Maternal smoking during pregnancy, other prenatal and perinatal factors, and the risk of Legg-Calve-Perthes disease

OBJECTIVE. The causes of Legg-Calve-Perthes disease are largely unknown, but this pediatric disease seems to result from interruption of the blood supply to the proximal femur and is considered a vascular disease. Because maternal smoking during pregnancy influences fetal development and is associated with cardiovascular diseases in offspring, we hypothesized that this exposure is a risk for Legg-Calve-Perthes disease and also investigated other markers of impaired fetal development and early-life exposures. MATERIALS AND METHODS. The Swedish Inpatient Register identified 852 individuals with a diagnosis of Legg-Calve-Perthes disease from 1983 to 2005, individually matched by year of birth, age, sex, and region of residence with 4432 randomly selected control subjects. Linkage with the Swedish Medical Birth Register provided information on prenatal factors, including maternal smoking. Conditional logistic regression examined associations of maternal smoking during pregnancy and the other measures with the risk of Legg-Calve-Perthes disease in offspring, adjusted for socioeconomic index and other potential confounding factors. RESULTS. Maternal smoking during pregnancy was associated with an increased Legg-Calve-Perthes disease risk, and heavy smoking was associated with a risk increase of almost 100%. Very low birth weight and cesarean section were independently associated with similar to 240% and 36% increases in the risk of Legg-Calve-Perthes disease, respectively. CONCLUSION. Maternal smoking during pregnancy and other factors indicated by impaired fetal development may be associated with an increased risk of Legg-Calve-Perthes disease.