BACKGROUND: It has been suggested that pregnancy and early life may influence the development of asthma in the offspring, but published studies have not carefully controlled for potential biases. METHODS: In a large British birth cohort of 4065 natural children of 2583 mothers, we investigated whether in utero and perinatal influences contribute to the development and the severity of asthma in childhood, allowing for possible confounders of the relationship, and considering the nonindependence of familial data. RESULTS: Child asthma (10.1%) was more frequently reported by mothers when there had been health complications during pregnancy (prevalence =14.3%; adjusted odds ratio [ORadj] =2.01; 95% confidence interval, 1.52-2.67), labor, or delivery (19.3%, ORadj =1.35, 1.01-1.81); child illness or health complications during the first week of life (22.6%, ORadj =1.35, 1.01-1.82); and birth weight of < 2.5 kg (7.0%, ORadj =1.57, 1.10-2.25). Specific causes of health complications during pregnancy which significantly related to asthma were early or threatened labor (ICD: 644) (4.8%, ORadj =1.58, 1.03-2.40) and the malposition or malpresentation of the fetus (ICD: 652) (1.6%, ORadj =3.63, 1.47-8.91). CONCLUSION: The results provide further evidence that in utero and perinatal factors may increase the risk of developing asthma.