BACKGROUND:Early pregnancy represents a critical developmental period and may influence later development of respiratory and allergic diseases in children. A growing body of evidence links prenatal exposures to atopic diseases, such as asthma, with sex-specific differences. METHODS:Children from the F2-generation (i.e., children born to male or female F1 participants of the original 1989 birth cohort) of the Isle of Wight Birth Cohort (IOWBC) (n = 617) were followed from pregnancy through 10 years. Prenatal exposures (12 weeks), including cooking heat source, dampness or fungi in the home, air pollution and vehicle traffic near the home, were determined via standardized questionnaires. The status of wheezing, asthma, allergic rhinitis, and eczema status were also determined through questionnaires. Generalized linear mixed models analyzed the association of these early in utero exposures with the risk of childhood atopic disease status and respiratory symptoms. RESULTS:Increased vehicle traffic near the home (10+ per hour) was associated with increased risk of wheezing during childhood (RR: 1.74; 95% CI: 1.02-2.99); particularly in girls. Any increased vehicle traffic was also associated with higher risk of repeated wheezing in girls compared to infrequent traffic. A significant additive interaction between outdoor air pollution and sex was observed for repeated wheezing (RERI = 0.46; 95% CI: 0.10-0.82), indicating that the combined effect of prenatal air pollution exposure and female sex exceeded the sum of their individual effects. However, no prenatal environmental factors were associated with increased risk of diagnosed asthma, allergic rhinitis, or eczema. CONCLUSIONS:Our findings suggest that prenatal exposures to vehicle traffic near home are associated with an increased risk of repeated childhood wheezing, and such associations are likely to be different between boys and girls. Early exposures to vehicle traffic and outdoor air pollution increase susceptibility to childhood wheeze without increasing the risk of atopic diseases.