	Pape et al 42
Parents’ place of upbringing reported by offspring		Offspring report of parents’ place of upbringing was dependent on own place of upbringing, this did not bias the associations of place of upbringing with asthma.43		Parents: ECRHS/RHINE Offspring: RHINESSA	Timm et al 43
Birth characteristics reported by mothers		High validity for mother’s report of birth and pregnancy parameters. Risk-associations were similar when using maternal vs registry-based information.		Bergen RHINE, Medical Birth Registry of Norway	Skulstad et al 44
Current body silhouettes validated against measured and reported height/weight		Current body silhouettes were highly correlated with BMI calculated from either measured or self-reported weight and height.		ECRHS, RHINE	Dratva et al 45
Retrospective body silhouettes validated against previously measured and reported height/ weight		Retrospective body silhouettes from adult ages correlated well with BMI calculated from measured height/weight at corresponding ages in the past, and allowed differentiation of obesity and non-obesity		ECRHS, RHINE	Lønnebotn et al 46

BMI, body mass index; ECRHS, European Community Respiratory Heath Survey; FEV1, Forced Expiratory Volume in 1 second; FVC, Forced Vital Capacity; RHINE, Respiratory Health In Northern Europe; RHINESSA, Respiratory Health in Northern Europe, Spain and Australia.