Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes

Roberto Romero, Jezid Miranda, Piya Chaemsaithong, Tinnakorn Chaiworapongsa, Juan P. Kusanovic, Zhong Dong, Ahmed I. Ahmed, Majid Shaman, Kia Lannaman, Bo Hyun Yoon, Sonia S. Hassan, Chong Jai Kim, Steven Jai Korzeniewski, Lami Yeo, Yeon Mee Kim

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Objective: The objectives of this study were to: (1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and (2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM. Methods: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations and the occurrence of adverse obstetrical/perinatal outcomes. Results: (1) PCR/ESI-MS, AF culture, and the combination of these two tests each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; (2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; (3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [ 29% (17/59)]: however, the prevalence of each differed according to the gestational age when PROM occurred; (4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; (5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and (6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) versus 38% (6/16); p = 0.001]. Conclusions: (1) The frequency of microorganisms in preterm PROM is 40% using both cultivation techniques and PCR/ESI-MS; (2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than AF culture; and (3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation.

Original languageEnglish
Pages (from-to)1394-1409
Number of pages16
JournalJournal of Maternal-Fetal and Neonatal Medicine
Issue number12
StatePublished - 13 Aug 2015


  • Infection
  • Sneathia sp.
  • polymerase chain reaction with electrospray ionization mass spectrometry
  • pregnancy
  • prematurity
  • preterm delivery

Cite this

Romero, R., Miranda, J., Chaemsaithong, P., Chaiworapongsa, T., Kusanovic, J. P., Dong, Z., Ahmed, A. I., Shaman, M., Lannaman, K., Yoon, B. H., Hassan, S. S., Kim, C. J., Korzeniewski, S. J., Yeo, L., & Kim, Y. M. (2015). Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. Journal of Maternal-Fetal and Neonatal Medicine, 28(12), 1394-1409.