Cord blood thyroid-stimulating hormone level is affected by various perinatal factors. The aim of this study is to investigate the relative impact of these factors on the cord blood thyroid-stimulating hormone results in singleton pregnancies. The study group consisted of 20,086 consecutive singleton deliveries over a 3 year period. The effect of mode of delivery, infant sex, gestation at birth, birth weight, and duration of labor on the incidence of false elevation of cord blood thyroid-stimulating hormone was assessed by univariate analysis and logistic regression. There was an independent positive association between false elevation of cord blood thyroid-stimulating hormone (> or =15.0 mIU/L) and birth weight (p=0.005), male infant sex (p<0.001), and instrumental delivery (p<0.001). Both elective and emergency cesarean section were negatively associated with elevated cord thyroid-stimulating hormone level (p<0.001). When the cutoff level was raised to 40.0 mIU/L, none of the variables examined were significant. The incidence of false positive tests (> or =15.0 mIU/L) was higher in neonates born by cesarean section for failed instrumental delivery and fetal distress than for failure to progress of labor (34.7% vs 4.5% vs 1.3% respectively, p<0.001). While the incidence of false positive screening was significantly affected by various perinatal factors when the thyroid-stimulating hormone cutoff level is low, it was unaffected at a high cutoff level. The present study also provides further evidence that cord blood thyroid-stimulating hormone level reflects fetal response to perinatal stress events.