There is increasing evidence that the development of the fetal immune system can be influenced by environmental exposure in utero. We investigated whether prenatal exposure is associated with a high neonatal total IgE level and sensitization at the age of 1 and 4 yr. Data from 1027 infants were collected in a Dutch birth cohort study (PIAMA study). Total IgE was measured in heel prick blood collected in the first week of life. Sensitization was defined as a specific IgE level in serum of ≥0.35 IU/ml against house dust mite, cat, dog, milk or egg. Logistic regression analysis was performed to study independent relationships between risk factors and a high neonatal total IgE (≥0.50 IU/ml) or sensitization. A high neonatal total IgE was found in 12.2% of boys and 6.2% of girls. A dog at home during pregnancy was negatively associated with a high neonatal total IgE [odds ratio (95% CI) 0.5 (0.2–1.0)]. A cat at home [OR 0.6 (0.4–1.0) and maternal smoking (OR 0.4 (0.2–1.0)] were negatively associated with sensitization at 12 months, but not at 4 yr. The presence of older siblings, season of birth, birth weight, mode of delivery, gestational age and maternal age were not associated with a high neonatal total IgE or sensitization. The higher total IgE level and prevalence of sensitization at 4 yr in boys compared with girls was only present in children from allergic mothers. Our results suggest a short-lasting protective effect of prenatal exposure to pets on total IgE at birth and early sensitization.