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. 2009 Jan;30(1):56-61.
doi: 10.1016/j.placenta.2008.09.017. Epub 2008 Nov 28.

The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: clinical implications

Chan-Wook Park  1 , Kyung Chul Moon, Joong Shin Park, Jong Kwan Jun, Roberto Romero, Bo Hyun Yoon
Affiliations

The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: clinical implications

Chan-Wook Park et al. Placenta. 2009 Jan.

Abstract

Objective: Amnionitis (inflammation of the amnion) is the final stage of extra-placental chorioamniotic inflammation. We propose that patients with "amnionitis", rather than "chorionitis" have a more advanced form of intra-uterine inflammation/infection and, thus, would have a more intense fetal and intra-amniotic inflammatory response than those without "amnionitis".

Study design: The relationship between the presence of amnionitis, and a fetal and an intra-amniotic inflammatory response was examined in 290 singleton preterm births (<or=36 weeks) with histologic chorioamnionitis. The fetal inflammatory response was determined by plasma C-reactive protein (CRP) concentrations in umbilical cord and the presence of funisitis. The intra-amniotic inflammatory response was assessed by matrix metalloproteinase-8 (MMP-8) concentration and white blood cell (WBC) count in 156 amniotic fluid (AF) samples obtained within 5 days of birth. AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay.

Results: (1) Amnionitis was present in 43.1% of cases with histologic chorioamnionitis. (2) Patients with amnionitis had a significantly higher rate of funisitis and positive AF culture and a higher median umbilical cord plasma CRP, AF MMP-8 level and AF WBC count than those without amnionitis (p<0.001 for each). (3) Among cases with amnionitis, the presence or absence of funisitis was not associated with significant differences in the median cord plasma CRP, AF MMP-8 level and AF WBC count. (4) However, the presence of amnionitis in cases with funisitis was associated with a higher median umbilical cord plasma CRP, AF MMP-8 level and AF WBC count than the absence of amnionitis in those with funisitis (p<0.05 for each). (5) Multiple logistic regression analysis demonstrated that amnionitis was a better independent predictor of proven or suspected early-onset neonatal sepsis (odds ratio 3.8, 95% confidence interval (CI) 1.1-13.2, p<0.05) than funisitis (odds ratio 1.8, 95% CI 0.5-6.1, not significant) after correction for the contribution of other potential confounding variables.

Conclusion: The involvement of the amnion in the inflammatory process of the extraplacental membranes is associated with a more intense fetal and intra-amniotic inflammatory response than chorionitis alone. This observation has clinical implications because it allows staging of the severity of the inflammatory process and assessment of the likelihood of fetal involvement.

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Figures

Figure 1
Figure 1
CRP concentrations in umbilical cord plasma at birth (a), and AF MMP-8 concentrations (b) and AF WBC counts (c) according to the presence or absence of amnionitis. Cord plasma CRP: amnionitis (−), median, 29.1 ng/ml (range, 1.9–7401.8 ng/ml) vs. amnionitis (+), median, 520.8 ng/ml (range, 2.2–10897.4 ng/ml) (p < 0.001); AF MMP-8: amnionitis (−), median, 29.2 ng/ml (range, 0.3–4202.7 ng/ml) vs. amnionitis (+), median, 416.2 ng/ml (range, 0.3–6142.6 ng/ml) (p < 0.001); AF WBC: amnionitis (−), median, 6 cells/mm3 (range, 0–4320 cells/mm3) vs. amnionitis (+), median, 884 cells/mm3 (range, 0–19764 cells/mm3) (p < 0.001).
Figure 1
Figure 1
CRP concentrations in umbilical cord plasma at birth (a), and AF MMP-8 concentrations (b) and AF WBC counts (c) according to the presence or absence of amnionitis. Cord plasma CRP: amnionitis (−), median, 29.1 ng/ml (range, 1.9–7401.8 ng/ml) vs. amnionitis (+), median, 520.8 ng/ml (range, 2.2–10897.4 ng/ml) (p < 0.001); AF MMP-8: amnionitis (−), median, 29.2 ng/ml (range, 0.3–4202.7 ng/ml) vs. amnionitis (+), median, 416.2 ng/ml (range, 0.3–6142.6 ng/ml) (p < 0.001); AF WBC: amnionitis (−), median, 6 cells/mm3 (range, 0–4320 cells/mm3) vs. amnionitis (+), median, 884 cells/mm3 (range, 0–19764 cells/mm3) (p < 0.001).
Figure 2
Figure 2
CRP concentrations in umbilical cord plasma at birth (a), and AF MMP-8 concentrations (b) and AF WBC counts (c) according to the involvement of the inflammation in amnion or umbilical cord. Cord plasma CRP: amnionitis (−) & funisitis (−), median, 22.1 ng/ml (range, 1.9–7401.8 ng/ml) vs. amnionitis (−) & funisitis (+), median, 120.8 ng/ml (range, 4.9–5555.0 ng/ml) vs. amnionitis (+) & funisitis (−), median, 125.6 ng/ml (range, 3.0–5315.8 ng/ml) vs. amnionitis (+) & funisitis (−), median, 750.7 ng/ml (range, 2.2–10897.4 ng/ml); AF MMP-8: amnionitis (−) & funisitis (−), median, 8.7 ng/ml (range, 0.3–4202.7 ng/ml) vs. amnionitis (−) & funisitis (+), median, 69.6 ng/ml (range, 0.3–3836.8 ng/ml) vs. amnionitis (+) & funisitis (−), median, 373.1 ng/ml (range, 0.3–642.1 ng/ml) vs. amnionitis (+) & funisitis (+), median, 444.1 ng/ml (range, 0.3–6142.6 ng/ml); AF WBC: amnionitis (−) & funisitis (−), median, 3 cells/mm3 (range, 0–4320 cells/mm3) vs. amnionitis (−) & funisitis (−), median, 45 cells/mm3 (range, 0–2880 cells/mm3) vs. amnionitis (+) & funisitis (−), median, 543 cells/mm3 (range, 0–5400 cells/mm3) vs. amnionitis (+) & funisitis (+), median, 937 cells/mm3 (range, 0–19764 cells/mm3). (Each p values is shown in graphs.)
Figure 2
Figure 2
CRP concentrations in umbilical cord plasma at birth (a), and AF MMP-8 concentrations (b) and AF WBC counts (c) according to the involvement of the inflammation in amnion or umbilical cord. Cord plasma CRP: amnionitis (−) & funisitis (−), median, 22.1 ng/ml (range, 1.9–7401.8 ng/ml) vs. amnionitis (−) & funisitis (+), median, 120.8 ng/ml (range, 4.9–5555.0 ng/ml) vs. amnionitis (+) & funisitis (−), median, 125.6 ng/ml (range, 3.0–5315.8 ng/ml) vs. amnionitis (+) & funisitis (−), median, 750.7 ng/ml (range, 2.2–10897.4 ng/ml); AF MMP-8: amnionitis (−) & funisitis (−), median, 8.7 ng/ml (range, 0.3–4202.7 ng/ml) vs. amnionitis (−) & funisitis (+), median, 69.6 ng/ml (range, 0.3–3836.8 ng/ml) vs. amnionitis (+) & funisitis (−), median, 373.1 ng/ml (range, 0.3–642.1 ng/ml) vs. amnionitis (+) & funisitis (+), median, 444.1 ng/ml (range, 0.3–6142.6 ng/ml); AF WBC: amnionitis (−) & funisitis (−), median, 3 cells/mm3 (range, 0–4320 cells/mm3) vs. amnionitis (−) & funisitis (−), median, 45 cells/mm3 (range, 0–2880 cells/mm3) vs. amnionitis (+) & funisitis (−), median, 543 cells/mm3 (range, 0–5400 cells/mm3) vs. amnionitis (+) & funisitis (+), median, 937 cells/mm3 (range, 0–19764 cells/mm3). (Each p values is shown in graphs.)
Figure 3
Figure 3
CRP concentrations in umbilical cord plasma at birth (a) AF MMP-8 concentrations (b) and AF WBC counts (c) according to the results of amniotic fluid culture and the presence or absence of amnionitis. Patients with amnionitis had significantly higher median umbilical cord plasma CRP, AF MMP-8 concentrations and AF WBC counts than those without amnionitis among cases with a positive AF culture. Cord plasma CRP: median, 551.4 ng/ml (range, 9.5–4885.5 ng/ml) vs. median, 78.3 ng/ml (range, 16.3–2586.7 ng/ml); AF MMP-8: median, 594.0 ng/ml (range, 0.3–5019.5 ng/ml) vs. median, 26.0 ng/ml (range, 0.7–870.8 ng/ml); AF WBC: median, 981 cells/mm3 (range, 18–19764 cells/mm3) vs. median, 6 cells/mm3 (range, 0–1000 cells/mm3)) and also among cases with a negative AF culture (Cord plasma CRP: median, 639.8 ng/ml (range, 2.2–4545.6 ng/ml) vs. median, 27.9 ng/ml (range, 1.9–7401.8 ng/ml); AF MMP-8: 373.1 ng/ml (range, 0.5–6142.6 ng/ml) vs. median, 41.8 ng/ml (range, 0.3–4202.7 ng/ml); AF WBC: median, 876 cells/mm3 (range, 0–5800cells/mm3) vs. median, 5 cells/mm3 (range, 0–4320 cells/mm3). (Each p values is shown in graphs.)
Figure 3
Figure 3
CRP concentrations in umbilical cord plasma at birth (a) AF MMP-8 concentrations (b) and AF WBC counts (c) according to the results of amniotic fluid culture and the presence or absence of amnionitis. Patients with amnionitis had significantly higher median umbilical cord plasma CRP, AF MMP-8 concentrations and AF WBC counts than those without amnionitis among cases with a positive AF culture. Cord plasma CRP: median, 551.4 ng/ml (range, 9.5–4885.5 ng/ml) vs. median, 78.3 ng/ml (range, 16.3–2586.7 ng/ml); AF MMP-8: median, 594.0 ng/ml (range, 0.3–5019.5 ng/ml) vs. median, 26.0 ng/ml (range, 0.7–870.8 ng/ml); AF WBC: median, 981 cells/mm3 (range, 18–19764 cells/mm3) vs. median, 6 cells/mm3 (range, 0–1000 cells/mm3)) and also among cases with a negative AF culture (Cord plasma CRP: median, 639.8 ng/ml (range, 2.2–4545.6 ng/ml) vs. median, 27.9 ng/ml (range, 1.9–7401.8 ng/ml); AF MMP-8: 373.1 ng/ml (range, 0.5–6142.6 ng/ml) vs. median, 41.8 ng/ml (range, 0.3–4202.7 ng/ml); AF WBC: median, 876 cells/mm3 (range, 0–5800cells/mm3) vs. median, 5 cells/mm3 (range, 0–4320 cells/mm3). (Each p values is shown in graphs.)
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