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Updated: Apr 24, 2026
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes
Roberto Romero1, Jezid Miranda, Piya Chaemsaithong
1a Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development , NIH , Detroit , MI , USA .
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.
Insights
Microorganisms are found in 40% of preterm prelabor rupture of membranes (PROM) cases, with sterile inflammation also prevalent. Early gestational age at PROM correlates with increased inflammation, impacting pregnancy outcomes.
Area of Science:
- Reproductive Medicine
- Microbiology
- Obstetrics
Background:
- Preterm prelabor rupture of membranes (PROM) is a major cause of preterm birth.
- Intra-amniotic infection and inflammation are significant complications of PROM.
- The role of microorganisms and sterile inflammation in preterm PROM requires further elucidation.
Purpose of the Study:
- To determine the microbial profile of amniotic fluid in patients with preterm PROM.
- To investigate the association between intra-amniotic inflammation (microbial and sterile) and adverse pregnancy outcomes in preterm PROM.
- To compare the diagnostic capabilities of cultivation techniques and PCR/ESI-MS for detecting amniotic fluid microorganisms.
Main Methods:
- Amniotic fluid samples were collected from 59 women with preterm PROM.
- Microbiology was assessed using cultivation and broad-range PCR/ESI-MS.
- Interleukin-6 (IL-6) levels in amniotic fluid were measured by ELISA.
- Results were correlated with IL-6 concentrations and obstetrical/perinatal outcomes.
Main Results:
- Microorganisms were detected in 41% of preterm PROM cases when combining cultivation and PCR/ESI-MS.
- Sneathia species and Ureaplasma urealyticum were the most common microorganisms identified.
- Microbial-associated and sterile intra-amniotic inflammation occurred in 29% of cases, with prevalence varying by gestational age at PROM.
- Earlier gestational age at PROM was associated with higher frequencies of both microbial and sterile inflammation.
- Acute placental inflammation was significantly more frequent in cases with microbial-associated inflammation.
Conclusions:
- A combined approach of cultivation and PCR/ESI-MS detects microorganisms in 40% of preterm PROM cases.
- PCR/ESI-MS identified 50% more microorganisms than AF culture alone.
- Sterile intra-amniotic inflammation is present in 29% of preterm PROM patients and can be as or more common than microbial-associated inflammation after 24 weeks gestation.
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