Accumulation of interleukin-1beta and interleukin-6 in amniotic fluid: a sequela of labour at term and preterm.

From the finding of micro-organisms or inflammatory mediators, or both, in amniotic fluid (AF), it has been proposed that intrauterine infection is one cause of preterm labour (PTL, intact fetal membranes). This theory, however, remains unproved, i.e. the accumulation of micro-organisms and inflammatory mediators in AF after labour is in progress may be the consequence, not the cause, of labour both at term and preterm. This study was conducted to evaluate this possibility by a comparison of the concentrations of interleukin (IL)-1beta and IL-6 in AFs collected before and during PTL (<34 weeks gestation) with those in AFs collected at term (before labour and from the forebag and upper compartments of the amniotic sac during labour). The concentrations of IL-1beta and IL-6 in AF were also analysed as a function of the duration of labour (term or preterm) before fluid collection. In addition, studies were conducted to define the source of IL-1beta in AF. A total of 666 AFs were evaluated. IL-1beta was not detected (<50 pg/ml) in AFs collected before the onset of labour at any stage of gestation (n = 320), including 170 fluids obtained at term. During labour, IL-1beta was detected (>50 pg/ml) in 58 out of 106 (54.7%), 17 out of 64 (26.6%) and 60 out of 176 (34%) of AF samples obtained during PTL, term labour (upper compartment) and term labour (forebag) respectively. AF sampling, as well as labour and delivery, were completed in <18 h in all term pregnancies. However, labour (with cervical dilation) was in progress for >18 h before AF was collected in 39 out of 106 (37%) PTL pregnancies. The incidence of IL-1beta-positive samples among AFs collected before 18 h of PTL (23 out of 67; 34%) was indistinguishable from that in AFs collected during labour at term. However, in AFs collected after >18 h PTL, the incidence of IL-1beta-positive samples was 35 out of 39 (89.7%) The concentrations of IL-1beta (pg/ml; mean +/- SEM) in AFs collected during PTL (2680 +/- 730; n = 106) were greater than those in AFs collected from the upper compartment and forebag during term labour (436 +/- 244, n = 64; and 468 +/- 119, n = 176) respectively; this difference, however, was attributable to very high concentrations of IL-1beta in AFs in which PTL was in progress for >18 h before AF collection (6021 +/- 1832; n = 39). The concentrations of IL-6 in AF were correlated with those of IL-1beta (P < 0.001). We conclude that IL-1beta and IL-6 accumulate in AF in a similar proportion of pregnancies during the first 18 h of term and preterm labour. Therefore, the accumulation of these cytokines in AF cannot be taken as evidence for a role for infection in the pathogenesis of PTL.