A Fetal and an Intra-Amniotic Inflammatory Response Is More Severe in Preterm Labor than in Preterm PROM in the Context of Funisitis: Unexpected Observation in Human Gestations

OBJECTIVE: Although intra-amniotic(IA) infection is present in both preterm labor and intact membranes(PTL) and preterm premature rupture of membranes(preterm-PROM), it is more common in preterm-PROM than in PTL. Microorganisms and their products in the amniotic-cavity can elicit an inflammatory-response in fetus as well as in amniotic-cavity in the progression of acute histologic chorioamnionitis(acute-HCA). A fundamental question is whether a fetal and an IA inflammatory-response is more severe in preterm-PROM than in PTL, in the same-context of acute-HCA with or without fetal-involvement. The purpose of current-study was to answer this-question. STUDY-DESIGN: Study population consisted of 213 singleton preterm-gestations(<34 weeks) delivered within 4 days of amniocentesis due to PTL(120 cases) or preterm-PROM(93 cases). The intensity of fetal and IA inflammatory-responses was compared between PTL and preterm-PROM, according to placental inflammatory conditions:1)placenta without inflammatory-lesion;2)acute-HCA without funisitis;3)acute-HCA with funisitis. IA inflammatory response was assessed by amniotic-fluid(AF) matrix metalloproteinase-8(MMP-8), and fetal inflammatory response(FIR) by umbilical-cord plasma(UCP) C-reactive protein(CRP) at birth. RESULTS: 1) Patients with preterm-PROM had higher rates of IA infection, acute-HCA, and acute-HCA with funisitis than those with PTL did(p<.01 for each);2) there were no significant differences in the intensity of fetal and IA inflammatory-responses and the rate of cervical dilatation≥3 cm or 4 cm between patients with PTL and those with preterm-PROM in the context of both placenta without inflammatory-lesion and acute-HCA without funisitis(p>.05 for each);3) however, acute-HCA with funisitis was associated with a significantly higher median AF MMP-8 and UCP CRP concentration and higher rate of cervical dilatation≥3 cm or 4 cm in PTL than in preterm-PROM(AF MMP-8, 675 ng/mlvs.417 ng/ml; UCP CRP, 969 ng/mlvs.397 ng/ml;each for p<.05), despite less common IA infection in PTL than in preterm-PROM(29%vs.57%;p<.05). CONCLUSIONS: A fetal and an IA inflammatory-response is more severe in PTL than in preterm-PROM in the context of funisitis, despite less common IA infection. This unexpected observation may indicate the fundamental difference in the pathogenesis between PTL and preterm-PROM.