Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome

Kunze, Mirjam; Klar, Maximilian; Morfeld, C; Thorns, Beena; Schild, R. L.; Markfeld-Erol, F; Rasenack, R; Proempeler, Heinrich; Hentschel, Roland; Schaefer, W.R.

doi:10.1016/j.ajog.2016.01.181

Cited by 66 publications

(76 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Amniotic fluid analysis, including rapid tests for the detection of inflammation [95–98] and molecular microbiologic methods [34, 45, 72, 81–87, 99–107], are likely to become important in the management of preterm clinical chorioamnionitis. Recent observations suggest that assessment of AF retrieved using an AF collector [65] and the measurement of inflammatory mediators could be of value in the assessment of patients with preterm PROM [108]. …”

Section: Discussionmentioning

confidence: 99%

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation

Kim

Hong

et al. 2017

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

Background Recent studies on clinical chorioamnionitis at term suggest that some patients with this diagnosis have neither intra-amniotic infection nor intra-amniotic inflammation. A false-positive diagnosis of clinical chorioamnionitis in preterm gestation may lead to unwarranted preterm delivery. Objective To determine the frequency of intra-amniotic inflammation and microbiologically proven amniotic fluid infection in patients with preterm clinical chorioamnionitis. Study design Amniocentesis was performed in singleton pregnant women with preterm clinical chorioamnionitis (<36 weeks of gestation). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8 concentration. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture; intra-amniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration of >23 ng/mL. Non-parametric and survival techniques were used for analysis. Results Among patients with preterm clinical chorioamnionitis, 24% (12/50) had microbiologic evidence of neither intra-amniotic infection nor intra-amniotic inflammation. Microbial invasion of the amniotic cavity was present in 34% (18/53) and intra-amniotic inflammation in 76% (38/50) of patients. The most common microorganisms isolated from the amniotic cavity were the Ureaplasma species. Finally, patients without microbial invasion of the amniotic cavity or intra-amniotic inflammation had significantly lower rates of adverse outcomes (including lower gestational age at delivery, a shorter amniocentesis-to-delivery interval, acute histologic chorioamnionitis, acute funisitis, and significant neonatal morbidity) than those with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation. Conclusion Among patients with preterm clinical chorioamnionitis, 24% had no evidence of either intra-amniotic infection or intra-amniotic inflammation, and 66% had negative amniotic fluid cultures, using standard microbiologic techniques. These observations call for a re-examination of the criteria used to diagnose preterm clinical chorioamnionitis.

show abstract

Section: Discussionmentioning

confidence: 99%

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation

Kim

Hong

et al. 2017

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

show abstract

“…Amniotic fluid IL-6 and TNF-α seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with PPROM. The noninvasive techniques of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and could be in this respect preferable to invasive amniocentesis [80]. With the implementation of a vaginal fluid collector it is possible to detect the vaginal fluid cytokine in everyday routine clinical procedures.…”

Section: Amniotic Fluid Sampling From Vaginal Secretionsmentioning

confidence: 99%

“…Kunze et al measured AI-6 and TNF-α in vaginal secretions of 99 patients with PPROM [80]. The median vaginal concentrations of AI-6 and TNF-α were significantly higher in the FIRS group.…”

Section: Amniotic Fluid Sampling From Vaginal Secretionsmentioning

confidence: 99%

Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome

Tchirikov

Schlabritz‐Loutsevitch

Mäher

et al. 2017

Journal of Perinatal Medicine

176

153

View full text Add to dashboard Cite

Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long-and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/anhydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane -either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intraamniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR) = 0.66), neonatal infections (RR = 0.67) and abnormal ultrasound scan of neonatal brain (RR = 0.67)]. The positive effect of continuo...

show abstract

“…Moreover, this point-of-care alternative might serve as a noninvasive test of intra-amniotic environment in women with PPROM [15,16]. Therefore, this type of test is important from a clinical point of view, since the entire procedure of sampling followed by a rapid evaluation of IL-6 in a fresh sample can be performed directly in a Labor and Delivery ward.…”

Section: Introductionmentioning

confidence: 99%

“…In recent studies, a point-of-care IL-6 test has been shown to be effective in the identification of MIAC, intraamniotic inflammation, and fetal inflammatory response syndrome [7,[11][12][13][14][15][16]. Moreover, this point-of-care alternative might serve as a noninvasive test of intra-amniotic environment in women with PPROM [15,16].…”

Section: Introductionmentioning

confidence: 99%

Preterm Prelabor Rupture of Membranes between 34 and 37 Weeks: A Point-of-Care Test of Vaginal Fluid Interleukin-6 Concentrations for a Noninvasive Detection of Intra-Amniotic Inflammation

et al. 2017

View full text Add to dashboard Cite

Objective: The aim of this study was to investigate whether a previously reported vaginal fluid point-of-care interleukin (IL)-6 cut-off value of 2,500 pg/mL can be used for the identification intra-amniotic inflammation in women with preterm prelabor rupture of membranes (PPROM) between 34 and 37 weeks. Material and Methods: A prospective cohort study was conducted in women with singleton gestation complicated by PPROM between 34 + 0 and 36 + 6 weeks.Vaginal fluid was successfully obtained in 118 women from the posterior vaginal fornix via aspiration using a sterile urine sample tube with a suction tip. Amniotic fluid was obtained via transabdominal amniocentesis. IL-6 concentrations were assessed in both fluids immediately after sampling. Intra-amniotic inflammation was defined as an amniotic fluid point-of-care IL-6 concentration of ≥745 pg/mL. Results: The tested vaginal fluid IL-6 cut-off value had a sensitivity of 91%, specificity of 91%, positive predictive value of 50%, negative predictive value of 99%, positive likelihood ratio of 9.7, and negative likelihood ratio of 0.1 for the identification of intra-amniotic inflammation. Conclusion: The point-of-care vaginal fluid IL-6 test with a cut-off value of 2,500 pg/mL shows good sensitivity, specificity, and negative predictive value for the identification of intra-amniotic inflammation in PPROM between 34 and 37 weeks.

show abstract

Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome

Cited by 66 publications

References 41 publications

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation

Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome

Preterm Prelabor Rupture of Membranes between 34 and 37 Weeks: A Point-of-Care Test of Vaginal Fluid Interleukin-6 Concentrations for a Noninvasive Detection of Intra-Amniotic Inflammation

Contact Info

Product

Resources

About