Vaginal bleeding and nausea in early pregnancy as predictors of clinical pregnancy loss

Background: Although nausea and vaginal bleeding are commonly experienced in early pregnancy, their prognostic value in predicting clinical pregnancy loss is not well understood. Objective: This study aimed to understand whether timing of bleeding and nausea symptoms can be used to predict risk of pregnancy loss among women with ultrasound-confirmed pregnancies. Study Design: A cohort of 701 women with clinically confirmed pregnancies and 1 to 2 previous pregnancy losses were preconceptionally enrolled in the Effects of Aspirin in Gestation and Reproduction trial (2006–2012). Participants completed daily symptom diaries from 2 to 8 weeks’ gestation and were prospectively monitored for detection of pregnancy loss. The risk of pregnancy loss was estimated for each observed bleeding and nausea pattern, and positive and negative predictive values for each pattern were calculated. Results: Among 701 women, 211 (30.1%) reported any vaginal bleeding, and 639 (91.2%) reported any nausea. Most bleeding experienced by women was spotting and contained within a single episode. Within 2 to <4, 4 to <6, and 6 to 8 weeks’ gestation, vaginal bleeding occurred in 5.9% (41) (5.7% live birth, 7.1% clinical pregnancy loss), 14.6% (102) (13.9% live birth, 18.6% clinical pregnancy loss), and 20.8% (146) (18.4% live birth, 32.4% clinical pregnancy loss) of women, respectively. Within the same gestational periods, nausea was reported in 22.7% (159) (23.2% live birth, 20.4% clinical pregnancy loss), 65.9% (462) (67.5% live birth, 58.4% clinical pregnancy loss), and 87.0% (610) (90.6% live birth, 69.0% clinical pregnancy loss) of women. Women who had bleeding without nausea between 6 and 8 weeks’ gestation (3.6% prevalance) had the greatest risk of clinical pregnancy loss (risk difference=56.1%; 95% confidence interval, 37.6–74.7), a positive predictive value of 68.0% (49.7%, 86.3%), negative predictive value of 85.8% (83.2%, 88.4%), positive likelihood ratio of 11.1 (2.04, 20.1), and negative likelihood ratio of 0.86 (0.79, 0.93). Nausea and bleeding are clinical factors that predicted clinical pregnancy loss (area under the curve, 0.87; 95% confidence interval, 0.81–0.88) similar to age, body mass index, blood pressure, and waist-to-hip ratio (area under the curve, 0.81; 95% confidence interval, 0.78–0.88) measured preconceptionally. Conclusion: Women experiencing bleeding without nausea between 6 and 8 weeks’ gestation had an increased risk of clinical pregnancy loss. Bleeding and nausea were not predictive risk factors of clinical pregnancy loss prior to 6 weeks’ gestation.