Background/Purpose: Immunologic, angiogenic, and anti-angiogenic factors have been associated with spontaneous abortion (SAB), yet early identification of those pregnant women who ultimately undergo SAB remains very limited. B-cell activating factor (BAFF; a vital B cell survival factor), a proliferation-inducing ligand (APRIL; a vital plasma cell survival factor), placental growth factor (PlGF; a vital angiogenic factor), and soluble fms-like tyrosine kinase-1 (sFlt-1; a vital anti-angiogenic factor) may play a role in the development of SAB and, hence, may serve singly or in combination as an early biomarker of SAB. The present study was performed to evaluate serum levels of sFlt-1, PIGF, BAFF, and APRIL in the first trimester of pregnancy and to assess associations and predictive values of first-trimester levels of these factors with SAB.

Methods: 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 predictive values of first-trimester sFlt-1, PIGF, BAFF, and APRIL levels with development of SAB were tested.

Results: Serum samples from 286 women (48 non-pregnant controls and 238 pregnant women) were evaluated. Median serum BAFF levels were significantly lower and median serum sFlt-1 levels were significantly higher in the first trimester of pregnancy than in non-pregnant controls (0.900 ng/ml versus 1.000 ng/ml, p = 0.007, for BAFF; 0.454 ng/ml versus 0.103 ng/ml, p < 0.001 for sFlt-1). No differences in serum APRIL or PlGF levels were appreciated. SAB developed in 27 of the pregnant women (11.3%). While first-trimester levels of APRIL and PIGF were not associated with SAB, first-trimester serum BAFF was significantly elevated and first-trimester serum sFlt-1 was significantly reduced in women with SAB compared to those who maintained their pregnancies (p = 0.005 and p < 0.001, respectively). Using the optimal cut-offs generated through receiver operating characteristics curves for BAFF and sFlt-1, respectively, the positive predictive values for SAB when taking serum levels of both BAFF and sFlt-1 into consideration were 0.3529 (p < 0.0001) for all subjects (N = 236), 0.4667 (p < 0.001) for subjects without an underlying chronic medical disorder (N = 131), and 0.3750 (p = 0.0045) for subjects with an underlying chronic medical disorder (N = 105; including 20 subjects with systemic rheumatic diseases). The corresponding negative predictive values for SAB were 0.9808 (p = 0.0009) for all subjects, 0.9706 (p = 0.0140) for subjects without an underlying chronic medical disorder, and 1.0000 (p = 0.0362) for subjects with an underlying chronic medical disorder.

Conclusion: The combination of serum first-trimester levels of BAFF and sFlt-1 greatly increases the ability to positively and negatively predict SAB. Identification of pregnant women at high risk for SAB through testing of serum BAFF and sFlt-1 levels could assist in their counseling and ultimately facilitate clinical trials that test candidate therapeutic interventions.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/combined-first-trimester-serum-baff-and-sflt-1-levels-as-an-early-biomarker-of-spontaneous-abortion/