First-trimester serum BAFF:sFlt-1 ratio as a candidate early biomarker of spontaneous abortion.

Abstract

Immunologic, angiogenic, and anti-angiogenic factors are associated with spontaneous abortion (SAB). B cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) may play a role in SAB and may serve singly or in combination as an early biomarker of SAB. In this prospective observational study, serum sFlt-1, PIGF, BAFF, and APRIL levels were measured in the first trimester of pregnancy in a medically diverse group of women and in non-pregnant controls. Associations and discriminative values of first-trimester sFlt-1, PIGF, BAFF, and APRIL levels and the corresponding APRIL:BAFF, BAFF:sFlt-1, and sFlt-1:PlGF ratios with development of SAB were tested. Median serum BAFF level was lower (p=.007) and median serum sFlt-1 level was higher (p<.001), in the first trimester of pregnancy than in non-pregnant controls. SAB developed in 27 of the pregnant women (11.3%), and first-trimester levels of BAFF (but not APRIL) and sFlt-1 (but not PIGF) were associated with SAB. Using optimal cutoffs determined through receiver operating characteristics curves, the best discriminator of SAB was the serum BAFF:sFlt-1 ratio, specifically among non-nulliparous women and women with prior SAB. First-trimester serum BAFF:sFlt-1 ratio is a candidate indicator/predictor of SAB among non-nulliparous women and women with prior SAB. If validated through additional studies, then early identification of pregnant women at high risk for SAB through this simple blood test would assist in counseling and facilitate clinical trials of therapeutic interventions.