Research
Obstetrics
Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes

Presented at the 33rd annual meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 11-16, 2013.
https://doi.org/10.1016/j.ajog.2013.11.032Get rights and content

Objective

The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes.

Study Design

Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL).

Results

The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2–11.2, OR, 3.1; 95% CI, 1.5–6.4, and OR, 1.8; 95% CI, 0.6–5.5, respectively).

Conclusion

We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Section snippets

Materials and Methods

This report involved a subset of subjects from a larger multicenter study, the goal of which was to develop a noninvasive test to screen for intraamniotic infection based on cervicovaginal proteins. The protocol was approved by the local institutional review board at each participating site.

Results

From September 2007 through November 2009, 338 women who met all the inclusion criteria were enrolled at 16 sites. Of these, 18 women withdrew or were lost to follow-up evaluation, and 15 were excluded because of inadequate specimens, which left 305 women for the analyses presented here. The number of women at each site and the gestational ages at amniocentesis are tabulated in Table 1.

Comment

Our results confirm previous observations that women in preterm labor have high rates of intraamniotic infection and inflammation, especially at early gestational ages.2, 3, 4 We also confirm that intraamniotic inflammation, which is evidenced by high IL-6 levels, is associated with short latency and high rates of perinatal morbidity and mortality whether or not microbes are detected in the amniotic fluid.3, 4

We present 4 novel findings: (1) In the inflammation groups, the absence of MIAC was

Conclusion

In preterm labor with intact membranes, there is a high rate of intraamniotic infection and inflammation, especially at early gestational ages. Latency and perinatal morbidity and death are related more closely to the degree of the inflammatory response than to the presence or absence of microbes in the amniotic fluid. Microbial colonization without inflammatory response may be relatively benign.

Acknowledgments

ProteoGenix/Obstetrix Collaborative Research Network

Investigative sites. Obstetrix Medical Group, Phoenix Perinatal Associates, Phoenix, AZ: William Clewell, MD; Banner Good Samaritan Medical Center, Phoenix, AZ: Melissa Ingersoll, RN, CRC; Banner Desert Samaritan Medical Center, Phoenix, AZ: Ana Braescu, RN, MS; Obstetrix Medical Group of Arizona, Tucson Medical Center, Tucson, AZ: Hugh Miller, MD and Diane Mercer, RN, CCRC; Obstetrix Medical Group of Colorado, Presbyterian Saint Luke's

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  • Cited by (0)

    Supported by a research grant from ProteoGenix, Inc; statistical analyses supported by Hologic, Inc.

    Each author had grant support, consulting arrangements, employment, or equity interests with the sponsor, ProteoGenix, Inc. C.A.C. and T.J.G. have served on advisory boards; J.L. has a consulting arrangement, and J.K.B. has an unrelated research grant with Hologic, Inc, which acquired ProteoGenix in 2010.

    Reprints not available from the authors.

    Cite this article as: Combs CA, Gravett M, Garite TJ, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol 2014;210:125.e1-15.

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