The associations between the two outcomes and child’s sex, gestational age, season of birth, parity, type of delivery, mother’s and father’s age, pre-pregnancy BMI, household income, marital status, mother’s and father’s smoking status during pregnancy, mother’s and father’s allergy, breast milk, nursery, lower respiratory infection, mold at home, pet, passive smoke, and mother’s and father’s educational levels were investigated using Fisher’s exact test or chi-square test (supplemental analysis).

To impute missing values for participants with missing data (7.1% of all data except for 15 regional units that had no missing data), the information was replaced using multiple imputations (25 imputed datasets) based on the assumption that data were missing at random. The variables included in the imputation model were as follows: 15 regional centers, wheezing, doctor-diagnosed asthma, child sex, gestational age, season of birth, parity, type of delivery, mother’s and father’s age, pre-BMI, household income, marital status, mother’s and father’s smoking status during pregnancy, mother’s and father’s allergy, breast milk, nursery, lower respiratory infection, mold at home, pet, passive smoke, and mother’s and father’s educational levels. Using the imputed datasets, the crude odds ratios (ORs) of each variable for childhood wheezing and doctor-diagnosed asthma were calculated (supplemental analysis).

Next, we conducted multilevel logistic regression analyses in which individual-level factors were at the first level and 15 regional centers at the second level to estimate ORs for childhood wheezing (primary outcome) and doctor-diagnosed asthma (secondary outcome: additional analysis) with 95% confidence intervals (95% CIs). First, mothers’ and fathers’ educational levels were separately introduced (crude model). In Model 1, mothers’ and fathers’ educational levels was simultaneously introduced. In Model 2, child sex, gestational age, season of birth, parity, type of delivery, mother’s and father’s age, pre-pregnancy BMI, marital status, mother’s and father’s allergy, household income and mother’s and father’s smoking status breast milk, nursery, the number of lower respiratory infections, mold, pet at home, and passive smoke were added. Then, to confirm the combination exposure effects of the mother and father’s educational levels, the combination variable was introduced in crude and full adjusted models (additional analysis).

Two-sided P-values <0.05 were considered statistically significant. All analyses were conducted using Stata statistical software version 15.0 for Windows (StataCorp, College Station, TX, USA).

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