Second‐trimester amniotic fluid proteins changes in subsequent spontaneous preterm birth

INTRODUCTION: The global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix‐related proteins (procollagen, osteopontin and IL‐33), and of cytokines (IL‐19, IL‐6, IL‐20, TNFα, TGFβ, and IL‐1β) in asymptomatic women with and without subsequent spontaneous preterm delivery. MATERIAL AND METHODS: We used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks' gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad‐range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double‐blind, placebo‐controlled trial to perform a nested case–control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix‐related proteins and cytokines measured by immunoassays were compared for two study groups. ClinicalTrials.gov: NCT00718705. RESULTS: Between July 2008 and July 2011, in 12 maternal‐fetal medicine centers in France, 166 women with available PCR‐negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL‐19, IL‐6, IL‐20, IL‐33, TNFα, TGFβ, and IL‐1β were compared between the 37 who gave birth preterm and the 129 women with full‐term delivery. Amniotic fluid levels of procollagen, osteopontin, IL‐19, IL‐33, and TNFα were significantly higher in the preterm than the full‐term group. IL‐6, IL‐20, TGFβ, and IL‐1β levels did not differ between the groups. CONCLUSIONS: In amniotic fluid 16 S rDNA PCR negative samples obtained during second‐trimester amniocentesis, extracellular matrix‐related protein concentrations (procollagen, osteopontin and IL‐33), together with IL‐19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.