Vaginal bleeding in early pregnancy and preterm birth: systemic review and analysis of heterogeneity

Abstract

Objective To systemically review published studies of vaginal bleeding and the risk of preterm birth (PTB) and explore sources of heterogeneity between them. Methods The literature was searched for peer-reviewed articles from 1980–2009 in which the primary analysis was the risk of PTB among low risk subjects with and without bleeding. Heterogeneity was assessed through I2 statistics and sources of heterogeneity were explored through subgroup analyses and meta-regression. Results 218 studies were initially identified, 64 reviewed and 23 included. The pooled Odds Ratio for PTB was 1.74, though significant heterogeneity was present (I2=49.7%). Meta-regression demonstrated a significant association between a study’s incidence of bleeding and quality assessment and subsequent odds ratio, such that studies with a lower quality assessment or lower incidence of bleeding demonstrated an increased odds of preterm birth. Conclusions Bleeding in early pregnancy is associated with an increased risk of PTB, however excessive heterogeneity exists among published studies. The heterogeneity arises in part from differences in the reported incidence of bleeding within study populations. Presumably studies that identify bleeding in a larger percentage of subjects consequently dilute the magnitude of the risk.

Evaluation of perinatal outcome in women presented with first trimester vaginal bleeding: our experience

“…[15][16][17] Because of impaired implantation and inadequate invasion of trophoblasts, spontaneous abortion may occur in early pregnancy while preterm delivery, PPROM, placental ablation and preeclampsia may happen in late period. 16,18,19 Preterm delivery and PPROM rates were increased in this group of patients because of increased free iron deposits from subchorionic bleeding, hydroxyl radical is catalysed damaging the membrane. 17,18 The other point in PPROM etiology is the chronic inflammatory reaction within the deciduas and placental membranes which causes rupture of the membranes, decidual thrombosis, ischaemia and necrosis results in vaginal bleeding along with inflammatory response and thrombosis formation.…”

Vaginal bleeding in early pregnancy and circulating markers of thrombin generation

“…Though thrombin generation markers have been studied with regards to outcome in subjects with preterm labor with and without bleeding[3–4] and in subjects who were asymptomatic at the time of the measurement[2, 6, 12], the relationship with future outcomes in subjects with acute early bleeding events has not been evaluated. The presence of an association potentially could address the significant problem of suboptimal quantification measures and lack of uniform definitions which complicate the literature on bleeding and obstetrical outcomes[1]. In much the same way, sonographic cervical lengths and vaginal fetal-fibronectin have added needed quantization to the clinical entities of cervical “competence” and preterm labor.…”

“…[1] Their risk of preterm delivery is significantly increased, making clinical bleeding one of the most common risk factors for preterm birth. The literature on clinical bleeding events, however, is limited by substantial heterogeneity among study results.…”

“…The literature on clinical bleeding events, however, is limited by substantial heterogeneity among study results. For example, the incidence of “bleeding” within published cohorts ranges from 1% to 25%, with the resultant Odds Ratios for preterm birth ranging from 1.1 to 3.0[1]. This significant heterogeneity complicates both patient counseling and clinical research efforts.…”

Definition of bleeding events in studies evaluating prophylactic antithrombotic therapy in pregnant women: A systematic review and a proposal from the ISTH SSC

“…However, the exact frequencies of bleeding events in pregnancy are unknown, as is their severity. Indeed, during the antepartum period, there is no consistent definition of bleeding including early vaginal bleeding, the most frequent antepartum bleeding event . Some authors have defined early vaginal bleeding as at least one episode of spotting whereas others have defined it as bleeding greater than menses or involving a risk of abortion or sufficient to prompt an ultrasound examination .…”