Maternal Smoking during Pregnancy and Early Childhood and Development of Asthma and Rhinoconjunctivitis – a MeDALL Project

Background: The role of tobacco smoke exposure in the development and persistence of asthma and rhinoconjunctivitis through childhood into adolescence is unclear. Objectives: We assessed the associations of parental smoking from fetal life through adolescence with asthma and rhinoconjunctivitis during childhood and adolescence. Methods: We analyzed data for 10,860 participants of five European birth cohort studies from the Mechanisms of the Development of Allergy (MeDALL) consortium. Parental smoking habits and health outcomes (early transient, persistent, and adolescent-onset asthma and rhinoconjunctivitis) were based on questionnaires covering the period from pregnancy to 14–16 y of age. Data were combined and analyzed using a one-stage and two-stage individual participant data meta-analysis. Results: Overall, any maternal smoking during pregnancy tended to be associated with an increased odds of prevalent asthma [adjusted odds ratio (aOR)=1.19 (95% CI: 0.98, 1.43)], but not prevalent rhinoconjunctivitis [aOR=1.05 (95% CI: 0.90, 1.22)], during childhood and adolescence. In analyses with phenotypes related to age of onset and persistence of disease, any maternal smoking during pregnancy was associated with early transient asthma [aOR=1.79 (95% CI: 1.14, 2.83)]. Maternal smoking of ≥10 cigarettes/day during pregnancy was associated with persistent asthma [aOR=1.66 (95% CI: 1.29, 2.15)] and persistent rhinoconjunctivitis [aOR=1.55 (95% CI, 1.09, 2.20)]. Tobacco smoke exposure during fetal life, infancy, childhood, and adolescence was not associated with adolescent-onset asthma or rhinoconjunctivitis. Conclusions: Findings from this combined analysis of five European birth cohorts strengthen evidence linking early exposure to tobacco smoke with asthma during childhood and adolescence. Children with high early-life exposure were more likely than unexposed children to have early transient and persistent asthma and persistent rhinoconjunctivitis. https://doi.org/10.1289/EHP2738

. Definitions of smoking variables in the participating birth cohorts. Table S2. Definitions of asthma and rhinoconjunctivitis variables in the participating birth cohorts. Table S3. Overview of follow-ups of participating cohorts and outcome assessment intervals. Table S4. Participant characteristics of five European birth cohorts at baseline. Table S5. Association between SHS exposure during pregnancy and during infancy in relation to prevalent asthma and rhinoconjunctivitis up to 14 to 16 years from one-stage IPD-MA. Table S6. The development of early-onset and persistent phenotypes of asthma and rhinoconjunctivitis in relation to intensity of SHS during infancy. Table S7. Asthma and rhinoconjunctivitis development in relation to smoking during pregnancy stratified by parental allergy. Table S8. Asthma and rhinoconjunctivitis development in relation to smoking during infancy stratified by parental allergy. Table S9. Asthma and rhinoconjunctivitis development in relation to smoking during pregnancy stratified by sex. Table S10. Asthma and rhinoconjunctivitis risk in relation to smoking during infancy stratified by sex. Table S11. Association between SHS exposure during pregnancy and during infancy in relation to prevalent asthma and rhinoconjunctivitis up to 14 to 16 years from one-stage IPD-MA excluding preterm infants. Figure S1. Prevalence of parental tobacco smoking in five European birth cohorts.   Figure S4. Association between maternal smoking during pregnancy and asthma only, rhinoconjunctivitis only, or concurrent asthma and rhinoconjunctivitis up to 14 to 16 years of age in five European birth cohorts. Cohort specific odds ratios (OR) and 95% confidence intervals (CI) were obtained by GEE models adjusted for sex, parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance. Combined OR and 95% CI were derived from cohort-specific OR and 95% CI using a random effects model. Figure S5. Association between parental smoking during infancy and asthma only, rhinoconjunctivitis only, or concurrent asthma and rhinoconjunctivitis up to 14 to 16 years of age in five European birth cohorts. Cohort specific odds ratios (OR) and 95% confidence intervals (CI) were obtained by GEE models adjusted for sex, parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance. Combined OR and 95% CI were derived from cohort-specific OR and 95% CI using a random effects model. Figure S6. Associations between maternal smoking during pregnancy only, SHS during infancy only, and both in relation to asthma and rhinoconjunctivitis. Figure S7. Associations between any tobacco smoke exposure during pregnancy or SHS during infancy and prevalence of asthma and rhinoconjunctivitis up to 14 to 16 years of age in five European birth cohorts. Cohort specific odds ratios (OR) and 95% confidence intervals (CI) were obtained by generalized estimating equation models adjusted for sex, parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance. Combined OR and 95% CI were derived from cohort-specific OR and 95% CI using a random effects model. Participants unexposed to tobacco smoke during pregnancy and infancy comprised the reference category. Cigarettes, pipes, cigars smoked in the house by mother, father and/or other household member at age 3 months.
Cigarettes, pipes, cigars smoked in the house by mother, father and/or other household member at age 2 years.
Cigarettes, pipes, cigars smoked in the house by mother, father and/or other household member at age 4 years.
Cigarettes, pipes, cigars smoked in the house by mother, father and/or other household member at age 8 years.
Cigarettes, pipes, cigars smoked in the house by mother, father and/or other household member at age 14 years. Table S2. Definitions of asthma and rhinoconjunctivitis variables in the participating birth cohorts.

Outcome Age 4-6 years Age 8-10 years Age 14-16 years Asthma
Positive answer to two out of three: 1) Doctors diagnosed asthma ever (parental reported); 2) Asthma medication in the past 12 months (parental reported); 3) Wheezing in the past 12 months (parental reported).
Positive answer to two out of three: 1) Doctors diagnosed asthma ever (parental reported); 2) Asthma medication in the past 12 months (parental reported); 3) Wheezing in the past 12 months (parental reported).
Positive answer to two out of three: 1) Doctors diagnosed asthma ever (parental reported); 2) Asthma medication in the past 12 months (child reported, if available); 3) Wheezing in the past 12 months and/or breathing difficulties, where available (child reported, if available).

Rhinoconjunctivitis
Positive answer to the following questions: 1) In the past 12 months problems with sneezing, or a runny, or blocked nose when child did not have a cold or flu (parental reported); 2) In the past 12 months, has this nose problem been accompanies by itchy-watery eyes (parental reported).
Positive answer to the following questions: 1) In the past 12 months problems with sneezing, or a runny, or blocked nose when child did not have a cold or flu (parental reported); 2) In the past 12 months, has this nose problem been accompanies by itchy-watery eyes (parental reported).
Positive answer to the following questions: 1) In the past 12 months problems with sneezing, or a runny, or blocked nose when child did not have a cold or flu (child reported, if available); 2) In the past 12 months, has this nose problem been accompanies by itchy-watery eyes (child reported, if available).
X indicates all follow-ups conducted in each cohort. X indicates outcome interval used. X c indicates where children reported symptoms were utilized.   N = total number of exposed children and n = number of exposed cases. b ORs and 95% CIs obtained from multinomial logistic regression analyses adjusted for sex, parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance. ORs and 95% CIs obtained from GEE analyses adjusted for sex, parental education level, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance.  ORs and 95% CIs obtained from GEE analyses adjusted for parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance.   .3 .5 .8 1 2 3 5 7 Odds ratio (95% CI) Early-transient Persistent Adolescent-onset Asthma Rhinoconjunctivitis * OR and 95% CI were obtained by logistic regression adjusted for sex, parental education, parental allergy, maternal smoking during pregnancy, siblings, breastfeeding, study center, intervention arm, and early day-care attendance. Figure S3. Secondhand smoking during infancy and the development of early-transient, persistent, and adolescent-onset disease phenotypes.* Figure S4. Association between maternal smoking during pregnancy and asthma only, rhinoconjunctivitis only, or concurrent asthma and rhinoconjunctivitis up to 14 to 16 years of age in five European birth cohorts. Cohort specific odds ratios (OR) and 95% confidence intervals (CI) were obtained by GEE models adjusted for sex, parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance. Combined OR and 95% CI were derived from cohort-specific OR and 95% CI using a random effects model. Odds ratio C. Maternal smoking during pregnancy and overall risk of both asthma and rhinoconjunctivitis Figure S5. Association between parental smoking during infancy and asthma only, rhinoconjunctivitis only, or concurrent asthma and rhinoconjunctivitis up to 14 to 16 years of age in five European birth cohorts. Cohort specific odds ratios (OR) and 95% confidence intervals (CI) were obtained by GEE models adjusted for sex, parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance. Combined OR and 95% CI were derived from cohort-specific OR and 95% CI using a random effects model.  Figure S6. Associations between maternal smoking during pregnancy only,SHS during infancy only, and both in relation to asthma and rhinoconjunctivitis.* Figure S7. Associations between any tobacco smoke exposure during pregnancy or SHS during infancy and prevalence of asthma and rhinoconjunctivitis up to 14 to 16 years of age in five European birth cohorts. Cohort specific odds ratios (OR) and 95% confidence intervals (CI) were obtained by generalized estimating equation models adjusted for sex, parental education level, parental allergy, older siblings, breastfeeding, study center, intervention arm, and early day-care attendance. Combined OR and 95% CI were derived from cohort-specific OR and 95% CI using a random effects model. Participants unexposed to tobacco smoke during pregnancy and infancy comprised the reference category.