276 ©2005 Blackwell Publishing Ltd. Paediatric and Perinatal Epidemiology, 19, 276–283 Blackwell Science, LtdOxford, UKPPEPaediatric and Perinatal Epidemiology0269-5022Blackwell Publishing Ltd, 200519 ••276283Original ArticlePredictors of gestational bleedingJ. Yang et al. Correspondence: Juan Yang, PhD, California Department of Health Services, CDIC/Tobacco Control Section, MS 7206, 1616 Capitol Avenue, Suite 74.516, Sacramento, CA 95814, USA. E-mail: jyang@dhs.ca.gov Original articles Predictors of vaginal bleeding during the first two trimesters of pregnancy Juan Yang a,b , David A. Savitz a,b , Nancy Dole b , Katherine E. Hartmann a,c , Amy H. Herring d , Andrew F. Olshan a,b and John M. Thorp, Jr b,c a Department of Epidemiology, School of Public Health, b Carolina Population Center, c Department of Obstetrics and Gynecology, School of Medicine, and d Department of Biostatistics, School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Summary This study evaluates maternal age, race, cigarette smoking, prior spontaneous abor- tion, prior induced abortion, and prior preterm birth in relation to vaginal bleeding during the first two trimesters of pregnancy. Information on vaginal bleeding and predictors came from the Pregnancy, Infection, and Nutrition Study, which enrolled 2806 pregnant women at 24–29 weeks’ gestation during 1995–2000 in central North Carolina, USA. Generalised estimating equations were applied to take into account repeated episodes of vaginal bleeding during pregnancy. Women with advanced maternal age and passive smoking exposure were more likely to experience more intense vaginal bleeding during pregnancy, as were women with prior preterm birth. More intense bleeding was also more likely to be reported among women with mul- tiple prior spontaneous abortions or multiple prior induced abortions, but not among women with a single prior spontaneous or induced abortion. The combination of prior spontaneous and induced abortion showed a dose–response association with the occurrence of vaginal bleeding during pregnancy. Introduction Vaginal bleeding is a common complication that may occur at any time during pregnancy. Up to 22% of women asked at delivery reported that vaginal bleed- ing occurred at some time during pregnancy. 1,2 The likely causes of vaginal bleeding change over the course of pregnancy. The causes in early pregnancy include ectopic pregnancy, trophoblastic disease, spon- taneous abortion, and threatened abortion. Causes in mid- and late pregnancy include incompetent cervix and placental abnormalities, such as placenta praevia or abruption. Genital infections, trauma, or systemic diseases can result in bleeding any time throughout pregnancy. 3–6 However, more than 50% of episodes are of unknown origin. 7,8 Vaginal bleeding in pregnancy has been associated with adverse pregnancy outcomes, including preterm birth, low birthweight, stillbirth, and perinatal death. 1 The reason that vaginal bleeding predicts adverse pregnancy outcome is not clear. For those bleeding episodes with identifiable causes (e.g. placental abrup- tion), bleeding is a biological indicator. However, more than half of bleeding episodes have unknown origin yet remain predictive of unfavourable pregnancy out- comes. Recent studies suggest that vaginal bleeding and consequent thrombin generation lead to a pro- teolytic cascade capable of damaging the fetal mem- branes and stimulating uterine contractions, which could result in preterm premature rupture of the mem- branes and preterm labour. 9 If correct, vaginal bleeding during pregnancy would be of concern as a harmful exposure in its own right. Finding ways to reduce bleeding occurrence might directly reduce adverse outcomes of pregnancy. Predictors of vaginal bleeding during pregnancy have received limited attention relative to studies of its consequences. Maternal age, race, cigarette smoking, and adverse obstetric history have been examined as risk factors for vaginal bleeding in pregnancy, though the results are inconclusive. 10–16 Previous studies