Associations between maternal blood lead concentration during pregnancy and trajectories of wheezing and asthma in offspring: The Japan Environment and Children’s study (JECS)

• We examined associations between prenatal lead (Pb) exposure and child wheeze/asthma. • Trajectory modelling identified four wheeze/asthma phenotypes at ages 1–4 years. • Higher maternal blood Pb (Q3–Q5) was associated with persistent asthma. • Prenatal Pb exposure may have long-term impacts on child respiratory health. Background: Asthma is a major chronic disease in childhood. Environmental factors such as air pollution, tobacco smoke, and dust have been associated with asthma prevalence. Lead (Pb) exposure can cause adverse health outcomes, yet epidemiologic evidence linking prenatal maternal Pb exposure during pregnancy and childhood wheeze/asthma is mixed, and longitudinal studies characterising early-life respiratory phenotypes at contemporary low exposure levels remain limited. Objectives: To examine the association between maternal Pb exposure during pregnancy and trajectories of wheezing and asthma in children up to 4 years of age in the Japan Environment and Children’s Study (JECS). Methods: We analysed data of 87,041 mother–child dyads from JECS, a large nationwide birth cohort study with a broad geographic coverage throughout Japan. Maternal blood Pb concentrations were measured in samples collected during the second or third trimester. Childhood wheezing and asthma were assessed annually from ages 1 to 4 years using the International Study of Asthma and Allergies in Childhood questionnaire. Latent trajectories were identified using group-based trajectory modelling, and associations with maternal blood Pb concentrations (BLL; quintiles) were examined using Bayesian binomial logistic regression models. Results: Median (interquartile range) maternal BLL was 5.8 (4.7–7.3) ng/g (≈ 0.6 [0.5–0.8] µg/dl). Four trajectory groups were identified for both wheezing and asthma: never-or-infrequent, transient-early, early-onset, and persistent. Higher maternal BLL (third–fifth quintiles) was associated with increased risks of transient-early and persistent wheezing and of persistent asthma, compared with the never-or-infrequent group. These associations were observed within the low exposure range typical of contemporary populations. Conclusions: Prenatal Pb exposure, even at low levels, may increase the risk of persistent wheezing and asthma in early childhood, underscoring the importance of minimising Pb exposure during pregnancy.