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Elevated Angiogenic Factors Across Gestation In Women With Postpartum Hemorrhage
Abstract Number: GM-05
Abstract Type: Original Research
Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. While clinical risk factors are known, the molecular basis for PPH is not understood. Biomarkers to predict PPH could greatly improve care by triaging high-risk women to tertiary care centers for delivery. Given that PPH is closely linked to placental delivery, we hypothesized that levels of angiogenic factors (i.e., sFlt-1, PlGF) involved in placental implantation and development would be altered in women with PPH.
This is a secondary analysis of data from an IRB-approved prospective longitudinal cohort study designed to evaluate sFlt-1 and PlGF as biomarkers for preeclampsia. Women were recruited during routine prenatal care at Brigham & Women's Hospital in Boston, MA and serum samples were collected at 4 visits (< 15 (T1), 16-20 (T2), 24-28 (T3), and 34-38 (T4) weeks' gestation). Levels of sFlt-1 and PlGF were assayed. PPH cases were identified by ICD-9 code (666.xx) and verified by two physician review. PPH was defined as ≥ 500 or 1000 mL following vaginal delivery or cesarean section, respectively. PPH cases not due to atony or retained placenta were excluded. The geometric mean sFlt-1 and PlGF concentrations were calculated at each time point and compared using the Wilcoxon rank sum test.
In this cohort of 1233 women, we identified 43 cases of PPH (3.5%). Women with PPH were more likely to be non-White, self-pay or Medicaid, and pregnant with a multifetal gestation (p <0.05). Levels of sFlt-1 were significantly increased in cases at T2 (p <0.05), T3 (p <0.1), and T4 (p<0.1), while PlGF levels were significantly increased only at T2 (p <0.05) (Figure 1). The ratio of sFlt-1/PlGF was not different between cases and controls. The differences in sFlt-1 levels remained after adjusting for maternal age, BMI, race, multifetal gestation, and preeclampsia.
Angiogenic factors are increased during gestation, particularly in the second trimester, in women who ultimately have PPH. This suggests that altered placental development and invasion may be a risk factor for PPH, even in women with PPH due to atony. Future work aims to identify biomarkers that can predict PPH at delivery. Ultimately, improved understanding of PPH pathophysiology could significantly reduce maternal deaths due to hemorrhage.