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Background: A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7–8 years of life in a large Amsterdam born birth cohort. Methods: For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes “ever being diagnosed with asthma” and “wheezing in the past 12 months” on questionnaires. We measured offspring height and weight at age 5–6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma. Results: At the age of 7–8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49–3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28–3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma. Conclusions: Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child’s own BMI. [ABSTRACT FROM AUTHOR]