Signs and Symptoms of Early Pregnancy Loss: A Systematic Review

Approximately one-third of pregnancies end in loss; however, the natural history of early pregnancy loss, including signs and symptoms preceding loss, has yet to be fully described and its underlying mechanisms fully understood. We searched PubMed/MEDLINE and Embase to identify articles with prospective ascertainment of signs and symptoms, including vaginal bleeding, nausea, and vomiting, of pregnancy loss < 20 weeks gestation in spontaneous conceptions to ascertain existing literature on symptomatology of pregnancy loss. Two preconception and 16 pregnancy cohort studies that ascertained information on bleeding and/or nausea/vomiting prior to pregnancy loss ascertainment were included. Data from these studies indicated increased risk of loss with vaginal bleeding and decreased risk of loss with nausea/vomiting, though these studies were mostly comprised of pregnancies surviving into late first trimester. While such associations are biologically plausible, these study designs are subject to bias, given recruitment of women at later gestational ages and reliance on women presenting to care. Reporting symptoms to clinicians and over long periods may introduce reporting error. Data gaps remain regarding (1) relationships between signs and symptoms and losses occurring very early, prior to care entry; (2) empirical testing of whether relationships between signs and symptoms and loss differ across gestational age; (3) whether similar relationships between signs and symptoms and loss are observed in populations using assisted reproductive technologies; (4) the patterning of multiple signs and symptoms in relation to loss; and (5) how hormonal and physiologic adaptions to early pregnancy relate to symptomatology and pregnancy loss.