Prospective Birth Cohort Investigation of Integrated Maternal Exposure to a Legacy Flame-Retardant Mixture during Early Pregnancy and De Novo Asthma Diagnosis in the Child

• We conducted the first human study of prenatal PBDE/PCBs on childhood asthma. • Maternal PBDE/PCB dose captures first-trimester transfer and susceptibility. • Disentangling embryo/fetus-toxicant interplay could prevent pre-clinical asthma onset. • Exquisite vulnerability of girls to BDE-99 is shown for the first time. • Persistent and bioaccumulative toxicants warrant stringent protective regulations. Despite being globally banned, Polychlorinated arepersistent, bioaccumulative, and toxic. Time-integrated maternal dose and the development of de novo asthma risk in their children has never been investigated. To test the hypothesis that the maternal plasma dose of PCB and PBDE congeners significantly increases the risk of asthma in their children at age six. A prospective birth cohort study of 342 healthy, nonsmoking pregnant women with no known thyroid disease was conducted in the French-speaking Eastern Townships of Canada. Maternal plasma doses of four PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) and three PCBs (PCB-138, PCB-153, and PCB-180) were measured at the first prenatal care visit. Asthma diagnosis was ascertained through medical record review. At age 6, 33 (10%) children had clinically confirmed asthma. Asthmatic girls had higher medians for all four BDE (all Ps > 0.05) and three PCB congeners (all Ps < 0.01) than asymptomatic girls. The highest quartile of maternal BDE-99 dose during the first trimester was associated with a 5.8-fold greater risk (95% CI, 1.6–22.2; P = 0.006) of asthma diagnosis after adjustment for putative confounders, among girls only. In a sensitivity analysis using the Cox proportional hazards model, the highest quartile of BDE-99 was associated with a 4.5-fold greater hazard of asthma (95% CI, 1.04–9.86) compared with the lower quartiles among girls. Maternal exposure to BDE-99, but no other congeners, significantly increased the risk of asthma diagnosis among girls at age six.