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

Abstract Background While nausea and vaginal bleeding are commonly experienced in early pregnancy, their prognostic value in predicting clinical pregnancy loss is not well understood. Objective To understand whether timing of bleeding and nausea symptoms can be used to predict risk of pregnancy loss among women with ultrasound confirmed pregnancies. Methods A cohort of 701 women with clinically confirmed pregnancies and 1-2 prior pregnancy losses were preconceptionally enrolled in the EAGeR trial (2006-2012). Participants completed daily symptom diaries from 2 to 8 weeks’ gestation and were prospectively followed 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, 38% reported any vaginal bleeding and 92% reported any nausea. Most bleeding was spotting and contained within a single episode. Vaginal bleeding occurred in 16% (16% live birth, 16% clinical loss), 15% (15% live birth, 20% clinical loss), and 21% (19% live birth, 33% clinical loss) of women within weeks 2-4, 4-6, and 6-8, respectively. Nausea was reported in 33% (34% live birth, 29% clinical loss), 66% (68% live birth, 60% clinical loss), and 87% (91% live birth, 69% clinical loss) of women within these respective epochs. Bleeding in the absence of nausea at 6-8 weeks’ gestation (3.6% prevalence) had the greatest risk of clinical loss (RD = 56%, 95% CI [38, 75]), a positive predictive value of 68% [50, 86], negative predictive value of 86% [83, 88], positive likelihood ratio of 11 [2.0, 20], and negative likelihood ratio of 0.86 [0.79, 0.93]. This symptom pattern predicted clinical pregnancy loss similar to (AUC = 0.85 [0.82, 0.90]) age, BMI, blood pressure, and waist to hip ratio (AUC = 0.81 [0.78, 0.88]) measured preconceptionally. Conclusions Women experiencing bleeding 6-8 weeks’ gestation without accompanying nausea had an elevated risk of clinical pregnancy loss. Bleeding or nausea prior to 6 weeks’ gestation were not predictive of risk of clinical loss.