In this study, we sought to determine in a prospective and blinded fashion whether a previously identified proteomic profile comprised of four protein biomarkers (neutrophil defensins-1 and −2 and calgranulins A and C) is reproducible and maintains its highly accurate “signature” when compared to previously established or proposed markers of intra-amniotic fluid inflammation or infection: glucose, white blood cell (WBC) count, lactate dehydrogenase (LDH), Gram stain, interleukin-6 (IL-6), and matrix metalloprotease-8 (MMP-8). Here, IL6 is linked to infection.